My good friend Bill Bestermann, MD, a preventive vascularist at the Holston Medical Group in Kingsport, TN, has published an important article in CardioRenal Medicine. This paper, a long time coming, is not research but a highly informed thought piece that explains a new, previously unappreciated potential mechanism for the diabetes drug Metformin. It has far reaching implications for the management of many chronic diseases.
What’s most important about this most recent paper is that it was rigorously reviewed for CardioRenal Medicine, and so has at least the initial imprimatur of scientific credibility. I hope it now gets the additional attention I believe it deserves.
I’d urge all my clinician colleagues to review it carefully. I believe you’ll be appropriately inspired by both its elegance and its profound clinical ramifications.
Brian’s Note: With yesterday’s announcement that Siddhartha Mukherjee’s The Emperor of All Maladies had won the Pulitzer for General Non-Fiction, I thought it might be appropriate to rerun this review from last December 5, 2010.
The opening page of Siddhartha Mukherjee’s The Emperor of All Maladies begins with a quote by Susan Sontag that is so on-point, yet so rare and fresh, that one can’t help being excited by the prospect of what’s to come.
Illness is the night-side of life, a more onerous citizenship. Everyone who is born holds dual citizenship in the kingdom of the well and in the kingdom of the sick.
Although we all prefer to use only the good passport, sooner or later each of us is obliged, at least for a spell, to identify ourselves as citizens of that other place.
You open the book with great expectations. It is weighty, yes – 570 pages, 100 of which are end notes – but beginning, you immediately find its expansive scholarship wrapped in a writing style so fluid and lyrically engaging that it instantly dispels any hesitancy, and you are captured.
Note by Bill Bestermann, MD. Dr. David Carmouche works at the Baton Rouge Clinic in Baton Rouge, Louisiana. He runs a Center for Cardiovascular Disease Prevention within the clinic and works full time in clinical practice producing optimal medical therapy in high risk patients. Dr. Carmouche is certified in lipid management by the National Lipid Association, and is recognized by his peers as an expert in lipid management.
He is actively involved in multiple leadership roles that are characterized by the common theme of more effectively treating cardiovascular disease with lifestyle and medical interventions. A group of about 20 academic and community cardiovascular risk experts asked him to lead the development of the cholesterol treatment section of a program describing optimal medical therapy for metabolic syndrome patients.
Brian’s Note: In the post below, Dr. Bestermann, a highly regarded vascular physician, has developed and posted a field-tested protocol for the treatment of vascular conditions deemed high priority by the Institute of Medicine.
This is a work in progress that is likely to undergo significant change as new data emerges. But it is here and available in hopes that clinicians will make use of it, patients will benefit from it, and that by sharing important information we can provide better care for lower cost.
This protocol is field tested, weight-centric and has been used in my personal practice for ten years with ongoing adjustment to reflect newer knowledge and products, . Consistently applied, the protocol accomplishes risk factor control levels consistent with optimal medical therapy while facilitating weight loss and renal function improvement in most patients.
There may be no more striking disconnect between new compelling science and current practice than we see in the treatment of women with chest pain. Just today, I saw a woman in her early 50s who has had recurrent chest pain for over two years. She has a family history of heart attack and she is prediabetic with high cholesterol, LDL cholesterol , and triglycerides. She has low HDL or good cholesterol. She is a high risk patient for cardiovascular disease. Her pain was not characteristic of exertional angina as we might see in a man. She had the pain that we frequently see in women that is brought on by stress or may just occur spontaneously. Her pain lasts for several minutes and it is reliably relieved by nitroglycerin. She had a normal stress test 6 months ago and another 2 years ago.
The current scientific paradigms that shape our view of chronic conditions are simply inadequate. Clinical medical scientists might think much more seriously about questions like these: Why is it that metformin reduces the risk of heart attack, stroke, and cancer while other drugs lower the glucose and do not protect from these conditions? Why is it that studies of patients treated with insulin suggest an increase in cancer? Why is it that a single dose of metformin or a statin-type drug reduces heart attack size by half in experimental animals? Why are patients who take certain medications for high blood pressure more likely to develop diabetes.
Today, basic scientists have laid the foundations to begin to answer these questions and the answers are important as we work to improve the quality of care. In practical terms, our scientific literature places little value on work that translates new science into practice. That is part of the reason that there is a large gap between what is known and what we do. This is the first of a series of articles that we hope will serve to help in closing that gap. The link between cancer and other chronic conditions is important. If we can reduce the risk of cancer even slightly by refining the way we manage other chronic diseases, then that is important work.
