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| Diabetes in the Elderly Chapter 5 – Samira Kirmiz, MD Fellow in Endocrinology, UCLA/WLA VAH Jane E. Weinreb, MD Assoc Professor of Medicine, Chief Diabetes Program, VA Greater LA Health Care System Updated 13 May 2008 TO OBTAIN A DOWNLOAD OF THIS CHAPTER IN WORD OR PDF FORMAT, CLICK HERE |
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The geriatric population has a very high prevalence of diabetes. In fact, 5.4 million elderly American individuals have already been diagnosed with diabetes and an additional 2.4 million have diabetes and are yet to be diagnosed (1). Additionally, diabetes is a major cause of morbidity and mortality in this population, with the latter largely attributable to macrovascular complications. Older diabetics also carry a disproportionate burden from microvascular complications, presumably related to longer duration of diabetes (2). The National Health and Nutrition Examination Survey (NHANES III 1988-1994) indicated that patients older than 65 years make up 40% of the diabetic population in the United States, and it is projected that this will increase to 66% by the year 2025 (3, 4). This chapter deals with diabetes care and goals of care for the geriatric population.
Age and weight are both risk factors for the development of diabetes. It has been noted that in normal aging there is a two mg/dL/decade rise in fasting plasma glucose, placing elderly patients at increased risk for the development of diabetes. Weight gain is often seen with rising age, resulting in worsened insulin resistance at the level of muscle and fat. Hence, beta cell function is taxed not only by impaired function with age per se, but also through worsening insulin resistance in the setting of weight gain. Additionally, in the elderly there are often concomitant diseases, decreased activity, and medications which can worsen insulin resistance.
The types of diabetes in the elderly population include Type 1, Type 2, latent autoimmune diabetes of adulthood, and other types. The last classification group includes diabetes due to underlying defined genetic syndromes; drug, toxin, or endocrinopathy induced diabetes; and a variety of other relatively uncommon etiologies (see the American Diabetes Association [ADA] diabetes classification for further details) (5).
Type 1 diabetes mellitus results from autoimmune destruction of the beta-cells of the pancreas, ultimately leading to insulin deficiency. It occurs in genetically susceptible people and is influenced by environmental factors. Latent autoimmune diabetes of adulthood is a subset of type 1 diabetes seen in adults. These patients have a slower loss of beta cell function than do traditional type 1 patients. Hence, they may initially be able to achieve glycemic control on oral agents for a period of time before needing to be transitioned to insulin. These patients are more often relatively thin and may lack a family history of diabetes. They need to be closely monitored for transition to insulin and for development of ketosis (5).
Type 2 diabetes mellitus results from increased insulin resistance which is superimposed on an inability of the pancreas to keep up with the insulin needs of the person(5). Type 2 diabetes can generally be treated with lifestyle changes and oral agents early in its course. However, beta cell function progressively declines, often with ultimate beta cell failure, thereby requiring insulin treatment. 85-90% of diabetics are type 2; they tend to be overweight or obese and have a strong family history of diabetes (1).
The diagnostic criteria for diabetes remains constant across all ages. Diabetes is diagnosed with fasting glucose greater than or equal to 126 mg/dl; symptoms of hyperglycemia and a random glucose equal to or greater than 200 mg/dl; or a 75 gram oral glucose tolerance test with a two hour value equal to or greater than 200 mg/dl. For diagnosis each of these tests must be confirmed on another day unless unequivocal symptoms of hyperglycemia are present (6).
In an elderly population, screening for diabetes should be considered in light of its increased prevalence. The ADA recommends that all adults over age 45 are screened with a fasting plasma glucose, and if this is normal (<100 mg/dl), it can be repeated in three years. If the patient is found to have impaired fasting glucose (100-125 mg/dl) or impaired glucose tolerance (2 hour glucose 140-199 mg/dl on 75 gram oral glucose tolerance test), screening is recommended yearly (6).
