An increase in insulin sensitivity and basal beta‐cell function in diabetic subjects treated with pioglitazone in a placebo‐controlled randomized study

Abstract Aims To investigate the effect of treatment with pioglitazone on beta‐cell function and insulin sensitivity in Type 2 diabetes. Methods Thirty subjects with diet‐controlled Type 2 diabetes were randomized to 3 months treatment with pioglitazone ( n = 19) or placebo ( n = 11). All subjects underwent basal sampling for homeostatic model assessment (HOMA), followed by an intravenous glucose tolerance test and hyperglycaemic clamp, followed by an euglycaemic hyperinsulinaemic clamp; at baseline and after treatment. Results All results are expressed as mean ( sem ). Pioglitazone increased basal insulin sensitivity by 24.7% (7.8) HOMA‐%S vs. 2.1% (5.9) in the placebo group ( P = 0.02). Stimulated insulin sensitivity, M/I, increased in the pioglitazone group compared with placebo: +15.1 (2.8) l kg −1 min −1 vs. +3.2 (2.9) l kg −1 min −1 , respectively ( P = 0.009). Pioglitazone increased adiponectin by 39.3 (6.3), ng/ml compared with a decrease of 0.8 (1.3) ng/ml with placebo ( P = 0.00004). HOMA‐%B increased with pioglitazone, +11.5% (4.8) vs. −2.0% (4.8) with placebo ( P = 0.049), but there was no change in stimulated beta‐cell function as determined by hyperglycaemic clamps. There was a significant reduction in the proinsulin/insulin ratio in the pioglitazone group, −0.057 (0.02) compared with placebo, +0.004 (0.02) ( P = 0.03). There was a significant reduction in HbA 1c of 0.6% (0.1) in the pioglitazone group compared with placebo ( P = 0.003). There was no significant weight gain associated with pioglitazone therapy: +0.7 ( sem 0.6) kg vs. +1.1 ( sem 0.5) kg in placebo group ( P = NS). Conclusions Basal beta‐cell function and insulin sensitivity improved following pioglitazone therapy. The improvement in proinsulin to insulin ratio suggests that beta‐cells are under less stress.