Publications by year
In Press
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
Nakanga WP, Crampin AC, Mkandawire J, Banda L, Andrews RC, Hattersley AT, Nyirenda MJ, Rodgers LR (In Press). Waist circumference and glycaemia are strong predictors of progression to diabetes in individuals with prediabetes in sub-Saharan Africa: 4-year prospective cohort study in Malawi.
Abstract:
Waist circumference and glycaemia are strong predictors of progression to diabetes in individuals with prediabetes in sub-Saharan Africa: 4-year prospective cohort study in Malawi
ABSTRACTIntroductionSub-Saharan Africa is projected to have the highest increase in the number of people with diabetes worldwide. However, the drivers of diabetes in this region have not been clearly elucidated. The aim of this study was to evaluate the incidence of diabetes and the predictors of progression in a population-based cohort with impaired fasting glucose (IFG) in Malawi.MethodsWe used data from an extensive rural and urban non-communicable disease survey. One hundred seventy-five, of 389 individuals with impaired fasting glucose (IFG) at baseline, age 48 ±15 years and body mass index 27.5 ±5.9 kg/m2 were followed up for a median of 4.2 years (714 person-years). Incidence rates were calculated, and predictors of progression to diabetes were analysed using multivariable logistic regression models, with overall performance determined using receiver operator characteristics (ROC) curves.ResultsThe median follow-up was 4.2 (IQR 3.4 – 4.7) years. Forty-five out of 175 (26%) progressed to diabetes. Incidence rates of diabetes were 62.9 per 1000 person-years 95% CI, 47.0-84.3. The predictors of progression were higher; age (odds ratio [OR] 1.48, 95% CI 1.01-2.19, P=0.046), BMI (OR 1.98, 95% CI 1.34-2.94,P=0.001), waist circumference (OR 2.50, 95% CI 1.60-3.91,P<0.001), waist-hip ratio (OR 1.40, 95%CI 0.98-2.01,P=0.03), systolic blood pressure (OR 1.56, 95% CI 1.10-2.21,P=0.01), fasting plasma glucose (OR 1.53, 95%CI 1.08-2.16,P=0.01), cholesterol (OR 1.44, 95% CI 1.00-2.08,P=0.05) and low-density lipoprotein cholesterol (OR 1.80, 95% 1.23-2.64,P=0.002). A simple model combining fasting plasma glucose and waist circumference was predictive of progression to diabetes (ROC area under the curve=0.79)ConclusionThe incidence of diabetes in people with IFG in Malawi is higher than those seen in Europe (35.0 per 1,000 person-years) but similar to those seen in India (61.0 per 1,000 person-years). Predictors of progression are like those seen in other populations. A simple chart with probabilities of progression to diabetes based on waist circumference and fasting plasma glucose could be used to identify those at risk of progression in clinical settings in sub-Saharan Africa.
Abstract.
2023
(2023). <scp>Roux‐en‐Y</scp> gastric bypass, gastric banding, or sleeve gastrectomy for severe obesity: Baseline data from the <scp>By‐Band‐Sleeve randomized controlled trial</scp>.
Obesity,
31(5), 1290-1299.
Abstract:
Roux‐en‐Y gastric bypass, gastric banding, or sleeve gastrectomy for severe obesity: Baseline data from the By‐Band‐Sleeve randomized controlled trial
AbstractObjectiveThis paper reports the study design, participant characteristics, and recruitment results of By‐Band‐Sleeve, which investigated the clinical and cost‐effectiveness of gastric bypass, gastric banding, and sleeve gastrectomy in adults with severe obesity in the UK.MethodsA pragmatic open adaptive noninferiority trial with 3‐year follow‐up was conducted. Participants were randomly assigned to bypass or band initially and to sleeve after the adaptation. Co‐primary end points are weight loss and health‐related quality of life assessed using the EQ‐5D utility index.ResultsBetween December 2012 and August 2015, the study recruited into two groups and, after the adaptation, into three groups until September 2019. The study screened 6960 patients; 4732 (68%) were eligible and 1351 (29%) were randomized; 5 subsequently withdrew consent to use data, leaving 462, 464, and 420 assigned to bypass, band, and sleeve, respectively. Baseline data showed high levels of obesity (mean BMI = 46.4 kg/m2; SD: 6.9) and comorbidities (e.g. 31% diabetes), low scores for health‐related quality of life, and high levels of anxiety and depression (e.g. 25% abnormal scores). Nutritional parameters were poor, and the average equivalized household income was low (£16,667).ConclusionsBy‐Band‐Sleeve fully recruited. Participant characteristics are consistent with contemporary patients having bariatric surgery, and therefore the results will be generalizable.
Abstract.
Scott SN, Hayes C, Zeuger T, Davies AP, Andrews RC, Cocks M (2023). Clinical Considerations and Practical Advice for People Living with Type 2 Diabetes Who Undertake Regular Exercise or Aim to Exercise Competitively. Diabetes Spectrum, 36(2), 114-126.
Bourne JE, Leary S, Page A, Searle A, England C, Thompson D, Andrews RC, Foster C, Cooper AR (2023). Electrically assisted cycling for individuals with type 2 diabetes mellitus: a pilot randomized controlled trial. Pilot and Feasibility Studies, 9(1).
Cockcroft EJ, Wooding EL, Narendran P, Dias RP, Barker AR, Moudiotis C, Clarke R, Andrews RC (2023). Factors affecting the support for physical activity in children and adolescents with type 1 diabetes mellitus: a national survey of health care professionals' perceptions.
BMC Pediatr,
23(1).
Abstract:
Factors affecting the support for physical activity in children and adolescents with type 1 diabetes mellitus: a national survey of health care professionals' perceptions.
BACKGROUND: Many children and adolescents with Type 1 Diabetes Mellitus (T1DM) don't meet the recommended levels of physical activity. Healthcare professionals (HCPs) have a key role in supporting and encouraging children and adolescents with T1DM to be physically active. This study aims to understand the perspectives of HCPs in relation to supporting physical activity and implementing guidelines relating to physical activity. METHODS: an online mixed methods survey was circulated to HCPs in pediatric diabetes units in England and Wales. Participants were asked about how they support physical activity in their clinic and their perceptions of barriers/enablers of providing physical activity support to children and adolescents with T1DM. Quantitative data were analysed descriptively. An deductive thematic approach was applied to the free text responses using the Capability Opportunity Motivation model of Behaviour (COM-B) as a framework. RESULTS: Responses were received from 114 individuals at 77 different pediatric diabetes units (45% of pediatric diabetes units in England and Wales). HCPs surveyed felt that the promotion of physical activity is important (90%) and advised patients to increase levels of physical activity (88%). 19% of the respondents felt they did not have sufficient knowledge to provide support. HCPs reported limited knowledge and confidence, time and resources as barriers to providing support. They also felt the current guidance was too complicated with few practical solutions. CONCLUSION: Pediatric HCPs need training and support to be able to encourage and support children and adolescents with T1D to be a physical activity. In addition, resources that provide simple and practical advice to manage glucose around exercise are needed.
Abstract.
Author URL.
Ahmed AMG, Andrews RC (2023). Medical Management of Obesity. In (Ed) Obesity, Bariatric and Metabolic Surgery, 63-81.
Morris A, Bright C, Cocks M, Gibson N, Goff L, Greaves C, Griffin S, Jane B, Kinnafick F, Robb P, et al (2023). Recommendations from Diabetes UK's 2022 diabetes and physical activity workshop.
Diabet Med,
40(9).
Abstract:
Recommendations from Diabetes UK's 2022 diabetes and physical activity workshop.
AIMS: to describe the process and outputs of a workshop convened to identify key priorities for future research in the area of diabetes and physical activity and provide recommendations to researchers and research funders on how best to address them. METHODS: a 1-day research workshop was conducted, bringing together researchers, people living with diabetes, healthcare professionals, and members of staff from Diabetes UK to identify and prioritise recommendations for future research into physical activity and diabetes. RESULTS: Workshop attendees prioritised four key themes for further research: (i) better understanding of the physiology of exercise in all groups of people: in particular, what patient metabolic characteristics influence or predict the physiological response to physical activity, and the potential role of physical activity in beta cell preservation; (ii) designing physical activity interventions for maximum impact; (iii) promoting sustained physical activity across the life course; (iv) designing physical activity studies for groups with multiple long-term conditions. CONCLUSIONS: This paper outlines recommendations to address the current gaps in knowledge related to diabetes and physical activity and calls on the research community to develop applications in these areas and funders to consider how to stimulate research in these areas.
Abstract.
Author URL.
Niwaha AJ, Rodgers LR, Hattersley AT, Andrews RC, Shields BM, Nyirenda MJ, Jones AG (2023). The impact of prolonged walking on fasting plasma glucose in type 2 diabetes: a Randomised controlled crossover study.
2022
Nakanga WP, Balungi P, Niwaha AJ, Shields BM, Hughes P, Andrews RC, Mc Donald TJ, Nyirenda MJ, Hattersley AT (2022). Alternative pre-analytic sample handling techniques for glucose measurement in the absence of fluoride tubes in low resource settings.
PLoS One,
17(2).
Abstract:
Alternative pre-analytic sample handling techniques for glucose measurement in the absence of fluoride tubes in low resource settings.
INTRODUCTION: Sodium fluoride (NaF) tubes are the recommended tubes for glucose measurements, but these are expensive, have limited number of uses, and are not always available in low resource settings. Alternative sample handling techniques are thus needed. We compared glucose stability in samples collected in various tubes exposed to different pre-analytical conditions in Uganda. METHODS: Random (non-fasted) blood samples were drawn from nine healthy participants into NaF, Ethylenediaminetetraacetic acid (EDTA), and plain serum tubes. The samples were kept un-centrifuged or centrifuged with plasma or serum pipetted into aliquots, placed in cool box with ice or at room temperature and were stored in a permanent freezer after 0, 2, 6, 12 and 24 hours post blood draw before glucose analysis. RESULTS: Rapid decline in glucose concentrations was observed when compared to baseline in serum (declined to 64%) and EDTA-plasma (declined to 77%) after 6 hours when samples were un-centrifuged at room temperature whilst NaF-plasma was stable after 24 hours in the same condition. Un-centrifuged EDTA-plasma kept on ice was stable for up to 6 hours but serum was not stable (degraded to 92%) in the same conditions. Early centrifugation prevented glucose decline even at room temperature regardless of the primary tube used with serum, EDTA-plasma and NaF-plasma after 24 hours. CONCLUSION: in low resource settings we recommend use of EDTA tubes placed in cool box with ice and analysed within 6 hours as an alternative to NaF tubes. Alternatively, immediate separation of blood with manual hand centrifuges will allow any tube to be used even in remote settings with no electricity.
Abstract.
Author URL.
Dawson S, Duncan L, Ahmed A, Gimson A, Henderson EJ, Rees J, Strong E, Drake MJ, Cotterill N, Huntley AL, et al (2022). Assessment and Treatment of Nocturia in Endocrine Disease in a Primary Care Setting: Systematic Review and Nominal Group Technique Consensus.
European Urology Focus,
8(1), 52-59.
Abstract:
Assessment and Treatment of Nocturia in Endocrine Disease in a Primary Care Setting: Systematic Review and Nominal Group Technique Consensus
Context: Salt and water homeostasis is regulated hormonally, so polyuria can result from endocrine disease directly or via secondary effects. These mechanisms are not consistently considered in primary care management of nocturia. Objective: to conduct a systematic review (SR) of nocturia in endocrine disease and reach expert consensus for primary care management. Evidence acquisition: Four databases were searched from January 2000 to April 2020. A total of 4382 titles and abstracts were screened, 36 studies underwent full-text screening, and 14 studies were included in the analysis. Expert and public consensus was achieved using the nominal group technique (NGT). Evidence synthesis: Twelve studies focused on mechanisms of nocturia, while two evaluated treatment options; none of the studies took place in a primary care setting. NGT consensus identified key clinical evaluation themes, including the presence of thirst, a medical background of diabetes mellitus or insipidus, thyroid disease, oestrogen status, medications (fluid loss or xerostomia), and general examination including body mass index. Proposed investigations include a bladder diary, renal and thyroid function, calcium, and glycated haemoglobin. Morning urine osmolarity should be examined in the context of polyuria of >2.5 l/24 h persisting despite fluid advice, with urine concentration >600 mOsm/l after fluid restriction excluding diabetes insipidus. Treatment should involve education, including adjustment of lifestyle and medication where possible. Any underlying endocrine disorder should be managed according to local guidance. Referral to endocrinology is needed if there is hyperthyroidism, hyperparathyroidism, or morning urine osmolarity
Abstract.
Smith M, Dawson S, Andrews RC, Eriksson SH, Selsick H, Skyrme-Jones A, Udayaraj U, Rees J, Strong E, Henderson EJ, et al (2022). Evaluation and Treatment in Urology for Nocturia Caused by Nonurological Mechanisms: Guidance from the PLANET Study.
Eur Urol Focus,
8(1), 89-97.
Abstract:
Evaluation and Treatment in Urology for Nocturia Caused by Nonurological Mechanisms: Guidance from the PLANET Study.
