Lipid lowering therapy in type 2 diabetes.

The primary defect underlying abnormalities in lipoprotein transport in type 2 diabetes is insulin resistance, which leads to increased triglycerides in the fasting and postprandial states, preponderance of small, dense LDL and low concentrations of dysfunctional HDL. Concentrations of LDL-cholesterol (LDL-C) are most often not remarkably abnormal. Based on this lipoprotein profile, it seems somewhat counterintuitive to prioritize LDL-C lowering in type 2 diabetes. Nevertheless, ≈20 years of statins trials in >18,000 diabetic patients have unequivocally established this priority. Patients with type 2 diabetes without manifest atherosclerosis should reach an LDL-C goal <100 mg/dl or a Non-HDLcholesterol (NHDL-C) goal <130 mg/dl. If their baseline LDL-C is already between 70 and 100 mg/dl LDL-C should be lowered by 30 to 40%. Thus, the majority of these patients can be managed successfully with monotherapy using standard-intensity statins (e.g. simvastatin 40 mg/d). Patients with type 2 diabetes with manifest CHD should reach an LDL-C goal <70 mg/dl or an NHDL-C goal <100 mg/dl. A sizable fraction of these patients will require high-intensity statins (e.g. atorvastatin 80 mg/d or rosuvastatin 20-40 mg/d). If LDL-C goals are still not reached or high-intensity statins are not tolerated, combination of statins with ezetimibe is advisable. In patients with persistent pronounced dyslipidemic features, i.e. high TG/low HDL-C despite maximal lifestyle intervention and optimized statin dosage, pioglitazone should be incorporated in the antidiabetic management and combinations of statins with either niacin or fenofibrate should be considered. However, it has to be recognized that evidence supporting HDL-raising therapy is currently still much weaker than evidence supporting LDL lowering with statins.