Statins and Diabetes
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Statins may slightly increase the risk of diabetes, with higher doses appearing to have a larger effect. A laboratory study has shown for the first time that coenzyme Q10 offsets cellular changes that may be linked to a side-effect of some statin drugs - an increased risk of adult-onset diabetes. Statins are some of the most widely prescribed drugs in the world, able to reduce LDL, or bad cholesterol levels, and the risk of heart attacks or other cardiovascular events. However, their role in raising the risk of diabetes has only been observed and studied in recent years.
The possibility of thousands of statin-induced diabetics is a growing concern, and led last year to new labeling and warnings by the Food and Drug Administration about the drugs, especially when taken at higher dosage levels.
The best-selling statin atpresent is atorvastatin or Lipitor. As of 2010, a number of statins are on the market: atorvastatin (Lipitor and Torvast), fluvastatin (Lescol), lovastatin (Mevacor, Altocor, Altoprev), pitavastatin (Livalo, Pitava), pravastatin (Pravachol, Selektine, Lipostat), rosuvastatin (Crestor) and simvastatin (Zocor, Lipex).
The findings of the new research were published as a rapid communication in Metabolic Syndrome and Related Disorders, and offer another clue to a possible causative mechanism of this problem.
Pharmacy researchers at Oregon State University who authored the study said the findings were made only in laboratory analysis of cells, and more work needs to be done with animal and ultimately human studies before recommending the use of coenzyme Q10 to help address this concern.
"A number of large, randomized clinical trials have now shown that use of statins can increase the risk of developing type-2 diabetes by about 9 percent," said Matthew K. Ito, an OSU professor of pharmacy and president-elect of the National Lipid Association.
"This is fairly serious, especially if you are in the large group of patients who have not yet had a cardiovascular event, but just take statin drugs to lower your risks of heart disease," Ito said.
A suspect in this issue has been altered levels of a protein called GLUT4, which is part of the cellular response mechanism, along with insulin, that helps to control blood sugar levels. A reduced expression of GLUT4 contributes to insulin resistance and the onset of type-2 diabetes, and can be caused by the use of some statin drugs.
The statins that reduce cholesterol production also reduce levels of coenzyme Q10, research has shown. Coenzyme Q10 is needed in cells to help create energy and perform other important functions. And this study showed in laboratory analysis that if coenzyme Q10 is supplemented to cells, it prevents the reduction in GLUT4 induced by the statins.
Coenzyme Q10, also known as ubiquinone, ubidecarenone, coenzyme Q, is a 1,4-benzoquinone, where Q refers to the quinone chemical group, and 10 refers to the number of isoprenyl chemical subunits in its tail.
This oil-soluble, vitamin-like substance is present in most eukaryotic cells, primarily in the mitochondria. It is a component of the electron transport chain and participates in aerobic cellular respiration, generating energy in the form of ATP.
Not all statin drugs, however, appear to cause a reduction in GLUT4.
The problems were found with one statin, simvastatin, that is lipophilic, which means it can more easily move through the cell membrane. Some of the most commonly used statins are lipophilic, including simvastatin, atorvastatin, and lovastatin. All of these statins are now available as generic drugs, and high dosage levels have been most often linked with the increase in diabetes.
Tests in the new study done with a hydrophilic statin, in this case pravastatin, did not cause reduced levels of GLUT4. Pravastatin is also available as a generic drug.
"The concern about increasing levels of diabetes is important," Ito said. "We need to better understand why this is happening. There’s no doubt that statins can reduce cardiovascular events, from 25-45 percent, and are very valuable drugs in the battle against heart disease. It would be significant if it turns out that use of coenzyme Q10 can help offset the concerns about statin use and diabetes."
For further information see Statin Effects.
Pill image via Wikipedia.