There is a distinction between diabetes diagnosed at an earlier age as opposed to diagnosis while elderly. Patients who have had diabetes for a longer period of time have an increased rate of microvascular complications compared with those with a diagnosis of diabetes at a later age. The incidence of macrovascular complications appears to be similar in elderly diabetics regardless of duration of the disease (4).
This section will address some common diabetes management issues in an elderly population. Please see the chapters of the Endotext on modalities of treatment of diabetes for further details.
The American Geriatrics Society (AGS) guidelines for the management of diabetes in the elderly identify syndromes which elderly patients with diabetes are at increased risk of having in comparison to age matched non-diabetic patients (Table 1) (4, 7). Care of the elderly diabetic patient should include heightened screening and treatment of these syndromes.
In addition to the areas targeted by the AGS, other targeted areas of therapy of elderly diabetic patients include: hypoglycemia, hyperglycemia, medication errors, and vision problems (4, 7).
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Table 1. Associated syndromes in elderly diabetic patients. |
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Polypharmacy Depression Cognitive Impairment Urinary Incontinence Injurious Falls Pain |
The AGS guidelines (4) indicate that elderly diabetics are often on multiple prescription medications secondary to their diabetes as well as other comorbidities. This can lead to increased side effects, drug-drug interactions and confusion about how and when to take medications. Each assessment of an elderly patient with diabetes should address and document what medications a patient is taking and how they are being taken. Documentation of potential adverse effects as well as benefits and risks of a medication should occur with each new medication prescribed (4).
When compared with age matched non-diabetic patients, elderly diabetic patients are at increased risk of depression. Additionally, the AGS guidelines identify that there is underdetection and undertreatment of this problem in the elderly diabetic population. It is therefore recommended that one screens for depression on an initial visit. In addition, when an elderly diabetic patient presents with new symptoms, consideration should be given to depression as an etiology of these symptoms (4).
There is an increased risk of cognitive impairment in elderly diabetic patients (8). This impairment may hinder their ability to comply with treatment recommendations and medications (4), and may contribute to increased mortality (9). The AGS recommends an assessment of cognitive status with the initial visit of a diabetic patient and with any change in clinical condition (4).
Elderly female diabetics have an increased risk of urinary incontinence; this should be kept in mind in the evaluation and management of these patients. An initial assessment and examination to evaluate the etiology of urinary incontinence should be performed. The AGS guidelines note that factors which may exacerbate urinary incontinence in female diabetics include: polyuria due to hyperglycemia, neurogenic bladder, fecal impaction, bladder prolapse, atrophic vaginitis, vaginal candidiasis, and urinary tract infections (4).
The AGS recognizes that elderly diabetic patients are at increased risk of falls resulting in injury. These falls result in significant morbidity and mortality in the elderly population. Factors which may contribute to increased fall risk include frailty, visual impairment, peripheral neuropathy, hypoglycemia, and polypharmacy. It is recommended that one screen for fall risk as well as provide education on fall prevention (4, 10).
Elderly diabetic patients are at risk of neuropathic pain. This pain is often undertreated. The AGS recommends screening for and treatment of this pain (4).
Hypoglycemia in the elderly population may not be as apparent as in younger diabetics. Lethargy and confusion as well as the traditional hypoglycemic symptoms such as hunger, sweating, irritability, anxiety and shaking should prompt a concern for hypoglycemia and a capillary blood glucose level should be checked. Additionally, family members and caregivers of elderly diabetics should be educated regarding the signs of hypoglycemia, permitting its rapid identification and treatment.
The UKPDS showed that hypoglycemia was one of the limiting factors in achieving optimal glycemic control (11). In fact, as tighter glycemic control is obtained, risk of hypoglycemia increases. Hypoglycemia can be even more worrisome in older patients who are frail or have significant comorbid conditions. The ramifications of hypoglycemia may be more severe, especially in the setting of delayed recognition, hence delaying treatment.
Treatment goals in older diabetics should be individualized based on patient and/ or family goals, comorbidities and willingness to comply with medication and lifestyle recommendations (8, 12). Additionally, patients with dementia represent a unique challenge that may necessitate modification of treatment goals. Lastly, treatment goals should also reflect a high level of concern over the risks associated with hypoglycemia in the elderly population (13).
