title: The Diabetes Remission Clinical Trial (DiRECT): protocol for a cluster randomised trial.
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
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Current Controlled Trials ISRCTN03267836 . Date of Registration 20/12/2013.
authors.affiliation: University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK. Wilma.Leslie@glasgow.ac.uk.
authors.forename: Wilma S
authors.initials: WS
authors.lastname: Leslie
authors.affiliation: University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK. Ian.Ford@glasgow.ac.uk.
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.affiliation: University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK. Naveed.Sattar@glasgow.ac.uk.
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.affiliation: Newcastle University, Newcastle upon Tyne, Tyne and Wear, NE1 7RU, UK. kieren.hollingsworth@ncl.ac.uk.
authors.forename: Kieren G
authors.initials: KG
authors.lastname: Hollingsworth
authors.affiliation: Newcastle University, Newcastle upon Tyne, Tyne and Wear, NE1 7RU, UK. ashley.adamson@ncl.ac.uk.
authors.forename: Ashley
authors.initials: A
authors.lastname: Adamson
authors.affiliation: Newcastle University, Newcastle upon Tyne, Tyne and Wear, NE1 7RU, UK. falko.sniehotta@ncl.ac.uk.
authors.forename: Falko F
authors.initials: FF
authors.lastname: Sniehotta
authors.affiliation: Counterweight Ltd, Edinburgh, UK. Louise.McCombie@counterweight.org.
authors.forename: Louise
authors.initials: L
authors.lastname: McCombie
authors.affiliation: University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK. Naomi.Brosnahan@glasgow.ac.uk.
authors.forename: Naomi
authors.initials: N
authors.lastname: Brosnahan
authors.affiliation: Counterweight Ltd, Edinburgh, UK. Hazel.Ross@counterweight.org.
authors.forename: Hazel
authors.initials: H
authors.lastname: Ross
authors.affiliation: Newcastle University, Newcastle upon Tyne, Tyne and Wear, NE1 7RU, UK. john.mathers@ncl.ac.uk.
authors.forename: John C
authors.initials: JC
authors.lastname: Mathers
authors.affiliation: Newcastle University, Newcastle upon Tyne, Tyne and Wear, NE1 7RU, UK. Carl.Peters@ncl.ac.uk.
authors.forename: Carl
authors.initials: C
authors.lastname: Peters
authors.affiliation: University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK. George.Thom@glasgow.ac.uk.
authors.forename: George
authors.initials: G
authors.lastname: Thom
authors.affiliation: Newcastle University, Newcastle upon Tyne, Tyne and Wear, NE1 7RU, UK. Alison.Barnes@ncl.ac.uk.
authors.forename: Alison
authors.initials: A
authors.lastname: Barnes
authors.affiliation: University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK. Sharon.Kean@glasgow.ac.uk.
authors.forename: Sharon
authors.initials: S
authors.lastname: Kean
authors.affiliation: University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK. Yvonne.McIlvenna@glasgow.ac.uk.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: McIlvenna
authors.affiliation: Newcastle University, Newcastle upon Tyne, Tyne and Wear, NE1 7RU, UK. Angela.Rodrigues@ncl.ac.uk.
authors.forename: Angela
authors.initials: A
authors.lastname: Rodrigues
authors.affiliation: Newcastle University, Newcastle upon Tyne, Tyne and Wear, NE1 7RU, UK. Lucia.Rehackova@ncl.ac.uk.
authors.forename: Lucia
authors.initials: L
authors.lastname: Rehackova
authors.affiliation: Newcastle University, Newcastle upon Tyne, Tyne and Wear, NE1 7RU, UK. Sviatlana.Zhyzhneuskaya@ncl.ac.uk.
authors.forename: Sviatlana
authors.initials: S
authors.lastname: Zhyzhneuskaya
authors.affiliation: Newcastle University, Newcastle upon Tyne, Tyne and Wear, NE1 7RU, UK. Roy.Taylor@ncl.ac.uk.
authors.forename: Roy
authors.initials: R
authors.lastname: Taylor
authors.affiliation: University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK. Mike.Lean@glasgow.ac.uk.
authors.forename: Mike E J
authors.initials: ME
authors.lastname: Lean
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D004038:Diet, Reducing / Q000379:methods*; D004739:England; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000628:therapy*; D011320:Primary Health Care / Q000379:methods*; D012074:Remission Induction; D012606:Scotland; D061217:Weight Reduction Programs / Q000379:methods*; D055815:Young Adult
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; C517652:hemoglobin A1c protein, human