Insulin-mediated FFA suppression is associated with triglyceridemia and insulin sensitivity independent of adiposity

Abstract

Context: A central/visceral fat distribution and excess free fatty acid (FFA) availability are associated with dyslipidemia and insulin resistance. However, these two characteristics often coexist, making it difficult to detect the independent contributions of each. Whether FFA suppression is more closely linked to metabolic abnormalities is not clear.

Objective: The aim of the study was to examine the relationship between FFA suppression, body fat distribution, and fitness as contributors toward insulin resistance and hypertriglyceridemia.

Design: We measured systemic palmitate turnover using an iv infusion of [9,10-(3)H]palmitate; upper body sc adipose tissue (UBSQ) and visceral adipose tissue (VAT) with dual-energy x-ray absorptiometry and a single-slice abdominal computed tomography scan; fitness with a graded exercise treadmill test; and insulin sensitivity with both the iv glucose tolerance test (IVGTT) (SI(IVGTT)) and mixed meal tolerance test (SI(Meal)).

Setting: The study was conducted at a General Clinical Research Center.

Participants: Baseline data were obtained from 140 elderly adults (age, 60-88 yr; 83 males) and 60 young adults (age, 18-31 yr; 31 males) who participated in a previously published trial assessing the effects of 2-yr supplementation of dehydroepiandrosterone or testosterone on body composition, glucose metabolism, and bone density.

Interventions: There were no interventions.

Main outcome measures: We measured fasting plasma triglyceride (TG) concentrations, SI(IVGTT), and SI(Meal).

Results: Using multivariate regression analysis, the strongest combined predictors of TG concentrations were VAT, postmeal nadir FFA concentrations, sex, and age. The best predictors of SI(IVGTT) were IVGTT nadir palmitate concentration, VAT, UBSQ fat, fitness, and age, whereas the best predictors of SI(Meal) were meal nadir palmitate concentration, UBSQ fat, fitness, and sex.

Conclusions: FFA suppression is associated with both fasting TG concentrations and insulin sensitivity, independent of measures of adiposity.

Trial registration: ClinicalTrials.gov NCT00254371.

Figures

Fig. 1.

Top, Plasma palmitate concentrations during a MMTT (left) and IVGTT (right). Bottom, Plasma insulin concentrations during a MMTT (left) and IVGTT (right) in elderly males (●), elderly females (■), young males (○), and young females (□).

Fig. 2.

Independent associations of nadir palmitate concentrations during a MMTT (left) and IVGTT (right) with fasting plasma TG concentrations adjusted for age group, sex, and VAT. Partial R, 0.34 (MMTT) and 0.45 (IVGTT); P < 0.001 for both.

Fig. 3.

Independent associations of nadir palmitate concentration with insulin sensitivity determined from a MMTT (left) adjusted for UBSQ, VO2 max, and sex (partial R, −0.31; P < 0.001) and from an IVGTT (right) adjusted for VAT and UBSQ, VO2 max, and age group (partial R, −0.31; P < 0.001).