INSULIN RESISTANCE AND ACTION IN HYPERTRIGLYCERIDEMIA

To define further the characteristics of insulin insensitivity associated with hypertriglyceridemia, the metabolic responses to the euglycemic insulin clamp were evaluated in 6 hypertriglyceridemic male patients and compared to 5 normal male controls. At baseline, the hypertriglyceridemic patients had elevated triglycerides (687 +/- 172 vs 78 +/- 7 mg/dl, P < 0.005) and free fatty acids (702 +/- 36 vs 444 +/- 42-mu-M/l, P < 0.005) concentrations. During the euglycemic insulin clamp, steady-state plasma glucose concentrations were similar in both groups (90.2 +/- 1.5 vs 88.8 +/- 2.3 mg/dl*, ns) as were steady state insulin levels (142 +/- 10.1 vs 132.2 +/- 6.8-mu-U/ml**). The amount of glucose metabolized during the last hour of the clamp (M) was significantly reduced in the hypertriglyceridemic patient (2.9 +/- 0.4 vs 6.2 +/- 0.7 mg.min-1.kg-1, P < 0.001). Changes in free fatty acid, glycerol, B-hydroxybutyrate, lactate and pyruvate during the euglycemic insulin clamp were similar indicating a preserved antilipolytic, antiketogenic and glycolytic intermediate (lactate + pyruvate) response to insulin and glucose infusion in the hypertriglyceridemic patients. In summary, hypertriglyceridemia is associated with insulin resistance as it relates to muscle glucose utilization. However, this is not universal, as a number of other insulin responsive pathways appear to be unaffected.