Treatment of Older Adults with Diabetes
Caroline S. Blaum
Jeffrey B. Halter
Despite the continual expansion of knowledge about diabetes, including the importance of control of risk factors and glycemia in decreasing the complications of diabetes, much of this knowledge does not specifically address issues in older adults, even though about 50% of people with diabetes in the United States are 60 years and older (1). For example, in the United Kingdom Prospective Diabetes Study (UKPDS), the mean age of participants was 53, although a few older people were enrolled and their number increased during the study. People with significant complications or comorbidities at diagnosis were excluded (2). Therefore, the implications of the results of the UKPDS for the millions of older people with prevalent as well as incident diabetes, many of whom have multiple comorbid conditions, are not yet clear (3).
Clearly, diabetes in older adults is a major health problem (Table 43.1), and older patients with diabetes face major health problems. Those who develop diabetes during middle age will face its debilitating complications as they age or will die prematurely. Those who develop diabetes later in life face an increase in co-occurring risks and complications and comorbidities as they become very old. These older patients and their physicians have no clear clinical guidelines for diabetes management; recommendations must be extrapolated from studies of other age groups. Clinicians confronted with great heterogeneity in the older population and with rapidly changing knowledge about diabetes and its management must understand the similarities and differences in the pathophysiology and management of diabetes in older versus middle-aged adults.
TABLE 43.1. Diabetes: A Key Problem in Older Adults | ||||
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EPIDEMIOLOGY AND DIAGNOSIS OF DIABETES IN OLDER ADULTS
Diabetes is a highly prevalent, and expanding, chronic health problem for older people. The Third National Health and Nutrition Examination Survey (NHANES III), conducted by the National Center for Health Statistics from 1988 through 1994, provided the most recent estimates of the prevalence of diagnosed and undiagnosed diabetes mellitus in the United States among individuals 20 years and older. Among those 60 to 74 and those 75 years and older, respectively, 12.6% and 13.2% had previously diagnosed diabetes and 6.2% and 5.7% had newly diagnosed diabetes according to the criterion for fasting glucose levels established by the American Diabetes Association (ADA). An additional 5% to 6% of people age 60 to 74 met diabetes criteria based only on an oral glucose tolerance test (OGTT) value of more than 200 mg/dL at 2 hours. An overall prevalence of diabetes of approximately 25% among people age 60 to 74 years was confirmed in the Cardiovascular Health Study of older people in the United States and extended to the population over age 75 years. In addition to the high prevalence of diabetes, 20% had impaired glucose tolerance (IGT) by the 1997 ADA diagnostic criteria (4). The incidence of new diagnosis of diabetes mellitus also increased with age until about age 75 and then stabilized. The incidence rate was approximately two per 1,000 among those individuals aged 25 to 44 and increased to approximately five per 1,000 among individuals older than 45 (5).
Most individuals with diabetes who are older than 65 years have type 2 diabetes. However, type 1 diabetes occurs in this age group as well, including some with newly diagnosed diabetes (6). In addition, a small percentage of older individuals who initially have type 2 diabetes become insulin-dependent over time. While the HLA-DR3 allele is more common in older adults who require insulin treatment than in those who do not require insulin, the frequency of antibodies to islet cells in this group is not increased (6).
As in patients with type 2 diabetes in general, atherosclerotic complications are the most significant cause of morbidity and mortality in older patients with diabetes. Observational studies of older adults have suggested that poor glycemic control in
older people with diabetes contributes to excess risk of stroke and cardiovascular events (7,8). Atherosclerotic macrovascular disease accounts for 75% of the mortality among people with diabetes in the United States (9). In the UKPDS, 20% of patients with newly diagnosed diabetes developed macrovascular complications after 9 years, whereas only 9% developed microvascular complications (2).
older people with diabetes contributes to excess risk of stroke and cardiovascular events (7,8). Atherosclerotic macrovascular disease accounts for 75% of the mortality among people with diabetes in the United States (9). In the UKPDS, 20% of patients with newly diagnosed diabetes developed macrovascular complications after 9 years, whereas only 9% developed microvascular complications (2).
