PATHOPHYSIOLOGY OF DIABETES IN OLDER ADULTS
EDUCATION AND SELF-MANAGEMENT SUPPORT
Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia due to abnormalities in insulin secretion, insulin action, or both. It is one of the most common chronic diseases affecting older persons. Estimates of the prevalence among persons aged 65 years and over range between 15% and 20%. Because the general population is aging and rates of obesity are increasing among middle-aged adults, people aged 65 and older will constitute the majority of diabetic persons in the United States and in other developed countries in the coming decades. In the United States, people aged 65 and older now account for more than 40% of all people with diabetes.
The age-adjusted prevalence of diabetes mellitus is higher among black Americans and Hispanic Americans than white Americans. Further, black Americans have been found to suffer from complications of diabetes at disproportionately higher rates than white Americans. Research is only starting to decipher the effects of race on diabetes development and outcomes.
Because diabetes may be asymptomatic for many years, it is estimated that up to one third of older adults with diabetes mellitus are unaware of their condition. Despite the early asymptomatic period, diabetes mellitus is a serious condition associated with significant morbidity and a shortened survival. Older persons with diabetes can expect a 10-year reduction in life expectancy and a mortality rate nearly twice that of persons without this disease. In addition, older adults disproportionately experience the clinical complications and comorbidities associated with diabetes. These complications include atherosclerosis, neuropathies, loss of vision, and renal insufficiency. The rates of myocardial infarction, stroke, and kidney failure are increased approximately twofold, and the risk of blindness is increased approximately 40% in older persons with diabetes. Most patients aged 65 and older who require dialysis have diabetes.
Recent research is accumulating about important clinical consequences of diabetes that are common in older adults and have serious consequences to health status and quality of life. When diabetes is poorly controlled in older patients, hyperglycemia alone can be the cause of insidious decline characterized by fatigue, weight loss, muscle weakness, and decline in function. Older adults with diabetes are at higher risk than those without diabetes for geriatric syndromes, including incontinence, falls, frailty, cognitive impairment, and depressive symptoms. They also have a higher prevalence of functional impairment and disability than older adults without diabetes. Mobility disability is about 2 to 3 times more likely, and disability in activities of daily living is about 1.5 times more likely, in older adults with diabetes than in those without.
The American Diabetes Association classifies diabetes mellitus affecting older adults into three types. Type 1 is the result of an absolute deficiency in insulin secretion due to autoimmune destruction of the β cells of the pancreas. Type 2 is most commonly due to tissue resistance to insulin action and relative insulin deficiency. A third category is reserved for other specific types of diabetes: injuries to the exocrine pancreas; endocrinopathies characterized by excesses of hormones, such as growth hormone, cortisol, glucagon, and epinephrine, which antagonize insulin action; drug- or chemical-induced diabetes; and infections leading to the destruction of the β cells of the pancreas.
In about 90% of cases, older adults with diabetes have the type 2 form of the disease. Most older adults with type 2 diabetes have had years of glucose intolerance, insulin resistance, and the metabolic syndrome. This “pre-diabetes” syndrome is also associated with increased risk for atherosclerotic disease, as well as development of type 2 diabetes.
The prevalence of both type 2 diabetes and glucose intolerance increases with age. The reasons for the increased prevalence of glucose intolerance and type 2 diabetes among older persons are not fully known; there appears to be an interaction among several factors, including genetics, life style, and aging influences. Obesity and decreased physical activity, common among older persons, contribute to impairments in insulin action. Glucose intolerance has also been shown to be related to aged-associated decline in pancreatic β-cell function and to reductions with aging of the insulin-signaling mechanisms that limit the mobilization of glucose transporters needed for insulin-mediated glucose uptake and metabolism in muscle and fat. Changes in body composition that occur with aging, such as increased visceral fat leading to insulin resistance, may also contribute to alterations in carbohydrate metabolism in aging. Decreased levels of physical activity that may occur in some older adults may exacerbate age-related changes in body composition and increased carbohydrate intolerance. An altered inflammatory environment with aging may also contribute to the higher rates of diabetes in older adults.
In addition to intrinsic physiologic mechanisms, external factors may contribute to glucose intolerance and type 2 diabetes. Some medications commonly used by older adults—diuretics, estrogen, sympathomimetics, glucocorticoids, niacin, and olanzapine—alter carbohydrate metabolism and increase glucose levels. Intercurrent illnesses, such as infections, myocardial infarction, and stroke, as well as other physiologic stresses can lead to worsened hyperglycemia. The heterogeneity in the severity of hyperglycemia among older patients with type 2 diabetes is related to the varying contributions of each of these factors in each individual.
