Diabetes mellitus is a chronic condition characterized by elevated blood glucose that occurs as a result of impaired insulin action or production. This article focuses on current recommendations for the treatment of type 2 diabetes and methods of controlling co-occurring conditions.
According to the American Diabetes Association (ADA), 18.8 million people in the United States have been diagnosed with diabetes, and another 7 million are thought to have the disease but have not yet been diagnosed.1 An additional 79 million Americans have prediabetes, which is a condition that indicates that the patient has a high risk for developing diabetes. The majority of patients with diabetes are 20 years old or older, of whom about 13 million are men and 12.6 million are women.1 In 2010, about 1.9 million people aged 20 years or older were newly diagnosed with diabetes.
The indirect and direct costs of diabetes are increasing. In 2007, the total cost of diabetes was approximately $174 billion dollars. Medical expenses for patients with diabetes were 2 times higher than for those without diabetes. Indirect costs for diabetes total approximately $58 billion dollars, including workplace absenteeism and unemployment due to diabetes related disabilities.1
In 2007, diabetes was the seventh leading cause of death in the United States, although the incidence of diabetes-related death is likely underreported.1 Diabetes is also the leading cause of several health conditions, including kidney disease, heart disease, blindness and stroke. Uncontrolled diabetes can lead to complications such as periodontal disease, impaired immune system response, blindness, hypertension, sexual dysfunction and complications in pregnancy.1
There are 4 different types of diabetes, each with different insulin defects. Type 1 diabetes (resulting from B-cell destruction, and leading to absolute insulin deficiency), type 2 diabetes (resulting from progression of insulin secretory defects with insulin resistance), gestational diabetes mellitus (GDM) (diabetes discovered during pregnancy that was not overt diabetes) and diabetes induced by other causes (drug- or chemical-induced, genetic defects in B-cell function, genetic defects in insulin action, and disease of the exocrine pacreas).2 Type 2 diabetes is by far the most prevalent form in the United States, accounting for more than 90% of adult diabetes cases.1 This review will focus on type 2 diabetes treatments and recommendations.
SIGNS AND SYMPTOMS
The hallmark symptoms of hyperglycemia are polyuria, polydipsia, and polyphagia. Patients with type 1 diabetes usually present with rapid onset of symptoms, however patients with type 2 diabetes are often asymptomatic for many years and experience a gradual progression of symptoms and chronic complications.2 In order to identify diabetes in asymptomatic patients, routine screening of patients at high risk for developing type 2 diabetes is recommended. Testing should begin at any age for adults with a Body Mass Index (BMI) ≥25 kg/m2 and a known risk factor for diabetes (physical inactivity, history of cardiovascular disease (CVD), women with polycystic ovary syndrome). All patients should be screened for diabetes starting at aged 45 and should be retested at least every 3 years. The recommendations for screening are listed in Table 1 (page 56).
Unlike other disease states, the laboratory tests used to screen and diagnose diabetes are the same. The 4 laboratory values used to diagnose and screen diabetes are fasting plasma glucose, random plasma glucose, an A1c level, and an oral glucose tolerance test with a 75 gram load (Table 2, page 57). It is important to note that the ADA has established guidelines to determine if patients have impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). These are used to identify patients with prediabetes. The 3 laboratory values that indicate increased risk for diabetes (prediabetes) are fasting plasma glucose from 100-125 mg/dl, an A1c between 5.7%–6.4%, and a 2-hour plasma glucose from an oral glucose tolerance test with a 75 gram load between 140-199 mg/dl.
Once a diagnosis of prediabetes or diabetes has been established, slowing the progression of the disease and reducing the risk of complications should become the focus of therapy. Patients with diabetes often have cardiovascular risk factors such as dyslipidemia, hypertension and obesity. Treating the risk factors is an important part of reducing cardiometabolic risk.2 A diabetes evaluation should include a complete medical history, physical examination, laboratory evaluation, and other possible referrals.2 Several key issues of importance to pharmacists include diabetes-related complications, hypoglycemia awareness, comprehensive foot examinations, laboratory testing for fasting lipid panel, liver function tests, serum creatinine, and urine albumin excretion. Because pharmacists have access to patients’ prescription records, it is important to make recommendations to other providers based on these findings, especially if the patient sees multiple specialists.
