Impact of Pioglitazone on Pancreatic Alpha-Cell Function in Subjects with Impaired Glucose Tolerance.

Postabsurptive plasma glucose concentrations are regulated not just by insulin secretion but also glucagon concentrations. Both fasting and postprandial glucagon concentrations are elevated in subjects with impaired glucose tolerance (IGT) compared to subjects with normal glucose tolerance. The aim of the study was to investigate the effects of pioglitazone on glucagon secretion in subjects with IGT. 15 subjects (9 male) with IGT (WHO criteria) were recruited into this randomised, double-blind, placebo controlled study. All subjects undertook a standard 500kcal meal tolerance (MTT) and intravenous glucose tolerance (FSIVGTT) test on consecutive days following an overnight fast. Plasma glucose (PGs) and glucagon (PGn) were measured following the MTT. Insulin sensitivity (SI) was calculated from the FSIVGTT using the CIBA GEIGY programme. Following 6 months treatment with either placebo or Pioglitazone (Pio 30mg od) all tests were repeated. In the placebo group, subjects were aged (mean±SEM) 60.3±4.2years, with weight 75.7±7.1kg, BMI 27.4±1.6 kg/m² and HbA[sub 1c]5.6±0.2% and in the Pio group age 61.7±3.3years, weight 74.8±3.9kg, BM127.8 ±1. 1 kg/m² and HbA[sub 1c] 5.8±0:1%. There were no significant differences between groups or between baseline and follow up. There was a significant decrease in fasting PGs following Pin (5.8±0.2 vs 5.5±0.1 mmol/L; p=0.018) compared to placebo (6.0±0.2 vs 5.6 ±0.2 mmol/L; 10=0.398). However there were no differences in area under the prandial PGs profiles (AUC[sub PGs-0-4hr])) after 6 months in either treatment group. There was a significant increase in SI following Pio (0.53±0.26x10[sup -4] vs. 1.06±0.35 1/min*microU/ml p--0.043) with a significant decrease in the placebo treated group (2.48±0.22 vs. 1.554-0.24 xl0[sup -4] 1/min*microU/ml p=0.043). Compared to the change observed on placebo (82.5q-8.7 vs 88.8±6.9), Pio significantly decreased (p=0.046) fasting glucagon concentrations after 6 months (124.8±22.4 vs 113.8±23.0pg/ml). There were no differences in AUC[sub PGn-0-4hr) after 6 months in either the placebo (358.9±28.3vs.363.4±19. lpg.h/ml) or Pio (479.3±64.1 vs.445.8±64.2pg.h/ml) groups. In this small cohort of subjects with impaired glucose tolerance, pioglitazone improved insulin sensitivity and thereby lowered both fasting glucagon and glucose concentrations. [ABSTRACT FROM AUTHOR]