Slower activation of insulin action in upper body obesity

To determine the influence of body fat distribution on kinetic aspects of insulin action, we have monitored the rate of increase of glucose infusion during 6-hour hyperinsulinemic (40 mU/m2/min) euglycemic clamps in 10 patients with upper body obesity (body mass index BMI], 41 +/- 3 kg/m2; waist-to-hip ratio WHR], > 1.00 for men and > 0.85 for women), 12 patients with lower body obesity (BMI, 40 +/- 2 kg/m2; WHR, < 1.00 for men and < 0.85 for women), and 5 control subjects (BMI, < 30 kg/m2; WHR, < 1.00 for men and < 0.85 for women). In all subjects, glucose infusion rate (GIR) to maintain euglycemia increased during the clamp studies to achieve maximal, steady state values after the fourth to fifth hour. During the first 2 hours of clamp, mean GIR (GIR20-120min) (traditional approach to assess insulin sensitivity) was lower (P < 0.05) in the upper body obesity group than in the lower body obesity group (2.12 +/- 0.14 and 3.03 +/- 0.33 mg/kg per min, respectively). In contrast, the maximal steady-state GIR (GIRMAX) (calculated as mean GIR during the sixth hour of clamp) was similar in the upper body and in the lower body obesity groups (4.48 +/- 0.45 and 4.57 +/- 0.36 mg/kg per min, respectively). Control subjects exhibited higher values of both GIR20-120min and GIRMAX (5.57 +/- 0.67 and 7.05 +/- 0.59 mg/kg per min, respectively) than those of both groups of obese patients. The time to reach half-maximal GIR (T1/2) was greater (P < .05) in the upper body obesity (94 +/- 12 min) than that in the lower body obesity (41 +/- 5 min) and in the control group (30 +/- 5 min). In pooled subjects, BMI correlated with GIRMAX (n = 27, R = -.75, P < .001), but not with T1/2 (R = .21). Similarly, whole body percent fat mass, as assessed by bioelectrical impedance analysis, correlated with GIRMAX (n = 16, R = -.79, P < .001), but not with T1/2 (R = .10). In contrast, WHR closely correlated with T1/2 (n = 27, R = .78, P < .001), but not with GIRMAX (R = .11). We conclude that upper body obesity is associated with a slower rate of activation of insulin action on glucose metabolism, whereas total body adiposity selectively affects the maximal, steady-state insulin effect.