Microvascular complications are also a significant problem in older adults. In the United States, diabetes is the major cause of renal failure and dialysis in people older than 65 years (10). Diabetic retinopathy is a major cause of visual loss in older adults, and even if it does not lead to blindness, it is associated with disability and depression (11,12). Peripheral neuropathy and peripheral vascular disease are particularly prevalent in older age groups (13). The prevalence of amputations increases with age, as do balance problems, mobility impairment, and chronic pain related to diabetic nerve disorders (14).
The prevalence of disability and functional impairment is greater in older people with diabetes than in older people without diabetes. Older adults with diabetes are about two to three times more likely to have physical limitations (15) and 1.5 times more likely to have ADL (activities of daily living) disability (16) than are those without diabetes. Much of this excess disability is a direct result of complications of diabetes, such as eye disease, stroke, cardiovascular disease, neuropathy, and peripheral vascular disease (15).
Because the hyperglycemia cutoff points for risk of diabetes complications appear to apply similarly to older and younger populations, the ADA diagnostic criteria for diabetes in adults are not modified by the patient’s age. Recently, several studies comparing the groups identified by the previous criteria of the World Health Organization (17) versus the ADA fasting glucose criteria (18,19,20,21) have been published. Most have found a decreased prevalence of diabetes with the ADA criteria (19,22), although effects have varied in different populations (21). Although this difference in prevalence is small in middle-aged people, it increases with age because older people are more likely to have an elevated 2-hour postchallenge glucose level than an elevated fasting blood glucose level. In addition, the two criteria identify different groups who may have different risks for complications and different outcomes. Studies have suggested that fasting glucose levels may not predict progression to cardiovascular disease or mortality as well as an abnormal postchallenge glucose level (20). Similarly, the ADA category of impaired fasting glucose (IFG) may not predict progression to type 2 diabetes as well as IGT as defined by an OGTT (23). Again this discrepancy may be more pronounced in older adults.
Regardless of the effect of the current diagnostic criteria on determinations of diabetes prevalence in older adults, it is far more common in routine clinical practice to obtain a fasting glucose level than an OGTT. The clinician can use the results of the fasting glucose determination along with a 2-hour glucose level if IFG or other diabetes risk factors are present. It is important to have a high index of suspicion because of the high prevalence of known type 2 diabetes, previously undiagnosed diabetes, and IGT in older people, all of which are associated with excess risk for atherosclerotic disease and mortality. Therefore, any elevated fasting blood glucose should be evaluated, and if present on more than one occasion, should mandate the start of patient education regarding glucose intolerance and diabetes, management of associated risks for atherosclerotic disease, and if frank diabetes is present, management of hyperglycemia.
CHANGES IN CARBOHYDRATE METABOLISM WITH AGING
The prevalence of diabetes and glucose intolerance increases with advancing age. These abnormalities in carbohydrate metabolism have features in common, and the glucose intolerance associated with aging increases the risk for development of overt diabetes (24). There is no evidence to suggest that the pathophysiology of type 2 diabetes is any different in older adults than in younger adults. However, physiologic changes that appear to accompany the aging process produce alterations of glucose metabolism even in very healthy older individuals (25). These changes are manifested primarily as an elevation in postprandial blood glucose levels, which may increase by as much as 15 mg/dL (0.8 mmol/L) per decade after the age of 30. The tendency for older adults to have increased postchallenge glucose levels relative to fasting glucose levels has implications for prevalence of diabetes in older adults as defined by the 1997 ADA diagnostic criteria (discussed in previous section).
The pathophysiology of the changes in glucose tolerance associated with aging has been reviewed (25). Glucose absorption following glucose ingestion may be slowed with increasing age, and suppression of hepatic glucose production is delayed (most likely as a result of delayed insulin secretion). A number of age-related changes in regulation of insulin secretion and insulin action have been described.