Patients with nocturia are commonly referred to urology clinics, including many for whom a nonurological medical condition is responsible for their symptoms. The PLanning Appropriate Nocturia Evaluation and Treatment (PLANET) study was established to develop practical approaches to equip healthcare practitioners to deal with the diverse causes of nocturia, based on systematic reviews and expert consensus. Initial assessment and therapy need to consider the possibility of one or more medical conditions falling into the "SCREeN" areas of Sleep medicine (insomnia, periodic limb movements of sleep, parasomnias, and obstructive sleep apnoea), Cardiovascular (hypertension and congestive heart failure), Renal (chronic kidney disease), Endocrine (diabetes mellitus, thyroid disease, pregnancy/menopause, and diabetes insipidus), and Neurology. Medical and medication causes of xerostomia should also be considered. Some key indicators for these conditions can be identified in urology clinics, working in partnership with the primary care provider. Therapy of the medical condition in some circumstances lessens the severity of nocturia. However, in many cases there is a conflict between the two, in which case the medical condition generally takes priority on safety grounds. It is important to provide patients with a realistic expectation of therapy and awareness of limitations of current therapeutic options for nocturia. PATIENT SUMMARY: Nocturia is the symptom of waking at night to pass urine. Commonly, this problem is referred to urology clinics. However, in some cases, the patient does not have a urological condition but actually a condition from a different speciality of medicine. This article describes how best the urologist and the primary care doctor can work together to assess the situation and make sensible and safe treatment suggestions. Unfortunately, there is sometimes no safe or effective treatment choice for nocturia, and treatment needs to focus instead on supportive management of symptoms.
Abstract.
Author URL.
Andrews RC, Narendran P, Cockcroft E (2022). Exercise testing in diabetes. In (Ed) Sport and Exercise Physiology Testing Guidelines, 231-240.
Garbutt J, England C, Jones AG, Andrews RC, Salway R, Johnson L (2022). Is glycaemic control associated with dietary patterns independent of weight change in people newly diagnosed with type 2 diabetes? Prospective analysis of the Early-ACTivity-In-Diabetes trial.
BMC Medicine,
20(1).
Abstract:
Is glycaemic control associated with dietary patterns independent of weight change in people newly diagnosed with type 2 diabetes? Prospective analysis of the Early-ACTivity-In-Diabetes trial
Abstract
. Background
. It is unclear whether diet affects glycaemic control in type 2 diabetes (T2D), over and above its effects on bodyweight. We aimed to assess whether changes in dietary patterns altered glycaemic control independently of effects on bodyweight in newly diagnosed T2D.
.
. Methods
. We used data from 4-day food diaries, HbA1c and potential confounders in participants of the Early-ACTivity-In-Diabetes trial measured at 0, 6 and 12 months. At baseline, a ‘carb/fat balance’ dietary pattern and an ‘obesogenic’ dietary pattern were derived using reduced-rank regression, based on hypothesised nutrient-mediated mechanisms linking dietary intake to glycaemia directly or via obesity. Relationships between 0 and 6 month change in dietary pattern scores and baseline-adjusted HbA1c at 6 months (n = 242; primary outcome) were assessed using multivariable linear regression. Models were repeated for periods 6–12 months and 0–12 months (n = 194 and n = 214 respectively; secondary outcomes).
.
. Results
. Reductions over 0–6 months were observed in mean bodyweight (− 2.3 (95% CI: − 2.7, − 1.8) kg), body mass index (− 0.8 (− 0.9, − 0.6) kg/m2), energy intake (− 788 (− 953, − 624) kJ/day), and HbA1c (− 1.6 (− 2.6, -0.6) mmol/mol). Weight loss strongly associated with lower HbA1c at 0–6 months (β = − 0.70 [95% CI − 0.95, − 0.45] mmol/mol/kg lost). Average fat and carbohydrate intakes changed to be more in-line with UK healthy eating guidelines between 0 and 6 months. Dietary patterns shifting carbohydrate intakes higher and fat intakes lower were characterised by greater consumption of fresh fruit, low-fat milk and boiled/baked potatoes and eating less of higher-fat processed meats, butter/animal fats and red meat. Increases in standardised ‘carb/fat balance’ dietary pattern score associated with improvements in HbA1c at 6 months independent of weight loss (β = − 1.54 [− 2.96, − 0.13] mmol/mol/SD). No evidence of association with HbA1c was found for this dietary pattern at other time-periods. Decreases in ‘obesogenic’ dietary pattern score were associated with weight loss (β = − 0.77 [− 1.31, − 0.23] kg/SD) but not independently with HbA1c during any period.
.
. Conclusions
. Promoting weight loss should remain the primary nutritional strategy for improving glycaemic control in early T2D. However, improving dietary patterns to bring carbohydrate and fat intakes closer to UK guidelines may provide small, additional improvements in glycaemic control.
.
. Trial registration
. ISRCTN92162869. Retrospectively registered on 25 July 2005
.
Abstract.
Carroll HA, Toumpakari Z, Andrews RC, Falconer C, James LJ, Betts JA, England C, Cooper AR, Johnson L (2022). The association between sugar at breakfast and energy intake in people with or at high risk of type 2 diabetes: a within-person analysis of STAMP-2 data.
2021
CARR A, ORAM RA, NARENDRAN P, ANDREWS RC (2021). 153-OR: Measurement of C-Peptide at Diagnosis Informs Glycemic Control but Not Hypoglycemic Risk in Type 1 Diabetes. Diabetes, 70(Supplement_1).
COCKCROFT E, NARENDRAN P, WOODING E, ANDREWS RC (2021). 931-P: Supporting Physical Activity in Children with Type 1 Diabetes: a Survey of Health Care Professionals. Diabetes, 70(Supplement_1).
Beese S, Price M, Andrews R, Tomlinson C, Sharma P, Moore D, Narendran P, Syst BT1D (2021). A systematic review and meta-analysis of interventions to preserve insulin-secreting beta cell function in people newly diagnosed with type 1 diabetes: Results from intervention studies aimed at improving glucose control.
Author URL.
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:
Choice of HbA1c threshold for identifying individuals at high risk of type 2 diabetes and implications for diabetes prevention programmes: a cohort study
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.
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.
Ahmed AMG, Andrews RC (2021). Medical Management of Obesity. In (Ed) Obesity, Bariatric and Metabolic Surgery, 1-19.
Hesketh K, Low J, Andrews R, Jones CA, Jones H, Jung ME, Little J, Mateus C, Pulsford R, Singer J, et al (2021). Mobile Health Biometrics to Enhance Exercise and Physical Activity Adherence in Type 2 Diabetes (MOTIVATE-T2D): protocol for a feasibility randomised controlled trial.
BMJ Open,
11(11).
Abstract:
Mobile Health Biometrics to Enhance Exercise and Physical Activity Adherence in Type 2 Diabetes (MOTIVATE-T2D): protocol for a feasibility randomised controlled trial.
INTRODUCTION: Exercise and physical activity (PA) are fundamental to the treatment of type 2 diabetes. Current exercise and PA strategies for newly diagnosed individuals with type 2 diabetes are either clinically effective but unsuitable in routine practice (supervised exercise) or suitable in routine practice but clinically ineffective (PA advice). Mobile health (mHealth) technologies, offering biometric data to patients and healthcare professionals, may bridge the gap between supervised exercise and PA advice, enabling patients to engage in regular long-term physically active lifestyles. This feasibility randomised controlled trial (RCT) will evaluate the use of mHealth technology when incorporated into a structured home-based exercise and PA intervention, in those recently diagnosed with type 2 diabetes. METHODS AND ANALYSIS: This feasibility multicentre, parallel group RCT will recruit 120 individuals with type 2 diabetes (diagnosis within 5-24 months, aged 40-75 years) in the UK (n=60) and Canada (n=60). Participants will undertake a 6-month structured exercise and PA intervention and be supported by an exercise specialist (active control). The intervention group will receive additional support from a smartwatch and phone app, providing real-time feedback and enabling improved communication between the exercise specialist and participant. Primary outcomes are recruitment rate, adherence to exercise and loss to follow-up. Secondary outcomes include a qualitative process evaluation and piloting of potential clinical outcome measures for a future RCT. ETHICS AND DISSEMINATION: the trial was approved in the UK by the South East Scotland Research Ethics Committee 01 (20/SS/0101) and in Canada by the Clinical Research Ethics Board of the University of British Columbia (H20-01936), and is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Results will be published in peer-reviewed journals and presented at national and international scientific meetings. TRIAL REGISTRATION NUMBERS: ISRCTN14335124; ClinicalTrials.gov: NCT04653532.
Abstract.
Author URL.
2020
Narendran P, Greenfield S, Troughton J, Doherty Y, Quann N, Thompson C, Litchfield I, Andrews RC, EXTOD Education Programme Development Team (2020). Development of a group structured education programme to support safe exercise in people with Type 1 diabetes: the EXTOD education programme.
Diabet Med,
37(6), 945-952.
Abstract:
Development of a group structured education programme to support safe exercise in people with Type 1 diabetes: the EXTOD education programme.
AIM: to develop a structured education programme for individuals with Type 1 diabetes who are engaging in regular exercise. METHOD: a multidisciplinary team of experts in supporting exercise and physical activity for people with Type 1 diabetes, alongside researchers with experience of developing self-management education, developed an exercise programme using the Medical Research Council framework. The programme was informed by a review of the evidence relating to Type 1 diabetes and exercise, the behaviour change literature (including the behaviour change taxonomy), and qualitative interviews with stakeholders. The programme and supporting resources were refined using an iterative process of testing, delivery and collecting feedback from participants and the wider development team. RESULTS: the outcome of the intervention development was the design of a feasible and acceptable intervention for people with Type 1 diabetes to support safe exercise. The pilot allowed refinement of the intervention prior to testing in a two-site feasibility randomized controlled trial. Key findings from the pilot informed minor restructuring of the timetable (timings and order) and adaptation of supporting educational materials (participant handbook and teaching materials). CONCLUSION: the 'EXercise in people with Type One Diabetes' (EXTOD) education programme has been developed using robust methodology for the generation of educational interventions. It now needs testing in a randomized controlled trial.
Abstract.
Author URL.
Cockcroft EJ, Narendran P, Andrews RC (2020). Exercise‐induced hypoglycaemia in type 1 diabetes.
Experimental Physiology,
105(4), 590-599.
Abstract:
Exercise‐induced hypoglycaemia in type 1 diabetes
New Findings
What is the topic of this review?
Hypoglycaemia is a commonly cited barrier to exercise in type 1 diabetes mellitus (T1D). Knowledge of approaches to prevent or manage exercise‐induced hypoglycaemia can support patients to exercise and help clinicians to give advice. This review presents evidence‐based strategies to prevent exercise‐induced hypoglycaemia in T1D.
What advances does it highlight?
This review highlights approaches that can be used before, during and after exercise to mitigate the risk of hypoglycaemia. The approaches include the timing of exercise, the type of exercise, adjustments to insulin and carbohydrate, use of novel technology and education.
AbstractExercise is a key component for the management of type 1 diabetes mellitus (T1D) and is associated with reduced risk of cardiovascular disease, decreased daily insulin requirements and improved quality of life. Owing to these benefits, people with T1D are recommended to undertake regular physical activity, 150 min per week for adults and 60 min per day for children and adolescents. Despite the recommendations, many people do not meet these targets. One of the commonly cited barriers to exercise is fear of hypoglycaemia along with limited knowledge of effective preventative strategies. Hypoglycaemia can be difficult to predict, and symptoms are often masked during exercise or stress of competition. For athletes with T1D, hypoglycaemia can also limit sporting success. Hypoglycaemia before an event increases the risks of hypoglycaemia during competition and can reduce performance. To avoid hypoglycaemia, people with T1D may avoid exercise altogether or consume excessive amounts of carbohydrates, which mitigates many of the health benefits of exercise. Increased understanding of approaches to prevent or manage hypoglycaemia is therefore important to help increase levels of physical activity in people with T1D and to support athletes with T1D to compete at the highest level. This review outlines the prevalence of exercise‐related hypoglycaemia, its underlying physiology and the strategies that can be used to prevent and manage exercise‐induced hypoglycaemia in T1D. Our hope is that this knowledge will be used by people with T1D and their clinicians to find individual approaches to manage exercise‐related hypoglycaemia.
Abstract.
Hopkins M, Andrews R, Salem V, Taylor R, le Roux CW, Robertson E, Burns E (2020). Improving understanding of type 2 diabetes remission: research recommendations from Diabetes UK’s 2019 remission workshop.
Diabetic Medicine,
37(11), 1944-1950.
Abstract:
Improving understanding of type 2 diabetes remission: research recommendations from Diabetes UK’s 2019 remission workshop
AbstractAimTo describe the process and outputs of a workshop convened to identify key priorities for future research in the area of remission of type 2 diabetes, and provide recommendations to researchers and research funders on how best to address them. With the ultimate aim of enabling the remission of type 2 diabetes to become a possibility for more people.MethodsA 1‐day research workshop was conducted, bringing together 31 researchers, people living with diabetes, healthcare professionals and members of staff from Diabetes UK to identify and prioritize recommendations for future research into remission of type 2 diabetes.ResultsWorkshop attendees identified 10 key themes for further research. Four of these themes were prioritized for further focus: (i) understanding how to personalize lifestyle approaches based on biology, patient choice and subtypes; (ii) understanding the biology of remission; (iii) understanding the most effective approaches to implementation of lifestyle interventions; and (iv) understanding the best approaches to combining therapies (gut hormones, other drugs, lifestyle approaches and bariatric surgery).ConclusionsThis paper outlines recommendations to address the current gaps in knowledge related to remission of type 2 diabetes.
Abstract.
England CY, Andrews RC (2020). James Lind Alliance research priorities: should diet and exercise be used as an alternative to drugs for the management of type 2 diabetes or alongside them?.
Diabetic Medicine,
37(4), 564-572.
Abstract:
James Lind Alliance research priorities: should diet and exercise be used as an alternative to drugs for the management of type 2 diabetes or alongside them?
