Epidemiology Of Dyslipidemia In Type Diabetes

Given the predicted increase in the prevalence of diabetes worldwide and the progressive Westernization of lifestyles in developing countries, cardiovascular disease, which is increased two to five times in people with diabetes, has and will continue to have major implications for health and healthcare provision. Although the development of atherosclerosis and clinical vascular disease is multifactorial, dyslipidemia is a major contributing risk factor.

Dyslipidemia is common in patients with type 2 diabetes; it is present at the time of diagnosis, and even in the pre-diabetic phase. It persists despite usual hypoglycemic therapy and its expression will be affected by genetic and lifestyle characteristics, such as gender, obesity, exercise levels, diet, alcohol intake, poor glycemic control, smoking, hypothyroidism, as well as renal and hepatic function. It is also affected by concomitant drugs and the presence of primary dyslipidemia, such as familial combined hyperlipidemia.

The hallmarks of diabetic dyslipidemia are moderate hypertriglyceridemia (usually 1.5 to 3-fold increased) and reduced HDL cholesterol (approximately 10-20%); total and low-density lipoprotein (LDL) cholesterol are generally not different quantitatively from non-diabetics. For example, in the prospective cardiovascular munster (PROCAM) study in the North of Germany 39% of patients with diabetes had triglyceride concentrations >200 mg/dL (>2.3 mmol/L), versus 21% in non-diabetics, and 27% had low HDL cholesterol i.e. <35 mg/dL (<0.9mmol/L), compared with 16% in non-diabetics (13).

Qualitative changes in the LDL of patients with diabetes, however, suggest increased atherogenicity. In specific, LDL apoprotein B is susceptible to glycation and this decreases its affinity for the LDL receptor and increases its susceptibility to oxidative modification. In addition, the LDL subfraction distribution is altered in patients with diabetes. In specific, LDL is smaller and denser, a form more susceptible to oxidation and therefore more atherogenic (14).

Of the 347 978 men screened for participation in the multiple risk factor intervention trial (MRFIT) (15), 5163 were identified as having diabetes through reporting of medication. In the 12-year follow-up of this cohort, the absolute risk of cardiovascular death was increased threefold in patients with diabetes after adjustment for age, race, income, serum cholesterol, systolic blood pressure and cigarette smoking. With increasing serum cholesterol cardiovascular deaths increased both in men with and without diabetes; however, for given cholesterol level, men with diabetes had a two- to three-fold excess risk of cardiovascular disease. This was also true for two other major risk factors, cigarette smoking and hypertension, and for the three factors combined. These findings supported the notion that in diabetes rigorous intervention to control risk factors, including cholesterol levels, is needed.

In the UK prospective diabetes study (UKPDS), LDL cholesterol was the major determinant for CHD (16). Triglycerides and CHD have been the subjects of much debate over the last two decades particularly in relation to the independence of their relationship. In both, the PROCAM population (17) and the Helsinki Heart Study (18), hypertriglyceridemia was associated with CHD risk in individuals with an LDL:HDL cholesterol ratio >5. This clustering of lipid abnormalities is often referred to as the atherogenic lipoprotein profile.

Hypertriglyceridemia is associated with several important atherogenic mechanisms in type 2 diabetes. Some triglyceride-rich particles that are directly atherogenic, namely the remnant particles, accumulate in patients with diabetes (19). These cholesterol-rich particles, containing apoproteins B and C-III also accumulate in the rare Type III dyslipidemia (remnant particle disease or broad beta disease), which is associated with premature and extensive atherosclerosis. Hypertriglyceridemia is also associated with significant abnormalities in thrombosis and coagulation, particularly increased levels of plasminogen activator inhibitor-1, and prolonged as well as elevated postprandial lipemia. Haffner etal. (20) investigated 1734 individuals prospectively over 7 years in the San Antonio Heart Study. They found that the 195 individuals who developed type 2 diabetes had a higher body mass index (BMI), as well as waist-to-hip ratio, higher blood pressure, elevated plasma triglycerides and lower HDL-cholesterol levels.

Couillard etal. (19) has shown that high triglyceride levels and low HDL-cholesterol concentrations are associated with postprandial hyperlipidemia. Sixty-three men with low (<0.9 mmol/L, <35 mg/dL) fasting HDL-cholesterol and either low (<2 mmol/L, <176 mg/dL) or high (>2 mmol/L, >176 mg/dL) triglyceride levels were investigated. A significant relation between postprandial triglyceride increase and HDL-cholesterol levels in the fasting state was shown. Normolipidemic controls and men with low HDL-cholesterol as well as low triglyceride levels showed a comparable postprandial lipid increase and no signs of insulin resistance. Individuals with low HDL-cholesterol and high triglyceride levels had a greater increase in postprandial lipemia associated with visceral obesity and insulin resistance.

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