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.


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.


Diabetes UK

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at