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Professor Timothy J McDonald

Consultant Biochemist/ Hon. Professor

+44 (0) 1392 403699

RILD Building

University of Exeter Medical School, RILD Building, RD&E Hospital Wonford, Barrack Road, Exeter, EX2 5DW, UK

Overview

Professor Tim McDonald is the Clinical Director and Consultant Clinical Scientist of the Blood Sciences Laboratories at the Royal Devon and Exeter Hospital. He holds an NIHR Senior Clinical Lecturer fellowship

Broad research specialisms

His broad research interest is in the use of laboratory diagnostics to improve treatment outcomes and differential diagnosis. He has specific interests in diabetes and gastroenterology.

Qualifications

BSc, PgC, MSc, PhD, FRCPath

Research group links

Institute of Biomedical and Clinical Science

Research

Research interests

Dr McDonald's research interest involve using biomarkers to identify patients with monogenic forms of diabetes. They have developed clinical predication models to help clinicians identify patients with rare genetic causes of diabetes. The advantage being that these patients can often be treated with tablets, rather than insulin injections.

Assessment of endogenous insulin production is another area of active research. They have investigated the possibility of measuring C-peptide in urine rather than in a blood sample, identifying the clinical utility and optimal storage parameters that enable measurement from a posted urine sample. The measurement of urinary C-peptide/Creatinine ratio (UCPCR) is now provided as a routine NHS pathology test to assess endogenous insulin secretion and is requested by over 100nclinical laboratories in the UK.

In 2012, He was awarded the Department of Health’s Young Healthcare Scientist of the year award for translational research and the ACB professors prize in 2016.

Research projects

DIRECT (EU IMI funded project)– identifying biomarkers and clinical variables to identify repid glycaemic deteriation and variable treatment response in type 2 diabetes
MASTERMIND (MRC funded)- Stratification of treatment response in type 2 diabetes.

Grants/Funding

NIHR CSO Fellowship 2013-2017 (£250,000)
RD&E project grant £9000
ACB small project grant £3000

Research grants

2017 NIHR Faculty
NIHR Senior Clinical Lectureship
2016 Diabetes UK
.
2016 Helmsley Foundation
.
2015 Diabetes, UK.
Equipment Grant: Single tube diagnosis and classification of diabetes, £21,375
2012 National Institute for Health Research
Integration of multi-disciplinary pathology investigations and clinical characteristics to improve targeted genetic testing for MODY (maturity onset diabetes of the young) NIHR
2012 EU-IMI
Diabetes REseraCh on patient stratification (DIRECT)
2010 Association of Clinical Biochemists
Assay Development grant
0 Juvenile Diabetes Research Foundation
Reference 3-SRA-2014-314-M-R $1.1 million(Co-PI)

Publications

Key publications | Publications by category | Publications by year

Publications by category

Journal articles

Lynam A, McDonald T, Hill A, Dennis J, Oram R, Pearson E, Weedon M, Hattersley A, Owen K, Shields B, et al (In Press). Development and validation of multivariable clinical diagnostic models to identify type 1 diabetes requiring rapid insulin therapy in adults aged 18 to 50. BMJ Open

Bailey SER, Abel GA, Atkins A, Byford R, Davies S-J, Mays J, McDonald TJ, Miller J, Neck C, Renninson J, et al (In Press). Diagnostic performance of the faecal immunochemical test for patients with low-risk symptoms of colorectal cancer in primary care: a service evaluation in the South West of England. Abstract.

Koivula RW, Forgie IM, Kurbasic A, Viñuela A, Heggie A, Giordano GN, Hansen TH, Hudson M, Koopman A, Rutters F, et al (In Press). Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: an overview of the data from the epidemiological studies within the IMI DIRECT Consortium.

Abstract/SummaryBackground and aims:Understanding the aetiology, clinical presentation and prognosis of type 2 diabetes (T2D) and optimizing its treatment might be facilitated by biomarkers that help predict a person’s susceptibility to the risk factors that cause diabetes or its complications, or response to treatment. The IMI DIRECT (Diabetes Research on Patient Stratification) Study is a European Union (EU) Innovative Medicines Initiative (IMI) project that seeks to test these hypotheses in two recently established epidemiological cohorts. Here, we describe the characteristics of these cohorts at baseline and at the first main follow-up examination (18-months).Materials and methods:From a sampling-frame of 24,682 European-ancestry adults in whom detailed health information was available, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm and enrolled into a prospective cohort study (n=2127) undertaken at four study centres across Europe (Cohort 1: prediabetes). We also recruited people from clinical registries with recently diagnosed T2D (n=789) into a second cohort study (Cohort 2: diabetes). The two cohorts were studied in parallel with matched protocols. Endogenous insulin secretion and insulin sensitivity were modelled from frequently sampled 75g oral glucose tolerance (OGTT) in Cohort 1 and with mixed-meal tolerance tests (MMTT) in Cohort 2. Additional metabolic biochemistry was determined using blood samples taken when fasted and during the tolerance tests. Body composition was assessed using MRI and lifestyle measures through self-report and objective methods.Results:Using ADA-2011 glycaemic categories, 33% (n=693) of Cohort 1 (prediabetes) had normal glucose regulation (NGR), and 67% (n=1419) had impaired glucose regulation (IGR). 76% of the cohort was male, age=62(6.2) years; BMI=27.9(4.0) kg/m2; fasting glucose=5.7(0.6) mmol/l; 2-hr glucose=5.9(1.6) mmol/l [mean(SD)]. At follow-up, 18.6(1.4) months after baseline, fasting glucose=5.8(0.6) mmol/l; 2-hr OGTT glucose=6.1(1.7) mmol/l [mean(SD)]. In Cohort 2 (diabetes): 65% (n=508) were lifestyle treated (LS) and 35% (n=271) were lifestyle + metformin treated (LS+MET). 58% of the cohort was male, age=62(8.1) years; BMI=30.5(5.0) kg/m2; fasting glucose=7.2(1.4)mmol/l; 2-hr glucose=8.6(2.8) mmol/l [mean(SD)]. At follow-up, 18.2(0.6) months after baseline, fasting glucose=7.8(1.8) mmol/l; 2-hr MMTT glucose=9.5(3.3) mmol/l [mean(SD)].Conclusion:The epidemiological IMI DIRECT cohorts are the most intensely characterised prospective studies of glycaemic deterioration to date. Data from these cohorts help illustrate the heterogeneous characteristics of people at risk of or with T2D, highlighting the rationale for biomarker stratification of the disease - the primary objective of the IMI DIRECT consortium.Abbreviations:ASATAbdominal subcutaneous adipose tissueDIRECTDiabetes Research on Patient StratificationEUEuropean UnionMMTTMixed-meal tolerance testMRIMagnetic resonance imaginghpfVMHigh-pass filtered vector magnitudeIAATIntra-abdominal adipose tissueIGRImpaired glucose regulationIMIInnovative Medicines InitiativeMEmultiechoNGRNormal glucose regulationOGTTOral glucose tolerance testPAPhysical activityTAATTotal abdominal adipose tissueT2DType 2 Diabetes

Abstract.

Clissold R, Fulford J, Hudson M, Shields B, McDonald T, Ellard S, Hattersley A, Bingham C (In Press). Exocrine pancreatic dysfunction is common in HNF1B-associated renal disease and can be symptomatic. Clinical Kidney Journal

Young KG, McDonald TJ, Shields BM (In Press). Glycated haemoglobin measurements from UK Biobank are different to those in linked primary care records: implications for combining biochemistry data from research studies and routine clinical care. Abstract.

Sazonovs A, Kennedy N, Moutsianas L, Heap GA, Rice DL, Reppell M, Bewshea C, Walker G, Perry MH, McDonald TJ, et al (In Press). HLA-DQA1*05 is associated with the development of antibodies to anti-TNF therapy. Abstract.

Jones AG, mcdonald TJ, Shields BM, Hill AV, Hyde CJ, Knight BA, Hattersley AT (In Press). Markers of beta cell failure predict poor glycemic response to GLP-1 receptor agonist therapy in type 2 diabetes. Diabetes Care

Peters J, Anderson R, Shields B, Hudson M, Shepherd M, McDonald T, Hattersley A, Hyde C (In Press). Strategies to Identify Individuals with Monogenic Diabetes: Results of an Economic Evaluation. BMJ Open

Leete P, Oram R, McDonald T, Ziller C, Hattersley A, Richardson S, Morgan N (In Press). Studies of insulin and proinsulin in pancreas and serum support the existence of aetiopathological endotypes of type 1 diabetes associated with age at diagnosis. Diabetologia

Johnson M, Patel K, De Franco E, McDonald T, Hudson M, Dobbs R, Ellard S, Flanagan S, Hattersley A, Oram R, et al (In Press). Type 1 Diabetes can present before the age of 6 months and is characterised by autoimmunity and rapid loss of beta-cells. Diabetologia

FUHRI SNETHAGE C, MCDONALD TJ, RAMPANELLI E, DE GROEN P, SCHIMMEL AWM, VAN RAALTE D, BROUWER CB, ORAM RA, ROEP BO, NIEUWDORP M, et al (2023). 27-OR: Residual Beta-Cell Function Associates with Lower Glycaemic Variability and More Time in Range in Individuals with Type 1 Diabetes. Diabetes, 72(Supplement_1).

Thomas NJ, Hill AV, Dayan CM, Oram RA, McDonald TJ, Shields BM, Jones AG, Simon G, Ramos A, Norris A, et al (2023). Age of Diagnosis Does Not Alter the Presentation or Progression of Robustly Defined Adult-Onset Type 1 Diabetes. Diabetes Care, 46(6), 1156-1163.

. OBJECTIVE
. To determine whether presentation, progression, and genetic susceptibility of robustly defined adult-onset type 1 diabetes (T1D) are altered by diagnosis age.
.
.
. RESEARCH DESIGN AND METHODS
. We compared the relationship between diagnosis age and presentation, C-peptide loss (annual change in urine C-peptide–creatinine ratio [UCPCR]), and genetic susceptibility (T1D genetic risk score [GRS]) in adults with confirmed T1D in the prospective StartRight study, 1,798 adults with new-onset diabetes. T1D was defined in two ways: two or more positive islet autoantibodies (of GAD antibody, IA-2 antigen, and ZnT8 autoantibody) irrespective of clinical diagnosis (n = 385) or one positive islet autoantibody and a clinical diagnosis of T1D (n = 180).
.
.
. RESULTS
. In continuous analysis, age of diagnosis was not associated with C-peptide loss for either definition of T1D (P &gt; 0.1), with mean (95% CI) annual C-peptide loss in those diagnosed before and after 35 years of age (median age of T1D defined by two or more positive autoantibodies): 39% (31–46) vs. 44% (38–50) with two or more positive islet autoantibodies and 43% (33–51) vs. 39% (31–46) with clinician diagnosis confirmed by one positive islet autoantibody (P &gt; 0.1). Baseline C-peptide and T1D GRS were unaffected by age of diagnosis or T1D definition (P &gt; 0.1). In T1D defined by two or more autoantibodies, presentation severity was similar in those diagnosed before and after 35 years of age: unintentional weight loss, 80% (95% CI 74–85) vs. 82% (76–87); ketoacidosis, 24% (18–30) vs. 19% (14–25); and presentation glucose, 21 mmol/L (19–22) vs. 21 mmol/L (20–22) (all P ≥ 0.1). Despite similar presentation, older adults were less likely to be diagnosed with T1D, insulin-treated, or admitted to hospital.
.
.
. CONCLUSIONS
. When adult-onset T1D is robustly defined, the presentation characteristics, progression, and T1D genetic susceptibility are not altered by age of diagnosis.
.

Abstract.

Allesøe RL, Lundgaard AT, Hernández Medina R, Aguayo-Orozco A, Johansen J, Nissen JN, Brorsson C, Mazzoni G, Niu L, Biel JH, et al (2023). Author Correction: Discovery of drug-omics associations in type 2 diabetes with generative deep-learning models. Nat Biotechnol, 41(7). Author URL.

McDonald TJ (2023). Commentary on Abnormal Hb A1c Result from a Diabetic Patient Leads to Unexpected Diagnosis. Clin Chem, 69(7), 688-689. Author URL.

Allesøe RL, Lundgaard AT, Hernández Medina R, Aguayo-Orozco A, Johansen J, Nissen JN, Brorsson C, Mazzoni G, Niu L, Biel JH, et al (2023). Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models. Nature Biotechnology, 41(3), 399-408. Abstract.

Bowman P, Patel KA, McDonald TJ, Holst JJ, Hartmann B, Leveridge M, Shields BM, Hammersley S, Spaull SR, Knight BA, et al (2023). Incretin hormone responses to carbohydrate and protein/fat are preserved in adults with sulfonylurea-treated KCNJ11 neonatal diabetes. J Diabetes Investig Abstract. Author URL.

Happ HC, Sadleir LG, Zemel M, de Valles-Ibáñez G, Hildebrand MS, McConkie-Rosell A, McDonald M, May H, Sands T, Aggarwal V, et al (2023). Neurodevelopmental and Epilepsy Phenotypes in Individuals with Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5. Neurology, 100(6), e603-e615.

Background and objectivesKCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo KCNH5 variants.MethodsWe screened 893 individuals with developmental and epileptic encephalopathies for KCNH5 variants using targeted or exome sequencing. Additional individuals with KCNH5 variants were identified through an international collaboration. Clinical history, EEG, and imaging data were analyzed; seizure types and epilepsy syndromes were classified. We included 3 previously published individuals including additional phenotypic details.ResultsWe report a cohort of 17 patients, including 9 with a recurrent de novo missense variant p.Arg327His, 4 with a recurrent missense variant p.Arg333His, and 4 additional novel missense variants. All variants were located in or near the functionally critical voltage-sensing or pore domains, absent in the general population, and classified as pathogenic or likely pathogenic using the American College of Medical Genetics and Genomics criteria. All individuals presented with epilepsy with a median seizure onset at 6 months. They had a wide range of seizure types, including focal and generalized seizures. Cognitive outcomes ranged from normal intellect to profound impairment. Individuals with the recurrent p.Arg333His variant had a self-limited drug-responsive focal or generalized epilepsy and normal intellect, whereas the recurrent p.Arg327His variant was associated with infantile-onset DEE. Two individuals with variants in the pore domain were more severely affected, with a neonatal-onset movement disorder, early-infantile DEE, profound disability, and childhood death.DiscussionWe describe a cohort of 17 individuals with pathogenic or likely pathogenic missense variants in the voltage-sensing and pore domains of Kv10.2, including 14 previously unreported individuals. We present evidence for a putative emerging genotype-phenotype correlation with a spectrum of epilepsy and cognitive outcomes. Overall, we expand the role of EAG proteins in human disease and establish KCNH5 as implicated in a spectrum of neurodevelopmental disorders and epilepsy.

Abstract.

Liu Z, Le K, Zhou X, Alexander JL, Lin S, Bewshea C, Chanchlani N, Nice R, McDonald TJ, Lamb CA, et al (2023). Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study. Lancet Gastroenterol Hepatol, 8(2), 145-156.

BACKGROUND: Anti-TNF drugs, such as infliximab, are associated with attenuated antibody responses after SARS-CoV-2 vaccination. We aimed to determine how the anti-TNF drug infliximab and the anti-integrin drug vedolizumab affect vaccine-induced neutralising antibodies against highly transmissible omicron (B.1.1.529) BA.1, and BA.4 and BA.5 (hereafter BA.4/5) SARS-CoV-2 variants, which possess the ability to evade host immunity and, together with emerging sublineages, are now the dominating variants causing current waves of infection. METHODS: CLARITY IBD is a prospective, multicentre, observational cohort study investigating the effect of infliximab and vedolizumab on SARS-CoV-2 infection and vaccination in patients with inflammatory bowel disease (IBD). Patients aged 5 years and older with a diagnosis of IBD and being treated with infliximab or vedolizumab for 6 weeks or longer were recruited from infusion units at 92 hospitals in the UK. In this analysis, we included participants who had received uninterrupted biological therapy since recruitment and without a previous SARS-CoV-2 infection. The primary outcome was neutralising antibody responses against SARS-CoV-2 wild-type and omicron subvariants BA.1 and BA.4/5 after three doses of SARS-CoV-2 vaccine. We constructed Cox proportional hazards models to investigate the risk of breakthrough infection in relation to neutralising antibody titres. The study is registered with the ISRCTN registry, ISRCTN45176516, and is closed to accrual. FINDINGS: Between Sept 22 and Dec 23, 2020, 7224 patients with IBD were recruited to the CLARITY IBD study, of whom 1288 had no previous SARS-CoV-2 infection after three doses of SARS-CoV-2 vaccine and were established on either infliximab (n=871) or vedolizumab (n=417) and included in this study (median age was 46·1 years [IQR 33·6-58·2], 610 [47·4%] were female, 671 [52·1%] were male, 1209 [93·9%] were White, and 46 [3·6%] were Asian). After three doses of SARS-CoV-2 vaccine, 50% neutralising titres (NT50s) were significantly lower in patients treated with infliximab than in those treated with vedolizumab, against wild-type (geometric mean 2062 [95% CI 1720-2473] vs 3440 [2939-4026]; p

Abstract. Author URL.

Liu Z, Le K, Zhou X, Alexander J, Lin S, Bewshea C, Chanchlani N, Nice R, McDonald T, Lamb C, et al (2023). OP24 Neutralising antibody potency against SARS-CoV-2 wild-type and Omicron BA.1 and BA.4/5 variants in infliximab and vedolizumab treated patients with Inflammatory Bowel Disease after three doses of COVID-19 vaccine: a prospective multicentre cohort study. Journal of Crohn's and Colitis, 17(Supplement_1), i32-i34.

Carbery I, Lin S, Chanchlani N, Janjua M, Nice R, McDonald TJ, Bewshea C, Kennedy NA, Ahmad T, Goodhand JR, et al (2023). P649 Does serum triiodothyronine-to-thyroxine (T3/T4) ratio predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn’s disease?. Journal of Crohn's and Colitis, 17(Supplement_1), i778-i778.

Lin S, Chanchlani N, Smith R, Roberts C, Nice R, McDonald TJ, Hamilton B, Bewshea C, Kennedy NA, Goodhand JR, et al (2023). P662 Pre-treatment vitamin D concentrations do not predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn’s disease. Journal of Crohn's and Colitis, 17(Supplement_1), i791-i793.

Chanchlani N, Lin S, Hamilton B, Bewshea C, Thomas A, Smith R, Roberts C, Nice R, McDonald TJ, Goodhand JR, et al (2023). P798 Understanding anti-TNF treatment failure: mechanisms and management of loss of response to anti-TNF therapy, three-year data from the PANTS study. Journal of Crohn's and Colitis, 17(Supplement_1), i928-i930.

Dawed AY, Mari A, Brown A, McDonald TJ, Li L, Wang S, Hong M-G, Sharma S, Robertson NR, Mahajan A, et al (2023). Pharmacogenomics of GLP-1 receptor agonists: a genome-wide analysis of observational data and large randomised controlled trials. The Lancet Diabetes & Endocrinology, 11(1), 33-41.

Chanchlani N, Lin S, Smith R, Roberts C, Nice R, McDonald TJ, Hamilton B, Bishara M, Bewshea C, Kennedy NA, et al (2023). Pretreatment Vitamin D Concentrations Do Not Predict Therapeutic Outcome to Anti-TNF Therapies in Biologic-Naïve Patients with Active Luminal Crohn’s Disease. Crohn's & Colitis 360, 5(3). Abstract.

Fuhri Snethlage CM, McDonald TJ, Oram RD, de Groen P, Rampanelli E, Schimmel AWM, Holleman F, Siegelaar S, Hoekstra J, Brouwer CB, et al (2023). Residual β-Cell Function is Associated with Longer Time in Range in Individuals with Type 1 Diabetes. Diabetes Care Abstract.

Hall LA, McKay SC, Halle-Smith J, Soane J, Osei-Bordom D-C, Goodburn L, Magill L, Pinkney T, Radhakrishna G, Valle JW, et al (2023). The impact of the COVID-19 pandemic upon pancreatic cancer treatment (CONTACT Study): a UK national observational cohort study. British journal of cancer, 128(10), 1922-1932. Abstract.

Katte JC, McDonald TJ, Sobngwi E, Jones AG (2023). The phenotype of type 1 diabetes in sub-Saharan Africa. Frontiers in Public Health, 11 Abstract.

Kennedy NA, Janjua M, Chanchlani N, Lin S, Bewshea C, Nice R, McDonald TJ, Auckland C, Harries LW, Davies M, et al (2023). Vaccine escape, increased breakthrough and reinfection in infliximab-treated patients with IBD during the Omicron wave of the SARS-CoV-2 pandemic. Gut, 72(2), 295-305. Abstract. Author URL.

Chanchlani N, Lin S, Chee D, Hamilton B, Nice R, Arkir Z, Bewshea C, Cipriano B, Derikx LAAP, Dunlop A, et al (2022). Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients. J Crohns Colitis, 16(3), 389-397. Abstract. Author URL.

Lin S, Kennedy NA, Saifuddin A, Sandoval DM, Reynolds CJ, Seoane RC, Kottoor SH, Pieper FP, Lin K-M, Butler DK, et al (2022). Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab. Nat Commun, 13(1). Abstract. Author URL.

Taylor GS, Shaw AC, Smith K, Wason J, McDonald TJ, Oram RA, Stevenson E, Shaw JAM, West DJ (2022). Capturing the real-world benefit of residual β-cell function during clinically important time-periods in established Type 1 diabetes. Diabet Med, 39(5).

