Author(s): Christoph H Saely 1 2 3 , Veronika Drexel 1 , Alexander Vonbank 1 2 3 , Heinz Drexel [[dagger]â ] 4
anion exchange resins; ezetimibe; fibrates; lipid therapy; niacin; omega-3 fatty acids; pioglitazone; statins; Type 2 diabetes
Cardiovascular disease determines prognosis in patients with Type 2 diabetes
Atherosclerosis determines the prognosis of patients with diabetes. Cardiovascular risk in Type 2 diabetic patients is increased by a factor of two to three, and diabetes approximately doubles the risk of death after cardiovascular events. Mainly owing to their increased cardiovascular risk, the life expectancy of patients with Type 2 diabetes is reduced by more than 7 years  . Lipids and lipoproteins play a key role in the pathogenesis of atherosclerosis; therefore, lipid therapy in diabetic patients is of paramount importance.
Lipid metabolism in Type 2 diabetes
The typical lipid problem in patients with Type 2 diabetes is not high low-density lipoprotein (LDL)-cholesterol but rather a combination of low high-density lipoprotein (HDL)-cholesterol, high triglycerides and highly atherogenic small, dense LDL particles  . This cluster of lipid abnormalities is referred to as diabetic dyslipidemia.
Diabetic dyslipidemia is closely related to insulin resistance, the key pathophysiological feature of Type 2 diabetes  . Insulin resistance is associated with an increased release of free fatty acids from adipose tissue and consequently with an increased production of triglycerides, which are secreted from the liver packed in very-low-density lipoprotein (VLDL) particles. Blood triglycerides thus increase. Mediated by the cholesteryl ester transfer protein (CETP), triglycerides from the triglyceride-rich VLDL particles are exchanged for cholesterol from the cholesterol-rich LDL and HDL particles. From these triglyceride-enriched LDL and HDL particles triglycerides are then removed by lipases, rendering both LDL and HDL particles smaller than before the modification.
Smaller LDL particles enter into the vessel wall more readily, are oxidized more rapidly and are therefore more atherogenic than larger LDL particles. In addition, given the smaller size of LDL particles in patients with Type 2 diabetes, more LDL particles are present at a given LDL-cholesterol level in these patients than in nondiabetic individuals. More LDL particles, in turn, mean more danger for the vessel walls. With respect to HDL, the smaller particles are more rapidly cleared from circulation, which explains the low HDL-cholesterol observed in diabetic patients. Moreover, the smaller HDL particles are dysfunctional and have impaired atheroprotective properties  .
We and others have demonstrated that diabetic dyslipidemia is not only characteristic for patients with diabetes but that it is also an important cardiovascular risk factor in diabetic individuals. In a large population of coronary patients who have undergone angiography we found that the triad of low HDL-cholesterol, high triglycerides and small LDL particles is a better predictor of cardiovascular events than serum levels of LDL-cholesterol  . This observation concords with an important sub-group analysis of the Treating to New Targets (TNT) trial, which demonstrated that even with LDL-cholesterol levels lowered to less than 70 mg/dl, low HDL-cholesterol is significantly associated with a high incidence of cardiovascular events  . In particular, we found that high...