Insulin binding in non-insulin-dependent diabetes mellitus (NIDDM) is correlated with glycemic control: clinical evidence for abnormal receptor regulation in NIDDM.
Insulin binding has been reported to be decreased in non-insulin-dependent diabetes mellitus (NIDDM). Although elevated basal insulin concentrations have been correlated with decreased insulin binding in obesity, this relationship has not been found in NIDDM. To determine the potential cause(s) of the decrease, we measured 125I-insulin binding to circulating monocytes isolated from 31 non-insulin-treated patients with NIDDM who had a fasting plasma glucose (FPG) concentration greater than 7.8 mmol/L and 13 control subjects. We examined the influence of obesity, insulin concentration, glycemic control, and treatment with oral hypoglycemic agents on insulin binding in a cross-sectional study. Insulin binding was significantly decreased in the entire NIDDM group (mean +/- SEM, %/10(7) monocytes: 4.65 +/- 0.33) as compared with controls (6.45 +/- .70, P < .02). Subgroups defined by obesity (relative body weight > 1.2) and poor glycemic control (FPG > 11.1 mmol/L) and those not taking oral hypoglycemic agents had significantly lower insulin binding (P < .02). However, neither relative body weight nor insulin concentrations (basal or stimulated) correlated with insulin binding. Stepwise linear regression analysis showed that only FPG significantly correlated with insulin binding (r = -.45, P = .002) even when oral hypoglycemic agent-treated patients were removed from the analysis (r = -.50, P = .003). There was no significant contribution to explain insulin binding by the other variables, including diagnosis of diabetes, obesity, insulin concentration, or treatment with oral hypoglycemic agents. We conclude that poor metabolic control is associated with an alteration in insulin receptor regulation in NIDDM.
Kelly
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CM
Department of Medicine, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
Fantus
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D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D005215:Fasting; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D011972:Receptor, Insulin / Q000378:metabolism*; D012016:Reference Values
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D011972:Receptor, Insulin