Protective role of pravastatin in the pathogenesis of the metabolic syndrome.
The metabolic syndrome is strongly associated with insulin resistance and consists of a constellation of factors such as hypertension and hyperlipidemia that raise the risk for cardiovascular diseases and diabetes mellitus. There is a growing body of evidence to show that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, reduce cardiovascular-related morbidity and mortality in patients with or without coronary artery disease. Recent clinical observations argue for a simple strategy of considering routine statin therapy for patients with type 2 diabetes. Furthermore, statin therapy is also found to be effective in allowing LDL-cholesterol goal achievement in hypercholesterolemic high-risk patients with the metabolic syndrome. However, the effects of statins on the pathogenesis of the metabolic syndrome remain to be elucidated. Several types of statins are commercially available now. Among them, pravastatin is unique because it is the only statin that has been shown to have protective role against the development of diabetes in a large clinical trial. Moreover, a recent clinical study revealed that pravastatin treatment improved insulin sensitivity in 25 women with the metabolic syndrome with impaired glucose intolerance. These observations let us to speculate that pravastatin is a promising strategy for the treatment of hypercholesterolemic patients with the metabolic syndrome. It may improve the insulin sensitivity in these patients and subsequently prevent the development of type 2 diabetes. In this paper, we would like to propose the possible ways of testing our hypothesis as follows. (1) Does pravastatin treatment improve insulin resistance in patients of the metabolic syndrome or in insulin resistant hypertensive or obese patients? If the answers are yes, are these beneficial effects of pravastatin superior to those of other anti-hyperlipidemic statins with equihypolipidemic properties? (2) Does pravastatin treatment actually reduce the development of diabetes in these insulin resistant patients? At that time, does pravastatin treatment increase serum levels of adiponectin, a key adipokine with insulin-sensitizing property? How about the effects of pravastatin treatment on adipokines that could elicit insulin resistance such as tumor necrosis factor-alpha? These clinical studies will provide further information whether pravastatin treatment can improve insulin resistance and subsequently reduce the development of diabetes in insulin resistant patients with the metabolic syndrome.
Yamagishi
S
S
Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. shoichi@med.kurume-u.ac.jp
Matsui
T
T
Sato
T
T
Takeuchi
M
M
D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000473:pathology*; D008954:Models, Biological; D008962:Models, Theoretical; D009765:Obesity / Q000188:drug therapy; D017035:Pravastatin / Q000494:pharmacology*
D017035:Pravastatin