Impaired Glucose Tolerance in Obesity is Associated with Insensitivity to Insulin in Multiple Aspects of Metabolism as Assessed by a Low Dose Incremental Insulin Infusion Technique

Abstract

To determine whether Impaired Glucose Tolerance gives rise to additional defects in insulin action in lipid and ketone metabolism, thirty-two obese subjects were studied by low-dose incremental insulin infusion. Sixteen had Impaired Glucose Tolerance and 16 had normal glucose tolerance. Body mass index was 36.9-80.9 kg m-2 and was similar in each group. In patients with Impaired Glucose Tolerance, plasma insulin was higher in the fasted state (logarithmic mean 14.5 (9.8-21.6) (-SD(-)+SD) vs 9.6 (6.4-14.5) mU l-1, p less than 0.01) and during the infusion (p less than 0.001). The metabolic clearance rate for insulin at the highest infusion rate was lower (14.2 +/- 0.8 (+/- SE) vs 18.9 +/- 2.1 ml kg-1 min-1, p less than 0.05) in these subjects. Basal hepatic glucose production was higher in subjects with Impaired Glucose Tolerance (6.3 +/- 0.4 vs 4.5 +/- 0.6 mol kg-1 min-1, p less than 0.02) and remained elevated during infusion (p less than 0.01). Glucose disposal per unit circulating insulin at the maximal infusion rate was approximately half in subjects with Impaired Glucose Tolerance (0.022 +/- 0.010 vs 0.047 +/- 0.017 ml kg-1 min-1 mU-1 l, p less than 0.01). When simultaneous insulin and metabolite concentrations during the infusion are plotted as dose-response relationships, a difference in relative sensitivity to insulin in Impaired Glucose Tolerance over subjects with normal glucose tolerance is suggested for non-esterified fatty acids 0.72 (95% CI 0.62-0.84) and glycerol 1.85 (1.37-2.49).(ABSTRACT TRUNCATED AT 250 WORDS)