Changes in insulin secretion and insulin sensitivity in relation to the glycemic outcomes in subjects with impaired glucose tolerance in the Indian Diabetes Prevention Programme-1 (IDPP-1)

Abstract

Objective: The Indian Diabetes Prevention Programme-1 (IDPP-1) showed that lifestyle modification (LSM) and metformin were effective for primary prevention of diabetes in subjects with impaired glucose tolerance (IGT). Among subjects followed up for 3 years (n = 502), risk reductions versus those for the control group were 28.5, 26.4, and 28.2% in LSM, metformin (MET), and LSM plus MET groups, respectively. In this analysis, the roles of changes in secretion and action of insulin in improving the outcome were studied.

Research design and methods: For this analysis, 437 subjects (93 subjects with normoglycemia [NGT], 150 subjects with IGT, and 194 subjects with diabetes) were included. Measurements of anthropometry, plasma glucose, and plasma insulin at baseline and at follow-up were available for all of them. Indexes of insulin resistance (homeostasis model assessment of insulin resistance) and beta-cell function (insulinogenic index [DeltaI/G]: 30-min fasting insulin divided by 30-min glucose) were also analyzed in relation to the outcome.

Results: Subjects with IGT showed a deterioration in beta-cell function with time. Individuals with higher insulin resistance and/or low beta-cell function at baseline had poor outcome on follow-up. In relation to no abnormalities, the highest incidence of diabetes occurred when both abnormalities coexisted (54.9 vs. 33.7%, chi(2) = 7.53, P = 0.006). Individuals having abnormal insulin resistance (41.1%) or abnormal DeltaI/G (51.2%, chi(2) = 4.87, P = 0.027 vs. no abnormalities) had lower incidence. Normal beta-cell function with improved insulin sensitivity facilitated reversal to NGT, whereas deterioration in both resulted in diabetes. The beneficial changes were better with intervention than in the control group. Intervention groups had higher rates of NGT and lower rates of diabetes.

Conclusions: In the IDPP-1 subjects, beneficial outcomes occurred because of improved insulin action and sensitivity caused by the intervention strategies.

Figure 1

Median values of HOMA-IR (A, left panel) and ΔI/G (A, right panel) were calculated in relation to glycemic status (NGT, IGT [B], and diabetes [C]) at annual follow-up. The median values at the 1st-, 2nd-, and 3rd-year follow-up in comparison with the corresponding baseline values in these participants are shown in each category of glucose tolerance. A: 1st year n = 160, 2nd year n = 155, 3rd year n = 93. B: 1st year n = 201, 2nd year n = 152, 3rd year n = 150. C: 1st year n = 70, 2nd year n = 60, 3rd year n = 64. ▩, baseline; ▨, follow-up. *P < 0.05 vs. baseline values.