Clinical Significance of Insulin Sensitivity in Adipose Tissue in Apparently Healthy Nonobese Men

Increased plasma free fatty acid (FFA) level is reported to be an important cause of obesity-associated insulin resistance in muscle and liver. Increased plasma FFA level in obesity is induced by insufficient suppression of plasma FFA by insulin and this is defined as impaired insulin sensitivity in adipose tissue (Adipo-IS). However, significance of impaired Adipo-IS in non-obese healthy subjects is totally unknown. To clarify this, we studied 49 non-obese (BMI< 25kg/m2) apparently healthy Japanese men without any cardiometabolic risk factors (mean age; 40.2±5.3 y.o, mean BMI; 23.1±1.0 kg/m²). We performed a 2-step hyperinsulinemic euglycemic clamp test (10 and 20 mU/m2 per min, 3h for each) to measure insulin sensitivity in muscle and liver. In addition, plasma FFA levels were also measured at fasting and 2nd step during the glucose clamp. Ectopic fat levels in muscle and liver and visceral fat area (VFA) were measured by 1H-MRS and MRI, respectively. The plasma FFA level was decreased from 530.6±139.1μEq/l to 62.4±64.2μEq/l during hyperinsulinemic euglycemic clamp. Thus, the mean Adipo-IS, defined as %FFA suppression during glucose clamp, was 88.8±10.3%; however, there was a large individual variations in Adipo-IS. Interestingly, Adipo-IS was positively correlated to insulin sensitivity in muscle (r=0.60, p