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Steve Freed: This is Steve Freed with Diabetes in Control and we’re here at the American Diabetes Association 77th Scientific Sessions 2017. We are here to present you some really exciting interviews with some of the top endos from all across the world. We’re here with a special guest, Dr. Mark Molitch who comes from the same area that I’m in and that’s the Chicago area and maybe we can start out with telling us a little bit about yourself and your practice.
Mark Molitch: Okay, I’m at the Northwestern in the endocrinology division. I see patients 3 half-days a week. I do clinical research, a lot of teaching of the resident students and nurses about various endocrinology topics in addition to diabetes.
Steve Freed: That’s interesting that you teach medical students…
Mark Molitch: I do.
Steve Freed: and diabetes is a disease that has a lot to do with knowledge and education, at least from my experience. If you don’t know what a carbohydrate is, you’re doomed for failure.
Mark Molitch: Absolutely.
Steve Freed: Is that one of the things that you teach? Realistically, physicians don’t have the time to educate and they can’t get paid for it. So, what do you teach them to do?
Mark Molitch: In a practice situation, we have dietitians that work with the patients; the nurses can work with the patients. Teach them about carbohydrate counting, how much insulin to use, how much carbohydrates in a meal. It’s hard to teach the students that level of detail. I mean they get general nutrition principles during a medical school education but, then the much more specifics about how to use that in diabetes management is hard to do in that setting and they don’t remember it over the next few years anyway.
Steve Freed: You know, I tell people we should all live like we have diabetes and it’s healthy for everyone. I really think it has to come from the doctors and the education process. Diabetes has changed dramatically over the years and the knowledge we gained in the last 5 years is equal to the knowledge we have gained in the last 50 years. God only knows what it’s going to be over the next five years.
Mark Molitch: We only hope it will continues that progress.
Steve Freed: I always ask the question when you leave here today, if you called Uber to take you to the airport, and a car pulls up and there’s no driver in it and a voice comes up and it says, “Dr. Molitch, Great to have you. Where would you like to go?” Would you get in the car today?
Mark Molitch: Yes, it’s not gonna be far away from that.
Steve Freed: So, technology is really changing. It is changing in medicine. With the CGM systems that we now have and the new ones that will be coming out. Number one, what do you think in the advancement of technology is going to be able to help you take care of your patients with diabetes?
Mark Molitch: We are getting close to a true artificial pancreas, certainly with the integrated pumps in the CGMs that now can sorta semi-automate the basal rates and clearly there’s experimental data showing that you can automate the boluses as well. It hasn’t gotten to the market yet, but it is coming soon. Although I must say that I thought everything was in place 25 years ago to do all that and we’re just kind of now getting to that point, so I see a completely automated, integrated insulin pump continuous glucose monitoring system in the next 5 years on the market and that will really revolutionize care.
Steve Freed: That’s really change dramatically when you were in school. When you were in school, and I presume you remember the days when people had urine strips and they had to pee on a strip and we only had one drug for diabetes, sulfonylureas, and it was a pretty simple, easy decision…
Mark Molitch: We even had a second drugthen, a biguanide, phenformin. That’s since gone by-bye.
Steve Freed: That came 50 years later.
Mark Molitch: No, phenformin, not metformin.
Steve Freed: So, we had 2 drugs.
Mark Molitch: Right, but that one caused too much lactic acidosis.
Steve Freed: So, when you were in school it was easy. What do you do today to teach these students? We have over a couple million possible combinations if you add insulin into it. Single, double, triple, quadruple therapy. It’s gets a little confusing. So how do you teach that to the new people?
Mark Molitch: We do the stepwise approach that you know the ADA has certainly advocated and others as well. Since you started with lifestyle change and then metformin is the first drug and then once you get to the second and third drugs, it becomes more difficult but I think one of the things in fact it was emphasized today is that we need to start thinking about things other than just glucose-lowering when picking that second and third drug. Picking drugs that have cardiovascular benefits or adverse effects of weight gain and hypoglycemia, trying to put all that together when you started picking the second and third drug.
Steve Freed: You heard ADA announced some breakthrough studies possibly. What do you think is the most exciting thing coming out of this conference?
Mark Molitch: I’m waiting to hear about tomorrow. I think tomorrow is going to be most important study from a clinical perspective, which is the CANVA study to see if that duplicates what EMPA-REG did for canagliflozin versus empagliflozin or if it doesn’t, and if it doesn’t then this is a unique drug effect verus a class effect and I think that would be a very important to see the results of.
Steve Freed: You’re presenting at a symposium. It’s called Primer on Transplantation with a Clinician: Addressing Hyperglycemia After Transplantation from Post-Transplant Diabetes to Reoccurrence of Hypoglycemia After Islet Pancreas Transplant. Can you explain that?
