MedicalConspiracies- Cholesterol meds: Statin Induced Diabetes

Statin Induced Diabetes

By Dr. Duane Graveline, M.D., M.P.H.

Study after study has documented that statins can cause diabetes or aggravate pre-existing diabetes. The JUPITER study (Ref 1) was one of the first major studies to document diabetes as a side effect.

In this study men and women with no significant cardiovascular risk on the basis of history and LDL cholesterol and who were positive when tested for elevated (hs)CRP ( high sensitivity C-reactive protein ) were selected for the study group and placed in either the test (treated with a statin) or control group (treated with placebo).
Those treated with modest doses of a statin had such benefit in terms of fewer heart attacks and strokes after 18 months compared with the placebo group that the study was stopped by the ethics committee.

In the statin treated group a substantially increased (5-7 percent) incidence of diabetes was reported compared with the control group. These JUPITER findings are supported by two recent meta-analyses of large-scale placebo controlled and standard care controlled studies.

The placebo group reported a 9 percent increased incidence of diabetes. The standard care group reported a 13 percent increased incidence of diabetes. Similar increased risk of diabetes or aggravation of previously diagnosed diabetes was reported in a recent analysis of 345,000 patients in the Veteran Affairs Healthcare System (Ref 2).

The evidence is in. There is no doubt that statin use is associated with a substantial risk of diabetes.

A study reported in the June 2011 issue of JAMA ( Journal of the American Medical Association ) (Ref 3) analyzed five earlier trials, involving a total of 32,752 patients, to tease out the effect of statin dosage. Those getting intensive treatment were 12 percent more likely to be diagnosed with diabetes, the study found. Patients also were 16 percent less likely to have a heart attack, stroke or surgery to clear their arteries or to die from cardiovascular disease during a five-year period than those given a smaller amount, according to the researchers.
Clinicians must be aware that they will be very substantially increasing the risk of diabetes with the use of statins and also that all evidence thus far indicates that cholesterol lowering is irrelevant. It is the anti-inflammatory effect of statin drugs that appears to be responsible for any benefit.
Physicians no longer should be focused on cholesterol lowering. The old guideline that if your starting dose does not work well enough, increase it, will only increase adverse reactions. What doctors need today are guidelines for what constitutes a proper starting dose when inflammation suppression is the goal. My research over the past decade tells me that this dose must be one that does not block the mevalonate pathway significantly.
From a practical viewpoint the risk of diabetes completely offsets any gain in cardiovascular disease control. Just as Uffe Ravnskov reported a decade ago in his book, The Cholesterol Myths, cancer deaths from statin use almost completely offsets the reduction in deaths from heart attacks and strokes.
Meanwhile Uchechukwu K and others of the Atherosclerosis Research Unit at Vanderbilt ask the question, "are statins diabetogenic?" (Ref 4) and suggest that a loss of the functional integrity of the islet b-cells may be central to this process. At the same time this research team is praising the effectiveness of statins in reducing cardiovascular complications so that even if statins cause a few cases of diabetes the total effect of statin use is beneficial because of improved cardiovascular status.
Need I say here that 12 percent is not a few cases of diabetes. Most doctors would have a great deal of trouble accepting this degree of disease provocation when from the very beginning they are told, "First do no harm."
Although this team of investigators cite the JUPITER study they completely disregarded the fact that the JUPITER study was the first to establish once and for all the irrelevance of cholesterol as a cause of atherosclerosis. The JUPITER study dramatically brought into public focus the powerful anti-inflammatory role of statin drugs. It is not cholesterol lowering that has contributed to statin benefit, it is this novel anti-inflammatory role.
The focus on cholesterol lowering and the use of higher and higher doses of reductase inhibitors (statins) has resulted in increasing degrees of mevalonate blockade. With this has come inevitable inhibition of CoQ10 allowing mitochondrial DNA mutations from excess free radical formation.

This process occurs in every tissue of the body. The effect is much greater in those tissues requiring larger amounts of energy such as muscles, kidney and brain, but the same process occurs everywhere - the liver, lungs, gastrointestinal system, endocrine glands and the pancreas.

With sufficient mitochondrial DNA loss, cell loss must follow and with sufficient cell loss organ failure is the inevitable consequence. Many cases of pancreatitis associated with statin use have been reported. When the islets of Langerhan ( areas of the pancreas that contain the cells that produce hormones ) are involved in this process of free radical damage to mitochondrial DNA, frank diabetes will appear at some point. If the victim already is diabetic the effect will be aggravation of diabetes as vital structures in the insulin secretion pathways are gradually affected.

Very few really understand this sequence of events. It is true that many people can take statins for years with no apparent adverse reactions ( emphasis on the word apparent ). Investigators have reported microscopic evidence of muscle damage in completely asymptomatic statin users. So who can say that they have been on statins for years with no problems?

Inability to measure due to lack of relevant testing material may also be at work with personality change, depression, aggressiveness, etc. In any of these behavioral and emotional attributes the range of normal varies greatly and substantial changes can easily be missed or blamed on other factors.

Then we have the statin damage gene study report (Ref 5) that some 24 percent of North Americans and Europeans carry a gene that predisposes them to statin adverse effects. This effect is especially prominent with the use of simvastatin but is shared by all reductase inhibitors.

Additionally we have the fact that CoQ10, the critical protective biochemical involved in free radical damage to mitochondrial DNA, has a widely variable pattern of metabolism in the human body. Most of us lose completely the ability to synthesize this vital biochemical during mid-life. But there is wide variation from person to person in the metabolism of CoQ10.

From midlife on our source of CoQ10 must come from diet or supplements. Some of us lose the ability to synthesize CoQ10 much earlier in life, greatly enhancing the sensitivity to statins. This, too, is genetically predetermined.

We have learned that many factors contribute to the effect of statins and that lack of awareness of adverse effects does not mean no adverse effects. The bottom line is that if you spend but a few moments reviewing basic biochemistry, you soon realize that CoQ10 and dolichols must be blocked any time one uses a statin in sufficient quantities to inhibit cholesterol. It is inevitable. Do not fight Mother Nature - understand her.

Back to diabetes and the use of statins. It is true that the incidence of diabetes will be increased by some 7 to 12 percent with the use of statins. To say that this monumental black mark is turned white because at the same time statins decrease cardiovascular risk makes no sense to me. Damage is damage.

It seems far better to understand that this increased incidence of diabetes is purely a function of mevalonate blockade and the gradual accumulation of mitochondrial DNA damage due to CoQ10 inhibition. Our programs to lower cholesterol will be regarded by historians of the future as one of man's greatest medical blunders.

The JUPITER study has enabled us to look beyond this blunder and see that a dramatic reduction in the statin dose, too low to block the mevalonate pathway, might preserve CoQ10 and at the same time be an effective anti-inflammatory dose. JUPITER was on the right track but the dosage was still far too high. Repeat this with a truly low dose statin and you could have a really good study.

Duane Graveline MD MPH
Former USAF Flight Surgeon
Former NASA Astronaut
Retired Family Doctor

Ref 1: http://www.ncbi.nlm.nih.gov/pubmed/18997196
Ref 2: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2752927/
Ref 3: http://jama.ama-assn.org/content/305/24/2556.short
Ref 4: http://journals.lww.com/co-cardiology/Abstract/2011/07000/Are_statins_diabetogenic_.13.aspx
Ref 5: https://helda.helsinki.fi/bitstream/handle/10138/22995/pharmaco.pdf?sequence=2

June 2011

http://www.spacedoc.com/statin_induced_diabetes