Improved Plasma FFA/Insulin Homeostasis Is Independently Associated With Improved Glucose Tolerance After a 1-Year Lifestyle Intervention in Viscerally Obese Men

OBJECTIVE Elevated plasma free fatty acids (FFAs) are one important link between excess visceral adiposity, insulin resistance, and the development of type 2 diabetes. Effects of lifestyle interventions on FFA metabolism are poorly known. This open-label study was conducted to test the effects of a 1-year healthy eating/physical activity intervention program on plasma FFA homeostasis in 117 viscerally obese men with dyslipidemia associated with insulin resistance (waist circumference≥90 cm, triglycerides≥1.69 mmol/L, and/or HDL-cholesterol<1.03 mmol/L). RESEARCH DESIGN AND METHODS Body weight, body composition, and fat distribution were assessed by dual-energy X-ray absorptiometry/computed tomography. Oral loads of lipid (60 g fat/m2 body surface area) and glucose (75 g) were measured before and after the intervention. RESULTS After 1 year of lifestyle intervention, visceral adiposity was reduced by -26% (95% CI -29 to -23), whereas cardiorespiratory fitness improved by +20% (95% CI +16 to +24). After 1 year, the suppression of FFAs after the glucose load improved, whereas insulin concentrations were drastically reduced. After the oral lipid load, the late increase in FFA was reduced together with reduced circulating insulin. We calculated an insulin sensitivity index to reflect the concentration of insulin needed to manage plasma FFAs after the oral lipid load, which increased after the intervention and was associated with improved glucose tolerance, independent of changes in visceral or total adiposity. CONCLUSIONS A 1-year healthy eating/physical activity intervention improved the suppression of FFAs after oral glucose and lipid load tests in viscerally obese men, possibly due to improved responsiveness to insulin. This insulin-mediated regulation of postprandial plasma FFA levels could be a link between visceral obesity and impaired glucose homeostasis.