The Diabetes Remission Clinical Trial (DiRECT): protocol for a cluster randomised trial

Wilma S Leslie, Ian Ford, Naveed Sattar, Kieren G Hollingsworth, Ashley Adamson, Falko F Sniehotta, Louise McCombie, Naomi Brosnahan, Hazel Ross, John C Mathers, Carl Peters, George Thom, Alison Barnes, Sharon Kean, Yvonne McIlvenna, Angela Rodrigues, Lucia Rehackova, Sviatlana Zhyzhneuskaya, Roy Taylor, Mike E J Lean, Wilma S Leslie, Ian Ford, Naveed Sattar, Kieren G Hollingsworth, Ashley Adamson, Falko F Sniehotta, Louise McCombie, Naomi Brosnahan, Hazel Ross, John C Mathers, Carl Peters, George Thom, Alison Barnes, Sharon Kean, Yvonne McIlvenna, Angela Rodrigues, Lucia Rehackova, Sviatlana Zhyzhneuskaya, Roy Taylor, Mike E J Lean

Abstract

Background: Despite improving evidence-based practice following clinical guidelines to optimise drug therapy, Type 2 diabetes (T2DM) still exerts a devastating toll from vascular complications and premature death. Biochemical remission of T2DM has been demonstrated with weight loss around 15kg following bariatric surgery and in several small studies of non-surgical energy-restriction treatments. The non-surgical Counterweight-Plus programme, running in Primary Care where obesity and T2DM are routinely managed, produces >15 kg weight loss in 33% of all enrolled patients. The Diabetes UK-funded Counterpoint study suggested that this should be sufficient to reverse T2DM by removing ectopic fat in liver and pancreas, restoring first-phase insulin secretion. The Diabetes Remission Clinical Trial (DiRECT) was designed to determine whether a structured, intensive, weight management programme, delivered in a routine Primary Care setting, is a viable treatment for achieving durable normoglycaemia. Other aims are to understand the mechanistic basis of remission and to identify psychological predictors of response.

Methods/design: Cluster-randomised design with GP practice as the unit of randomisation: 280 participants from around 30 practices in Scotland and England will be allocated either to continue usual guideline-based care or to add the Counterweight-Plus weight management programme, which includes primary care nurse or dietitian delivery of 12-20weeks low calorie diet replacement, food reintroduction, and long-term weight loss maintenance. Main inclusion criteria: men and women aged 20-65 years, all ethnicities, T2DM 0-6years duration, BMI 27-45 kg/m(2). Tyneside participants will undergo Magnetic Resonance (MR) studies of pancreatic and hepatic fat, and metabolic studies to determine mechanisms underlying T2DM remission. Co-primary endpoints: weight reduction ≥ 15 kg and HbA1c <48 mmol/mol at one year. Further follow-up at 2 years.

Discussion: This study will establish whether a structured weight management programme, delivered in Primary Care by practice nurses or dietitians, is a viable treatment to achieve T2DM remission. Results, available from 2018 onwards, will inform future service strategy.

Trial registration: Current Controlled Trials ISRCTN03267836 . Date of Registration 20/12/2013.