ASSESSMENT OF GLUCOSE CONTROL
ADA and the American Association of Clinical Endocrinologists (AACE) have each established criteria for glycemic control for A1c, and for preprandial and 2-hour postprandial numbers. Glycemic control is the fundamental aspect of diabetes management.2,3 Please refer to Table 3 (page 57) for specific goals for each of the 2 organizations. Glycemic control can be monitored through a combination of A1c testing and self-monitoring of blood glucose. The A1c test measures glucose control over time, usually reflecting blood glucose levels in the blood over 6 to 12 weeks prior to administration of the test. For patients who are at goal and well controlled, twice a year A1c testing is recommended. Quarterly testing of A1c is recommended for those who are not meeting goals or who have received changes to their regimens.2 Monitoring A1c is a convenient way for healthcare providers to determine the effectiveness of treatment protocols, especially for those individuals who tend not to monitor their blood glucose regularly at home.
Successful home-monitoring of blood glucose is dependent on the patient’s ability to successfully use the blood glucose monitoring equipment, and willingness to be compliant with the recommended schedule. Results from self-monitoring can be used to evaluate treatment response, determine if glycemic targets are being met, identify hypo- and hyperglycemia and to adjust the treatment plan. It is recommended that patients receiving insulin injections multiple times per day check their blood glucose at least 3 times daily.2 However, patients with diabetes using less frequent insulin injections, noninsulin therapy or lifestyle modifications may be able to test blood glucose less frequently. Pharmacists can be instrumental in helping patients to understand how to properly use self-glucose testing equipment.
Diabetes management requires collaborative efforts from multidisciplinary care teams including physicians, nurses, pharmacists and dietitians. Experts appear to have reached a consensus that the management of diabetes is multifactorial and needs to be patient specific. Providers must treat each patient individually, taking into consideration the patient’s comorbid conditions, the ability of the patient to be compliant with medication therapy and monitoring, and the cost of treatment options when deciding on treatment regimens. The position statement issued jointly by the ADA and the European Association for the Study of Diabetes (EASD) describes options for treating diabetes.4 This was in line with the AACE and the American College of Physician Guidelines.3,5
The 7 key points that were addressed in the ADA/EASD position statement are:4
1. Individualized glycemic targets and glucose lowering therapies
2. Diet, education and exercise are the foundation for type 2 diabetes treatments plans
3. Use of metformin as the optimal first line drug unless contraindicated
4. After metformin, limited data guides treatments. Combination therapy with 1 or 2 additional agents is reasonable, minimizing side effects
5. Ultimately, insulin therapy alone or with other agents to maintain glucose control
6. Treatment decisions, when possible, should involve the patient focusing on their needs, values, and preferences.
7. A major focus on comprehensive cardiovascular risk reduction.
The goals of controlling blood glucose are to avoid acute symptoms of hypoglycemia, avoid instability in blood glucose over time, and to prevent or delay the development of diabetes complications without adversely affecting quality of life.4 When beginning medication therapy, consideration should be given to tolerability as well as cost of the drug as these are critical issues in patient compliance. The position statement of the ADA and EASD provides a stepwise approach to type 2 diabetes therapy. Once a patient is diagnosed, lifestyle modifications including diet, weight loss and exercise are encouraged.
Metformin monotherapy should be started at, or soon after diagnosis unless contraindicat
ed. The guidelines recommend checking A1c after 3 months and suggest adding a second agent if not at goal. Second-line agents include sulfonylureas, thiazolidinediones, DPP-4 inhibitors, GLP-1 agonists or insulin (basal).4 After a repeat A1c in 3 months, a third agent can be added if still not at goal. Table 4 (pages 65–66) provides an overview of the antihyperglycemic agents (not including insulin) used in type 2 diabetes. Combination products are available to increase patient adherence with taking medications, but this may limit providers from reaching maximum doses of individual components.
A major problem associated with diabetes is macrovascular complications. One of these complications, cardiovascular disease (CVD), is the major cause of morbidity and mortality for individuals with diabetes and is one of the largest contributors to the cost of diabetes.2 Hypertension and dyslipidemia are 2 common risk factors for CVD that often co-exist with type 2 diabetes. The ADA recommends routine blood pressure monitoring at each appointment for patients with diabetes. The 2013 ADA Guidelines now suggest a target blood pressure goal for diabetic patients of <140/<80 mmHg. This is a change from the previous target of <130/<80 mmHg. Lower systolic blood pressures, such as <130 mmHg may be appropriate for certain individuals if this level can be achieved without undue treatment burden.2 One clinical trial that led to changes in the blood pressure goal was the ACCORD trial. This examined whether lowering blood pressure to <120 mmHg provided greater cardiovascular protection compared to a blood pressure of 130 to 140mmHg in patients with Type 2 diabetes at high risk for CVD.9 The primary end points (nonfatal myocardial infarction, nonfatal stroke and CVD death) in the intensive treatment group had a hazard ratio of 0.88 (95% CI, .73-1.06; P=.20).9 From the prespecified secondary end points, only stroke and nonfatal stroke were statistically significantly reduced by the intensive blood pressure treatment at P=.01 and P=.03. The number needed to treat to prevent 1 stroke in the intensive arm was 89 and serious adverse events such as syncope and hyperkalemia were higher with intensive management. Lifestyle modifications are considered first line for blood pressure control including weight loss, moderation of alcohol intake, reduction of sodium and increase in potassium intake, and increased physical activity. Medication treatment should include either an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB). These medications are not only good for blood pressure control but also for diabetic nephropathy that is discussed later in the article.
