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Complexities of Diabetes Treatment: Type 1, Type 2 and the New PCSK9 Inhibitors

Aug 13, 2016

Eckel2Exclusive interview from AACE Orlando, May 2016

This is Part 1 of a 3-part interview. Part 2 | Part 3


Robert H. Eckel, M.D., University of Colorado; Charles A. Boettcher Endowed Chair in Atherosclerosis; Professor of Medicine; Division of Endocrinology, Metabolism and Diabetes, and Cardiology; Professor of Physiology and Biophysics; Program Director, Adult General Clinical Research Center

With Steve Freed, Publisher, Diabetes in Control

Dr. Eckel:  I’m a professor of medicine and also of physiology and biophysics at the University of Colorado, Anschutz Medical Campus at Aurora, Colorado. I have an endowed chair in atheroclerosis related research. I’m really a transitional scientist, meaning I have a basic science lab and also work as a preventive cardiologist. Although I’m an endocrinologist, I have a joint appointment in cardiology and that’s where my clinic is. I’m interested in how diabetes relates to heart disease and how to prevent heart disease in patients with diabetes.

Steve Freed: Why are you here at AACE 2016?

Dr. Eckel: I’ve been asked to give several talks, but the one we’ll emphasize right now is on a new form of therapy, recently approved by the FDA, meaning within the last year. That’s the PCSK9 therapeutics. PCSK9 inhibitors are molecules that inhibit PCSK9 and have dramatic effects on the LDL cholesterol lowering. The FDA has granted indications for those drugs as of last summer and I see a lot of very complicated patients. Some with diabetes, some without, that relate to this. I also should say personally, diabetes relates to me as an individual. I’ve had type 1 diabetes my whole life, since, it’s the first thing I can remember, having type 1 diabetes. I’m now nearly 65 years with type 1 diabetes, two children with type 1 diabetes, I am actually on the board of the American Diabetes Association. So I’m obviously personally interested in diabetes and its treatment and also the prevention of complications.

Steve: Now that you mention that, that your family has type 1 diabetes…

Dr. Eckel:  Pump and sensor on my belt.

Steve: I’ve been involved and you’ve certainly been involved a lot longer than I have, but I’ve been involved since ’95. The first day I was involved, I read that we’ll have a cure for type 1 in 5 years. 2000 came along and there’s no cure, 2005 came along and there’s no cure, and we keep going on and on and on. Because I’m exposed to a lot of the research, just like you, there’s so many avenues now open to possible cure for type 1. We’ve got the artificial pancreas, that’s not a cure, but it’s a treatment. So from your expertise, when will we have a cure? We are so close I think at this point in time.

Dr. Eckel:  I’m not sure I agree with that. I think type 1 and type 2 need to be distinguished. By the way, there’s a movement to reclassify diabetes into 7 different types. That is maybe beneficial and maybe somewhat harmful. I think for the average health care professional who deals with diabetes more frequently, I think type 1 and type 2 make it easy. We all know patients as adults who are older who have antibodies that may have type 1, but anyway, in general I think type 1 and type 2 make it easy. Back to your question, I think the cure for type 1 is perhaps possible, but I think there is a major unanswered question. We know about the genetic predisposition. I have those genes, two of my five children have those genes. Ultimately then, what’s the black box of the environmental exposure. So, in other words, if you look at identical twins who have the same genetics, only half get type 1 diabetes. That means there’s something outside the box that has influence on genetic predisposition. So when we identify, is it milk protein, is it wheat germ, is it a viral infection, is it ultimately climate, which we know does influence onset of type 1 and prevalence of type 1. When one or many of the environmental influences can be identified, that ultimately relate to the genetic cause of diabetes, then a cure is possible. But until then, that’s a big black box. Now you stated correctly, the closed loop system will give advantage to many patients, in terms of not having to think about their diabetes in the way they do now. I never cease thinking about where am I at now, where was I a half hour to an hour ago, where am I going in the next hour, based on my activity, on my diet, and ultimately whether I’m sitting all day, or whatever. So that’s something I integrate day in and day out. That’s where the closed loop system is going to help, because the glucose can be maintained without knowledge or input of the patient, we hope. Now type 2 is a whole different ball game. Here’s where I may disagree with you a little bit. People have been looking for decades now for what the defect in insulin secretion is that relates to type 2 diabetes. We know the foundation of type 2 is insulin resistance. So almost all patients with type 2 diabetes, before they’re diagnosed, have had insulin resistance for years. So that puts a strain on the beta cell to make insulin. What the defect is that makes the beta cell, if you will, wear out trying to keep up with the insulin resistance is really going to be a very difficult challenge. Now that’s biochemistry, but yet people have looked at multiple mechanisms that relate to why people don’t secrete enough insulin who have type 2 diabetes. Right now you could pick 15 and pick which one you want to choose as the mechanism for that. So I think type 2 is more of a challenge and more difficult, whereas type 1 I think is genetics plus this environmental factor we don’t know.

Steve:  Certainly type 2 is even more difficult to treat, because like you said, there’s different aspects, different reasons for the pancreas not producing insulin. It could be a gut issue. There’s so many different areas, it could be a pancreas issue. But yet, you really have to look at it as a lifestyle disease. Because from your experience, you see patients, before they’re actually put on any medication and you can actually reverse it. So I always consider them two completely different diseases, they’re treated differently. Actually I would think, but it’s not true, that type 1 would actually be easier because you have to take insulin and you can control what you eat and so forth. With type 2, there’s emotional factors, there’s finances, there’s so many variables in there that it makes it very difficult and getting someone to change lifestyles at the age of 60 isn’t that easy.

Dr. Eckel: It’s kind of a new momentum scientifically into surgery as an indication for earlier onset type 2 diabetes. I was part of that diabetes surgery summit too in London last fall. This next issue in diabetes is going to be entirely devoted to diabetes surgeries, so called metabolic surgery. It doesn’t mean everybody deserves an operation, but it means we need to think about being more aggressive earlier on in people whose weight reduction, particularly when they’re early onset, can maybe have long term remissions that follow. So I think that’s an area of science that really is evolving and maybe it affects clinical care. I think it’s not a matter of you looking in the yellow pages for a surgeon, but you need a carefully operational system to make sure people who take care of patients know their surgeon and when to consider operation. So I think that’s not mainline treatment but it’s increasingly the science of why surgery works as being looked at very, very carefully.


Continue to  Part 2