AIMS: Many individuals with type 1 diabetes retain residual β-cell function, with increased endogenous insulin secretion associated with reduced hyperglycaemia, hypoglycaemia and glycaemic variability. However, it is unknown when these improvements occur during the day. Dysglycaemia is common in overnight and postprandial periods and associated with diabetes complications. Therefore, this study aimed to determine the influence of residual β-cell function upon nocturnal and postprandial glycaemic control in established type 1 diabetes. METHODS: Under free-living conditions, 66 participants wore a blinded continuous glucose monitor (CGM), kept a food diary, and completed a stimulated urine C-peptide creatinine (UCPCR) test. Nocturnal, and postprandial CGM outcomes (participant means and discrete event analysis) were compared between UCPCR groups: undetectable (Cpepund ), low (Cpeplow : 0.001-0.19 nmol/mmol) and high (Cpephigh : ≥0.2 nmol/mmol). RESULTS: Greater β-cell function was associated with incremental improvements in glycaemia. Cpephigh spent significantly greater time in normoglycaemia than Cpepund overnight (76 ± 20% vs. 58 ± 20%, p = 0.005) and 0-300 mins postprandially (68 ± 22% vs. 51 ± 22%, p = 0.045), while also having reducing nocturnal variability (SD 1.12 ± 0.41 vs. 1.52 ± 0.43 mmol/L, p = 0.010). Analysis of individual events, controlling for diabetes duration, BMI, basal insulin, use of a continuous or flash glucose monitor and (for postprandial) meal type, carbohydrate and bolus insulin intake, replicated the group findings, additionally demonstrating Cpepund had increased hyperglycaemia versus Cpeplow overnight and increased postprandial hypoglycaemic events compared with Cpephigh. For all participants, breakfast had a significantly higher incremental area under the curve than lunch and dinner. CONCLUSIONS: Residual β-cell function is associated with improved nocturnal and postprandial glycaemic control. These data may be of clinical importance for identifying specific periods and individuals where further glycaemic management strategies would be beneficial.

Abstract. Author URL.

Wesolowska-Andersen A, Brorsson CA, Bizzotto R, Mari A, Tura A, Koivula R, Mahajan A, Vinuela A, Tajes JF, Sharma S, et al (2022). Four groups of type 2 diabetes contribute to the etiological and clinical heterogeneity in newly diagnosed individuals: an IMI DIRECT study. Cell Reports Medicine, 3(1), 100477-100477.

Chanchlani N, Lin S, Auth MK, Lee CL, Robbins H, Looi S, Murugesan SV, Riley T, Preston C, Stephenson S, et al (2022). Implications for sequencing of biologic therapy and choice of second <scp>anti‐TNF</scp> in patients with inflammatory bowel disease: results from the <scp>IMmunogenicity</scp> to Second <scp>Anti‐TNF</scp> therapy (<scp>IMSAT</scp>) therapeutic drug monitoring study. Alimentary Pharmacology & Therapeutics, 56(8), 1250-1263.

SummaryBackgroundAnti‐drug antibodies are associated with treatment failure to anti‐TNF agents in patients with inflammatory bowel disease (IBD).AimTo assess whether immunogenicity to a patient's first anti‐TNF agent would be associated with immunogenicity to the second, irrespective of drug sequenceMethodsWe conducted a UK‐wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti‐TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti‐TNF agent, defined at any timepoint as an anti‐TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab.ResultsIn patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27–3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46–4.80, p < 0.001). For each 10‐fold increase in anti‐infliximab and anti‐adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38–2.17, p < 0.001) and 1.99 (95%CI 1.34–2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39–4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti‐TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure.ConclusionIrrespective of drug sequence, immunogenicity to the first anti‐TNF agent was associated with immunogenicity to the second, which was mitigated by the introduction of an immunomodulator in patients with immunogenic, but not pharmacodynamic treatment failure.

Abstract.

Grace SL, Bowden J, Walkey HC, Kaur A, Misra S, Shields BM, McKinley TJ, Oliver NS, McDonald TJ, Johnston DG, et al (2022). Islet Autoantibody Level Distribution in Type 1 Diabetes and Their Association with Genetic and Clinical Characteristics. J Clin Endocrinol Metab, 107(12), e4341-e4349. Abstract. Author URL.

Lin S, Kennedy NA, Saifuddin A, Muñoz Sandoval D, Reynolds CJ, Seoane RC, Kottoor SH, Pieper FP, Lin KM, Butler DK, et al (2022). OP22 Antibody decay, T cell immunity and breakthrough infections following SARS-CoV-2 vaccination in infliximab- and vedolizumab-treated patients. Journal of Crohn's & colitis, 16(Suppl 1), i023-i025. Abstract.

Nice R, Goodhand JR, Kennedy N, Ahmad T, Winyard P, McDonald TJ (2022). P196 Pre-treatment antibodies to infliximab and adalimumab are common but are not associated with anti-TNF treatment failure. Journal of Crohn's and Colitis, 16(Supplement_1), i256-i256.

Shields BM, Dennis JM, Angwin CD, Warren F, Henley WE, Farmer AJ, Sattar N, Holman RR, Jones AG, Pearson ER, et al (2022). Patient stratification for determining optimal second-line and third-line therapy for type 2 diabetes: the TriMaster study. Nature Medicine, 29(2), 376-383.

Chee D, Nice R, Hamilton B, Jones E, Hawkins S, Redstone C, Cairnes V, Pohl K, Chanchlani N, Lin S, et al (2022). Patient-led Remote IntraCapillary pharmacoKinetic Sampling (fingerPRICKS) for Therapeutic Drug Monitoring in patients with Inflammatory Bowel Disease. J Crohns Colitis, 16(2), 190-198.

BACKGROUND AND AIMS: Because of COVID-19 public health restrictions, telemedicine has replaced conventional outpatient follow up for most patients with chronic immune-mediated inflammatory disorders treated with biologic drugs. Innovative solutions to facilitate remote therapeutic drug monitoring are therefore required. Low-volume intracapillary blood sampling can be undertaken by patients at home and samples returned by post to central laboratories. We sought to report the effect of the COVID-19 pandemic on requests for therapeutic drug monitoring and the equivalence, acceptability and effectiveness of low volume Patient-led Remote IntraCapillary pharmacoKinetic Sampling [fingerPRICKS] compared to conventional venepuncture. METHODS: We undertook a cross-sectional blood sampling methods comparison study and compared sample types using linear regression models. Drug and antidrug antibody levels were measured using standard ELISAs. Acceptability was assessed using a purpose-designed questionnaire. RESULTS: Therapeutic drug monitoring requests for adalimumab (96.5 [70.5-106] per week to 52 [33.5-57.0], p < 0.001) but not infliximab (184.5 [161.2-214.2] to 161 [135-197.5], p = 0.34) reduced during the first UK stay-at-home lockdown compared with the preceding 6 months. Fingerprick sampling was equivalent to conventional venepuncture for adalimumab, infliximab, vedolizumab and ustekinumab drug, and anti-adalimumab and anti-infliximab antibody levels. The median [interquartile range] volume of serum obtained using intracapillary sampling was 195 µL [130-210]. More than 87% [90/103] of patients agreed that intracapillary testing was easy and 69% [71/103] preferred it to conventional venepuncture. In routine care, 75.3% [58/77] of patients returned two blood samples within 14 days to permit remote assessment of biologic therapeutic drug monitoring. CONCLUSIONS: Therapeutic drug monitoring can be undertaken using patient-led remote intracapillary blood sampling and has the potential to be a key adjunct to telemedicine in patients with immune-mediated inflammatory diseases.

Abstract. Author URL.

Meek CL, Oram RA, McDonald TJ, Feig DS, Hattersley AT, Murphy HR (2022). Response to Comment on Meek et al. Reappearance of C-Peptide During the Third Trimester in Type 1 Diabetes Pregnancy: Pancreatic Regeneration or Fetal Hyperinsulinism? Diabetes Care 2021;44:1826-1834. Diabetes Care, 45(2), e43-e44. Author URL.

Eason RJ, Thomas NJ, Hill AV, Knight BA, Carr A, Hattersley AT, McDonald TJ, Shields BM, Jones AG, Grp SS, et al (2022). Routine islet autoantibody testing in clinically diagnosed adult-onset type 1 diabetes can help identify misclassification and guide successful insulin cessation. DIABETOLOGIA, 65(SUPPL 1), S153-S154. Author URL.

Taylor GS, Shaw A, Scragg JH, Smith K, Campbell MD, McDonald TJ, Shaw JA, Ross MD, West DJ (2022). Type 1 Diabetes Patients with Different Residual Beta-Cell Function but Similar Age, HBA1c, and Cardiorespiratory Fitness Have Differing Exercise-Induced Angiogenic Cell Mobilisation. Frontiers in Endocrinology, 13 Abstract.

Lin S, Chanchlani N, Carbery I, Janjua M, Nice R, McDonald TJ, Bewshea C, Kennedy NA, Ahmad T, Selinger CP, et al (2022). Understanding <scp>anti‐TNF</scp> treatment failure: does serum triiodothyronine‐to‐thyroxine (<scp>T3</scp>/<scp>T4</scp>) ratio predict therapeutic outcome to <scp>anti‐TNF</scp> therapies in biologic‐naïve patients with active luminal Crohn's disease?. Alimentary Pharmacology & Therapeutics, 56(5), 783-793. Abstract.

(2021). 57th EASD Annual Meeting of the European Association for the Study of Diabetes. Diabetologia, 64(Suppl 1), 1-380.

Chee D, Nice R, Hamilton B, Jones E, Hawkins S, Redstone C, Cairnes V, Pohl K, Kennedy N, Ahmad T, et al (2021). 855 PATIENT-LED REMOTE INTRACAPILLARY PHARMACOKINETIC SAMPLING (FINGERPRICKS): VALIDATION AND ACCEPTABILITY FOR HOME THERAPEUTIC DRUG MONITORING IN PATIENTS WITH IBD IN THE COVID-19 PANDEMIC. Gastroenterology, 160(6), s-173.

MEEK CL, ORAM RA, MCDONALD TJ, FEIG D, HATTERSLEY AT, MURPHY HR (2021). 94-OR: Reappearance of C-Peptide during the Third Trimester in Type 1 Diabetes Pregnancy: Pancreatic Regeneration or Fetal Hyperinsulinism?. Diabetes, 70(Supplement_1).

Kennedy NA, Goodhand JR, Bewshea C, Nice R, Chee D, Lin S, Chanchlani N, Butterworth J, Cooney R, Croft NM, et al (2021). Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab. Gut, 70(5), 865-875.

ObjectiveAntitumour necrosis factor (anti-TNF) drugs impair protective immunity following pneumococcal, influenza and viral hepatitis vaccination and increase the risk of serious respiratory infections. We sought to determine whether infliximab-treated patients with IBD have attenuated serological responses to SARS-CoV-2 infections.DesignAntibody responses in participants treated with infliximab were compared with a reference cohort treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody that is not associated with impaired vaccine responses or increased susceptibility to systemic infections. 6935 patients were recruited from 92 UK hospitals between 22 September and 23 December 2020.ResultsRates of symptomatic and proven SARS-CoV-2 infection were similar between groups. Seroprevalence was lower in infliximab-treated than vedolizumab-treated patients (3.4% (161/4685) vs 6.0% (134/2250), p<0.0001). Multivariable logistic regression analyses confirmed that infliximab (vs vedolizumab; OR 0.66 (95% CI 0.51 to 0.87), p=0.0027) and immunomodulator use (OR 0.70 (95% CI 0.53 to 0.92), p=0.012) were independently associated with lower seropositivity. In patients with confirmed SARS-CoV-2 infection, seroconversion was observed in fewer infliximab-treated than vedolizumab-treated patients (48% (39/81) vs 83% (30/36), p=0.00044) and the magnitude of anti-SARS-CoV-2 reactivity was lower (median 0.8 cut-off index (0.2–5.6) vs 37.0 (15.2–76.1), p<0.0001).ConclusionsInfliximab is associated with attenuated serological responses to SARS-CoV-2 that were further blunted by immunomodulators used as concomitant therapy. Impaired serological responses to SARS-CoV-2 infection might have important implications for global public health policy and individual anti-TNF-treated patients. Serological testing and virus surveillance should be considered to detect suboptimal vaccine responses, persistent infection and viral evolution to inform public health policy.Trial registration numberISRCTN45176516.

Abstract.

Greiner R, Nyirenda M, Rodgers L, Asiki G, Banda L, Shields B, Hattersley A, Crampin A, Newton R, Jones A, et al (2021). Associations between low HDL, sex and cardiovascular risk markers are substantially different in sub-Saharan Africa and the UK: analysis of four population studies. BMJ Global Health, 6(5), e005222-e005222.

IntroductionLow high-density lipoprotein (HDL) is widely used as a marker of cardiovascular disease risk, although this relationship is not causal and is likely mediated through associations with other risk factors. Low HDL is extremely common in sub-Saharan African populations, and this has often been interpreted to indicate that these populations will have increased cardiovascular risk. We aimed to determine whether the association between HDL and other cardiovascular risk factors differed between populations in sub-Saharan Africa and the UK.MethodsWe compared data from adults living in Uganda and Malawi (n=26 216) and in the UK (n=8747). We examined unadjusted and adjusted levels of HDL and applied the WHO recommended cut-offs for prevalence estimates. We used spline and linear regression to assess the relationship between HDL and other cardiovascular risk factors.ResultsHDL was substantially lower in the African than in the European studies (geometric mean 0.9–1.2 mmol/L vs 1.3–1.8 mmol/L), with African prevalence of low HDL as high as 77%. Total cholesterol was also substantially lower (geometric mean 3.3–3.9 mmol/L vs 4.6–5.4 mmol/L). In comparison with European studies the relationship between HDL and adiposity (body mass index, waist to hip ratio) was greatly attenuated in African studies and the relationship with non-HDL cholesterol reversed: in African studies low HDL was associated with lower non-HDL cholesterol. The association between sex and HDL was also different; using the WHO sex-specific definitions, low HDL was substantially more common among women (69%–77%) than men (41%–59%) in Uganda/Malawi.ConclusionThe relationship between HDL and sex, adiposity and non-HDL cholesterol in sub-Saharan Africa is different from European populations. In sub-Saharan Africans low HDL is a marker of low overall cholesterol and sex differences are markedly attenuated. Therefore low HDL in isolation is unlikely to indicate raised cardiovascular risk and the WHO sex-based cut-offs are inappropriate.

Abstract.

Rodgers LR, Hill AV, Dennis JM, Craig Z, May B, Hattersley AT, McDonald TJ, Andrews RC, Jones A, Shields BM, et al (2021). Choice of HbA1c threshold for identifying individuals at high risk of type 2 diabetes and implications for diabetes prevention programmes: a cohort study. BMC Medicine, 19(1).

Abstract
. Background
. Type 2 diabetes (T2D) is common and increasing in prevalence. It is possible to prevent or delay T2D using lifestyle intervention programmes. Entry to these programmes is usually determined by a measure of glycaemia in the ‘intermediate’ range. This paper investigated the relationship between HbA1c and future diabetes risk and determined the impact of varying thresholds to identify those at high risk of developing T2D.
.
. Methods
. We studied 4227 participants without diabetes aged ≥ 40 years recruited to the Exeter 10,000 population cohort in South West England. HbA1c was measured at study recruitment with repeat HbA1c available as part of usual care. Absolute risk of developing diabetes within 5 years, defined by HbA1c ≥ 48 mmol/mol (6.5%), according to baseline HbA1c, was assessed by a flexible parametric survival model.
.
. Results
. The overall absolute 5-year risk (95% CI) of developing T2D in the cohort was 4.2% (3.6, 4.8%). This rose to 7.1% (6.1, 8.2%) in the 56% (n = 2358/4224) of participants classified ‘high-risk’ with HbA1c ≥ 39 mmol/mol (5.7%; ADA criteria). Under IEC criteria, HbA1c ≥ 42 mmol/mol (6.0%), 22% (n = 929/4277) of the cohort was classified high-risk with 5-year risk 14.9% (12.6, 17.2%). Those with the highest HbA1c values (44–47 mmol/mol [6.2–6.4%]) had much higher 5-year risk, 26.4% (22.0, 30.5%) compared with 2.1% (1.5, 2.6%) for 39–41 mmol/mol (5.7–5.9%) and 7.0% (5.4, 8.6%) for 42–43 mmol/mol (6.0–6.1%). Changing the entry criterion to prevention programmes from 39 to 42 mmol/mol (5.7–6.0%) reduced the proportion classified high-risk by 61%, and increased the positive predictive value (PPV) from 5.8 to 12.4% with negligible impact on the negative predictive value (NPV), 99.6% to 99.1%. Increasing the threshold further, to 44 mmol/mol (6.2%), reduced those classified high-risk by 59%, and markedly increased the PPV from 12.4 to 23.2% and had little impact on the NPV (99.1% to 98.5%).
.
. Conclusions
. A large proportion of people are identified as high-risk using current thresholds. Increasing the risk threshold markedly reduces the number of people that would be classified as high-risk and entered into prevention programmes, although this must be balanced against cases missed. Raising the entry threshold would allow limited intervention opportunities to be focused on those most likely to develop T2D.
.

Abstract.

Obura M, Beulens JWJ, Slieker R, Koopman ADM, Hoekstra T, Nijpels G, Elders P, Dekker JM, Koivula RW, Kurbasic A, et al (2021). Clinical profiles of post-load glucose subgroups and their association with glycaemic traits over time: an IMI-DIRECT study. Diabet Med, 38(2). Abstract. Author URL.

Koivula RW, Atabaki-Pasdar N, Giordano GN, White T, Adamski J, Bell JD, Beulens J, Brage S, Brunak S, De Masi F, et al (2021). Correction to: the role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study (Diabetologia, (2020), 63, 4, (744-756), 10.1007/s00125-019-05083-6). Diabetologia, 64(1), 260-261. Abstract.

Bailey SER, Abel GA, Atkins A, Byford R, Davies S-J, Mays J, McDonald TJ, Miller J, Neck C, Renninson J, et al (2021). Diagnostic performance of a faecal immunochemical test for patients with low-risk symptoms of colorectal cancer in primary care: an evaluation in the South West of England. Br J Cancer, 124(7), 1231-1236. Abstract. Author URL.

Tikhonova IA, Yang H, Bello S, Salmon A, Robinson S, Hemami MR, Dodman S, Kharechko A, Haigh RC, Jani M, et al (2021). Enzyme-linked immunosorbent assays for monitoring TNF-alpha inhibitors and antibody levels in people with rheumatoid arthritis: a systematic review and economic evaluation. Health Technol Assess, 25(8), 1-248.

BACKGROUND: Rheumatoid arthritis is a chronic autoimmune disease that primarily causes inflammation, pain and stiffness in the joints. People with severe disease may be treated with biological disease-modifying anti-rheumatic drugs, including tumour necrosis factor-α inhibitors, but the efficacy of these drugs is hampered by the presence of anti-drug antibodies. Monitoring the response to these treatments typically involves clinical assessment using response criteria, such as Disease Activity Score in 28 joints or European League Against Rheumatism. Enzyme-linked immunosorbent assays can also be used to measure drug and antibody levels in the blood. These tests may inform whether or not adjustments to treatment are required or help clinicians to understand the reasons for treatment non-response or a loss of response. METHODS: Systematic reviews were conducted to identify studies reporting on the clinical effectiveness and cost-effectiveness of using enzyme-linked immunosorbent assays to measure drug and anti-drug antibody levels to monitor the response to tumour necrosis factor-α inhibitors [adalimumab (Humira®; AbbVie, Inc. North Chicago, IL, USA), etanercept (Enbrel®; Pfizer, Inc. New York, NY, USA), infliximab (Remicade®, Merck Sharp & Dohme Limited, Hoddesdon, UK), certolizumab pegol (Cimzia®; UCB Pharma Limited, Slough, UK) and golimumab (Simponi®; Merck Sharp & Dohme Limited)] in people with rheumatoid arthritis who had either achieved treatment target (remission or low disease activity) or shown primary or secondary non-response to treatment. A range of bibliographic databases, including MEDLINE, EMBASE and CENTRAL (Cochrane Central Register of Controlled Trials), were searched from inception to November 2018. The risk of bias was assessed using the Cochrane ROBINS-1 (Risk of Bias in Non-randomised Studies - of Interventions) tool for non-randomised studies, with adaptations as appropriate. Threshold and cost-utility analyses that were based on a decision tree model were conducted to estimate the economic outcomes of adding therapeutic drug monitoring to standard care. The costs and resource use were considered from the perspective of the NHS and Personal Social Services. No discounting was applied to the costs and effects owing to the short-term time horizon of 18 months that was adopted in the economic analysis. The impact on the results of variations in testing and treatment strategies was explored in numerous clinically plausible sensitivity analyses. RESULTS: Two studies were identified: (1) a non-randomised controlled trial, INGEBIO, that compared standard care with therapeutic drug monitoring using Promonitor® assays [Progenika Biopharma SA (a Grifols-Progenika company), Derio, Spain] in Spanish patients receiving adalimumab who had achieved remission or low disease activity; and (2) a historical control study. The economic analyses were informed by INGEBIO. Different outcomes from INGEBIO produced inconsistent results in both threshold and cost-utility analyses. The cost-effectiveness of therapeutic drug monitoring varied, from the intervention being dominant to the incremental cost-effectiveness ratio of £164,009 per quality-adjusted life-year gained. However, when the frequency of testing was assumed to be once per year and the cost of phlebotomy appointments was excluded, therapeutic drug monitoring dominated standard care. LIMITATIONS: There is limited relevant research evidence and much uncertainty about the clinical effectiveness and cost-effectiveness of using enzyme-linked immunosorbent assay-based testing for therapeutic drug monitoring in rheumatoid arthritis patients. INGEBIO had serious limitations in relation to the National Institute for Health and Care Excellence scope: only one-third of participants had rheumatoid arthritis, the analyses were mostly not by intention to treat and the follow-up was 18 months only. Moreover, the outcomes might not be generalisable to the NHS. CONCLUSIONS: Based on the available evidence, no firm conclusions could be made about the cost-effectiveness of therapeutic drug monitoring in England and Wales. FUTURE WORK: Further controlled trials are required to assess the impact of using enzyme-linked immunosorbent assays for monitoring the anti-tumour necrosis factors in people with rheumatoid arthritis. STUDY REGISTRATION: This study is registered as PROSPERO CRD42018105195. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 8. See the NIHR Journals Library website for further project information.

Abstract. Author URL.

(2021). Erratum to: Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications (Diabetes Care 2021; 44: 390–398). Diabetes Care, 44(4). Abstract.

Jeyam A, Colhoun H, McGurnaghan S, Blackbourn L, McDonald TJ, Palmer CNA, McKnight JA, Strachan MWJ, Patrick AW, Chalmers J, et al (2021). Erratum. Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications. Diabetes Care 2021;44:390-398. Diabetes Care

Niwaha AJ, Rodgers LR, Greiner R, Balungi PA, Mwebaze R, McDonald TJ, Hattersley AT, Shields BM, Nyirenda MJ, Jones AG, et al (2021). HbA1c performs well in monitoring glucose control even in populations with high prevalence of medical conditions that may alter its reliability: the OPTIMAL observational multicenter study. BMJ Open Diabetes Research & Care, 9(1), e002350-e002350.

