Diabetes is an important health condition for the aging population. More than 20% of individuals over the age of 60 years have diabetes, and another 14% have impaired glucose tolerance (IGT). It is anticipated that these numbers will continue to increase in the coming decades. It is therefore almost certain that those involved in the care of patients in this age group will encounter those with some disorder of glucose tolerance.
Both IGT and diabetes are associated with enhanced morbidity and mortality due to macrovascular and cardiovascular disease (CVD); an increase in risk for microvascular complications (retinopathy, neuropathy) that impair the ability to maintain independence; changes in cognitive function; and depression. Older individuals with diabetes have more functional disability and coexisting illnesses such as hypertension, coronary heart disease (CHD), and stroke than those without diabetes. Older adults with diabetes are also at greater risk for urinary incontinence, injurious falls, and issues related to polypharmacy.
Early diagnosis and appropriate intervention can help to avoid some of the adverse consequences of hyperglycemia, while also improving health-related quality of life (HRQL) in this age group. In 2003, the American Geriatric Society published guidelines that are useful in guiding the care of the older person with diabetes. These recommendations are now included as part of the standards of care published annually by the American Diabetes Association.
Aging and the Physiology of Carbohydrate Intolerance
Normal aging is associated with a gradual increase in both fasting (1 mg/dL [0.6 mmol/L] per decade) and glucose-stimulated blood glucose (BG) (5 mg/dL [0.28 mmol/L] per decade) levels, even in lean, physically active individuals with normal body weight. Normoglycemic elderly subjects have higher glucose and insulin levels during an oral glucose tolerance test (OGTT) than body mass index (BMI)-matched young subjects. These changes in BG are more profound in those who have risk factors for abnormal glucose tolerance.
Type 2 diabetes is characterized by defects in both insulin secretion and sensitivity. Although the majority of people with type 2 diabetes are insulin-resistant, insulin resistance by itself is not sufficient to lead to hyperglycemia. Age-related impairments in beta cell function that include reduced conversion of proinsulin to insulin and abnormal insulin secretion are important contributors to the development of hyperglycemia in elderly individuals. Lean elderly patients with type 2 diabetes have a greater impairment in insulin secretion than insulin sensitivity while obese patients have both impaired insulin secretion and sensitivity in muscle and liver (Figure 23–6).
The pathogenesis of type 2 diabetes mellitus in obese elderly and lean elderly.
Several abnormalities of beta cell function contribute to the decline in insulin secretory capacity with advancing age. These include an accumulation of intracellular lipid within the beta cell; a decrease in glucose transporter (GLUT) 2 number; and a reduced sensitivity to the incretin hormones, glucagon-like peptide 1 (GLP1), and glucose insulinotropic peptide (GIP) that acts to augment the postprandial insulin response. Genetic susceptibility also plays a role. In individuals without diabetes who carry five or more risk alleles that are associated with development of diabetes, impairments in insulin secretion are observed at an earlier age than those with fewer alleles. Evidence of autoimmunity with antibodies directed against beta cell proteins has been demonstrated as a cause of impaired insulin secretion in up to 12% of elderly individuals.
These impairments in beta cell function can be unmasked by an increase in insulin resistance that occurs with normal aging. The insulin resistance that accompanies aging is associated with the accumulation of intracellular fat and a progressive decline in the number and function of mitochondria resulting in reduced oxidative glucose metabolism and phosphorylation activity. Insulin resistance is augmented by weight gain; reductions in lean body mass and increases in fat mass; physical inactivity; and use of some medications (ie, glucocorticoids and atypical antipsychotics). Insulin resistance occurs in muscle, where there is a reduction in insulin-mediated glucose uptake following a meal; in adipose tissue where impaired regulation of hormone-sensitive lipase results in increases in circulating levels of free fatty acids (FFA); and liver where there is overproduction of glucose in the fasting state and failure to adequately suppress glucose production after a meal.
The metabolic syndrome refers to a clustering of metabolic abnormalities outlined in Table 23–2 that are associated with an increase in risk for type 2 diabetes and CVD. This syndrome is more common in the elderly, increasing from approximately 7% of the population in the third decade to 44% in the seventh decade. Lifestyle interventions targeting modifications in dietary intake, regular exercise, and weight reduction are effective in reducing the progression to overt type 2 diabetes among individuals above age 60 years.
