Associations between insulin sensitivity, and free fatty acid and triglyceride metabolism independent of uncomplicated obesity

Abstract

Insulin resistance is associated with hypertriglyceridemia and elevated free fatty acid (FFA) concentrations in obese and diabetic individuals, but it is unclear to what extent this relationship is independent of obesity and is present in healthy individuals. We studied 92 healthy middle-aged males selected from the top, middle, and lowest quintiles of the insulin sensitivity index (S i) determined in a group of 182 men using the minimal model of glucose disappearance. Plasma FFA, triglyceride, glucose, insulin, and C-peptide concentrations were measured during a 3-hour intravenous glucose tolerance test (IVGTT). The low-S i (most insulin-resistant) group had more central body fat distribution (subscapular/triceps skinfold thickness) and a higher median body mass index (BMI) of 26.8 (range, 21.1 to 41.1) kg · m −2 ( P < .05). Relatively minor glucose intolerance in the low-S i group was no longer significant when central adiposity was accounted for. Glucose tolerance was maintained by increased insulin secretion, leading to IVGTT insulin responses twofold and fourfold higher in the middle- and low-S i groups, respectively, compared with the high-S i group ( P < .01). Fasting FFA and triglyceride concentrations were increased in the low-S i group relative to the other groups independent of BMI or central adiposity ( P < .01). During the IVGTT, FFA decreased to similar minimum concentrations in all three groups. Triglyceride concentrations during the IVGTT increased above their minimum levels, particularly in the low-S i group ( P < .001). The increase in triglyceride concentrations correlated with the incremental insulin area ( r = .54, P < .001) independent of FFA and basal triglyceride concentrations. These results are consistent with the differential sensitivity of the antilipolytic and glucoregulatory actions of insulin and support the possibility that insulin can stimulate triglyceride release. Insulin sensitivity appears to be an important independent determinant of the variation of FFA and triglyceride concentrations in otherwise healthy men.