A decline in glucose tolerance with age is a common finding that leads to an increased incidence of type 2 diabetes (T2DM) in the elderly. By age 60, 18.3% of persons have diabetes. Nearly 50% of individuals with T2DM are over the age of 65 years.
Elderly persons have reduced insulin sensitivity and impaired insulin-mediated glucose uptake in peripheral tissues, especially skeletal muscle. Impaired insulin action with age is not generally accompanied by change in insulin membrane receptors in target cells. Exercise in middle-aged subjects with T2DM has been shown to elevate levels of GLUT-4 in skeletal muscle and improve glucose tolerance.
Exercise in elderly men has been shown to increase the resting metabolic rate and possibly decrease circulating insulin levels and insulin-to-glucose ratios, implying an increase in insulin sensitivity. The pancreatic islets show an increased sensitivity to inhibition of insulin release by somatostatin. The insulin-to- glucose ratio is usually decreased, suggesting relative islet cell resistance to glucose-stimulated insulin re- lease. In rats, secretion of glucagon from pancreatic islets increases with aging. The age-related change in glucagon secretion may be secondary to altered glucose homeostasis or to reduced pancreatic a-cell responsiveness to glucose or paracrine regulatory factors.
Aging may accelerate the onset of complications due to synergistic effects of aging and diabetes on cellular carbohydrate metabolism. Both aging and diabetes can cause oxidative imbalance, leading to increased production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Increased ROS and RNS are associated with increased damage to DNA and impaired protein intake function.
Advanced glycation end products (AGEs) form spontaneously from glucose-derived Amadori products and accumulate on long-lived tissue protein. AGEs have been implicated in the pathophysiology of both aging and diabetes.
Pentosidine, a glycation reaction product found in skin and glomerular basement membrane, increases with age. Vibratory perception and thermal discrimination decrease with both age and diabetes. A number of age-related coexisting disorders may complicate the management of diabetes in the elderly. In normal aging, the pancreas shows loss of compact structure of islets with hyalinization, increased amyloid deposition, and increased incidence of tumors, especially islet cell tumors. Amyloid deposits, which are associated with increased b-cell death and reduced b-cell mass, are present in the pancreatic islets of approximately 60% of elderly diabetic subjects.