Table 23–2 National Cholesterol Education Program Criteria for Diagnosis of Metabolic Syndrome. ||Download (.pdf)
Table 23–2 National Cholesterol Education Program Criteria for Diagnosis of Metabolic Syndrome.
Diagnosis requires three of the following:
- Abdominal obesity
- Waist circumference >40 in (>102 cm) men
- Waist circumference > 35 in (>88 cm) women
- Triglycerides ≥150 mg/dL or drug treatment
- HDL-C <40 men or <50 women or drug treatment
- Blood pressure ≥130/85 mm Hg or drug treatment
- Fasting glucose ≥ 110 mg/dL or drug treatment
Establishing the Diagnosis of Diabetes Mellitus
The majority of elderly individuals with diabetes will have type 2 diabetes. The typical symptoms usually associated with hyperglycemia may either not be present or may have developed so gradually that they may not be perceived as being abnormal. The use of diuretics can mask polyuria and polydipsia as manifestations of hyperglycemia. An age–related decrease in thirst may blunt these usual symptoms. It is therefore important that laboratory measurement of BG be performed on at least an annual basis in individuals above the age of 60.
A diagnosis of diabetes can be established by one of three established criteria outlined in Table 23–3. Oral glucose tolerance testing is performed infrequently in clinical practice and is not required to establish the diagnosis, particularly in elderly individuals. Measurement of an A1c is now accepted as an alternative tool in establishing a diagnosis of diabetes, with values ≥6.5% consistent with a diagnosis of diabetes. A1c values of 6.0% to 6.4% identify those at high risk for development of type 2 diabetes. A reasonable approach would be to measure an A1c in any elderly person with abnormal glucose values.
Table 23–3 Criteria for Diagnosis of Type 2 Diabetes. ||Download (.pdf)
Table 23–3 Criteria for Diagnosis of Type 2 Diabetes.
|• Fasting glucose ≥126 mg/dL (7.0 mmol/L)|
|• Any glucose ≥200 mg/dL (11.1 mmol/L) with symptoms|
|• 2-h PG ≥200 mg/dL (11.1 mmol/L) during a 75-g OGTT|
|Newly proposed criterion: A1c ≥6.5%|
Both the ADA and the American Geriatrics Society recommend that functional, cognitively intact older adults who have significant anticipated life expectancy be treated to similar glycemic goals as younger adults. This means guiding therapy to achieve HbA1c of <7% for the majority of people with diabetes. Achieving this level requires that fasting glucose levels be maintained between 80 and 130 mg/dL, and 2-hour postprandial BG at <180 mg/dL. These recommendations are not absolute. While the goal is to maintain an A1c values as close to normal (<6%) as possible, this goal can be modified in patients who are at high risk for hypoglycemia, who are older, who have comorbid conditions that limit life expectancies. These contingencies have particular relevance to the elderly population who may experience variability in appetite or food intake, or often have other medical problems requiring medications (eg, beta blockers, anxiolytics) that can increase vulnerability to hypoglycemia. On the other hand, uncontrolled diabetes is also associated with undesirable effects in elderly individuals, including fluid and electrolyte abnormalities, problems with urinary incontinence and cognitive function, indicating the need for a reasonable degree of glycemic control even with advanced age. Efforts to achieve A1c levels of <7% are reasonable in some elderly patients, provided that the risk for weight gain and hypoglycemia is minimized. Therapy can be modified to achieve A1c targets of 8% in others as a way of minimizing risk for treatment-associated concerns. However, symptomatic hyperglycemia that can increase risk for an acute hyperglycemic crisis should be avoided in all patients.
