Another Round in the Debate on Diabetes and Statins
by Roger Blumenthal
Let me start by saying that I am proud to have Eric Topol as a friend and a trusted advisor over the past 20 years. His work has been an inspiration to cardiovascular health professionals for several decades. His new book, The Creative Destruction of Medicine: How the Digital Revolution Will Create Better Health Care, should be required reading by all physicians and in all medical schools. It is simply that good.
Eric is a strong believer that we need to have more personalized medicine. I agree. I predict that he and his research group will lead the way to help us understand why certain people benefit more from certain medications and others may not. So far, the only ways we have to decide which asymptomatic persons would benefit from statin therapy are the traditional risk factors which make up the Framingham risk score, hsCRP, and coronary calcium measurements. Both of the latter two tests have been given a class IIa indication from the AHA for use in intermediate risk adults (Framingham score of 10-20% risk of an MI over the next decade.)
Eric is concerned about the apparent increased risk of diabetes with statin use. A 2010 meta-analysis in the Lancet found about a 10% increased risk in statin users. Eric rightly points out that the relative risk was higher with the more potent rosuvastatin in JUPITER. Yet, that is where we saw a significant decrease in total mortality and the largest relative risk reduction in CVD events.
Dr. Topol is one of the country’s leading geneticists and thought-leaders. He may be an invited guest to Stockholm in the next decade to accept a great award. If that is the case, I would like to be on his invitation list.
No one is right all the time – just ask my wife. We know that chlorthalidone reduces clinical events and reduces mortality in persons with a systolic blood pressure greater than 160 but it also raises blood sugar. We also know that niacin raised blood sugar in the Coronary Drug Project, but it reduced events and mortality as a single agent.
We don’t know why certain adults go from a glucose of 115-125 and then go over that magic 125 threshold more frequently. Though this has not been published, I have been told by several statin investigators that the vast majority of the persons who crossed the 125 line were clearly insulin resistant with glucoses between 115-125. We are not talking about going from a glucose of 90 to 140!
Before we throw out the NCEP guidelines on primary prevention, I think that we need to be more skeptical of the diabetes fear from statins. The benefit is very clear in high risk primary prevention patients. Please refer to Professor C. Michael Minder’s latest paper on the American Journal of Medicine website. It is a masterpiece. Just like William Shakespeare’s Much Ado About Nothing. My favorite line from that play was “Let every eye negotiate for itself and trust no agent.”
All of us await the ATP guidelines and how to make sense of the benefits and possible risks of the hyperglycemia seen with the more potent statins. In the meantime, please read Dr. Topol’s book. It is fabulous and thought-provoking. And by the way if your statin patient’s glucose goes above 125, simply remind them of the importance of dropping a few pounds and exercising more. Eat Less, eat smarter and move more. A lot more.
I look forward to teeing it up with my friend, and trusted mentor Eric Topol at Torrey Pines and Congressional sometime in 2012! Dr.Topol may prove to be correct on this topic but my view of statins is much more optimistic in high risk primary prevention patients.
Those “high risk” primary prevention people are high risk because they have self-destructive lifestyles, namely addiction to junk food or tobacco or both. Statins never be prescribed to such people until they have corrected those high risk habits. The likely reason such people develop DM2 on statins is because their addictions worsen when they believe they can eat anything as long as their “cholesterol” is low while taking high dose statins and they become more obese. In JUPITER the subjects were told their lipid numbers and adjusted their behavior according depending upon their susceptibility to magical thinking.
Careful there, Roger. If Eric stops suddenly your head could be in danger of disappearing!
Being male, having inherited hypercholesteremia (at low weight and regular intensive exercise), along with multiple early MIs in immediate family hx are not reflective of a “self-destructive lifestyle.”
Glucose elevation in a genetically pre-disposed person to become diabetic is the natural history of the disease, as they get older. A person with fasting blood glucose of 139 in 1979 was not labeled as diabetic but another person in 1997 became diabetic when the fasting blood glucose reached 126. We equate elevation of blood glucose to a medical diagnosis of Diabetes and we keep changing the number and we may even change the current diagnostic criteria for diabetes in the near future.
Diabetes, hypertension, hyperlipidemia and obesity come as clusters -metabolic syndrome – and they appear in different ages for each person, depending on different diagnostic criteria that we keep changing. These CVD risk factors are mostly inherited and may not appear altogether at the same time or in any sequence or with the same severity. From the studies in the last 2 decades it appears that the blood glucose level or control, has the minimum influence on atherosclerosis and cardiovascular events compared to lipids and blood pressure.
The clinical relevance of slight blood glucose elevation due to thiazide diuretic, niacin or statin has been minimum if not negligent in the real world clinical practice from my personal experience of 34 years, caring for 53,000 patients following some of them for up to more than 25 years.
Modern medical scientists including the so-called thought leaders in the world have become the blind men identifying the elephant. So we are obliged to be skeptics and critics and use common sense to practice modern medicine. Many of our gold standards have tuned out to be gold-plated standards as we along.
Joseph Chemplavil, MD
Cardiovascular Endocrinologist