The effect of ageing on insulin sensitivity and insulin secretion in non-obese healthy subjects

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Abstract
The relationship of age to insulin sensitivity was studied in 74 non-obese healthy subjects with normal fasting plasma glucose concentration, ranging in age from 17-65 yr. Glucose tolerance and early and late insulin responses were characterized by means of a 2 h glucose infusion test (12 mg/kg per min) primed by an initial injection of 0.33 g/kg body wt glucose. Glucose tolerance did not markedly differ between young (< 30 yr; 31) and middle-aged subjects (31-45 yr; 29) but deteriorated significantly in the elder group (> 45 yr; 14). Early and late insulin responses to glucose were not appreciably altered during aging in this selected healthy population. For the determination of insulin sensitivity a 1 h priming dose-constant infusion technique (two 30 min periods of 8 and 16 mU/kg, insulin ''MC-Actrapid'', initiated by a start injection of 1 and 2 mU/kg, respectively) was used. The percent decrease of plasma glucose, free fatty acid and glycerol levels serves as a measure of the whole body sensitivity to exogenous insulin. Under conditions of identical steady-state insulin levels the decrease in plasma glucose was significantly reduced in elderly (24 .+-. 5%) vs. young (34 .+-. 2%) subjects (P < 0.05). However, a marked sensitivity to the antilipolytic effect of insulin was demonstrated in elderly subjects considered to be resistant to its glucose-lowering action. There was no evidence that disappeared time and metabolic clearance rate of insulin were altered with advancing age. The impaired insulin sensitivity to glucose metabolism seems to be the primary factor responsible for the deterioration of glucose tolerance with advancing age.