Glycemic Control and Complications
Because the complications of diabetes mellitus are related to the duration of disease, elderly patients who live long enough suffer the same complications of nephropathy, neuropathy, and retinopathy as their younger counterparts. The United Kingdom Prospective Diabetes Study (UKPDS) examined the relationship between improved glycemic control and the prevention of complications in 3067 patients with type 2 diabetes (mean age 54 years) assigned to intensive (goal of fasting blood glucose <108 mg/dL) or conventional therapy. After a median follow-up of 10 years, the incidence of microvascular complications (retinopathy, neuropathy, and nephropathy) was reduced by 25% with intensive treatment. There was no difference in the incidence of macrovascular complications, but there was a tendency for fewer myocardial infarctions in the intensive therapy group. A 10-year follow-up report from the UKPDS demonstrated a significant favorable legacy effect of early intensive therapy in preventing both microvascular and macrovascular complications.
Elderly diabetic patients have an impaired counterregulatory response to hypoglycemia which can interfere with recovery from a hypoglycemic event. In addition, the ability to sense hypoglycemia declines, as does the ability to take corrective action. Coupled with the diminished cortical reserve due to the higher prevalence of age-associated conditions such as stroke, lacunar infarction, amyloid angiopathy, and Alzheimer disease, the older brain is less able to recover fully from hypoglycemic insult.
CVD is a major cause of morbidity and mortality in elderly people with diabetes. For this reason, interventions recommended for the secondary prevention of recurrent coronary events in individuals without diabetes are recommended for all individuals with diabetes independent of known heart disease. This includes control of blood pressure, treatment of hyperlipidemia, and use of low-dose aspirin therapy in those without contraindications. While tight glycemic control has been demonstrated to reduce the risk for microvascular and neuropathic complications, the role of tight glycemic control for prevention of macrovascular disease and CVD has been addressed in several recent clinical trials.
Three recent large, randomized, prospective clinical trials with relevance to an elderly population were conducted in an effort to define the effect of lowering A1c to levels lower than those currently recommended by the ADA on cardiovascular outcomes in patients with type 2 diabetes. The average age of these subjects, all of whom had a history of a CVD event or were at high risk for an event, ranged from 60 to 66 years.
In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, the goal of intensive glycemic therapy was to achieve an A1c <6% versus <8% with conventional treatment. The glycemic control study was stopped 18 months early due to the observation of a 22% increase in the relative risk for CVD death with intensive therapy. In the Action in Diabetes and Vascular Disease (ADVANCE) study, the goal of intensive therapy was to achieve an A1c <6.5% using the sulfonylurea, gliclazide (not available in the United States). A reduction in microvascular complications, primarily risk for proteinuria, was observed with intensive therapy, but there were no group differences for CVD events. In the Veterans Affairs Diabetes Trial (VADT), the goal of intensive therapy was to achieve an A1c <6%. There were no significant group differences in the composite outcome of CVD events; however, there were more CVD deaths (36 vs 29) and more sudden deaths in intensively treated subjects (11 vs 4) (p = NS). Severe hypoglycemia within the preceding 90 days was a predictor of CVD events and mortality.
What do these results mean to the practicing physician? It is important to note that all three trials included participants with long-standing type 2 diabetes and varying degrees of established atherosclerosis at time of study entry. In addition, the glycemic targets in these trials were well below what is recommended by the ADA (7%) and may not be appropriate in elderly individuals where the risk for hypoglycemia and related adverse sequellae is greater. Other CVD risk factors (eg, hypertension and hyperlipidemia) were treated to a moderate or high degree, resulting in rates of CVD events that were lower than predicted with standard therapy. This places emphasis on the importance of treating nonglycemic CVD risk factors in patients with diabetes.
Treatment Strategies for Achieving Glycemic Goals in the Elderly
The therapeutic goals for any patient with diabetes, including the elderly, are to avoid symptoms of hyperglycemia and hypoglycemia, to minimize risk for acute and chronic diabetes-related complications, and to achieve an optimal health-related quality of life. While the majority of newly diagnosed elderly individuals will have type 2 diabetes, many individuals with type 1 diabetes are enjoying longer survival, making it likely that these patients will require care during advancing years. Insulin therapy, either alone or in combination with oral agents, is often required to maintain desired glycemic control in the face of progressive beta cell dysfunction in those with type 2 diabetes. For these reasons, knowledge of insulin and noninsulin injectable medications is as important as that of the five different classes or oral hypoglycemic agents (Table 23–4) indicated for the treatment of type 2 diabetes.