Mark Molitch: Really, there’s a couple different aspects to this. One is just looking at patients who had solid organ transplants such as liver or kidney, lung and heart, and the hyperglycemia that occurs after surgery in these patients. So, for some of these people, it’s just diabetes that they had before that is now a little worse with the stress of surgery. For some of those patients it’s diabetes that had not been discovered prior to surgery but it was clearly there, it just hadn’t been diagnosed and yet to some where you just have hyperglycemia related to the stress of the surgery. And finally some people recover from the stress of the surgery. but then develop diabetes months to a few years later related to some of the immunosuppressant drugs that they get for the transplant management. There are several different sub-categories there that need to be addressed and in my discussion, I covered all that information.
Steve Freed: When you think of transplantation …in Canada where they started this whole thing wishing that people go back to diabetes that they require insulin after a transplant. From your experience, would you call that a success, transplantation, and more diabetics type 1 should consider it if we had the beta…
Mark Molitch: You’re referring now to the islet cell transplant, which is a little bit different from what I was talking about, although I did address that in my discussion. So, the islet of transplants, when they’re done now, they’re done primarily for people who have hypoglycemic unawareness after long-standing diabetes; they can’t control their diabetes because of repeated episodes of hypoglycemia. One of the issues is that they don’t like to have patients going for islet cell transplant who have any degree of kidney disease because of the potential kidney toxicity of drugs. So, it’s been relatively successful. You know most patients, probably 80% of people are insulin free at the end of one year, but then that starts to go down pretty dramatically at 3 years and 5 years. At about 5 years, we’re down to well less than 50% that are still not insulin requiring. So it’s a temporizing type of thing. On the other hand, even at 4 or 5 years, even if they require some insulin, they are still much better than they were before, much less hypoglycemia, better controlled, even though they’re not completely insulin independent. But you’re right; you raise a question is this truly a viable type of treatment. It is very, very limited. It requires two or three sets of islets from two to three donors for a single recipient, which makes it fairly difficult to apply this on a widescale basis.
Steve Freed: Being an endocrinologist, you have seen all these new drugs coming out. It’s like you go to sleep one night and you wake up and it’s a whole new class of drugs. And it took us so long to get to this point. There’s so many new drugs in the pipeline. What are your thoughts about the most recent class, which is the SGLT2 drugs, that we’ve found can actually prevent you from dying by 38%? And most people with diabetes, as you’re well aware, they don’t die from diabetes, they die from cardiovascular disease, heart attacks and strokes. What are your feelings about it? A lot of physician would say, “Well, let’s wait 5 more year and let’s really see what the effects are.” You remember Troglitazone, we had that issue. So, what are your personal feelings about it?
Mark Molitch: This class has now been out for three or four years and the five-year data actually are there from the EMPA-REG study, showing empagliflozin to have cardiovascular benefits and we’ll find out tomorrow whether canagliflozin also has this benefit. I don’t see any reason to keep waiting before using these drugs. They’re really fairly effective drugs with very minimum in the way of side effects and we’ll have to see how much benefit that we get. It really only two drugs that show to have cardiovascular benefits and that liraglutide and now empagliflozin. And we’ll see tomorrow about canagliflozin. So, they put them higher up on the list when you start to choose those as treatments.
Steve Freed: So where do you put it on the list? You look at metformin like it’s almost the gold standard to start somebody and then we start to add drugs. Where do you see adding SGLT2?
Mark Molitch: I think maybe as a second line drug, especially with empagliflozin, again maybe canagliflozin. The long-term cardiovascular study for dapagliflozin is ongoing whether this is class effect or single drug effect we don’t know yet.
Steve Freed: Have the changes in diabetes care over the years made a difference in the number of people who develop end-stage renal disease, that is those that require dialysis or transplantation?
Mark Molitch: Absolutely, there has been a dramatic change in the number of people who develop kidney disease to begin with is dramatically reduced. The ones who go on to progress in their kidney disease to require dialysis or transplant is dramatically reduced. And there’s data now from the Diabetes Control and Complications Trial, which has now been following people for over 30 years, duration of diabetes, and it’s really down for one or two percent of individuals having kidney failure. When I first started, you know almost 40 years ago now, we are talking about 20% to 30% of patients that need dialysis, so it’s been cut to 10% of what it was before, so that’s a pretty dramatic difference.
Steve Freed: The next question is, what changes have occurred that account for this improvement?
Mark Molitch: Probably at least two or maybe more. Certainly blood sugar control has made a difference, people getting onto meds, better diabetes glycemic control. I think blood pressure control has also made a big difference and trying to get blood pressure lower compared to what they used to be before. Then of course some of the drugs that are use for blood pressure control that block the RASS has also been shown to have, what appears to be some selective further benefits of (unintelligible) renin and angiotensin blockers have really made a big difference.
