Clinical Geriatrics

This article is the fourth in a continuing series on diabetes in the elderly. The third article in the series, “Diabetes Agents in the Elderly: An Update of New Therapies and a Review of Established Treatments,” was published in the June issue of the Journal. The remaining articles in the series will discuss such topics as the role of exercise and dietary supplements in the management of diabetes, and microvascular and macrovascular complications of diabetes.

According to the Third National Health And Nutrition Examination Survey (NHANES III), approximately 20% of the U.S. population develops diabetes by the age of 75,1 and at least half of these patients are unaware that they have the disease. ² Both insulin resistance and relative insulin deficiency characterize type 2 diabetes. Therapy should entail diet, weight reduction, and exercise. Patients with persistent hyperglycemia are often started on one or more oral hypoglycemic drugs. Many patients with type 2 diabetes will require insulin as their beta cell function declines over time. Insulin is usually started when full doses of oral hypoglycemic agents are not achieving acceptable glycemic control. The clinician’s options have increased with new insulin analogues that physiologically attempt to match the insulin peaks of the normal glycemic state, enabling patients to achieve tighter glycemic control in a potentially safer way. In this article, we discuss the role of human insulin and new insulin analogues in managing diabetes in the elderly population.

Overview
Most diabetes guidelines emphasize intensive glucose control with a reduction in microvascular complications. However, too low a glycosylated hemoglobin (HbA1c) value can be associated with increased hypoglycemia. Clinical trials have demonstrated that it requires at least 8 years of treatment to get the long-term benefit of glycemic control.³ However, the benefit of lipid and blood pressure control takes only 2-3 years.^4,5 This may suggest that a less aggressive glucose management might be appropriate in a frail elderly population, while more emphasis should be given to aggressive blood pressure and lipid management and aspirin therapy. On the other hand, in 2005, a 65-year-old patient had a predicted 17-20–year life expectancy,⁶ and this span provides time to incur long-term complications. Thus, an individualized approach in managing elderly persons with diabetes is appropriate, acknowledging the variability and complexity of this population.

Age-related changes in functional ability, cognitive functions, eyesight, and impaired manual dexterity may affect the patient’s ability to administer insulin, monitor blood glucose, and manage hypoglycemia, which is a consideration in starting insulin therapy in the elderly population. The benefits and disadvantages of insulin therapy, including hypoglycemia, must be explained to and understood by the patients and family.⁷ The term conventional insulin therapy has been used to describe simpler insulin regimens, such as single daily injections, or two injections per day of combined regular and neutral protamine Hagedorn (NPH) insulin given in fixed amounts before breakfast and dinner. Intensive insulin therapy usually entails utilizing basal insulin with multiple premeal injections of a rapidly-acting insulin to provide a tighter glycemic control. The time to peak and the duration of action of human insulin preparations (NPH and regular insulin) do not replicate endogenous basal and postprandial insulin secretion. Thus, insulin analogues (lispro, aspart, glulisine, glargine, detemir) were developed with the goal of more nearly replicating endogenous insulin secretion.

Insulin is a polypeptide molecule with a molecular weight of 5808 dalton, consisting of an A and B chain connected by two disulfide bridges.