Insulin action in obese non-insulin-dependent diabetics and in their isolated adipocytes before and after weight loss

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Abstract
To determine the effects of weight loss on insulin action in patients with non-insulin-dependent diabetes mellitus (NIDDM) and in their isolated adipocytes, we studied nine weight-stabilized Pima Indians [7 females and 2 males; age 39 ± 3 yr; wt 99.9 ± 8.2 kg; body fat 39 ± 2% (means ± SE)] before and after a 6.7 ± 1.3-kg weightloss and decrease in fasting plasma glucose from 250 ± 11 to 148 ± 15 mg/dl. Invivo insulin action was measured during a 3-insulin-step, hyperglycemic (∼310 mg/dl) clamp with somatostatin (250 μ/h). At a clamp plasma insulin concentration of ∼10 μU/ml, glucose disposal rates did not change after weight loss; at ∼100 μU/ml, glucose disposal rates increased by 21% [from 4.3 ± 0.2 to 5.3 ± 0.4 mg · min−1 · kg−1 of fat-free mass (FFM), P < .01] mostly due to increased carbohydrate oxidation rates (2.0 ± 0.3 to 2.8 ± 0.3 mg min−1 kg−1 FFM, P < .02); at ∼2400 μU/ml, glucose disposal rates increased by 37% (11.4 ± 0.6 to 15.6 ± 1.4 mg min−1 kg−1 FFM, P < .02) mostly due to increased nonoxidative carbohydrate disposal rates or storage (7.5 ± 0.6 to 10.9 ± 1.3 mg min−1 kg−1 FFM, P < .04). Sensitivity of glucose disposal to insulin in the physiologic range (measured as change in glucose disposal rate per unit change in insulin concentration between clamps at ∼10 and ∼100μU/ml) was very low in these diabetic subjects and did not change after weight loss. Adipocyte cell size, basal and maximal insulin-stimulated glucose transport, and half-miximal rate for transport did not change after weight loss. The data suggest that insulin in the physiologic range has no apparent effect on glucose disposal in patients with NIDDM before or after weight loss. However, a moderate weight loss isassociated with enhanced capacity to transport and metabolizeglucose in vivo. The discrepancy between in vivo and in vitro results suggests that the adipocytemay not always reflect in vivo insulin action.