Figures

Fig. 1
Fig. 1
Study flow chart

References

    1. Walker A. The cost of doing nothing: the economics of obesity in Scotland. Robertson Centre for Biostatistics, University of Glasgow, June 2003.
    1. Chan JM, Rimm EB, Colditz GA, Stampfer MJ, Willett WC. Obesity, fat distribution and weight gain as risk factors for clinical diabetes in men. Diab Care. 1994;17(9):961–9. doi: 10.2337/diacare.17.9.961.
    1. UKPDS UK Prospective Diabetes Study (UKPDS) VIII. Study, design, progress and performance. Diabetol. 1991;34(12):877–90. doi: 10.1007/BF00400195.
    1. Lean ME, Powrie JK, Anderson AS, Garthwaite PH. Obesity, weight loss and prognosis in type 2 diabetes. Diabet Med. 1990;7(3):228–33. doi: 10.1111/j.1464-5491.1990.tb01375.x.
    1. Scottish Health Survey. 2008. (accessed May 2012)
    1. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walkder EA, et al. Diabetes Prevention Programme Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. NEJM. 2002;346:393–403. doi: 10.1056/NEJMoa012512.
    1. Penn L, White M, Lindström J, den Boer AT, Blaak E, Eriksson JG, et al. Importance of weight loss maintenance and risk prediction in the prevention of type 2 diabetes: analysis of European Diabetes Prevention Study RCT. PLoS One. 2013;8(2) doi: 10.1371/journal.pone.0057143.
    1. Miras AD, Chuah LL, Lascaratos G, Faruq S, Mohite AA, Shah PR, et al. Bariatric Surgery Does not Exacerbate and may be beneficial for the Microvascular complications of Type 2 Diabetes. Diab Care. 2012;35:e81. doi: 10.2337/dc11-2353.
    1. Rowe R, Cowx M, Poole C, McEwan P, Morgan C, Walker M. The effects of orlistat in patients with diabetes: improvement in glycaemic control and weight loss. Curr Med Res Opin. 2005;21(11):1885–90. doi: 10.1185/030079905X74943.
    1. Redmon JB, Bertoni AG, Connelly S, Feeney PA, Glasser SP, Glick H, et al. Effect of the look AHEAD study intervention on medication use and related cost to treat cardiovascular disease risk factors in individuals with type 2 diabetes. Diab Care. 2010;33(6):1153–8. doi: 10.2337/dc09-2090.
    1. SIGN. Management of obesity No 115. (accessed May 2012)
    1. NICE: obesity guidelines. 2006. (accessed May 2012)
    1. Quality and Outcomes Framework (QOF).
    1. Dixon JB, O’Brien PE, Playfair J, Chapman L, Schachter LM, Skinner S, et al. Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomised controlled trial. JAMA. 2008;299(3):316–23. doi: 10.1001/jama.299.3.316.
    1. Gregg EW, Chen H, Wagenknecht LE, Clark JM, Delahanty LM, Bantle J, et al. Association of an intensive lifestyle intervention with remission of type 2 diabetes. JAMA. 2012;308(23):2489–96. doi: 10.1001/jama.2012.67929.
    1. Lim EL, Kg H, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetol. 2011;54:2506–14. doi: 10.1007/s00125-011-2204-7.
    1. Guidone C, Manco M, Valera-Mora E, Iaconelli A, Gniuli D, Mari A, et al. Mechanisms of recovery from type 2 diabetes after malabsorptive bariatric surgery. Diabetes. 2006;55(7):2025–31. doi: 10.2337/db06-0068.
    1. Steven S, Carey PE, Small PK, Taylor R. Reversal of Type 2 diabetes after bariatric surgery is determined by the degree of achieved weight loss in both short- and long-duration diabetes. Diabetic Medicine. 2015;32(1):47–53. doi: 10.1111/dme.12567.
    1. Taylor R. Type 2 diabetes: etiology and reversibility. Diabetes Care. 2013;36(4):1047–55. doi: 10.2337/dc12-1805.
    1. Stevens S, Lim EL, Taylor R. Population response to the reversibility of Type 2 diabetes. Diabet Med. 2013;30:e135–8. doi: 10.1111/dme.12116.
    1. Lean M, Brosnahan N, McCloone P, McCombie L, Biggs AB, Ross H, et al. Feasibility and indicative results from a 12-month low-energy liquid diet treatment and maintenance programme for sever obesity. Br J Gen Pract. 2013;63(607):e115–24. doi: 10.3399/bjgp13X663073.
    1. Rehackova L, Arnott B, Araujo-Soares V, Adamson A., Taylor R, Sniehotta FF. Efficacy and acceptability of Very Low Energy Diets in overweight and obese people with Type 2 diabetes mellitus: a systematic review with meta-analyses. Diabet. Med. 2015. doi: 10.1111/dme.13005
    1. Steven S, Taylor, R. Restoring normoglycaemia by use of a very low calorie diet in long- and short-duration Type 2 diabetes. Diabet Med. 2015. doi: 10.1111/dme.12722
    1. Food Standards Agency. The eatwell plate. 2010.
    1. Catenacci VA, Ogden LG, Stuht J, Phelan S, Wing RR, Hill JO. Physical Activity Patterns in the National Weight Control Registry. Obesity (Silver Spring) 2008;16(1):153–61. doi: 10.1038/oby.2007.6.
    1. Tudor-Locke C, Craig CL, Brown WJ, Clemes SA, De Cocker K, Giles-Corti B, et al. How Many Steps/day are Enough? For Adults. Int. J. Behav. Nutr. Phys. Act. 2011;8:79. doi: 10.1186/1479-5868-8-79.
    1. Al-Shayji I, Gill J, Cooney J, Siddiqui S, Caslake M. Development of a novel method to determine very low density lipoprotein kinetics. J Lipid Res. 2007;48:2086–95. doi: 10.1194/jlr.D600044-JLR200.
    1. Blond E, Maitrepierre C, Normand S, Sothier M, Roth H, Goudable J, et al. A new indirect calorimeter is accurate and reliable for measuring basal energy expenditure, thermic effect of food and substrate oxidation in obese and healthy subjects. Eur. e-J. Clin. Nutr. Metab. 2011;6:e7ee15.
    1. Francis JJ, Johnston M, Robertson C, Glidewell L, Entwistle V, Eccles MP, et al. What is an adequate sample size? Operationalising data saturation for theory-based interview studies. Psychol. Health. 2010;25(10).
    1. Penn L, Dombrowski SU, Sniehotta FF, White M. Participants' perspectives on making and maintaining behavioural changes in a lifestyle intervention for type 2 diabetes prevention: a qualitative study using the theory domain framework. BMJ Open. 2013;28:3(6). doi: 10.1136/bmjopen-2013-002949.
    1. Nwaneri C, Bowen-Jones D, Cooper H, Chikkaveerappa K, Afolabi BA. Falling mortality rates in Type 2 diabetes mellitus in the Wirral Peninsula: a longitudinal and retrospective cohort population-based study. Postgrad Med J. 2012;88(1046):679–83. doi: 10.1136/postgradmedj-2012-130877.
    1. Emerging Risk Factors Collaboration Association of Cardiometabolic Multimorbidity With Mortality. JAMA. 2015;314(1):52–60. doi: 10.1001/jama.2015.7008.
    1. Hex N, Bartlett C, Wright D, Taylor M, Varley D. Estimating the current and future costs of Type 1 and Type 2 diabetes in the UK, including direct health costs and indirect societal and productivity costs. Diabet Med. 2012;29(7):855–62. doi: 10.1111/j.1464-5491.2012.03698.x.
    1. Diabetes Prevention Programme Research Group Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393–403. doi: 10.1056/NEJMoa012512.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