Clinical Features of Nonobese, Apparently Healthy, Japanese Men With Reduced Adipose Tissue Insulin Sensitivity.

Abstract

CONTEXT\nAdipose tissue insulin resistance has been observed in obese subjects and is considered an early metabolic defect that precedes insulin resistance in muscle and liver. Although Asians can readily develop metabolic disease without obesity, the clinical features of nonobese, apparently healthy, Asians with reduced adipose tissue insulin sensitivity (ATIS) have not been elucidated.\n\n\nOBJECTIVE\nTo investigate the clinical parameters associated with reduced ATIS in nonobese, apparently healthy (body mass index <25 kg/m2), Japanese men.\n\n\nMETHODS\nWe studied 52 nonobese Japanese men without cardiometabolic risk factors. Using a two-step hyperinsulinemic euglycemic clamp with a glucose tracer, we evaluated the insulin sensitivity in muscle, liver, and adipose tissue. ATIS was calculated as the percentage of free fatty acid (FFA) suppression/insulin concentration during the first step of the glucose clamp.\n\n\nRESULTS\nUsing the median ATIS value, the subjects were divided into low- and high-FFA suppression groups. The low-FFA suppression group had moderate fat accumulation in the abdominal subcutaneous adipose tissue and liver. Compared with the high-FFA group, they also had a lower fitness level, decreased insulin clearance, impaired insulin sensitivity in muscle, moderately elevated triglycerides, and lowered high-density lipoprotein cholesterol levels. All these factors correlated significantly with ATIS. Hepatic insulin sensitivity was comparable between the two groups.\n\n\nCONCLUSIONS\nIn nonobese, apparently healthy, Japanese men, reduced ATIS was associated with moderate fat accumulation in subcutaneous fat and liver, lower insulin clearance, muscle insulin resistance, and moderate lipedema. These data suggest that reduced ATIS can occur early in the development of the metabolic syndrome, even in nonobese, apparently healthy, men.