INTERACTION OF CARBOHYDRATE AND FAT FUELS IN HUMAN SKELETAL-MUSCLE - IMPACT OF OBESITY AND NIDDM

The current study was undertaken to examine the impact that obesity an d non-insulin-dependent diabetes mellitus (NIDDM) have on the ability of glucose to stimulate its own uptake and oxidation in muscle. Euglyc emic and hyperglycemic clamp experiments were performed with somatosta tin infusions so that insulin could be replaced to basal levels or to physiological hyperinsulinemia. Arteriovenous leg balance methods were used to measure the pathways of leg muscle glucose uptake, oxidation, and storage. Percutaneous biopsies of the vastus lateralis muscle wer e taken to determine the pyruvate dehydrogenase complex or glycogen sy nthase activities. During basal insulin replacement, obese compared wi th lean nondiabetic subjects had higher values for glucose uptake, res piratory quotient, and glucose oxidation (all P < 0.05) and a higher p roportion of leg energy expenditure derived from glucose. Obese NIDD p atients had a greater reliance on fat calories than lean diabetics dur ing basal insulin replacement (P < 0.05). Hyperinsulinemia increased l eg glucose metabolism (P < 0.001) in all groups, but obese NIDD patien ts were significantly more insulin resistant. Hyperglycemia in NIDDM c ompensated for insulin resistance to the extent that rates of glucose metabolism were the same as those for nondiabetics studied at euglyemi a. When nondiabetics were studied at hyperglycemia matched to the diab etics, the insulin resistance was still readily apparent.