Pathogenesis of Diabetes Mellitus in the Elderly

A strong genetic predisposition to type 2 diabetes in middle-aged and elderly patients exists. The specific genes responsible have not been discovered. Patients with a family history of diabetes are more likely to develop the illness as they age. Elderly patients with peripheral insulin resistance and reduced glucose-induced insulin release are more likely to develop type 2 diabetes than those without. In elderly identical twins discordant for type 2 diabetes, subjects without diabetes have evidence of impaired glucose metabolism.

Physiologic and environmental factors compound genetic predisposition. Lower testosterone levels in men and higher testosterone levels in women are risk factors for diabetes development. Elderly individuals who have a high intake of fat and sugar and a low intake of complex carbohydrates are more likely to develop diabetes.

Physical inactivity and central fat distribution predispose to diabetes in the elderly. Unlike younger patients, fasting hepatic glucose production is normal in elderly patients with type 2 diabetes. Elderly type 2 diabetes patients have specific alterations in carbohydrate metabolism. The primary metabolic defect in lean elderly subjects is an impairment in glucose-induced insulin release; the primary abnormality in obese elderly subjects is resistance to insulin-mediated glucose disposal.

Glucose uptake occurs by insulin-mediated and noninsulin-mediated mechanisms. Recently, it has been demonstrated that nonmediated glucose uptake (glucose effectiveness) is markedly impaired in elderly patients with type 2 diabetes. The mechanism for this defect is unclear, but impaired glucose effectiveness is a contributing factor to elevated glucose levels in elderly diabetes patients. Given that several interventions, including glucagon-like peptide 1 (GLP-1), have been shown to enhance glucose effectiveness in younger patients, these findings may have important therapeutic relevance for elderly patients with diabetes.

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Few studies have evaluated molecular biologic abnormalities in elderly patients with diabetes and more are required. The glucokinase gene is the glucose sensor for the β-cell. Some studies have found that this gene acts as a marker for abnormal glucose tolerance in the elderly, but others have not. Insulin receptor number and affinity are normal in elderly patients, but insulin receptor tyrosine kinase activity in skeletal muscle is reduced.