No abstract

OBJECTIVE -To assess the effect of age on glucose metabolism by examining 1) glucose metabolism in young and middle-aged subjects when total or regional adiposity is taken into account and 2) in vitro glucose transport in adipose tissue explants from young and middle-aged women paired for total and abdominal adiposity.RESEARCH DESIGN AND METHODS -Study 1: body composition, subcutaneous abdominal and visceral adipose tissue areas, and fasting and oral glucose-stimulated glucose and insulin were measured in 84 young and 81 middle-aged men and in 110 young and 91 middleaged women. Study 2: glucose uptake in subcutaneous abdominal and visceral adipose tissue explants were measured in eight young and eight middle-aged women.RESULTS -Study 1: young and middle-aged men showed similar subcutaneous abdominal tissue area, whereas fat mass and visceral adipose tissue were greater in middle-aged than in young men (P Ͻ 0.01). Fat mass and subcutaneous and visceral adipose tissue areas were greater in middle-aged as compared with young women (P Ͻ 0.01). Fasting plasma glucose and the glucose response to an oral glucose tolerance test were significantly higher in middle-aged than in young men and women (P Ͻ 0.001). Statistical control for visceral adipose tissue area eliminated the difference seen in glucose response in men and women. Study 2: glucose transport in subcutaneous and omental adipose tissue did not differ between young and middle-aged women.CONCLUSIONS -1) Visceral obesity, more than age per se, correlates with glucose intolerance in middle-aged subjects; 2) aging does not influence in vitro adipose tissue glucose uptake. Diabetes Care 26:480 -484, 2003A diposity has a potent effect on insulin sensitivity (1). Insulin resistance in obesity is commonly believed to manifest by decreased insulin-stimulated glucose transport in skeletal muscle and by impaired suppression of hepatic glucose output (1). The view that diminished glucose uptake into fat accounts for decreased whole-body glucose uptake in obesity has recently gained popularity since adipose-selective depletion of the major insulin-responsive glucose transporter, GLUT4, leads to whole-body insulin resistance in transgenic mice (2).The notion that adipose tissue plays a key role in glucose homeostasis has also been reinforced by the severe insulin-resistant state found in lipodystrophic individuals (3) and mice (4,5).Impairment in glucose tolerance is a common feature of human aging (6). Previous studies suggested that this could be due to a defect in insulin secretory capacity and/or insulin action (7,8). In an attempt to elucidate the cellular mechanisms of the insulin resistance associated with aging, Fink et al. (9) and YkiJarvinen et al. (10) observed an impairment in insulin-stimulated glucose uptake in isolated adipocytes from middle-aged compared with young subjects. Others have disclaimed that the pathogenesis of age-related glucose intolerance was caused by insulin deficiency and/or resistance (11,12). The transition of young to middle age in human...