AbstractAimTo review evidence on whether diet and exercise should be used as an alternative to drug therapy for the management of type 2 diabetes or alongside.MethodWe present a narrative review that draws on evidence from other systematic reviews and meta‐analyses, narrative reviews, trials and cohort studies. We focused mainly on glycaemic control rather than control of blood pressure or cholesterol.ResultsGood‐quality dietary advice that results in weight loss of >5% and physical activity interventions of >150 min/week of moderate to vigorous physical activity, combined with resistance exercise, can produce improvements in HbA1c similar to those produced by the addition of glucose‐lowering drugs. These improvements can be seen at all stages of the disease. There are recognized interactions between glucose‐lowering drugs and physical activity which may not be synergistic, but these are not well understood, and it is not clear if they are considered in clinical practice. Studies that explicitly compare drugs with diet or physical activity or control for drug use found that lifestyle could delay or reduce medication use, but most people eventually needed to progress to drug treatment. There are few studies, however, that provide strategies for the long‐term maintenance of weight loss or physical activity.ConclusionDiet and physical activity are of key importance in type 2 diabetes management, and attention to them improves glycaemic control and cardiovascular disease risk, but it is not yet known whether maintained lifestyle changes provide an alternative to drug therapy in the long term.
Abstract.
Glyn TC, Ho MW, Lambert AP, Thomas JDJ, Douek IF, Andrews RC, King RJ (2020). Patients with morbid obesity should not be routinely screened for Cushing's syndrome: Results of retrospective study of patients attending a specialist weight management service. Clinical Obesity, 10(3).
England C, Leary S, Thompson C, Lorimer C, Andrews R (2020). Sensitivity to change of the UK Diabetes and Diet Questionnaire in a specialist weight management service.
Author URL.
Curran M, Drayson MT, Andrews RC, Zoppi C, Barlow JP, Solomon TPJ, Narendran P (2020). The benefits of physical exercise for the health of the pancreatic beta-cell: a review of the evidence.
EXPERIMENTAL PHYSIOLOGY,
105(4), 579-589.
Author URL.
2019
Scott SN, Shepherd SO, Andrews RC, Narendran P, Purewal TS, Kinnafick F, Cuthbertson DJ, Atkinson-Goulding S, Noon T, Wagenmakers AJM, et al (2019). A Multidisciplinary Evaluation of a Virtually Supervised Home-Based High-Intensity Interval Training Intervention in People with Type 1 Diabetes.
DIABETES CARE,
42(12), 2330-2333.
Author URL.
Bourne JE, Page A, Leary S, Andrews RC, England C, Cooper AR (2019). Electrically assisted cycling for individuals with type 2 diabetes mellitus: protocol for a pilot randomized controlled trial. Pilot and Feasibility Studies, 5(1).
Scott SN, Cocks M, Andrews RC, Narendran P, Purewal TS, Cuthbertson DJ, Wagenmakers AJM, Shepherd SO (2019). Fasted High-Intensity Interval and Moderate-Intensity Exercise Do Not Lead to Detrimental 24-Hour Blood Glucose Profiles.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM,
104(1), 111-117.
Author URL.
Scott SN, Cocks M, Andrews RC, Narendran P, Purewal TS, Cuthbertson DJ, Wagenmakers AJM, Shepherd SO (2019). High-Intensity Interval Training Improves Aerobic Capacity Without a Detrimental Decline in Blood Glucose in People with Type 1 Diabetes.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM,
104(2), 604-612.
Author URL.
Litchfield I, Andrews RC, Narendran P, Greenfield S, Doherty Y, Sorensen J, Barnette J, Gallen I, Nagi D, Davies M, et al (2019). Patient and Healthcare Professionals Perspectives on the Delivery of Exercise Education for Patients with Type 1 Diabetes.
FRONTIERS IN ENDOCRINOLOGY,
10 Author URL.
Litchfield IJ, Andrews R, Narendran P, Greenfield S (2019). Patient and healthcare professionals perspectives on the delivery of exercise education for patients with Type 1 diabetes.
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).
Abstract:
Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-K ATP -channel pathways
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.
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.
Narendran P, Quann N, Nagi D, Gallen I, Gorton J, Daly H, Thompson C, Bhupendra Jaicim N, Davies M, Andrews RC, et al (2019). Rationale and methods for the Exercise for Type 1 Diabetes Education program: a pilot randomized controlled trial of an education program to support adults with type 1 diabetes mellitus (T1DM) to undertake exercise.
BMJ Open Diabetes Research and Care,
7(1).
Abstract:
Rationale and methods for the Exercise for Type 1 Diabetes Education program: a pilot randomized controlled trial of an education program to support adults with type 1 diabetes mellitus (T1DM) to undertake exercise
Objective: Regular exercise in people with type 1 diabetes mellitus (T1DM) can result in considerable improvements in health and reduction in cardiovascular events and death. However, a large proportion of people with T1DM are not active. Fear of hypoglycemia and lack of knowledge on how to manage their diabetes are major barriers to exercise in people with T1DM, but few patients receive specific advice about how to adjust insulin and carbohydrate for activity. Furthermore, healthcare professionals (HCP) currently lack the knowledge to advise patients on how to manage their diabetes when active and would like formal training in exercise prescription for people with T1DM. Research design and methods: This study is divided into two stages. The first stage develops an education program aimed to support people with T1DM to exercise using the Medical Research Council framework. The second stage is a pilot randomized controlled trial (RCT) that aims to collect the key variables to design a definitive trial to test the efficacy and cost-effectiveness of the education package. We aim to recruit 96 patients with T1DM at two UK hospitals. Conclusions: This article outlines the protocol for a pilot RCT to develop a program of education that will support adults with T1DM to undertake safe and effective exercise. This is accompanied by training for HCPs to deliver this educational intervention. Successful completion of this program of work will address some of the barriers to exercise in adults with T1DM, and should facilitate an increase in exercise for this group of people.
Abstract.
Thompson C, Williams A, Cruickshank I, Quann N, Jaicim N, Narendran P, Andrews RC, Team EXTODE (2019). Recruitment to and retention of participants to the EXercising for Type 1 Diabetes (EXTOD) Education, pilot randomised controlled trial (RCT).
Author URL.
Chetan MR, Charlton MH, Thompson C, Dias RP, Andrews RC, Narendran P (2019). The Type 1 diabetes 'honeymoon' period is five times longer in men who exercise: a case-control study.
Diabet Med,
36(1), 127-128.
Author URL.
Curran M, Campbell J, Drayson M, Andrews R, Narendran P (2019). Type 1 diabetes impairs the mobilisation of highly-differentiated CD8(+) T cells during a single bout of acute exercise.
EXERCISE IMMUNOLOGY REVIEW,
25, 78-96.
Author URL.
Curran M, Campbell J, Drayson M, Andrews R, Narendran P (2019). Type 1 diabetes impairs the mobilisation of highly-differentiated CD8+T cells during a single bout of acute exercise.
Exerc Immunol Rev,
25, 64-82.
Abstract:
Type 1 diabetes impairs the mobilisation of highly-differentiated CD8+T cells during a single bout of acute exercise.
Type 1 diabetes (T1D) is a T cell mediated autoimmune disease that targets and destroys insulin-secreting pancreatic beta cells. Beta cell specific T cells are highly differentiated and show evidence of previous antigen exposure. Exerciseinduced mobilisation of highly-differentiated CD8+ T cells facilitates immune surveillance and regulation. We aimed to explore exercise-induced T cell mobilisation in T1D. In this study, we compared the effects of a single bout of vigorous intensity exercise on T cell mobilisation in T1D and control participants. N=12 T1D (mean age 33.2yrs, predicted VO2 max 32.2 mL/(kg·min), BMI 25.3Kg/m2) and N=12 control (mean age 29.4yrs, predicted VO2 max 38.5mL(kg.min), BMI 23.7Kg/m2) male participants completed a 30-minute bout of cycling at 80% predicted VO2 max in a fasted state. Peripheral blood was collected at baseline, immediately post-exercise, and 1 hour post-exercise. Exercise-induced mobilisation was observed for T cells in both T1D and control groups. Total CD8+ T cells mobilised to a similar extent in T1D (42.7%; p=0.016) and controls (39.7%; p=0.001). CD8 effector memory CD45RA+ (EMRA) subset were the only T cell lineage subset to be significantly mobilised in both groups though the percentage increase of CD8+ EMRA was blunted in T1D (T1D (26.5%) p=0.004, control (66.1%) p=0.010). Further phenotyping of these subsets revealed that the blunting was most evident in CD8+ EMRA that expressed adhesion (CD11b: T1D 37.70%, Control 91.48%) and activation markers (CD69: T1D 29.87%, Control 161.43%), and appeared to be the most differentiated (CD27-CD28-: T1D 7.12%, Control 113.76%). CD4+ T cells mobilised during vigorous intensity exercise in controls (p=0.001), but not in T1D. The blunted mobilisation response of particular T cell subsets was not due to CMV serostatus or apparent differences in exertion during the exercise bout as defined by heart rate and RPE. Predicted VO2 max showed a trend to be lower in the T1D group than the control group but is unlikely to contribute to this blunted response. We postulate the reasons for a blunted mobilisation of differentiated CD8+ EMRA cells includes differences in blood glucose, adrenaline receptor density, and sequestration of T cells in the pancreas of T1D participants. In conclusion, mobilisation of CD8+ EMRA and CD4+ subsets T cells is decreased in people with T1D during acute exercise.
Abstract.
Author URL.
2018
Sebire SJ, Toumpakari Z, Turner KM, Cooper AR, Page AS, Malpass A, Andrews RC (2018). "I've made this my lifestyle now": a prospective qualitative study of motivation for lifestyle change among people with newly diagnosed type two diabetes mellitus.
BMC PUBLIC HEALTH,
18 Author URL.
Redondo MJ, Geyer S, Steck AK, Sharp S, Wentworth JM, Weedon MN, Antinozzi P, Sosenko J, Atkinson M, Pugliese A, et al (2018). A Type 1 Diabetes Genetic Risk Score Predicts Progression of Islet Autoimmunity and Development of Type 1 Diabetes in Individuals at Risk.
Diabetes Care,
41(9), 1887-1894.
Abstract:
A Type 1 Diabetes Genetic Risk Score Predicts Progression of Islet Autoimmunity and Development of Type 1 Diabetes in Individuals at Risk
. OBJECTIVE
. We tested the ability of a type 1 diabetes (T1D) genetic risk score (GRS) to predict progression of islet autoimmunity and T1D in at-risk individuals.
.
.
. RESEARCH DESIGN AND METHODS
. We studied the 1,244 TrialNet Pathway to Prevention study participants (T1D patients’ relatives without diabetes and with one or more positive autoantibodies) who were genotyped with Illumina ImmunoChip (median [range] age at initial autoantibody determination 11.1 years [1.2–51.8], 48% male, 80.5% non-Hispanic white, median follow-up 5.4 years). of 291 participants with a single positive autoantibody at screening, 157 converted to multiple autoantibody positivity and 55 developed diabetes. of 953 participants with multiple positive autoantibodies at screening, 419 developed diabetes. We calculated the T1D GRS from 30 T1D-associated single nucleotide polymorphisms. We used multivariable Cox regression models, time-dependent receiver operating characteristic curves, and area under the curve (AUC) measures to evaluate prognostic utility of T1D GRS, age, sex, Diabetes Prevention Trial–Type 1 (DPT-1) Risk Score, positive autoantibody number or type, HLA DR3/DR4-DQ8 status, and race/ethnicity. We used recursive partitioning analyses to identify cut points in continuous variables.
.
.
. RESULTS
. Higher T1D GRS significantly increased the rate of progression to T1D adjusting for DPT-1 Risk Score, age, number of positive autoantibodies, sex, and ethnicity (hazard ratio [HR] 1.29 for a 0.05 increase, 95% CI 1.06–1.6; P = 0.011). Progression to T1D was best predicted by a combined model with GRS, number of positive autoantibodies, DPT-1 Risk Score, and age (7-year time-integrated AUC = 0.79, 5-year AUC = 0.73). Higher GRS was significantly associated with increased progression rate from single to multiple positive autoantibodies after adjusting for age, autoantibody type, ethnicity, and sex (HR 2.27 for GRS &gt;0.295, 95% CI 1.47–3.51; P = 0.0002).
.
.
. CONCLUSIONS
. The T1D GRS independently predicts progression to T1D and improves prediction along T1D stages in autoantibody-positive relatives.
.
Abstract.
Matson RIB, Leary SD, Cooper AR, Thompson C, Narendran P, Andrews RC (2018). Adults recently diagnosed with Type 1 diabetes are less active than healthy adults.
Author URL.
Kennedy A, Narendran P, Andrews RC, Daley A, Greenfield SM, Grp EXTOD (2018). Attitudes and barriers to exercise in adults with a recent diagnosis of type 1 diabetes: a qualitative study of participants in the Exercise for Type 1 Diabetes (EXTOD) study.
BMJ OPEN,
8(1).
Author URL.
Tyrrell J, Yaghootkar H, Jones SE, Beaumont R, Wood AR, Tuke MA, Ruth KS, Andrews RC, Frayling TM (2018). Broad changes in body mass index between age 10 and adulthood are associated with type 2 diabetes risk independently of adult body mass index.
Author URL.
Troughton J, Sorenson J, Doherty Y, Thompson C, Gorton J, Greenfield S, Litchfield I, Davies M, Narendran P, Andrews R, et al (2018). Development of an education programme to support patients with Type 1 diabetes to exercise safely and effectively: the EXercising for Type One Diabetes education programme (EXTOD).
Author URL.
Oldershaw HS, Oram RA, Shields BM, Andrews RC (2018). Diet and diet plus physical activity improves treatment satisfaction with no adverse effect on quality of life and illness perception in early Type 2 diabetes: Data from the Early ACTID trial.
Author URL.
Narendran P, Andrews RC (2018). EXTOD: Exploring the barriers and benefits of physical exercise for people with type 1 diabetes. British Journal of Diabetes, 18(3), 97-99.
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.
Garbutt JDW, England C, Papadaki A, Andrews RC, Jones AG, Johnson L (2018). Is adherence to a Mediterranean diet associated with progression of Type 2 diabetes?.
Author URL.
Oldershaw HS, Oram RA, Dennis J, Andrews RC (2018). No deterioration in quality of life, treatment satisfaction and wellbeing over 6 years of follow up in people with recently diagnosed type 2 diabetes.
Author URL.
Matson RIB, Leary SD, Cooper AR, Thompson C, Narendran P, Andrews RC (2018). Objective Measurement of Physical Activity in Adults with Newly Diagnosed Type 1 Diabetes and Healthy Individuals.
FRONTIERS IN PUBLIC HEALTH,
6 Author URL.
Glyn T, Greenslade B, Andrews R (2018). Persistant hypoglycaemia post bariatric surgery. Endocrine Abstracts
Glyn T, Andrews R (2018). Persistant hypoglycaemia post bariatric surgery. Endocrine Abstracts
Henshall C, Narendran P, Andrews RC, Daley A, Stokes KA, Kennedy A, Greenfield S (2018). Qualitative study of barriers to clinical trial retention in adults with recently diagnosed type 1 diabetes.
BMJ OPEN,
8(7).
Author URL.
Bravis V, Kaur A, Walkey HC, Godsland IF, Misra S, Bingley PJ, Williams AJK, Dunger DB, Dayan CM, Peakman M, et al (2018). Relationship between islet autoantibody status and the clinical characteristics of children and adults with incident type 1 diabetes in a UK cohort.
BMJ OPEN,
8(4).
Author URL.
Glyn T, Ho M, Lambert AP, Thomas J, King R, Douek I, Andrews R (2018). Screening for Cushing's syndrome in a tier 3 weight management service. Endocrine Abstracts
Lam A, Oram R, Andrews R, Narendran P, Haller M, Senior P (2018). The BETA-2 score: a novel measure of beta cell function in type 1 diabetes intervention trials.
Author URL.
Chetan MR, Charlton MH, Thompson C, Andrews RC, Narendran P (2018). Type 1 diabetes 'honeymoon' is almost four times longer in people who exercise.
DIABETIC MEDICINE,
35, 14-14.
Author URL.
2017
Rogers CA, Reeves BC, Byrne J, Donovan JL, Mazza G, Paramasivan S, Andrews RC, Wordsworth S, Thompson J, Blazeby JM, et al (2017). Adaptation of the By-Band randomized clinical trial to By-Band-Sleeve to include a new intervention and maintain relevance of the study to practice.
British Journal of Surgery,
104(9), 1207-1214.
Abstract:
Adaptation of the By-Band randomized clinical trial to By-Band-Sleeve to include a new intervention and maintain relevance of the study to practice
Abstract
.
. Background
. Recruitment into surgical RCTs can be threatened if new interventions available outside the trial compete with those being evaluated. Adapting the trial to include the new intervention may overcome this issue, yet this is not often done in surgery. This paper describes the challenges, rationale and methods for adapting an RCT to include a new intervention.
.
.
. Methods
. The By-Band study was designed in the UK in 2009–2010 to compare the effectiveness of laparoscopic adjustable gastric band and Roux-en-Y gastric bypass for severe obesity. It contained a pilot phase to establish whether recruitment was possible, and the grant proposal specified that an adaptation to include sleeve gastrectomy would be considered if practice changed and recruitment was successful. Information on changing obesity surgery practice, updated evidence and expert opinion about trial design were used to inform the adaptation.
.
.
. Results
. The pilot phase recruited over 13 months in 2013–2014 and randomized 80 patients (79 anticipated). During this time, major changes in obesity practice in the UK were observed, with gastric band reducing from 32·6 to 15·8 per cent and sleeve gastrectomy increasing from 9·0 to 28·1 per cent. The evidence base had not changed markedly. The British Obesity and Metabolic Surgery Society and study oversight committees supported an adaptation to include sleeve gastrectomy, and a proposal to do so was approved by the funder.
.
.
. Conclusion
. Adaptation of a two-group surgical RCT can allow evaluation of a third procedure and maintain relevance of the RCT to practice. It also optimizes the use of existing trial infrastructure to answer an additional important research question. Registration number: ISRCTN00786323 (http://www.isrctn.com/).
.
Abstract.
Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, Shaw W, Law G, Desai M, Matthews DR, et al (2017). Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes.
The New England journal of medicine,
377(7), 644-657.
Abstract:
Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes.
Background Canagliflozin is a sodium-glucose cotransporter 2 inhibitor that reduces glycemia as well as blood pressure, body weight, and albuminuria in people with diabetes. We report the effects of treatment with canagliflozin on cardiovascular, renal, and safety outcomes. Methods the CANVAS Program integrated data from two trials involving a total of 10,142 participants with type 2 diabetes and high cardiovascular risk. Participants in each trial were randomly assigned to receive canagliflozin or placebo and were followed for a mean of 188.2 weeks. The primary outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results the mean age of the participants was 63.3 years, 35.8% were women, the mean duration of diabetes was 13.5 years, and 65.6% had a history of cardiovascular disease. The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P
Abstract.
England CY, Thompson JL, Jago R, Cooper AR, Andrews RC (2017). Development of a brief, reliable and valid diet assessment tool for impaired glucose tolerance and diabetes: the UK Diabetes and Diet Questionnaire.
PUBLIC HEALTH NUTRITION,
20(2), 191-199.
Author URL.
England CY, Cooper AR, Andrews RC (2017). Dietary vitamin D intake and supplement use in people at high risk of, or newly diagnosed with, Type 2 diabetes in 2014-2015 in the South West of England.
Author URL.
Bowman L, Hopewell JC, Chen F, Wallendszus K, Stevens W, Collins R, Wiviott SD, Cannon CP, Braunwald E, Sammons E, et al (2017). Effects of anacetrapib in patients with atherosclerotic vascular disease.
New England Journal of Medicine,
377(13), 1217-1227.
Abstract:
Effects of anacetrapib in patients with atherosclerotic vascular disease
BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of −18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo.
Abstract.
Paramasivan S, Rogers CA, Welbourn R, Byrne JP, Salter N, Mahon D, Noble H, Kelly J, Mazza G, Whybrow P, et al (2017). Enabling recruitment success in bariatric surgical trials: pilot phase of the By-Band-Sleeve study. International Journal of Obesity, 41(11), 1654-1661.
Narendran P, Jackson N, Daley A, Thompson D, Stokes K, Greenfield S, Charlton M, Curran M, Solomon TPJ, Nouwen A, et al (2017). Exercise to preserve β-cell function in recent-onset Type 1 diabetes mellitus (EXTOD) - a randomized controlled pilot trial.
Diabet Med,
34(11), 1521-1531.
Abstract:
Exercise to preserve β-cell function in recent-onset Type 1 diabetes mellitus (EXTOD) - a randomized controlled pilot trial.
AIM: Residual β-cell function is present at the time of diagnosis with Type 1 diabetes. Preserving this β-cell function reduces complications. We hypothesized that exercise preserves β-cell function in Type 1 diabetes and undertook a pilot trial to address the key uncertainties in designing a definitive trial to test this hypothesis. METHODS: a randomized controlled pilot trial in adults aged 16-60 years diagnosed with Type 1 diabetes within the previous 3 months was undertaken. Participants were assigned to control (usual care) or intervention (exercise consultation every month), in a 1 : 1 ratio for 12 months. The primary outcomes were recruitment rate, drop out, exercise adherence [weeks with ≥ 150 min of self-reported moderate to vigorous physical activity (MVPA)], and exercise uptake in the control group. The secondary outcomes were differences in insulin sensitivity and rate of loss of β-cell function between intervention and control at 6 and 12 months. RESULTS: of 507 individuals who were approached, 58 (28 control, 30 intervention) entered the study and 41 completed it. Participants were largely white European males, BMI 24.8 ± 3.8 kg/m2 , HbA1c 75 ± 25 mmol/mol (9 ± 2%). Mean level of objectively measured MVPA increased in the intervention group (mean 243 to 273 min/week) and 61% of intervention participants reached the target of ≥ 150 min/week of self-reported MVPA on at least 42 weeks of the year. Physical activity levels fell slightly in the control group (mean 277 to 235 min of MVPA/week). There was exploratory evidence that intervention group became more insulin sensitive and required less insulin. However, the rate of loss of β-cell function appeared similar between the groups, although the change in insulin sensitivity may have affected this. CONCLUSION: We show that it is possible to recruit and randomize people with newly diagnosed Type 1 diabetes to a trial of an exercise intervention, and increase and maintain their exercise levels for 12 months. Future trials need to incorporate measures of greater adherence to exercise training targets, and include more appropriate measures of β-cell function. (Clinical Trials Registry No; ISRCTN91388505).
Abstract.
Author URL.
Ali MA, Liu Y-F, Arif S, Tatovic D, Shariff H, Gibson VB, Yusuf N, Baptista R, Eichmann M, Petrov N, et al (2017). Metabolic and immune effects of immunotherapy with proinsulin peptide in human new-onset type 1 diabetes.
SCIENCE TRANSLATIONAL MEDICINE,
9(402).
Author URL.
Brocklebank LA, Andrews RC, Page A, Falconer CL, Leary S, Cooper A (2017). The Acute Effects of Breaking up Seated Office Work with Standing or Light-Intensity Walking on Interstitial Glucose Concentration: a Randomized Crossover Trial.
Journal of Physical Activity and Health,
14(8), 617-625.
Abstract:
The Acute Effects of Breaking up Seated Office Work with Standing or Light-Intensity Walking on Interstitial Glucose Concentration: a Randomized Crossover Trial
Background:The aim of this randomized, 3-period, 3-treatment crossover trial was to examine the acute effects of regularly breaking up seated office work with short bouts of standing or light-intensity walking on postprandial interstitial glucose concentration.Methods:Seventeen middle-aged office workers performed 3 5-hour trial conditions at their workplace in a random order: 1) uninterrupted sitting, 2) sitting interrupted by 2 minutes of standing every 20 minutes, and 3) sitting interrupted by 2 minutes of light-intensity walking every 20 minutes. Participants consumed 2 standardized test drinks at the start of each trial condition and an iPro2 continuous glucose monitoring system (CGMS) recorded average interstitial glucose concentration every 5 minutes for the duration of the study.Results:The 5-hour interstitial glucose incremental area under the curve (iAUC) was 55.5% lower after sitting interrupted by light-intensity walking compared with after uninterrupted sitting (95% CI, –104.2% to –6.8%). There was also a suggestion of a beneficial effect of regular standing breaks, particularly in overweight men, although they were not as effective as the walking breaks (mean difference [95% CI], –29.6% [–73.9% to 14.7%]).Conclusions:Regularly breaking up prolonged sitting lowers postprandial glycemia in middle-aged adults without metabolic impairment.
Abstract.
Doble B, Wordsworth S, Rogers CA, Welbourn R, Byrne J, Blazeby JM (2017). What Are the Real Procedural Costs of Bariatric Surgery? a Systematic Literature Review of Published Cost Analyses. Obesity Surgery, 27(8), 2179-2192.
2016
Coulman KD, Howes N, Hopkins J, Whale K, Chalmers K, Brookes S, Nicholson A, Savovic J, Ferguson Y, Owen-Smith A, et al (2016). A Comparison of Health Professionals’ and Patients’ Views of the Importance of Outcomes of Bariatric Surgery. Obesity Surgery, 26(11), 2738-2746.
Coulman KD, Hopkins J, Brookes ST, Chalmers K, Main B, Owen-Smith A, Andrews RC, Byrne J, Donovan JL, Mazza G, et al (2016). A Core Outcome Set for the Benefits and Adverse Events of Bariatric and Metabolic Surgery: the BARIACT Project.
PLOS MEDICINE,
13(11).
Author URL.
Chen MZ, Andrews RC (2016). Lifestyle Issues: Exercise. In (Ed) Textbook of Diabetes, 353-373.
Andrews RC (2016). Medical Management of Obesity. In (Ed) Obesity, Bariatric and Metabolic Surgery, 39-49.
Ali MA, Liu Y-F, Stenson R, Leech N, Andrews R, Peakman M, Dayan C (2016). Proinsulin peptide immunotherapy in new-onset type 1 diabetes is well-tolerated and associated with reduced daffy insulin usage.
Author URL.
Tatovic D, Luzio S, Dunseath G, Liu Y, Alhadj Ali M, Peakman M, Dayan CM (2016). Stimulated urine C-peptide creatinine ratio vs serum C-peptide level for monitoring of β-cell function in the first year after diagnosis of Type 1 diabetes. Diabetic Medicine, 33(11), 1564-1568.
Arora T, Chen MZ, Cooper AR, Andrews RC, Taheri S (2016). The Impact of Sleep Debt on Excess Adiposity and Insulin Sensitivity in Patients with Early Type 2 Diabetes Mellitus.
JOURNAL OF CLINICAL SLEEP MEDICINE,
12(5), 673-680.
Author URL.
2015
England CY, Thompson JL, Jago R, Andrews RC (2015). A new dietary questionnaire for clinical use with people with Type 2 diabetes is repeatable and comparable with food diaries: introducing the Bristol Diabetes and Diet Questionnaire.
DIABETIC MEDICINE,
32, 141-141.
Author URL.
