Slower activation of insulin action in upper body obesity

To determine the influence of body fat distribution on kinetic aspects of i nsulin action, we have monitored the rate of increase of glucose infusion d uring 6-hour hyperinsulinemic (40 mU/m(2)/min) euglycemic clamps in 10 pati ents with upper body obesity (body mass index [BMI], 41 +/- 3 kg/m(2); wais t-to-hip ratio [WHR], > 1.00 for men and > 0.85 for women), 12 patients wit h lower body obesity (BMI, 40 +/- 2 kg/m(2); WHR, < 1.00 for men and < 0.85 for women), and 5 control subjects (BMI, < 30 kg/m(2); WHR, < 1.00 for men and < 0.85 for women). In ail subjects, glucose infusion rate (GIR) to mai ntain euglycemia increased during the clamp studies to achieve maximal, ste ady state values after the fourth to fifth hour. During the first 2 hours o f clamp, mean clip (GIR(20-120min)) (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 (GIR(MAX)) (calc ulated 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 GIR(20-120min) and GIR(MAX) (5.57 +/- 0.67 and 7.05 +/- 0.59 mg/kg per min, respectively) than those of both groups of obese patients. The time t o reach half-maximal GIR (T-1/2) was greater (P < .05) in the upper body ob esity (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 wi th GIR(MAX) (n = 27, R = -.75, P < .001), but not with T-1/2 (R = .21). Sim ilarly, whole body percent fat mass, as assessed by bioelectrical impedance analysis, correlated with GIR(MAX) (n = 16, R = -.79, P < .001), but not w ith T-1/2 (R = .10). In contrast, WHR closely correlated with T-1/2 (n = 27 , R = .78, P < .001), but not with GIR(MAX) (R = .11). We conclude that upp er body obesity is associated with a slower rate of activation of insulin a ction on glucose metabolism, whereas total body adiposity selectively affec ts the maximal, steady-state insulin effect. Copyright (C) 2001 by W.B. Sau nders Company.