Whereas insulin resistance and obesity coexist, some obese individuals remain insulin sensitive.

We examined phenotypic and metabolic factors associated with insulin sensitivity in both muscle and liver in obese individuals.

Sixty-four nondiabetic obese adults (29 males) underwent hyperinsulinemic (15 and 80 mU/m² · min)-euglycemic clamps with deuterated glucose. Top tertile subjects for glucose infusion rate during the high-dose insulin clamp were assigned Muscle_sen and those in the lower two tertiles were assigned Muscle_res. Secondarily, top tertile subjects for endogenous glucose production suppression during the low-dose insulin clamp were deemed Liver_sen and the remainder Liver_res.

Clinical and laboratory parameters and visceral, subcutaneous, liver, and pancreatic fat were compared.

Muscle_sen and Muscle_res had similar body mass index and total fat (P > .16), but Muscle_sen had lower glycated hemoglobin (P < .001) and systolic (P = .01) and diastolic (P = .03) blood pressure (BP). Despite similar sc fat (P = 1), Muscle_sen had lower visceral (P < .001) and liver (P < .001) fat. Liver_sen had lower visceral (P < .01) and liver (P < .01) fat and C-reactive protein (P = .02) than Liver_res. When subjects were grouped by both glucose infusion rate during the high-dose insulin clamp and endogenous glucose production suppression, insulin sensitivity at either muscle or liver conferred apparent protection from the adverse metabolic features that characterized subjects insulin resistant at both sites. High-density lipoprotein-cholesterol, 1-hour glucose, systolic BP, and triglycerides explained 54% of the variance in muscle insulin sensitivity.

Obese subjects who were insulin sensitive at muscle and/or liver exhibited favorable metabolic features, including lower BP, liver and visceral adiposity. This study identifies factors associated with, and possibly contributing to, insulin sensitivity in obesity.