REDUCED POSTPRANDIAL SKELETAL-MUSCLE BLOOD-FLOW CONTRIBUTES TO GLUCOSE-INTOLERANCE IN HUMAN OBESITY

While it is well accepted that the disposal of an oral glucose load (OGL) occurs primarily in skeletal muscle, the mechanisms by which this occurs are not completely elucidated. Glucose uptake (GU) in skeletal muscle follows the Fick principal, such that GU equals the products of the arteriovenous glucose difference (AVGd) across and the blood flow (BF) into muscle. It is widely believed that in the postprandial period both insulin and glucose increase GU by increasing the AVGd; however, a role for increments in BF in the disposal and tolerance of an OGL has not been established. To investigate this issue, whole body GU (isotope dilution), leg GU (leg balance technique), leg BF, and cardiac index (CI) were measured after an overnight fast and over 180 min after an OGL (1 g/kg) in 8 lean (In) and 8 obese (ob) subjects [mean ± sem age, 36 ± 2 vs. 37 ± 2 yr (P = NS) and 60 ± 1 vs. 99 ± 5 kg (P < 0.01), respectively]. Serum glucose levels were higher in the ob than in the In subjects between 100 and 160 min, indicating reduced glucose tolerance. Fasting and post-OGL serum insulin levels were 2- to 3-fold higher in ob us. In at all times, indicating insulin resistance. Peak (40-80 min) incremental whole body GU above baseline was 32% lower in ob vs. In, (P < 0.05). Peak femoral AVGd was not different between ob and In (0.55 ± 0.16 vs. 0.66 ± 0.14 mmol/L; P = NS). Peak leg BF increased 36% over baseline in In (0.328 ± 0.052 to 0.449 ± 0.073 L/min; P < 0.05), while ob subjects displayed no change in leg BF from baseline. Consequently, peak leg GU was 44% lower in ob vs. In (P < 0.05). CI increased 24% from baseline at 60 min in In (P < 0.05), but was unchanged in ob. In summary, after an OGL 1) femoral AVGd increases in both In and ob subjects, but skeletal muscle BF and CI increase in In only; 2) since peak femoral AVGd values were similar in In and ob, differences in peak leg GU and (by inference) whole body GU are largely due to reduced BF to insulin-sensitive tissues; and 3) hemodynamics play an important role in the physiological disposal of an OGL, and therefore, hemodynamic defects can potentially contribute to reduced glucose tolerance and insulin resistance. © 1990 by The Endocrine Society.