In addition to intrinsic changes of aging, extrinsic factors may contribute to glucose intolerance. Both the decline in lean body mass and the increase in body fat that accompany aging may contribute to insulin resistance. Levels of physical activity decline with age, and such changes may precipitate or accelerate changes in body composition. Studies of both master athletes and older nonathletes suggest that some of these changes can be either prevented or modified with exercise. Drugs commonly used by older individuals, including diuretics, estrogen, sympathomimetics, glucocorticoids, niacin, phenytoin, and tricyclic antidepressants, can adversely affect glucose metabolism, exacerbating glucose intolerance. Stress states such as myocardial infarction, infection, burns, and surgery can worsen glucose intolerance and precipitate fasting hyperglycemia.
DIABETES AND THE PHYSIOLOGY OF AGING
Many effects of diabetes appear to accelerate age-related physiologic changes. For example, the presence of diabetes confers on diabetic women a risk of cardiovascular disease equal to that for men at the same age (26). Some of the mechanisms presumed to underlie this accelerated vascular aging include effects of diabetes on platelets, increased glycosylation of vascular tissues, and lipoprotein alterations associated with diabetes (27,28,29).
Changes that occur with diabetes and changes that occur with aging may interact, especially with respect to the general age-related decrease in physiologic reserve in many organ systems. Although most physiologic systems (cardiovascular, renal, pulmonary, central nervous system) in older people function
appropriately under normal stable conditions, they may be unable to cope with the increased demands posed by acute illness or injury. Complications of diabetes leading to end-organ damage may further accelerate this loss of physiologic reserve. In addition, the clinical manifestations of diabetes may stress physiologic systems even in the absence of frank pathology. For example, even a mild increase in urine volume in an older diabetic patient with poorly controlled hyperglycemia may exacerbate bladder dysfunction and lead to urinary incontinence. Glycosuria, even without polyuria, can lead to electrolyte imbalance and cardiac arrhythmias.
appropriately under normal stable conditions, they may be unable to cope with the increased demands posed by acute illness or injury. Complications of diabetes leading to end-organ damage may further accelerate this loss of physiologic reserve. In addition, the clinical manifestations of diabetes may stress physiologic systems even in the absence of frank pathology. For example, even a mild increase in urine volume in an older diabetic patient with poorly controlled hyperglycemia may exacerbate bladder dysfunction and lead to urinary incontinence. Glycosuria, even without polyuria, can lead to electrolyte imbalance and cardiac arrhythmias.
TREATMENT OF THE OLDER ADULT WITH DIABETES
Determining Treatment Goals
The goals of diabetes management for older patients are not different from those for other patients, and as with patients with diabetes of any age, include far more than treatment of hyperglycemia. These goals are summarized in Table 43.2.
TABLE 43.2. Treatment Goals for Older Patients with Diabetes | |||||||
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It is important to consider the similarities and differences between older and younger people with diabetes and their impact on diabetes management. Like younger people with diabetes, most older people with diabetes are highly functional and active and deserve the same attention to diabetes management as do younger patients. For both age groups, macrovascular complications are the major causes of morbidity and mortality related to diabetes. For both age groups, co-occurrence of other atherosclerotic risk factors are frequent, and the management of such associated risk factors has been shown to have a favorable impact on morbidity and mortality (30). Finally, the management of diabetes for most people with diabetes, regardless of age, has been shown to be inadequate, with poor physician and patient adherence to published guidelines and recommendations (31,32,33,34,35).
Some key differences between older and younger patients with diabetes can affect management. The older population is very heterogeneous both with respect to their diabetes and their general health status. An older patient with “newly diagnosed” diabetes may truly be a new diabetic patient, with no evidence of diabetes complications and comorbidities; may have had IGT or undiagnosed diabetes for years with complications present at diagnosis; or may have none or many related or unrelated comorbid diseases and disabilities. Some older patients may be more symptomatic from hyperglycemia than are younger patients but are also more prone to complications of treatment. Finally, special evaluation and treatment goals must be devised for frail elderly patients (i.e., those who have multiple comorbidities and disabilities and a significantly impaired physiologic reserve).
