The Pathogenic Role of an Insulin-receptor Defect in Diabetes Mellitus of the Obese

Abstract

I-125-insulin binding to circulating monocytes was measured in 12 obese, maturity-onset diabetic patients, in 10 obese subjects, and in 12 normal persons. The diabetic obese patients were extremely insulin resistant and had an impaired glucose tolerance, while the normoglycemic obese subjects were slightly insulin resistant and had borderline values of glucose tolerance. The insulin secretion pattern of diabetic obese patients after a glucose load differed from that of the normal and normoglycemic obese subjects, showing a low initial response. Insulin binding to monocytes from diabetic obese patients showed a 40 per cent decrease when compared with normal persons (p <0.05). Furthermore, insulin binding to monocytes was about 20 per cent lower in diabetic obese than in normoglycemic obese subjects. However, this difference was not statistically significant (p >0.1). In the total group of persons studied, the insulin binding correlated positively to both glucose tolerance (R = 0.69, p <0.001) and insulin sensitivity (R = 0.74, p <0.001). In the separate groups we also found a statistically significant correlation between insulin binding and insulin sensitivity in normoglycemic obese (R = 0.69, p <0.05) but not in diabetic obese subjects (R = 0.36, p > 0.1) After 10 days of treatment with a 1200-kcal. diet the diabetic patients exhibited significant increases in glucose tolerance (p < 0.01), in insulin sensitivity (p < 0.01), and in insulin binding (p < 0.01) We conclude that a close correlation exists between insulin binding and insulin sensitivity in the three groups studied. Among obese subjects the correlation was less pronounced (statistically insignificant) in diabetic obese persons, emphasizing that, especially in this group, there are other factors of importance for the insulin resistance in addition to the receptor defect.