England CY, Andrews RC, Jago R, Thompson JL (2015). A systematic review of brief dietary questionnaires suitable for clinical use in the prevention and management of obesity, cardiovascular disease and type 2 diabetes. European Journal of Clinical Nutrition, 69(9), 977-1003.
Arora T, Chen MZ, Omar OM, Cooper AR, Andrews RC, Taheri S (2015). An investigation of the associations among sleep duration and quality, body mass index and insulin resistance in newly diagnosed type 2 diabetes mellitus patients.
Therapeutic Advances in Endocrinology and Metabolism,
7(1), 3-11.
Abstract:
An investigation of the associations among sleep duration and quality, body mass index and insulin resistance in newly diagnosed type 2 diabetes mellitus patients
Objectives: to examine direct and indirect associations of sleep duration and quality with insulin resistance, considering body mass index (BMI) as a potential mediator in newly diagnosed type 2 diabetes mellitus patients. Methods: Cross-sectional data from patients enrolled in the Early Activity in Diabetes study. We studied 522 newly diagnosed type 2 diabetes mellitus patients, 65.9% male, mean age 63.5 ± 10.1 years. of the total sample 53% had a BMI of ⩾30 kg/m2. Participants completed a 7-day sleep diary and sleep questionnaire. Average sleep duration (minutes), average nap duration (minutes) and average number of night awakenings were derived. Objective measures of height and body weight were obtained for the BMI calculation (kg/m2). Insulin resistance was obtained using the homeostatic model assessment – insulin resistance (HOMA2-IR) standardized technique. Results: Average number of night awakenings was positively correlated with BMI ( r= 0.22, p < 0.001) and negatively associated with logged HOMA2-IR ( r= -0.16, p = 0.04). Path analysis demonstrated night awakenings were directly associated with BMI and indirectly associated with insulin resistance, whilst considering BMI as a potential mediator ( p < 0.05). Sleep duration was not associated with BMI or insulin resistance ( p > 0.05). Conclusions: Sleep quality, not sleep duration, plays an important role in insulin resistance in newly diagnosed type 2 diabetes mellitus patients. BMI may mediate the relationship between indicators of sleep quality and insulin resistance. There is a need to examine the impact of improving sleep quality on obesity and insulin resistance in patients with type 2 diabetes mellitus.
Abstract.
Chen MZ, Hudson CA, Vincent EE, de Berker DAR, May MT, Hers I, Dayan CM, Andrews RC, Tavaré JM (2015). Bariatric surgery in morbidly obese insulin resistant humans normalises insulin signalling but not insulin-stimulated glucose disposal.
PLoS One,
10(4).
Abstract:
Bariatric surgery in morbidly obese insulin resistant humans normalises insulin signalling but not insulin-stimulated glucose disposal.
AIMS: Weight-loss after bariatric surgery improves insulin sensitivity, but the underlying molecular mechanism is not clear. To ascertain the effect of bariatric surgery on insulin signalling, we examined glucose disposal and Akt activation in morbidly obese volunteers before and after Roux-en-Y gastric bypass surgery (RYGB), and compared this to lean volunteers. MATERIALS AND METHODS: the hyperinsulinaemic euglycaemic clamp, at five infusion rates, was used to determine glucose disposal rates (GDR) in eight morbidly obese (body mass index, BMI=47.3 ± 2.2 kg/m(2)) patients, before and after RYGB, and in eight lean volunteers (BMI=20.7 ± 0.7 kg/m2). Biopsies of brachioradialis muscle, taken at fasting and insulin concentrations that induced half-maximal (GDR50) and maximal (GDR100) GDR in each subject, were used to examine the phosphorylation of Akt-Thr308, Akt-473, and pras40, in vivo biomarkers for Akt activity. RESULTS: Pre-operatively, insulin-stimulated GDR was lower in the obese compared to the lean individuals (P
Abstract.
Author URL.
Leiter LA, Astrup A, Andrews RC, Cuevas A, Horn DB, Kunešová M, Wittert G, Finer N (2015). Identification of educational needs in the management of overweight and obesity: results of an international survey of attitudes and practice. Clinical Obesity, 5(5), 245-255.
Pfeffer MA, Claggett B, Diaz R, Dickstein K, Gerstein HC, Køber LV, Lawson FC, Ping L, Wei X, Lewis EF, et al (2015). Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome.
The New England journal of medicine,
373(23), 2247-2257.
Abstract:
Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome.
BackgroundCardiovascular morbidity and mortality are higher among patients with type 2 diabetes, particularly those with concomitant cardiovascular diseases, than in most other populations. We assessed the effects of lixisenatide, a glucagon-like peptide 1-receptor agonist, on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event.MethodsWe randomly assigned patients with type 2 diabetes who had had a myocardial infarction or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined standards of care. The trial was designed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo, as defined by an upper boundary of the 95% confidence interval for the hazard ratio of less than 1.3 and 1.0, respectively, for the primary composite end point of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina.ResultsThe 6068 patients who underwent randomization were followed for a median of 25 months. A primary end-point event occurred in 406 patients (13.4%) in the lixisenatide group and in 399 (13.2%) in the placebo group (hazard ratio, 1.02; 95% confidence interval [CI], 0.89 to 1.17), which showed the noninferiority of lixisenatide to placebo (P
Abstract.
Ali MA, Liu Y-F, Stenson R, Clifford G, Adams L, Powrie J, Kyne D, Leech N, Green K, Andrews R, et al (2015). Proinsulin peptide immunotherapy in type 1 diabetes: safety data of a first in new-onset type 1 diabetes phase 1b trial.
Author URL.
Bentley-Lewis R, Aguilar D, Riddle MC, Claggett B, Diaz R, Dickstein K, Gerstein HC, Johnston P, Køber LV, Lawson F, et al (2015). Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo.
American heart journal,
169(5), 631-638.e7.
Abstract:
Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo.
BackgroundCardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated.MethodsELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy.ResultsEnrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events.ConclusionELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk.
Abstract.
FALCONER CL, PAGE AS, ANDREWS RC, COOPER AR (2015). The Potential Impact of Displacing Sedentary Time in Adults with Type 2 Diabetes. Medicine & Science in Sports & Exercise, 47(10), 2070-2075.
Emadian A, Andrews RC, England CY, Wallace V, Thompson JL (2015). The effect of macronutrients on glycaemic control: a systematic review of dietary randomised controlled trials in overweight and obese adults with type 2 diabetes in which there was no difference in weight loss between treatment groups.
British Journal of Nutrition,
114(10), 1656-1666.
Abstract:
The effect of macronutrients on glycaemic control: a systematic review of dietary randomised controlled trials in overweight and obese adults with type 2 diabetes in which there was no difference in weight loss between treatment groups
AbstractWeight loss is crucial for treating type 2 diabetes mellitus (T2DM). It remains unclear which dietary intervention is best for optimising glycaemic control, or whether weight loss itself is the main reason behind observed improvements. The objective of this study was to assess the effects of various dietary interventions on glycaemic control in overweight and obese adults with T2DM when controlling for weight loss between dietary interventions. A systematic review of randomised controlled trials (RCT) was conducted. Electronic searches of Medline, Embase, Cinahl and Web of Science databases were conducted. Inclusion criteria included RCT with minimum 6 months duration, with participants having BMI≥25·0 kg/m2, a diagnosis of T2DM using HbA1c, and no statistically significant difference in mean weight loss at the end point of intervention between dietary arms. Results showed that eleven studies met the inclusion criteria. Only four RCT indicated the benefit of a particular dietary intervention over another in improving HbA1c levels, including the Mediterranean, vegan and low glycaemic index (GI) diets. However the findings from one of the four studies showing a significant benefit are questionable because of failure to control for diabetes medications and poor adherence to the prescribed diets. In conclusion there is currently insufficient evidence to suggest that any particular diet is superior in treating overweight and obese patients with T2DM. Although the Mediterranean, vegan and low-GI diets appear to be promising, further research that controls for weight loss and the effects of diabetes medications in larger samples is needed.
Abstract.
Chen MZ, Greenwood RJ, Le Roux C, Andrews RC (2015). Weight loss contributes more to the glycaemic improvement seen with bariatric surgery than GLP-1.
Author URL.
Hopkins J, Howes N, Chalmers K, Whale K, Savovic J, Coulman K, Nicholson A, Byrne J, Whistance R, Welbourn R, et al (2015). What are important outcomes of bariatric surgery? an in-depth analysis to inform the development of a core outcome set and a comparison between the views of surgeons and other health professionals (the BARIACT study).
Lancet,
385 Suppl 1Abstract:
What are important outcomes of bariatric surgery? an in-depth analysis to inform the development of a core outcome set and a comparison between the views of surgeons and other health professionals (the BARIACT study).
BACKGROUND: Outcome reporting in bariatric surgery needs uniformity. A core outcome set is an agreed minimum set of outcomes reported in all studies of a particular condition, but members of the bariatric multidisciplinary team might value outcomes differently. The aim of this study was to summarise existing outcome reporting in bariatric surgery, to inform the development of a core outcome set, and to compare outcomes selected as important by type of health professional. METHODS: Outcomes reported in randomised controlled trials (RCTs) and large non-randomised studies, identified by a systematic review, were listed verbatim. Frequency of outcome reporting and uniformity of definition were assessed. A questionnaire to rate the importance of each outcome was completed by members of the bariatric multidisciplinary team. Responses to each item were scored as 1 (not essential) to 9 (absolutely essential). We ranked outcomes according to percentage deemed important (7-9) and according to respondents by type of health professional. FINDINGS: We identified 1088 individual outcomes from 90 studies (39 RCTs), grouped them into health domains, and presented them as a questionnaire with 131 items to 489 multidisciplinary team members. Most outcomes (n=920, 85%) were reported only once. The largest outcome domain was surgical complications, and 432 outcomes (42%) corresponded to an adverse event. Only a quarter of outcomes (n=461) were defined, and were often contradictory. For questionnaire responders (n=164, response rate 33·5%), most were surgeons (n=80, 48·8%), followed by dietitians (n=31, 18·9%), nurses (n=24, 14·6%), physicians (n=12, 7·3%), and others (n=16, 9·9%). Improvement in diabetes was the top outcome for all health professionals. Seven of the surgeon's top ten outcomes were adverse events, compared with three for other health professionals. Groups valued a measure of weight differently (third vs 15th for other health professionals and surgeons, respectively). INTERPRETATION: This study shows that the assessment of bariatric surgery focuses largely on adverse events and resolution of comorbidity, but that reporting is inconsistent and ill-defined. Substantial variation between the views of surgeons and those of other health professionals was evident. The next step is to provide feedback to participants and to survey their views again before a final consensus meeting to produce a core outcome set for the Benefits and Adverse events in BARIAtric surgery Clinical Trials (BARIACT) as a solution to this problem. FUNDING: National Institute for Health Research (NIHR), and the NIHR Health Technology Assessment programme. This work was also undertaken with the support of the MRC ConDuCT-II Hub (Collaboration and innovation for Difficult and Complex randomised controlled Trials in Invasive procedures, MR/K025643/1).
Abstract.
Author URL.
2014
Lascar N, Kennedy A, Hancock B, Jenkins D, Andrews RC, Greenfield S, Narendran P (2014). Attitudes and Barriers to Exercise in Adults with Type 1 Diabetes (T1DM) and How Best to Address Them: a Qualitative Study. PLoS ONE, 9(9), e108019-e108019.
England CY, Andrews R, Jago R, Thompson JL (2014). Changes in reported food intake in adults with type 2 diabetes in response to a nonprescriptive dietary intervention.
J Hum Nutr Diet,
27(4), 311-321.
Abstract:
Changes in reported food intake in adults with type 2 diabetes in response to a nonprescriptive dietary intervention.
OBJECTIVES: There is a lack of published data about the food intake of patients with type 2 diabetes and the changes that they make in response to patient-centred dietary advice. The present study describes the changes reported in response to a nonprescriptive dietary intervention based upon UK dietary guidelines. METHODS: Two hundred and sixty-two patients (87 women and 175 men) from the Early ACTivity in Diabetes (ACTID) trial who received the dietary intervention returned 4 days food diaries at baseline and 6 months. Nonparametric tests were used to examine changes in meal patterns, total energy intake and energy from food groups between baseline and 6 months. RESULTS: Mean (SD) number of reported meals day(-1) was 3.0 (0.3) and mean (SD) number of snacks was 1.1 (0.6) at both baseline and 6 months for men and women. Men reported decreasing energy intake by a mean (SD) of 912 (1389) KJ/day [218 (332) kcal day(-1) ] (P < 0.001) and women by 515 (1130) KJ/day [123 (270) kcal day(-1) ] (P < 0.001). Men reported reducing energy from alcoholic drinks [-234 (527) KJ day(-1) ; P < 0.001], white bread [-113 (402) KJ day(-1) ; P = 0.001], biscuits [i.e. cookies -67 (205) KJ day(-1) ; P < 0.001] and cakes [-50 (410) KJ day(-1) ; P = 0.0012]. Women reported reducing energy from mixed main meals [-134 (456) KJ day(-1) ; P = 0.036], pasta and rice [-79 (326) KJ day(-1) ; P = 0.019], high-energy drinks [-59 (159) KJ day(-1) ; P = 0.001] and white bread [-59 (368) KJ day(-1) ; P = 0.042]. CONCLUSIONS: Men and women in the Early ACTID study reported small changes in higher-energy and lower-fibre foods and drinks in response to patient-centred dietary advice.
Abstract.
Author URL.
England CY, Thompson JL, Jago R, Cooper AR, Andrews RC (2014). Dietary changes and associations with metabolic improvements in adults with type 2 diabetes during a patient-centred dietary intervention: an exploratory analysis.
BMJ Open,
4(6).
