Diabetes mellitus in the elderly: insulin resistance and/or impaired insulin secretion?

Abstract

Elderly people are more glucose intolerant and insulin resistant than young individuals, and many of them will develop type 2 diabetes. It remains, however, controversial whether this decrease in function is due to an inevitable consequence of "biological aging" or due to environmental or lifestyle variables. Indeed, increased adiposity/altered fat distribution, decreased fat free mass/abnormal muscle composition, poor dietary habits and physical inactivity all contribute to reduce insulin sensitivity. Insulin resistance in elderly people appears to predominate in skeletal muscle, whereas hepatic glucose output seems to be almost unaffected. Several abnormalities in islet beta-cell and insulin secretion were also pointed out in elderly people such as increased amyloid deposition and decreased amylin secretion, impaired insulin secretion pulsatility, decreased insulin sensitivity of pancreatic beta-cells to insulinotropic gut hormones and diminished insulin response to non-glucose stimuli such as arginine. Controversial results were reported concerning the effects of aging on absolute insulin secretion in response to oral or intravenous glucose. However, insulin secretion appears to decrease with age, with significantly diminished beta-cell sensitivity and acute insulin response to glucose, provided it is analyzed relative to concomitant decreased insulin sensitivity. Thus, there is an interplay between decreased insulin secretion and increased insulin resistance that largely explains the abnormal glucose metabolism seen in elderly. Weight loss, especially reduction of abdominal adiposity, and increased physical activity may contribute to improve insulin sensitivity and glucose tolerance, and prevent the development of type 2 diabetes in elderly people.