IntroductionThe utility of HbA1c (glycosylated hemoglobin) to estimate glycemic control in populations of African and other low-resource countries has been questioned because of high prevalence of other medical conditions that may affect its reliability. Using continuous glucose monitoring (CGM), we aimed to determine the comparative performance of HbA1c, fasting plasma glucose (FPG) (within 5 hours of a meal) and random non-fasting glucose (RPG) in assessing glycemic burden.Research design and methodsWe assessed the performance of HbA1c, FPG and RPG in comparison to CGM mean glucose in 192 Ugandan participants with type 2 diabetes. Analysis was undertaken in all participants, and in subgroups with and without medical conditions reported to affect HbA1c reliability. We then assessed the performance of FPG and RPG, and optimal thresholds, in comparison to HbA1c in participants without medical conditions thought to alter HbA1c reliability.Results32.8% (63/192) of participants had medical conditions that may affect HbA1c reliability: anemia 9.4% (18/192), sickle cell trait and/or hemoglobin C (HbC) 22.4% (43/192), or renal impairment 6.3% (12/192). Despite high prevalence of medical conditions thought to affect HbA1c reliability, HbA1c had the strongest correlation with CGM measured glucose in day-to-day living (0.88, 95% CI 0.84 to 0.91), followed by FPG (0.82, 95% CI 0.76 to 0.86) and RPG (0.76, 95% CI 0.69 to 0.81). Among participants without conditions thought to affect HbA1c reliability, FPG and RPG had a similar diagnostic performance in identifying poor glycemic control defined by a range of HbA1c thresholds. FPG of ≥7.1 mmol/L and RPG of ≥10.5 mmol/L correctly identified 78.2% and 78.8%, respectively, of patients with an HbA1c of ≥7.0%.ConclusionsHbA1c is the optimal test for monitoring glucose control even in low-income and middle-income countries where medical conditions that may alter its reliability are prevalent; FPG and RPG are valuable alternatives where HbA1c is not available.

Abstract.

Kennedy NA, Lin S, Goodhand JR, Chanchlani N, Hamilton B, Bewshea C, Nice R, Chee D, Cummings JF, Fraser A, et al (2021). Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD. Gut, 70(10), 1884-1893. Abstract. Author URL.

Jones AG, McDonald TJ, Shields BM, Hagopian W, Hattersley AT (2021). Latent Autoimmune Diabetes of Adults (LADA) is Likely to Represent a Mixed Population of Autoimmune (Type 1) and Nonautoimmune (Type 2) Diabetes. Diabetes Care, 44(6), 1243-1251.

Latent autoimmune diabetes of adults (LADA) is typically defined as a new diabetes diagnosis after 35 years of age, presenting with clinical features of type 2 diabetes, in whom a type 1 diabetes–associated islet autoantibody is detected. Identifying autoimmune diabetes is important since the prognosis and optimal therapy differ. However, the existing LADA definition identifies a group with clinical and genetic features intermediate between typical type 1 and type 2 diabetes. It is unclear whether this is due to 1) true autoimmune diabetes with a milder phenotype at older onset ages that initially appears similar to type 2 diabetes but later requires insulin, 2) a disease syndrome where the pathophysiologies of type 1 and type 2 diabetes are both present in each patient, or 3) a heterogeneous group resulting from difficulties in classification. Herein, we suggest that difficulties in classification are a major component resulting from defining LADA using a diagnostic test—islet autoantibody measurement—with imperfect specificity applied in low-prevalence populations. This yields a heterogeneous group of true positives (autoimmune type 1 diabetes) and false positives (nonautoimmune type 2 diabetes). For clinicians, this means that islet autoantibody testing should not be undertaken in patients who do not have clinical features suggestive of autoimmune diabetes: in an adult without clinical features of type 1 diabetes, it is likely that a single positive antibody will represent a false-positive result. This is in contrast to patients with features suggestive of type 1 diabetes, where false-positive results will be rare. For researchers, this means that current definitions of LADA are not appropriate for the study of autoimmune diabetes in later life. Approaches that increase test specificity, or prior likelihood of autoimmune diabetes, are needed to avoid inclusion of participants who have nonautoimmune (type 2) diabetes. Improved classification will allow improved assignment of prognosis and therapy as well as an improved cohort in which to analyze and better understand the detailed pathophysiological components acting at onset and during disease progression in late-onset autoimmune diabetes.

Abstract.

Katte JC, Lemdjo G, Dehayem MY, Jones AG, McDonald TJ, Sobngwi E, Mbanya JC (2021). Mortality amongst children and adolescents with type 1 diabetes in. <scp>sub‐Saharan</scp>. Africa: the case study of the Changing Diabetes in Children program in Cameroon. Pediatric Diabetes, 23(1), 33-37.

Kennedy NA, Goodhand J, Bewshea C, Nice R, Chee D, Lin S, Chanchlani N, Butterworth J, Cooney R, Croft N, et al (2021). OP03 Anti-SARS-CoV2 antibody responses are attenuated in patients with Inflammatory Bowel Disease treated with infliximab. Journal of Crohn's & colitis, 15(Suppl 1), S002-S004. Abstract.

Tura A, Grespan E, Göbl CS, Koivula RW, Franks PW, Pearson ER, Walker M, Forgie IM, Giordano GN, Pavo I, et al (2021). Profiles of Glucose Metabolism in Different Prediabetes Phenotypes, Classified by Fasting Glycemia, 2-Hour OGTT, Glycated Hemoglobin, and 1-Hour OGTT: an IMI DIRECT Study. Diabetes, 70(9), 2092-2106. Abstract. Author URL.

Meek CL, Oram RA, McDonald TJ, Feig DS, Hattersley AT, Murphy HR, CONCEPTT Collaborative Group (2021). Reappearance of C-Peptide During the Third Trimester of Pregnancy in Type 1 Diabetes: Pancreatic Regeneration or Fetal Hyperinsulinism?. Diabetes Care, 44(8), 1826-1834. Abstract. Author URL.

Nice R, Chanchlani N, Green H, Bewshea C, Ahmad T, Goodhand JR, McDonald TJ, Perry MH, Kennedy NA (2021). Validating the positivity thresholds of drug-tolerant anti-infliximab and anti-adalimumab antibody assays. Aliment Pharmacol Ther, 53(1), 128-137. Abstract. Author URL.

Grace SL, Cooper A, Jones AG, McDonald TJ (2021). Zinc transporter 8 autoantibody testing requires age-related cut-offs. BMJ Open Diabetes Research & Care, 9(1), e002296-e002296. Abstract.

(2020). 56th EASD Annual Meeting of the European Association for the Study of Diabetes. Diabetologia, 63(S1), 1-485.

TAYLOR GS, SMITH K, SCRAGG J, BASHIR A, FLATT A, STEVENSON EJ, MCDONALD TJ, ORAM RA, SHAW JA, ROSS MD, et al (2020). 680-P: Residual ß-Cell Function in Long-Term Type 1 Diabetes is Associated with a Fivefold Greater Mobilization of Endothelial Progenitor Cells after Exercise. Diabetes, 69(Supplement_1).

Bar N, Korem T, Weissbrod O, Zeevi D, Rothschild D, Leviatan S, Kosower N, Lotan-Pompan M, Weinberger A, Le Roy CI, et al (2020). A reference map of potential determinants for the human serum metabolome. Nature, 588(7836), 135-140. Abstract.

Jeyam A, Colhoun H, McGurnaghan S, Blackbourn L, McDonald TJ, Palmer CNA, McKnight JA, Strachan MWJ, Patrick AW, Chalmers J, et al (2020). Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications. Diabetes Care, 44(2), 390-398. Abstract.

Eriksen R, Perez IG, Posma JM, Haid M, Sharma S, Prehn C, Thomas LE, Koivula RW, Bizzotto R, Prehn C, et al (2020). Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk: an IMI DIRECT study. EBioMedicine, 58, 102932-102932.

Sazonovs A, Kennedy NA, Moutsianas L, Heap GA, Rice DL, Reppell M, Bewshea CM, Chanchlani N, Walker GJ, Perry MH, et al (2020). HLA-DQA1*05 Carriage Associated with Development of Anti-Drug Antibodies to Infliximab and Adalimumab in Patients with Crohn's Disease. Gastroenterology, 158(1), 189-199.

BACKGROUND & AIMS: Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies. METHODS: We performed a genome-wide association study to identify variants associated with time to development of anti-drug antibodies in a discovery cohort of 1240 biologic-naïve patients with Crohn's disease starting infliximab or adalimumab therapy. Immunogenicity was defined as an anti-drug antibody titer ≥10 AU/mL using a drug-tolerant enzyme-linked immunosorbent assay. Significant association signals were confirmed in a replication cohort of 178 patients with inflammatory bowel disease. RESULTS: the HLA-DQA1*05 allele, carried by approximately 40% of Europeans, significantly increased the rate of immunogenicity (hazard ratio [HR], 1.90; 95% confidence interval [CI], 1.60-2.25; P = 5.88 × 10-13). The highest rates of immunogenicity, 92% at 1 year, were observed in patients treated with infliximab monotherapy who carried HLA-DQA1*05; conversely the lowest rates of immunogenicity, 10% at 1 year, were observed in patients treated with adalimumab combination therapy who did not carry HLA-DQA1*05. We confirmed this finding in the replication cohort (HR, 2.00; 95% CI, 1.35-2.98; P = 6.60 × 10-4). This association was consistent for patients treated with adalimumab (HR, 1.89; 95% CI, 1.32-2.70) or infliximab (HR, 1.92; 95% CI, 1.57-2.33), and for patients treated with anti-TNF therapy alone (HR, 1.75; 95% CI, 1.37-2.22) or in combination with an immunomodulator (HR, 2.01; 95% CI, 1.57-2.58). CONCLUSIONS: in an observational study, we found a genome-wide significant association between HLA-DQA1*05 and the development of antibodies against anti-TNF agents. A randomized controlled biomarker trial is required to determine whether pretreatment testing for HLA-DQA1*05 improves patient outcomes by helping physicians select anti-TNF and combination therapies. ClinicalTrials.gov ID: NCT03088449.

Abstract. Author URL.

Nice R, Chanchlani N, Green H, Bewshea C, Kennedy N, Ahmad T, Goodhand J, McDonald T, Perry M (2020). OP21 Positivity thresholds of total infliximab and adalimumab anti-drug antibody assay: the prevalence of clearing and transient anti-drug antibodies in a national therapeutic drug monitoring service. Journal of Crohn's and Colitis, 14(Supplement_1), s018-s019.

Tikhonova IA, Bello S, Salmon A, Robinson S, Hemami MR, Haigh RC, Jani M, McDonald TJ, Hoyle M (2020). PMS68 PROMONITOR FOR THERAPEUTIC DRUG MONITORING IN PATIENTS WITH SEVERE RHEUMATOID ARTHRITIS TREATED WITH ADALIMUMAB IN ENGLAND AND WALES. Value in Health, 23

Shepherd M, Knight BA, Laskey K, McDonald TJ (2020). Parental experiences of a diagnosis of neonatal diabetes and perceptions of newborn screening for glucose: a qualitative study. BMJ Open, 10(11). Abstract.

P B, TJ M, BA K, SE F, M L, SR S, BM S, S H, MH S, RC A, et al (2020). Patterns of post-meal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-K ATP -channel pathways.

Obura M, Beulens JWJ, Slieker R, Koopman ADM, Hoekstra T, Nijpels G, Elders P, Koivula RW, Kurbasic A, Laakso M, et al (2020). Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes: an IMI-DIRECT study. PLoS ONE, 15(11 November). Abstract.

Katte J-C, Poka-Mayap V, Niwaha A, Nakanga W, Jones A, McDonald TJ, Sobgnwi E (2020). Post-meal Urinary C-peptide creatinine ratio is a moderate measure of insulin secretion in diabetes patients in Cameroon: results from a cross-sectional study. PAMJ Clinical Medicine, 3

Taylor GS, Smith K, Capper TE, Scragg JH, Bashir A, Flatt A, Stevenson EJ, McDonald TJ, Oram RA, Shaw JA, et al (2020). Postexercise Glycemic Control in Type 1 Diabetes is Associated with Residual β-Cell Function. Diabetes Care, 43(10), 2362-2370. Abstract.

Atabaki-Pasdar N, Ohlsson M, Viñuela A, Frau F, Pomares-Millan H, Haid M, Jones AG, Thomas EL, Koivula RW, Kurbasic A, et al (2020). Predicting and elucidating the etiology of fatty liver disease: a machine learning modeling and validation study in the IMI DIRECT cohorts. PLOS Medicine, 17(6), e1003149-e1003149.

Flatt AJS, Little SA, Speight J, Leelarathna L, Walkinshaw E, Tan HK, Bowes A, Lubina-Solomon A, Holmes-Truscott E, Chadwick TJ, et al (2020). Predictors of Recurrent Severe Hypoglycemia in Adults with Type 1 Diabetes and Impaired Awareness of Hypoglycemia During the HypoCOMPaSS Study. Diabetes Care, 43(1), 44-52. Abstract. Author URL.

Walker GJ, Chanchlani N, Thomas A, Lin S, Moore L, Heerasing NM, Hendy P, Abdelrahim M, Mole S, Perry MH, et al (2020). Primary care faecal calprotectin testing in children with suspected inflammatory bowel disease: a diagnostic accuracy study. Arch Dis Child, 105(10), 957-963. Abstract. Author URL.

Bizzotto R, Jennison C, Jones AG, Kurbasic A, Tura A, Kennedy G, Bell JD, Thomas EL, Frost G, Eriksen R, et al (2020). Processes Underlying Glycemic Deterioration in Type 2 Diabetes: an IMI DIRECT Study. Diabetes Care, 44(2), 511-518. Abstract.

Jones AG, Shields BM, Dennis JM, Hattersley AT, McDonald TJ, Thomas NJ (2020). The challenge of diagnosing type 1 diabetes in older adults. Diabet Med, 37(10), 1781-1782. Author URL.

Koivula RW, Atabaki-Pasdar N, Giordano GN, White T, Adamski J, Bell JD, Beulens J, Brage S, Brunak S, De Masi F, et al (2020). The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study. Diabetologia, 63(4), 744-756.

AIMS/HYPOTHESIS: it is well established that physical activity, abdominal ectopic fat and glycaemic regulation are related but the underlying structure of these relationships is unclear. The previously proposed twin-cycle hypothesis (TC) provides a mechanistic basis for impairment in glycaemic control through the interactions of substrate availability, substrate metabolism and abdominal ectopic fat accumulation. Here, we hypothesise that the effect of physical activity in glucose regulation is mediated by the twin-cycle. We aimed to examine this notion in the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) Consortium cohorts comprised of participants with normal or impaired glucose regulation (cohort 1: N ≤ 920) or with recently diagnosed type 2 diabetes (cohort 2: N ≤ 435). METHODS: We defined a structural equation model that describes the TC and fitted this within the IMI DIRECT dataset. A second model, twin-cycle plus physical activity (TC-PA), to assess the extent to which the effects of physical activity in glycaemic regulation are mediated by components in the twin-cycle, was also fitted. Beta cell function, insulin sensitivity and glycaemic control were modelled from frequently sampled 75 g OGTTs (fsOGTTs) and mixed-meal tolerance tests (MMTTs) in participants without and with diabetes, respectively. Abdominal fat distribution was assessed using MRI, and physical activity through wrist-worn triaxial accelerometry. Results are presented as standardised beta coefficients, SE and p values, respectively. RESULTS: the TC and TC-PA models showed better fit than null models (TC: χ2 = 242, p = 0.004 and χ2 = 63, p = 0.001 in cohort 1 and 2, respectively; TC-PA: χ2 = 180, p = 0.041 and χ2 = 60, p = 0.008 in cohort 1 and 2, respectively). The association of physical activity with glycaemic control was primarily mediated by variables in the liver fat cycle. CONCLUSIONS/INTERPRETATION: These analyses partially support the mechanisms proposed in the twin-cycle model and highlight mechanistic pathways through which insulin sensitivity and liver fat mediate the association between physical activity and glycaemic control.

Abstract. Author URL.

Gudmundsdottir V, Pedersen HK, Mazzoni G, Allin KH, Artati A, Beulens JW, Banasik K, Brorsson C, Cederberg H, Chabanova E, et al (2020). Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study. Genome Medicine, 12(1).

AbstractBackgroundThe rising prevalence of type 2 diabetes (T2D) poses a major global challenge. It remains unresolved to what extent transcriptomic signatures of metabolic dysregulation and T2D can be observed in easily accessible tissues such as blood. Additionally, large-scale human studies are required to further our understanding of the putative inflammatory component of insulin resistance and T2D. Here we used transcriptomics data from individuals with (n = 789) and without (n = 2127) T2D from the IMI-DIRECT cohorts to describe the co-expression structure of whole blood that mainly reflects processes and cell types of the immune system, and how it relates to metabolically relevant clinical traits and T2D.MethodsClusters of co-expressed genes were identified in the non-diabetic IMI-DIRECT cohort and evaluated with regard to stability, as well as preservation and rewiring in the cohort of individuals with T2D. We performed functional and immune cell signature enrichment analyses, and a genome-wide association study to describe the genetic regulation of the modules. Phenotypic and trans-omics associations of the transcriptomic modules were investigated across both IMI-DIRECT cohorts.ResultsWe identified 55 whole blood co-expression modules, some of which clustered in larger super-modules. We identified a large number of associations between these transcriptomic modules and measures of insulin action and glucose tolerance. Some of the metabolically linked modules reflect neutrophil-lymphocyte ratio in blood while others are independent of white blood cell estimates, including a module of genes encoding neutrophil granule proteins with antibacterial properties for which the strongest associations with clinical traits and T2D status were observed. Through the integration of genetic and multi-omics data, we provide a holistic view of the regulation and molecular context of whole blood transcriptomic modules. We furthermore identified an overlap between genetic signals for T2D and co-expression modules involved in type II interferon signaling.ConclusionsOur results offer a large-scale map of whole blood transcriptomic modules in the context of metabolic disease and point to novel biological candidates for future studies related to T2D.

Abstract.

TAYLOR GS, SMITH K, SCRAGG J, BASHIR A, ORAM RA, MCDONALD TJ, STEVENSON EJ, SHAW JA, WEST DJ (2019). 294-OR: Type 1 Diabetes Patients with Residual Beta-Cell Function Display Improved Time in Euglycemia and Less Glycaemic Fluctuation after Exercise. Diabetes, 68(Supplement_1).

Koivula RW, Forgie IM, Kurbasic A, Viñuela A, Heggie A, Giordano GN, Hansen TH, Hudson M, Koopman ADM, Rutters F, et al (2019). Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium. Diabetologia, 62(9), 1601-1615.

AIMS/HYPOTHESIS: Here, we describe the characteristics of the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) epidemiological cohorts at baseline and follow-up examinations (18, 36 and 48 months of follow-up). METHODS: from a sampling frame of 24,682 adults of European ancestry enrolled in population-based cohorts across Europe, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm (based on age, BMI, waist circumference, use of antihypertensive medication, smoking status and parental history of type 2 diabetes) and enrolled into a prospective cohort study (n = 2127) (cohort 1, prediabetes risk). We also recruited people from clinical registries with type 2 diabetes diagnosed 6-24 months previously (n = 789) into a second cohort study (cohort 2, diabetes). Follow-up examinations took place at ~18 months (both cohorts) and at ~48 months (cohort 1) or ~36 months (cohort 2) after baseline examinations. The cohorts were studied in parallel using matched protocols across seven clinical centres in northern Europe. RESULTS: Using ADA 2011 glycaemic categories, 33% (n = 693) of cohort 1 (prediabetes risk) had normal glucose regulation and 67% (n = 1419) had impaired glucose regulation. Seventy-six per cent of participants in cohort 1 was male. Cohort 1 participants had the following characteristics (mean ± SD) at baseline: age 62 (6.2) years; BMI 27.9 (4.0) kg/m2; fasting glucose 5.7 (0.6) mmol/l; 2 h glucose 5.9 (1.6) mmol/l. At the final follow-up examination the participants' clinical characteristics were as follows: fasting glucose 6.0 (0.6) mmol/l; 2 h OGTT glucose 6.5 (2.0) mmol/l. In cohort 2 (diabetes), 66% (n = 517) were treated by lifestyle modification and 34% (n = 272) were treated with metformin plus lifestyle modification at enrolment. Fifty-eight per cent of participants in cohort 2 was male. Cohort 2 participants had the following characteristics at baseline: age 62 (8.1) years; BMI 30.5 (5.0) kg/m2; fasting glucose 7.2 (1.4) mmol/l; 2 h glucose 8.6 (2.8) mmol/l. At the final follow-up examination, the participants' clinical characteristics were as follows: fasting glucose 7.9 (2.0) mmol/l; 2 h mixed-meal tolerance test glucose 9.9 (3.4) mmol/l. CONCLUSIONS/INTERPRETATION: the IMI DIRECT cohorts are intensely characterised, with a wide-variety of metabolically relevant measures assessed prospectively. We anticipate that the cohorts, made available through managed access, will provide a powerful resource for biomarker discovery, multivariate aetiological analyses and reclassification of patients for the prevention and treatment of type 2 diabetes.

Abstract. Author URL.

Myngheer N, Allegaert K, Hattersley A, McDonald T, Kramer H, Ashcroft FM, Verhaeghe J, Mathieu C, Casteels K (2019). Erratum: Fetal macrosomia and neonatal hyperinsulinemic hypoglycemia associated with transplacental transfer of sulfonylurea in a mother with KCNJ11-related neonatal diabetes (Diabetes Care (2014) 37 (3333–3335) DOI: 10.2337/dc14-1247). Diabetes Care, 42(7). Abstract.

Wilman HR, Parisinos CA, Atabaki-Pasdar N, Kelly M, Thomas EL, Neubauer S, Jennison C, Ehrhardt B, Baum P, Schoelsch C, et al (2019). Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration. Journal of Hepatology, 71(3), 594-602. Abstract.

Lampasona V, Pittman DL, Williams AJ, Achenbach P, Schlosser M, Akolkar B, Winter WE, Watson K, Weets I, Tao Y, et al (2019). Islet Autoantibody Standardization Program 2018 Workshop: Interlaboratory Comparison of Glutamic Acid Decarboxylase Autoantibody Assay Performance. CLINICAL CHEMISTRY, 65(9), 1141-1152. Author URL.

Bowman P, McDonald TJ, Knight BA, Flanagan SE, Leveridge M, Spaull SR, Shields BM, Hammersley S, Shepherd MH, Andrews RC, et al (2019). Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-K ATP -channel pathways. BMJ Open Diabetes Research and Care, 7(1).

