Effect of gender on lipid-induced insulin resistance in obese subjects

Objective: In obese subjects, chronically elevated plasma concentrations of non-esterified fatty acids (NEFAs) exert a marked risk to contract insulin resistance and subsequently type 2 diabetes. When NEFA is acutely increased due to i.v. infusion of lipid, glucose disposal during a hyperinsulinemic-euglycemic clamp is reduced. This effect has been explained by a NEFA-induced decrease in skeletal muscle insulin sensitivity caused by accumulation of the lipid intermediates Such as ceramide and diacylglycerol in the myocytes. However, neither the lipid-induced reduction of glucose disposal nor the intramyocellular lipid deposition has been compared directly in obese females and males. Design: We studied eight obese females and eight obese males (body mass index (BMI): 32.6+/-1.4 and 32.8+/-0.8 respectively. non significant (NS)) matched for cardiorespiratory fitness relative to lean body mass (43.7+/-1..6 and 47.6+/-1.3 ml/kg min respectively, NS). Methods: Each subject underwent two hyperinsulinemic-euglycemic clamps with infusion of lipid or saline respectively. Furthermore, the subjects exercised during the last half an hour of each clamp. Results: The lipid-induced reduction in glucose disposal during the clamp was similar in females and males (46+/-10 and 60+/-4%,, respectively, NS). However, whole-body insulin sensitivity as well as non-oxidative glucose disposal was higher in obese females compared with obese males both during lipid and saline infusion (P