Table 23–4 Oral Hypoglycemic Agents Available for Treatment of Type 2 Diabetes. ||Download (.pdf)
Table 23–4 Oral Hypoglycemic Agents Available for Treatment of Type 2 Diabetes.
|Class||Mechanism Action||Side Effects||Agents|
|Sulfonylureas||Stimulates insulin production||Hypoglycemia|
|Short-acting insulin secretagogues|
↑ Insulin sensitivity
|Nausea, diarrhea, rarely lactic acidosis||Metfomin|
|Thiazolidinediones||Reduce insulin resistance|
Decrease bone density
|α-Glucosidase inhibitors||Decrease rate of carbohydrate absorption||Bloating, abdominal discomfort, diarrhea||Acarbose miglitol|
|DPP IV inhibitors|
Prolongs action GLP1
Increases insulin release
Therapeutic Lifestyle Intervention
The essential components of therapeutic lifestyle intervention (TLI) include dietary modifications and exercise. Weight reduction is recommended for overweight and obese individuals. Recommendations to obtain an adequate amount of sleep as either one uninterrupted sleep cycle or with daily naps may help reduce risk for progression to overt diabetes in those with impairments in glucose intolerance.
Dietary interventions for treatment of diabetes promote appropriate dietary caloric intake with an appropriate distribution of calories among carbohydrates, protein, and fat. There is contradictory information in the literature regarding the optimal diet that should be recommended for patients with diabetes. Studies comparing different diets for achieving weight loss have yielded inconsistent results. In general, obese patients can be encouraged to follow a weight reduction regimen that is most acceptable to their taste, as this is more likely to result in a reasonable degree of compliance.
The Mediterranean diet which emphasizes the intake of fresh fruits and vegetables, whole grains, beans, nuts, and olive oil, may have some advantages over traditional low-fat diets in the elderly population. In one European study of more than 2000 subjects aged 70 to 90 years, the integration of a Mediterranean style diet with other healthy lifestyle interventions reduced all-cause mortality by more than 50%. The Mediterranean diet not only promotes weight loss, but also has demonstrated favorable effects on circulating lipids and BG levels.
In the ongoing Look AHEAD Study, subjects with type 2 diabetes between the ages of 45 and 74 years were able to achieve a 9% weight loss and 21% increase in fitness level with 30 minutes of exercise and 1200 to 1800 calorie intake each day. Exercise prescriptions and encouragement to maintain a reasonable level of physical activity are as important in the elderly as in the younger population. There is no longer a requirement to perform cardiac stress testing before recommending an exercise program. To optimize compliance with exercise prescriptions, it is important to encourage activities that are enjoyed, that can be performed safely, and that can be incorporated into a daily routine. Some insurance companies now provide health club memberships as a way of encouraging activity. Many elderly individuals have difficulty with aerobic activity as a form of exercise. For those who are housebound or who have difficulty walking for any distance due to presence of spinal stenosis, peripheral neuropathy, claudication or other medical problems, stationary bicycling, arm lifts with weights, or leg lifts can be encouraged. Progressive resistance training has been proposed as a more reasonable and beneficial form of exercise in these patients.
TLI is rarely adequate at achieving and maintaining glycemic control without pharmacologic therapy in the majority of patients with type 2 diabetes, including the elderly. This means that some form of pharmacologic therapy will almost always be required. While there is no absolute contraindication to use of any of the oral or injectable agents available for treating diabetes, there are special considerations for prescribing and monitoring of these agents in older adults. As a general rule, medications should be started at the lowest dose and gradually titrated upward as tolerated until glycemic targets are reached. In some cases, it becomes necessary to add on a second agent before maximal doses are reached with one agent as a way of minimizing adverse reactions. For example, the incidence of gastrointestinal side-effects increases with increasing doses of the biguanide, metformin. There are many patients who may be unable to tolerate the maximal dose of 2 g of metformin each day, but who are able to tolerate 1 to 1.5 g/d. In these instances, it may be desirable to continue metformin at a lower dose and add an insulin secretogogue to achieve the desired level of glycemic control. A discussion of pharmacologic therapy in this review is presented with consideration of this strategy in an elderly population (see Table 23–4).
