A conversation with Robert H. Eckel, MD

September 12, 2021

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Eckel RH. Award for Luminary in Cardiometabolic Medicine. Presented at: Heart in Diabetes Annual Meeting; 10.-12. September 2021 (hybrid meeting).

Disclosure:
Eckel does not report any relevant financial information.

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To the Robert H. Eckel, MD, The desire to learn more about the underlying mechanisms that cause disease sparked an early interest in groundbreaking research in the areas of lipid metabolism and cardiometabolic health.

“Halfway through my specialist training in internal medicine, I realized that medicine is more than just making a diagnosis and making people better,” said Eckel, professor emeritus for medicine in the fields of cardiology and endocrinology, diabetes and metabolism Professor of Physiology and Biophysics and Charles A. Boettcher II Chair of Atherosclerosis at the University of Colorado’s Anschutz Medical Campus, Healio said. “I became incredibly curious about disease mechanisms and why certain drug paradigms weren’t working. I felt the need to get answers and research experience. “

Eckel is Professor Emeritus of Medicine in Cardiology and Endocrinology, Diabetes and Metabolism, Professor Emeritus of Physiology and Biophysics, and Charles A. Boettcher II. Chair of Atherosclerosis at the Anschutz Medical Campus of the University of Colorado.

Eckel, also a past president of the American Heart Association and past president of medicine and science for the American Diabetes Association, would have an outstanding career in lipid and lipoprotein metabolism, nutrition, obesity, and cardiovascular risk prevention. He was one of the world’s leading researchers in understanding the biology and pathophysiology of lipoprotein lipase (LPL) and showed that LPL activity in humans is regulated by insulin. For his life’s work, Eckel received the Luminary in Cardiometabolic Medicine Award at this year’s Heart in Diabetes CME Conference.

Healio spoke to Eckel about his many mentors, his interest in lipids and cardiometabolic health, and the importance of staying curious.

Healio: What brought you to cardiometabolic medicine?

Eckel: At medical school, I worked in a bacteriology lab, so that’s where I learned some basic science. Ultimately, when trying to decide on a medical and research scholarship, I made my choice between infectious diseases or endocrinology and metabolism. By that time, in the mid-1970s, lipids were an emerging area of ​​interest, and we were all learning more about the link between cholesterol and heart disease. I’ve also had type 1 diabetes all my life. I decided that if I didn’t feel like doing research, I could go into practice as an endocrinologist.

The late one Edwin L. Biermann, MD, the department head at the University of Washington tried me. I am infinitely grateful to him for taking this opportunity. My scholarship years have been an outstanding, career-changing experience.

I had five great job opportunities resulting from my scholarship. I chose the University of Colorado – where I’ve stayed for 40 years – because of Jerrold M. Olefsky, MD, the then new head of department. He brought many cutting-edge technologies to understand insulin sensitivity and related aspects of metabolism, diabetes and obesity. Under his guidance, I was able to develop some of the earliest technologies applied to lipid and lipoprotein metabolism, including euglycemic brace and adipocyte biology in the laboratory. This started a career for me that brought lipids and diabetes and CVD together very well for me.

Healio: How did you start your work to learn more about LPL?

Eckel: In the laboratory, this began with the cultivation of preadipocytes. Today this is a well developed technology. The late one Howard Green, A pioneer of regenerative medicine, at MIT at the time, recently discovered that stromovascular cells – so-called fibroblasts – can be removed from adipose tissue and shown in the laboratory that these cells can be differentiated into adipocytes. That paper was 1 or 2 years old when I asked, “Is it possible that these fat cells contain lipoprotein lipase?” That started a 40-year career that has focused in part on LPL as a protein involved with metabolism and less with atherosclerosis related. When I arrived in Denver, I was among the first to use the euglycemic bracket to understand the tissue-specific regulation of LPL and fatty acid metabolism and other aspects of lipid and lipoprotein metabolism.

Healio: Your research also turned to the brain. What did this work focus on?

Eckel: Work with Richard J. Robbins, MD, and Daniel H. Bessen, MD, Over the next decade, we identified LPL in the brain and its regionalization. We finally identified the presence of LPL in the peripheral nerve and its relationship to diabetic neuropathy and to nerve injury and regeneration.

More recently, for the last 5 to 6 years, now headed the laboratory for Kimberly D. Bruce, PhD, We worked on how LPL is related to neurodegenerative diseases like multiple sclerosis and Alzheimer’s.

Healio: What does this work have to do with obesity, metabolic syndrome and diabetes?

Eckel: We have used clinical research and animal models to show that the LPL in adipose tissue is increased in obesity, but increases significantly, especially after weight loss, as a predictor of weight gain. We also conducted a number of studies that showed that LPL in adipose tissue is regulated by insulin and that the regulation is resistant in obesity. However, once people lose weight, they become insulin sensitive.

Later I took down a piece of work Scott M. Grundy, MD, and Paul Z. Zimmet, MD, in The Lancet in 2005 that helped define metabolic syndrome and I was later part of redefining metabolic syndrome. We described the mechanism of the metabolic syndrome as being insulin resistant. We eventually worked with coworkers to develop a model that turns off LPL in skeletal muscles, and these animals developed metabolic syndrome and had weight gain.

We also did some work in the diabetes field to investigate how a decrease in LPL activity is related to nerve dysfunction. We also showed how prediabetes can be distinguished from obesity using muscle biopsies.

Healio: How do these conditions converge to increase CV risk, and what can be done to reduce risk?

Eckel: The 1990s marked the beginning of a new era for metabolic syndrome. Ronald M. Krauss, MD, and I published an article in Circulation in 1998 entitled “The American Heart Association Call to Action: Obesity as a Major Risk Factor for Coronary Artery Disease.” This paper began in depth the AHA’s interest in this important topic.

As part of my AHA presidential address in 2005, I sketched a 3-minute lifestyle interview that has now been incorporated into the AHA Lifestyle Guidelines and used as the standard approach for cardiologists and other busy practitioners to assess a patient’s lifestyle in the Assess clinic. relating to diet and physical activity. As obesity continues to rise, metabolic syndrome follows, along with a higher incidence of type 2 diabetes and cardiovascular disease.

The idea of ​​a new subspecialty in cardiometabolic medicine is something I was promoting Michael J. Blaha, MD, and we have published a number of articles on this idea.

Healio: You are the only person who serve as a former president the AHA, the ADA and the Obesity Society. What perspective did that give you?

Eckel: All of my research is metabolism driven. Anyone who knows me knows that I am interested in these areas. I waved the flag for the Obesity Society to promote obesity as the main comorbidity of many diseases. The management of the AHA came as a surprise – I was an endocrinologist. But in 2005 they felt the time was right to focus on metabolic disorders. At ADA, it has always been important to me to go beyond glucose. For example, there is so much about diabetes related to CVD that goes beyond glucose. Of course, that doesn’t mean that glucose isn’t important.

Curiosity is an incredibly important motivator for me. I am still so curious. But the more you learn, the more you realize what you don’t know. This is what drives you scientifically – to know more and better understand mechanisms.

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