The decline in glucose metabolism with advancing age does not occur as an isolated process, but is usually accompanied by changes in lifestyle, including: (a) physical inactivity; (b) increased body fat; and (c) the development of disease. The hypothesis is that in the absence of disease, the age-associated decline in glucose tolerance and insulin sensitivity is not due to biologic aging but is affected significantly, by secondary aging processes or changes in lifestyle. Physical inactivity and dietary indiscretion cause older people to gain weight in upper body sites, predisposing to diabetes, obesity and hyperlipidemia, risk factors for atherosclerosis. To study mechanisms by which physical inactivity and weight gain affect glucose and fat metabolism requires measurement of the effects of one lifestyle habit, while others are controlled. Rigorous medical screening for overt asymptomatic diseases, including silent ischemia (exercise electrocardiogram and thallium scan), diabetes mellitus, dyslipoproeinemia, and obesity identified healthy men. Hydodensitometry selects 65 lean (less than 20% fat) and 30 overweight (20-30% fat) men, and maximal aerobic capacity (VO2 max, ml/kg min) categorizes master athletes (VO2 max:50+), athletes (VO2 max:40-49) and inactive (VO2 max:25- 39) men. To determine mechanisms by which physical activity affects metabolism, cross-sectional measurements include: (a) whole body and hepatic sensitivity and maximal responsiveness to insulin during hyperinsulinemi: euglycemic clamps; (b) Insulin secretion and peripheral tissue and hepatic sensitivity to insulin during hyperglycemic clamps; (c) insulin binding and stimulated tyrosine kinase activity in erythrocyte receptors in vitro and their relationship to insulin sensitivity in vivo in (a); (d) lipoprotein lipase activity and responsiveness to adrenergic regulators of lipolysis in subcutaneous fat biopsied from upper and lower body sites; and (e) the relationship of determinations in (d) to fat cell size, V02 max and the mass (kg) and regional distribution of body fat. Longitudinal studies of conditioning (with and without weight loss) and deconditioning converge subjects toward comparable V02 max and % fat to assess mechanisms by which change in activity status and body fat affect glucose metabolism. Reevaluation tests whether or not glucose metabolism in older men is fixed or varies with change in physical activity. This differences effects of biologic aging from those of lifestyle on glucose metabolism, and demonstrates the potential of physical conditioning to reduce risk factors for atherosclerosis.
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