Because of this complexity and heterogeneity, selecting appropriate management goals for older patients with diabetes should be based on a detailed evaluation. A complete history and physical examination should be done at the time of diagnosis, when control of hyperglycemia and risk factors is inadequate, or when a reassessment of the patient’s status is needed. Diabetes complications and the presence of risk factors for diabetic complications, as well as co-occurring diseases and disorders and general functioning, must be assessed.
A key component of the medical history for all patients with diabetes, but especially older patients, is a thorough evaluation of their medications, including prescription and over-the-counter drugs, “alternative medications,” and dietary supplements. Older patients commonly take several medications, and drug–drug interactions, drug–disease interactions, and increased expense can be problematic in patients taking multiple drugs.
Laboratory evaluations and subspecialty referrals recommended for older patients with diabetes are not substantially different from those for middle-aged patients with type 2 diabetes, except in unusual circumstances such as severe debilitation or advanced dementia. Laboratory evaluation should include determinations of fasting serum glucose level, glycosylated hemoglobin (HbA1c) (to assess previous level of control and to be used as a baseline), fasting lipid profile, and serum creatinine; urinalysis with examination for proteinuria or microalbuminuria; and an electrocardiogram. The ADA recommends ophthalmologic evaluation at the time of diagnosis and yearly for all patients with type 2 diabetes (12), a recommendation that applies to elderly patients as well, who are at high risk for ocular diseases other than retinopathy.
Recently, the American Geriatrics Society and the California Healthcare Foundation convened a multidisciplinary expert panel to develop evidence-based guidelines to improve diabetes management in older adults (36). A major recommendation was that management be individualized according to health status and preferences of the older diabetes patient. They also recommended that an evaluation of an older diabetes patient include screening and management of geriatric syndromes: polypharmacy, cognitive impairment, depression, falls, urinary incontinence, and pain. Geriatric syndromes are more common in older adults with diabetes than in those without diabetes. (See referenced guidelines for details.)
For many older patients with diabetes, especially those with several comorbid conditions and “geriatric syndromes” and/or problems managing their diabetes, a comprehensive geriatric evaluation, sometimes also referred to as a geriatric or functional assessment, is indicated (36a,37). This is a multifaceted assessment of the patient’s capabilities for self-care, including ADL (bathing, grooming, dressing, feeding, toileting, and transferring) and instrumental ADL (e.g., shopping, telephoning, finances, and housework), and indicates the amount of assistance, if any, that the patient needs. It also includes assessment of nutritional status, evaluation for possible depression or cognitive impairment, and evaluation of the patient’s social support systems, financial and insurance status, and advance medical directives. Nursing and social-work assistance is invaluable for both geriatric assessment and diabetes teaching and self-management support. These health professionals can help patients and their families access support services available in the community. For some patients, referral to a geriatrician may be necessary.
Symptomatic Hyperglycemia in Older Patients
Aging-related changes and increased comorbid conditions make older patients with diabetes particularly vulnerable to
symptoms of hyperglycemia, even if those symptoms are not the “classic” symptoms. Symptoms such as falls, fatigue, dizziness, and increased incontinence may often be traced back to hyperglycemia-associated polyuria. Glycosuria may also be associated with weight loss caused by the loss of calories in the urine. Older people may be at increased risk for depletion of trace nutrients and minerals caused by osmotic diuresis. Magnesium and potassium deficiencies can have deleterious effects on cardiac conduction. Glycosuria can also increase phosphate excretion, which can accelerate calcium loss from bone (38). An impaired central thirst response in older people may contribute to the volume depletion due to osmotic diuresis from hyperglycemia. Clearly, elimination of glycosuria is an important therapeutic goal (blood glucose level approximately 200 mg/dL or 11 mmol/L) in older people with diabetes.