Patients with type 2 diabetes have an increased prevalence of lipid abnormalities that can contribute to their high risk of CVD. The ADA recommends that patients be screened annually or more frequently until lipid goals are achieved. The primary goal is low-density lipoprotein (LDL) <100 mg/dl. Triglyceride levels <150mg/dl and high-density lipoprotein cholesterol >40 mm/dl in men and >50 m/dl in women are desired, but are secondary to LDL goals. Statins, in combination with lifestyle modifications, are the treatment of choice for LDL levels above goal. Unless otherwise contraindicated, all diabetic patients with overt CVD and patients over aged 40 years with at least one CVD risk factor (family history of CVD, hypertension, smoking, dyslipidemia or albuminuria) should be started on a statin regardless of initial LDL level.
Aspirin therapy has been shown to be effective for secondary prevention in reducing cardiovascular morbidity and mortality in diabetic patients with a history of CVD.2 A position statement from the ADA, the American Heart Association (AHA) and the American College of Cardiology Foundation (ACCF) in 2010, provided an updated recommendation for primary prevention in diabetic patients.10 It is reasonable to use low dose aspirin in diabetic patients with no history of CVD who are at an increased CVD risk (10 year risk of CVD events over 10%) as primary prevention. This generally includes most men over aged 50 years and women over age 60 years who have 1 or more of the following major risk factors: smoking, hypertension, dyslipidemia, family history of CVD and albuminuria.10 Clinical judgment should be used to determine if aspirin therapy is appropriate for those at intermediate risk until further research is available.
Microvascular complications associated with diabetes include retinopathy, nephropathy and neuropathy. The risk of these complications can be reduced when the A1c is controlled around 7%.2 Diabetic retinopathy can range from mild to severe and can lead to blindness. All patients with diabetes should have a dilated eye exam upon diagnosis and then yearly thereafter.2 Nearly 20% to 40% of diabetic patients develop diabetic nephropathy and it is the leading cause of end stage renal disease. A marker for the development of nephropathy is maintaining a persistent albuminuria in the range of 30 to 299 mg/24 hours, historically called microalbuminuria.2 Screening for increased urinary albumin excretion should be performed yearly by measurement of the albumin-to-creatinine ratio in a random spot collection. The most common neuropathies associated with diabetes are chronic sensorimotor distal symmetric polyneuropathy and autonomic neuropathy. All patients with diabetes should be screened for diabetic peripheral neuropathy (DPN) starting at diagnosis and then at least yearly thereafter. Early diagnosis is important because up to 50% of patients with DPN may be asymptomatic.2 This can be done by using tests such as the monofilament pressure sensation, vibration perception and pinprick sensation. Autonomic neuropathies can include constipation, erectile dysfunction and gastroparesis. These are often discovered upon history and physical examination during a provider visit. Treatments for the specific autonomic neuropathy may improve a patient’s quality of life, but they do not change the disease process.2
There are several vaccinations that patients with diabetes should receive. An annual influenza vaccine should be administered to all patients with diabetes greater than 6 months of age. A pneumococcal polysaccharide vaccine should be given once to patients greater than 2 years of age and then readministered after aged 64 years, with 5 years between vaccinations. Anyone who received the pneumococcal vaccine before 65 years of age can be given a second dose if 5 years have passed since the first dose, and immunocompromised or asplenic patients aged 19 to 64 years should be given a second dose five years after the first. A new recommendation is to administer the hepatitis B vaccine to any unvaccinated diabetic adult between aged 19 and 59 years. This change occurred in late 2012 at the request from the Advisory Committee on Immunization Practices of the CDC.2 Another vaccination to consider is the tetanus and pertussis vaccination, since patients may be using insulin needles and lancets.