Objective Insulin secretion in sulfonylurea-treated KCNJ11 permanent neonatal diabetes mellitus (PNDM) is thought to be mediated predominantly through amplifying non-K ATP -channel pathways such as incretins. Affected individuals report symptoms of postprandial hypoglycemia after eating protein/fat-rich foods. We aimed to assess the physiological response to carbohydrate and protein/fat in people with sulfonylurea-treated KCNJ11 PNDM. Research design and methods 5 adults with sulfonylurea-treated KCNJ11 PNDM and five age, sex and body mass index-matched controls without diabetes had a high-carbohydrate and high-protein/fat meal on two separate mornings. Insulin(i) and glucose(g) were measured at baseline then regularly over 4 hours after the meal. Total area under the curve (tAUC) for insulin and glucose was calculated over 4 hours and compared between meals in controls and KCNJ11 cases. Results in controls, glucose values after carbohydrate and protein/fat were similar (median glucose tAUC 0-4h 21.4 vs 19.7 mmol/L, p=0.08). In KCNJ11 cases glucose levels were higher after carbohydrate than after protein/fat (median glucose tAUC 0-4h 58.1 vs 31.3 mmol/L, p=0.04). These different glycemic responses reflected different patterns of insulin secretion: in controls, insulin secretion was greatly increased after carbohydrate versus protein/fat (median insulin tAUC 0-4h 727 vs 335 pmol/L, p=0.04), but in KCNJ11 cases insulin secretion was similar after carbohydrate and protein/fat (median insulin tAUC 0-4h 327 vs 378 pmol/L, p=0.50). Conclusions Individuals with sulfonylurea-treated KCNJ11 PNDM produce similar levels of insulin in response to both carbohydrate and protein/fat meals despite carbohydrate resulting in much higher glucose levels and protein/fat resulting in relatively low glucose levels. This suggests in an inability to modulate insulin secretion in response to glucose levels, consistent with a dependence on non-K ATP pathways for insulin secretion. Trial registration number NCT02921906.

Abstract.

Marren SM, Hammersley S, McDonald TJ, Shields BM, Knight BA, Hill A, Bolt R, Tree TI, Roep BO, Hattersley AT, et al (2019). Persistent C-peptide is associated with reduced hypoglycaemia but not HbA1c in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice?. Diabet Med, 36(9), 1092-1099. Abstract. Author URL.

McKeigue PM, Spiliopoulou A, McGurnaghan S, Colombo M, Blackbourn L, McDonald TJ, Onengut-Gomuscu S, Rich SS, a Palmer CN, McKnight JA, et al (2019). Persistent C-peptide secretion in Type 1 diabetes and its relationship to the genetic architecture of diabetes. BMC Med, 17(1). Abstract. Author URL.

Bewshea CM, Ahmad T, Kennedy N, Goodhand J, McDonald T, Green H (2019). Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn's disease: a prospective, multicentre, cohort study. Lancet Gastroenterology and Hepatology

Chapman DP, Gooding KM, McDonald TJ, Shore AC (2019). Stability of urinary albumin and creatinine after 12 months storage at -20 °C and -80 °C. Pract Lab Med, 15 Abstract. Author URL.

Koopman ADM, Beulens JW, Voerman E, Rauh SP, van der Heijden AA, McDonald TJ, Langendoen-Gort M, Rutters F (2019). The association between GAD65 antibody levels and incident Type 2 Diabetes Mellitus in an adult population: a meta-analysis. Metabolism, 95, 1-7. Abstract. Author URL.

Yaghootkar H, Abbasi F, Ghaemi N, Rabbani A, Wakeling MN, Eshraghi P, Enayati S, Vakili S, Heidari S, Patel K, et al (2019). Type 1 diabetes genetic risk score discriminates between monogenic and Type 1 diabetes in children diagnosed at the age of <5 years in the Iranian population. Diabet Med, 36(12), 1694-1702. Abstract. Author URL.

Dawed AY, Zhou K, van Leeuwen N, Mahajan A, Robertson N, Koivula R, Elders PJM, Rauh SP, Jones AG, Holl RW, et al (2019). Variation in the Plasma Membrane Monoamine Transporter (PMAT) (Encoded by SLC29A4) and Organic Cation Transporter 1 (OCT1) (Encoded by SLC22A1) and Gastrointestinal Intolerance to Metformin in Type 2 Diabetes: an IMI DIRECT Study. Diabetes Care, 42(6), 1027-1033.

OBJECTIVE: Gastrointestinal adverse effects occur in 20-30% of patients with metformin-treated type 2 diabetes, leading to premature discontinuation in 5-10% of the cases. Gastrointestinal intolerance may reflect localized high concentrations of metformin in the gut. We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe gastrointestinal adverse effects. RESEARCH DESIGN AND METHODS: the study included 286 severe metformin-intolerant and 1,128 metformin-tolerant individuals from the IMI DIRECT (Innovative Medicines Initiative: DIabetes REsearCh on patient straTification) consortium. We assessed the association of patient characteristics, concomitant medication, and the burden of mutations in the SLC29A4 and SLC22A1 genes on odds of intolerance. RESULTS: Women (P < 0.001) and older people (P < 0.001) were more likely to develop metformin intolerance. Concomitant use of transporter-inhibiting drugs increased the odds of intolerance (odds ratio [OR] 1.72, P < 0.001). In an adjusted logistic regression model, the G allele at rs3889348 (SLC29A4) was associated with gastrointestinal intolerance (OR 1.34, P = 0.005). rs3889348 is the top cis-expression quantitative trait locus for SLC29A4 in gut tissue where carriers of the G allele had reduced expression. Homozygous carriers of the G allele treated with transporter-inhibiting drugs had more than three times higher odds of intolerance compared with carriers of no G allele and not treated with inhibiting drugs (OR 3.23, P < 0.001). Use of a genetic risk score derived from rs3889348 and SLC22A1 variants found that the odds of intolerance were more than twice as high in individuals who carry three or more risk alleles compared with those carrying none (OR 2.15, P = 0.01). CONCLUSIONS: These results suggest that intestinal metformin transporters and concomitant medications play an important role in the gastrointestinal adverse effects of metformin.

Abstract. Author URL.

Patel KA, Weedon MN, Shields BM, Pearson ER, Hattersley AT, McDonald TJ, UNITED study team (2019). Zinc Transporter 8 Autoantibodies (ZnT8A) and a Type 1 Diabetes Genetic Risk Score can Exclude Individuals with Type 1 Diabetes from Inappropriate Genetic Testing for Monogenic Diabetes. Diabetes Care, 42(2), e16-e17. Author URL.

Grubb A, McDonald T, Rutters F, Donnelly L, Hattersley A, Oram R, Palmer C, van der Heijden A, Carr F, Elders P, et al (2018). A Type 1 Diabetes Genetic Risk Score can Identify Patients with GAD65 Autoantibody–Positive Type 2 Diabetes Who Rapidly Progress to Insulin Therapy. Diabetes Care

Johnson MBJ, Patel K, De Franco E, Houghton J, McDonald T, Ellard S, Flanagan S, Hattersley A (2018). A Type 1 diabetes genetic risk score can discriminate monogenic autoimmunity with diabetes from early onset clustering of polygenic autoimmunity with diabetes. Diabetologia

Knight AR, Taylor EL, Lukaszewski R, Winyard PG (2018). A high-sensitivity electrochemiluminescence-based ELISA for the measurement of the oxidative stress biomarker, 3-nitrotyrosine, in human blood serum and cells. Free Radical Biology and Medicine

Shields B, McDonald T, Oram R, Hill A, Hudson M, Leete P, Pearson E, Richardson S, Morgan N, Hattersley A, et al (2018). C-peptide decline in type 1 diabetes has two phases: an initial exponential fall and a subsequent stable phase. Diabetes Care

Jones AG, McDonald TJ (2018). Comment on: "Dulaglutide treatment results in effective glycaemic control in latent autoimmune diabetes in adults (LADA): a post-hoc analysis of the AWARD-2, -4 and -5 trials". Diabetes Obes Metab, 20(6), 1549-1550. Author URL.

Clissold RL, Fulford J, Hudson M, Shields BM, McDonald TJ, Ellard S, Hattersley AT, Bingham C (2018). Exocrine pancreatic dysfunction is common in hepatocyte nuclear factor 1β-associated renal disease and can be symptomatic. Clin Kidney J, 11(4), 453-458. Abstract. Author URL.

Walker GJ, Moore L, Heerasing N, Hendy P, Perry MH, McDonald TJ, Debenham T, Bethune R, Bewshea C, Hyde C, et al (2018). Faecal calprotectin effectively excludes inflammatory bowel disease in 789 symptomatic young adults with/without alarm symptoms: a prospective UK primary care cohort study. Aliment Pharmacol Ther, 47(8), 1103-1116. Abstract. Author URL.

MCKEIGUE P, SPILIOPOULOU A, MCGURNAGHAN S, COLOMBO M, MCDONALD TJ, COLHOUN H (2018). Genotypic Associations with C-Peptide Persistence in People with Type 1 Diabetes. Diabetes, 67(Supplement_1).

Perry MH, McDonald TJ (2018). Method Comparison Between ELISAs Suggests Therapeutic Ranges for Infliximab Should be Assay-Specific. J Appl Lab Med, 3(3), 515-517. Author URL.

Dennis J, Shields B, Hill A, Knight B, McDonald T, Rodgers L, Weedon M, Henley W, Sattar N, Holman R, et al (2018). Precision medicine in Type 2 diabetes: Clinical markers of insulin resistance are associated with altered short- and long-term glycemic response to DPP-4 inhibitor therapy. Diabetes Care

Teare HJA, de Masi F, Banasik K, Barnett A, Herrgard S, Jablonka B, Postma JWM, McDonald TJ, Forgie I, Chmura PJ, et al (2018). The governance structure for data access in the DIRECT consortium: an innovative medicines initiative (IMI) project. Life Sci Soc Policy, 14(1). Abstract. Author URL.

Thomas N, Grubb A, McDonald T, Hill A, Weedon M, Oram R, Hattersley A, Jones A (2018). Type 1 diabetes leading to severe insulin deficiency occurs after 30 years of age and is commonly treated as type 2 diabetes in clinical practice. DIABETOLOGIA, 61, S152-S152. Author URL.

McDonald T (2017). AIDS to correct genetic diagnosis in mody: being smarter with laboratory medicine. Pathology, 49

Chakera AJ, McDonald TJ, Knight BA, Vaidya B, Jones AG (2017). Current laboratory requirements for adrenocorticotropic hormone and renin/aldosterone sample handling are unnecessarily restrictive. Clin Med (Lond), 17(1), 18-21. Abstract. Author URL.

McDonald T (2017). Heterogeneity of type 1 diabetes. Pathology, 49

McDonald T (2017). Neonatal biochemistry: advances in neonatal diabetes. Pathology, 49

Shields B, Shepherd M, Hudson M, McDonald T, Colclough K, Peters J, Knight B, Hyde C, Ellard S, Pearson E, et al (2017). Population-based assessment of a biomarker-based screening pathway to aid diagnosis of monogenic diabetes in young-onset patients. Diabetes Care

Davidson J, McDonald T, Sutherland C, Mostazir M, VanAalten L, Wilkin T (2017). Proinsulin is stable at room temperature for 24 hours in EDTA: a clinical laboratory analysis (adAPT 3). PLoS One, 12(4). Abstract. Author URL.

Hope SV, Knight BA, Shields BM, Hill AV, Choudhary P, Strain WD, McDonald TJ, Jones AG (2017). Random non-fasting C-peptide testing can identify patients with insulin-treated type 2 diabetes at high risk of hypoglycaemia. Diabetologia

McDonald TJ, Besser RE, Perry M, Babiker T, Knight BA, Shepherd MH, Ellard S, Flanagan SE, Hattersley AT (2017). Screening for neonatal diabetes at day 5 of life using dried blood spot glucose measurement. Diabetologia, 60(11), 2168-2173. Abstract.

Shepherd M, Colclough K, McDonald TJ (2017). Tests aiding diagnosis of monogenic diabetes. Practical Diabetes, 34(6), 217-220a.

McDonald T (2017). The sequencer will see you now: getting the correct genetic diagnosis in maturity onset diabetes of the young. Pathology, 49

Oram RA, Patel K, Hill A, Shields B, McDonald TJ, Jones A, Hattersley AT, Weedon MN (2016). A Type 1 Diabetes Genetic Risk Score can Aid Discrimination Between Type 1 and Type 2 Diabetes in Young Adults. Diabetes Care, 39(3), 337-344. Abstract. Author URL.

Perry M, O'Connor J, James AJ, Cudmore AP, Lewis AV, Salzmann MB, McDonald TJ (2016). A cautionary tale: Unforeseen consequences of lean processing in a blood sciences laboratory. Clin Biochem, 49(16-17), 1311-1312. Author URL.

Williams GM, Long AE, Wilson IV, Aitken RJ, Wyatt RC, McDonald TJ, Wong FS, Hattersley AT, Williams AJK, Bingley PJ, et al (2016). Beta cell function and ongoing autoimmunity in long-standing, childhood onset type 1 diabetes. Diabetologia, 59(12), 2722-2726. Abstract. Author URL.

McDonald TJ, Perry MH (2016). Detection of C-Peptide in Urine as a Measure of Ongoing Beta Cell Function. Methods Mol Biol, 1433, 93-102. Abstract. Author URL.

Seelig E, Timper K, Falconnier C, Stoeckli R, Bilz S, Oram R, McDonald TJ, Donath MY (2016). Interleukin-1 antagonism in type 1 diabetes of long duration. Diabetes Metab, 42(6), 453-456. Author URL.

Johnson MB, Flanagan SE, Martins TB, Hill HR, Hattersley AT, McDonald TJ (2016). Low IgE is a Useful Tool to Identify STAT3 Gain-of-Function Mutations. Clin Chem, 62(11), 1536-1538. Author URL.

McDonald TJ, Besser REJ, Perry MH, Babiker T, Hattersley AT (2016). Newborn screening by blood spot glucose can diagnose neonatal diabetes at day 5 of life. DIABETIC MEDICINE, 33, 73-73. Author URL.

Hope SV, Knight BA, Shields BM, Hattersley AT, McDonald TJ, Jones AG (2016). Random non-fasting C-peptide: bringing robust assessment of endogenous insulin secretion to the clinic. Diabet Med, 33(11), 1554-1558. Abstract. Author URL.

Shepherd M, Shields B, Hammersley S, Hudson M, McDonald TJ, Colclough K, Oram RA, Knight B, Hyde C, Cox J, et al (2016). Systematic Population Screening, Using Biomarkers and Genetic Testing, Identifies 2.5% of the U.K. Pediatric Diabetes Population with Monogenic Diabetes. Diabetes Care, 39(11), 1879-1888. Abstract. Author URL.

Oram RA, Hill A, Mcdonald TJ, Patel KA, Jones AG, Hattersley AT, Weedon MN (2015). 3. A Novel, Inexpensive Test can Discriminate between Type 1 and Type 2 Diabetes (1745-P). Nederlands Tijdschrift voor Diabetologie, 13(3), 57-57.

Parfitt C, Church D, Armston A, Couchman L, Evans C, Wark G, McDonald TJ (2015). Commercial insulin immunoassays fail to detect commonly prescribed insulin analogues. CLINICAL BIOCHEMISTRY, 48(18), 1354-1357. Author URL.

Perry M, Bewshea C, Brown R, So K, Ahmad T, McDonald T (2015). Infliximab and adalimumab are stable in whole blood clotted samples for seven days at room temperature. Ann Clin Biochem, 52(Pt 6), 672-674. Abstract. Author URL.

McDonald TJ, Oram RA, Vaidya B (2015). Investigating hyperkalaemia in adults. BMJ, 351 Author URL.

Oram RA, McDonald TJ, Shields BM, Hudson MM, Shepherd MH, Hammersley S, Pearson ER, Hattersley AT, UNITED Team (2015). Most people with long-duration type 1 diabetes in a large population-based study are insulin microsecretors. Diabetes Care, 38(2), 323-328. Abstract. Author URL.

McDonald TJ, Oram RA, Vaidya B (2015). RATIONAL TESTING Investigating hyperkalaemia in adults. BMJ-BRITISH MEDICAL JOURNAL, 351 Author URL.

Espeland MA, Probstfield J, Hire D, Redmon JB, Evans GW, Coday M, Lewis CE, Johnson KC, Wilmoth S, Bahnson J, et al (2015). Systolic blood pressure control among individuals with type 2 diabetes: a comparative effectiveness analysis of three interventions. American Journal of Hypertension, 28(8), 995-1009. Abstract.

Flanagan SE, Haapaniemi E, Russell MA, Caswell R, Allen HL, De Franco E, McDonald TJ, Rajala H, Ramelius A, Barton J, et al (2014). Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease. Nat Genet, 46(8), 812-814. Abstract. Author URL.

McDonald TJ, Warren RE (2014). Diagnostic confusion? Repeat HbA1c for the diagnosis of diabetes. DIABETIC MEDICINE, 31, 72-72. Author URL.

Koivula RW, Heggie A, Barnett A, Cederberg H, Hansen TH, Koopman AD, Ridderstråle M, Rutters F, Vestergaard H, Gupta R, et al (2014). Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: Rationale and design of the epidemiological studies within the IMI DIRECT Consortium. Diabetologia, 57(6), 1132-1142. Abstract.

Koivula RW, Heggie A, Barnett A, Cederberg H, Hansen TH, Koopman AD, Ridderstråle M, Rutters F, Vestergaard H, Gupta R, et al (2014). Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: rationale and design of the epidemiological studies within the IMI DIRECT Consortium. Diabetologia

Jones AG, McDonald TJ, Hattersley AT, Shields BM (2014). Effect of the holiday season in patients with diabetes: Glycemia and lipids increase postholiday, but the effect is small and transient. Diabetes Care, 37(5).

Oram RA, Jones AG, Besser RE, Knight BA, Shields BM, Brown RJ, Hattersley AT, McDonald TJ (2014). Erratum to: the majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells. Diabetologia, 57(1). Author URL.

Myngheer N, Allegaert K, Hattersley A, McDonald T, Kramer H, Ashcroft FM, Verhaeghe J, Mathieu C, Casteels K (2014). Fetal macrosomia and neonatal hyperinsulinemic hypoglycemia associated with transplacental transfer of sulfonylurea in a mother with KCNJ11-related neonatal diabetes. Diabetes Care, 37(12), 3333-3335. Abstract. Author URL.

Babiker T, Perry M, McDonald T, Brooke A, O'Connor J (2014). High testosterone? Look again!. Endocrine Abstracts

Oram RA, Brooks AM, Forbes S, Eckoldt S, Smith RM, Choudhary P, Rosenthal MJ, Johnson P, Rutter MK, Burling KA, et al (2014). Home urine C-peptide creatinine ratio can be used to monitor islet transplant function. Diabetes Care, 37(6), 1737-1740. Abstract. Author URL.

Aitken RJ, Wilson IV, Long AE, Williams AJK, McDonald TJ, Gillespie KM, Wong FS, Hattersley AT, Bingley PJ (2014). Residual beta cell function in long-standing childhood onset Type 1 diabetes. DIABETIC MEDICINE, 31, 19-20. Author URL.

Hamilton AJ, Bingham C, McDonald TJ, Cook PR, Caswell RC, Weedon MN, Oram RA, Shields BM, Shepherd M, Inward CD, et al (2014). The HNF4A R76W mutation causes atypical dominant Fanconi syndrome in addition to a β cell phenotype. J Med Genet, 51(3), 165-169. Abstract. Author URL.

Thong KY, Mcdonald TJ, Hattersley AT, Blann AD, Ramtoola S, Duncan C, Carr S, Adamson K, Nayak AU, Khurana R, et al (2014). The association between postprandial urinary C-peptide creatinine ratio and the treatment response to liraglutide: a multi-centre observational study. Diabetic Medicine, 31(4), 403-411.

Aims: the response to glucagon-like peptide 1 receptor agonist treatment may be influenced by endogenous β-cell function. We investigated whether urinary C-peptide creatinine ratio assessed before or during liraglutide treatment was associated with treatment response. Methods: a single, outpatient urine sample for urinary C-peptide creatinine ratio was collected 2 h after the largest meal of the day among two separate groups: (1) subjects initiating liraglutide (0.6 → 1.2 mg daily) or (2) subjects already treated with liraglutide for 20-32 weeks. The associations between pretreatment and on-treatment urinary C-peptide creatinine ratio and HbA1c change at 32 weeks were assessed using univariate and multivariate analyses (the ratio was logarithm transformed for multivariate analyses). Changes in HbA1c according to pretreatment urinary C-peptide creatinine ratio quartiles are shown. Results: One hundred and sixteen subjects (70 pretreatment, 46 on treatment) with Type 2 diabetes from 10 diabetes centres were studied. In univariate analyses, neither pretreatment nor on-treatment urinary C-peptide creatinine ratio correlated with HbA1c change (Spearman rank correlation coefficient, r = -0.17, P = 0.17 and r = -0.20, P = 0.19, respectively). In multi-linear regression analyses, entering baseline HbA1c and log urinary C-peptide creatinine ratio, pretreatment and on-treatment log urinary C-peptide creatinine ratio became significantly associated with HbA1c change (P = 0.048 and P = 0.040, respectively). Mean (sd) HbA1c changes from baseline in quartiles 1 to 4 of pretreatment urinary C-peptide creatinine ratio were -3 ± 17 mmol/mol (-0.3 ± 1.6%) (P = 0.52), -12 ± 15 mmol/mol (-1.1 ± 1.4%) (P = 0.003), -11 ± 13 mmol/mol (-1.0 ± 1.2%) (P = 0.002) and -12±17 mmol/mol (-1.1±1.6%) (P=0.016), respectively. Conclusions: Postprandial urinary C-peptide creatinine ratios before and during liraglutide treatment were weakly associated with the glycaemic response to treatment. Low pretreatment urinary C-peptide creatinine ratio may be more useful than higher values by predicting poorer glycaemic response. © 2013 Diabetes UK.

Abstract.

Oram RA, Jones AG, Besser REJ, Knight BA, Shields BM, Brown RJ, Hattersley AT, McDonald TJ (2014). The majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells. Diabetologia, 57(1), 187-191. Abstract.

