Relationship of body fat topography to insulin sensitivity and metabolic profiles in premenopausal women

Abstract

The relationship of body fat distribution to metabolic profiles was determined in 80 healthy premenopausal white women of a wide range of obesity levels [percentage of ideal body weight (% IBW) 92–251]. Distribution of fat between the upper and lower body was assessed from the waist/hips girth ratio (WHR), which varied from 0.64 to 1.02. In 23 women, in vivo insulin sensitivity was also determined from the steady-state plasma glucose (SSPG) level at comparable insulin levels of approximately 100 μU/mL attained by the intravenous infusion of somatostatin, glucose, and insulin. Increasing WHR was accompanied by progressively increasing fasting plasma insulin levels ( r = 0.47, P < 0.001), insulin and glucose areas after glucose challenge ( r = 0.53, P < 0.001; r = 0.50, P < 0.001, respectively) and fasting plasma triglyceride concentrations ( r = 0.48, P < 0.001). Obesity level was similarly correlated with these metabolic indices. Partial and multiple regression analysis and analysis of variance with a linear contrast model revealed that the effects of body fat topography were independent of, and additive to, those of obesity level. Within obese subjects alone (%IBW: 130), %IBW had no predictive value, but WHR remained a significant predictor of plasma glucose, insulin, and triglyceride concentrations. The WHR also correlated with the plasma cholesterol level, but this association was largely dependent on its relationship to %IBW. Both WHR and %IBW correlated with the insulin resistance index, SSPG ( r = 0.60, P < 0.01; r = 0.61, P < 0.01, respectively). After adjustment for the effects of %IBW, WHR was independently correlated with SSPG and after adjustment for WHR, %IBW correlated significantly with SSPG. The combined effects of WHR and %IBW were additive. The SSPG level, in turn, correlated with the fasting plasma insulin level ( r = 0.89, P < 0.001), glucose area ( r = 0.64, P < 0.01), insulin area ( r = 0.52, P < 0.05) and fasting plasma triglyceride concentration ( r = 0.62, P < 0.01). Significant interactions among these metabolic variables were also present. After adjustment for the effects of WHR and %IBW, the strength of these associations was greatly diminished, but the relationship between the SSPG and fasting plasma insulin levels and between the fasting plasma insulin level, insulin area, and fasting plasma triglyceride level remained significant. Our results suggest that in obese premenopausal women, the sites of body fat localization and obesity level influence the degree of insulin sensitivity and, in turn, plasma glucose, insulin, and lipid levels. Recognition of the sites of fat predominance hence may identify the susceptibility of obese women to insulin resistance and metabolic aberrations. Other factors, however, must also be considered.