Approximately 80% of individuals with type 2 diabetes are overweight or obese.11 A patient with a BMI between 25 and 25.9 is classified as overweight, while a patient with a BMI of 30 or greater is classified as obese.12 The 2013 ADA Guidelines recommend medical nutrition therapy (MNT) as a major component of diabetes prevention, management and self-management education. Prevention of diabetes should include implementation of lifestyle changes that that induce a moderate weight loss (7% body weight) with dietary strategies that reduce calories and intake of dietary fats.2 Alcoholic drinks should be limited to one drink per day for adult women and two drinks per day for adult men. Patients with type 2 diabetes are encouraged to perform moderate intensity aerobic physical activity for at least 150 min/week spread over 3 days/week. Additionally, patients should be encouraged to perform resistance training at least twice a week.2 Smoking cessation should be encouraged in all diabetic patients to reduce the risk of cardiovascular complications. Smoking cessation should combine use of nicotine replacement products along with counseling for optimal success.
Prevention of hypoglycemia is a key component of diabetes management. Mild hypoglycemia can be frightening to patients with diabetes and severe hypoglycemia can cause acute harm because it can cause falls, motor vehicle accidents or other injury.2 Hypoglycemia (a plasma glucose <70 mg/dl) requires ingestion of glucose or carbohydrate foods. The preferred treatment is 15 to 20 grams of glucose and then blood sugar should be checked 15 minutes after ingestion of the glucose. Once glucose levels have returned to normal, the patient should consume a meal or snack to prevent the recurrence of hypoglycemia.
Proper management of diabetes requires patients and caregivers to be educated and informed about all facets of the disease. Short-term daily complications like hyper- and hypoglycemia are common, but patients also need to be educated about skin, dental and eye care, as diabetes affects many components of a patient’s life. Table 5 shows complications of diabetes and the risk reductions associated with the preventive care interventions mentioned earlier. Preventing diabetic complications requires vigilance by both the patient and the healthcare team. The 2013 ADA Guidelines focus on Diabetes Self-Management Education Support (DSMS), which address’s self-management, quality of life, psychosocial issues, and emotional well being as associated with positive diabetes outcomes. The care of diabetes patients is shifting to a more patient-centered approach and places the patient at the center of the care model while working in collaboration with a variety of healthcare professionals.2
It is currently estimated that 8.3% of the population of the United States has diabetes.1 Worldwide, the incidence of type 2 diabetes is also increasing, and the total number is expected to rise to 552 million by 2030 according to the International Diabetes Federation Diabetes Atlas.13 As the incidence of obesity rises, so will the rates of type 2 diabetes. Patients will need individual care plans to address multifactorial areas of their diabetes care for success in meeting goals.
1. Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011.
2. American Diabetes Association. Standards of medical care in diabetes 2013. Diabetes Care 2013; 36(Suppl 1); S11-S66.
3. Handelsman Y, Mechanick JI, Blonde L, et al.; AACE Task Force for Developing Diabetes Comprehensive Care Plan. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract 2011;17(Suppl. 2):1–53.
4. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Diabetes Care. 2012;35:1364–1379.
5. Qaseem A, Humphrey LL, Sweet DE, Starkey M, Shekelle P. Clinical Guidelines Committee of the American College of Medicine. Oral Pharmacologic treatment of type 2 diabetes: a clinical practice treatment guideline from the American College of Physicians. Ann Intern Med. 2012;156:218–231.
6. Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32:193-203.
7. Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract 2009;15:540-59.
8. Lexi-Comp, Inc. (Lexi-DrugsTM ). Lexi-Comp, Inc.; December 22, 2012.
9. Cushman WC, Evans GW, Byington RP, et al. ACCORD Study Group. Effect of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575-1585.
10. Pignone M, Alberts MJ, Colwell JA, et al. Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Circulation 2010;121:2694–2701.
11. Sluik D, Boeing H, Montoned J, et al. Associations between general and abdominal adiposity and mortality in individuals with diabetes mellitus. Am J Epidemiol 2011;174:22–34.
12. Defining overweight and obesity. Department of Health and Human Services, Centers for Disease Control and Prevention website. http://www.cdc.gov/obesity/adult/defining.html. Accessed December 14, 2012.
13. International Diabetes Federation. IDF Diabetes Atlas, 5th edn. Brussels, Belgium: International Diabetes Federation, 2011. http://www.idf.org/diabetesatlas. Accessed December 28, 2012.