CIPLADOC - Cardiology Update - Cardiology Publications - Diabetic Dyslipidemia - Prevalence and Nature of dyslipidemia in diabetes mellitus

CARDIOLOGY - Publications

Practical Guidelines For the Management of
Diabetic Dyslipidemia

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Prevalence and Nature of dyslipidemia in diabetes mellitus

Diabetes mellitus is associated with an increased risk of cardiovascular disease. In both types of diabetes, abnormalities of lipid metabolism are prevalent, but the nature of these abnormalities is different.
In case of type 1 (insulin-dependent) diabetes mellitus, poor glycemic control and the presence of nephropathy is associated with lipid abnormalities.
Dyslipidemia is observed in practically all patients of type 2 (noninsulin-dependent) diabetes. Lipid abnormalities are observed even in those with good glycemic control and in the absence of any renal disease. The most common pattern of dyslipidemia in these patients is elevated triglyceride levels and decreased HDL cholesterol levels. The concentration of LDL cholesterol in type 2 diabetic patients is usually not significantly different from nondiabetic individuals. However, type 2 diabetic patients typically have a preponderance of smaller, denser LDL particles, which increases atherogenicity even if concentration of LDL is not significantly increased. Insulin resistance is a strong candidate as the underlying abnormality responsible for all these changes.
The following table outlines the lipid abnormalities observed in diabetic patients.

Lipid and lipoprotein abnormalities in diabetes mellitus

Diabetes Category	Lipids and Lipoproteins
Type 1 diabetes
Usual levels of glycemia (Euglycemia)	Similar to non-diabetic population
Poor glycemic control	Increased triglycerides Increased LDL susceptibility to oxidation
Diabetic nephropathy	Increased LDL cholesterol Decreased HDL cholesterol Increased lipoprotein(a)
Type 2 diabetes
Usual levels of glycemia (Euglycemia)	Increased triglycerides Decreased HDL cholesterol Small, dense, LDL particles Increased LDL susceptibility to oxidation
Poor glycemic control	Worsening of hypertriglyceridemia
Diabetic nephropathy Increased triglycerides	Decreased HDL cholesterol Increased lipoprotein (a)

Risks associated with diabetic dyslipidemia

Both type 1 and type 2 diabetes mellitus are associated with increased risk of CHD.
Studies have shown that blood glucose and/or insulin levels may be associated with an increased risk of CHD in diabetic patients.
Further, the risk of CHD among diabetic patients is directly related to the levels of blood pressure, cigarette smoking and total cholesterol. At any level of these risk factors, diabetic patients probably have four to five times the risk of CHD among NIDDM patients.

The Joslin Clinic study showed that 35% of patients with type 1 diabetes died from CHD before the age of 55. In patients with type 1 diabetes, the presence of nephropathy increases the risk of CHD 15 fold.
The Framingham study showed that risk of cardiovascular death was increased 4.5 fold in women and 2 fold in men with predominantly type 2 diabetes.
Seventy five to 80% of adult diabetic patients die from coronary heart disease (CHD), cerebrovascular disease and/or peripheral vascular disease.

Etiology of diabetic dyslipidemia

Insulin deficiency reduces lipoprotein lipase (LPL) activity and results in defective removal of triglyceride-rich lipoproteins. The dyslipidemia seen in many diabetic patients - high triglycerides and low HDL cholesterol - is associated with low LPL activity.
Low cholesteryl ester transfer protein (CETP) is observed in NIDDM patients while its activity tends to be high in IDDM patients. Cholesteryl ester transfer protein mediates the exchange of cholesteryl esters in HDL particles for triglycerides in VLDL particles. It may be therefore important for reverse cholesterol transport. Accordingly, high CETP activity might inhibit atherosclerosis by accelerating the removal of excess cholesterol from the arterial wall. However, CETP produces VLDL particles that are cholesteryl-ester enriched and ultimately decreases HDL levels - two potentially atherogenic lipoprotein changes observed commonly in diabetes.
LDL levels may not be significantly elevated in diabetic patients. However, they may be modified to forms that promote atherogenesis. For example, nonenzymatic glycation may cause LDL to be rapidly internalized by macrophages, thus accelerating the process of atherosclerosis. Elevated glucose levels may also favour the production of oxidized LDL, the first step in the process of atherosclerosis.
Reduced HDL cholesterol levels may be due to increased catabolism, resulting from increased hepatic triglyceride lipase action of HDL particles with higher triglyceride content.

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