Insulin resistance is a characteristic finding in obesity and in non insulin dependent (Type II) diabetes mellitus. However, the interaction between diabetes and obesity has been poorly characterized and the metabolic disturbances contributing to the defect in insulin-mediated glucose uptake have not been defined. To examine these questions euglycemic and hyperinsulinemic clamp studies (40 mU/m2/min) were performed in 10 control non-obese subjects, 10 non diabetic obese subjects, 8 normal weight Type II diabetics, and 12 obese Type II diabetics. During the insulin clamp study total body glucose uptake in the obese non diabetics (157 ± 18 mg/m2·min, p < 0.01), the normal weight diabetics (159 ± 21, p < 0.01) and the obese diabetics (125 ± 11, p < 0.001) was significantly reduced compared to the non-obese non diabetic control group (249 ± 22 mg/m2·min). The impairment in total body glucose uptake was the result mainly of a defect in non-oxidative glucose disposal. Indeed non-oxidative glucose disposal was blunted by 50% in the obese groups (p < 0.01), somewhat less significantly in the non-obese diabetic group (p < 0.05) but more when obesity and diabetes mellitus were combined (p < 0.001). Total glucose oxidation was significantly diminished (p < 0.01) in both diabetic groups but not in the obese non diabetic group when compared to lean control. A significant inverse correlation between the fasting free fatty acids levels and total glucose uptake (r = -0.453, p < 0.001) and total glucose oxidation (r = -0.466, p < 0.001) during the clamp was observed. It is concluded that: 1) Both obesity per se and diabetes mellitus are associated with moderate to severe impairment in insulin-mediated glucose uptake; 2) the combination of obesity and diabetes causes a further, albeit modest reduction in insulin-mediated glucose uptake; 3) both impaired non oxidative glucose disposal and to a lesser extent diminished glucose oxidation contribute to the impairment of glucose disposal and insulin resistance; 4) elevated plasma FFA levels and enhanced lipid oxidation may be important factors contributing to the observed defects in oxidative and non oxidative glucose disposal.
|Original language||English (US)|
|Number of pages||9|
|Journal||Diabete et Metabolisme|
|State||Published - 1988|
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism