Finding the Real Issue

As a physician, I began my work with diabetes in 1990 during my surgical residency at the University of Utah. These were incredibly busy years, but also intellectually stimulating due in large part to our chief of surgery, Dr. Gregg Young. We were constantly being trained to be scientists, to question the cause of diseases rather than to simply treat them. This period in my life taught me how to analyze a problem and find what the root cause was, stripped of all ornament. Then it was necessary to develop a simple, but elegant method to discover the answer.

This process of logical thinking has served me well in both my professional and non-professional arenas in life. During this time, the underlying causes of atherosclerosis (hardening of the arteries) were just beginning to be understood. It was being led by Dr. Ross from Massachusetts General Hospital. I remember sitting in one of his lectures, when he noted that the biology of atherosclerosis was beginning to be unraveled but why atherosclerosis in Diabetes was accelerated three- to four-fold was not understood at all. My interest was sparked. How could a slight elevation in blood sugar have such catastrophic effects on circulation?

During the next few years, between surgeries and patient care, I could always be found in the Lab searching for the still elusive “root cause” of my diabetic question. Well, as with anything in life, diabetes has turned out to be an incredibly complicated problem. There is no one cause of diabetes, but it is instead multifaceted. There are hundreds of chemical reactions and genes that go awry in this disease and then somehow this results in poor circulation, among many other problems. In 1995, I was well established in my practice of limb-salvage in diabetic patients. I spent most of my time treating wounds, doing skin grafts and flaps, in order to preserve and prevent amputation of feet and legs. However, the enigma of diabetic atherosclerosis was always at the back of my mind. I was not able to spend as much time in the lab because of work and because I had recently married, and to my surprise, my wife wanted to have a husband at home, not “playing in the Lab.” My wife was extremely persuasive (as I presume most wives are), so I curtailed my lab time and converted it to home time. One of the best decisions “I” had ever made.

All of my research time was now relegated to the clinic, which, as it turned out, had huge advantages. I was able to get information from patients on what helped their circulation. After questioning, we found several common factors for those that had improved circulation:

1. Patients who took certain types of blood pressure medications e.g. nitrates, ace-inhibitors.
2. Those that had recently broken a leg.
3. Those who took large doses of amino acids.

What was the connection? To add to the confusion, researchers at UCLA and Harvard had recently discovered a small chemical they called EDRF in the blood, which caused blood vessels to open, but they had yet to uncover the structure. How did all these interrelate, or did they?