Statins and Diabetes


dr_duane_graveline_m.d._134By Duane Graveline, M.D., M.P.H.

It has been well established that statins can cause diabetes and it is well known that with diabetes firmly in place in your body, your risk of heart attack and stroke is much higher.

Ever since Siddals and others first published the paper titled "Abrogation of Insulin-like Growth Factor-I (IGF-I) and Insulin Action by Mevalonic Acid Depletion" I had been waiting for this diabetes "shoe" to drop, reflecting yet another side effect of the statin class of drugs. (Ref 1.)

Siddals (et al.) reported that "HMG-CoA reductase inhibitors" (statins) "disrupt cellular processes by the depletion of isoprenoids and dolichol. Insulin and insulin-like growth factor (IGF) signaling appear particularly prone to such disruption as intracellular receptor processing requires dolichol for correct N-glycosylation and gycosylation inhibitors mimicked the effect of statin treatment."

They went on to say that "We and others have recently found that abnormally low levels of IGF-I are associated with the premature development of type 2 diabetes." Dr. Kausik K. Ray reported in the June 22 - 29 2011 issue of the Journal of the American Medical Association that a meta-analysis of several statin trials showed a significant increase in cases of new-onset diabetes in those on high dose statins compared to those on a more moderate dose. (Ref 2.)

Once again this highlights that diabetes is yet another of the side effects of statins that appear to be dose sensitive. The higher the dose, the more likely the side effect is to occur.

The latest study to document an increased incidence of diabetes with statin use has been the Women's Health Initiative (WHI) based upon the study of the effects of statin use in postmenopausal women (Ref 3).

Nearly 154,000 women were in the study and the WHI compared all the statins in current use documenting that this higher incidence of diabetes in those taking a statin ( 48% more likely ) is a general statin effect not just specific to some brand of statin.A consequence of statin therapy is their effect on our dolichols.

This is not a chance occurrence; this is inevitable with the use of reductase inhibitors which is what every statin drug is. All statins are designed to blockade the mevalonate pathway to cholesterol synthesis. This process also blocks dolichol synthesis since the same pathway is used.

Dolichols are mandatory for glycoprotein synthesis. The term glycosylation refers to the attachment of sugars to the growing amino acid strand in the endoplasmic reticulum where glycoproteins are created. Now, if the use of statin drugs can cause diabetes with worrisome frequency, what about if you already have diabetes and your doctor now wants to add a statin to your treatment plan? "To reduce the likelihood of peripheral neuropathy," he says, by way of justification.

In May 2002, after performing a population-based study to estimate the relative risk of idiopathic polyneuropathy in users of statins, Gaist (et al.) concluded that "Long-term exposure to statins may substantially increase the risk of polyneuropathy." (Ref 4.)

In April 2005, the Australian Adverse Drug Reactions Advisory Committee (ADRAC) reported that they had received "received 281 reports of peripheral neuropathy or symptoms consistent with this diagnosis attributed to statins." (Ref 5.)

Some doctors will look at the increase in the incidence of diabetes resulting from statin treatment and say, "That is the price you must pay to treat heart disease." Diabetes is a major cause of the same microvasculature damage that leads to heart attacks and strokes. The major cause of death in diabetics is heart attacks and strokes.

Think about it. You can't have it both ways. Something is drastically wrong here and what is wrong is that the full range of statin drug side effects are not well understood. Causation of diabetes mellitus is rarely discussed.

I credit Dr. Beatrice Golomb for having made the greatest advance in understanding the onset of this condition. She credits mitochondrial DNA mutation as the underlying cause of most statin damage.

Undoubtedly cholesterol and dolichol inhibition play important roles in explaining statin drug adverse reactions but CoQ10 inhibition secondary to statin inhibition, I believe, plays the most important role leading directly to mitochondrial damage as CoQ10 seeks to replace their missing electrons.

Located directly within our mitochondria, CoQ10 serves as our most important antioxidant. It is inhibition of CoQ10 by statins that allows all this to happen. The higher the statin dose the more severe the inhibition of these vital biochemicals such as dolichols and CoQ10.

Cholesterol is not our enemy and cholesterol lowering never should have been the goal of statin dosing. The benefit from statins appears to be because of some new anti-inflammatory action we are only beginning to learn about.

With progressive mitochondrial damage comes mitochondrial failure then pancreatic tissue cell and B cell failure and finally organ failure, the clinical phase of diabetes mellitus when the pancreas is no longer sufficient to meet our needs.

It is of interest that this same sequence of events explains most statin damage from myopathy, to hepatitis to neuropathy to cardiac failure. The failure of the pancreas and diabetes is a direct result of excessively high statin dosing.

