Type 2 Diabetes

Posted by • April 6th, 2012

The latest article in our Clinical Practice series provides a framework for establishing glycemic targets for patients with type 2 diabetes, taking into account both psychosocial and clinical factors, and discusses strategies to achieve the targets. First-line treatments and additional therapies are discussed.

T2DM is the leading cause of blindness, nontraumatic lower-limb amputation, and chronic kidney disease in the United States. It is a major cause of cardiovascular disease (CVD), leading to early mortality. According to the Centers for Disease Control and Prevention, the number of persons with T2DM in the United States will more than triple by 2050 from the current estimate of 26 million. The increasing incidence of T2DM is largely attributable to changes in lifestyle (diet and activity levels) and obesity.

Clinical Pearls

• What are the American Diabetes Association criteria for diagnosis of Type 2 diabetes mellitus?

The diagnosis of T2DM, as outlined by the American Diabetes Association (ADA), is based on a HbA1c level greater than or equal to 6.5%, or fasting plasma glucose level greater than or equal to 126 mg/dl (7.0 mmol/l), or a 2-hour plasma glucose greater than or equal to 200 mg/dl (11.1 mmol/l) during an oral glucose tolerance test. The diagnosis can also be established by classic symptoms of hyperglycemia and a random plasma glucose greater than or equal to 200 mg/dl. Test results need confirmation using the above criteria, unless the diagnosis is obvious based on symptoms.

• What are the goals of glycemic control in patients with type 2 diabetes?

Long-term follow-up of patients with newly-diagnosed T2DM enrolled in the U.K. Prospective Diabetes Study showed a reduced risk of CVD events 10 years after the end of the trial among those initially randomized to intensive glycemic management, as compared with conventional therapy (average HbA1c of 7.0% versus 7.9%). Results of three trials in older patients with established T2DM and a history of or risk factors for CVD showed no reduction in total mortality or CVD-related mortality (and increased mortality in the ACCORD study) from intensive lowering of glucose to near- ormal levels using multiple agents, compared to standard glycemic control. A first step in glycemic management is setting an appropriate glycemic target in each individual patient. Current guidelines specify HbA1c targets of <7.0% or <6.5%. However, the appropriateness of these goals vary with different clinical characteristics and psychosocial factors, including the patient’s capacity for self-management and home support systems. In general, in patients with recently recognized T2DM and few (or no) complications (especially younger patients), a near-normal glycemic target aimed at prevention of complications over the many years of life can be suggested. In contrast, in older individuals with CVD (or multiple CVD risk factors) higher targets are often appropriate.

Figure 2. Suggested Goals for Glycemic Treatment in Patients with Type 2 Diabetes.

Morning Report Questions

Q: What are appropriate lifestyle modifications for patients with Type 2 DM?

A: Weight loss and exercise are important nonpharmacologic approaches to improve glycemic control. A balanced diet rich in fiber, whole grains, and legumes, containing <7% saturated fat and reduced trans fats, and limited in calories and high glycemic index foods, is recommended by the ADA. Exercise has an additive effect to caloric restriction on glycemic control. Patients should be encouraged to perform at least 150 minutes per week of moderate-intensity aerobic exercise.

Q: What are the guidelines for medical treatment in Type 2 DM?

A: Of the potential strategies for glycemic control, lifestyle modification and metformin are preferred and are cost- ffective. By stimulating AMP-activated protein kinase, metformin reduces hepatic glucose production. It causes no weight gain or slight weight loss, and rarely causes hypoglycemia. Patients with high chronic baseline HbA1c (~9.0%) are unlikely to achieve adequate glycemic control with metformin alone, and in patients with significant hyperglycemia (>300  to 400 mg/dl; HbA1c >10-12%), initial insulin therapy should be considered. If metformin monotherapy cannot be used, other oral agents such as a sulfonlyureas (insulin secretagogues), dipeptidyl peptidase IV inhibitors (e.g., sitagliptin, inhibits the degradation of GLP-1 and results in modest elevations of circulating GLP-1 levels; does not cause weight gain), pioglitazone (activates PPAR-gamma, which enhances insulin sensitivity in peripheral tissue and reduces hepatic glucose production) or a GLP-1 receptor agonist (e.g., exenetide or liraglutide, injectable agents that are structurally similar to endogenous GLP-1) can be initiated. Over time, additional medications become necessary for glycemic control. A logical strategy is to consider agents with complementary modes of action. Strong evidence is lacking to support any one particular second agent over another. Perhaps due to reluctance of patients and providers, insulin is generally added much later than medically indicated.

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