Nowak N, Szopa M, Thanabalasingham G, McDonald TJ, Colclough K, Skupien J, James TJ, Kiec-Wilk B, Kozek E, Mlynarski W, et al (2013). Cystatin C is not a good candidate biomarker for HNF1A-MODY. ACTA DIABETOLOGICA, 50(5), 815-820. Author URL.

Oram RA, Jones AG, Besser REJ, Knight BA, Shields BM, Brown RJ, Hattersley AT, McDonald TJ (2013). Erratum to: the majority of patients with long-duration type 1 diabetes are insulin microsecretors and have functioning beta cells. Diabetologia, 57(1), 262-262.

Besser REJ, Shields BM, Hammersley SE, Colclough K, McDonald TJ, Gray Z, Heywood JJN, Barrett TG, Hattersley AT (2013). Home urine C-peptide creatinine ratio (UCPCR) testing can identify type 2 and MODY in pediatric diabetes. Pediatr Diabetes, 14(3), 181-188. Abstract. Author URL.

Flanagan SE, MacKay DJG, Greeley SAW, McDonald TJ, Mericq V, Hassing J, Richmond EJ, Martin WR, Acerini C, Kaulfers AM, et al (2013). Hypoglycaemia following diabetes remission in patients with 6q24 methylation defects: Expanding the clinical phenotype. Diabetologia, 56(1), 218-221.

Flanagan SE, Mackay DJG, Greeley SAW, McDonald TJ, Mericq V, Hassing J, Richmond EJ, Martin WR, Acerini C, Kaulfers AM, et al (2013). Hypoglycaemia following diabetes remission in patients with 6q24 methylation defects: expanding the clinical phenotype. Diabetologia, 56(1), 218-221. Author URL.

Oram RA, McDonald TJ, Vaidya B (2013). Investigating hypokalaemia. BMJ, 347 Author URL.

McDonald TJ, Ellard S (2013). Maturity onset diabetes of the young: identification and diagnosis. Ann Clin Biochem, 50(Pt 5), 403-415. Abstract. Author URL.

Steele AM, Wensley KJ, Brewer E, Shields BM, Hattersley AT, McDonald TJ (2013). Preanalytical sample handling of venous blood: How to ensure your glucose measurement is accurate and reliable. Practical Diabetes, 30(3), 128-131. Abstract.

Thong KY, Mcdonald TJ, Hattersley AT, Blann AD, Ramtoola S, Duncan C, Carr S, Adamson K, Nayak AU, Khurana R, et al (2013). The association between postprandial urinary C-peptide creatinine ratio and the treatment response to liraglutide: a multi-centre observational study. Diabetic Medicine

Hope SV, Jones AG, Goodchild E, Shepherd M, Besser REJ, Shields B, Mcdonald T, Knight BA, Hattersley A (2013). Urinary C-peptide creatinine ratio detects absolute insulin deficiency in Type 2 diabetes. Diabetic Medicine, 30(11), 1342-1348.

Aims: to determine the prevalence and clinical characteristics of absolute insulin deficiency in long-standing Type 2 diabetes, using a strategy based on home urinary C-peptide creatinine ratio measurement. Methods: We assessed the urinary C-peptide creatinine ratios, from urine samples taken at home 2 h after the largest meal of the day, in 191 insulin-treated subjects with Type 2 diabetes (diagnosis age ≥45 years, no insulin in the first year). If the initial urinary C-peptide creatinine ratio was ≤0.2 nmol/mmol (representing absolute insulin deficiency), the assessment was repeated. A standardized mixed-meal tolerance test with 90-min stimulated serum C-peptide measurement was performed in nine subjects with a urinary C-peptide creatinine ratio ≤ 0.2 nmol/mmol (and in nine controls with a urinary C-peptide creatinine ratio >0.2 nmol/mmol) to confirm absolute insulin deficiency. Results: a total of 2.7% of participants had absolute insulin deficiency confirmed by a mixed-meal tolerance test. They were identified initially using urinary C-peptide creatinine ratio: 11/191 subjects (5.8%) had two consistent urinary C-peptide creatinine ratios ≤ 0.2 nmol/mmol; 9 of these 11 subjects completed a mixed-meal tolerance test and had a median stimulated serum C-peptide of 0.18 nmol/l. Five of these 9 had stimulated serum C-peptide 0.2 had endogenous insulin secretion confirmed by the mixed-meal tolerance test. Compared with subjects with a urinary C-peptide creatinine ratio >0.2 nmol/mmol, those with confirmed absolute insulin deficiency had a shorter time to insulin treatment (median 2.5 vs. 6 years, P=0.005) and lower BMI (25.1 vs. 29.1 kg/m2, P=0.04). Two out of the five patients with absolute insulin deficiency were glutamic acid decarboxylase autoantibody-positive. Conclusions: Absolute insulin deficiency may occur in long-standing Type 2 diabetes, and cannot be reliably predicted by clinical features or autoantibodies. Absolute insulin deficiency in Type 2 diabetes may increase the risk of hypoglycaemia and ketoacidosis, as in Type 1 diabetes. Its recognition should help guide treatment, education and management. The urinary C-peptide creatinine ratio is a practical non-invasive method to aid detection of absolute insulin deficiency, with a urinary C-peptide creatinine ratio > 0.2 nmol/mmol being a reliable indicator of retained endogenous insulin secretion. © 2013 the Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

Abstract.

Hope SV, Jones AG, Goodchild E, Shepherd M, Besser REJ, Shields B, McDonald T, Knight BA, Hattersley A (2013). Urinary C-peptide creatinine ratio detects absolute insulin deficiency in Type 2 diabetes. Diabet Med, 30(11), 1342-1348.

AIMS: to determine the prevalence and clinical characteristics of absolute insulin deficiency in long-standing Type 2 diabetes, using a strategy based on home urinary C-peptide creatinine ratio measurement. METHODS: We assessed the urinary C-peptide creatinine ratios, from urine samples taken at home 2 h after the largest meal of the day, in 191 insulin-treated subjects with Type 2 diabetes (diagnosis age ≥45 years, no insulin in the first year). If the initial urinary C-peptide creatinine ratio was ≤0.2 nmol/mmol (representing absolute insulin deficiency), the assessment was repeated. A standardized mixed-meal tolerance test with 90-min stimulated serum C-peptide measurement was performed in nine subjects with a urinary C-peptide creatinine ratio ≤ 0.2 nmol/mmol (and in nine controls with a urinary C-peptide creatinine ratio >0.2 nmol/mmol) to confirm absolute insulin deficiency. RESULTS: a total of 2.7% of participants had absolute insulin deficiency confirmed by a mixed-meal tolerance test. They were identified initially using urinary C-peptide creatinine ratio: 11/191 subjects (5.8%) had two consistent urinary C-peptide creatinine ratios ≤ 0.2 nmol/mmol; 9 of these 11 subjects completed a mixed-meal tolerance test and had a median stimulated serum C-peptide of 0.18 nmol/l. Five of these 9 had stimulated serum C-peptide 0.2 had endogenous insulin secretion confirmed by the mixed-meal tolerance test. Compared with subjects with a urinary C-peptide creatinine ratio >0.2 nmol/mmol, those with confirmed absolute insulin deficiency had a shorter time to insulin treatment (median 2.5 vs. 6 years, P=0.005) and lower BMI (25.1 vs. 29.1 kg/m(2) , P=0.04). Two out of the five patients with absolute insulin deficiency were glutamic acid decarboxylase autoantibody-positive. CONCLUSIONS: Absolute insulin deficiency may occur in long-standing Type 2 diabetes, and cannot be reliably predicted by clinical features or autoantibodies. Absolute insulin deficiency in Type 2 diabetes may increase the risk of hypoglycaemia and ketoacidosis, as in Type 1 diabetes. Its recognition should help guide treatment, education and management. The urinary C-peptide creatinine ratio is a practical non-invasive method to aid detection of absolute insulin deficiency, with a urinary C-peptide creatinine ratio > 0.2 nmol/mmol being a reliable indicator of retained endogenous insulin secretion.

Abstract. Author URL.

Oram RA, Rawlingson A, Shields BM, Bingham C, Besser REJ, McDonald TJ, Knight BA, Hattersley AT (2013). Urine C-peptide creatinine ratio can be used to assess insulin resistance and insulin production in people without diabetes: an observational study. BMJ Open, 3(12). Abstract. Author URL.

Oram RA, Brooks AMS, Smith R, Rutter MK, Johnson PR, Choudhary P, Rosenthal M, Forbes S, McDonald TJ, Hattersley AT, et al (2013). Urine c-peptide creatinine ratio can be used for home monitoring of islet transplant function. DIABETIC MEDICINE, 30, 87-87. Author URL.

Jones AG, Besser REJ, Shields BM, McDonald TJ, Hope SV, Knight BA, Hattersley AT (2012). Assessment of endogenous insulin secretion in insulin treated diabetes predicts postprandial glucose and treatment response to prandial insulin. BMC Endocrine Disorders, 12 Abstract.

McDonald TJ, Perry MH, Peake RWA, Pullan NJ, O'Connor J, Shields BM, Knight BA, Hattersley AT (2012). EDTA improves stability of whole blood C-peptide and insulin to over 24 hours at room temperature. PLoS One, 7(7). Abstract. Author URL.

McDonald TJ, McEneny J, Pearson ER, Thanabalasingham G, Szopa M, Shields BM, Ellard S, Owen KR, Malecki MT, Hattersley AT, et al (2012). Lipoprotein composition in HNF1A-MODY: Differentiating between HNF1A-MODY and Type 2 diabetes. Clinica Chimica Acta, 413(9-10), 927-932. Abstract.

McDonald TJ, McEneny J, Pearson ER, Thanabalasingham G, Szopa M, Shields BM, Ellard S, Owen KR, Malecki MT, Hattersley AT, et al (2012). Lipoprotein composition in HNF1A-MODY: differentiating between HNF1A-MODY and type 2 diabetes. Clin Chim Acta, 413(9-10), 927-932. Abstract. Author URL.

Shields BM, McDonald TJ, Ellard S, Campbell MJ, Hyde C, Hattersley AT (2012). The development and validation of a clinical prediction model to determine the probability of MODY in patients with young-onset diabetes. Diabetologia, 55(5), 1265-1272. Abstract. Author URL.

Thomas NJ, Shields BM, Besser REJ, Jones AG, Rawlingson A, Goodchild E, Leighton C, Bowman P, Shepherd M, Knight BA, et al (2012). The impact of gender on urine C-peptide creatinine ratio interpretation. Ann Clin Biochem, 49(Pt 4), 363-368. Abstract. Author URL.

Besser REJ, Jones AG, McDonald TJ, Shields BM, Knight BA, Hattersley AT (2012). The impact of insulin administration during the mixed meal tolerance test. Diabet Med, 29(10), 1279-1284. Abstract. Author URL.

Besser REJ, Jones J, McDonald TJ, Smith R, Shepherd MH, Hattersley AT (2012). Using highly sensitive C-reactive protein measurement to diagnose MODY in a family with suspected type 2 diabetes. BMJ Case Reports Abstract.

Bowman P, McDonald TJ, Shields BM, Knight BA, Hattersley AT (2012). Validation of a single-sample urinary C-peptide creatinine ratio as a reproducible alternative to serum C-peptide in patients with Type 2 diabetes. Diabet Med, 29(1), 90-93. Abstract. Author URL.

McDonald TJ, Perry MH, Jones AG, Donohoe M, Salzmann MB, O'Connor J (2011). A novel case of a raised testosterone and LH in a young man. Clinica Chimica Acta, 412(21-22), 1999-2001. Abstract.

McDonald TJ, Shields BM, Lawry J, Owen KR, Gloyn AL, Ellard S, Hattersley AT (2011). High-sensitivity CRP discriminates HNF1A-MODY from other subtypes of diabetes. Diabetes Care, 34(8), 1860-1862. Abstract. Author URL.

McDonald TJ, Colclough K, Brown R, Shields B, Shepherd M, Bingley P, Williams A, Hattersley AT, Ellard S (2011). Islet autoantibodies can discriminate maturity-onset diabetes of the young (MODY) from Type 1 diabetes. Diabet Med, 28(9), 1028-1033.

AIM: Maturity-onset diabetes of the young is a monogenic form of familial, young-onset diabetes. It is rare (∼1% diabetes) and may be misdiagnosed as Type 1 diabetes and inappropriately treated with insulin. Type 1 diabetes is characterized by the presence of islet autoantibodies, including glutamate decarboxylase (GAD) and islet antigen-2 (IA-2) antibodies. The prevalence of islet autoantibodies is unknown in maturity-onset diabetes of the young and may have the potential to differentiate this form of diabetes from Type 1 diabetes. The aim of this study was to determine the prevalence of GAD and IA-2 antibodies in patients with maturity-onset diabetes of the young and Type 1 diabetes. METHODS: We measured plasma GAD and IA-2 antibodies in 508 patients with the most common forms of maturity-onset diabetes of the young (GCK: n = 227; HNF1A: n = 229; HNF4A: n = 52) and 98 patients with newly diagnosed Type 1 diabetes (diagnosed < 6 months). Autoantibodies were considered positive if ≥ 99th centile of 500 adult control subjects. RESULTS: GAD and/or IA-2 antibodies were present in 80/98 (82%) patients with Type 1 diabetes and 5/508 (< 1%) patients with maturity-onset diabetes of the young. In the cohort with Type 1 diabetes, both GAD and IA-2 antibodies were detected in 37.8% of patients, GAD only in 24.5% and IA-2 only in 19.4%. All five patients with maturity-onset diabetes of the young with detectable antibodies had GAD antibodies and none had detectable IA-2 antibodies. CONCLUSION: the prevalence of GAD and IA-2 antibodies in maturity-onset diabetes of the young is the same as in control subjects (< 1%). The finding of islet autoantibodies, especially IA-2 antibodies, makes the diagnosis of maturity-onset diabetes of the young very unlikely and genetic testing should only be performed if other clinical characteristics strongly suggest this form of diabetes rather than Type 1 diabetes. This supports routine islet autoantibody testing before proceeding to more expensive molecular genetic testing.

Abstract. Author URL.

McDonald TJ, Owen KR, Gloyn AL, Hattersley AT (2011). Response to comment on: McDonald et al. High-Sensitivity CRP discriminates HNF1A-MODY from other subtypes of diabetes. Diabetes Care 2011;34: 1860-1862. Diabetes Care, 34(12).

Besser REJ, Shepherd MH, McDonald TJ, Shields BM, Knight BA, Ellard S, Hattersley AT (2011). Urinary C-peptide creatinine ratio is a practical outpatient tool for identifying hepatocyte nuclear factor 1-{alpha}/hepatocyte nuclear factor 4-{alpha} maturity-onset diabetes of the young from long-duration type 1 diabetes. Diabetes Care, 34(2), 286-291. Abstract. Author URL.

Besser REJ, Ludvigsson J, Jones AG, McDonald TJ, Shields BM, Knight BA, Hattersley AT (2011). Urine C-peptide creatinine ratio is a noninvasive alternative to the mixed-meal tolerance test in children and adults with type 1 diabetes. Diabetes Care, 34(3), 607-609. Abstract. Author URL.

Jones AG, Besser REJ, McDonald TJ, Shields BM, Hope SV, Bowman P, Oram RA, Knight BA, Hattersley AT (2011). Urine C-peptide creatinine ratio is an alternative to stimulated serum C-peptide measurement in late-onset, insulin-treated diabetes. Diabet Med, 28(9), 1034-1038.

AIMS: Serum C-peptide measurement can assist clinical management of diabetes, but practicalities of collection limit widespread use. Urine C-peptide creatinine ratio may be a non-invasive practical alternative. The stability of C-peptide in urine allows outpatient or community testing. We aimed to assess how urine C-peptide creatinine ratio compared with serum C-peptide measurement during a mixed-meal tolerance test in individuals with late-onset, insulin-treated diabetes. METHODS: We correlated the gold standard of a stimulated serum C-peptide in a mixed-meal tolerance test with fasting and stimulated (mixed-meal tolerance test, standard home meal and largest home meal) urine C-peptide creatinine ratio in 51 subjects with insulin-treated diabetes (diagnosis after age 30 years, median age 66 years, median age at diagnosis 54, 42 with Type 2 diabetes, estimated glomerular filtration rate > 60 ml min(-1) 1.73 m(-2) ). RESULTS: Ninety-minute mixed-meal tolerance test serum C-peptide is correlated with mixed-meal tolerance test-stimulated urine C-peptide creatinine ratio (r = 0.82), urine C-peptide creatinine ratio after a standard breakfast at home (r = 0.73) and urine C-peptide creatinine ratio after largest home meal (r = 0.71). A stimulated (largest home meal) urine C-peptide creatinine ratio cut-off of 0.3 nmol/mmol had a 100% sensitivity and 96% specificity (area under receiver operating characteristic curve = 0.99) in identifying subjects without clinically significant endogenous insulin secretion (mixed-meal tolerance test-stimulated C-peptide < 0.2 nmol/l). In detecting a proposed serum C-peptide threshold for insulin requirement (stimulated serum C-peptide < 0.6 nmol/l), a stimulated (largest home meal) urine C-peptide creatinine ratio cut-off of 0.6 nmol/mmol had a sensitivity and specificity of 92%. CONCLUSION: in patients with insulin-treated diabetes diagnosed after age 30 years, urine C-peptide creatinine ratio is well correlated with serum C-peptide and may provide a practical alternative measure to detect insulin deficiency for use in routine clinical practice.

Abstract. Author URL.

Musich S, McDonald T, Chapman LS (2009). Health promotion strategies for the "boomer" generation: Wellness for the mature worker. American Journal of Health Promotion, 23(3), 1-9.

McDonald TJ, Knight BA, Shields BM, Bowman P, Salzmann MB, Hattersley AT (2009). Stability and reproducibility of a single-sample urinary C-peptide/creatinine ratio and its correlation with 24-h urinary C-peptide. Clin Chem, 55(11), 2035-2039. Abstract. Author URL.

Gerstein HC, Miller ME, Byington RP, Goff DC, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH, et al (2008). Effects of intensive glucose lowering in type 2 diabetes. New England Journal of Medicine, 358(24), 2545-2559. Abstract.

Wang F, McDonald T, Bender J, Reffitt B, Miller A, Edington DW (2006). Association of healthcare costs with per unit body mass index increase. Journal of Occupational and Environmental Medicine, 48(7), 668-674. Abstract.

Yen L, Schultz AB, McDonald T, Champagne L, Edington DW (2006). Participation in employer-sponsored wellness programs before and after retirement. American Journal of Health Behavior, 30(1), 27-38. Abstract.

Wang F, McDonald T, Reffitt B, Edington DW (2005). BMI, physical activity, and health care utilization/costs among medicare retirees. Obesity Research, 13(8), 1450-1457. Abstract.

Musich S, Lu C, McDonald T, Champagne LJ, Edington DW (2004). Association of Additional Health Risks on Medical Charges and Prevalence of Diabetes Within Body Mass Index Categories. American Journal of Health Promotion, 18(3), 264-268. Abstract.

Wright D, Adams L, Beard MJ, Burton WM, Hirschland D, McDonald T, Napier D, Galante S, Smith T, Edington DW, et al (2004). Comparing excess costs across multiple corporate populations. Journal of Occupational and Environmental Medicine, 46(9), 937-945. Abstract.

Wang F, McDonald T, Champagne LJ, Edington DW (2004). Relationship of Body Mass Index and Physical Activity to Health Care Costs among Employees. Journal of Occupational and Environmental Medicine, 46(5), 428-436. Abstract.

Yen L, McDonald T, Hirschland D, Edington DW (2003). Association Between Wellness Score from a Health Risk Appraisal and Prospective Medical Claims Costs. Journal of Occupational and Environmental Medicine, 45(10), 1049-1057. Abstract.

Musich S, McDonald T, Hirschland D, Edington DW (2003). Erratum: Examination of risk status transitions among active employees in a comprehensive worksite health promotion program (Journal of Occupational and Environmental Medicine (April)). Journal of Occupational and Environmental Medicine, 45(6).

Musich S, McDonald T, Hirschland D, Edington DW (2003). Examination of risk status transitions among active employees in a comprehensive worksite health promotion program. Journal of Occupational and Environmental Medicine, 45(4), 393-399. Abstract.

Musich S, Faruzzi SD, Lu C, McDonald T, Hirschland D, Edington DW (2003). Pattern of Medical Charges after Quitting Smoking among those with and without Arthritis, Allergies, or Back Pain. American Journal of Health Promotion, 18(2), 133-142.

Purpose. To examine the time frame of changes in medical charges after smoking cessation among (I) those with arthritis, allergies, or back pain and (2) those with none of these chronic conditions. Design. Cross-sectional study using smoking status determined in 1996 and 4-year average medical charges measured from 1996 to 1999. Setting. Nationwide manufacturing corporation (General Motors Corporation). Subjects. A total of 20,332 employees and spouses who completed a health risk appraisal in 1996 were younger than 64 years, were enrolled in indemnity or preferred provider organization health insurance plans during 1996 to 1999, and self-reported no preexisting primary diseases. Measures. Participants were categorized according to 1996 self-reported smoking status into six subgroups: current smokers, former smokers by years since cessation (0-4, 5-9, 10-14, and ≥15 years), and never smokers. Average annual medical charges (1996-1999) among those with chronic conditions (arthritis, allergies, or back pain; N = 11, 921) or without chronic conditions (N = 8411) were examined independently. Never smokers in each group were compared to respective smoker and former smoker subgroups. Results. Current smokers and former smokers without chronic conditions who quit fewer than 5 years earlier had higher medical charges compared with never smokers ($2613 and $3356 vs. $2203, respectively). Among those with chronic conditions, current smokers, former smokers who quit 0 to 4 years ago, and former smokers who quit 5 to 9 years ago had higher medical charges than never smokers ($4208, $4027, and $4050 vs. $3108, respectively). Conclusions. It took approximately 5 years for former smokers without chronic conditions and nearly 10 years for former smokers with chronic conditions to reduce their medical charges to levels close to their respective never smokers. Health promotion practitioners and other decision makers should consider the impact of chronic conditions on the course of medical savings when implementing smoking cessation programs at the worksite.

Abstract.

Wang F, Schultz AB, Musich S, McDonald T, Hirschland D, Edington DW (2003). The relationship between National Heart, Lung, and Blood Institute weight guidelines and concurrent medical costs in a manufacturing population. American Journal of Health Promotion, 17(3), 183-189. Abstract.

Musich S, McDonald T, Hirschland D, Edington DW (2002). Excess healthcare costs associated with excess health risks in diseased and non-diseased Health Risk Appraisal participants. Disease Management and Health Outcomes, 10(4), 251-258.

