Effects of tolazamide and exogenous insulin on pattern of postprandial carbohydrate metabolism in patients with non-insulin-dependent diabetes mellitus. Results of randomized crossover trial

To determine whether therapy with exogenous insulin or sulfonylureas results in a postprandial pattern of carbohydrate metabolism in patients with non-insulin-dependent diabetes mellitus (NIDDM) that resembles that in nondiabetic individuals, we employed a dual-isotope technique combined with forearm catheterization to examine meal disposition in NIDDM patients, before and after 3 mo of therapy with tolazamide and after 3 mo of therapy with exogenous insulin, with a randomized crossover design. Results were compared with those observed in nondiabetic subjects. Although both forms of therapy improved chronic glycemic control (glycosylated hemoglobin concentration went from 9.6 ± 0.7 to 7.6 ± 0.5 and 7.1 ± 0.2%, respectively, P < .01), exogenous insulin resulted in a lower postprandial glycemic response than tolazamide (P < .001). Both agents comparably increased (P < .01) fasting and integrated postprandial insulin concentrations. However, the initial rate of postprandial increase was greater with exogenous insulin (P < .05). Tolazamide (P < .05) but not exogenous insulin increased postprandial C-peptide concentrations. However, tolazamide did not improve the deficient early insulin release. Both agents (P < .05) lowered postabsorptive hepatic glucose release (from 2.8 ± 0.3 to 2.3 ± 0.2 mg·kg^-1·min^-1), but not to normal rates (1.8 ± 0.1 mg·kg^-1·min^-1). Endogenous glucose release after carbohydrate ingestion was lowered (P < .001) by insulin (from 633 ± 52 to 460 ± 41 mg·kg^-1·7 h^-1) but not by tolazamide (625 ± 62 mg·kg^-1·7 h^-1) to rates observed in nondiabetic subjects (470 ± 32 mg·kg^-1·7 h^-1). Unmetabolized meal glucose reaching the systemic circulation did not differ before or after therapy with either insulin or tolazamide. Total postprandial glucose uptake was not changed by tolazamide (1308 ± 85 mg·kg^-1·7 h^-1) but was lowered (P < .01) by exogenous insulin (from 1269 ± 57 to 1088 ± 67 mg·kg^-1·17 h^-1) to normal rates (1023 ± 64 mg·kg^-1·7 h^-1). Forearm glucose uptake did not differ among any group. We conclude that, although tolazamide and exogenous insulin, as administered in this study, both improve carbohydrate tolerance, therapy with exogenous insulin results in a pattern of postprandial carbohydrate metabolism that more closely approximates that observed in nondiabetic subjects.