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		Literature Compendium

Current Concepts in Type 2 Diabetes

Volume 3
Special Considerations in the Management of Diabetes and Its Complications

Chapter 2
Management of Global Cardiovascular Risk Factors in Type 2 Diabetes

While controlling blood glucose is important in people with Type 2 diabetes, managing cardiovascular risk factors is equally, if not more, important. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in those with Type 2 diabetes, and hypertension and dyslipidaemia are major risk factors for CVD. Treating these modifiable risk factors is a major component of diabetes management.

Obesity is a major risk factor for CVD and has been strongly associated with insulin resistance and diabetes. Insulin resistance may be a mechanism by which obesity leads to CVD. Weight loss has been shown to improve cardiovascular risk, decrease insulin concentration, and increase insulin sensitivity. Obesity and insulin resistance also have been shown to be associated with other risk factors, such as hypertension.

Physical inactivity is another modifiable major risk factor for diabetes and CVD. Exercising and losing weight have been shown to prevent or delay the onset of Type 2 diabetes, reduce blood pressure, and help to reduce the risk for heart attack and stroke. It is likely that any type of physical activity is similarly beneficial.

Hypertension has long been recognized as a major risk factor for CVD. The positive association between hypertension and insulin resistance is well recognized. When a person has both hypertension and diabetes—a common combination—the risk for CVD roughly doubles.

Atherogenic dyslipidaemia, often called diabetic dyslipidaemia in persons with diabetes, is a condition associated with insulin resistance and diabetes. This type of dyslipidaemia is characterized by hypertriglyceridaemia, high levels of low-density lipoprotein (LDL) cholesterol, and low levels of high-density lipoprotein (HDL) cholesterol. This 'lipid triad' often occurs in individuals with early coronary heart disease. Growing evidence suggests that all of the components of the lipid triad can contribute to the development of atherosclerosis.

In this chapter, 3 key papers addressing the management of global cardiovascular risk in individuals with diabetes are reviewed.

The American Diabetes Association (ADA) has published guidelines for the management of dyslipidaemia¹ and hypertension² in adults with diabetes. Management of these conditions—each an independent risk factor for CVD—is particularly important in persons with diabetes because Type 2 diabetes itself is associated with a 2- to 4-fold excess in the risk of CVD. The ADA dyslipidaemia guideline¹ discusses the prevalence of dyslipidaemia in persons with Type 2 diabetes, presents the results of clinical trials assessing lipid lowering in those with diabetes, and reviews the evidence base evaluating the lipid-lowering effects of medical nutrition therapy, physical activity, and anti-diabetic pharmacotherapy. It provides specific recommendations for screening and treatment of lipid disorders. The experts who developed the guideline state that aggressive therapy of diabetic dyslipidaemia will reduce the risk of CVD in individuals with diabetes and that primary therapy should be directed first at lowering levels of LDL cholesterol. The ADA hypertension guideline² reviews the evidence base for hypertension as a risk factor for diabetic complications, summarizes the results of landmark studies supporting target blood pressure levels in individuals with diabetes, and discusses the relative value of non-pharmacological and pharmacological approaches to the management of hypertension in individuals with diabetes. The experts who developed the guideline state that there is a strong epidemiological connection between hypertension and adverse outcomes in persons with diabetes. Current evidence supports the efficacy of antihypertensive pharmacotherapy in reducing the risk of CVD and other diabetes-related adverse outcomes. The authors recommend a target blood pressure of <130/80 mm Hg in persons with diabetes. They state that treatment decisions should be individualized based on the overall clinical condition of the patient—with particular emphasis on comorbidities, drug tolerability, personal preferences, and cost.

In a review of global risk management in individuals with Type 2 diabetes, Davidson³ discusses the implications for risk reduction of recent clinical trials, including the PROactive (PROspective pioglitAzone Clinical Trial In macrovascular Events) study, the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, and the Atorvastatin Study for Prevention of Coronary Heart Disease End Points in Non-Insulin-Dependent Diabetes Mellitus (ASPEN) study. All of these trials failed to meet their primary end points for reduction of cardiovascular events in diabetic populations; however, each demonstrated reduced risk in the secondary analyses. Based on these results, the author makes the case for achieving global CVD risk reduction in individuals with diabetes through LDL cholesterol reduction, blood pressure control, and glucose management. Emerging targets for risk reduction—including apolipoprotein B, triglyceride:HDL cholesterol ratio, LDL particle number, LDL particle size, and inflammatory markers—are also discussed.

As the papers reviewed in this section suggest, it is likely that the combination of hypertension, Type 2 diabetes, and dyslipidaemia produces an enhanced atherogenic environment within the circulation. In keeping with a global, multifactorial approach to CVD risk reduction, intensive glycaemic control could have multiple beneficial effects on the metabolic and vascular systems of individuals with Type 2 diabetes.

References

1. American Diabetes Association. Dyslipidemia management in adults with diabetes. Diabetes Care. 2004;27(suppl 1):S68-S71.

2. American Diabetes Association. Hypertension management in adults with diabetes. Diabetes Care. 2004;27(suppl 1):S65-S67.

3. Davidson MH. Global risk management in patients with type 2 diabetes mellitus. Am J Cardiol. 2007;99(suppl):41B-50B.

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The Literature Compendium is funded by an educational grant from Pfizer Inc.

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