Abstract:
Dietary changes and associations with metabolic improvements in adults with type 2 diabetes during a patient-centred dietary intervention: an exploratory analysis.
OBJECTIVES: Describe dietary intake of participants enrolled in a non-prescriptive dietary intervention and dietary changes at 6
months and explore whether these changes had a role in observed improvements in glycated haemoglobin (HbA1c), weight, lipids and blood pressure. DESIGN: Secondary analysis of data from the Early ACTivity in Diabetes randomised controlled trial. PARTICIPANTS: 262 patients with newly diagnosed type 2 diabetes randomised to the dietary intervention. OUTCOMES AND ANALYSIS: Changes in energy intake, macronutrients, fibre and alcohol and in weight, waist circumference, lipids, HbA1c and blood pressure at baseline and 6
months. Multivariate models were used to examine associations between dietary changes and metabolic variables. RESULTS: Men reported reducing mean energy intake from 1903±462
kcal to 1685
kcal±439
kcal (p
Abstract.
Author URL.
Thompson D, Walhin J-P, Batterham AM, Stokes KA, Cooper AR, Andrews RC (2014). Effect of Diet or Diet Plus Physical Activity Versus Usual Care on Inflammatory Markers in Patients with Newly Diagnosed Type 2 Diabetes: the Early ACTivity in Diabetes (ACTID) Randomized, Controlled Trial.
JOURNAL OF THE AMERICAN HEART ASSOCIATION,
3(3).
Author URL.
Hopkins JC, Howes N, Chalmers K, Savovic J, Whale K, Coulman KD, Welbourn R, Whistance RN, Andrews RC, Byrne JP, et al (2014). Outcome reporting in bariatric surgery: an in-depth analysis to inform the development of a core outcome set, the BARIACT Study. Obesity Reviews, 16(1), 88-106.
Falconer CL, Cooper AR, Walhin JP, Thompson D, Page AS, Peters TJ, Montgomery AA, Sharp DJ, Dayan CM, Andrews RC, et al (2014). Sedentary time and markers of inflammation in people with newly diagnosed type 2 diabetes.
Nutr Metab Cardiovasc Dis,
24(9), 956-962.
Abstract:
Sedentary time and markers of inflammation in people with newly diagnosed type 2 diabetes.
BACKGROUND AND AIMS: We investigated whether objectively measured sedentary time was associated with markers of inflammation in adults with newly diagnosed type 2 diabetes. METHODS AND RESULTS: We studied 285 adults (184 men, 101 women, mean age 59.0 ± 9.7) who had been recruited to the Early ACTivity in Diabetes (Early ACTID) randomised controlled trial. C-reactive protein (CRP), adiponectin, soluble intracellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), and accelerometer-determined sedentary time and moderate-vigorous physical activity (MVPA) were measured at baseline and after six-months. Linear regression analysis was used to investigate the independent cross-sectional and longitudinal associations of sedentary time with markers of inflammation. At baseline, associations between sedentary time and IL-6 were observed in men and women, an association that was attenuated following adjustment for waist circumference. After 6 months of follow-up, sedentary time was reduced by 0.4 ± 1.2 h per day in women, with the change in sedentary time predicting CRP at follow-up. Every hour decrease in sedentary time between baseline and six-months was associated with 24% (1, 48) lower CRP. No changes in sedentary time between baseline and 6 months were seen in men. CONCLUSIONS: Higher sedentary time is associated with IL-6 in men and women with type 2 diabetes, and reducing sedentary time is associated with improved levels of CRP in women. Interventions to reduce sedentary time may help to reduce inflammation in women with type 2 diabetes.
Abstract.
Author URL.
Chen MZ, Greenwood R, Andrews RC (2014). Slow but steady weight loss is better than rapid weight loss at normalising glycaemia after bariatric surgery: the tortoise beats the hare.
Author URL.
Coulman KD, Owen-Smith A, Andrews RC, Chalmers K, Ferguson Y, Norton S, Welbourn R, Whale K, Blazeby JM (2014). THE PATIENT PERSPECTIVE OF BARIATRIC SURGERY OUTCOMES: DEVELOPING a 'CORE' SET OF PATIENT-REPORTED OUTCOMES.
Author URL.
Rogers CA, Welbourn R, Byrne J, Donovan JL, Reeves BC, Wordsworth S, Andrews R, Thompson JL, Roderick P, Mahon D, et al (2014). The By-Band study: gastric bypass or adjustable gastric band surgery to treat morbid obesity: study protocol for a multi-centre randomised controlled trial with an internal pilot phase.
Trials,
15Abstract:
The By-Band study: gastric bypass or adjustable gastric band surgery to treat morbid obesity: study protocol for a multi-centre randomised controlled trial with an internal pilot phase.
BACKGROUND: the prevalence of severe and complex obesity is increasing worldwide and surgery may offer an effective and lasting treatment. Laparoscopic adjustable gastric band and Roux-en-Y gastric bypass surgery are the two main surgical procedures performed. DESIGN: This open parallel-group randomised controlled trial will compare the effectiveness, cost-effectiveness and acceptability of gastric band (Band) versus gastric bypass (Bypass) in adults with severe and complex obesity. It has an internal pilot phase (in two centres) with integrated qualitative research to establish effective and optimal methods for recruitment. Adults with a body mass index (BMI) of 40 kg/m2 or more, or a BMI of 35 kg/m2 or more and other co-morbidities will be recruited. At the end of the internal pilot the study will expand into more centres if the pre-set progression criteria of numbers and rates of eligible patients screened and randomised are met and if the expected rates of retention and adherence to treatment allocation are achieved. The trial will test the joint hypotheses that Bypass is non-inferior to Band with respect to more than 50% excess weight loss and that Bypass is superior to Band with respect to health related quality of life (HRQOL, EQ-5D) at three years. Secondary outcomes include other weight loss measures, waist circumference and remission/resolution of co-morbidities; generic and symptom-specific HRQOL; nutritional blood test results; resource use; eating behaviours and adverse events. A core outcome set for reporting the results of obesity surgery will be developed and a systematic review of the evidence for sleeve gastrectomy undertaken to inform the main study design. DISCUSSION: By-Band is the first pragmatic study to compare the two most commonly performed bariatric surgical procedures for severe and complex obesity. The design will enable and empower surgeons to learn to recruit and participate in a randomised study. Early evidence shows that timely recruitment is possible. TRIAL REGISTRATION: Current Controlled Trials ISRCTN00786323.
Abstract.
Author URL.
Narendran P, Solomon TP, Kennedy A, Chimen M, Andrews RC (2014). The time has come to test the beta cell preserving effects of exercise in patients with new onset type 1 diabetes. Diabetologia, 58(1), 10-18.
Andrews RC, Chen MZ, Logue J (2014). ‘Bariatric surgery for type 2 diabetes always produces a good outcome’. Practical Diabetes, 31(9), 376-380.
2013
Kennedy A, Nirantharakumar K, Chimen M, Pang TT, Hemming K, Andrews RC, Narendran P (2013). Does Exercise Improve Glycaemic Control in Type 1 Diabetes? a Systematic Review and Meta-Analysis. PLoS ONE, 8(3), e58861-e58861.
Lascar N, Kennedy A, Jackson N, Daley A, Dowswell G, Thompson D, Stokes K, Greenfield S, Holder R, Andrews R, et al (2013). Exercise to preserve beta cell function in recent-onset type 1 diabetes mellitus (EXTOD) - a study protocol for a pilot randomized controlled trial.
TRIALS,
14 Author URL.
Abdelrahman T, Coulman K, Owen-Smith A, Andrews RC, Welbourn R, Blazeby JM (2013). Health related quality of life reporting in bariatric surgery: a systematic review of current practice.
Author URL.
Coulman KD, Abdelrahman T, Owen-Smith A, Andrews RC, Welbourn R, Blazeby JM (2013). Patient-reported outcomes in bariatric surgery: a systematic review of standards of reporting.
Obes Rev,
14(9), 707-720.
Abstract:
Patient-reported outcomes in bariatric surgery: a systematic review of standards of reporting.
Bariatric surgery is increasingly being used to treat severe obesity, but little is known about its impact on patient-reported outcomes (PROs). For PRO data to influence practice, well-designed and reported studies are required. A systematic review identified prospective bariatric surgery studies that used validated PRO measures. Risk of bias in randomized controlled trials (RCTs) was assessed, and papers were examined for reporting of (i) who completed PRO measures; (ii) missing PRO data and (iii) clinical interpretation of PRO data. Studies meeting all criteria were classified as robust. Eighty-six studies were identified. of the eight RCTs, risk of bias was high in one and unclear in seven. Sixty-eight different PRO measures were identified, with the Short Form (SF)-36 questionnaire most commonly used. Forty-one (48%) studies explicitly stated measures were completed by patients, 63 (73%) documented missing PRO data and 50 (58%) interpreted PRO data clinically. Twenty-six (30%) met all criteria. Although many bariatric surgery studies assess PROs, study design and reporting is often poor, limiting data interpretation and synthesis. Well-designed studies that include agreed PRO measures are needed with reporting to include integration with clinical outcomes to inform practice.
Abstract.
Author URL.
Coulman K, Owen-Smith A, Andrews R, Norton S, Welbourn R, Blazeby J (2013). The patient perspective of outcomes of bariatric surgery: the need for a 'core' set of patient-reported outcomes.
Author URL.
Kennedy A, Dowswell G, Andrews R, Greenfield S, Narendran P (2013). What are the barriers to exercise in patients newly diagnosed with Type 1 diabetes?.
DIABETIC MEDICINE,
30, 124-124.
Author URL.
2012
Stokes KA, Gilbert KL, Hall GM, Andrews RC, Thompson D (2012). Different responses of selected hormones to three types of exercise in young men. European Journal of Applied Physiology, 113(3), 775-783.
Coulman K, Abdelrahman T, Owen-Smith A, Andrews R, Welbourn R, Blazeby J (2012). Measuring patient reported outcomes in bariatric surgery: standards of reporting and synthesis with clinical data.
Author URL.
Hopkins J, Andrews R, Byrne J, Donovan J, Reeves B, Roderick P, Rogers C, Thompson J, Welbourn R, Wordsworth S, et al (2012). Reporting clinical outcomes of bariatric surgery: the need for a core outcome set.
Author URL.
Cooper AR, Sebire S, Montgomery AA, Peters TJ, Sharp DJ, Jackson N, Fitzsimons K, Dayan CM, Andrews RC (2012). Sedentary time, breaks in sedentary time and metabolic variables in people with newly diagnosed type 2 diabetes.
Diabetologia,
55(3), 589-599.
Abstract:
Sedentary time, breaks in sedentary time and metabolic variables in people with newly diagnosed type 2 diabetes.
AIMS/HYPOTHESIS: We investigated whether objectively measured sedentary time and interruptions in sedentary time are associated with metabolic factors in people with type 2 diabetes. METHODS: We studied 528 adults (30-80 years) with newly diagnosed type 2 diabetes, who were participants in a diet and physical activity intervention. Waist circumference (WC), fasting HDL-cholesterol, insulin and glucose levels, HOMA of insulin resistance (HOMA-IR) and physical activity (accelerometer) were measured at baseline and at 6 months follow-up. Linear regression models were used to investigate cross-sectional and longitudinal associations of accelerometer-derived sedentary time and breaks in sedentary time (BST) with metabolic variables. RESULTS: in cross-sectional analyses each hour of sedentary time was associated with larger WC (unstandardised regression coefficient [B] [95% CI] 1.89 cm [0.94, 2.83]; p < 0.001), higher insulin (B = 8.22 pmol/l [2.80, 13.65]; p = 0.003) and HOMA-IR (B = 0.42 [0.14, 0.70]; p = 0.004), and lower HDL-cholesterol (B = -0.04 mmol/l [-0.06, -0.01]; p = 0.005). Adjustment for WC attenuated all associations. Each BST was associated with lower WC (B = -0.15 cm [- 0.24, -0.05]; p = 0.003) and there was evidence of a weak linear association with HDL-cholesterol, but no association with insulin levels or HOMA-IR. Volume of sedentary time at baseline predicted HDL-cholesterol (B = -0.05 mmol/l [-0.08, -0.01]; p = 0.007), insulin levels (B = 8.14 pmol/l [0.1.51, 14.78]; p = 0.016) and HOMA-IR (B = 0.49 [0.08, 0.90]; p = 0.020) at 6 months, though not WC. Baseline BST did not substantially predict any metabolic variables at follow-up. No change was seen in sedentary time or BST between baseline and 6 months follow-up. CONCLUSIONS/INTERPRETATION: Higher sedentary time is associated with a poorer metabolic profile in people with type 2 diabetes.
Abstract.
Author URL.
Chimen M, Kennedy A, Nirantharakumar K, Pang TT, Andrews R, Narendran P (2012). What are the health benefits of physical activity in type 1 diabetes mellitus? a literature review.
DIABETOLOGIA,
55(3), 542-551.
Author URL.
2011
Andrews RC, Cooper AR, Montgomery AA, Peters TJ, Sharp DJ, Dayan CM (2011). Diet or diet plus physical activity in patients with early type 2 diabetes Reply.
LANCET,
378(9809), 2067-2068.
Author URL.
Andrews RC, Cooper AR, Montgomery AA, Norcross AJ, Peters TJ, Sharp DJ, Jackson N, Fitzsimons K, Bright J, Coulman K, et al (2011). Diet or diet plus physical activity versus usual care in patients with newly diagnosed type 2 diabetes: the Early ACTID randomised controlled trial.
Lancet,
378(9786), 129-139.
Abstract:
Diet or diet plus physical activity versus usual care in patients with newly diagnosed type 2 diabetes: the Early ACTID randomised controlled trial.
