Insulin secretion, peripheral insulin sensitivity and insulin-receptor binding in subjects with different degrees of obesity

Objectives: The aim of the present study was to investigate insulin secretion, insulin-receptor binding and peripheral insulin sensitivity in subjects with different degrees of obesity. Methods: 36 obese subjects with normal glucose tolerance and different degrees of obesity and 40 healthy normal-weight subjects participated in the study. Peripheral insulin sensitivity was measured by using the euglycaemic hyperinsulinaemic clamp technique, and insulin-receptor binding-on circulating mononuclear blood cells. Insulin secretion was studied during intravenous tolbutamide test. Results: The subjects with 1 degree of obesity demonstrated a significant decrease in the number of total (p < 0.0001) and high-affinity (p < 0.01) insulin receptors per cell, as well as significantly higher insulin receptor affinity (p < 0.01) as compared to the normal-weight subjects. The subjects with II degree of obesity also demonstrated a significant decrease in the number of total (p < 0.0001) and high-affinity receptors (p < 0.001) per cell as well as an increase (p < 0.001) in insulin-receptor affinity as compared to the controls. The significantly decreased receptor number in the subjects with I and II degree of obesity was accompanied by an increase in insulin receptor affinity; thus their insulin-receptor binding being maintained similar to the controls. The subjects with III degree obesity presented a significant decrease (p < 0.0001) in the number of both the total and high-affinity insulin receptors as well as a reduction in insulin receptor affinity as compared to the controls. Therefore the percentage of specifically bound insulin was significantly lower (p < 0.01) as compared to that of the control group. Insulin resistance in the obese subjects is associated with secondary hyperinsulinaemia, which is present in subjects with I and II degree of obesity; while in severely obese subjects exhaustion of beta-cell secretory capacity is observed. Conclusion: We consider that III degree of obesity appears to be a risk factor for type 2 diabetes mellitus as the alterations in insulin sensitivity, insulin-receptor binding and beta-cell secretion are quite similar to the reported in diabetic patients.