Treatment of Diabetes - Geriatric Medicine
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- Kenneth L. Minaker
The benefits of aggressive treatment in terms of delaying or preventing complications in the elderly diabetic are clear. Life expectancy for the older diabetic person is approximately two-thirds that of a healthy elderly individual. This fact is not an argument against aggressive treatment; in fact, reductions in life expectancy are in large part because most older diabetics have adequate time to develop and suffer from chronic complications of diabetes mellitus.
Recent studies confirm that many of the vascular and renal complications of diabetes develop at a relatively similar rate in types 1 and 2 diabetes. Other diabetic complications are aggravated by changes inherent in aging. Creatinine clearance declines with normal aging and may accelerate or enhance risk for diabetic renal failure. Age is also an independent risk factor for the development of peripheral neuropathy, a common condition in diabetes mellitus.
The initial approach to the older adult with diabetes mellitus requires assessment of the patient's current medical status and estimated life expectancy. Motivation and commitment of the patient and family also play a large role in determining what level of treatment is appropriate. Support services available in the community and financial status should also be considered.
Following evaluation, one of two levels of care can be recommended: symptom-preventing care or aggressive care. The decision is made jointly by the patient and the primary caregiver. Family members and consultants such as geriatricians, diabetologists, cardiologists, and nephrologists may be helpful. These consultants provide a clearer picture of the current medical condition and estimates of life expectancy.
Symptom-preventing care is indicated for those individuals for whom the primary goal of treatment is avoidance of metabolic complications. The average glucose levels necessary to achieve this goal are approximately 200 mg/dL (11 mM) or the glucose level at which glycosuria is minimal. The elimination of glycosuria removes the risk of volume depletion and the risk of secondary problems related to hypotension and poor tissue perfusion.
Hyperglycemic hyperosmolar nonketotic coma due to dehydration and glycosuria is the most dramatic expression of this phenomenon. Glycosuria also is associated with weight loss caused by the loss of calories in the urine. The resultant catabolic state leads to a loss of lean body tissue. The long-term consequences of poor nutrition include increased risk of infections.
Aggressive care has prevention of long-term complications as its goal. Euglycemia is defined as (1) a fasting glucose level lower than 115 mg/dL (6.4 mM), (2) a mean glucose level between 110 and 140 mg/dL (6-8 mM), and (3) normal levels of glycosylated hemoglobin. Prevention of long-term complications in type I patients results from this level of control. These benefits are believed to extrapolate to elderly patients within NIDDM.
Aggressive management programs for older adults with diabetes require high levels of skill, commitment, and diabetes education. Most older individuals are fully able to learn the complicated concepts and tasks required. Older adults lead a less hectic, more ordered life than younger adults. Consequently, making the adjustments in lifestyle necessary for adherence to a good diabetes treatment program may at times be easier.
All older adults with diabetes mellitus should receive a standard basic care program regardless of the treatment goal chosen. These standards (Table 46.1) include a complete history and physical examination to detect any complications of diabetes mellitus and any risk factors for complications. A geriatric assessment, emphasizing a functional assessment, should be performed at the time of diagnosis. Skills in the basic activities involved in daily life (bathing, grooming, dressing, feeding, toileting, and transferring) and the instrumental activities of daily life (e.g., shopping, telephoning, finances, and housework) should be assessed. Social support systems and financial and insurance status often should also be assessed, by nursing and social work staff. Laboratory evaluation at diagnosis includes determinations of fasting serum glucose level, glycosylated hemoglobin (to assess previous level of control and to be used as a baseline), fasting lipid profile, and serum creatinine; urinalysis with examination for proteinuria; and an electrocardiogram. Ophthalmologic evaluation at the time of diagnosis is recommended by the American Diabetes Association for all patients with NIDDM. This recommendation is particularly relevant for elderly patients who are at high risk for ocular diseases including cataract and glaucoma. Dietary assessment provides an initial dietary therapy for the diabetic patient.
Standard diabetes therapy includes diet, exercise, and if necessary use of oral hypoglycemic agents or administration of insulin.
Oral Hypoglycemic Agents
Increasingly, therapy for type 2 diabetes builds on diet and exercise and has become more mechanistically focused. Single or combination chemotherapy is used. A significant amount of improvement can be expected with improved therapy. Currently, 54% of elderly diabetic patients have hemoglobin A1c levels above normal and 27%of the total had A1c levels greater than 8. Thus, nearly a quarter have "poor" control. Current best practices require a normal hemoglobin A1c, certainly less than 7. For those individuals in whom the demands of therapy are too great, medication side effects are too great, or access to monitoring is not possible, a reduction in expectations and greater complication rates will be higher. Medications currently available can promote insulin secretion, increase insulin sensitivity, or slow the digestion/processing of complex carbohydrates.
Diet
Diet alone has varying degrees of success. Elderly patients with diabetes are able to improve diabetes control with diet and weight loss. However, they may find it difficult to adhere to a strict dietary regimen and maintain weight loss. Older adults with mobility problems may find exercise to increase caloric expenditure impossible. If dramatic dietary restriction is employed to reduce weight, nutrient and vitamin deficiencies may develop. Aggressive dietary management cannot be recommended under these circumstances. Other considerations specific to older adults may limit the effectiveness of dietary therapy (Table 46.2).
A diabetic diet is relatively high in carbohydrates (50%-60% of total calories), low in fat (30% of total calories from fat, with 10% saturated fat, 10% polyunsaturated fat, and 10% monosaturated fat), and moderate in protein (~20% of total calories). If malnourished or chronically ill, the elderly patient should increase protein and energy intake. Vitamin and mineral supplements are indicated when caloric intake falls below 1000 kilocalories per day.