Initiation of metformin together with TLI is recommended at the time of diagnosis of type 2 diabetes. Side-effects with use of metformin that have particular relevance to elderly patients include anorexia, nausea, abdominal cramping, and diarrhea that preclude the use of this drug in approximately 5% of all individuals. Reductions in vitamin B12 levels have also been observed. Given the high prevalence of vitamin B12 deficiency in the elderly population, it is reasonable to monitor its levels and/or recommend vitamin B12 supplementation at a dose of 50 μg/d or more.
The most feared complication of therapy with metformin is lactic acidosis. This can be avoided by following prescribing guidelines that recommend against use of metformin in those with renal insufficiency, defined as a serum creatinine ≥1.5 mg/dL in men, ≥1.4 mg/dL in women; or a creatinine clearance of <60 mL/min. The observed age-related decline in glomerular filtration rate (GFR), as a measure of creatinine clearance, raises concerns for using metformin in the elderly; however, the formulas used to estimate GFR (eGFR) do not always provide accurate results in this population. When there is doubt as to whether metformin can be initiated or continued in a patient with a normal serum creatinine but a reduced eGFR, measurement of a creatinine clearance with 24-hour urine collections can provide a more accurate measure of renal function. In patients assessed as having normal renal function at the time metformin is started; renal function needs to be reassessed with changes in clinical status. Caution is suggested in patients >80 years of age, although there are no data demonstrating a higher incidence of lactic acidosis in this population, provided that renal function is normal.
There may in fact be advantages to metformin therapy. In a study of patients age 72 years with type 2 diabetes and congestive heart failure (CHF), those treated with metformin experienced lower morbidity and mortality when compared to those treated with sulfonylurea monotherapy. There are also epidemiologic data that suggest that treatment with metformin is associated with a lower incidence of cancer and cancer-related deaths.
Alternative or additional pharmacologic therapy is required for patients for whom metformin therapy is contraindicated, who do not tolerate the medication, or who do not achieve the desired level of glycemic control. Insulin secretogogues include long-acting sulfonylureas and shorter-acting meglitinides, which have similar efficacy in lowering A1c levels by 1.5%. The sulfonylureas reduce both fasting and postprandial glucose levels while the shorter-acting meglitinides reduce postprandial glucose excursions. Both renal insufficiency and increasing age are risk factors for hypoglycemia with use of these agents in the elderly when used as either monotherapy or combination therapy. Glipizide and glimepiride are less likely to cause prolonged hypoglycemia in the elderly than glyburide, which has active metabolites. The shorter- acting meglitinides administered immediately prior to a meal can be useful in reducing the risk for hypoglycemia in the elderly who experience variability in appetite or the timing of meals.
When insulin secretogogues are prescribed, it is important that patients and their family members be educated in how to both recognize and treat a low-BG reaction (Table 23–5). Many individuals are unaware of what these symptoms are and can mistake this for simple fatigue or a cardiac event, resulting in potentially dangerous delays in therapy. It is important that patients be instructed to carry a glucose source with them at all times. This can be in the form of hard candy or glucose tablets.
Table 23–5 Symptoms of Hypoglycemia. ||Download (.pdf)
Table 23–5 Symptoms of Hypoglycemia.
|Sensation of warmth|
|Inability to concentrate|
|Loss of memory|
|Loss of consciousness|
The two thiazolidinediones available for clinical use are pioglitazone and rosiglitazone. Both agents reduce HA1c levels by 0.8% to 1.5%, with pioglitazone having more favorable effects on circulating triglycerides. Caution is warranted when using this class of medications in elderly individuals due to their potential to cause weight gain, edema, CHF, and reductions in bone mineral density (BMD) with increased fracture risk. In one report investigating outcomes with glitazones in individuals age >65, treatment with rosiglitazone was associated with a 60% increased risk of new-onset CHF, a 40% increased risk for MI, and a 29% increase in mortality. As both the incidence and prevalence CHF increase with age in those with diabetes, caution is required when using these agents in elderly patients. If a decision is made to use these agents, close monitoring for onset of edema, weight gain, and shortness of breath is important. Regular monitoring of 25-hydroxyvitamin D levels and BMD measurements is also indicated to address fracture risk.