BACKGROUND: Lifestyle changes soon after diagnosis might improve outcomes in patients with type 2 diabetes mellitus, but no large trials have compared interventions. We investigated the effects of diet and physical activity on blood pressure and glucose concentrations. METHODS: We did a randomised, controlled trial in southwest England in adults aged 30-80 years in whom type 2 diabetes had been diagnosed 5-8 months previously. Participants were assigned usual care (initial dietary consultation and follow-up every 6 months; control group), an intensive diet intervention (dietary consultation every 3 months with monthly nurse support), or the latter plus a pedometer-based activity programme, in a 2:5:5 ratio. The primary endpoint was improvement in glycated haemoglobin A(1c)(HbA(1c)) concentration and blood pressure at 6 months. Analysis was done by intention to treat. This study is registered, number ISRCTN92162869. FINDINGS: of 593 eligible individuals, 99 were assigned usual care, 248 the diet regimen, and 246 diet plus activity. Outcome data were available for 587 (99%) and 579 (98%) participants at 6 and 12 months, respectively. At 6 months, glycaemic control had worsened in the control group (mean baseline HbA(1c) percentage 6·72, SD 1·02, and at 6 months 6·86, 1·02) but improved in the diet group (baseline-adjusted difference in percentage of HbA(1c) -0·28%, 95% CI -0·46 to -0·10; p=0·005) and diet plus activity group (-0·33%, -0·51 to -0·14; p
Abstract.
Author URL.
Pournaras DJ, Aasheim ET, Søvik TT, Andrews R, Mahon D, Welbourn R, Olbers T, le Roux CW (2011). Effect of the definition of type II diabetes remission in the evaluation of bariatric surgery for metabolic disorders.
British Journal of Surgery,
99(1), 100-103.
Abstract:
Effect of the definition of type II diabetes remission in the evaluation of bariatric surgery for metabolic disorders
Abstract
.
. Background
. The American Diabetes Association recently defined remission of type II diabetes as a return to normal measures of glucose metabolism (haemoglobin (Hb) A1c below 6 per cent, fasting glucose less than 5·6 mmol/l) at least 1 year after bariatric surgery without hypoglycaemic medication. A previously used common definition was: being off diabetes medication with normal fasting blood glucose level or HbA1c below 6 per cent. This study evaluated the proportion of patients achieving complete remission of type II diabetes following bariatric surgery according to these definitions.
.
.
. Methods
. This was a retrospective review of data collected prospectively in three bariatric centres on patients undergoing gastric bypass, sleeve gastrectomy and gastric banding.
.
.
. Results
. Some 1006 patients underwent surgery, of whom 209 had type II diabetes. Median follow-up was 23 (range 12–75) months. HbA1c was reduced after operation in all three surgical groups (P &lt; 0·001). A total of 72 (34·4 per cent) of 209 patients had complete remission of diabetes, according to the new definition; the remission rates were 40·6 per cent (65 of 160) after gastric bypass, 26 per cent (5 of 19) after sleeve gastrectomy and 7 per cent (2 of 30) after gastric banding (P &lt; 0·001 between groups). The remission rate for gastric bypass was significantly lower with the new definition than with the previously used definition (40·6 versus 57·5 per cent; P = 0·003).
.
.
. Conclusion
. Expectations of patients and clinicians may have to be adjusted as regards remission of type II diabetes after bariatric surgery. Focusing on improved glycaemic control rather than remission may better reflect the benefit of this type of surgery and facilitate improved glycaemic control after surgery. Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
.
Abstract.
Bennett-Britton I, Kingsly A, White P, Jackson NA, Chen MZ, Andrews RC (2011). Effects of diet and diet plus physical activity on psychological outcomes in newly diagnosed type 2 diabetes mellitus: results of a randomised controlled trial.
Author URL.
Parker R, Guthrie N, Patel N, Woltersdorf W, Andrews R, Dayan C, McCune CA, ACTID E (2011). PREVALENCE OF ABNORMAL LIVER FUNCTION AND RESPONSE TO LIFESTYLE INTERVENTIONS IN NEWLY DIAGNOSED TYPE 2 DIABETES: PRELIMINARY RESULTS OF a UK RANDOMISED CONTROLLED STUDY.
Author URL.
Parker R, Guthrie N, Patel N, Woltersdorf W, Andrews R, Dayan CM, ACTID E (2011). PREVALENCE OF ABNORMAL LIVER FUNCTION AND RESPONSE TO LIFESTYLE INTERVENTIONS IN NEWLY DIAGNOSED TYPE 2 DIABETES: PRELIMINARY RESULTS OF a UK RANDOMISED CONTROLLED STUDY.
Author URL.
Thong KY, Jose B, Sukumar N, Cull ML, Mills AP, Sathyapalan T, Shafiq W, Rigby AS, Walton C, Ryder REJ, et al (2011). Safety, efficacy and tolerability of exenatide in combination with insulin in the Association of British Clinical Diabetologists nationwide exenatide audit.
Diabetes Obes Metab,
13(8), 703-710.
Abstract:
Safety, efficacy and tolerability of exenatide in combination with insulin in the Association of British Clinical Diabetologists nationwide exenatide audit.
AIM: to assess the extent, safety, efficacy and tolerability of reported off-licence exenatide use through a nationwide audit. METHODS: the Association of British Clinical Diabetologists hosted a password-protected, online collection of anonymized data of exenatide use in real clinical practice. Three hundred and fifteen contributors from 126 centres across UK provided data on 6717 patients. HbA1c and weight changes, exenatide discontinuation, adverse events and treatment satisfaction were compared between non-insulin and insulin-treated patients. RESULTS: Four thousand eight hundred and fifty-seven patients had baseline and follow-up treatment status with mean (±s.d.) baseline HbA1c 9.45 ± 1.69% and BMI 40.0 ± 8.2 kg/m(2). of the 4857 patients, 1921 (39.6%) used exenatide with insulin. Comparing patients who continued insulin with exenatide with non-insulin-treated patients, mean (±s.e.) latest HbA1c and weight reduction (median 26 weeks) were 0.51 ± 0.06 versus 0.94 ± 0.04% (p < 0.001) and 5.8 ± 0.2 versus 5.5 ± 0.1 kg (p = 0.278). Insulin-treated patients had higher rates of exenatide discontinuation (31.0 vs. 13.9%, p < 0.001), hypoglycaemia (8.9 vs. 6.1%, p < 0.001), gastrointestinal side effects (28.4 vs. 25.0%, p = 0.008) and treatment dissatisfaction (20.8 vs. 5.7%, p < 0.001). However, 34.2% of the patients continuing insulin still achieved HbA1c reduction ≥1%. There was significant insulin discontinuation, dose reduction and greater sulphonylurea discontinuation among insulin-treated patients. CONCLUSIONS: Addition of exenatide to obese, insulin-treated patients can improve glycaemia and weight. Adverse events were statistically but probably not clinically significantly higher, but combination treatment was less well tolerated. Overall, exenatide was less effective in lowering HbA1c among insulin-treated patients, although significant number of insulin-treated patients still achieved significant HbA1c, weight and insulin reductions. Further research into identifying obese, insulin-treated patients who will tolerate and benefit from exenatide treatment is urgently needed.
Abstract.
Author URL.
2009
Pang TTL, Goble E, Weaver K, Chinem M, Eldershaw SA, Gough SC, Andrews R, Narendran P (2009). Adiponectin receptor expression on peripheral blood mononuclear cells is reduced in autoimmune diabetes and can be upregulated with lifestyle intervention.
Author URL.
Chen M, Andrews R (2009). Obesity and Other Diseases. In (Ed) Obesity: Science to Practice, 323-343.
Idris I, Hall AP, O'Reilly J, Barnett A, Allen M, Andrews R, Grunstein P, Lewis K, Goenka N, Wilding JP, et al (2009). Obstructive sleep apnoea in patients with type 2 diabetes: aetiology and implications for clinical care.
DIABETES OBESITY & METABOLISM,
11(8), 733-741.
Author URL.
Malpass A, Andrews R, Turner KM (2009). Patients with Type 2 Diabetes experiences of making multiple lifestyle changes: a qualitative study.
Patient Educ Couns,
74(2), 258-263.
Abstract:
Patients with Type 2 Diabetes experiences of making multiple lifestyle changes: a qualitative study.
OBJECTIVES: to explore patients newly diagnosed with Type 2 Diabetes Mellitus (T2DM) experiences of making single (diet) or multiple (diet and physical activity) changes in order to (1) assess whether patients experienced increases in physical activity as supporting or hindering dietary changes and vice versa, and (2) whether patients found making multiple lifestyle changes counterproductive or beneficial. METHODS: In-depth interviews with 30 individuals taking part in a randomised controlled trial that aimed to determine the effect of diet and physical activity on T2DM. Interviewees had been randomised to receive usual care, intensive dietary advice, or intensive dietary advice plus information on physical activity. Respondents were interviewed 6 and 9 months post-randomisation. They were asked about their experiences of making lifestyle changes. Data were analysed thematically. RESULTS: Findings suggest providing diet and physical activity information together encourages patients to use physical activity in strategic ways to aid disease management and that most patients find undertaking multiple lifestyle changes helpful. CONCLUSION: Increasing physical activity can act as a gateway behaviour, i.e. behaviour that produces positive effects in other behaviours. PRACTICE IMPLICATIONS: Practitioners should provide diet and physical activity information together to encourage patients to use physical activity strategically to maintain dietary changes.
Abstract.
Author URL.
Chen M, Andrews R (2009). Special Considerations in Managing Obesity. In (Ed) Obesity: Science to Practice, 471-495.
2008
Pang TTL, Kiyani S, Boora U, Gough SCL, Andrews R, Narendran P (2008). Adipocytokines and their receptors are expressed by peripheral blood mononuclear cells (PBMCs), and this expression is modified by exercise-induced weight loss.
IMMUNOLOGY,
125, 108-109.
Author URL.
ONTARGET Investigators, Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, Schumacher H, Dagenais G, Sleight P, Anderson C, et al (2008). Telmisartan, ramipril, or both in patients at high risk for vascular events.
The New England journal of medicine,
358(15), 1547-1559.
Abstract:
Telmisartan, ramipril, or both in patients at high risk for vascular events.
BackgroundIn patients who have vascular disease or high-risk diabetes without heart failure, angiotensin-converting-enzyme (ACE) inhibitors reduce mortality and morbidity from cardiovascular causes, but the role of angiotensin-receptor blockers (ARBs) in such patients is unknown. We compared the ACE inhibitor ramipril, the ARB telmisartan, and the combination of the two drugs in patients with vascular disease or high-risk diabetes.MethodsAfter a 3-week, single-blind run-in period, patients underwent double-blind randomization, with 8576 assigned to receive 10 mg of ramipril per day, 8542 assigned to receive 80 mg of telmisartan per day, and 8502 assigned to receive both drugs (combination therapy). The primary composite outcome was death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure.ResultsMean blood pressure was lower in both the telmisartan group (a 0.9/0.6 mm Hg greater reduction) and the combination-therapy group (a 2.4/1.4 mm Hg greater reduction) than in the ramipril group. At a median follow-up of 56 months, the primary outcome had occurred in 1412 patients in the ramipril group (16.5%), as compared with 1423 patients in the telmisartan group (16.7%; relative risk, 1.01; 95% confidence interval [CI], 0.94 to 1.09). As compared with the ramipril group, the telmisartan group had lower rates of cough (1.1% vs. 4.2%, P
Abstract.
2007
Norcross AJ, Andrews RC, Actid E (2007). Misdiagnosis of Type 2 diabetes in the southwest of England.
Author URL.
Fitzsimons KJ, Cooper AR, Andrews R (2007). Physical Activity and Fitness in Adults with Newly Diagnosed Type 2 Diabetes. Medicine & Science in Sports & Exercise, 39(5).
Fitzsimons KJ, Cooper AR, Andrews R (2007). Physical activity in adults with newly diagnosed Type 2 diabetes: the early ACTID Study.
Author URL.
Chen MZ, Hudson CA, Vincent EE, Dayan CM, DeBerker D, Tavare JM, Andrews RC (2007). Weight loss resulting from bariatric surgery in morbidly obese insulin resistant individuals leads to improvements in insulin signaling.
Author URL.
2005
Sandeep TC, Andrew R, Homer NZM, Andrews RC, Smith K, Walker BR (2005). Increased in vivo regeneration of cortisol in adipose tissue in human obesity and effects of the 11beta-hydroxysteroid dehydrogenase type 1 inhibitor carbenoxolone.
Diabetes,
54(3), 872-879.
Abstract:
Increased in vivo regeneration of cortisol in adipose tissue in human obesity and effects of the 11beta-hydroxysteroid dehydrogenase type 1 inhibitor carbenoxolone.
11beta-Hydroxysteroid dehydrogenase type 1 (11HSD1) regenerates cortisol from cortisone within adipose tissue and liver. 11HSD1 inhibitors may enhance insulin sensitivity in type 2 diabetes and be most efficacious in obesity when 11HSD1 is increased in subcutaneous adipose biopsies. We examined the regeneration of cortisol in vivo in obesity, and the effects of the 11HSD1 inhibitor carbenoxolone. We compared six lean and six obese men and performed a randomized, placebo-controlled crossover study of carbenoxolone in obese men. The obese men had no difference in their whole-body rate of regenerating cortisol (measured with 9,11,12,12-[(2)H(4)]cortisol tracer), but had more rapid conversion of [(3)H]cortisone to [(3)H]cortisol in abdominal subcutaneous adipose tissue (measured with microdialysis). During insulin infusion, adipose 11HSD1 activity fell markedly in lean but not in obese men. Carbenoxolone inhibited whole-body cortisol regeneration, but did not significantly inhibit adipose 11HSD1 and had no effects on insulin sensitivity (measured by [(2)H(2)]glucose infusion with or without hyperinsulinemia). Thus, in vivo cortisol generation is increased selectively within adipose tissue in obesity, perhaps reflecting resistance to insulin-mediated downregulation of 11HSD1. However, obese men are less susceptible than lean men to the insulin-sensitizing effects of carbenoxolone. To be useful in obese patients, 11HSD1 inhibitors will need to inhibit the enzyme more effectively in adipose tissue.