Background: Concerns regarding the effectiveness and impact of disease management are largely based on disease compliance measures. Although disease management programs have measured improvements in compliance and quality of life and cost savings from reductions in hospitalizations and emergency room visits, few programs have focused on changing behavioral health risks not directly related to the specific disease. The basic relationship between behavioral health risks and healthcare costs shows that those individuals with more high-risk behaviors are associated with higher healthcare costs compared with those with low-risk behaviors. The concept of excess costs associated with excess risks is a calculation of theoretical maximum percent savings for an entire group assuming everyone reduces to low risk, and changes in healthcare costs follow the changes in risks. Objective: to establish the magnitude of excess healthcare costs associated with excess health risks, given a diagnosed chronic disease. Methods: 135 251 current and retired employees of General Motors Corporation who had completed a Health Risk Appraisal (I-IRA) were evaluated. Participants were continuously enrolled in traditional or Preferred Provider Organization (PPO) medical plans from 1996 to 1999 and had completed at least one HRA between 1996 and 1998. Results: Those with and without self-reported disease averaged 19.2 and 9.1% excess healthcare costs associated with excess health risks, respectively. However, the magnitude of the impact differed across age groups and diseases. Individuals less than 45 years of age with self-reported disease were most affected by the presence of additional health risks (44% excess costs) while those aged ≥65 years without disease were least affected (8.2% excess costs). Among those with diseases, those with diabetes mellitus and bronchitis/emphysema were most affected (19.2 and 21.0%, respectively). Conclusions: Disease management programs should ideally provide a systematic approach to assist patients with interventions that improve overall health, as well as focusing on disease compliance measures. The implications for disease management programs are that, even given the presence of disease, promoting and/or maintaining low-risk status can result in potential cost savings.

Abstract.

Schultz AB, Lu C, Barnett TE, Yen LTC, McDonald T, Hirschland D, Edington DW (2002). Influence of participation in a worksite health-promotion program on disability days. Journal of Occupational and Environmental Medicine, 44(8), 776-780. Abstract.

Yen L, Edington MP, McDonald T, Hirschland D, Edington DW (2001). Changes in health risks among the participants in the United Auto Workers - General Motors lifesteps health promotion program. American Journal of Health Promotion, 16(1), 7-15. Abstract.

Braunstein A, Li Y, Hirschland D, McDonald T, Edington DW (2001). Internal associations among health-risk factors and risk prevalence. American Journal of Health Behavior, 25(4), 407-417. Abstract.

Musich S, Ignaczak A, McDonald T, Hirschland D, Edington DW (2001). Self-reported utilization of preventive health services by retired employees age 65 and older. Journal of the American Geriatrics Society, 49(12), 1665-1672. Abstract.

Chapters

Clark P, McDonald T (2013). Diabetes Mellitus. In (Ed) The Immunoassay Handbook, 783-794.

Conferences

Chanchlani N, Lin S, Hamilton B, Bewshea C, Thomas A, Smith R, Roberts C, Nice R, McDonald T, Goodhand J, et al (2023). O59 Understanding anti-TNF treatment failure: mechanisms and management of loss of response to anti-TNF therapy, three-year data from the PANTS study. Oral presentations.

Smith R, Liu Z, Laskey K, Lin S, Chanchlani N, Nice R, Roberts C, Alexander J, McDonald TJ, Bewshea C, et al (2023). P115 Vitamin D concentrations are not associated with anti-SARS-CoV-2 antibody responses following mRNA COVID-19 vaccine in IBD patients treated with infliximab. Poster presentations.

Smith R, Lin S, Chanchlani N, Roberts C, Nice R, McDonald TJ, Hamilton B, Bewshea C, Kennedy NA, Goodhand JR, et al (2023). P82 Pre-treatment vitamin D concentrations do not predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn’s disease. Poster presentations.

Hill AV, Bolt R, Aldred M, Tippett PW, Nice R, McDonald TJ, Jones AG (2022). A novel, patient-focused approach to home sample collection improves rate of return & sample quality and enables research to continue during the covid-19 pandemic. Author URL.

Thomas N, Hill A, Bolt R, Tippett P, Shields B, McDonald T, Jones A (2022). Age of onset does not affect progression of robustly defined adult onset type 1 diabetes. Author URL.

Russon C, Vaughan N, Pulsford R, Andrews R, Allen M (2022). Glycaemic events during exercise can be effectively predicted with machine learning using only start glucose and duration. European Association for the Study of Diabetes (EASD). 19th - 23rd Sep 2022. Abstract.

Brackley SM, Thomas N, Hill A, Shields B, Fox C, McDonald T, Huber J, Jones AG (2022). In adults with new onset type 1 diabetes baseline psychological resilience is prospectively associated with HbA1c. Author URL.

Simpson VE, Thomas N, Hill AV, Deshmukh S, Shields BM, McDonald T, Jones AG (2022). In people with suspected type 1 diabetes or rapid progression to insulin, a single positive islet autoantibody confirms the genetic characteristics and progression of classical type 1 diabetes. Author URL.

Grace SL, Long AE, Gillespie KM, Williams AJK, Lampasona V, Achenbach P, Pearson ER, McDonald TJ, Jones AG (2022). Rapid insulin progression in glutamate decarboxylase autoantibody positive adult-onset diabetes can be better predicted by detecting autoantibodies to n-terminally truncated GAD(96-585). Author URL.

Eason RJ, Thomas NJ, Hill AV, Deshmukh S, Hattersley AT, Shields BM, McDonald TJ, Jones AG (2022). Routine islet autoantibody testing in newly diagnosed adult-onset type 1 diabetes can guide clinical reclassification and successful insulin cessation. Author URL.

Katte JC, Sobngwi E, Dehayem MY, Deshmukh S, Patel KA, Shields BM, McDonald TJ, Jones AG (2022). The majority of young people diagnosed with type 1 diabetes in Cameroon do not have evidence of islet autoimmunity: Results from the Young-Onset Diabetes in sub-Saharan Africa (YODA) study. Author URL.

Kennedy NA, Goodhand J, Bewshea C, Nice R, Chee D, Lin S, Chanchlani N, Butterworth J, Cooney R, Croft N, et al (2021). Anti-SARS-CoV2 antibody responses are attenuated in patients with Inflammatory Bowel Disease treated with infliximab. Author URL.

Grace SL, Walkey HC, Kaur A, Misra S, Oliver NS, McDonald TJ, Johnston DG, Jones G, Patel KA (2021). Glutamate decarboxylase and islet antigen-2 autoantibody titres at diagnosis in people with type 1 diabetes showed bimodal distribution and an association with age at diagnosis and HLA genotype. Author URL.

Bowman P, Patel KA, McDonald TJ, Holst JJ, Hartmann B, Leveridge M, Knight BA, Shepherd MH, Andrews RC, Hattersley AT, et al (2021). Incretin hormone responses to carbohydrate and protein/fat are preserved in adults with sulphonylurea-treated KCNJ11 neonatal diabetes, when compared with healthy controls. Author URL.

Carr A, Oram R, Narendran P, Andrews R (2021). MEASUREMENT OF C-PEPTIDE AT DIAGNOSIS INFORMS GLYCEMIC CONTROL BUT NOT HYPOGLYCEMIC RISK IN TYPE 1 DIABETES. Author URL.

Meek CL, Oram R, McDonald T, Feig DS, Hattersley AT, Murphy HR (2021). Maternal C-peptide reappearance in type 1 diabetes pregnancy: Evidence of beta cell regeneration or fetal hyperinsulinism?. Author URL.

Nice R, Chanchlani N, Kennedy NA, Green HD, Lin S, Gordon C, Chee D, Hamilton B, Bewshea C, Goodhand J, et al (2021). POSITIVITY THRESHOLDS OF TOTAL INFLIXIMAB AND ADALIMUMAB ANTI-DRUG ANTIBODY ASSAYS AND IMPACT IN CLINICAL PRACTICE. Author URL.

Eason R, Hill A, Shields B, Tippett P, McDonald T, Hattersley A, Oram R, Knight B, Thomas N, Jones A, et al (2021). The absence of islet autoantibodies when routinely tested in adult-onset type 1 diabetes is associated with a high prevalence of treatment change and successful insulin cessation. Author URL.

Shaw AC, Taylor GS, McDonald TJ, Oram RA, Shaw JAM, West DJ (2021). The influence of residual beta cell function upon free-living postprandial and nocturnal glycaemic control in individuals with type 1 diabetes. Author URL.

Tippett PW, Hill AV, Bolt R, Lynam AL, Carr ALJ, Hattersley AT, McDonald TJ, Oram RA, Shields BM, Jones AG, et al (2020). A clinical prediction model combining clinical features and type 1 diabetes genetic risk has high accuracy for classification of adult onset diabetes at diagnosis. Author URL.

Shields BM, Baptist A, Bandopadhyay S, Phatak S, Bhat D, Kamat R, Hudson M, McDonald TJ, Hattersley AT, Yajnik CS, et al (2020). C-peptide decline follows a similar biphasic pattern in both UK and Indian type 1 diabetes patients. Author URL.

(2020). Clinical care and other categories posters: Type 1 diabetes.

Greiner RS, Hill A, Knight BA, McDonald T, Shields B, Jones AG, Rodgers LR (2020). HbA(1c) thresholds have substantial impact in screening procedures for those at risk of developing type 2 diabetes. Author URL.

Frayling TM, Pitt A, Hudson M, Knight B, Nice R, McDonald T, Jones A, Hattersley AT (2020). In vivo estimates of beta cellmass in 251 normoglycaemic individuals are strongly associated with BMI and insulin resistance. Author URL.

Shepherd MH, Knight BA, Laskey K, McDonald TJ (2020). Newborn screening for glucose: 'An absolutely fantastic idea'. Author URL.

Tikhonova IA, Bello S, Salmon A, Robinson S, Hemami RM, Haigh RC, Jani M, McDonald TJ, Hoyle M (2020). PROMONITOR FOR THERAPEUTIC DRUG MONITORING IN PATIENTS WITH SEVERE RHEUMATOID ARTHRITIS TREATED WITH ADALIMUMAB IN ENGLAND AND WALES. Author URL.

Thomas N, Hill A, Tippett P, McDonald T, Knight B, Carr A, Oram R, Hattersley A, Weedon M, Jones A, et al (2020). Patterns of autoimmunity of genetically defined adult onset type 1 diabetes are different above and below 30 years of age, without impacting on clinical presentation. Author URL.

Greiner R, Hill A, Knight BA, McDonald T, Shields BM, Jones AG, Rodgers L (2020). Performance and implications of NICE-recommended screening for identifying those at risk of type 2 diabetes: Results from a UK population cohort. Author URL.

Nice R, Chanchlani N, Green H, Bewshea C, Kennedy N, Ahmad T, Goodhand J, McDonald T, Perry M (2020). Positivity thresholds of total infliximab and adalimumab anti-drug antibody assay: the prevalence of clearing and transient anti-drug antibodies in a national therapeutic drug monitoring service. Author URL.

Taylor GS, Smith K, Scragg J, Bashir A, McDonald T, Oram R, Stevenson EJ, Shaw JA, West DJ (2020). Stimulated c-peptide, but not glucagon, is associated with improved glycaemic control after exercise in individuals with type 1 diabetes. Author URL.

Elyas S, Allen G, Mcdonald T (2020). THE IDENTIFICATION OF STROKE BIO-MARKERS TO DISTINGUISH STROKE FROM STROKE MIMICS, a PILOT STUDY AND CONCEPT. Author URL.

Grace SL, Cooper A, Jones AG, McDonald TJ (2020). Zinc transporter 8 autoantibody testing requires age-specific cut-offs. Author URL.

Shields B, McDonald T, Owen K, Malecki M, Jones A, Colclough K, Hattersley A (2019). Improving the MODY calculator for use in insulin treated patients with the addition of C-peptide and islet autoantibodies. Author URL.

Long AE, Wilson IV, Aitken RJ, McDonald TJ, Wong FS, Williams AJK, Gillespie KM (2019). Insulin autoantibody level at diagnosis predicts long-term residual beta cell function. Author URL.

Hill AV, Tippett P, McDonald TJ, Knight BA, Hattersley AT, Jones AG (2019). No single clinical feature can robustly classify diabetes at diagnosis, but approaches that integrate clinical features have high diagnostic accuracy. Author URL.

Bowman P, Patel KA, McDonald TJ, Knight BA, Leveridge M, Flanagan SE, Hammersley S, Shepherd MH, Andrews RC, Hattersley AT, et al (2019). Physiological assessment of individuals with sulphonylurea-treated KCNJ11 permanent neonatal diabetes following carbohydrate and protein meals shows markedly reduced KATP mediated insulin secretion but relatively intact non-KATP pathways. Author URL.

Jones AG, Hill AV, Trippett PW, Hattersley AT, McDonald TJ, Shields BM (2019). The utility of clinical features and glycaemia at diagnosis in classifying young adult onset diabetes. Author URL.

Rodgers LR, Hill AV, Hattersley AT, McDonald TJ, Jones A, Shields BM (2019). Time to revise HbA(1c) thresholds for diabetes risk? Evidence from a prospective study of 4010 participants. Author URL.

Hattersley A, McDonald T, Shepherd M, Hudson M, Colclough K, Ellard S, Pearson E, Shields B (2019). Use of the MODY probability calculator in the real-world setting. Author URL.

Niwaha A, Nakanga W, Katte J-C, Shields B, Jones A, Nyirenda M, McDonald T (2019). When there is no haemolysis, plasma C-peptide levels are stable up to 5 days at 4 degrees C. Author URL.

Grubb AL, Donnelly LA, Slieker RC, McDonald TJ, Rutters F, 't Hart LM, Pearson ER, Hattersley AT, Shields BM, Jones AG, et al (2018). A Type 1 diabetes genetic risk score can identify patients with glutamic acid decarboxylase (GAD) antibody-positive Type 2 diabetes with and without rapid progression to insulin therapy. Author URL.

Dawed AY, Mari A, McDonald TJ, Robertson NR, Mahajan A, Walker M, Gough S, Zhou K, Forgie I, Ruetten H, et al (2018). Common variants in the GLP-1 receptor are associated with glycaemic response to GLP-1 receptor agonists in observational and large RCT data: an IMI-DIRECT study. Author URL.

Grubb AL, Patel K, Oram RA, Hill AV, Angwin C, McDonald TJ, Weedon MN, Hattersley AT, Owen KR, Shields BM, et al (2018). Development and validation of a clinical prediction model to identify adult patients (aged 18-50) with type 1 diabetes requiring early insulin therapy. Author URL.

Mcdonald TJ, Flanagan SE, Knight B (2018). Differential diagnosis of hyperglycaemia at day five of life: Implications for a new born screening programme. Author URL.

Bowman P, Shepherd MH, McDonald TJ, Andrews RC, Spaull SR, Statton S, Hammersley S, Leveridge M, Shields BM, Flanagan SE, et al (2018). Excess insulin secretion with a high protein meal in sulphonylurea treated KCNJ11 neonatal diabetes patients shows the limitations of amplifying insulin secretion pathways. Author URL.

Dawed AY, Mari A, McDonald TJ, Hong M-G, Sharma S, Robertson NR, Mahajan A, Walker M, Gough S, Zhou K, et al (2018). GLP-1 RECEPTOR VARIANTS MARKEDLY DIFFERENTIATE GLYCAEMIC RESPONSE TO GLP-1 RECEPTOR AGONISTS: a DIRECT STUDY. Author URL.

Oram RA, McDonald TJ, Sabbah S, Bloem S, Shields B, Hill A, Bolt R, Begom S, Khatri L, Tree T, et al (2018). Older age of diagnosis is the major feature of persistent long term endogenous insulin secretion in type 1 diabetes. Author URL.

Shakweh EY, Shields BM, Angwin CD, Rodgers LR, McDonald TJ, Pearson ER, Hattersley AT, Jones AG, Consortium M (2018). Precision medicine in Type 2 diabetes: is variation in response to sitagliptin and gliclazide therapy related to drug levels?. Author URL.

Marren SM, Hammersley S, Knight B, Bolt R, Hill A, Hattersley AT, McDonald TJ, Jones AG, Oram RA (2018). Preserved beta cell function in long-duration Type 1 diabetes is associated with markedly lower hypoglycaemia and insulin dose but no improvements in HbA1c, suggesting the need to intensify therapy. Author URL.

Tippett PW, Hill AV, McDonald TJ, Hattersley AT, Jones AG (2018). Prevalence and clinical associations of ZnT8 islet autoantibodies in the first year of adult diabetes. Author URL.

Oram RA, Hammersley S, Knight BA, Bolt R, Hill A, Jones AG, Hattersley AT, McDonald TJ (2018). Proinsulin measurement suggests persistent beta cells even in those with undetectable c-peptide in long-duration Type 1 diabetes: Evidence for disordered insulin processing. Author URL.

Huber JW, Fox C, Hill A, McDonald T, Shields B, Jones A (2018). Psychological resilience in Type 1 diabetes carries independent benefits for blood glucose control. Author URL.

Colombo M, McDonald TJ, McKeigue PM, Colhoun HM, Investigators SDRNTBIO (2018). Relationship of C-peptide persistence and HbA(1c) in type 1 diabetes. Author URL.

Leete P, Oram R, McDonald TJ, Ziller C, Shields B, Hattersley AT, Richardson SJ, Morgan NG, Team TTS, Team TTS, et al (2018). Studies of insulin-related peptides in pancreas and plasma support the existence of two distinct aetiological subtypes of type 1 diabetes associated with age at diagnosis. Author URL.

Yaghootkar H, Patel K, Colclough K, Moleirinho A, Ghaemi N, Heidari S, Vakili S, Enayati S, Rabbani A, Abbasi F, et al (2018). Type 1 diabetes genetic risk score discriminates between monogenic and type 1 diabetes in patients with diabetes presented below five years of age in Iranian population. Author URL.

Chan TYH, Patel K, Colclough K, Hattersley AT, McDonald TJ (2018). Zinc transporter 8 autoantibody is comparable to established autoantibodies in excluding patients for genetic analysis in Maturity Onset Diabetes of the Young (MODY). Author URL.

Hammersley SE, Bolt RL, Hill AV, McDonald TJ, Oram RA, Hattersley AT (2017). A novel patient focused approach enables study participation and aids recruitment rate in Type 1 diabetes research. Author URL.

Oram RA, Leete P, Shields B, Richardson S, Hill A, McDonald T, Morgan N, Hattersley A (2017). C-peptide measurements support the existence of two distinct subtypes of Type 1 diabetes as defined by pancreatic immunopathology. Author URL.

Dennis JM, Shields BM, Henley WE, Knight BA, McDonald TJ, Hill AV, Weedon MN, Rodgers LR, Hattersley AT, Jones AG, et al (2017). Clinical markers of insulin resistance predict reduced glycaemic response with DPP4-inhibitors: a MASTERMIND stratified medicine study. Author URL.

Shields B, Richardson S, Oram R, Leete P, Hill A, McDonald T, Morgan N, Hattersley A (2017). Cross-sectional c-peptide data and histological analysis of pancreas samples suggest two phases of beta cell decline in Type 1 diabetes. Author URL.

Grubb AL, Patel KA, Oram RA, Hill AV, Angwin C, McDonald TJ, Weedon MN, Hattersley AT, Shields BV, Jones AG, et al (2017). Development of a risk calculator to identify patients with Type 1 diabetes who will require early insulin therapy. Author URL.

Dawed AY, Mari A, McDonald TJ, Hong MG, Sharma S, Robertson NR, Mahajan A, Walker M, Gough S, Zhou K, et al (2017). GLP-1 receptor variants markedly differentiate glycaemic response to GLP-1 receptor agonists: a DIRECT study. Author URL.

Hope SV, Knight BA, Shields BM, Hill A, Choudhary P, Strain WD, Hattersley AT, McDonald TJ, Jones G (2017). RANDOM NON-FASTING C-PEPTIDE CAN BE USED AS a RISK ASSESSMENT TOOL FOR HYPOGLYCAEMIA IN ELDERLY NSULIN-TREATED PATIENTS WITH TYPE 2 DIABETES. Author URL.

Juszczak A, James TJ, McDonald TJ, Vaxillaire M, Klimes I, Malecki MT, Hansen T, Njolstad PR, Tuomi T, Gloyn AL, et al (2016). Assessing the likely function of HNF1A missense variants using CRP and allele frequency data. Author URL.

Patel KA, Oram RA, Mcdonald TJ, Hudson M, Colclough K, Ellard S, Weedon MN, Pearson EZ, Hattersley AT (2016). Classifying the unclassified using Type 1 diabetes genetic risk score: patients with young onset diabetes who are islet autoantibody negative and have preserved c-peptide. Author URL.

Dawed AY, Jones AG, McDonald TJ, Walker M, Mari A, Franks PW, Pearson ER, Project IMI-DIRECT (2016). Determinants of glucagon secretion in prediabetes and recently diagnosed type 2 diabetes: an IMI-DIRECT study. Author URL.

Oram RA, Hammersley S, Hill A, Shields B, Hattersley A, McDonald T (2016). Longitudinal study of extremely low c-peptide: evidence for persistent beta cells in all people with Type 1 diabetes. Author URL.

Hope SV, Knight BA, Shields BM, Hattersley AT, McDonald TJ, Jones AG (2016). Random non-fasting c-peptide provides an accurate measure of endogenous insulin secretion for clinical practice. Author URL.

Umapathysivam MM, McDonald T, Humphreys S, Neville M, Gloyn AL, McCarthy MI, Hattersley AT, Karpe F, Frayling TM (2016). Strategies for improving statistical power for detailed physiological characterisation of individuals with type 2 diabetes-associated variants. Author URL.

Peters JL, Anderson R, Shields BM, King S, Hudson M, Shepherd M, McDonald TJ, Pearson E, Hattersley AT, Hyde C, et al (2016). Strategies to identify individuals with MODY: results of a health economic model. Author URL.

Craig ZV, Hill AV, McDonald TJ, Hattersley AT, Jones AG, Shields BM (2016). Time to change the HbA1c cut-off for prediabetes. Author URL.

Weedon MN, Hill AV, McDonald TJ, Patel KA, Jones A, Hattersley AT, Oram R (2015). A novel inexpensive test can discriminate between Type 1 and Type 2 diabetes. Author URL.

Mcdonald TJ, Parfitt C, Armston A, Church D, Couchman L, Evans C, Wark G (2015). Commercial insulin immunoassays fail to detect commonly prescribed insulin analogues. Author URL.