Exercise
The role of formalized exercise programs in the management of diabetes mellitus remains controversial. The beneficial effects of exercise on glucose tolerance have been well documented. The effectiveness of exercise in lowering plasma glucose levels is unclear. The effects of exercise on glucose tolerance are disappointingly transient, lessening within days of stopping an exercise program. Exercise for older adults with diabetes may pose additional problems. Perhaps four-fifths of older men with newly diagnosed mild diabetes are unable to participate in a regular training program because of other diseases or treatments. Exercise for control of hyperglycemia may thus not be feasible for many older adults. These benefits and the risks of exercise in older adults are outlined in Table 46.3. Because of the prevalence of silent coronary artery disease in this population, older adults with diabetes should be given an exercise tolerance test before they begin any exercise program.
Agents Increasing Insulin Secretion
Sulfonylureas
First-generation agents such as chlorpropamide (Diabinese) are largely of historical interest. Because of chlorpropamide's very long half-life (up to 60 h), risk of hypoglycemia, and production of hyponatremia from stimulation of excess antidiuretic hormone, it is rarely used today. Second-generation agents in the sulfonylurea class have largely replaced chlorpropamide. Glipizide (Glucotrol and Glucotrol XL) and Glyburide (Micronase, Glynase, and Diabeta) have been standards for many years. All, however, are associated with weight gain and hypoglycemia and are of less utility the higher the fasting glucose. These drugs rarely produce hyponatremia from central stimulation of antidiuretic hormone. Once fasting glucose levels rise above 200 mg/dL, insulin secretory reserve is very limited and these agents are less likely to be successful. As a general principle, dosing with second-generation agents should be initiated at the lowest end of the dosing range until individual susceptibility to hypoglycemia is known. Dosing is each morning, or twice a day.
Meglitinides
Repaglinide (Prandin) is an agent given before each meal, as it has a short half-life and is a shorter and more rapidly acting agent than classic sulfonylureas. It is therefore most useful when postprandial elevation of glucose dominates the clinical picture. Weight gain and hypoglycemia are shared side effects with sulfonylureas. However, in the treatment design for an individual experiencing between-meal hypoglycemia while taking sulfonylureas, Repaglinide is attractive.
d-Phenylalanine
Nateglinide (Starlix), which is a chemical derivative of the amino acid phenylalanine, has a similar profile and mode of action as Repaglinide. Because of its very short action, it is most useful in early diabetes when fasting glucoses are only mildly elevated.
Agents Increasing Insulin Action
Because of the recognition of insulin resistance as a fundamental component of noninsulin-dependent diabetes mellitus, agents increasing tissue sensitivity and responsiveness to endogenous insulin have become cornerstones of treatment. A very beneficial treatment side effect is the promotion of weight loss by these agents.
Metformin
Metformin (Glucophage, Glucophage XL) is given once (XL) or twice a day and assists altered diabetes physiology by improving insulin-mediated effects on the liver. The result is improvement in fasting hyperglycemia. On initiating treatment, bloating, cramps, and diarrhea may result. There is still a rare risk of lactic acidosis in individuals with renal, cardiac, or liver failure or in individuals undergoing contrast studies where borderline renal function is already present. Because of this, it is suggested that metformin doses be withheld temporarily in high-risk settings, such as hospitalization, dehydration, or planned radiologic studies. When creatinine clearance is low (when serum creatinine is greater than 1.5 mg/dl), or there is advanced liver, cardiac, or pulmonary disease, this agent should be avoided. Creatinines greater than 1.5 are seen in approximately 5% of all elderly individuals.
Thiazolidinediones
Rosiglitazone (Avandia) and Pioglitazone (Actos), both once or twice per day medicines taken with food that specifically assist in insulin action on muscle and fat, are useful alternatives to metformin. As with metformin, hypoglycemia is rare. However, monthly monitoring of liver function is required as approximately 10% develop hepatic enzyme elevations, and rare fatal hepatitis has occurred. Being new, these drugs are much more expensive than sulfonylureas.
Agents Slowing Carbohydrate Processing in the Gut
The alpha-glucosidase inhibitors Acarbose (Precose) and Miglitol (Glyset) both reduce postprandial increases in blood sugars by inhibiting the breakdown of dietary carbohydrate. These agents are taken with the first food intake of every meal. While they are useful adjunctive therapy for more severe diabetes, Acarbose and Miglitol are helpful in impaired glucose tolerance and mild diabetes as well. High doses of bran have also been associated with improved glucose intolerance and have the additional benefit of lowering cholesterol. The common side effect of all these agents is gas, bloating, and diarrhea.
Combination Therapy
In recent times, the use of drug combinations has increased to avoid or minimize insulin therapy and its inconvenience, hypoglycemia, weight gain, and possible acceleration of other atherogenesis. Several drug combinations have emerged, based on successful experience in combining drugs with complementary mechanisms of action.
Stepwise addition of agents is the practical approach. The most studied combination is sulfonylurea and insulin. Clearly some secretion of endogenous insulin must still be present. In this combination, insulin is given at night and sulfonylurea is given before each meal to produce insulin increments in the postprandial state. Insulin and metformin have been used in combination, with the goal of improving insulin action. Two oral hypoglycemics have been studied in combination, sulfonylurea and metformin; this is an attractive combination as the first produces insulin release, now able to stimulate tissues that have been sensitized by metformin. A three-drug regimen has been described combining NPH insulin at night, preprandial glipizide three times a day, and metformin twice a day. Although this intense regimen will minimize weight gain due to lower overall dosing with insulin, it poses a complexity challenge for elderly individuals.
Combination therapy will be increasingly popular, as combination effects on lipids, hypoglycemic events, and progression of disease is better defined in future years.
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