symptoms of hyperglycemia, even if those symptoms are not the “classic” symptoms. Symptoms such as falls, fatigue, dizziness, and increased incontinence may often be traced back to hyperglycemia-associated polyuria. Glycosuria may also be associated with weight loss caused by the loss of calories in the urine. Older people may be at increased risk for depletion of trace nutrients and minerals caused by osmotic diuresis. Magnesium and potassium deficiencies can have deleterious effects on cardiac conduction. Glycosuria can also increase phosphate excretion, which can accelerate calcium loss from bone (38). An impaired central thirst response in older people may contribute to the volume depletion due to osmotic diuresis from hyperglycemia. Clearly, elimination of glycosuria is an important therapeutic goal (blood glucose level approximately 200 mg/dL or 11 mmol/L) in older people with diabetes.
Weight loss caused by uncontrolled hyperglycemia can be a significant problem. Patients with weight loss may be in a constant catabolic state, which can lead to loss of muscle mass, weakness, and potentially to falls and injury. Older patients may not perceive increased hunger, in some cases exacerbating poor nutritional status. The associated catabolic state may predispose to infections and other complications of malnutrition.
An increased concentration of glucose or its metabolites in the lens and aqueous humor of the eye can lead to visual problems. Hyperglycemia may predispose patients to bacterial and fungal infection and increased pain perception (39) and may alter platelet adhesiveness, worsening intermittent claudication. Lipid abnormalities also worsen with poor glycemic control, and high triglyceride levels can predispose to pancreatitis. A careful search for such symptoms of hyperglycemia is clearly indicated in elderly diabetic patients.
In many older patients, symptoms associated with diabetes and hyperglycemia may be atypical. For example, hyperglycemia does not usually lead to dramatic polyuria and polydipsia; more often there will be increased incontinence, a urinary tract infection, or increased lethargy or mental confusion. Similarly, undiagnosed or unmanaged diabetes may manifest as increased bacterial or fungal infections of the skin, unexplained weight loss, increased fatigue, or slow wound healing. Increased paresthesias and weakness, orthostatic hypotension with falls, or decreased vision also should raise suspicion for undiagnosed or inadequately managed diabetes.
The most severe complication of diabetes in older individuals is hyperglycemic hyperosmolar nonketotic coma. This condition is seen almost exclusively in older patients with diabetes. It is often precipitated by a catastrophic event, such as myocardial infarction or stroke, and can sometimes occur in people not previously known to have diabetes. Details of inpatient management are discussed elsewhere in this volume (Chapter 65).
Management of Atherosclerotic Risks and Complications
Findings from the UKPDS and other studies have made it clear that treatment of associated risks for atherosclerotic disease is a major goal of diabetes management (40). A higher proportion of older than younger patients with diabetes have associated hypertension, hyperlipidemia, and atherosclerotic arterial disease (41,42,43,44,45). Although fewer older than younger people smoke cigarettes, smoking-cessation programs should be encouraged for those who do smoke (46). Older patients with diabetes have been shown to benefit as much as or more than patients without diabetes from treatment of hypertension (47). Meta-analysis has shown aspirin use to be beneficial in older patients with diabetes who are at risk for atherosclerosis or have atherosclerosis (48). Treatment of hyperlipidemia in diabetic patients with cardiovascular disease has been shown to be beneficial and may decrease mortality among those who may develop cardiovascular disease; no age limit has been defined (3), although the data available on people older than 75 years are limited. Peripheral vascular occlusive disease and amputations increase with age; therefore, monitoring and evaluation for circulatory problems are indicated. Preventative treatment and monitoring for complications are not appropriate for the few older patients who are in a preterminal state or have advanced dementia. Most older people, even those with comorbidities and disability, will benefit from interventions shown to prevent or slow an increasing burden of illness over a period of several years.
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