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Effects of pioglitazone and metformin on -cell function in nondiabetic subjects at high risk for type 2 diabetes

¹The Central Arkansas Veterans Healthcare System and the Department of Medicine, Division of Endocrinology; and the ²Department of Obstetrics and Gynecology, University of Arkansas for Medical Sciences, College of Medicine, Little Rock, Arkansas

Submitted 10 May 2006 ; accepted in final form 6 September 2006

Thiazolidinediones (TZDs) and metformin decreased the incidence of diabetes in subjects at risk for developing diabetes and improved peripheral or hepatic insulin sensitivity, respectively. Whether they also directly improved -cell function is not clear. In vitro studies showed improved -cell function in response to TZDs and metformin; however, the effects of TZDs or metformin on -cell function in humans are still uncertain. We hypothesized that both TZDs and metformin directly affect -cell function. We evaluated -cell function and insulin sensitivity (S_I) in subjects with impaired glucose tolerance or a history of gestational diabetes using oral and intravenous glucose tolerance tests in addition to the glucose-potentiated arginine stimulation test. In contrast to metformin, pioglitazone improved S_I, glucose tolerance, and insulin-independent glucose disposal [glucose effectiveness (S_G)]. Neither pioglitazone nor metformin significantly improved -cell compensation for insulin resistance [disposition index (DI)], but the change in DI significantly correlated with baseline S_I. Insulin secretion in response to arginine at maximally potentiating glucose levels (AIR_max) tended to increase after metformin and to decrease after pioglitazone; however, when adjusted for S_I, the changes were not significant. Our results demonstrate that, in nondiabetic subjects at risk for diabetes, pioglitazone, but not metformin, significantly improved glucose tolerance by improving S_I and S_G. We did not find any evidence that either pioglitazone or metformin improved -cell function. Improved -cell compensation was observed primarily in the subgroup of subjects that had the lowest S_I at baseline.

insulin sensitizer; prediabetes

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