The pathophysiology of the complications of diabetes is similar in younger and older persons. Prolonged hyperglycemia leads to glycosylation of proteins; the accumulation of these abnormal proteins can cause tissue damage. Also, metabolic products of the aldose-reductase system, such as sorbitol, accumulate in the presence of hyperglycemia. These products can impair cellular energy metabolism and contribute to cell injury and death.
Physiologic changes that occur with diabetes and its complications may interact with physiologic changes associated with aging to further decrease physiologic reserve. Type 2 diabetes and obesity are associated with inflammatory dysregulation, which may also be associated with aging and lead to clinical sequelae such as sarcopenia. Aging is associated with decreased physiologic reserve in multiple organ systems (renal, cardiovascular, central nervous system), which may interact with end-organ damage due to diabetes, resulting in increased vulnerability to physiologic stressors.
The current American Diabetes Association diagnostic criteria for diabetes mellitus do not include any adjustments that are based on age. Three ways to establish the diagnosis of diabetes mellitus are possible, and each must be confirmed, on a subsequent day, by any one of the three methods:
In clinical practice, the presence of two fasting glucose levels of ≥ 126 mg/dL is the most common method of diagnosis. Older adults with fasting blood glucoses from 110 to 125 mg/dL are defined as having impaired fasting glucose (IFG), a condition associated with increased risk for diabetes development. Some older adults have isolated postchallenge hyperglycemia (IPH) but do not have high fasting blood glucoses; many of these people would be diagnosed as type 2 diabetes by oral glucose tolerance testing criteria. IPH does appear to confer increased risk for atherosclerotic complications, but not as much as diagnosed type 2 diabetes.
Several recent diabetes prevention trials demonstrated that in people with glucose intolerance, progression to type 2 diabetes can be prevented by medications and life-style changes. Life-style changes were found to be slightly more efficacious in older than in younger adults and superior to medications in the older group. These results demonstrate the importance of preventive measures and life-style changes in older adults who are at risk for developing type 2 diabetes.
Older patients with diabetes require a comprehensive evaluation, which in the primary care setting may be done over several patient visits. For patients with significant functional impairments and comorbidities, including those with psychosocial problems and caregiver requirements, a formal, comprehensive geriatric assessment may be needed. Regardless of how the comprehensive evaluation of an older adult with diabetes mellitus is handled, four issues deserve special attention.
First, the history and physical examination must include evaluation of risk factors for atherosclerotic disease and the presence of all comorbid diseases. Diabetes is a well-established risk factor for atherosclerotic cardiovascular disease, so other risk factors such as smoking, family history, hypertension, and hyperlipidemia should also be explored. Diabetes is also associated with multiple vascular complications that may be subclinical or clinical. The presence of coronary artery disease, peripheral vascular disease, neuropathy, foot problems, and medical eye disease must be determined. In many cases, subspecialty consultation (as for retinopathy) and laboratory testing will be indicated. In addition, older adults with diabetes are also likely to have prevalent chronic diseases that are not necessarily associated with their diabetes, such as osteoarthritis.
Second, a thorough drug history is important. As previously stated, certain medications can contribute to hyperglycemia. More often, older patients may be on multiple medications for multiple comorbidities and may experience adverse drug effects or trouble with medication management or finances.
Third, an assessment of functional status is important in order to help determine whether the patient is able to independently manage his or her diabetes, or whether caregiver input is also needed. Functional assessment will also assist the clinician and the patient in setting diabetes management targets.
Fourth, older patients should be screened for the use of multiple medications, depression, cognitive impairment, urinary incontinence, injurious falls, and pain. Multiple observational studies have shown that these geriatric conditions are more common in older people with diabetes than without. Finally, assess each patient’s needs for diabetes education and self-management support, and whether to involve a caregiver.