Abstract.
Author URL.
Andrews RC, Chau WF, Allen SE, Douek IF (2005). Women after gestational diabetes - does the adrenal gland play a role in the future development of type 2 diabetes?.
Author URL.
2003
Andrews RC, Rooyackers O, Walker BR (2003). Effects of the 11 beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone on insulin sensitivity in men with type 2 diabetes.
J Clin Endocrinol Metab,
88(1), 285-291.
Abstract:
Effects of the 11 beta-hydroxysteroid dehydrogenase inhibitor carbenoxolone on insulin sensitivity in men with type 2 diabetes.
11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) regenerates cortisol from inactive cortisone in liver and adipose tissue. Inhibition of 11 beta-HSD1 offers a novel potential therapy to lower intracellular cortisol concentrations and thereby enhance insulin sensitivity and hepatic lipid catabolism in type 2 diabetes, obesity, and hyperlipidemia. We evaluated this approach using the nonselective 11 beta-HSD inhibitor, carbenoxolone, in healthy men and lean male patients with type 2 diabetes. Six diet-controlled nonobese diabetic patients with hemoglobin A(1c) less than 8%, and six matched controls participated in a double-blind, cross-over comparison of carbenoxolone (100 mg every 8 h, orally, for 7 d) and placebo. They were admitted overnight for infusions of insulin (as required to maintain arterialized plasma glucose of 5.0 mM) and [13C6]glucose. Glucose kinetics were measured in the fasted state from 0700-0730 h, during a 3-h euglycemic hyperinsulinemic clamp (including somatostatin infusion and replacement of physiological GH and glucagon levels), and during a 2-h euglycemic hyperinsulinemic clamp with a 4-fold increase in glucagon levels. Data are the mean +/- SEM. Carbenoxolone had the expected effects of raising blood pressure and lowering plasma potassium. Carbenoxolone reduced total cholesterol in healthy subjects (5.25 +/- 0.34 vs. 4.78 +/- 0.40 mM; P < 0.01), but had no effect on other serum lipids or on cholesterol in diabetic patients. Carbenoxolone did not affect the rate of glucose disposal or the suppression of free fatty acids during hyperinsulinemia. However, carbenoxolone reduced the glucose production rate during hyperglucagonemia in diabetic patients (1.90 +/- 0.2 vs. 1.53 +/- 0.3 mg/kg x min; P < 0.05). This was attributable to reduced glycogenolysis (1.31 +/- 0.2 vs. 1.01 +/- 0.2 mg/kg x min; P < 0.005) rather than altered gluconeogenesis. These observations reinforce the potential metabolic benefits of inhibiting 11 beta-HSD1 in the liver of patients with type 2 diabetes. Further studies in obesity and hyperlipidemia are now warranted. However, clinically useful therapeutic effects will probably require selective 11 beta-HSD1 inhibitors that lower intraadipose cortisol levels and enhance peripheral glucose uptake.
Abstract.
Author URL.
Pfeffer MA, McMurray JJV, Velazquez EJ, Rouleau JL, Kober L, Maggioni AP, Solomon SD, Swedberg K, Van de Werf F, White H, et al (2003). Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both.
NEW ENGLAND JOURNAL OF MEDICINE,
349(20), 1893-1906.
Author URL.
2002
Andrews RC, Herlihy O, Livingstone DEW, Andrew R, Walker BR (2002). Abnormal cortisol metabolism and tissue sensitivity to cortisol in patients with glucose intolerance.
J Clin Endocrinol Metab,
87(12), 5587-5593.
Abstract:
Abnormal cortisol metabolism and tissue sensitivity to cortisol in patients with glucose intolerance.
Recent evidence suggests that increased cortisol secretion, altered cortisol metabolism, and/or increased tissue sensitivity to cortisol may link insulin resistance, hypertension, and obesity. Whether these changes are important in type 2 diabetes mellitus (DM) is unknown. We performed an integrated assessment of glucocorticoid secretion, metabolism, and action in 25 unmedicated lean male patients with hyperglycemia (20 with type 2 diabetes and 5 with impaired glucose intolerance by World Health Organization criteria) and 25 healthy men, carefully matched for body mass index, age, and blood pressure. Data are mean +/- SE. Patients with hyperglycemia (DM) had higher HbA(1c) (6.9 +/- 0.2% vs. 6.0 +/- 0.1%, P < 0.0001) and triglycerides. Cortisol secretion was not different, as judged by 0900 h plasma cortisol and 24 h total urinary cortisol metabolites. However, the proportion of cortisol excreted as 5alpha- and 5beta-reduced metabolites was increased in DM patients. Following an oral dose of cortisone 25 mg, generation of plasma cortisol by hepatic 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD 1) was impaired in DM patients (area under the curve, 3617 +/- 281 nM.2 h vs. 4475 +/- 228; P < 0.005). In contrast, in sc gluteal fat biopsies from 17 subjects (5 DM and 12 controls) in vitro 11beta-HSD 1 activity was not different (area under the curve, 128 +/- 56% conversion.30 h DM vs. 119 +/- 21, P = 0.86). Sensitivity to glucocorticoids was increased in DM patients both centrally (0900 h plasma cortisol after overnight 250 micro g oral dexamethasone 172 +/- 16 nM vs. 238 +/- 20 nM, P < 0.01) and peripherally (more intense forearm dermal blanching following overnight topical beclomethasone; 0.56 +/- 0.92 ratio to vehicle vs. 0.82 +/- 0.69, P < 0.05). In summary, in patients with glucose intolerance, cortisol secretion, although normal, is inappropriately high given enhanced central and peripheral sensitivity to glucocorticoids. Normal 11beta-HSD 1 activity in adipose tissue with impaired hepatic conversion of cortisone to cortisol suggests that tissue-specific changes in 11beta-HSD 1 activity in hyperglycemia differ from those in primary obesity but may still be susceptible to pharmacological inhibition of the enzyme to reduce intracellular cortisol concentrations. Thus, altered cortisol action occurs not only in obesity and hypertension but also in glucose intolerance, and could therefore contribute to the link between these multiple cardiovascular risk factors.
Abstract.
Author URL.
2001
Holland JB, Furness JT, Griffiths SA, Mudge E, Parfitt VJ, Andrews RC (2001). 1 hour a week of exercise is enough: a study of a 3 and 6 month exercise program in patients with diabetes.
DIABETOLOGIA,
44, A254-A254.
Author URL.
McIntyre CA, Buckley CH, Jones GC, Sandeep TC, Andrews RC, Elliott AI, Gray GA, Williams BC, McKnight JA, Walker BR, et al (2001). Endothelium-derived hyperpolarizing factor and potassium use different mechanisms to induce relaxation of human subcutaneous resistance arteries.
Br J Pharmacol,
133(6), 902-908.
Abstract:
Endothelium-derived hyperpolarizing factor and potassium use different mechanisms to induce relaxation of human subcutaneous resistance arteries.
This investigation examined the hypothesis that release of K(+) accounts for EDHF activity by comparing relaxant responses produced by ACh and KCl in human subcutaneous resistance arteries. Resistance arteries (internal diameter 244+/-12 microm, n=48) from human subcutaneous fat biopsies were suspended in a wire myograph. Cumulative concentration-response curves were obtained for ACh (10(-9) - 3x10(-5) M) and KCl (2.5 - 25 mM) following contraction with noradrenaline (NA; 0.1 - 3 microM). ACh (E(max) 99.07+/-9.61%; -LogIC(50) 7.03+/-0.22; n=9) and KCl (E(max) 74.14+/-5.61%; -LogIC(50) 2.12+/-0.07; n=10)-induced relaxations were attenuated (P
Abstract.
Author URL.
2000
Andrews RC, Lightman SL (2000). A better use of corticosteroids. The Practitioner, 1613, 667-667.
1999
Finken MJJ, Andrews RC, Andrew R, Walker BR (1999). Cortisol Metabolism in Healthy Young Adults: Sexual Dimorphism in Activities of A-Ring Reductases, but not 11β-Hydroxysteroid Dehydrogenases<sup>1</sup>. The Journal of Clinical Endocrinology & Metabolism, 84(9), 3316-3321.
Finken MJ, Andrews RC, Andrew R, Walker BR (1999). Cortisol metabolism in healthy young adults: sexual dimorphism in activities of A-ring reductases, but not 11beta-hydroxysteroid dehydrogenases.
J Clin Endocrinol Metab,
84(9), 3316-3321.
Abstract:
Cortisol metabolism in healthy young adults: sexual dimorphism in activities of A-ring reductases, but not 11beta-hydroxysteroid dehydrogenases.
Cortisol is metabolized irreversibly by A-ring reductases (5alpha- and 5beta-reductases) and reversibly (to cortisone) by 11beta-hydroxysteroid dehydrogenases (11betaHSDs). In rats, estradiol down-regulates 11betaHSD1 expression. In humans, ratios of urinary cortisol/cortisone metabolites differ in men and women. In this study, urinary cortisol metabolites and hepatic 11betaHSD1 activity were measured in healthy young men and women at different phases of the menstrual cycle. Ten men and 10 women with regular menstrual cycles collected a 24-h urine sample, took 250 microg oral dexamethasone at 2300 h, took 25 mg oral cortisone at 0900 h (after fasting), and had blood sampled for plasma cortisol estimation over the subsequent 150 min. Women repeated the tests in random order in menstrual, follicular, and luteal phases. Women excreted disproportionately less A-ring-reduced metabolites of cortisol [median 5alpha-tetrahydrocortisol, 1811 (interquartile range, 1391-2300) microg/day in menstrual phase vs. 2723 (interquartile range, 2454-3154) in men (P = 0.01); 5beta-tetrahydrocortisol, 1600 (interquartile range, 1419-1968) vs. 2197 (interquartile range, 1748-2995; P = 0.03)] but similar amounts of cortisol, cortisone, and tetrahydrocortisone. Analogous differences were observed in urinary excretion of androgen metabolites. Conversion of cortisone to cortisol on hepatic first pass metabolism was not different (peak plasma cortisol, 733 +/- 60 nmol/L in women vs. 684 +/- 53 nmol/L in men; mean +/- SEM; P = 0.55). There were no differences in cortisol or androgen metabolism between phases of the menstrual cycle. We conclude that sexual dimorphism in cortisol metabolite excretion is attributable to less A-ring reduction of cortisol in women, rather than less reactivation of cortisone to cortisol by 11betaHSD1. This difference is not influenced acutely by gonadal steroids. 11BetaHSD1 has been suggested to modulate insulin sensitivity and body fat distribution, but caution must be exercised in extrapolating inferences about its regulation from rodents to man. A-Ring reductases may have an equally important influence on metabolic clearance of cortisol and intracellular cortisol concentrations.
Abstract.
Author URL.
ANDREWS RC, WALKER BR (1999). Glucocorticoids and insulin resistance: old hormones, new targets.
Clinical Science,
96(5), 513-523.
Abstract:
Glucocorticoids and insulin resistance: old hormones, new targets
Insulin resistance has been proposed as a mediator of the association between risk factors for cardiovascular disease in the population. The clinical syndrome of glucocorticoid excess (Cushing's syndrome) is associated with glucose intolerance, obesity and hypertension. By opposing the actions of insulin, glucocorticoids could contribute to insulin resistance and its association with other cardiovascular risk factors. In this review, we describe briefly the known mechanisms of insulin resistance and highlight the potential mechanisms for the effect of glucocorticoids. We then discuss factors which modulate the influence of glucocorticoids on insulin sensitivity; this highlights a novel therapeutic strategy to manipulate glucocorticoid action which may prove to be a useful tool in treating subjects with insulin resistance. Finally, we describe evidence from human studies that glucocorticoids make an important contribution to the pathophysiology of insulin resistance in the population.
Abstract.
Andrews RC, Walker BR (1999). Glucocorticoids and insulin resistance: old hormones, new targets.
Clin Sci (Lond),
96(5), 513-523.
Abstract:
Glucocorticoids and insulin resistance: old hormones, new targets.
Insulin resistance has been proposed as a mediator of the association between risk factors for cardiovascular disease in the population. The clinical syndrome of glucocorticoid excess (Cushing's syndrome) is associated with glucose intolerance, obesity and hypertension. By opposing the actions of insulin, glucocorticoids could contribute to insulin resistance and its association with other cardiovascular risk factors. In this review, we describe briefly the known mechanisms of insulin resistance and highlight the potential mechanisms for the effect of glucocorticoids. We then discuss factors which modulate the influence of glucocorticoids on insulin sensitivity; this highlights a novel therapeutic strategy to manipulate glucocorticoid action which may prove to be a useful tool in treating subjects with insulin resistance. Finally, we describe evidence from human studies that glucocorticoids make an important contribution to the pathophysiology of insulin resistance in the population.
Abstract.
Author URL.
1998
McIntyre CA, Andrews RC, Elliot A, Gray GA, Williams BC, McKnight JA, Walker BR, Hadoke PWF (1998). Endothelium-derived hyperpolarizing factor mediates to a large extent acetylcholine-induced relaxation of human subcutaneous resistance arteries.
Author URL.