Cardiovascular pleiotropic effects of statins and new onset diabetes: is there a common link: do we need to evaluate the role of KATP channels?

ABSTRACT

Introduction: Statins are considered the main stay of treatment in the prevention of cardio-vascular morbidity and mortality. They have multiple pleiotropic effects, like stabilization of atherosclerotic plaques, inhibition of platelet aggregation, and vascular smooth muscle proliferation; in addition to their lipid lowering action. Statins manifest these pleiotropic effects because they activate KATP channels in the cardiac and vascular tissue.

Simultaneous activation of the KATP channels by statins in β cells of pancreas may inhibit insulin release which may lead to diabetes.

Areas covered: Literature published between 1980 and 2016 on cholesterol biosynthesis, new onset diabetes and on the pleiotropic effects of statins, was reviewed. A comprehensive search on PubMed, Embase and Cochrane databases was carried out.

Expert opinion: Statins exert their beneficial pleiotropic effects on the cardiovascular system by activating KATP channels in the cardiac and vascular tissue. However, simultaneous activation of KATP channels in the beta cells of pancreas leads to inhibition of insulin release. This disturbs the carbohydrate metabolism and probably leads to diabetes. In our opinion, use of stains should be more judicious and restricted to secondary prevention only.

KEYWORDS:

• Statins
• new onset diabetes
• KATP channel
• glibenclamide
• rosuvastatin
• HMG CoA reductase inhibitor
• cholesterol biosynthesis

Article highlights

• Statins are beneficial not only because they lower lipids; but also, because they have pleiotropic effects.

• The pleiotropic effects of statins are because they act on KATP channels in various tissues and activate them.

• Activation of KATP channels present in the vascular and cardiac tissue improves myocardial function and inhibits endothelial dysfunction.

• Activation of KATP channels in the beta cells of pancreas leads to inhibition of insulin release because insulin secretion correlates inversely with KATP channel activity.

• KATP channel activation in the vascular and cardiac tissue improves endothelial and myocardial function; but a simultaneous activation of KATP channels by statins in the beta cells of pancreas leads to inhibition insulin release and carbohydrate intolerance.

• Statins should be prescribed judiciously in middle aged men with a diagnosed coronary artery disease.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.