Diet and exercise remain the cornerstones of therapy for diabetes and should be emphasized at each patient visit (5). Further therapeutic choices are broken down into oral hypoglycemia agents, insulin and the newer subcutaneous injectables.
α-Glucosidase Inhibitors: This class of medications includes acarbose (Precose) and miglitol (Glyset) and act to reduce absorption of glucose at the level of the small intestine by inhibiting α -glucosidase at the brush border. This results in a reduction of postprandial hyperglycemia, with a decrease in A1c by 0.5-1% (14). These medications have the benefit of not causing hypoglycemia when used as monotherapy. However, when used in conjunction with other agents, hypoglycemia can occur and needs to be treated with glucose specifically, as other carbohydrate absorption is delayed by inhibition of the intestinal breakdown.
The main side-effects which limit patient's compliance are abdominal bloating and diarrhea. These can be improved by limiting carbohydrate intake in a meal and by slowly titrating the medication.
Acarbose is contraindicated in patients with active hepatic disease. Miglitol is absorbed and excreted by the kidneys and is contraindicated with significant renal disease (14).
Amylin analogues: The only amylin analog on the market is pramlintide (Symlin). This agent acts by inhibiting postprandial glucagon release, thereby reducing hepatic glucose output, delaying gastric emptying, and enhancing satiety. These actions lead to improvement in postprandial hyperglycemia, and there may be some associated weight loss. A1C is decreased by 0.3-0.5% (15). Pramlintide is indicated as adjunctive therapy for patients with type 1 or 2 diabetes who inject insulin at mealtimes and have failed to achieve adequate glycemic control. Hypoglycemia associated with its use can be severe, especially in type 1 diabetics, and reduction of mealtime insulin doses is recommended when therapy with pramlintide is initiated. Additional drawbacks of pramlintide therapy include its high cost as well as the need to take additional subcutaneous injections prior to each meal.
Biguanides: The only biguanide available in the United States is metformin hydrocholoride. Metformin's mechanism of action has not been fully elucidated, but it appears to exert its major effect by reducing hepatic glucose production. It generally reduces A1c by 1-2% (16). Maximal effect is usually seen at a dose of 2000 mg/day, but the dose can be titrated as high as 3000 mg/day. Significant benefits of metformin include absence of hypoglycemia when used as monotherapy as well as absence of weight gain (16). The most common side-effects associated with metformin include, bloating, flatulence, and diarrhea. These generally improve with low dose initiation and slow titration.
The most worrisome, though very rare, side-effect of metformin is lactic acidosis. This can be lethal and results from accumulation of the medication (16). It is seen more often in patients with impaired renal function, active liver disease, sepsis, heart failure or advanced pulmonary disease. Hence, metformin often needs to be withheld during hospitalizations.
Since metformin is exclusively excreted by the kidneys, its use is contraindicated in women with serum creatinine above 1.4 mg/dl or men with creatinine above 1.5 mg/dl (17). Caution should be used in looking strictly at creatinine, rather than renal function, in the elderly population, as creatinine alone may underestimate renal impairment in this population due to declining muscle mass. Instead clinicians should focus on renal function and metformin should be avoided when the creatinine clearance is below 60 ml/min. Additionally, the medication should be temporarily suspended in situations in which renal function may rapidly decline such as during hospitalizations and at the time of iodine related contrast exams. It can be restarted when it is clear that renal function has not been compromised.
Metformin can also impact Vitamin B12 levels though this is rarely clinically relevant.
In general metformin is well tolerated and has a positive impact on glycemic control. It is an optimal starting agent in elderly population patients in whom it is important to avoid hypoglycemia. However, in an elderly population special attention should be paid to their renal function while using metformin.
