Insulin resistance in the aged: A quantitative evaluation of in vivo insulin sensitivity and in vitro glucose transport

It has recently been made clear that reduced sensitivity to exogenous insulin can be demonstrated in the course of aging. 1–3 This phenomenon has been further investigated with the aid of sophisticated techniques, such as the euglycemic clamp, which, when coupled with the measurement of hepatic glucose production, showed that “impaired tissue sensitivity to insulin is the primary factor responsible for the decrease of glucose tolerance in advancing age.” 4 Nevertheless, this study did not establish whether such impairment reflects reduced sensitivity (receptor deficiency) or reduced response (postreceptor or receptor plus postreceptor defect), as shown in other diseases. 5 Evidence in favor of the view that receptor deficiency is responsible can be seen in our observation of an approximately 50% reduction in receptors in a study of insulin binding on isolated human fat cells. 6 Two aspects of this question appeared to require further investigation: tissue sensitivity to receptor-saturating insulin concentration (euglycemic clamp at about 1000 μU/mL plasma insulin), 5 and the glucose transport system coupled to the receptor. 7 A decrease in receptors alone should shift the insulin sensitivity curve to the right, both in vivo (euglycemic clamp) and in vitro (glucose transport), with no reduction of the maximum effect. 8 A solution to this question is proposed in the light of a study conducted on young volunteers and subjects over 65 years old.