Steve Freed: You still looking at the long range of the DCCT trials. One of the mystifying things is that for those people that had intensive control came up better in the study and what we’re learning now after all this time that has gone by, those people that actually participated in the intensive group are still seeing benefits even though their A1C may have gone up.
Mark Molitch: The two groups in the EDIC Trial, which is the long-term follow-up, A1C sort of merged together so the intensive group from 7% to 8%, the conventional group from 9% down to 8%. So, their control over the years has been very much similar, but there is this thing of metabolic memory, if you will, that shows that very intensive control for those intensive people still seems to be showing some benefit in reducing long-term complications.
Steve Freed: Do you share that information with patients and with other doctors that, you know, it’s not something that people have to do…you know, they should do it the rest of their lives, but if they’re normal they’re going to fall off the wagon and their blood sugar are going to go up but they’ll still have the benefit.
Mark Molitch: They don’t go up that much. If you go from 7 to 8, it’s not going from 7 to 10 or 7 to 11, so I think they still have to maintain pretty good control. They can’t totally fall off the wagon.
Steve Freed: So, are there any special precautions in the management of diabetes in the patient with progressing kidney disease? Does it always have to go to end stage renal disease or can we stop it?
Mark Molitch: I think that blood pressure control and glucose control can retard the progression of that. Sometimes it stops it in its tracks; most of the time it just delays progression, but I’ve certainly had patients where it’s just kind of stopped and it’s sitting there, maybe at forty or fifty percent of baseline function and doesn’t continue to progress. I think in some individuals it kinda stops. One of the important things to remember is that many of the medications that we use need dose adjustments as the kidneys progressively fail so that you just have to be sure that as you’re adjusting dose that the patient doesn’t start getting hypoglycemic from too much medications.
Steve Freed: What kind of diabetes control is necessary after a kidney transplant?
Mark Molitch: Well, that’s a very uncertain answer to that question, because we don’t really know. What you want to do is to try to prevent that new kidney from developing diabetic nephropathy again and so we would like the control down in the 7% range if we possibly can, but sometimes that’s a very difficult thing to do.
Steve Freed: From your experience, someone who diagnosed with end-stage renal disease and immediately put him on dialysis and they put their name on the waiting list in fairly “healthy condition” except for that. Where is he on the list? How long does a person have to wait?
Mark Molitch: Somebody like that can be on the list for 3 or 4 years, 5 years even and people with diabetes on that list don’t do well. People on dialysis with diabetes don’t do very well at all. In fact, the 5-year mortality rate is about 80%, only 20% of people are alive at the end of 5 years if they don’t get a kidney transplant, if they stay on dialysis all that time. They’ll be on that list for three, four, five years sometimes.
Steve Freed: So, you are saying, once you go on dialysis, your average lifespan is about 5 years
Mark Molitch: That’s not the average, only 20% of people are alive then, so the average is about 2 and half years. But I mean it’s not from getting dialysis. It’s because everything else is progressing at the same time, the heart disease, the kidney disease, the eyes disease at the same time. The body’s kind of falling apart, but if they get a transplant they do much better.
Steve Freed: The sign of a good presenter is that they take your information that you presented and they use it in their practice. So, what are you trying to get across in your presentation? And I know it was specific.
Mark Molitch: I think the important thing for the presentation that I did the other day was to try to have people stay in good glycemic control that you need to reduce doses of medications but to avoid hypoglycemia while the same time maintaining reasonable glycemic control. You have to be careful about what drug you can use at what level of decrease in GFR and of course in patients who’ve already had a transplant then try to control their glucose level after transplant to prevent them from further complication
Steve Freed: So once the person has a transplant, how important is blood sugar control?
Mark Molitch: It’s still important. That person still can get eye disease, they get heart disease, they get peripheral neuropathy and foot problems, so they still need to stay under good control.
Steve Freed: So, once a person does get a transplant, the success rate is fairly high, is it not?
Mark Molitch: Oh yeah. For somebody with diabetes, their long-term success of the donor organ – their graft, that liver or that kidney – is very close to the normal population, so, there’s no reason that they shouldn’t continue to do well.
Steve Freed: Obviously, you can only do so many because there’s only so many, but you can actually have a family member donate one and that will go directly to you if it’s a match.
Mark Molitch: Absolutely, the best kind of donor is a living donor and a living related donor is by far is the best. So, if you can get a living kidney, that is far better than a cadaver kidney.
Steve Freed: But there are certain requirements that allow a person to use a family member, but there’s also issues that prevent you from using even if it’s a match. If person has an immediate relative and that relative has type 2 diabetes, would that be a candidate or would they not allow that to happen?
Mark Molitch: In general, they don’t like that to happen, because that person’s kidney may have kidney disease already from their diabetes. Of course, they have to have the right transplantation antigens that match, blood types has to match, there’s a variety of other things, the donor has to be in pretty good shape too.
Steve Freed: Thank you for your time. I thought it was very interesting.