Role of body fat distribution in the decline in insulin sensitivity and glucose tolerance with age

Abstract

The relationships of body composition and physical fitness [maximal aerobic capacity (VO2max)] to the decline in insulin sensitivity with age were examined in healthy older (47-73 yr; n = 36) and young (19-36 yr; n = 13) men. In 18 older men with normal glucose tolerance (OGTT), glucose disposal rates (M) during hyperinsulinemic euglycemic clamps correlated negatively with the waist to hip ratio (WHR; r = -0.77; P < .001) and percent body fat (r = -0.46; P < 0.05) and positively with VO2max (r = 0.54; P < 0.05), but not with age. Similar relationships existed in the 36 older men with a spectrum of OGTT responses; however, only WHR was independently related to M (r2 = 0.32; P < 0.01). In the older men with normal OGTT, M (mean +/- SEM, 7.88 +/- 0.43 mg/kg fat-free mass.min) was not different from that in the young men (8.56 +/- 0.47; P = NS). Furthermore, in older and young men with normal OGTT matched for WHR, percent fat, or VO2max, glucose disposal was comparable at sequential 15-min intervals during the clamp and in its relationship to insulin concentrations at the tissue level (multicompartmental analysis). In contrast, despite higher steady state plasma insulin levels during the clamp, M was significantly lower in the older men with a higher WHR, greater percent fat, lower VO2max, or impaired OGTT. Thus, in healthy older men up to the age of 73 yr, insulin sensitivity and glucose tolerance are affected primarily by the regional body fat distribution, not age, obesity, or VO2max.

Resistance Training for Glycemic Control, Muscular Strength, and Lean Body Mass in Old Type 2 Diabetic Patients: A Meta-Analysis

“…Two primary risk factors for development of T2D in the elderly are central obesity and physical inactivity [2]. Lack of physical activity is closely associated with the reduction of muscular strength and muscle mass, which may aggravate diabetes through decreased vascular supply and peripheral neuropathy [51].…”

“…The mechanism behind high susceptibility to T2D in the elderly still remains unclear. However, it has been suggested that alteration of lifestyle factors in the elderly, such as decreased physical activity and increased abdominal obesity, mainly contribute to developing insulin resistance [2]. In addition to insulin resistance in the body, elderly people with T2D are susceptible to diabetic-related physical frailty.…”

The physiology of endocrine systems with ageing

“…The degree of relative obesity and the site of fat deposition appear to be the crucial variables determining the efficacy of insulin action. 110,111 These factors are in turn influenced by total caloric intake, decreasing physical activity, medications, and illnesses. 112 However, although exercise improves insulin action and slows the onset of diabetes, no evidence shows that exercise reverses age-related changes occurring in β cells.…”

Age-Related Impairment of Pancreatic Beta-Cell Function: Pathophysiological and Cellular Mechanisms

“…Insulin resistance could increase with age in relation to several well-known age-related changes, such as: (i) increased adiposity (with particular reference to abdominal fat mass) (5); (ii) decreased lean muscle mass (sarcopenia) (25–27); (iii) mitochondrial dysfunctions (28–32); (iv) hormonal changes (33, 34); (v) increased oxidative stress and inflammation (35–39); (vi) changes in dietary habits (40–42); (vii) reduced physical activity (43, 44). However, it has also been claimed that these factors alone cannot fully account for the age-related glucose-intolerance (11), and other studies seem to indicate that age per se could be not responsible for the increased insulin resistance (45–47). …”