We are only now learning the full impact to the human body from the statin class of drugs and in retrospect the increased incidence of diabetes was inevitable. With less expensive generic versions of statins becoming available and with increasing recommendations for the use of statins, diabetes and diabetes provocation will continue to be a problem. 

These are some of the reports received from readers regarding statins and diabetes. 

1.) I started taking Vytorin 10\20 last September and since then my Humalog insulin requirements have steadily increased for any semblance of blood sugar control. To give you an idea of what I am describing, last September my morning dose of Humalog was 8 units and NPH 16 units. Today, after a steady increase on a sliding scale, I took 18 units of Humalog and 16 NPH. Don't know that Vytorin is responsible but given its interaction with the liver I suspect it is possible. 

2.) I am at my wits' end--I just don't know what to do about all this.  After being on Lipitor for a while, I was diagnosed with Type 2 Diabetes--and I suspect Lipitor caused it. My Dr. has not suggested any alternatives to Lipitor, and we are not on our previously friendly basis!

3.) In researching the subject of diabetes and cholesterol, I've discovered that the American Diabetic Association recommends lower cholesterol levels for diabetics and recommends cholesterol-lowering drugs if necessary. They polly-parrot the company lines about statin side effects.

There are a myriad of articles on studies touting the benefits of statins for diabetics. Some say that all diabetics should be on statins. I haven't found much to balance that view. However, it seems to me that the primary risk factor is artery damage from high blood glucose, which will result in inflammation and plaque build up, regardless of cholesterol levels. The "benefit" of statins to diabetics probably comes from the anti-inflammatory effect, rather than the lower cholesterol. I'd like to find more information on diabetics and statins, but my internet searches have turned up mostly pro-statin propaganda.

4.) Since going on Lipitor 80 my husband has been diagnosed as having pre-diabetes. For pre-diabetes they have prescribed the glucotrol XL and he has been testing his sugar once a day AM.

5.) My husband takes 10mg of Crestor for cholesterol every day and his cholesterol levels are now normal but recently he has developed Type II Diabetes and is on Glyburide. Now my husband has been experiencing some "spells" (I don't know what else to call them) since early June of this year.

6.) I have been on Lipitor 20 mg for several years. Now I have type 2 diabetes, non-insulin, and take 1500 mg metformin. Now my GP doc says take the Lisinopril to protect my kidneys from effects of diabetes. I am pretty healthy except for blood glucose.
 
My cholesterol was high and my doctor put me on Baycol, which I took for about a year before it was found to cause major problems and taken off the market.  As far as I know I had no side effects but about then I was diagnosed with type II diabetes.  (No family history at all of diabetes.) 

After Baycol, I was put on Zocor. I have taken Zocor for about close to 5 years (one-half of an 80 mg tablet every evening).  Several years ago, I had a massive heart attack and was in a coma for several days.  My wife and family were told that I was not going to make it, but I did recover and had triple bypass surgery. 

7.) I have been doing a lot of research since my diabetic mother was just diagnosed with possible ALS in August.  She has been suffering from symptoms since her doctor put her on Lipitor approx 9 years ago.

She complained as soon as she started taking it about leg pain and stomach pain.  Eventually instead of taking her off, he just kept switching her to different cholesterol reducing medicines, all of which contain "statins".  Finally in Jan. of this year she started falling, and after going to 3 different neurologists in the area who could find nothing, we took her to Mayo clinic where she was diagnosed with ALS in Aug.

(Late stages--as of now she is alsmost completely wheelchair bound with extreme difficulty in swallowing, speaking, and eating in just 11 months.) 

A new ALS Specialist we just found this month, has asked her to get all her medical history records becasue he was contacted by the FDA to do research showing his findings of his patients with ALS that have been taking Lipitor, Zocor, etc...because of the increasing similarities in people taking "statins" and getting ALS.

I'm extremely upset because the medication did not indicate these possible adverse conditions, and her family doctor went 9 years without any "supposed"  knowledge of the side effects. My mother has had diabetes for almost 50 years.  And she has worked so hard her whole life to stay healthy and maintain her diabetes, and up until Jan. 2006 she was still square dancing, traveling, enjoying life.  And now to think that after all these years, she could possibly be dying because of a cholesterol medication that was labeled completely safe.

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

Ref 1 http://www.jbc.org/content/279/37/38353.full
Ref 2 http://www.nlm.nih.gov/medlineplus/news/fullstory_113465.html
Ref 3 http://archinte.ama-assn.org/cgi/content/short/archinternmed.2011.625
Ref 4 http://www.neurology.org/content/58/9/1333.abstract
Ref 5 http://www.tga.gov.au/hp/aadrb-0504.htm

 
Updated January 2012


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