The clinician develops goals for diabetes management and individualized clinical targets with each older adult with diabetes, involving the caregiver when appropriate. The goals of diabetes management in older adults include
Although these goals are similar for older and younger people with diabetes, the management of older patients is complicated by the medical and functional heterogeneity of this group. In fact, this heterogeneity is a key consideration for clinicians in developing individualized diabetes management interventions and clinical targets for older diabetes patients. Some may have developed diabetes in middle age and have developed multiple related comorbidities. Functional heterogeneity is found among older diabetics. Some may be recently diagnosed but may have had undiagnosed diabetes for years and have complications at diagnosis. Others may have just converted from impaired glucose tolerance to diabetes and may have few complications or comorbidities, may be disabled and frail, with advanced cognitive impairment, multiple comorbidities and complications, or significant limitations in functioning. Still others may be healthy and active with minimal comorbidities and excellent function. Many older diabetes patients are in between, with mild or early functional limitations, several related comorbidities, and multiple risks for worsening morbidity.
Another consideration in treating older diabetic patients is life expectancy and the time needed for clinical benefit from a specific intervention. Clinical trials have demonstrated that approximately 8 years are needed before the benefits of glycemic control are reflected in a reduction in microvascular complications such as diabetic retinopathy or kidney disease, but that only 2 to 3 years are required to see benefits from better control of blood pressure and lipids. It is important to remember that the median remaining life expectancy for a 70-year-old woman is 14 years, which is plenty of time for the development of diabetes complications. Therefore, for a person in her or his early 70s who is newly diagnosed or highly functional, diabetes management is no different from that of younger people. However, management must be designed to fit the clinical status of older adults who are significantly functionally impaired or have multiple comorbidities. In all cases, patient preferences and quality of life must be considered.
Solid evidence supports the effectiveness of several components of diabetes care, including control of lipids and blood pressure, control of hyperglycemia, aspirin use, smoking cessation, appropriate eye and foot care, prevention of nephropathy, and diabetes education and self-management support for medication adherence, blood-glucose self-management, appropriate nutrition, weight loss if indicated, and increased physical activity. However, very few of the data supporting these interventions were obtained from research studies of older people. It is likely that many management guidelines can be generalized to many older adults with diabetes, particularly those who are healthy and functional. These older adults should have the same opportunity as younger adults for intensive diabetes management, reduction of the risks associated with diabetes, and treatment of comorbid conditions that can lead to worse disease and poorer health status in the future. However, intensive diabetes management of all diabetes-associated conditions may not be feasible for some older patients, and clinicians may have to prioritize the reduction of some risks over others. For some older patients, particularly those with severe comorbidities and disabilities, aggressive management is not likely to provide benefit and may even result in harm, such as hypoglycemia with aggressive glycemic control or hypotension with aggressive blood-pressure control.
Therefore, it is important to establish individual diabetes management goals and clinical targets with patients, to re-evaluate the clinical, functional and social status of the patient if these goals and targets are not being met, and to determine if caregiver support or specialty input is needed (Table 48.1).
The California Healthcare Foundation and the American Geriatrics Society collaborated to develop guidelines for improving the care of the older person with diabetes mellitus (see the annotated references at the end of the chapter). Many of the specific management interventions outlined below are adapted from this guideline.
Older adults with diabetes are at high risk for atherosclerosis and its complications. In fact, virtually all older adults with diabetes have been shown to have either clinical or preclinical atherosclerotic disease. Therefore, interventions that reduce the risk of atherosclerotic diseases are extremely important (Table 48.2). Smoking cessation counseling and pharmacologic intervention should be offered to any older diabetic person who smokes. Daily aspirin therapy should be offered to older adults with diabetes if there is not a contraindication to aspirin. Available evidence suggests that doses from 81 to 325 mg per day are appropriate.
There is strong evidence from a number of randomized controlled trials that the management of hypertension in older adults reduces cardiovascular events and mortality; some of these studies included substantial numbers of older people with diabetes. The best target blood pressure for older diabetic patients is not clear, but in the majority of patients the target blood pressure should be 140/80. Observational studies suggest that lowering blood pressure to less than 130/80 may provide increased benefit. Because some older adults may not be able to tolerate aggressive blood-pressure lowering, hypertension should be treated gradually to avoid complications. Patient preference and medication side effects should be considered. (See also Hypertension.)
Evidence for medication choice in older patients with diabetes suggests that most classes chosen (diuretics, angiotensin-converting enzyme inhibitors, β-blockers, and calcium channel blockers) have comparable effectiveness in reducing cardiovascular disease and mortality. Evidence suggests that angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers have cardiovascular and renal benefit for persons with diabetes.