Dipeptidylpeptidase IV inhibitors: Sitagliptin is the first agent available in this class. This agent inhibits the breakdown of intrinsically made GLP-1 and GIP, thereby enhancing glucose stimulated insulin secretion and suppressing glucagon secretion. Data in vitro and in animal models suggest this class of drugs may also help preserve beta cell mass. Sitagliptin reduces A1c by 0.5-0.8%. It can be used as monotherapy or in combination with metformin or thiazolidinedione. It does not appear to cause hypoglycemia when used as monotherapy or in combination with metformin or thiazolidenediones. It is renally cleared and the dose needs to be adjusted for renal insufficiency (18). We still await long term data with this relatively new class of drugs.
Incretin mimetics: Exenatide is the first agent available in this class and exerts its effect by acting as an analog of the incretin glucagon-like peptide-1. It thereby enhances glucose stimulated insulin secretion, inhibits secretion of glucagon in a glucose dependent manner, slows gastric emptying, and acts centrally to promote satiety. Exenatide therapy results in significant weight loss in most, but not all patients. It is indicated for use in combination with sulfonylureas and/or metformin (19).
Exenatide generally reduces A1c by 0.5-1%. Up to 40% of patients have gastrointestinal side effects including nausea, vomiting and abdominal discomfort. These tend to decrease over time, and infrequently require the drug to be stopped (19). There have been 30 case reports of pancreatitis in patients on exenatide; further information regarding this relationship is awaited. Patients should be cautioned to discontinue the medication if severe abdominal pain occurs. Additionally exenatide is associated with hypoglycemia when used in combination with sulfonylureas, and one may consider decreasing the dose of sulfonylurea when exenatide is initiated or titrated.
Exenatide is dosed twice daily by subcutaneous injection (19). However, long acting preparations are currently in the pipeline.
Insulin: Exogenous insulin replaces or augments the total insulin present to achieve glycemic control. Insulin can be added to oral therapy in the elderly diabetic population as a basal injection of intermediate or long acting insulin to achieve glycemic control (20). However, if this does not achieve glycemic control, transition can be made to an insulin regimen with basal and prandial components; in this case, most oral diabetes medications can be discontinued, thus helping to eliminate polypharmacy. In elderly patients with a variable appetite, one can dose the prandial insulin post meal to reduce the risk of hypoglycemia (21).
In the elderly population, special care has to be taken to avoid hypoglycemia. Hence, increases in insulin dosage should generally occur gradually. At present, insulin is available for patient use only in a subcutaneous preparation.
Visual impairment need not hinder insulin administration. This can be addressed with the use of a pen device to dispense insulin or the attachment of a magnifying glass to the syringe.
Insulin use has been associated with weight gain which can lead to further insulin resistance and the need to increase the insulin dose. Because insulin is degraded by the kidneys, care must be taken to reduce the dose in the setting of renal impairment to avoid hypoglycemia.
Elderly patients with diabetes who should be considered for insulin therapy at the onset include those with type 1 diabetes, diabetes secondary to pancreatic insufficiency, or those with a history of ketonuria, weight loss, or severe symptoms (22).
Meglitinide: Nateglinide (Starlix) and repaglinide (Prandin) are the two meglitinides on the U.S. market. These agents stimulate insulin release by binding to the sulfonylurea receptor. In contrast to the older sulfonylurea agents, the meglitinides have a rapid onset and offset of action. As a result, they need to be taken shortly before meals and are more effective in controlling postprandial hyperglycemia. These medications are used before each meal, and this may pose a compliance problem in the elderly population who may have difficulty remembering such frequent dosing. They are, however, ideally suited to patients with inconsistent meal times or variable appetites.
Meglitinides generally reduce A1c by 1-2%, although repaglinide is more efficacious in lowering A1C than nateglinide (23). Side effects include hypoglycemia and weight gain. These medications are metabolized in the liver and should not be used with active liver disease, but they are quite useful in older patients with renal insufficiency.
Sulfonylurea: Glyburide (Diabeta, Glynase, Micronase), glipizide (Glucotrol), and glimepiride (Amaryl). These medications bind to the sulfonylurea receptor and stimulate insulin release. They generally reduce A1c by 1-2% and have a long track record of safety with a very extensive history of use (17).
