ABDOMINAL FAT AND INSULIN-RESISTANCE IN NORMAL AND OVERWEIGHT WOMEN -DIRECT MEASUREMENTS REVEAL A STRONG RELATIONSHIP IN SUBJECTS AT BOTH LOW AND HIGH-RISK OF NIDDM

Insulin resistance appears to be central to obesity, NIDDM, hyperlipid emia, and cardiovascular disease. While obese women with abdominal (an droid) fat distribution are more insulin resistant than those with per ipheral (gynecoid) obesity, in nonobese women, the relationship betwee n abdominal fat and insulin resistance is unknown. By measuring region al adiposity with dual-energy X-ray absorptiometry and insulin sensiti vity by euglycemic-hyperinsulinemic clamp in 22 healthy women, with a mean +/- SE body BMI of 26.7 +/- 0.9 kg/m(2) and differing risk factor s for NIDDM, we found a strong negative relationship between central a bdominal (intra-abdominal plus abdominal subcutaneous) fat and whole-b ody insulin sensitivity (r = -0.89, P < 0.0001) and nonoxidative gluco se disposal (r = -0.77, P < 0.001), independent of total adiposity, fa mily history of NIDDM, and past gestational diabetes. There was a larg e variation in insulin sensitivity, with a similar variation in centra l fat, even in those whose BMI was <25 kg/m(2). Abdominal fat had a si gnificantly stronger relationship with insulin sensitivity than periph eral nonabdominal fat (r(2) = 0.79 vs. 0.44), and higher levels were a ssociated with increased fasting nonesterified fatty acids, lipid oxid ation, and hepatic glucose output. Because 79% of the variance in insu lin sensitivity in this heterogeneous population was accounted for by central fat, abdominal adiposity appears to be a strong marker and may be a major determinant of insulin resistance in women.