The alpha-glucosidase inhibitors, acarbose and miglitol, delay absorption of carbohydrate from the small intestine by inhibiting the enzymes that convert carbohydrates into monosaccharides. This results in a reduction in postprandial glucose excursions, with reductions in A1c of 0.5% to 0.8% when used alone or in combination with other oral agents or insulin. The main limitation to the use of these agents is the high incidence of GI side effects that are directly related to their mechanism of action. Abdominal bloating and distension, diarrhea, and cramping occur in approximately 50% of patients. Initiating therapy at a low dose of 25 mg once a day given with the main meal and allowing gradual upward titration can improve compliance with this group of medications. It is important that patients be instructed to use glucose tablets to treat hypoglycemia that may occur when taking this class of medications with sulfonylureas or insulin, as there can be delayed absorption of glucose from food sources.
There are now two relatively new classes of medications that address the role of the incretin hormone, GLP1, in glucose homeostasis: injectable GLP1 analogs and orally administered dipeptidyl peptidase IV inhibitors (DPP IV). GLP1 is a hormone that is normally secreted by L cells in the distal ileum in response to a meal (Figure 23–7). GLP1 acts directly on beta cells to enhance endogenous insulin secretion, and on alpha cells to reduce glucagon levels. Endogenously secreted GLP1 is degraded by the DPP IV, which contributes to its short circulating half-life. Exenatide is the first GLP1 mimetic approved for clinical use. Liraglutide is another agent in this class that has recently been approved for use. Sustained reductions in A1c of approximately 1% have been observed with use of these agents. The major side- effects include anorexia, nausea and vomiting, abdominal pain, diarrhea, and weight loss. However, these side-effects often abate over time and with exenatide are minimized by starting with doses of 5 μg administered twice a day for a month before increasing to 10 μg twice a day. Hypoglycemia is possible when used in combination with a sulfonylurea. There are at least 36 postmarketing reports of acute pancreatitis with use of exenatide, but the incidence of this disorder does not appear to be greater than in the general population with type 2 diabetes. Nevertheless, a high index of suspicion is recommended in patients who report abdominal pain with use of these agents. It is anticipated that a once- weekly preparation of exenatide will become available for clinical use in the next 1 to 2 years.
Hormonal regulation of insulin secretion and glucose homeostasis.
There are two DPP IV inhibitors available for clinical use, sitagliptin and saxagliptin. By prolonging the duration of action of endogenously secreted GLP1, these agents reduce A1c by 0.6% to 0.9%. The DPP IV inhibitors are weight neutral and do not cause hypoglycemia when used as monotherapy. The major side-effects of these agents are an increase in upper respiratory and lower urinary tract infections, headache, skin rash, sinusitis, and back pain. The higher incidence of infectious complications may have significance in the elderly population who are more likely to have asymptomatic bacteriuria. However, there is no absolute contraindication to use of these agents in the elderly. Dose adjustments are required in the presence of renal insufficiency with each of the available agents. The relatively benign side-effect profile can make them attractive for use; however, these agents are expensive and may have effects that are currently unknown. DPP IV is a ubiquitous enzyme that is also expressed in lymphocytes, raising concern for alterations in immune function.
When glycemic targets cannot be achieved with the agents discussed earlier, insulin therapy becomes necessary. In patients with isolated morning hyperglycemia, the addition of a bedtime dose of neutral protamine Hagedorn (NPH) can be effective in controlling fasting glucose levels. When both fasting and daytime BG levels are elevated, a long-acting insulin administered once daily can be more effective in lowering glucose levels throughout the day (Table 23–6). When BG levels remain elevated despite the use of basal insulin alone, premeal doses of a short- or rapid-acting insulin can be added.