Veale DA, McCulloch RW, McDonald TJ, Cudmore A, Parfitt C, O'Connor J, Kerr JP (2015). Current use of nephelometric quantification of serum free light chains (FLCs) in the management of plasma cell dyscrasias, and the potential benefits of point-of-care testing. Author URL.

Jones AG, Hill AV, Bolt R, McDonald TJ, Shields BM, Knight BA, Hattersley AT (2015). Insulin resistance and high fasting glucose are associated with reduced glycaemic response to dipeptidyl peptidase 4 (DPP-4) inhibitor therapy. Author URL.

Hope SV, McDonald TJ, Hill AV, Strain WD, Hattersley AT (2015). Low c-peptide is associated in insulin-treated patients with hypoglycaemia unawareness as well as hypoglycaemia frequency. Author URL.

Rodgers LR, Pearson ER, Angwin CD, Hammersley S, McDonald TJ, Shields BM, Hattersley AT, Jones AG, Consortium M (2015). Response to glucose lowering therapy can be assessed by a brief period of treatment withdrawal: a MASTERMIND study. Author URL.

Chapman DP, Gooding KM, McDonald TJ, Anning CM, Pamphilon N, Ball C, Casanova F, Shore AC (2015). Using clinical characteristics to account for variation of urinary creatinine excretion improves the accuracy of the albumin to creatinine ratio (ACR) to identify individuals with microalbuminuria. Author URL.

Oram RA, McDonald TJ, Shields BM, Pearson ER, Hattersley AT, Team UNITEDR (2014). A large, population-based study demonstrates that most people with long duration Type 1 diabetes are insulin microsecretors and produce their own endogenous insulin. Author URL.

Flanagan SE, Haapaniemi E, Russell MA, McDonald TJ, Barton J, Murphy NP, Seppanen M, Milenkovic T, Heiskanen K, Lernmark A, et al (2014). A novel syndrome of early-onset type 1 diabetes and multi-organ autoimmunity caused by activating germline mutations in STAT3. Author URL.

Shields BM, Hudson M, Shepherd M, Oram R, McDonald TJ, Ellard S, Pearson ER, Hattersley AT, Team UNITED (2014). Comparison of screening using clinical criteria and biomarkers to identify maturity-onset diabetes of the young (MODY) in a community based setting. Author URL.

Jones AG, Shields BM, Hill AV, McDonald TJ, Knight BA, Hattersley AT (2014). Defining good response to glucose lowering therapy: different definitions identify different individuals and associated characteristics. Author URL.

McDonald TJ, Warren R (2014). Diagnostic confusion? Repeat HbA1c for the diagnosis of diabetes. Author URL.

Jones AG, McDonald TJ, Hill AV, Stewart J, Shields BM, Knight BA, Hattersley AT (2014). Markers of beta cell failure are associated with reduced glycaemic response to GLP-1 agonists in Type 2 diabetes. Author URL.

McDonald TJ, Oram R, Shields B, Pearson E, Hattersley A (2014). Most people with long duration of type 1 diabetes are insulin microsecretors and produce their own endogenous insulin. Author URL.

Shepherd M, Shields B, Knight B, Weinand-Barnett S, Fox CJ, McDonald TJ, Hattersley AT (2014). Patients with Type 2 diabetes treated with analogue insulin require 40% more insulin to achieve the same level of HbA1c than those on non-analogue insulin. Author URL.

Bingley PJ, Aitken RJ, Wilson IV, Long AE, Williams AJK, McDonald T, Wong S, Hattersley AT, Gillespie KM (2014). Residual beta cell function in long-standing childhood onset type 1 diabetes. Author URL.

Hudson MM, Shepherd M, Oram RA, McDonald TJ, Ellard S, Shields BM, Hattersley AT, Team UR (2013). A population-based approach to genetic testing defines the prevalence of maturity onset diabetes of the young (MODY) in patients with diabetes diagnosed under 30 years as 3%. Author URL.

Jones AG, Hill AV, Stewart J, Githens-Mazer G, Shields BM, McDonald TJ, Knight BA, Hattersley AT (2013). Baseline HbA1c is the major clinical predictor of glycaemic response to incretin based agents in Type 2 diabetes. Author URL.

Jones AG, Hill AV, Stewart J, Shields BM, McDonald TJ, Knight BA, Hattersley AT (2013). Markers of insulin resistance and beta cell function do not predict response to incretin based treatments in type 2 diabetes. Author URL.

Hammersley S, Oram R, Shepherd M, Moudiotis C, Fraser B, Mallam K, Cox J, Smith B, McDonald TJ, Besser REJ, et al (2013). Prevalence of non-Type 1 diabetes in paediatric diabetes. Author URL.

Oram RA, McDonald TJ, Jones AG, Besser REJ, Hattersley AT (2013). The majority of patients with over five years of Type 1 diabetes are insulin microsecretors and have functioning beta cells. Author URL.

Hope SV, Jones AG, Shepherd M, Shields B, Strain D, McDonald T, Knight BA, Hattersley AT (2013). Urinary C-peptide creatinine ratio to detect absolute insulin deficiency in type 2 diabetes. Author URL.

Shields BM, McDonald TJ, Owen KR, Malecki MT, Besser REJ, Jones AG, Ellard S, Hattersley AT (2012). Integration of biomarkers and clinical characteristics provides the best method for identifying patients with MODY. Author URL.

Oram RA, Shepherd MH, Hudson M, Sanders T, Tiley S, Hammersley S, Shields B, McDonald TJ, Knight BA, Besser REJ, et al (2012). The prevalence of endogenous insulin production in a cohort of adults with type 1 diabetes. Author URL.

Nowak N, Szopa M, Thanabalasingham G, McDonald TJ, James TJ, Skupien J, Kiec-Wilk B, Mlynarski W, Hattersley AT, Owen KR, et al (2011). Cystatin C is not a good candidate biomarker for HNF1A MODY. Author URL.

Jones AG, Besser REJ, McDonald TJ, Shields BM, Hope SV, Bowman PA, Oram RA, Knight BA, Hattersley AT (2011). Measuring endogenous insulin secretion: does it matter in insulin treated patients?. Diabetes UK Annual Professional Conference 2011. 30th Mar - 1st Apr 2011.

Jones AG, Besser REJ, Shields BM, McDonald TJ, Hope SV, Oram RA, Knight BA, Hattersley AT (2011). Practical alternatives to the mixed meal tolerance test in insulin treated diabetes. Diabetes UK Annual Professional Conference 2011. 30th Mar - 1st Apr 2011.

Shields BM, McDonald TJ, Ellard S, Hyde C, Campbell M, Hattersley AT (2011). Should I test this patient for maturity onset diabetes of the young? a clinical prediction model to determine the probability of MODY. Author URL.

Thomas NJM, Besser REJ, Jones AG, McDonald TJ, Shields BM, Knight BA, Hattersley AT (2011). Simple and convenient alternatives to the mixed meal tolerance test. Author URL.

Hope SV, Jones A, Goodchild E, Shepherd M, Besser REJ, Shields B, McDonald T, Knight BA, Hattersley A (2011). URINARY C-PEPTIDE CREATININE RATIO (UCPCR) CAN BE USED AS a SCREENING TOOL TO DETECT ABSOLUTE INSULIN DEFICIENCY IN PEOPLE WITH TYPE 2 DIABETES. Author URL.

Hope SV, Jones AG, Goodchild E, Shepherd M, Besser REJ, Shields BM, McDonald TJ, Knight BA, Hattersley AT (2011). Urinary C-Peptide Creatinine Ratio (UCPCR) can be used as a screening tool to detect absolute insulin deficiency in type 2 diabetes. Diabetes UK Annual Professional Conference 2011. 30th Mar - 1st Apr 2011.

Besser REJ, Shepherd MH, McDonald TJ, Shields BM, Knight BA, Hammersley S, Ellard S, Hattersley AT (2011). Urinary C-peptide creatinine ratio is a practical outpatient tool in identifying MODY from type 1 diabetes in children with diabetes. Author URL.

Rawlingson A, Knight BA, Oram R, McDonald TJ, Shields BM, Hattersley AT (2010). A novel method for the assessment of insulin physiology: urinary C-peptide creatinine ratio can be used to assess insulin sensitivity and beta cell function in non-diabetic subjects. Author URL.

Jones AG, Hope SV, Shepherd M, Shields BM, Besser REJ, Wensley KJ, Githens-Mazer G, McDonald TJ, Knight BA, Hattersley AT, et al (2010). Do patients with Long-Standing Type 2 Diabetes Develop Absolute Insulin Deficiency?. Author URL.

Brooks AM, Shields BM, Knight BA, McDonald TJ, Mills S, Smith J, Dyer R, Paisey R, Hattersley AT (2010). Is Intensive Carbohydrate Counting Education a Treatment Option in Patients with Atypical Characteristics for Type 1 Diabetes?. Author URL.

Hope SV, Shepherd M, Shields BM, McDonald T, Knight BA, Hattersley AT (2010). Patients with long-standing type 2 diabetes can develop absolute insulin deficiency. Author URL.

Besser REJ, Shepherd MH, McDonald TJ, Shields BM, Colclough KJ, Githens-Mazer G, Wensley KJ, Knight BA, Ellard S, Hattersley AT, et al (2010). Postal Urinary C-Peptide Creatinine Ratio Discriminates Long Duration Type 1 Diabetes from HNF1A MODY. Author URL.

Jones AG, Besser REJ, McDonald TJ, Wensley KJ, Githens-Mazer G, Shields BM, Knight BA, Hattersley AT (2010). Serum Measurement of Endogenous C-Peptide after a Mixed Meal can be Replaced with a Single Post Meal Urine C-Peptide Creatinine Ratio (UCPCR). Author URL.

Shields BM, McDonald TJ, Bowman P, Jones AG, Besser REJ, Wensley KJ, Githens-Mazer G, Knight BA, Hattersley AT (2010). Urinary C-Peptide Creatinine Ratio (UCPCR) is a Reliable Measure of Endogenous Insulin Secretion, Even in Patients with Renal Impairment. Author URL.

Besser REJ, Jones AG, McDonald TJ, Shields BM, Githens-Mazer G, Wensley K, Knight BA, Hattersley AT (2010). Urinary C-Peptide Creatinine Ratio is a Novel Non Invasive Alternative to the Inpatient Mixed Meal Tolerance Test in Young Onset Type 1 Diabetes. Author URL.

Reports

Tikhonova I, Yang H, Salmon A, Bello S, Peters J, Robinson S, Coelho H, Kharechko A, Haigh R, Jani M, et al (2019). Therapeutic monitoring of TNF-alpha inhibitors in rheumatoid arthritis.

Publications by year

In Press

Abstract.

Atabaki-Pasdar N, Ohlsson M, Viñuela A, Frau F, Pomares-Millan H, Haid M, Jones AG, Thomas EL, Koivula RW, Kurbasic A, et al (In Press). Predicting and elucidating the etiology of fatty liver disease using a machine learning-based approach: an IMI DIRECT study. Abstract.

2023

Abstract.

McDonald TJ (2023). Commentary on Abnormal Hb A1c Result from a Diabetic Patient Leads to Unexpected Diagnosis. Clin Chem, 69(7), 688-689. Author URL.

Abstract.

Abstract. Author URL.

Katte JC, McDonald TJ, Sobngwi E, Jones AG (2023). The phenotype of type 1 diabetes in sub-Saharan Africa. Frontiers in Public Health, 11 Abstract.

2022

Thomas N, Hill A, Bolt R, Tippett P, Shields B, McDonald T, Jones A (2022). Age of onset does not affect progression of robustly defined adult onset type 1 diabetes. Author URL.

Abstract. Author URL.

Abstract.

Liu Z, Le K, Zhou X, Alexander JL, Lin S, Bewshea C, Chanchlani N, Nice R, McDonald T, Lamb CA, et al (2022). Neutralising Antibody Potency Against SARS-CoV-2 Ancestral and Omicron BA.1 and BA.4/5 Variants in Patients with Inflammatory Bowel Disease after Three Doses of COVID-19 Vaccine: a Prospective Multicentre Cohort Study (CLARITY).

Abstract. Author URL.

Dawed AY, Mari A, McDonald TJ, Li L, Wang S, Hong M-G, Sharma S, Robertson NR, Mahajan A, Wang X, et al (2022). Pharmacogenomics of GLP-1 Receptor Agonists: a genome wide analysis of observational data and large randomized controlled trials.

2021

(2021). 57th EASD Annual Meeting of the European Association for the Study of Diabetes. Diabetologia, 64(Suppl 1), 1-380.

Abstract.

Lin S, Kennedy NA, Saifuddin A, Sandoval DM, Reynolds CJ, Seoane RC, Kottoor SH, Pieper FP, Lin K-M, Butler DK, et al (2021). Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in infliximab- and vedolizumab-treated patients.

Abstract.

Lin S, Kennedy NA, Saifuddin A, Sandoval DM, Reynolds C, Seoane RC, Kottoor S, Pieper F, Lin K-M, Butler DK, et al (2021). Covid-19 vaccine-induced antibodies are attenuated and decay rapidly in infliximab treated patients.

Abstract. Author URL.

Abstract.

Atabaki-Pasdar N, Pomares-Millan H, Koivula RW, Tura A, Brown A, Viñuela A, Agudelo L, Coral D, van Oort S, Allin K, et al (2021). Inferring causal pathways between metabolic processes and liver fat accumulation: an IMI DIRECT study.

Kennedy NA, Lin S, Goodhand JR, Chanchlani N, Hamilton B, Bewshea C, Nice R, Chee D, Cummings F, Fraser A, et al (2021). Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines.

Grace SL, Bowden J, Walkey HC, Kaur A, Misra S, Shields BM, McKinley TJ, Oliver NS, McDonald T, Johnston DG, et al (2021). Islet autoantibody level distributions in type 1 diabetes and their association with genetic and clinical characteristics.

Abstract.

Carr A, Oram R, Narendran P, Andrews R (2021). MEASUREMENT OF C-PEPTIDE AT DIAGNOSIS INFORMS GLYCEMIC CONTROL BUT NOT HYPOGLYCEMIC RISK IN TYPE 1 DIABETES. Author URL.

Grace SL, Cooper A, Jones AG, McDonald TJ (2021). Zinc transporter 8 autoantibody testing requires age-related cut-offs. BMJ Open Diabetes Research & Care, 9(1), e002296-e002296. Abstract.

2020

(2020). 56th EASD Annual Meeting of the European Association for the Study of Diabetes. Diabetologia, 63(S1), 1-485.

(2020). Clinical care and other categories posters: Type 1 diabetes.

Abstract. Author URL.

Shepherd MH, Knight BA, Laskey K, McDonald TJ (2020). Newborn screening for glucose: 'An absolutely fantastic idea'. Author URL.

Chee D, Nice R, Hamilton B, Jones E, Hawkins S, Redstone C, Cairnes V, Pohl K, Kennedy NA, Ahmad T, et al (2020). Patient-Led Remote Intracapillary Pharmacokinetic Sampling (Fingerpricks): Validation and Acceptability for Home Therapeutic Drug Monitoring in Patients with Ibd in the COVID-19 Pandemic.

Elyas S, Allen G, Mcdonald T (2020). THE IDENTIFICATION OF STROKE BIO-MARKERS TO DISTINGUISH STROKE FROM STROKE MIMICS, a PILOT STUDY AND CONCEPT. Author URL.

Jones AG, Shields BM, Dennis JM, Hattersley AT, McDonald TJ, Thomas NJ (2020). The challenge of diagnosing type 1 diabetes in older adults. Diabet Med, 37(10), 1781-1782. Author URL.

Abstract. Author URL.

Abstract.

Grace SL, Cooper A, Jones AG, McDonald TJ (2020). Zinc transporter 8 autoantibody testing requires age-specific cut-offs. Author URL.

2019

Abstract. Author URL.

Long AE, Wilson IV, Aitken RJ, McDonald TJ, Wong FS, Williams AJK, Gillespie KM (2019). Insulin autoantibody level at diagnosis predicts long-term residual beta cell function. Author URL.

Abstract.

Chapman DP, Gooding KM, McDonald TJ, Shore AC (2019). Stability of urinary albumin and creatinine after 12 months storage at -20 °C and -80 °C. Pract Lab Med, 15 Abstract. Author URL.

Jones AG, Hill AV, Trippett PW, Hattersley AT, McDonald TJ, Shields BM (2019). The utility of clinical features and glycaemia at diagnosis in classifying young adult onset diabetes. Author URL.

Tikhonova I, Yang H, Salmon A, Bello S, Peters J, Robinson S, Coelho H, Kharechko A, Haigh R, Jani M, et al (2019). Therapeutic monitoring of TNF-alpha inhibitors in rheumatoid arthritis.

Hattersley A, McDonald T, Shepherd M, Hudson M, Colclough K, Ellard S, Pearson E, Shields B (2019). Use of the MODY probability calculator in the real-world setting. Author URL.

Abstract. Author URL.

Niwaha A, Nakanga W, Katte J-C, Shields B, Jones A, Nyirenda M, McDonald T (2019). When there is no haemolysis, plasma C-peptide levels are stable up to 5 days at 4 degrees C. Author URL.

2018

Mcdonald TJ, Flanagan SE, Knight B (2018). Differential diagnosis of hyperglycaemia at day five of life: Implications for a new born screening programme. Author URL.

Perry MH, McDonald TJ (2018). Method Comparison Between ELISAs Suggests Therapeutic Ranges for Infliximab Should be Assay-Specific. J Appl Lab Med, 3(3), 515-517. Author URL.

Tippett PW, Hill AV, McDonald TJ, Hattersley AT, Jones AG (2018). Prevalence and clinical associations of ZnT8 islet autoantibodies in the first year of adult diabetes. Author URL.

Huber JW, Fox C, Hill A, McDonald T, Shields B, Jones A (2018). Psychological resilience in Type 1 diabetes carries independent benefits for blood glucose control. Author URL.

Colombo M, McDonald TJ, McKeigue PM, Colhoun HM, Investigators SDRNTBIO (2018). Relationship of C-peptide persistence and HbA(1c) in type 1 diabetes. Author URL.

2017

McDonald T (2017). AIDS to correct genetic diagnosis in mody: being smarter with laboratory medicine. Pathology, 49

McDonald T (2017). Heterogeneity of type 1 diabetes. Pathology, 49

McDonald T (2017). Neonatal biochemistry: advances in neonatal diabetes. Pathology, 49

Shepherd M, Colclough K, McDonald TJ (2017). Tests aiding diagnosis of monogenic diabetes. Practical Diabetes, 34(6), 217-220a.

McDonald T (2017). The sequencer will see you now: getting the correct genetic diagnosis in maturity onset diabetes of the young. Pathology, 49

2016

McDonald TJ, Perry MH (2016). Detection of C-Peptide in Urine as a Measure of Ongoing Beta Cell Function. Methods Mol Biol, 1433, 93-102. Abstract. Author URL.

Johnson MB, Flanagan SE, Martins TB, Hill HR, Hattersley AT, McDonald TJ (2016). Low IgE is a Useful Tool to Identify STAT3 Gain-of-Function Mutations. Clin Chem, 62(11), 1536-1538. Author URL.

Craig ZV, Hill AV, McDonald TJ, Hattersley AT, Jones AG, Shields BM (2016). Time to change the HbA1c cut-off for prediabetes. Author URL.

2015

Weedon MN, Hill AV, McDonald TJ, Patel KA, Jones A, Hattersley AT, Oram R (2015). A novel inexpensive test can discriminate between Type 1 and Type 2 diabetes. Author URL.

Mcdonald TJ, Parfitt C, Armston A, Church D, Couchman L, Evans C, Wark G (2015). Commercial insulin immunoassays fail to detect commonly prescribed insulin analogues. Author URL.

McDonald TJ, Oram RA, Vaidya B (2015). Investigating hyperkalaemia in adults. BMJ, 351 Author URL.

McDonald TJ, Oram RA, Vaidya B (2015). RATIONAL TESTING Investigating hyperkalaemia in adults. BMJ-BRITISH MEDICAL JOURNAL, 351 Author URL.

2014

McDonald TJ, Warren RE (2014). Diagnostic confusion? Repeat HbA1c for the diagnosis of diabetes. DIABETIC MEDICINE, 31, 72-72. Author URL.

McDonald TJ, Warren R (2014). Diagnostic confusion? Repeat HbA1c for the diagnosis of diabetes. Author URL.

Koivula RW, Heggie A, Barnett A, Cederberg H, Hansen TH, Koopman AD, Ridderstråle M, Rutters F, Vestergaard H, Gupta R, et al (2014). Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: rationale and design of the epidemiological studies within the IMI DIRECT Consortium. Diabetologia

Babiker T, Perry M, McDonald T, Brooke A, O'Connor J (2014). High testosterone? Look again!. Endocrine Abstracts

McDonald TJ, Oram R, Shields B, Pearson E, Hattersley A (2014). Most people with long duration of type 1 diabetes are insulin microsecretors and produce their own endogenous insulin. Author URL.

Abstract.

2013

Clark P, McDonald T (2013). Diabetes Mellitus. In (Ed) The Immunoassay Handbook, 783-794.

Oram RA, McDonald TJ, Vaidya B (2013). Investigating hypokalaemia. BMJ, 347 Author URL.

McDonald TJ, Ellard S (2013). Maturity onset diabetes of the young: identification and diagnosis. Ann Clin Biochem, 50(Pt 5), 403-415. Abstract. Author URL.

Hammersley S, Oram R, Shepherd M, Moudiotis C, Fraser B, Mallam K, Cox J, Smith B, McDonald TJ, Besser REJ, et al (2013). Prevalence of non-Type 1 diabetes in paediatric diabetes. Author URL.

Abstract.

Abstract. Author URL.

2012

McDonald TJ, McEneny J, Pearson ER, Thanabalasingham G, Szopa M, Shields BM, Ellard S, Owen KR, Malecki MT, Hattersley AT, et al (2012). Lipoprotein composition in HNF1A-MODY: differentiating between HNF1A-MODY and type 2 diabetes. Clin Chim Acta, 413(9-10), 927-932. Abstract. Author URL.

2011

McDonald TJ, Perry MH, Jones AG, Donohoe M, Salzmann MB, O'Connor J (2011). A novel case of a raised testosterone and LH in a young man. Clinica Chimica Acta, 412(21-22), 1999-2001. Abstract.

Abstract. Author URL.