Another reason for this article and Urgent Science is a very personal one. Brian Klepper, the founder of CareandCost, has recorded the struggle that his brave wife Elaine endures with ovarian cancer now. I myself have been cured of a very aggressive type of lymphoma. How many of our friends and family have been struck down by these ailments. We need to improve our rate of translation. We invite you to read this first piece carefully and if you have refinements or additions that will help the broader medical community understand these problems better, we invite you to send us your constructive comments. We promise to take them seriously and use them to improve what we all know about the newest science and how it might be used to help our patients.
Bill Bestermann is a vascular physician at the Holston Medical Group in Kingsport, TN.
From Brian – The germ of today’s extremely provocative post by Bill Bestermann, MD was the moment in early May when he learned that my wife, Elaine, had primary peritoneal (ovarian) cancer. Bill’s focus for many years had been on vascular disease, but he dove into the literature on cancer, metformin and ADMA, and was energized by what he found.
He called a few days later and asked two questions. ”Did you know that diabetics on metformin get cancer at half the incidence of those not on metformin? Or that diabetics with breast cancer on metformin have their cancers ameliorate at triple the rate of those who are not on it?” I didn’t, but these facts intrigued Dr. Bestermann enough that he relentlessly pursued the science.
The article below, not original research but an important synthesis that leads us to a new understanding, is what came out of that effort. It’s message is ground-breaking – genuinely a paradigm shift in how we might think about chronic disease – and is an specifically aimed at practicing physicians. We have provided all citations, with links, not only to allow verification of source information, but also allow the interested reader to dive deeply into the topic. We are well aware that the science in this piece may be beyond lay readers, and we apologize for this divergence from a more general format.
We are delighted and humbled that Dr. Bestermann has allowed us to publish this piece here. It has been peer reviewed and found to be sound by several capable physician-scientists. One of the goals of Care & Cost is to make the science that can impact clinical practice immediately available.
That said, I believe the content in an article of this caliber and potential impact should also be recast and allowed to work through the more traditional physician publication machinery as well.
“The human body is composed of four cardinal fluids called humors….In the normal body, these four fluids were held in perfect if somewhat precarious balance. In illness, this balance was upset by the excess of one fluid.”
This review is about metformin and cancer, but within a much broader context. It points to an important new science involving critical common core pathways that underlie the origins of multiple common chronic conditions. These pathways involve traditional signaling modifications like phosphorylation, but they also involve a fascinating new science of epigenetics and the methylation of proteins that are involved in inappropriate gene activation.
Originally Published 12/6/10 on the Health Affairs Blog here.
A recent front-page article in the New York Times conveyed grim news about patient safety. The first large-scale study of hospital safety in a decade concluded that care has not gotten significantly safer since the Institute of Medicine’s 1999 estimate of up to 98,000 preventable deaths and 1 million preventable injuries annually.
As I was developing this site, I mentioned it to my good friend Bill Bestermann. Dr. Bestermann is a very progressive, leading edge and nationally recognized vascular physician. When you talk with Bill, it’s very clear that it really is all about the quality of the care. After he’d chewed on the idea of the site, he called with a suggestion. “You could have a section called ‘Urgent Science’ that clearly describes for clinicians the science behind modern management of chronic conditions. We could develop a straightforward resource that shows what actually works and why, so it can be easily translated into clinical practice.”
That seemed like a great idea. What follows is Dr. Bestermann’s explanation of how it can work, followed by an article he wrote almost two years ago called “The New Science of Vascular Disease.”
We are very proud to offer this approach, and hope that interested physicians with deep knowledge of a particular discipline will send us review articles that can be candidates for this service.
WILLIAM H. BESTERMANN, MD
The science and systems exist today to dramatically improve care and reduce costs. Despite multiple recommendations from the Institute of Medicine (IOM) and others credible professional groups, our system remains focused on the care of acute episodes and our approach to chronic diseases is largely ineffective. We spend nearly one dollar out of five on health care and the rate of increase continues to be a multiple of inflation. Most of the increased spending over the last two decades is related to patients with four or more chronic conditions. We have still done very little to improve the effectiveness of that spending and to improve the health of our friends, neighbors, and families. Education and exhortation have not worked. It is time to get serious about new science, new organizational structures, and new systems.
This article, published almost two years ago – on C&C, we’ll refer to these as Recycled but Relevant – is a perfect opening to our Urgent Science section.
If you agree that this kind of review article can be useful to clinicians, let us know. If you would like to write one like this about another topic, or know someone who would, let us know that as well.
Vascular disease and the conditions that produce arterial problems consume roughly one- third to one-half of the $2 trillion annual spend in American health care. The science and systems exist today to dramatically improve the quality and cost related to cardio-metabolic conditions but almost nothing has been done to implement these new tools since the Institute of Medicine (IOM) published “Crossing the Quality Chasm” in 2001.