Reducing cardiovascular complications of type 2 diabetes by targeting multiple risk factors.

Insulin resistance syndrome is characterized by hyperglycemia, atherogenic dyslipidemia, hypertension, and abdominal obesity. Hyperglycemia is the major risk factor for microvascular complications in type 2 diabetes. However, 70% to 80% of patients with type 2 diabetes will die of macrovascular disease. Atherogenic dyslipidemia-characterized by elevated triglyceride levels, low high-density lipoprotein cholesterol (HDL-c) levels, and a preponderance of small, dense, low-density lipoprotein (LDL) particles-is the major cause of atherosclerosis in individuals with type 2 diabetes. Therefore, treatment of type 2 diabetes must address hyperglycemia to prevent microvascular disease (retinopathy, neuropathy, and nephropathy) and atherogenic dyslipidemia to prevent macrovascular complications. Emerging evidence indicates lipid and glucose homeostasis are interrelated via bile acid-activated nuclear hormone receptor signaling pathways. Agents that act on these pathways could simultaneously address hyperglycemia and dyslipidemia in patients with type 2 diabetes. Recent studies have shown that bile acid sequestrants, including cholestyramine, colestimide, and colesevelam HCl, significantly improve glycemic control and reduce LDL cholesterol levels in patients with type 2 diabetes. This paper will review the effects of bile acid sequestrants on both glucose and lipid metabolism in patients with type 2 diabetes.