INSULIN RESISTANCE IN TYPE-2 (NON-INSULIN-DEPENDENT) DIABETIC-PATIENTS WITH HYPERTRIGLYCERIDEMIA

Hypertriglyceridaemia, which is frequently seen in Type 2 (non-insulin-dependent) diabetes mellitus, is associated with insulin resistance. The connection between hypertriglyceridaemia and insulin resistance is not clear, but could be due to substrate competition between glucose and lipids. To address this question we measured glucose and lipid metabolism in 39 Type 2 diabetic patients with hypertriglyceridaemia, i.e. mean fasting serum triglyceride level equal to or above 2 mmol/l (age 59 +/- 1 years, BMI 27.4 +/- 0.5 kg/m2 , HbA1c 8.0 +/- 0.2 %, serum triglycerides 3.2 +/- 0.2 mmol/l) and 41 Type 2 diabetic patients with normotriglyceridaemia, i.e. mean fasting serum triglyceride level below 2 mmol/l (age 58 +/- 1 years, BMI 27.0 +/- 0.7 kg/m2, HbA1c 7.8 +/- 0.2 %, serum triglycerides 1.4 +/- 0.1 mmol/l). Insulin sensitivity was assessed using a 340 pmol. (m2)-1 . min euglycaemic insulin clamp. Substrate oxidation rates were measured with indirect calorimetry and hepatic glucose production was estimated using a primed (25 muCi)-constant (0.25 muCi/min) infusion of [3-H-3]-glucose. Suppression of lipid oxidation by insulin was impaired in patients with hypertriglyceridaemia vs patients with normal triglyceride levels (3.5 +/- 0.2 vs 3.0 +/- 0.2 mumol . kg-1 . min-1; p < 0.05). Stimulation of glucose disposal by insulin was reduced in hypertriglyceridaemic vs normotriglyceridaemic patients (27.0 +/- 1.3 vs 31.9 +/- 1.6 mumol . kg-1 . min-1; p < 0.05) primarily due to impaired glucose storage (9.8 +/- 1.0 vs 14.6 +/- 1.4 mumol . kg-1 . min-1; p < 0.01). In contrast, insulin-stimulated glucose oxidation was similar in patients with hypertriglyceridaemia and in patients with normal triglyceride concentrations (16.9 +/- 0.8 vs 17.2 +/- 0.7 mumol . kg-1 . min-1). Hepatic glucose production in the basal state and during the clamp did not differ between the two groups. We conclude therefore that oxidative substrate competition between glucose and lipids does not explain insulin resistance associated with hypertriglyceridaemia in Type 2 diabetes. The question remains whether the reduced nonoxidative glucose disposal observed in the patients with hypertriglyceridaemia is genetically determined or a consequence of increased lipid oxidation.