Application of New Pathogenesis on the Drug Treatment of Diabetes
Young Seol Kim
Journal of the Korean Medical Association
P atients with type 2 diabetes mellitus are associated with insulin resistance and/or impaired insulin secretion. Previous observations indicate that patients with type 2 diabetes tend to have an impaired insulin response after a glycemic load. Recently it has been reported that hyperglycemia after a glucose load is itself a risk factor for the development of cardiovascular complications in the absence of elevated fasting plasma glucose. There are several points to be addressed for the
... on of new pathogenesis to diabetes treatment. One of them is the association between postprandial hyperglycemia and mortality from cardiovascular diseases. For the management of postprandial hyperglycemia inhibitors of glucosidase and rapid acting insulin secretagogues have beneficial effects. Alpha glucosidase inhibitors in combination with diet therapy ameliorate insulin resistance and reduce the blood sugar level. A rapidly acting insulin secretagogue, such as repaglinide, lowers postprandial glucose levels without a significant gain of body weight. These drugs may protect pancreatic cells from postprandial glucose toxicity and prevent the progression of diabetes. Both metformin and thiazolidinedione derivative (TZDs) improve insulin resistance, the major pathogenetic background of type 2 diabetes, and decrease blood glucose levels without stimulating insulin secretion. Metformin inhibits glucose output from the liver, while TZDs increase glucose utilization in the peripheral tissues. In addition, it has been indicated that these agents ameliorate the metabolic syndrome beyond lowering the glucose level. Molecular targets for these agents have recently been revealed ; AMP activated protein kinase for metformin and adiponectin, while PPAR for TZDs that induce gene expression of adipocyte glycerol kinase and adiponectin. Insulin sensitizing agents are clinically useful for obese diabetic patients with insulin resistance. However, periodical examinations are necessary to avoid serious adverse effects such as lactic acidosis, although rare, by metformin and liver injury by TZDs. The advantage of insulin therapy for type 2 diabetic patients is still controversial. However, in many intervention studies, the intensive insulin therapy provided promising effects on preventing cardiovascular diseases. Moreover, insulin has been shown to stimulate nitric oxide production by cultured endothelial cells and to suppress the expression of intercellular adhesion molecule 1 at least in vitro. In view of this anti inflammatory effect, long term insulin therapy may potentially have an antiatherogenic effect.