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Introduction
Diabetes mellitus (DM) is a dominant chronic disease in the older adult population in the United States as well as in many other countries of the world. The prevalence of DM in the future is only expected to grow with the increase in the population of older adults, the prevalence of obesity, and physical inactivity. Clinicians are faced with many unique challenges when caring for this older diabetic population. The clinician’s major challenges are (1) to avoid symptoms and complications of hyper- and hypoglycemia, (2) to minimize or delay micro- and macrovascular complications, if possible, and (3) to maximize daily functioning. Underlying these challenges is the realization that the geriatric population is a heterogeneous one. Goals of care and treatment decisions may vary, depending more on the patient’s functional abilities and on other comorbidities or coexisting geriatric syndromes, and less on the chronological age of the patient. This chapter will focus on specific aspects of diabetes care in the older adult.
Epidemiology
An estimated 11.2 million people or 25.9% of those 65 years of age or older in the United States are afflicted with DM, the majority of whom have type 2 disease.[1] About 40% of adult Americans with diabetes are 65 or older with an approximately even split between men and women. DM is more prevalent in minority groups. After adjusting for population age differences, Native Americans are 2.1 times as likely, non-Hispanic blacks and Hispanics are 1.7 times as likely, and Asian Americans are 1.2 times as likely to have DM as non-Hispanic whites. The direct costs of medical care are great with almost $176 billion being spent in 2012, with about 59% on older adults with DM.[2] The majority of this expense is for inpatient costs, with higher admission rates and longer lengths of stay. Most hospitalizations for chronic complications of DM are attributed to the care of cardiovascular conditions. As the US population ages, the absolute number of older persons with diabetes will continue to rise for at least three reasons: (1) older adults are more likely to develop diabetes, (2) there will be an increased percentage of the population of older adults in minority groups, and (3) older adults with DM are living longer.[3] If methods of detection improve, the numbers of clinically recognized diabetes in older adults may rise even further, since 27.8% of all ages were undiagnosed in 2012.[1]
Diagnosis
Although the “poly” symptoms (polydipsia, polyuria, and polyphagia) are considered by many to be pathognomonic of diabetes, this is often not true in older persons for several reasons. First, these symptoms are nonspecific and may be due to other conditions, such as urinary difficulties or diuretic use. Second, they may not be present due to age-related or disease-related changes in organ function. For example, thirst mechanisms often become impaired with age. Third, they may be masked by other conditions. Thus, relying on them will result in both false positives and false negatives. The challenge to the clinician is to maintain a high level of suspicion, yet be prudent with glucose testing.
To improve the predictive power of glucose testing, criteria for the diagnosis of diabetes were revised by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus in 1997.[4] Due to consistent correlation between A1c and complications related to diabetes and improved standardization of the A1c assay, the 2009 International Expert Committee recommended that the A1c assay supplant glucose testing as the first-line diagnostic test for diabetes. The current American Diabetes Association (ADA) criteria for the diagnosis of DM are (1) A1c ≥6.5%, or (2) a fasting plasma glucose level of 126 mg/dL or greater, or (3) an elevation in plasma glucose to ≥200 mg/dL two hours following a 75-gram oral glucose tolerance test, or (4) symptoms of diabetes and a random glucose level of ≥200 mg/dL.[5] The diagnosis should be confirmed by abnormal glucose levels on a different day unless the patient has obvious hyperglycemia.
The majority of elderly diabetics are classified as either type 1 or type 2. Type 1 diabetics require insulin and are ketosis prone. Type 2 diabetics are insulin resistant and ketosis resistant. Many elderly type 1 diabetics who started insulin in the 1930s are still alive; therefore, when caring for a diabetic patient, it is important to establish when and how the diagnosis of diabetes was made in order to institute proper therapy and to anticipate the types of complications that are likely to develop.
Screening
As with other conditions, screening for diabetes would be indicated if the treatment of asymptomatic patients resulted in better outcomes, if the burden of suffering associated with it were high, and if the screening test were sensitive and specific, simple and inexpensive, safe, and acceptable for both patients and practitioners.[6] Although no one would argue that the burdens associated with diabetes are great, the US Preventive Services Task Force recommends screening for type 2 diabetes in asymptomatic adults with sustained blood pressure over 135/80 mm Hg despite only moderate evidence (B level) that screening improves outcomes.[7] The ADA, in the Standards of Medical Care in Diabetes – 2014, recommends screening for diabetes in asymptomatic adults every three years who are overweight or obese with a body mass index (BMI) ≥25 kg/m2 and who have one additional risk factor for diabetes, also B level evidence.[8] The ADA recommends screening using fasting plasma glucose (FPG), A1c, or the 2-hour 75-gram oral glucose tolerance test. Once diabetes has been detected clinically, screening for complications, specifically for retinopathy and foot lesions, can be effective in reducing morbidity, as will be discussed.
Management
To the elderly person, receiving the diagnosis of diabetes may evoke multiple emotions including dread, fear, and sadness. Not only are complications devastating, but following complex dietary, medication, and monitoring regimens can be overwhelming. Daily functional, nutritional, and medical assistance from professional and lay caregivers is often necessary when patients are physically and/or cognitively impaired. When developing a treatment plan with the older diabetic patient, it is important to customize the plan to the individual and involve the patient in his or her own self-care, to the extent that this is possible, and to be sensitive to the patient’s perception of his or her quality of life, as it is affected by various therapeutic interventions.
The concept of collaborative management has received attention as a mechanism to better care for patients with chronic diseases such as diabetes. Collaborative management consists of (1) defining problems from the perspective of the patient and physician, (2) targeting key problems, goal setting, and planning methods to achieve goals, (3) creating patient education and support services, and (4) evaluating patient progress in a frequent and regular follow-up plan.[9] These elements can be implemented in a variety of practice models from the small group practice to the large health maintenance organization. It is important for all the members of the health-care team to provide as much education to the patient as possible in order to make the patient an active participant in his or her own diabetic management. Evidence suggests that interventions targeted at improving the diabetes care delivery system and promoting diabetes self-management lead to improved patient outcomes and metabolic control.[10, 11]
In 2003, the first guidelines for improving the care of the older adult with diabetes were created by the California Health Care Foundation (CHCF) and the American Geriatrics Society (AGS).[12] These published guidelines were the first to stress the importance of setting individualized goals of care using the best evidence available for the very heterogeneous group of older adults with diabetes. In 2012, the ADA convened a Consensus Development Conference on Diabetes and Older Adults to address questions about diabetes care in those adults ≥65 years old for which evidence from clinical trials is often lacking.[13] The guidelines also included recommendations for individualizing management of diabetes in the older adult considering eight geriatric syndromes, or conditions, for which there is evidence or strong consensus opinion that persons with diabetes are at greater risk. The conditions include cognitive dysfunction, functional impairment, falls and fractures, polypharmacy, depression, vision and hearing impairment, pain, and urinary incontinence. Most recently in 2013, the American Geriatrics Society Expert Panel on the Care of Older Adults with Diabetes Mellitus updated the previous CHCF/AGS guidelines from 2003.[14] Table 30.1 summarizes the key components of diabetes management.
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The remaining sections of this chapter will elaborate on diet and weight loss, exercise, smoking, glycemic control and therapy, monitoring, managing cardiovascular risk factors (specifically hypertension and hyperlipidemia), aspirin use, eye care, foot care, and nephropathy screening. More specific information on the screening for and management of the preceding geriatric syndromes can be found in other chapters of this book.
Diet and weight loss
In general, diabetes is closely related to being overweight or obese, although a subset of older patients is either of normal weight or underweight.[15] What constitutes an optimal diabetic diet for older persons has not yet been determined, but weight loss, even if modest, in obese older persons can improve metabolic control, thereby reducing symptoms of hyperglycemia.
Achieving weight loss and metabolic control is not easy. Lifelong dietary habits are difficult to change, as are notions of what constitutes a “healthy” diet. This may be compounded by the fact that older patients frequently must rely on someone else for food acquisition and preparation. They may live in households where food preferences are disparate. Limited financial resources may interfere with patients’ procuring appropriate foods, such as fresh fruits and vegetables. Furthermore, weight loss can be considered a syndrome that correlates with increased mortality in a certain subset of older adults. It can signify progression of underlying comorbidities (i.e., dementia or malignancy) and is not always a desirable outcome.
Weight loss in obese diabetics should be attempted to improve insulin sensitivity. A registered dietitian or nutritionist should be an active member of the diabetes management team to assist the patient and/or caregiver in creating an individualized diet plan. Although a recent systematic review was unable to find strong evidence for an ideal percentage of carbohydrates, fats and proteins in an individual’s diet with diabetes,[16] calorie consumption should be consistent with weight management goals. When weight loss is not possible, the best strategy for many patients should focus on achieving a balanced diet of all three macronutrients that includes high-fiber unprocessed carbohydrates, more unsaturated fats than saturated or trans fats, and leaner meats and meat alternatives for protein.[17] The amount of protein in the diet has not been shown to be associated with proteinuria or worsening glomerular filtration rate (GFR). Adequate fluid intake of non–sucrose containing beverages is also important. This alone may help to reduce glucose levels and will correct mild volume contraction related to osmotic diuresis.
Older diabetics living in long-term care facilities must have diets appropriate to prevent or correct malnutrition. The ADA recommends serving regular, unrestricted meals to institutionalized older adults with diabetes.[13] It is important for such patients to enjoy meal time to satisfy nutritional needs as well as to contribute to their quality of life.
Exercise
Weight maintenance and glycemic control may be added benefits of regular exercise, specifically with resistance training. Physical activity has been found to increase insulin sensitivity of muscle and other tissues that have insulin receptors. Other cardiovascular risk factors (e.g., hyperlipidemia and hypertension) may be reduced by regular exercise as well. Self-esteem, risk of falls, and quality of life may also improve. However, exercise in the older diabetic may not be without substantial risk. Exercise can exacerbate angina or ischemia in a patient with underlying cardiovascular disease. The presence of peripheral neuropathy may result in soft tissue or musculoskeletal injuries. Symptomatic hypoglycemia can also occur, especially in patients taking oral hypoglycemic drugs. The ADA recommends that type 2 diabetics who want to begin an exercise program “more vigorous than brisk walking” undergo an assessment for cardiovascular disease and for other conditions, such as uncontrolled hypertension, neuropathy, and retinopathy, which may increase the risks of harm from the exercise program.[18] Older adults with diabetes should also monitor their glucose levels following any workout.
Smoking
Although rates of cigarette smoking decline with age, an important subset of smokers survives to old age. Recent evidence suggests that the hazards of cigarette smoking for men and women, particularly with respect to cardiovascular mortality, extend into later life. Furthermore, the risk of death from cardiovascular disease for former smokers is similar to that of never smokers, independent of age at which people quit.[19] Taken together, these data should compel clinicians to work with their older diabetic smokers to help them to quit.
Glycemic control
Establishing individualized goals of therapy are of great importance when treating older adults with diabetes. In certain patients, such as the frail, demented nursing home resident with sporadic eating habits, controlling symptoms of hypoglycemia or hyperglycemia is more important than preventing macrovascular and microvascular complications of diabetes. Other older, more active patients with longer life expectancies may benefit from tighter glucose control. The benefits of improved glycemic control in reducing microvascular complications of diabetes, such as retinopathy and nephropathy, are seen at approximately eight years, according to the UK Prospective Diabetes Study (UKPDS) which excluded participants ≥65 years.[20]
To date, there is limited evidence from clinical trials that establishes recommendations for glycemic targets in adults ≥75 years. However, three recent trials were specifically designed to examine the independent effects of intensive glycemic control on cardiovascular disease (CVD) and mortality in middle-aged and older adults with diabetes. The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial randomized adults with a mean age of 62.2 years to intensive glycemic control (A1c <6%) or standard therapy (A1c 7%–7.9%).[21] The study was stopped after 3.5 years of follow up due to excessive deaths from any cause in the intensive group and no reduction in outcomes related to CVD. Hypoglycemia requiring assistance, greater polypharmacy, and other adverse treatment events were more common in the intensive group.
The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial was also designed to test the effect of intensive glycemic control (A1c <6.5%) on major cardiovascular events in subjects with diabetes ≥55 years.[22] Contrary to the results of the ACCORD trial, during a median follow-up of five years, there was no statistically significant difference in mortality or in macrovascular events in the intensive group compared to standard therapy, but there was a significant relative risk reduction in new or worsened nephropathy in the intensive group (RRR 21; 95% CI 7–34.)
The Veterans Affairs Diabetes Trial (VADT) randomized a sample of older veterans with uncontrolled type 2 diabetes (A1c ≥7.5%) to intensive or standard therapy aiming to reduce A1c levels in the intensive group by 1.5%.[23] Followed for a median of 5.6 years, the results were similar to the ADVANCE trial; there was no statistically significant difference in major cardiovascular events or death but there was found to be a reduction in the progression of albuminuria in the intensive group.
Whereas no independent effect of intensive glycemic control on cardiovascular events has been shown in the preceding randomized controlled trials, several cohort studies have examined the association between A1c values and mortality and cardiac events in adults with type 2 diabetes ≥50 years.[24, 25] It appears that there is a ∪-shaped curve with lower mortality between 6.0% and 9.0% compared to ≤6.0% and ≥11%. Given new evidence to support some loosening of glycemic targets, the 2013 update of the AGS Expert Panel on the Care of Older Adults with Diabetes Mellitus recommends A1c values between 7.5% and 8.0%. For older adults with “few comorbidities and good functional status,” A1c values of 7.0%–7.5% may be appropriate, while for those with “multiple comorbidities, poor health, and limited life expectancy,” A1c values of 8.0%–9.0% are acceptable.[17]
Dietary modifications, exercise, and weight loss, if appropriate, are recommended for elderly diabetics. As lifestyle modification is often difficult especially for the clinically complex older adult, engaging the help of a Certified Diabetes Educator, specialty physician care, or group adult education classes can improve the patient’s chances for success. Individualized education may be especially helpful for non-English speaking and culturally diverse older adults.[26] Drug therapy is warranted if the combination of diet, exercise, and weight loss are not successful in reaching glycemic control and if benefits outweigh potential risks of treatment.
Therapy
Multiple oral hypoglycemic agents are currently available including (1) the biguanide, metformin; (2) the sulfonylureas, such as glipizide, glyburide, and glimepiride; (3) the meglitinides, nateglinide and repaglinide; (4) the thiazolidinediones, pioglitazone and rosiglitazone; 5) the dipeptidyl peptidase-4 (DPP-4) inhibitors, sitagliptin, saxagliptin, linagliptin, and alogliptin; (6) the sodium-glucose cotransporter-2 (SGLT2) inhibitors, canagliflozin and dapagliflozin; and (7) the alpha-glucosidase inhibitors, acarbose and miglitol. Oral agents are easy to use and are frequently preferred by patients but vary significantly in cost and side-effect profiles (Table 30.2).
For reasons of low tolerability and limited effects on A1c values, SGLT2 inhibitors and alpha-glucosidase inhibitors are not often used in older adults and will not be discussed in detail here. The SGLT2 inhibitors work in the kidney to block reabsorption of glucose increasing glucosuria, which can lead to urinary tract and yeast infections, although alpha-glucosidase inhibitors block the breakdown of starch in the intestine leading to the significant side effects of intestinal gas and bloating. Pramlintide, an amylin mimetic, and exenatide, a glucagon-like peptide 1 (GLP-1) agonist and incretin mimetic, both decrease postprandial plasma glucose and suppress glucagon secretion and are administered subcutaneously before meals, but will also not be discussed here given their limited use. Multiple types of insulin are available, giving clinicians even more tools to individualize therapy for older adults.
Biguanides
The only biguanide currently available in the United States is metformin, which is considered initial therapy in type 2 diabetes. It is approved for oral treatment either alone or in combination with a sulfonylurea or insulin. Metformin is a unique treatment for diabetes in that it suppresses hepatic glucose production and improves insulin sensitivity to promote glucose uptake at the cellular level. Therefore, the drug alone does not cause hypoglycemia. It also has a positive effect on lipids by lowering triglycerides and LDL cholesterol, does not contribute to weight gain in the obese patient, and may even assist with weight loss. Data from the UKPDS showed a decrease in macrovascular complications of diabetes and in overall mortality in obese patients with newly diagnosed diabetes taking metformin independent of glucose control compared with patients on only dietary changes and with patients on a sulfonylurea after 10 years of follow-up.[27]
Given the cardiovascular benefits and side-effect profile that does not include hypoglycemia, metformin is an excellent first choice for the management of diabetes in the older adult. While age should not be a contraindication to the use of metformin, renal function should be monitored closely during treatment. It should be used with caution in patients with impaired glomerular filtration rates, probably less than 30 mL/min–60 ml/min, although there is no evidence to support a specific cut-off. It should probably be avoided in patients with conditions associated with renal insufficiency (e.g., hepatic or cardiac failure) and in patients with renal failure who are more susceptible to lactic acidosis. Drug clearance decreases with increase in age independent of renal function,[28] so low to moderate doses, 500 mg/day –2,000 mg/day, should be used in older adults. Side effects include nausea, vomiting, anorexia, diarrhea, most of which resolve within a few weeks and can be avoided with slowly titrating up the dose.
Contraindications to the use of metformin are drug hypersensitivity, administration of iodinated contrast dye in radiological studies, metabolic acidosis, and renal impairment (in men, a serum creatinine concentration >1.5 mg/dL and in women, a serum creatinine concentration >1.4 mg/dL). The drug should be stopped two days prior to radiological procedures involving contrast dyes. The most serious potential side effect of metformin is lactic acidosis but this is a much less common problem than with the biguanide phenformin, which is no longer available. Since the biguanides inhibit lactate metabolism, increased concentrations of the drug due to renal insufficiency can cause lactic acidosis. However, a Cochrane Collaboration meta-analysis of both prospective comparative and observational cohorts found that lactic acidosis occurs as often in patients with diabetes who are metformin-users as in non-metformin users.[29] The trials included 24% of patients over age 65 years, whereas 46% of the trials allowed inclusion of patients with renal insufficiency, defined as a creatinine >1.5 mg/dL. No trial listed any cases of lactic acidosis, but it was not clear how many patients with standard contraindications were included in the trials. A separate trial of 393 diabetic patients on metformin followed for four years with at least one contraindication to its use reported no cases of lactic acidosis either. All participants in this trial had creatinine levels of 1.5 mg/dL –2.5 mg/dL.[30]
Sulfonylureas
The sulfonylurea drugs are the most frequently prescribed and least expensive agents for treating hyperglycemia. They are generally efficacious especially in patients who are not obese and within the first two to five years after diagnosis. Given that their mechanism of action is to stimulate the beta cells to produce more insulin, their loss of efficacy with time is probably due to a progressive diminution in pancreatic beta cell function and increased insulin resistance. The sulfonylureas may contribute to modest weight gain probably due to the effect of increased circulating insulin.
All sulfonylureas are now available in generic form and are reasonably priced. The choice of sulfonylurea should take into account the following considerations. First, since all are metabolized at least in part by the liver, they should be used with care in patients with severe liver disease. Second, renal insufficiency and normal decline in kidney function will prolong the half-lives of the sulfonylureas. Third, because of its long half-life (36 hours), a risk factor for hypoglycemia, and its propensity to cause hyponatremia, chlorpropamide should be avoided in older persons. Fourth, longer acting sulfonylureas, such as glyburide, have the highest risk of hypoglycemia in older adults, and should be avoided.[31] Glipizide is preferable because it does not have any active metabolites and has a half-life of two to five hours. It must be taken 30 minutes before meals so as not to delay absorption.
Meglitinides
Nateglinide and repaglinide act similarly to the sulfonylureas in stimulating the pancreatic insulin release, but are very short acting, with half-lives of 1–1.5 hours. For this reason, they are less likely than sulfonylureas to cause hypoglycemia. These agents can be used when patients have erratic eating habits, such as those with dementia. The medication can be administered with a meal or held if the meal is not eaten. However, dosing schedules of two or three times daily add to the pill burden in older adults.
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