Table 23–6 Insulin Preparations. ||Download (.pdf)
Table 23–6 Insulin Preparations.
|Lispro/aspart/glulisine||5-15 min||1-2 h||4-6 h|
|Regular||30-60 min||2-3 h||6-10 h|
|NPH||2-4 h||4-10 h||12-18 h|
|Glargine||2-4 h||Flat||20-24 h|
|Detemir||2 h||Flat||6-24 h|
When adding NPH insulin at bedtime to oral agents, a low starting dose of 5 to 10 U allows an elderly patient to become accustomed to insulin injections with a low risk for hypoglycemia. The dose can then be titrated gradually over a period of several weeks until glucose levels are in the desired range. A commonly used strategy is to advise patients to increase by 1 or 2 U every 4 days until they achieve a fasting glucose of less than 140 mg/dL.
When initiating basal/bolus insulin, the starting dose of insulin can be calculated as 0.2 to 0.3 U/kg/d, with 50% of the dose administered as basal insulin and 50% as premeal insulin in divided doses prior to meals. For patients already receiving basal insulin who require the addition of premeal insulin, the dose of premeal insulin can be calculated as follows:
- If the BG is mildly elevated with the majority of readings below 200 mg/dL, the dose of basal insulin can be reduced by 50% with distribution of the remaining 50% into three premeal insulin doses.
- If the majority of BG levels are >200 mg/dL, premeal insulin doses can be started as approximately 25% to 30% of the current basal dose given before each meal. For example, if a patient is receiving 24 U of glargine or NPH each day, the starting dose of regular or humalog before each meal would be 6 to 8 U.
Many elderly individuals can be given instructions in how to advance their insulin doses or how to adjust the dose of insulin according to results of BG measurements. Correction insulin refers to the administration of supplemental doses of short or rapid-acting insulin when BG exceeds glycemic targets. A reasonable glycemic target may be to maintain all BG between 100 and 150 mg/dL. In these cases, the individual patient can be instructed to reduce their premeal insulin dose by 1 to 2 U if their BG is <100 mg/dL, and to increase by 1 U for every 50 mg/dL above 150 mg/dL.
There will be a minority of elderly patients who are unable to achieve adequate control of postprandial glucose excursions with insulin alone. Pramlintide, a synthetic analog of the beta cell hormone amylin, is effective at reducing postprandial BG levels when used in combination with insulin. This injectable medication is approved for use in combination with insulin for patients with both type 1 and type 2 diabetes. Side-effects of pramlintide include nausea and vomiting, which are more common in people with type 1 diabetes, and hypoglycemia. Nausea and vomiting can be minimized by starting at doses of 15 μg before each meal with gradual upward titration to 60 for people with type 1 diabetes. Those with type 2 diabetes can be started at a dose of 60 μg and titrated to 120 μg before meals. The risk for hypoglycemia can be reduced by reducing prandial insulin doses by 50% when pramlintide is initiated.
In summary, there are five classes of oral agents and two noninsulin injectable therapies, in addition to insulin, that are effective at achieving glycemic control as monotherapy or as part of combination therapy. The side-effect profile, risk for hypoglycemia, and cost need to be considered when choosing a regimen for an individual patient.
Screening for Diabetes-Related Complications in the Elderly
The care of older adults with diabetes is complicated by their clinical and functional heterogeneity. Some older individuals developed diabetes years earlier and may have significant complications. Others may be newly diagnosed but may already have complications related to the disease. Some older adults with diabetes are frail with limited physical or cognitive abilities due to the presence of other underlying chronic conditions. Life expectancies are highly variable for this population, but often longer than clinicians realize. Providers caring for older adults with diabetes must take this heterogeneity into consideration when setting and prioritizing treatment goals.
Screening for microvascular diabetes-related complications is as important in older adults as it is in younger individuals, with attention directed to complications that can result in functional impairments if these remain untreated. While the natural history of diabetic retinopathy is different in those above age 70, recommendations for periodic eye examinations to detect not only changes related to diabetic retinopathy, but also for cataracts, macular degeneration, or glaucoma are important in allowing for early detection of disorders that can progress to cause visual impairment.