Sulfonylureas are all hepatically metabolized and should be avoided in active liver disease. Glyburide has active metabolites and is renally cleared and thus should be avoided in those with renal disease as this can lead to profound hypoglycemia. Glipizide has inactive metabolites, and glimepiride is cleared through biliary circulation and thus may be safer in patients with renal impairment (17).
Side effects of sulfonylurea include hypoglycemia and weight gain. They should be used with caution in elderly patients with poor appetite or inconsistent meals, as their long duration of action in the setting of missed meals can lead to hypoglycemia. Glyburide is of most concern in this arena, making glipizide preferred in those >65 years of age.
Thiazolidinedione: Pioglitazone (Actos) and rosiglitazone
(Avandia). These medications activate
PPAR-gamma which leads to improved insulin sensitivity at the level of fat and
muscle. As a result, they may
preserve beta cell function to some degree and increase the duration until
additional therapy is required (24). Thiazolidinediones
generally have a very slow onset of action, and hence months may elapse before
their full impact on glycemic control is
evident. They lower A1c by 1-1.5%. They do not cause hypoglycemia when used as monotherapy
and can be dosed once daily (17).
Thiazolidinediones have several remarkable side effects. Weight gain has been noted due to increased fat deposition in the subcutaneous tissue. Both medications in this class cause fluid retention that can result in increased incidence of peripheral edema as well as heart failure; this has resulted in a black box warning by the FDA. A recent meta-analysis concluded that rosiglitazone may cause increased risk of myocardial infarction as well, although this needs to be confirmed (25). Additionally, both agents appear to cause increased appendicular bone loss and fractures (26). Lastly, these medications undergo hepatic metabolism and should not be used in patients with hepatic dysfunction.
The United Kingdom Prospective Diabetes Study (UKPDS) in type 2 diabetics and the Diabetes Control and Complications Trial (DCCT) in type 1 diabetics
revealed decreased onset and slowed progression of microvascular complications with tight glycemic control (11, 27). This came at the expense of increased frequency of hypoglycemia. Hence, in an elderly diabetic population which may be prone to frailty, one needs to carefully balance the expected benefits with risk. Therapeutic goals should address the wishes of the patient and family, and should take into consideration patient comorbidities as well as life expectancy. Hence, therapeutic goals need to be tailored for each individual patient.
In addition to a focus on glycemic control, care should also be undertaken in the elderly population to focus on additional goals of therapy. The elderly population with diabetes has a very high rate of macrovascular and microvascular complications, and hyperglycemia is only one of the contributors to these complications (27). Hence, other risk factors for complications, including hypertension, hyperlipidemia, and smoking cessation, need to be addressed in order to optimize outcomes.
The AGS
guidelines as well as the
The AGS as well as ADA treatment guidelines also address the microvascular complications and recommend a retinal exam at diagnosis and every year in higher risk patients (4, 6). This latter group includes elderly diabetic patients with symptomatic eye changes, retinopathy, glaucoma, cataracts, A1c > 8%, type 1 diabetes and blood pressure above goal (6). The AGS and ADA recommend foot screening at least annually (4, 5). The AGS guidelines recommend screening for microalbuminuria at diagnosis and annually with recommendations for therapy of microalbuminuria with an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker (4, 6).
Finally, the AGS and ADA guidelines recommend education of the patients regarding their diabetes. Education should include home capillary blood glucose monitoring, symptoms and treatment of hypoglycemia and hyperglycemia, nutrition counseling, exercise, as well as self foot care (4, 6).
The treatment of diabetes in the elderly population depends on clinical recognition and diagnosis of the disease. Individualized treatment goals can be achieved with individualized therapeutic regimens. These should be constructed with the cornerstones of therapy being diet and exercise. Care should be taken to avoid complications of therapy, especially hypoglycemia. Finally, aggressive prevention of microvascular and macrovascular complications should be undertaken, targeting the multiple contributors noted above, as the elderly diabetes population is especially at risk for these complications.