Thursday, February 25, 2010

12. Statins and Diabetes

The JUPITER trial of the statin drug Crestor was widely heralded as evidence that statin drugs can delay heart attacks for people who have high levels of an indicator of inflammation called C-reactive protein. However, what is less known about this trial is that it uncovered a clear link between statin drugs (or, at least, Crestor) and increased risk of diabetes (JUPITER Trial and Diabetes) [36]. According to Dr. Jay Cohen, the people who took Crestor in the trial had a 25% increased risk of developing diabetes, compared to the control group. This is alarming, because diabetes itself is an extremely strong risk factor for heart disease.

The pancreas synthesizes insulin in its beta cells, and defects in insulin production (either too little of it, or a lack of response to it) is the cause of diabetes. Insulin is used by the body's cells to catalyze the transport of glucose into the cell. Without insulin, or with poorly functioning insulin, sugar piles up in the blood and the cells become energy starved.

There have been a large number of studies on the biochemistry of the beta cells and their insulin-producing machinery, and it has been determined that beta cells require both cholesterol [46] and fats [11] to be present before they will release insulin. Inadequate cholesterol and poor quality phospholipids in the beta cell's outer membrane likely impair its ability to transport insulin across the membrane. Statin drugs, of course, reduce the bioavailability of cholesterol, but also of fatty acids, because these are transported in the blood stream via the same LDL particles that statins suppress. Thus, it is easy to see why statins would cause an increased risk to diabetes.

In addition to the above defects in the cell membrane, impaired function of the mitochondria in the beta cells has also been clearly implicated in diabetes, in studies involving diabetic mice with defective mitochondrial genes [39]. These mice exhibited reduced insulin secretion when they were only five weeks old, and their mitochondria were abnormal in appearance and were unable to maintain an adequate charge gradient across their membranes. In other words, they exhibited defects that are similar to what would be expected with reduced coenzyme Q10 as a consequence of statin exposure. Older mice with the same defect were severely deficient in insulin production, as many of their pancreatic beta cells had died off.

Insulin suppresses the release of fats from both the fat cells and the liver, and therefore there will be a fat shortage in the blood supply subsequent to insulin release, unless abundant fats are already present. Thus, it is a good strategy, biologically, for the beta cells to be sure fats and cholesterol are well supplied before injecting insulin into the blood stream. I have previously written extensively on this subject (Essay on Metabolic Syndrome).

A study published in March, 2009 [41] looked at the relationship between statin drug usage and fasting blood glucose levels, the test typically conducted to assess diabetes risk. They grouped 345,417 patients into two categories: with or without a previous diabetes diagnosis. They compared fasting glucose levels before they began taking statins and then after they had been on statins for an average of two years. In both groups, they obtained a highly significant (P < 0.0001) result of increased fasting glucose levels for those on statin therapy.

A reduction in the ability of glucose to enter muscle cells, consequential to a reduction in insulin supply, would add insult onto injury for the muscle cells trying to survive with a defective aerobic metabolism factory. Because the muscles are forced to switch to the much less efficient anaerobic metabolism of glucose in order to avoid oxidative damage, they require enormously more glucose to meet their energy supply than they would require if their mitochondrial energy-generating factory were functioning properly. Yet the reduced insulin is making it harder to get enough glucose in. This will force the cell into the starvation mode that leads to cannibalization of its internal muscle protein. The perceived result over time will be extreme muscle weakness.

1 comment:

pierce79 said...

well the diabetes is a sickness that need a lot of care also for a better helth you need some medications and exercise ,also theres any problem if i have diabetes and i take generic viagra ? cause i take it and i think that can affect me.