Evidence supports the use of lipid-lowering therapy and therapy to increase high-density lipoprotein (HDL) in older adults with diabetes; randomized controlled trials and meta-analysis have confirmed the benefit of the statin drugs. The use of fibrates in the setting of low HDL may also be of benefit. Therefore, lipid abnormalities should be corrected in the older adult with diabetes, as long as this is reasonable after considering the individual’s overall health status. Evidence suggests that target low-density lipoprotein (LDL) level is 100 mg/dL. Dietary modification can be tried for 6 months if the LDL level is 100 to 129 mg/dL. If the LDL level is 130 mg/dL or over, pharmacologic therapy is needed in addition to life-style modifications in diet and activity level. Older persons are always at risk for adverse drug effects, so when an older person with diabetes is prescribed a statin or niacin, or when the dose is increased, an alanine aminotransferase levels should be measured within 12 weeks of the dose initiation or change. Also, some people may develop muscle inflammation with the statins, so symptoms of muscle pain and weakness in the presence of statin therapy must be evaluated. If a fibrate has been started or increased, liver enzymes should be evaluated annually.
Microvascular complications of diabetes are major problems among older adults with diabetes and may be important contributors to disability. Diabetic retinopathy may result in decreased vision in older people with diabetes. It is important to remember that other medical eye diseases, such as glaucoma and cataracts, are also very common in older diabetic persons. Any older person with new-onset diabetes should have a screening dilated-eye examination by an eye-care specialist. If there is evidence of retinopathy, other medical eye disease, eye symptoms, or high risk (poorly controlled hyperglycemia or blood pressure), a dilated-eye examination should be done every year. If there is no eye disease or high risk, eye examinations can be performed every other year.
Serious foot problems and amputations are more common among older people with diabetes, so these patients should have a careful foot examination at least annually. The foot examination should be done more frequently if there is evidence of any problems. To screen for kidney disease, a test for the presence of microalbuminuria should be performed at diagnosis and annually if no abnormalities are detected. (See also Kidney Diseases and Disorders, the section on kidney disease and the vascular system.) Finally, given an elevated mortality among diabetic patients who develop pneumonia, pneumococcal vaccination is strongly recommended.
There are many options for drug therapy in older persons with type 2 diabetes and no clearly preferred algorithm. Regimens can consist of any of the classes of drugs shown in Table 48.3 and Table 48.4, used alone or in combination. It is important to adjust the regimen over the course of the illness as goals change, the disease progresses, or complications develop. Sulfonylurea preparations have a long record of safety and effectiveness. Hypoglycemia is a serious adverse effect, and these drugs must be used cautiously in patients with significant renal and hepatic insufficiency, since the liver is the primary site of metabolism and they are excreted by the kidneys. α-Glucosidase inhibitors impair the breakdown of carbohydrates in the gut and limit absorption. The residual carbohydrates in the intestinal lumen are responsible for diarrhea in about 25% of patients who use this drug. The biguanide preparations also have gastrointestinal side effects and can cause lactic acidosis in patients with renal insufficiency. Metformin is contraindicated for older men with a serum creatinine level of 1.5 mg/dL or higher, or older women with a serum creatinine level of 1.4 mg/dL or higher. If an older patient receives metformin, the serum creatinine should be measured at least annually and with any increase in dose. For those aged 80 or older or those suspected to have reduced muscle mass, a timed urine collection for creatinine clearance should be obtained. The thiazolidinediones are generally well tolerated, but there is a risk of idiosyncratic hepatic toxicity. Finally, insulin can be used effectively in patients with type 2 diabetes. It is often possible to achieve good glycemic control with one or two injections a day of an intermediate-acting insulin preparation. The greatest risk of insulin therapy is hypoglycemia, and some evidence suggests that frail older adults are at higher risk for serious hypoglycemia than are healthier, more functional older adults. The management plan for an older adult with diabetes who has severe or frequent hypoglycemia should be evaluated. The patient may require referral to subspecialty diabetes care, or more frequent contact with the health care team. Psychosocial reasons for hypoglycemia must be investigated and treated, such as an inability to understand self-management that is due to cognitive problems, inadequate diabetes knowledge, difficulty in implementing therapy that is due to disability, or lack of caregiver support.