Thomas NJM, Besser REJ, Jones AG, McDonald TJ, Shields BM, Knight BA, Hattersley AT (2011). Simple and convenient alternatives to the mixed meal tolerance test. Author URL.

Abstract. Author URL.

2010

Hope SV, Shepherd M, Shields BM, McDonald T, Knight BA, Hattersley AT (2010). Patients with long-standing type 2 diabetes can develop absolute insulin deficiency. Author URL.

2009

Musich S, McDonald T, Chapman LS (2009). Health promotion strategies for the "boomer" generation: Wellness for the mature worker. American Journal of Health Promotion, 23(3), 1-9.

2008

2006

2005

Wang F, McDonald T, Reffitt B, Edington DW (2005). BMI, physical activity, and health care utilization/costs among medicare retirees. Obesity Research, 13(8), 1450-1457. Abstract.

2004

2003

Abstract.

2002

Abstract.

2001

Timothy_McDonald Details from cache as at 2023-10-03 17:39:44

Refresh publications

External Engagement and Impact

Awards

HSJ Acute Service Innovation of the Year 2021: Patient led remote phlebotomy
HSJ Value Awards Finalist: Clinical and Medical Services, Cancer Initiative of the Year 2020.
Diabetes UK Lily Clinical Science Poster Award – Diabetes UK Professional conference winner 2018 (Senior Author)Excellence in Improving Outcomes for Patients. NHS Healthcare Science Awards 2019
The ACB Professors’ Prize - The Association of Clinical Biochemistry and Laboratory Medicine research contribution prize. FOCUS national conference 2016
Diabetes UK Lily Clinical Science Poster Award – Diabetes UK Professional conference winner 2016 (runner up 2014)
Innovators in Diabetes (IDIA)- Lilly/ DUK- Best research presentation prize 2016
NIHR Research presentation prize- NIHR faculty meeting 2014
NIHR CSO Clinical Research Fellow 2013-2017
Young Healthcare Scientist of the Year The Department of Health/ Chief Scientific Officers 2012

Diabetes UK Lily Clinical Science Poster Award – Diabetes UK Professional conference 2016

The ACB Professors’ Prize Lecture- The Association of Clinical Biochemistry and Laboratory Medicine research contribution prize. FOCUS national conference 2016

NIHR CSO Clinical Research Fellow 2013 (four years funding)

The Department of Health Young Healthcare Scientist of the Year 2012 (London)

The University of Exeter Impact Award- finalist Student Impact Award 2011 (Exeter)

The Association of Clinical Biochemists regional Young Researcher Award 2010 First prize for best presentation and research paper (Swansea)

Regional NHS audit meeting, 2008 (Weston-Super-mare). Awarded second prize in clinical audit competition

The Association of Clinical Biochemistry regional meeting, 2008 (Gloucester). Awarded first prize Siemens award for best research paper presentation.

Committee/panel activities

Association of Clinical Biochemistry South-West Regional Tutor

Invited lectures

Identifying unusual diabetes! Association of Biochemists Ireland: Dublin 2014

Precision Medicine- getting the diagnosis right. KEM Pune, India 2015.

Association of Clinical Biochemist Professors’ prize lecture, Warick 2016

C-peptide: time to think again? Bristol Diabetes Association. Bristol 213

The analyser will see you now!. Association of Clinical Biochemists. midlands scientific meeting, Birmingham 2013

Systematic approach to correct genetic diagnosis. Diabetes UK, Manchester 2013

Using biomarkers to identify MODY in our clinics. Advances in the Science and Care of Diabetes. Winthrop Hospital Symposium, New York. May 2012

Maturity Onset Diabetes of the Young (MODY). Correct classification with the use of biomarkers. ACB FOCUS national conference. Harrogate 2011

Urine C-peptide creatinine ratio: a new marker of insulin secretion? KEM, Pune, India 201

Diabetes autoantibodies can discriminate MODY from Type 1 diabetes. South West Peninsula Immunology symposium, Dartington Hall. 2010

Getting the diabetes right, Urine C-peptide creatinine ratio. Association of Clinical Biochemists SWW regional scientific meeting, Exeter 2010

Profile

Professor Timothy J McDonald

Consultant Biochemist/ Hon. Professor

Overview

Broad research specialisms

Qualifications

Links

Research group links

Research

Research interests

Research projects

Grants/Funding

Research grants

Publications

Publications by category

Journal articles

Abstract:Diagnostic performance of the faecal immunochemical test for patients with low-risk symptoms of colorectal cancer in primary care: a service evaluation in the South West of England

Abstract:Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: an overview of the data from the epidemiological studies within the IMI DIRECT Consortium

Abstract:Glycated haemoglobin measurements from UK Biobank are different to those in linked primary care records: implications for combining biochemistry data from research studies and routine clinical care

Abstract:HLA-DQA1*05 is associated with the development of antibodies to anti-TNF therapy

Abstract:Age of Diagnosis Does Not Alter the Presentation or Progression of Robustly Defined Adult-Onset Type 1 Diabetes

Abstract:Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models

Abstract:Incretin hormone responses to carbohydrate and protein/fat are preserved in adults with sulfonylurea-treated KCNJ11 neonatal diabetes.

Abstract:Neurodevelopmental and Epilepsy Phenotypes in Individuals with Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5.

Abstract:Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study.

Abstract:Pretreatment Vitamin D Concentrations Do Not Predict Therapeutic Outcome to Anti-TNF Therapies in Biologic-Naïve Patients with Active Luminal Crohn’s Disease

Abstract:Residual β-Cell Function is Associated with Longer Time in Range in Individuals with Type 1 Diabetes

Abstract:The impact of the COVID-19 pandemic upon pancreatic cancer treatment (CONTACT Study): a UK national observational cohort study.

Abstract:The phenotype of type 1 diabetes in sub-Saharan Africa

Abstract:Vaccine escape, increased breakthrough and reinfection in infliximab-treated patients with IBD during the Omicron wave of the SARS-CoV-2 pandemic.

Abstract:Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients.

Abstract:Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab.

Abstract:Capturing the real-world benefit of residual β-cell function during clinically important time-periods in established Type 1 diabetes.

Abstract:Implications for sequencing of biologic therapy and choice of second anti‐TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti‐TNF therapy (IMSAT) therapeutic drug monitoring study

Abstract:Islet Autoantibody Level Distribution in Type 1 Diabetes and Their Association with Genetic and Clinical Characteristics.

Abstract:OP22 Antibody decay, T cell immunity and breakthrough infections following SARS-CoV-2 vaccination in infliximab- and vedolizumab-treated patients

Abstract:Patient-led Remote IntraCapillary pharmacoKinetic Sampling (fingerPRICKS) for Therapeutic Drug Monitoring in patients with Inflammatory Bowel Disease.

Abstract:Type 1 Diabetes Patients with Different Residual Beta-Cell Function but Similar Age, HBA1c, and Cardiorespiratory Fitness Have Differing Exercise-Induced Angiogenic Cell Mobilisation

Abstract:Understanding anti‐TNF treatment failure: does serum triiodothyronine‐to‐thyroxine (T3/T4) ratio predict therapeutic outcome to anti‐TNF therapies in biologic‐naïve patients with active luminal Crohn's disease?

Abstract:Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab

Abstract:Associations between low HDL, sex and cardiovascular risk markers are substantially different in sub-Saharan Africa and the UK: analysis of four population studies

Abstract:Choice of HbA1c threshold for identifying individuals at high risk of type 2 diabetes and implications for diabetes prevention programmes: a cohort study

Abstract:Clinical profiles of post-load glucose subgroups and their association with glycaemic traits over time: an IMI-DIRECT study.

Abstract:Correction to: the role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study (Diabetologia, (2020), 63, 4, (744-756), 10.1007/s00125-019-05083-6)

Abstract:Diagnostic performance of a faecal immunochemical test for patients with low-risk symptoms of colorectal cancer in primary care: an evaluation in the South West of England.

Abstract:Enzyme-linked immunosorbent assays for monitoring TNF-alpha inhibitors and antibody levels in people with rheumatoid arthritis: a systematic review and economic evaluation.

Abstract:Erratum to: Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications (Diabetes Care 2021; 44: 390–398)

Abstract:HbA1c performs well in monitoring glucose control even in populations with high prevalence of medical conditions that may alter its reliability: the OPTIMAL observational multicenter study

Abstract:Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD.

Abstract:Latent Autoimmune Diabetes of Adults (LADA) is Likely to Represent a Mixed Population of Autoimmune (Type 1) and Nonautoimmune (Type 2) Diabetes

Abstract:OP03 Anti-SARS-CoV2 antibody responses are attenuated in patients with Inflammatory Bowel Disease treated with infliximab

Abstract:Profiles of Glucose Metabolism in Different Prediabetes Phenotypes, Classified by Fasting Glycemia, 2-Hour OGTT, Glycated Hemoglobin, and 1-Hour OGTT: an IMI DIRECT Study.

Abstract:Reappearance of C-Peptide During the Third Trimester of Pregnancy in Type 1 Diabetes: Pancreatic Regeneration or Fetal Hyperinsulinism?

Abstract:Validating the positivity thresholds of drug-tolerant anti-infliximab and anti-adalimumab antibody assays.

Abstract:Zinc transporter 8 autoantibody testing requires age-related cut-offs

Abstract:A reference map of potential determinants for the human serum metabolome

Abstract:Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications

Abstract:HLA-DQA1*05 Carriage Associated with Development of Anti-Drug Antibodies to Infliximab and Adalimumab in Patients with Crohn's Disease.

Abstract:Parental experiences of a diagnosis of neonatal diabetes and perceptions of newborn screening for glucose: a qualitative study

Abstract:Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes: an IMI-DIRECT study

Abstract:Postexercise Glycemic Control in Type 1 Diabetes is Associated with Residual β-Cell Function

Abstract:Predictors of Recurrent Severe Hypoglycemia in Adults with Type 1 Diabetes and Impaired Awareness of Hypoglycemia During the HypoCOMPaSS Study.

Abstract:Primary care faecal calprotectin testing in children with suspected inflammatory bowel disease: a diagnostic accuracy study.

Abstract:Processes Underlying Glycemic Deterioration in Type 2 Diabetes: an IMI DIRECT Study

Abstract:The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study.

Abstract:Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study

Abstract:Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium.

Abstract:Erratum: Fetal macrosomia and neonatal hyperinsulinemic hypoglycemia associated with transplacental transfer of sulfonylurea in a mother with KCNJ11-related neonatal diabetes (Diabetes Care (2014) 37 (3333–3335) DOI: 10.2337/dc14-1247)

Abstract:Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration

Abstract:Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-K ATP -channel pathways

Abstract:Persistent C-peptide is associated with reduced hypoglycaemia but not HbA1c in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice?

Abstract:Persistent C-peptide secretion in Type 1 diabetes and its relationship to the genetic architecture of diabetes.

Abstract:Stability of urinary albumin and creatinine after 12 months storage at -20 °C and -80 °C.

Abstract:The association between GAD65 antibody levels and incident Type 2 Diabetes Mellitus in an adult population: a meta-analysis.

Abstract:Type 1 diabetes genetic risk score discriminates between monogenic and Type 1 diabetes in children diagnosed at the age of <5 years in the Iranian population.

Abstract:Variation in the Plasma Membrane Monoamine Transporter (PMAT) (Encoded by SLC29A4) and Organic Cation Transporter 1 (OCT1) (Encoded by SLC22A1) and Gastrointestinal Intolerance to Metformin in Type 2 Diabetes: an IMI DIRECT Study.

Abstract:Exocrine pancreatic dysfunction is common in hepatocyte nuclear factor 1β-associated renal disease and can be symptomatic.

Abstract:Faecal calprotectin effectively excludes inflammatory bowel disease in 789 symptomatic young adults with/without alarm symptoms: a prospective UK primary care cohort study.

Abstract:The governance structure for data access in the DIRECT consortium: an innovative medicines initiative (IMI) project.

Abstract:Current laboratory requirements for adrenocorticotropic hormone and renin/aldosterone sample handling are unnecessarily restrictive.

Abstract:
Diagnostic performance of the faecal immunochemical test for patients with low-risk symptoms of colorectal cancer in primary care: a service evaluation in the South West of England

Abstract:
Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: an overview of the data from the epidemiological studies within the IMI DIRECT Consortium

Abstract:
Glycated haemoglobin measurements from UK Biobank are different to those in linked primary care records: implications for combining biochemistry data from research studies and routine clinical care

Abstract:
HLA-DQA1*05 is associated with the development of antibodies to anti-TNF therapy

Abstract:
Age of Diagnosis Does Not Alter the Presentation or Progression of Robustly Defined Adult-Onset Type 1 Diabetes

Abstract:
Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models

Abstract:
Incretin hormone responses to carbohydrate and protein/fat are preserved in adults with sulfonylurea-treated KCNJ11 neonatal diabetes.

Abstract:
Neurodevelopmental and Epilepsy Phenotypes in Individuals with Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5.

Abstract:
Neutralising antibody potency against SARS-CoV-2 wild-type and omicron BA.1 and BA.4/5 variants in patients with inflammatory bowel disease treated with infliximab and vedolizumab after three doses of COVID-19 vaccine (CLARITY IBD): an analysis of a prospective multicentre cohort study.

Abstract:
Pretreatment Vitamin D Concentrations Do Not Predict Therapeutic Outcome to Anti-TNF Therapies in Biologic-Naïve Patients with Active Luminal Crohn’s Disease

Abstract:
Residual β-Cell Function is Associated with Longer Time in Range in Individuals with Type 1 Diabetes

Abstract:
The impact of the COVID-19 pandemic upon pancreatic cancer treatment (CONTACT Study): a UK national observational cohort study.

Abstract:
The phenotype of type 1 diabetes in sub-Saharan Africa

Abstract:
Vaccine escape, increased breakthrough and reinfection in infliximab-treated patients with IBD during the Omicron wave of the SARS-CoV-2 pandemic.

Abstract:
Adalimumab and Infliximab Impair SARS-CoV-2 Antibody Responses: Results from a Therapeutic Drug Monitoring Study in 11 422 Biologic-Treated Patients.

Abstract:
Antibody decay, T cell immunity and breakthrough infections following two SARS-CoV-2 vaccine doses in inflammatory bowel disease patients treated with infliximab and vedolizumab.

Abstract:
Capturing the real-world benefit of residual β-cell function during clinically important time-periods in established Type 1 diabetes.

Abstract:
Implications for sequencing of biologic therapy and choice of second anti‐TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti‐TNF therapy (IMSAT) therapeutic drug monitoring study

Abstract:
Islet Autoantibody Level Distribution in Type 1 Diabetes and Their Association with Genetic and Clinical Characteristics.

Abstract:
OP22 Antibody decay, T cell immunity and breakthrough infections following SARS-CoV-2 vaccination in infliximab- and vedolizumab-treated patients

Abstract:
Patient-led Remote IntraCapillary pharmacoKinetic Sampling (fingerPRICKS) for Therapeutic Drug Monitoring in patients with Inflammatory Bowel Disease.

Abstract:
Type 1 Diabetes Patients with Different Residual Beta-Cell Function but Similar Age, HBA1c, and Cardiorespiratory Fitness Have Differing Exercise-Induced Angiogenic Cell Mobilisation

Abstract:
Understanding anti‐TNF treatment failure: does serum triiodothyronine‐to‐thyroxine (T3/T4) ratio predict therapeutic outcome to anti‐TNF therapies in biologic‐naïve patients with active luminal Crohn's disease?

Abstract:
Anti-SARS-CoV-2 antibody responses are attenuated in patients with IBD treated with infliximab

Abstract:
Associations between low HDL, sex and cardiovascular risk markers are substantially different in sub-Saharan Africa and the UK: analysis of four population studies

Abstract:
Choice of HbA1c threshold for identifying individuals at high risk of type 2 diabetes and implications for diabetes prevention programmes: a cohort study

Abstract:
Clinical profiles of post-load glucose subgroups and their association with glycaemic traits over time: an IMI-DIRECT study.

Abstract:
Correction to: the role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study (Diabetologia, (2020), 63, 4, (744-756), 10.1007/s00125-019-05083-6)

Abstract:
Diagnostic performance of a faecal immunochemical test for patients with low-risk symptoms of colorectal cancer in primary care: an evaluation in the South West of England.

Abstract:
Enzyme-linked immunosorbent assays for monitoring TNF-alpha inhibitors and antibody levels in people with rheumatoid arthritis: a systematic review and economic evaluation.

Abstract:
Erratum to: Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications (Diabetes Care 2021; 44: 390–398)

Abstract:
HbA1c performs well in monitoring glucose control even in populations with high prevalence of medical conditions that may alter its reliability: the OPTIMAL observational multicenter study

Abstract:
Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD.

Abstract:
Latent Autoimmune Diabetes of Adults (LADA) is Likely to Represent a Mixed Population of Autoimmune (Type 1) and Nonautoimmune (Type 2) Diabetes

Abstract:
OP03 Anti-SARS-CoV2 antibody responses are attenuated in patients with Inflammatory Bowel Disease treated with infliximab

Abstract:
Profiles of Glucose Metabolism in Different Prediabetes Phenotypes, Classified by Fasting Glycemia, 2-Hour OGTT, Glycated Hemoglobin, and 1-Hour OGTT: an IMI DIRECT Study.

Abstract:
Reappearance of C-Peptide During the Third Trimester of Pregnancy in Type 1 Diabetes: Pancreatic Regeneration or Fetal Hyperinsulinism?

Abstract:
Validating the positivity thresholds of drug-tolerant anti-infliximab and anti-adalimumab antibody assays.

Abstract:
Zinc transporter 8 autoantibody testing requires age-related cut-offs

Abstract:
A reference map of potential determinants for the human serum metabolome

Abstract:
Clinical Impact of Residual C-Peptide Secretion in Type 1 Diabetes on Glycemia and Microvascular Complications

Abstract:
HLA-DQA1*05 Carriage Associated with Development of Anti-Drug Antibodies to Infliximab and Adalimumab in Patients with Crohn's Disease.

Abstract:
Parental experiences of a diagnosis of neonatal diabetes and perceptions of newborn screening for glucose: a qualitative study

Abstract:
Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes: an IMI-DIRECT study

Abstract:
Postexercise Glycemic Control in Type 1 Diabetes is Associated with Residual β-Cell Function

Abstract:
Predictors of Recurrent Severe Hypoglycemia in Adults with Type 1 Diabetes and Impaired Awareness of Hypoglycemia During the HypoCOMPaSS Study.

Abstract:
Primary care faecal calprotectin testing in children with suspected inflammatory bowel disease: a diagnostic accuracy study.

Abstract:
Processes Underlying Glycemic Deterioration in Type 2 Diabetes: an IMI DIRECT Study

Abstract:
The role of physical activity in metabolic homeostasis before and after the onset of type 2 diabetes: an IMI DIRECT study.

Abstract:
Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study

Abstract:
Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium.

Abstract:
Erratum: Fetal macrosomia and neonatal hyperinsulinemic hypoglycemia associated with transplacental transfer of sulfonylurea in a mother with KCNJ11-related neonatal diabetes (Diabetes Care (2014) 37 (3333–3335) DOI: 10.2337/dc14-1247)

Abstract:
Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration

Abstract:
Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-K ATP -channel pathways

Abstract:
Persistent C-peptide is associated with reduced hypoglycaemia but not HbA1c in adults with longstanding Type 1 diabetes: evidence for lack of intensive treatment in UK clinical practice?

Abstract:
Persistent C-peptide secretion in Type 1 diabetes and its relationship to the genetic architecture of diabetes.

Abstract:
Stability of urinary albumin and creatinine after 12 months storage at -20 °C and -80 °C.

Abstract:
The association between GAD65 antibody levels and incident Type 2 Diabetes Mellitus in an adult population: a meta-analysis.

Abstract:
Type 1 diabetes genetic risk score discriminates between monogenic and Type 1 diabetes in children diagnosed at the age of <5 years in the Iranian population.

Abstract:
Variation in the Plasma Membrane Monoamine Transporter (PMAT) (Encoded by SLC29A4) and Organic Cation Transporter 1 (OCT1) (Encoded by SLC22A1) and Gastrointestinal Intolerance to Metformin in Type 2 Diabetes: an IMI DIRECT Study.

Abstract:
Exocrine pancreatic dysfunction is common in hepatocyte nuclear factor 1β-associated renal disease and can be symptomatic.

Abstract:
Faecal calprotectin effectively excludes inflammatory bowel disease in 789 symptomatic young adults with/without alarm symptoms: a prospective UK primary care cohort study.

Abstract:
The governance structure for data access in the DIRECT consortium: an innovative medicines initiative (IMI) project.

Abstract:
Current laboratory requirements for adrenocorticotropic hormone and renin/aldosterone sample handling are unnecessarily restrictive.

Abstract:
Proinsulin is stable at room temperature for 24 hours in EDTA: a clinical laboratory analysis (adAPT 3).

Abstract:
Screening for neonatal diabetes at day 5 of life using dried blood spot glucose measurement

Abstract:
A Type 1 Diabetes Genetic Risk Score can Aid Discrimination Between Type 1 and Type 2 Diabetes in Young Adults.

Abstract:
Beta cell function and ongoing autoimmunity in long-standing, childhood onset type 1 diabetes.

Abstract:
Detection of C-Peptide in Urine as a Measure of Ongoing Beta Cell Function.

Abstract:
Random non-fasting C-peptide: bringing robust assessment of endogenous insulin secretion to the clinic.

Abstract:
Systematic Population Screening, Using Biomarkers and Genetic Testing, Identifies 2.5% of the U.K. Pediatric Diabetes Population with Monogenic Diabetes.

Abstract:
Infliximab and adalimumab are stable in whole blood clotted samples for seven days at room temperature.

Abstract:
Most people with long-duration type 1 diabetes in a large population-based study are insulin microsecretors.

Abstract:
Systolic blood pressure control among individuals with type 2 diabetes: a comparative effectiveness analysis of three interventions

Abstract:
Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease.

Abstract:
Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes: Rationale and design of the epidemiological studies within the IMI DIRECT Consortium

Abstract:
Fetal macrosomia and neonatal hyperinsulinemic hypoglycemia associated with transplacental transfer of sulfonylurea in a mother with KCNJ11-related neonatal diabetes.

Abstract:
Home urine C-peptide creatinine ratio can be used to monitor islet transplant function.

Abstract:
The HNF4A R76W mutation causes atypical dominant Fanconi syndrome in addition to a β cell phenotype.

Abstract:
The association between postprandial urinary C-peptide creatinine ratio and the treatment response to liraglutide: a multi-centre observational study