title: Hyperinsulinemia of obesity is due to decreased clearance of insulin.
abstract: The hyperinsulinemia of obesity could result from a decrease in the metabolic clearance rate of insulin (MCR-I), an increase in the secretory rate of insulin (SR-I), or a combination of both these processes. Because C-peptide and insulin are secreted in an equimolar ratio, the plasma concentrations of C-peptide (C) and insulin (I) are inversely proportional to their rates of metabolic clearance (C/I = MCR-I/MCR-C). We obtained 24-h integrated concentrations (IC) of insulin (IC-I) and C-peptide (IC-C) in 23 obese and 45 nonobese subjects over a period of normal activity and food intake. The IC-I was 69% higher in the obese subjects (P less than 0.0001). A 13% increase in the IC-C (P = 0.04), with a constant rate of C-peptide clearance, indicates a proportionate increase in SR-I. A 33% decrease in the IC-C/IC-I in the obese group (P less than 0.005) reflects a decrease in MCR-I; hence, 75% of the hyperinsulinemia is due to a decrease in the clearance of insulin. Because peripheral MCR-I (pMCR-I) is similar in obese and nonobese subjects, the decrease in MCR-I may be due to a decrease in the hepatic clearance of insulin. This conclusion was supported by our comparison of 24-h IC-C/IC-I ratios in the obese and nonobese subjects. Whereas the 24-h IC-C/IC-I of the nonobese resembled the fasting state, the 24-h IC-C/IC-I of the obese resembled the postprandial state, when insulin removal by the liver is known to be suppressed. These data are consistent with a decreased 24-h hepatic MCR-I (hMCR-I) as the cause of the hyperinsulinemia of obesity.
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D001827:Body Height; D001835:Body Weight; D002096:C-Peptide / Q000378:metabolism; D005215:Fasting; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000209:etiology* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin