Current Geriatric Diagnosis & Treatment, 1st Edition

Section III - Common Disorders in the Elderly

33. Diabetes in the Elderly

Rossana D. Danese MD

David C. Aron MD, MS

ESSENTIALS OF DIAGNOSIS

  • Fasting (no caloric intake for ≥ 8 h) plasma glucose ≥ 126 mg/dL (7.0 mmol/L) or symptoms of diabetes plus casual plasma glucose concentration ≥ 200 mg/dL (11.1 mmol/L)
  • plasma glucose ≥ 200 mg/dL (11.1 mmol/L) during a 75-g oral glucose tolerance test confirmed on a subsequent day.

General Considerations

Aging is associated with declining beta cell function and relative insulinopenia independent of insulin resistance as well as insulin resistance itself. Furthermore, the risk of developing diabetes mellitus (DM) type 2 increases with obesity, lack of physical activity, and loss of muscle mass, all of which can occur with aging. The prevalence of DM (diagnosed and undiagnosed) in the elderly U.S. population has been estimated at 7 million, or 20% of all people 65 years of age and older. Native Americans, Hispanics, and blacks are at particularly high risk. The prevalence seems to decline slightly in those older than 75 compared with those 65–74 years old and decreases further in those older than 85. The dysmetabolic syndrome (syndrome X) consisting of the association among insulin resistance (DM type 2), hyperlipidemia, hypertension, and obesity increases in those 65–74 years old.

Boyle JP et al: Projection of diabetes burden through 2050: impact of changing demography and disease prevalence in the U.S. Diabetes Care 2001;24:1936. [PMID: 11679460]

Franse LV et al: Type 2 diabetes in older well-functioning people: who is undiagnosed? Data from the Health, Aging, and Body Composition study. Diabetes Care 2001;24:2065. [PMID: 11723084]

Rockwood K et al: Incidence and outcomes of diabetes mellitus in elderly people: report from the Canadian Study of Health and Aging. Can Med Assoc J 2000;162:769. [PMID: 10750461]

Shorr RI et al: Glycemic control of older adults with type 2 diabetes: findings from the Third National Health and Nutrition Examination Survey 1988–1994. J Am Geriatr Soc 2000;48:264. [PMID: 10733051]

National Center for Chronic Disease Prevention and Health Promotion: National diabetes fact sheet: http://www.cdc.gov/diabetes/pubs/estimates.htm

Pathogenesis

DM type 1 is an autoimmune disease that expresses a bimodal distribution (ie, an increased incidence in the very young and the old). Pancreatic beta cells are destroyed, resulting in absolute insulinopenia and subsequent hyperglycemia. Ketoacidosis may occur. Other autoimmune diseases such as vitamin B12deficiency, vitiligo, thyroid disease, or rheumatoid arthritis may be present. Exogenous insulin is required for survival and glucose control.

DM type 2 is less well understood, but it results from relative insulinopenia secondary to insulin resistance (in peripheral tissues). Early in insulin resistance, insulin production is increased to levels greater than normal to maintain euglycemia, a condition known as dysmetabolic syndrome. Associated features include acanthosis nigricans, central obesity, hypertension, dyslipidemia, and an increase in coronary heart disease risk. Over time, relative insulinopenia with hyperglycemia results. Exercise, carbohydrate control, and oral glucose-lowering agents with or without insulin are required for glucose control.

Secondary causes of DM type 2 include pancreatic disease (including pancreatic carcinoma), endocrinopathies (most commonly thyrotoxicosis), infection, and drugs (glucocorticoids, niacin, phenytoin, thiazides, protease inhibitors, and the newer atypical antipsychotic drugs and newer immunosuppressive agents).

Blackburn D et al: Quantification of the risk of corticosteroid-induced diabetes mellitus among the elderly. J Gen Intern Med 2002;17:717. [PMID: 12220369]

Prevention

An increasing incidence of diabetes and the introduction of safe medications with less adverse hypoglycemia have spurred studies in the prevention of DM type 2. In the Diabetes Prevention Program, a nationwide study sponsored by the National Institutes of Health,

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lifestyle modification (7% weight loss and minimum 150 min physical activity per week) achieved a reduction in incidence of diabetes of 58% compared with placebo, whereas metformin, 850 mg twice daily, reduced this incidence of diabetes by 31%. Among patients ≥ 60 years, the advantage of lifestyle modification over metformin was even greater. This landmark study will likely affect future recommendations for screening and prevention of DM type 2.

Clinical Findings

  1. SYMPTOMS & SIGNS

The classic symptoms of diabetes mellitus—polyuria (worsening incontinence), polydipsia, and polyphagia—exist mainly with plasma glucose > 200 mg/dL. Weight loss, blurred vision, and dehydration may also be present. Patients with lesser degrees of hyperglycemia may be asymptomatic or may present with weight loss or signs and symptoms of chronic infection, especially of the genitourinary tract, skin, or mouth. Diabetes is associated with reduced cognitive function in elderly patients, and the decline correlates with glucose control. Findings of other autoimmune disease may be present in patients with DM type 1; findings of the dysmetabolic syndrome may be present in those with DM type 2. On occasion, patients may present not with symptoms of hyperglycemia but with macrovascular complications (atherosclerotic disease) or signs and symptoms of microvascular complications, especially retinopathy or neuropathy. Restless leg syndrome, perhaps mimicking (or caused by) diabetic neuropathy, has an increased prevalence in diabetics.

In DM type 2 patients treated with insulin, sulfonylureas, or meglitinides, it is important to assess for symptoms of hypoglycemia as well as hyperglycemia and micro- and macrovascular complications. Both adrenergic (sweating, palpitations, tremors) and neuroglycopenic (confusion, nightmares, violence) symptoms should be sought because they are less often spontaneously reported by elderly diabetics. Severe hypoglycemia may present as transient hemiparesis or coma. Severe hypoglycemia may also precipitate angina. When appropriate (eg, when there is a significant risk for hypoglycemia), patients should be encouraged to check their fingerstick glucose before driving.

Sinclair AJ et al: Cognitive dysfunction in older subjects with diabetes mellitus: impact on diabetes self-management and use of care services. Diab Res Clin Prac 2000;50:203. [PMID: 11106835

  1. LABORATORY FINDINGS

The diagnosis of DM can be established in a symptomatic patient by a random glucose > 200 mg/dL or a fasting glucose ≥ 126 mg/dL. If required, a 75-g glucose tolerance test may be performed. In addition to hyperglycemia, hyponatremia (pseudohyponatremia), findings of dehydration, and hypomagnesemia and hypokalemia (resulting from osmotic diuresis) may also be present. The hemoglobin (Hgb) A1C should be obtained as a baseline value even though it is not used as a diagnostic test. Total cholesterol, particularly in poorly controlled DM type 2, is commonly elevated. The lipid profile commonly displays elevated triglycerides and low levels of high-density lipoproteins (HDLs). The low-density lipoprotein (LDL) cholesterol is not always elevated but consists of a higher proportion of small dense LDL, which is more atherogenic.

  1. SCREENING TESTS

The American Diabetes Association (ADA) recommends screening with fasting plasma glucose every 3 years beginning at age 45. Hemoglobin A1C is not recommended for screening because of lack of standardization among laboratories, but alternative approaches have been suggested. Those with risk factors for diabetes, including obesity, inactivity, hypertension, and dyslipidemia, all of which are increasingly common in the elderly, should be screened more frequently. Screening for DM is indicated in the elderly to relieve symptoms, improve quality of life, and prevent or delay subsequent complications.

Knowler WC et al: Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393. [PMID: 11832527]

  1. DIAGNOSTIC CRITERIA

The ADA criteria were developed to emphasize fasting glucose values in the diagnosis of DM and to ease establishing a diagnosis. Diagnostic criteria established by the World Health Organization in 1985 set a fasting plasma glucose ≥ 140 mg/dL but emphasized a 2-h plasma glucose ≥ 200 mg/dL. Because glucose intolerance is a characteristic of aging, the ADA criteria (with emphasis on fasting glucose) have been questioned for underestimating the incidence of DM in the elderly. Currently, a state of prediabetes or impaired glucose homeostasis is recognized and furthermore associated with cardiovascular disease. The ADA defines impaired fasting glucose as a fasting plasma glucose ≥ 110 mg/dL but < 126 mg/dL; impaired glucose tolerance is defined as 2-h glucose ≥ 140 mg/dL and ≤ 200 mg/dL.

American Diabetes Association: Clinical practice recommendations 2002. Diabetes Care 2002;25(suppl 1).

Barr RG et al: Tests of glycemia for the diagnosis of type 2 diabetes mellitus. Ann Intern Med 2002;137:263. [PMID: 12186517]

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Expert Committee on the Diagnosis and Classification of Diabetes Mellitus: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2002;25:S5. [PMID: 12017675]

Sinclair AJ et al: Prevalence of diabetes in care home residents. Diabetes Care 2001;24:1066. [PMID: 11375372]

Wahl PW et al: Diabetes in older adults: comparison of 1997 American Diabetes Association classification of diabetes mellitus with 1985 WHO classification. Lancet 1998;352:1012. [PMID: 9759743]

American Diabetes Association: Clinical practice recommendations 2002: http://www.care.diabetesjournals.org/content/vol25/suppl_1/

Complications

  1. ACUTE COMPLICATIONS

Acute complications are metabolic and infectious. Chronic complications include the microvascular (retinopathy, neuropathy, nephropathy) and macrovascular (cardiovascular disease) complications.

Ketoacidosis occurs in DM type 1 and results from a lack of insulin action in the presence of glucagon. Predisposing factors include infection, stroke, and myocardial infarction as well as missed insulin doses. Typically, patients present with symptoms of the precipitating factor, acidosis/hyperosmolality, and abdominal pain. Coma and mental status alteration may be present. Insulin is the mainstay of treatment in addition to fluid replacement. Identification and management of the precipitating factor are critical (eg, treatment of acute infection). Mortality rates are highest for the oldest patients, especially those with coexisting renal disease and infection. Ketoacidosis is rare in DM type 2.

Nonketotic hyperosmolar coma occurs predominantly in elderly patients with DM type 2 and results from osmotic diuresis caused by hyperglycemia and consequent dehydration. Predisposing factors include dementia, infection, stroke, and myocardial infarction. A decrease in the glomerular filtration rate promotes further hyperglycemia and dehydration through a vicious cycle. Glucose levels commonly reach ≥ 600 mg/dL, and serum osmolality often exceeds 320 mOsm/L. A fluid deficit of 5–10 L is typical. Fluids are thus the mainstay of treatment, usually given as normal saline if hemodynamic instability is present or 50% normal saline otherwise (because free water is typically lost in an osmotic diuresis). Insulin is also required as well as treatment of the precipitating factors. The coma/mental status alterations may take several days to clear, lagging behind correction of the serum osmolality. Mortality rates are relatively high; severe hyperosmolarity, advanced age, and nursing home residence are the major prognostic factors associated with death.

Elderly patients with diabetes are at particularly increased risk of severe and unusual infections, particularly malignant external otitis. Necrotizing infection resulting from Pseudomonas aeruginosa initially involves the external ear canal and progresses to the mastoid air cells, skull base, or temporal bone. The clinical presentation consists of fever, otalgia, otorrhea, and, less commonly, cranial nerve palsy. Treatment involves surgical débridement and antibiotics. Other infections associated with diabetes include rhinocerebral mucormycosis, necrotizing fasciitis, emphysematous cholecystitis, and emphysematous pyelonephritis. Elderly patients with diabetes are also at increased risk for renal papillary necrosis, presenting as insidious renal failure.

Kitabchi AE et al: Management of hyperglycemic crises in patients with diabetes. Diabetes Care 2001;24:131.

Malone ML et al: Characteristics of diabetic ketoacidosis in older versus younger adults. J Am Geriatr Soc 1992;40:1100. [PMID: 1401693]

  1. CHRONIC COMPLICATIONS
  2. Retinopathy—The major predictor of risk for retinopathy is the duration of diabetes mellitus. In addition to being the most threatening of the chronic microvascular complications associated with DM, diabetic retinopathy is a leading cause of blindness in the United States. Ischemia is believed to be the major culprit of diabetic retinopathy, and glucose control has been shown to be of major benefit.

The classification of retinopathy includes nonproliferative disease (NPDR), preproliferative disease, and proliferative retinopathy. NPDR includes microaneurysms (small outpouchings of the capillary vessel wall, which appear as small red dots on exam), hard exudates(shiny yellow deposits caused by damage of the blood retinal barrier and leakage of lipids, carbohydrates, and proteins), intraretinal hemorrhages, and macular edema. Preproliferative retinopathy, signifying an increased likelihood of proliferative retinopathy, includes cotton wool spots (white feathery spots resulting from capillary closure) and irregular and narrowed retinal arterioles and veins. Proliferative retinopathy is neovascularization at the disk or elsewhere, which can leak or bleed into the vitreous leading to visual loss. Fibrous tissue may also occur with neovascularization, possibly leading to retinal detachment.

Proliferative retinopathy is treated with panretinal photocoagulation, which is believed to decrease oxygen demand and induce regression of retinal neovascularization. Laser is also used to treat macular edema. Vitrectomy is undertaken if neovascularization leads to vitreous hemorrhage without adequate resorption or if retinal detachment occurs. In addition to good glycemic control, management of hypertension and dyslipidemia may reduce progression of retinopathy because each has been shown to be a risk factor for retinopathy. Hypertension

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is an independent risk factor for any retinopathy, and its tight control reduces progression of retinopathy. Aspirin has been shown to be of no risk or benefit.

Diabetics are also at increased risk of cataracts and glaucoma. Cataracts and glaucoma are 2 and 3 times more likely, respectively, in diabetic patients older than 65 than in their nondiabetic counterparts. On the basis of this increased risk of visual loss as a result of retinopathy, cataracts, and glaucoma and the subsequent effect of this loss on quality of life and risk of accidents, it has been recommended that elderly patients undergo a dilated eye exam by an ophthalmologist at diagnosis and yearly thereafter.

Vijan S et al: Cost-utility analysis of screening intervals for diabetic retinopathy in patients with type 2 diabetes mellitus. JAMA 2000;283:889.

  1. Neuropathy—Neuropathy is a distressing complication of DM and can lead to loss of sleep, limitation of activity, and depression. Diabetic neuropathies include focal neuropathies, polyneuropathy, and autonomic neuropathy. Focal neuropathies include entrapment syndromes and mononeuropathies. The most common entrapment syndrome is carpal tunnel syndrome, which may produce symptoms limited to the hand or the entire arm. The ulnar nerve and nerves of the feet may also be involved with entrapment syndromes, which generally are of slow onset and persist until treated. Focal neuropathies caused by mononeuritis, in contrast, are acute in onset, resolve spontaneously, and may be multiplex. These neuropathies are caused by vasculitis and subsequent ischemia. The most commonly involved nerves are cranial nerves III, IV, VI, and VII, but thoracic and peripheral nerves may be involved as well. Physical therapy may be necessary, but the neuropathy resolves spontaneously.

Proximal motor neuropathy (diabetic amyotrophy) primarily affects elderly patients. It begins with thigh pain, initially unilateral and then bilateral, which progresses to proximal muscle weakness and wasting. It may coexist with distal symmetric polyneuropathy. Treatment includes glycemic control (usually insulin) and physical therapy. Some forms of amyotrophy respond to immunotherapy. Distal symmetric polyneuropathy, more commonly recognized as “glove and stocking” sensory symptoms, is the most common neuropathy of elderly diabetics. Pain, which can interrupt sleep and limit activity, can be treated with multiple agents, including anticonvulsants (gabapentin, phenytoin, and carbamazepine) and antidepressants (tricyclics). However, the anticholinergic effects of the tricyclics limit their usefulness in the older patient. Dysesthesia of a burning quality is sometimes treated with topical capsaicin or oral mexiletine, although their role in treatment of older patients is not well established.

Patients with distal sensory polyneuropathy are predisposed to Charcot joints, which may mimic gout or degenerative joint disease. A plain film of the foot will usually differentiate the Charcot joint. Distal sensory polyneuropathy also predisposes to neuropathic foot ulcer, which remains the leading cause of foot amputation in the United States. The feet should be inspected at each office visit and daily self-examination encouraged. A monofilament identifies patients with sensory neuropathy. Therapeutic shoes, prescribed by a podiatrist and individually designed to prevent blisters, calluses, and ulcers, are covered by Medicare for peripheral neuropathy if any of the following conditions coexist: callus formation, poor circulation, foot deformity, or history of foot callus, ulcer, or amputation (partial or complete). One pair of shoes plus 3 pairs of inserts are covered annually.

Autonomic neuropathy can be the most life-threatening form of diabetic neuropathy. Tachycardia carries an increased risk of sudden death, whereas postural hypotension imparts an increased risk of syncope and falling with injury. Other forms of autonomic neuropathy include neurogenic bladder, sexual dysfunction, gastropathy (which is particularly sensitive to glycemic control), enteropathy, and gustatory sweating. Patients with autonomic neuropathy are more likely to have hypoglycemic unawareness.

Vinik AI: Diagnosis and management of diabetic neuropathy. Advances in the care of older people with diabetes. Clin Geriatr Med 1999;15:293. [PMID: 10339635]

Wheeler SG et al: Prospective study of autonomic neuropathy as a predictor of mortality in patients with diabetes. Diab Res Clin Pract 2002;58:131. [PMID: 12213355]

  1. Nephropathy—Elderly diabetics are at particular risk for development or progression of nephropathy. Independent risk factors for the development of proteinuria and renal insufficiency include degree and duration of glycemic control, hypertension, longer duration of diabetes, male sex, and higher total cholesterol levels. Smoking increases the risk of progression of nephropathy. Nephropathy progresses from microalbuminuria to overt proteinuria to renal insufficiency and end-stage renal disease (ESRD), although the course may be shorter than the typical 10–20 years observed in a younger population. Elderly patients are at risk for acute renal failure from renal insults such as administration of intravenous contrast agents in the course of radiological procedures, nephrotoxic drugs, and comorbid illness (eg, congestive heart failure).

The diagnosis of diabetic nephropathy is usually made clinically and not by renal biopsy. Diabetic nephropathy is defined as a urinary albumin excretion

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> 300 mg/day and an appropriate time course in the absence of other obvious secondary causes of renal disease in diabetes, with specificities of nearly 100% in DM type 1 and > 85% in DM type 2. Screening for microalbuminuria, the precursor of frank proteinuria and renal insufficiency, may be accomplished by measuring the urinary albumin-creatinine ratio on a spot urine specimen.

In DM types 1 and 2, good glycemic control reduces the risk of microalbuminuria, progression of albuminuria, and development of renal insufficiency. Lowering of blood pressure reduces the decline in glomerular filtration rate and albuminuria. Angiotensin-converting enzyme (ACE) inhibitors reduce the rate of progression of proteinuria and the rate of ESRD, although the data are stronger in patients with DM type 1. Similarly, angiotensin receptor blockers (ARBs) reduce proteinuria and loss of GFR in type 2 diabetes. Blood pressure should be controlled to reduce stroke and cardiovascular complications regardless of the presence or absence of microalbuminuria. Adverse events with ACE inhibitors and ARBs include renal insufficiency in patients with renal artery stenosis and hyperkalemia in the presence of type IV renal tubular acidosis (hyporeninemic hypoaldosteronism).

ESRD in elderly diabetics is increasing in number. The nephropathy in older diabetics is different from that seen in young diabetics. The pathological findings may suggest ischemia and hypertension, whereas the classic Kimmelsteil-Wilson lesions may be absent. As a clinical correlation, many patients present with ESRD typically after an episode of acute renal failure that does not resolve.

  1. Cardiovascular disease—Diabetes imparts at least a 2-fold risk in coronary heart disease. The conventional risk factors of hypertension, hyperlipidemia, smoking, and diabetes persist through old age. The role of glycemic control is well established for microvascular complications but less well established for macrovascular complications. Still, the data from the UKPDS and elsewhere suggest a benefit, and glycemic control should be optimized in the elderly. Aspirin therapy has been shown to be beneficial in secondary prevention of coronary events. It has been broadly recommended that all adults with diabetes take at least low-dose aspirin daily (81 mg) unless there is a specific contraindication (ADA guidelines).

Bonora E, Muggeo M: Postprandial blood glucose as a risk factor for cardiovascular disease in type 2 diabetes: the epidemiological evidence. Diabetologia 2001;44:2107. [PMID: 11793012]

DECODE Study Group on behalf of the European Diabetes Epidemiology Group: Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med 2001;161:397. [PMID: 11176766]

Treatment

The pathophysiological and psychosocial principles underlying management are similar for both young and elderly patients. Consideration is given to the patient's preferences, commitment, health beliefs, coexisting illnesses, and economic issues. Some factors, including life expectancy, functional status, and availability of support services, strongly impact the treatment goals for the elderly diabetic. Age-associated changes in cognitive function, visual function, physical functioning, dentition, and taste perception can affect the ability to implement various management approaches. The elderly diabetic may be at greater risk for hypoglycemia but can be taught to monitor for and treat hypoglycemia appropriately (Table 33-1). In addition, the frequent hospitalizations among the elderly can disrupt outpatient regimens.

  1. GLYCEMIC CONTROL

Aggressive glucose control in patients with DM type 1 is extremely important to reduce the risk of microvascular and macrovascular complications.

The ADA currently recommends goal HgbA1C levels < 7.0% with action suggested at levels > 8.0%. Premeal and bedtime home glucose monitoring should be maintained at 90–130 mg/dL and 110–150 mg/dL, respectively. The American College of Clinical Endocrinologists recommends preprandial glucose levels < 110 mg/dL, postprandial and bedtime glucose < 140 mg/dL, and HgbA1C < 6.5%. The benefits of this degree of control must be balanced against the risks, namely hypoglycemia and weight gain.

Age itself is an important factor in hypoglycemia. The Department of Veterans Affairs/Department of Defense guidelines recommend different HgbA1Ctargets based on the individual's risk of microvascular complications. Less stringent treatment goals may be

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appropriate in those with limited life expectancies and hypoglycemic unawareness and in individuals with comorbid conditions such as seizure, dementia, psychiatric illness, alcoholism, and coronary artery disease.

Table 33-1. Risk factors for hypoglycemia in the elderly diabetic.

Therapy with sulfonylureas or insulin
Renal insufficiency
Hepatic dysfunction
Cognitive impairment
Autonomic neuropathy and adrenergic blocking agents
Poor nutrition
Alcohol
Sedative agents
Complex regimens
Polypharmacy
Tight glycemic control
Recent hospitalization

Glycemic control in the hospital has traditionally been designed primarily to maintain safe levels of glucose (ie, 90–200 mg/dL to prevent hyperglycemia-induced dehydration and catabolism while avoiding hypoglycemia). Some studies have shown a benefit of good glycemic control in terms of in-hospital mortality.

The complex nature of geriatric patients and diabetes management requires a team approach. The physician, in conjunction with a certified diabetes educator, dietitian, social worker, and pharmacist, can best address the lifestyle modifications that diabetes management requires in the face of multiple comorbidities, difficult social situations, and polypharmacy. Moreover, careful attention to comorbid illness is essential. For example, many elderly patients with diabetes are depressed. Fluoxetine has been demonstrated to improve glycemic control in obese elderly patients who are depressed presumably because it results in weight loss. Because mortality in diabetes is primarily related to cardiovascular disease, the overall regimen should aim at reducing cardiovascular risk (eg, controlling blood pressure, lipid levels, and glucose levels) rather than focusing solely on management of glucose. In fact, blood pressure and lipid level control has been thought to confer greater benefit in terms of mortality than glucose control.

Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977. [PMID: 8366922]

Earnshaw SR et al: Optimal allocation of resources across four interventions for type 2 diabetes. Med Decision Mak 2002; 22;S80.

Eastman RC et al: Model of complications of NIDDM: I. Model construction and assumptions. Diabetes Care 1997;20:725. [PMID: 9135934]

Eastman RC et al: Model of complications of NIDDM: II. Analysis of the health benefits and cost-effectiveness of treating NIDDM with the goal of normoglycemia. Diabetes Care 1997;20:735. [PMID: 9135935]

Metchick LN et al: Inpatient management of diabetes mellitus. Am J Med 2002;113:317.

Van den Bergh G et al: Intensive insulin therapy in critically ill patients. N Engl J Med 2001;345:1359. [PMID: 11794168]

Vijan S et al: Estimated benefits of glycemic control in microvascular complications in type 2 diabetes. Ann Intern Med 1997;127:788. [PMID: 11028137]

  1. Nonpharmacological therapy—Consistent carbohydrate intake can help maintain euglycemia in some patients with DM type 2 and can be essential to maximize glycemic control in DM type 1. In elderly diabetics, malnutrition can be more of a concern than obesity, and dietary restrictions may be harmful. This is especially true for patients in long-term health care facilities who may be malnourished. These patients should be given unrestricted menus with consistent amounts of carbohydrate at meals and snacks and medications adjusted to control glucose if necessary. For community-dwelling patients, individualization of dietary therapy by a dietitian is recommended and, as of 2002, is covered by Medicare if at least 1 of the following criteria are met: newly diagnosed, HgbA1C> 8.5%, recent initiation of medication, or high risk for complications. Eligible beneficiaries receive up to 10 h of diabetes education with a certified diabetes educator or registered dietitian within a 12-mo period.

Exercise is of benefit in DM because it improves insulin resistance, increases muscle mass, reduces adiposity, improves weight, and improves lipids and blood pressure. Both aerobic and nonaerobic activity has been shown to be beneficial. The best time to exercise is 1–2 h after a meal when glucose levels tend to be highest. Both hypo- and hyperglycemia may be seen up to 24 h after exercise and medication adjustments must be advised. In short-term studies (up to 6 mo) the effect on glycemic control has been variable.

  1. Pharmacological therapy(Table 33-2)—
  2. Sulfonylureas—The sulfonylureas in common use include glipizide (Glucotrol), glyburide (Diabeta, Micronase, Glynase), and glimepiride (Amaryl). Sulfonylureas reduce glycated hemoglobin by 1–2% (which corresponds to a reduction in mean blood glucose values of 30–60 mg/dL). Generally, most of the therapeutic effect occurs with half of the maximum recommended dose. Because sulfonylureas act predominantly by increasing pancreatic insulin secretion, weight gain is common and hypoglycemia may occur. In addition to advanced age, risk factors for drug-induced hypoglycemia include renal dysfunction, missed or smaller meals, alcohol, infection, recent hospitalization, and use of other drugs that potentiate hypoglycemia, including salicylates, sulfonamides, and warfarin. Glyburide has shown a 2-fold relative risk of hypoglycemia compared with glipizide. Patients on β-blockers should be cautioned regarding the possible lack of warning (adrenergic) symptoms such as tachycardia. Sulfonylureas should be avoided or used cautiously in the elderly diabetic, especially those with renal insufficiency (because of increased risk of hypoglycemia with accumulation of active metabolites), liver disease, or sulfa allergy. If implemented, starting doses should be low, perhaps half that for younger patients, and education regarding hypoglycemia provided.

Table 33-2. Oral glucose-lowering agents.

Agent

Expected decrease HgbA1c (%)

Plasma half-life (h)

Contraindications

Side effects

Cost

Sulfonylureas

1–2

 

Renal insufficiency

Hypoglycemia

 

   Glipizide

 

2–4

Sulfa allergy

Weight gain

$

   Glyburide

 

10

Hepatic insufficiency

 

$

   Glimepiride

 

~9

 

 

$$

Meglitinides

1–2

 

Hepatic insufficiency

Hypoglycemia

 

   Repaglinide

 

1

 

 

$$$$

   Nateglinide

 

1.5

 

 

$$$$

α-Glucosidase

0.5–1

 

Small bowel disease

Flatulence

 

   Inhibitors

 

 

Severe renal insufficiency

Diarrhea/GIupset

 

   Acarbose

 

 

 

 

$$$

   Miglitol

 

6

 

 

 

Biguanides

1–2

 

Lactic acidosis predisposition

Lactic acidosis (rare)

 

   Metformin

 

 

Renal insufficiency

GI symptoms

$$

 

 

 

Hepatic insufficiency/alcohol

 

 

Thiazolidinediones

1–2

 

Congestive heart failure

Fluid retention/edema

 

   Rosiglitazone

 

3–4

Liver disease

Hepatotoxicity

$$$$

   Pioglitazone

 

6–24

 

 

$$$$

$ , lowest; $$$$ , highest, GI, gastrointestinal.

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  2. Ben-Ami H et al: Drug-induced hypoglycemic coma in 102 diabetic patients. Arch Intern Med 1999;159;281. [PMID: 9989540]
  3. Jollis JG et al: Relation between sulfonylurea therapy, complications, and outcome for elderly patients with acute myocardial infarction. Am Heart J 1999;138:S376. [PMID: 10539800]
  4. Shorr RI et al: Incidence and risk factors for serious hypoglycemia in older persons using insulin or sulfonylureas. Arch Intern Med 1997;157:1681. [PMID: 9250229]
  5. Biguanides—Metformin (Glucophage) is the only available biguanide in the United States. Metformin likely acts by decreasing hepatic glucose production and improving peripheral (muscle) insulin sensitivity. Because insulin production is not augmented but actually lessened, hypoglycemia does not occur with monotherapy. Weight loss is often an added benefit of biguanide use in obese diabetics.

Metformin lowers glycated hemoglobin by 1–2%. It should not be used in conditions with an increased tendency to lactic acidosis, such as renal or hepatic insufficiency, alcohol abuse, or poor peripheral perfusion and hypoxic states. In properly selected elderly patients, the risk for lactic acidosis is low with metformin use. However, it should be used with caution because the elderly are at increased risk for other conditions that predispose to lactic acidosis (eg, pneumonia, heart failure) or renal insufficiency (dehydration, stroke, myocardial infarction). In addition, patients with low muscle mass but normal creatinine may have reduced renal clearance. More commonly, the limiting side effect has been gastrointestinal distress (nausea, diarrhea). This can be minimized by taking the tablet at the end of a meal, gradually increasing the dosage, and using the extended-release formulation. Vitamin B12 deficiency has also been reported.

Gregorio F et al: Poorly controlled elderly type 2 diabetic patients: the effects of increasing sulfonylureas dosages or adding metformin. Diab Med 1999;16:1016. [PMID: 10656230]

  1. Meglitinides—The main effect of meglitinides is on postprandial hyperglycemia, which may be of particular benefit in the elderly, although definitive studies are lacking. Repaglinide (Prandin) and nateglinide (Starlix) increase pancreatic response to meal-related glucose loads; premeal dosing and a short duration of action promote glucose-dependent insulin release (by a mechanism different than sulfonylureas) that diminishes with low blood glucose concentrations. In clinical trials, however, the incidence of hypoglycemia in patients treated with repaglinide was comparable to that among patients treated with sulfonylureas. Likewise, glycated hemoglobin can be expected to improve 1–2%. The meglitinides do not contain a sulfur moiety and may be useful in patients who are allergic to sulfonylureas. They can also be used in renal insufficiency with dosage adjustment but should be used with caution in hepatic insufficiency because of extensive metabolism by the liver.
  2. α-glucosidase inhibitors—The main effect of the α-glucosidase inhibitors acarbose (Precose) and miglitol (Glyset) is on postprandial hyperglycemia.

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Taken with the first bite of a meal, these agents interfere with brush-border enzymes in the gut that digest disaccharides/polysaccharides to monosaccharides, thus reducing the rise in postprandial glucose. They do not augment insulin secretion and, when used as monotherapy, do not cause hypoglycemia or weight gain. Each reduces glycated hemoglobin by 0.5–1.5% and decreases postprandial glucose by ~50 mg/dL. Because α-glucosidase inhibitors are not absorbed at usual doses (in particular acarbose), they generally can be safely used in elderly patients and with either renal or hepatic insufficiency (although rare cases of dose-dependent elevated transaminases have been reported). Flatulence and diarrhea are the predominant side effects but diminish with continued use over several months. To minimize gastrointestinal distress, initial doses are low and gradually increased over several weeks. Miglitol has been shown to be useful and safe compared with sulfonylureas.

Johnston PS et al: Advantages of alpha-glucosidase inhibition as monotherapy in elderly type 2 diabetic patients. J Clin Endocrinol Metab 1998;83:1515. [PMID: 9589648]

  1. Thiazolidinediones—The thiazolidinediones (TZDs) rosiglitazone (Avandia) and pioglitazone (Actos) act as insulin sensitizers. They bind to and activate specific nuclear receptors (peroxisome proliferator activator receptors), which enhance the transcription of a number of genes involved in glucose metabolism. The initial effects of the glitazones may not be seen for 2–3 weeks, and maximal effects may require 3 mo of use. The overall efficacy is comparable to that of sulfonylureas and metformin, with a 1–2% improvement in glycated hemoglobin and a mean reduction in fasting plasma glucose of 30–60 mg/dL. Patients also using exogenous insulin are able to decrease insulin doses significantly. Troglitazone, a TZD removed from the market, was found to be effective in elderly diabetics. The TZDs may be of benefit in elderly diabetics; because they do not cause hypoglycemia when used as monotherapy, they are dispensed once daily and can be used with safety in renal failure. However, they should be avoided in hepatic insufficiency. The TZDs have also been recognized to cause fluid retention, resulting in lower extremity edema in up to 15% of patients and congestive heart failure in up to 3%. These agents should be avoided or used with caution at a low dose in patients with a history of congestive heart failure. Fluid retention, decreased glycosuria, and an increased differentiation and proliferation of adipocytes may be contributing factors to the weight gain not uncommonly associated with these agents.

Table 33-3. Insulin products in common use.

Type

Onset of action

Peak action

Duration

Cost

Lispro

15 min

30–90 min

2–4 h

$$

Aspart

15 min

30–90 min

 

$$

Regular

30–60 min

2–3 h

4–6 h

$

NPH

2–4 h

6–10 h

10–16 h

$

Glargine

22–24 h

$$

$ , lowest; $$ , highest.

  1. Because the oral agents work to lower glucose levels through different mechanisms, combinations of agents are quite effective at lowering blood glucose. When combination therapy is used, the effect of each agent on glucose control is additive.
  2. Insulin—Insulin is required in all patients with DM type 1. Insulin is also generally required in any patient with moderate or severe hyperglycemia, especially in the presence of renal or hepatic insufficiency. The trend in insulin use is to give smaller doses more frequently, allowing for better control of hyperglycemia (in particular postprandial hyperglycemia) and less hypoglycemia. In addition to human NPH and regular insulin (Table 33-3), newer insulin analogues with differing pharmacokinetics are available and offer increased flexibility of dosing and reduced risk of hypoglycemia. They have not been studied in elderly patients alone. Lispro (Humalog) and Aspart (Novolog) are genetically engineered human insulins with rapid absorption and onset of action within 15 min. The peak effect is reached by 120 min, and duration of action is ~4–5 h. These rapid-acting insulins are injected immediately before a meal and reduce the risk of late hypoglycemia seen with regular insulin. For patients with varying oral intake, these insulins are advantageous in that they can also be effectively administered after a meal and the dose can be adjusted for the carbohydrate eaten.

Glargine (Lantus) is marketed as a peakless, once-daily 24-h basal insulin, which can be used in place of twice-daily human NPH insulin or Ultralente. It is used as a basal insulin in patients uncontrolled despite

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double or triple oral therapy and in insulinopenic patients using premeal rapid-acting insulin boluses. It can be an ideal insulin in patients receiving a consistent amount of carbohydrate over 24 h (eg, continuous tube feeds). Glargine cannot be mixed in a syringe with any other insulin. Currently, the only disadvantage to its use is its cost. If fasting hyperglycemia is the main consideration and daytime glucoses can be controlled with oral agents, bedtime human NPH insulin in amounts necessary to normalize the morning glucose is safe, convenient, efficacious, and less expensive than glargine. If fasting glucose is controlled but the values rise in daytime, glargine is the better choice.

For simplicity, insulin mixtures such as 70/30 (70% human NPH, 30% regular insulin or 70% human NPH, 30% Aspart), 50/50 (50% human NPH, 50% regular insulin), and 75/25 (75% human NPH, 25% Lispro) may be particularly useful. The premixed insulins have been shown to be more accurate and acceptable in elderly patients with fewer errors and increased ease of use, although metabolic control and rate of hypoglycemia are unchanged. However, some patients may not achieve adequate glucose control with these fixed-dose regimens, and basal split-dose human NPH or glargine with regular insulin or rapid-acting insulin may be needed.

Elderly patients can learn insulin administration, especially with premixed insulins and pen-delivery systems. The majority of insulins are available in pen-delivery systems as well as vials. The pen systems, available as reusable pens with refillable cartridges or as prefilled disposabXle pens, require the user to attach a needle, set the dose by a dial, and depress the plunger to administer the dose. They are quick and easy to use and can be more precise than insulin syringes and vials. The pen systems are more acceptable, more efficacious, and as safe as conventional syringes. If conventional syringes are used, low-dose syringes (which hold up to 30 units or 50 units compared with 100 units and have more visible unit markings) should be prescribed whenever possible. Magnifying devices that attach to a syringe are also available.

Agurs-Collins TD et al: A randomized controlled trail of weight reduction and exercise for diabetes management in older African-American subjects. Diabetes Care 1997;200:1503. [PMID: 9314625]

Ligtenberg PC et al: Effects of physical training on metabolic control in elderly type 2 diabetes mellitus patients. Clin Sci 1997;93:127. [PMID: 9301427]

UK Prospective Diabetes Study (UKPDS) Group: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998;352:854. [PMID: 9742977]

UK Prospective Diabetes Study (UKPDS) Group: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837. [PMID: 9742796]

  1. INSULIN SELF-MANAGEMENT

Ideally, the best way to tailor an insulin regimen is by home glucose monitoring done pre- and postprandial and at bedtime. Elderly diabetics can be taught to reliably self-monitor blood glucose without adverse effects on quality of life. Currently, Medicare reimburses once-daily testing for non-insulin-treated patients and 3 times daily for insulin-treated patients. Newer glucometers and test strips, which use smaller amounts of blood and capillary action as well as alternate-site testing (forearm, upper arm, thigh, or calf), have made glucose monitoring significantly easier. The FreeStyle (Therasense), One Touch Ultra (Lifescan), and Soft Tac (Medisense) meters are approved for use with blood secured from alternate sites. The Soft Tac lances skin and automatically transfers blood to the test strip for ease of use. Talking glucometers are also available for blind patients. Devices that aid in the management of diabetes in the elderly are outlined in Table 33-4.

Harris MI: National Health and Nutrition Examination Survey (NHANES III). Frequency of blood glucose monitoring in relation to glycemic control in patients with type 2 diabetes. Diabetes Care 2001;24:979. [PMID: 11375356]

Heisler M et al: The relative importance of physician communication, participatory decision making, and patient understanding in diabetes self-management. J Gen Intern Med 2002; 17:243. [PMID: 11972720]

Hirsch IB et al: A multifaceted intervention in support of diabetes treatment guidelines: a controlled trial. Diab Res Clin Pract 2002;58:27. [PMID: 12161054]

Langa KM et al: Informal caregiving for diabetes and diabetic complications among elderly Americans. J Gerontol B Psychol Sci Soc Sci 2002;57:S177. [PMID: 11993744]

Prognosis

Diabetes imparts an ~2-fold risk of death in the elderly. Approximately 50% of patients die from cardiovascular disease. Otherwise, elderly patients have an ~1.5 relative risk of admission to an institution. This is likely

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due to microvascular complications of diabetes, which increase in incidence with the duration of diabetes. With target diabetes control and management of comorbid conditions, many patients may prevent or delay the onset of these complications and lead a quality life. Treatment of hypertension with diuretics and calcium channel blockers reduces mortality and risk of macrovascular complications in elderly patients with DM type 2.

Table 33-4. Devices to aid diabetes management in the elderly.

Insulin pen-delivery systems, especially premixed insulins
Low-dose syringes
Syringe-attached magnifying devices
Comfort Curve (Accucheck) test strips
Alternate site monitors (see text)
Talking glucometers for the blind

Gerstein H, Haynes RB (eds): Evidence-based diabetes care. BC Dekker, 2001.

RELEVANT WORLD WIDE WEB SITES

American Association of Clinical Endocrinologists: http://www.aace.com

American Diabetes Association: http://www.diabetes.org

Diabetes Monitor: http://www.diabetesmonitor.com

Diabetes UK (formerly British Diabetic Association): http://www.diabetes.org.uk

International Diabetes Federation: http://www.idf.org

Veterans Health Administration Diabetes Program: http://www.va.gov/diabetes