Glucose tolerance glucose utilization and insulin secretion in ageing

Dariush Elahi, Denis C. Muller*, Josephine M. Egan*, Reubin Andres*, Johannes Veldhuisf and Graydon S. Meneilly{

Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, *Laboratory of Clinical Physiology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore 21224, MD, {University of Virginia, Division of Endocrinology and Metabolism, Charlottesville, VA 22908, USA, and {Department of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada

Abstract. Ageing is associated with an increased incidence of hypertension, macrovascular disease and type 2 diabetes (non-insulin-dependent diabetes). It has been suggested that a common mechanism may be responsible for all of these pathological states since all of these conditions often cluster in the same individual. Epidemiological and clinical data have consistently demonstrated an association between insulin resistance and/or hyperinsulinaemia and glucose intolerance, dyslipidaemia and elevated systolic blood pressures. Therefore, insulin resistance and hyperinsulinaemia have been proposed as the causal link among the elements of the clusters. The elderly are more glucose intolerant and insulin resistant, but it remains controversial whether this decrease in function is due to an inevitable consequence of 'biological ageing' or due to environmental or lifestyle variables, noticeably increased adiposity/altered fat distribution and physical inactivity. An increase of these modifiable factors has been shown to result in increases in insulin resistance and hyperinsulinaemia and vice versa. However, insulin secretion appears to decrease with age even after adjustments for differences in adiposity, fat distribution and physical activity. The glucose intolerance of ageing may be due, in part, to decreased insulin sensitivity of pancreatic b cells to insulinotropic gut hormones (GLP1/GIP) and in part to alterations of hepatic glucose production.

2002 Endocrine facets of ageing. Wiley, Chichester (Novartis Foundation Symposium 242) p222-246

Ageing is associated with a decline in function in many, if not all, human physiological systems. Cardiovascular, haemodynamic, metabolic and renal functions generally decrease with advancing age. Insulin has been causally related in the aetiology of many of these decrements (Reaven 1988, Kaplan 1989, Stout 1990, DeFronzo & Ferrannini 1991). The reduction in whole-body carbohydrate metabolism in the elderly is one of the hallmarks of the ageing process and substantial evidence shows that increasing age is associated with decreased

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