Annual measurement of serum creatinine and urine microalbumin allow for identification of nephropathy and chronic kidney disease due to other causes that can have their progression modified by dietary interventions and use of medications to lower blood pressure. Annual measurement of a lipid profile with interventions to treat those identified as having dyslipidemia can modify risk for cardiovascular events, which are associated with morbidity, decreased quality of life, and mortality.
Regular foot examinations with identification of anatomic abnormalities and sensory deficits that can reduce mobility are recommended. Medicare will cover the cost of special shoe wear for individuals with diabetes complicated by neuropathy or foot deformity. Pedorthic shoe wear is characterized by increased depth with a wider toe box that reduces pressure points that predispose to ulcer formation. Many prescriptions for shoe wear also include orthotics that allow for more even pressure distribution, thus improving the ability to walk without concern for foot injury.
Acute Hyperglycemic Complications
Hyperglycemic hyperosmolar nonketotic syndrome (HHNS) is more common in elderly patients than diabetic ketoacidosis (DKA). HHNS can occur in patients with and without a history of type 2 diabetes. It is characterized by severe elevations in BG (>600-800 mg/dL), plasma hyperosmolarity (>320 mOsm/L), severe dehydration, and absent to mild acidosis. The development of HHNS in the elderly population can be attributed, in part, to an impaired thirst mechanism and an age-related increase in the renal threshold for reabsorption of glucose leading to an osmotic diuresis and intravascular volume contraction. Predisposing factors include myocardial infarction, pneumonia, infections, use of certain medications (eg, diuretics, phenytoin, glucocorticoids), or any acute medical illnesses. Patients often present with an altered mental status (lethargy, coma), marked volume depletion, orthostatic hypotension, and prerenal azotemia. Urine and serum ketones can be mildly elevated but usually not to the degree observed with diabetic ketoacidosis.
HHNS is a life-threatening disorder that requires prompt therapy with intravenous fluids and close monitoring of cardiac status. In addition to therapy directed toward treatment of the precipitating event (if known), extracellular fluid volume deficits, which can be profound, are replaced initially with normal saline followed by half-normal (0.45%) saline. Half of the fluid and electrolyte deficits can be replaced in the first 24 hours and the remainder over the next 48 hours.
Once volume replacement is addressed, low-dose intravenous infusions of insulin (5 U bolus followed by 1-5 U/h) can be initiated. The administration of insulin prior to volume correction can exacerbate intravascular fluid depletion and further compromise renal function as glucose shifts to the intracellular compartment. Potassium deficits can be addressed once urine output is established. Following resolution of the hyperglycemia, patients require careful evaluation of the cause of the deterioration as well as attention to the need for ongoing management of hyperglycemia with insulin or oral agents.
Care of the Elderly Patient with Diabetes in the Hospital
Hyperglycemia frequently accompanies acute illnesses that prompt hospitalization in patients with and without a history of diabetes. Newly recognized hyperglycemia adversely affects patient outcomes to a greater extent than established diabetes, with longer hospital length of stay, higher mortality, and increased likelihood of discharge to an extended care or rehabilitation facility. For these reasons, attention to glycemic control is as important during periods of hospitalization as it is in the outpatient setting.
The ability to achieve tight glycemic control in the hospital is hampered by rapid changes in clinical status, as well as by hospital routines that can increase risk for undetected hypoglycemic events that are associated with adverse patient outcomes. Current guidelines suggest glycemic targets of 140 to 180 mg/dL in both critically ill and non-critically ill-hospitalized patients. In critical care settings, this can be achieved with validated IV insulin infusion protocols. In non-critically ill patients, scheduled subcutaneous basal-bolus insulin is preferred. Less stringent glycemic targets may be appropriate for patients who have multiple comorbidities and reduced life expectancy, but in general, glucose levels should be maintained at values below 200 mg/dL to minimize fluid and electrolyte abnormalities, reduce renal complications, and avoid infections.
The practice of using sliding scale insulin as the only glycemic management strategy in hospitalized patients is discouraged. These regimens are associated with both hypoglycemia and hyperglycemia as they encourage reaction to a single BG value rather than a rational management strategy. Oral and injectable noninsulin glucose-lowering agents have a limited role for hospital use but may be appropriate for selected non-critically ill patients.