It is important that the patient understands the mechanisms of the metabolic derangements and their management and becomes fully involved in diabetes self-management, that is, monitoring and treating the disease and its complications. Therefore, diabetes education about diabetes and particularly diabetes self-management is a key part of effective care. Often, this can be accomplished in the primary care setting. However, for patients who are clinically complex, referral to a diabetes educator for one-on-one counseling or group classes, a comprehensive diabetes disease management program, or specialty physician care may improve control. It is important to note that annual diabetes self-management training is a covered benefit under Medicare Part B. Diabetes mellitus education programs may be particularly important in older adults with diabetes who are members of minority groups, particularly black Americans or Hispanic Americans, in whom diabetes is more prevalent than in white Americans. It is critically important to recognize when caregiver involvement in diabetes self-management activities is required. The caregiver must be highly involved and educated about diabetes and its self-management when the patient is cognitively impaired, is significantly disabled or frail, or has limited proficiency in English.
Diabetes self-management and support must cover several important areas. It is important that the older patient, and caregiver if appropriate, be educated about hypo- and hyperglycemia, including precipitating factors, prevention, symptoms, monitoring, treatment, and when to notify the physician. Although hypoglycemia is unusual in older adults when they are treated with sulfonylurea or insulin, older adults with diabetes are still at higher risk than middle-aged diabetics. When appropriate, the patients and caregiver should be taught blood-glucose self-monitoring, and their technique should be reassessed and reinforced periodically.
Diet and physical activity remain important components of the initial and ongoing management of patients with diabetes. Specific dietary recommendations must be tailored for each individual and includes assessment of cholesterol intake and weight management. Physical activity programs should also be individualized. The patient should be assessed regularly for level of physical activity and informed about the benefits of exercise and available resources for becoming more active.
An older adult with diabetes who is prescribed a new medication and any caregiver should receive education about the purpose of the drug, how to take it, the common side effects, and important adverse reactions, with reassessment and reinforcement periodically as needed. Finally, every older adult with diabetes and any caregiver should receive education about risk factors for foot ulcers and amputation. Physical ability to provide foot care should be evaluated, with periodic reassessment and reinforcement.
■ American Diabetes Association: Clinical Practice Recommendations 2004. Diabetes Care. 2005;28(Suppl 1):S1–S79.
This supplement is published annually and provides a concise summary of the American Diabetes Association’s diabetes mellitus care standards and guidelines. Topics include an expert committee report on diagnosis and classification of the disease, and position statements regarding screening, standards of medical care, nutrition, exercise, drug therapy, and managing the complications of diabetes.
■ Brown AF, Mangione CM, Saliba D, et al.; California Health Care Foundation/American Geriatrics Society Panel on Improving Care for Elders with Diabetes. Guidelines for improving the care of the older person with diabetes mellitus. J Am Geriatr Soc. 2003;51(5 Suppl Guidelines):S265–S280.
The American Geriatrics Society joined the California Health Care Foundation to support development of a diabetes management guideline specifically targeted to older adults. An expert panel that included geriatricians, primary care physicians, diabetologists, diabetes educators, and researchers reviewed evidence for diabetes management interventions, particularly as these interventions related to older adults. Not only does it recommend evidence-based management of diabetes in older people, but it gives well-considered rationales for all recommendations and has an extensive bibliography of randomized clinical trials and high-quality observational studies that form the basis for the current recommended management of diabetes. It breaks new ground by emphasizing the need for prevention and management of atherosclerotic and microvascular risks and complications in older adults with diabetes, highlighting the clinical diversity of older people with diabetes, recommending individualized therapy targets, and advocating the consideration of geriatric syndromes in older diabetic patients.
■ DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999;131(4):281–303.
This is a comprehensive review of the many different drug regimens used in the management of patients with type 2 diabetes. There is an overview of the pathophysiology of the disease and its complications, followed by details of pharmacologic therapy. For each class of medication, there is a review of the mechanism of action, efficacy, side effects, dosing schedule, safety, and costs. Combination therapies with multiple oral agents and with insulin and oral agents are also reviewed.
■ Halter JB. Diabetes mellitus. In: Hazzard WR, Blass JP, Halter JB, et al., eds. Principles of Geriatric Medicine and Gerontology. 5th ed. New York: McGraw-Hill Professional; 2003:949–965.
Clinical management issues and the pathophysiology of the disease are reviewed in this chapter on diabetes mellitus in older adults. There is particular emphasis on the interactions of diabetes with aging and the consequences of aging to altered metabolism in older adults.
Caroline S. Blaum, MD, MS