INSULIN-RESISTANCE IN THE REGULATION OF LIPOLYSIS AND KETONE-BODY METABOLISM IN NON-INSULIN-DEPENDENT DIABETES IS APPARENT AT VERY-LOW INSULIN CONCENTRATIONS

The insulin sensitivity of intermediary metabolism was studied in 8 no n-obese men with well-controlled diet-treated non-insulin dependent di abetes (NIDDM) using a low dose incremental insulin infusion (basal, 0 .005 and 0.01 U/kg h-1). Results were compared to 8 healthy male contr ol subjects matched (NIDDM vs. controls, mean +/- S.E.M.) for age (56 +/- 3 vs. 54 +/- 3 years, NS) and body mass index (24.6 +/- 0.7 vs. 25 .3 +/- 0.5 kg/m2, NS). Basal fasting concentrations of insulin (4.7 +/ - 0.8 vs. 3.2 +/- 0.8 mU/l, NS), glucose, total ketone bodies (TKB), a nd non-esterified fatty acids (NEFA) were not significantly different between the groups but glycerol concentrations were significantly elev ated in NIDDM patients (0.072 +/- 0.007 vs. 0.049 +/- 0.003 mmol/l, P < 0.05). During incremental insulin infusion, plasma insulin concentra tions rose to 12.8 +/- 1.5 vs. 10.0 +/- 1.0 mU/l in NIDDM patients vs. control and metabolite concentrations fell significantly (P < 0.001). Significant linear dose-response relationships were found between pla sma insulin (log) and glucose, TKB (log), NEFA, and glycerol concentra tions by analysis of variance applied to regression (all P < 0.001). F or glucose and TKB (log), the group regression lines were parallel but were significantly right-shifted in the NIDDM group (P < 0.001). In c ontrast, the relationships of insulin (log) and both glycerol and NEFA concentrations converged over the observed range of insulin concentra tions. Significant displacement of glycerol and NEFA dose-response rel ationships were found in NIDDM patients at an insulin concentration of 5 mU/l (P < 0.001) but not at 12.5 mU/1. These results indicate that even in non-obese NIDDM patients with normalised fasting glucose conce ntrations, abnormalities persist in the insulin sensitivity of multipl e aspects of intermediary metabolism but abnormal glycerol and NEFA re gulation was evident only at very low insulin concentrations.