66-OR: Remission of Type 2 Diabetes for Two Years Is Associated with Full Recovery of Beta-Cell Functional Mass in the Diabetes Remission Clinical Trial (DiRECT)

• Published in: Diabetes (New York, N.Y.) Vol. 68; no. Supplement_1
• Main Authors: ZHYZHNEUSKAYA, SVIATLANA V., AL-MRABEH, AHMAD, BARNES, ALISON C., ARIBISALA, BENJAMIN, HOLLINGSWORTH, KIEREN G., PILKINGTON, HELEN, SATTAR, NAVEED, LEAN, MICHAEL E., TAYLOR, ROY
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 01.06.2019
• Subjects: Arginine; Beta cells; Body weight loss; Clinical trials; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Drug therapy; Glucose; Hyperglycemia; Insulin; Insulin secretion; Recovery (Medical); Recovery of function; Remission; Remission (Medicine); Secretion
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db19-66-OR

Aims: Observational studies have suggested that beta cell functional mass inevitably decreases over time. We assessed this after 2 years in a geographically defined subgroup of DiRECT who achieved initial remission after diet-induced weight loss. Methods: A Stepped Insulin Secretion Test with Arginine (SISTA) was used to quantify functional beta cell mass (maximum insulin secretory response during hyperglycemia). Insulin secretion rates were estimated by de-convolution; 40 subjects initially achieved remission (HbA1c<6.5% and FPG <126mg/dl on no antidiabetic drug therapy). At 2 years 20 subjects (13M/7F) remained in remission, 13 gained weight and relapsed, and 7 lost to follow-up. A nondiabetic Comparator (NDC) group, matched for age/gender of DiRECT intervention group participants after weight loss, was studied. Results: In the responder group, median (IQ range) maximum rate of insulin secretion increased from 0.58 (0.48 to 0.81) at baseline to 0.74 (0.54 to 1.00) at 5 months, 0.94 (0.57 to 1.24) (p=0.017 from baseline) at 12 months, and 0.94(0.64 to 1.44) (p=0.030 from baseline) nmol/min/m2 at 24 months. This was comparable to NDC (1.02(0.86 to 1.51) nmol/min/m2) by 12 (p=0.064) and 24 months (p=0.244). Median first phase insulin response increased in responders from 0.042 (0.004 to 0.0637) at baseline to 0.108 (0.058 to 0.163) nmol/min/m2 (p<0.0001) at 5 months, to (0.110(0.059 to 0.201) then 0.125(0.066 to 0.166) nmol/min/m2; p<0.0001)] at 12 and 24 months. Those who failed to maintain remission were characterized by more weight regain 5-24 months (11. 3±1.9 vs. 6.6±1.0 kg, p=0.036). In responders mean HBA1C was 6.0±0.0% at 24 months. Conclusion: Provided weight regain is minimized, remission of type 2 diabetes is durable over 2 years, with a gradual increase to normal beta cell functional mass. Disclosure S.V. Zhyzhneuskaya: None. A. Al-Mrabeh: None. A.C. Barnes: None. B. Aribisala: None. K.G. Hollingsworth: None. H. Pilkington: None. N. Sattar: Advisory Panel; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S. Consultant; Self; NAPP Pharmaceuticals Limited. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Speaker's Bureau; Self; Amgen Inc., Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Roche Diagnostics France, Sanofi. M.E. Lean: Consultant; Self; Counterweight Ltd., Novo Nordisk A/S. Research Support; Self; Novo Nordisk A/S. R. Taylor: Advisory Panel; Self; Wilmington Healthcare. Speaker's Bureau; Self; Lilly Diabetes, Novartis AG. Funding Diabetes UK