Time Course of Normalization of Functional β-Cell Capacity in the Diabetes Remission Clinical Trial After Weight Loss in Type 2 Diabetes.

Objective: To assess functional β-cell capacity in type 2 diabetes during 2 years of remission induced by dietary weight loss.

Research Design And Methods: A Stepped Insulin Secretion Test with Arginine was used to quantify functional β-cell capacity by hyperglycemia and arginine stimulation. Thirty-nine of 57 participants initially achieved remission (HbA <6.5% [<48 mmol/mol] and fasting plasma glucose <7 mmol/L on no antidiabetic drug therapy) with a 16.4 ± 7.7 kg weight loss and were followed up with supportive advice on avoidance of weight regain. At 2 years, 20 participants remained in remission in the study. A nondiabetic control (NDC) group, matched for age, sex, and weight after weight loss with the intervention group, was studied once.

Results: During remission, median (interquartile range) maximal rate of insulin secretion increased from 581 (480-811) pmol/min/m at baseline to 736 (542-998) pmol/min/m at 5 months, 942 (565-1,240) pmol/min/m at 12 months ( = 0.028 from baseline), and 936 (635-1,435) pmol/min/m at 24 months ( = 0.023 from baseline; = 20 of 39 of those initially in remission). This was comparable to the NDC group (1,016 [857-1,507] pmol/min/m) by 12 ( = 0.064) and 24 ( = 0.244) months. Median first-phase insulin response increased from baseline to 5 months (42 [4-67] to 107 [59-163] pmol/min/m; < 0.0001) and then remained stable at 12 and 24 months (110 [59-201] and 125 [65-166] pmol/min/m, respectively; < 0.0001 vs. baseline) but lower than that of the NDC group (250 [226-429] pmol/min/m; < 0.0001).

Conclusions: A gradual increase in assessed functional β-cell capacity occurred after weight loss, becoming similar to that of NDC group participants by 12 months. This result was unchanged at 2 years with continuing remission of type 2 diabetes.