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The New Diabetes Classification

This is part 1 of an exclusive interview from AACE 2016.  Click here for video.

Steve Freed: This is Steve Freed with Diabetes in Control and we’re here at AACE 2016 in Orlando, Florida and with us we have actually one of our board members, Dr. Stanley Schwartz, and he’s going to be talking about something very interesting that can affect every single one of us and that is a possible new classification for diabetes. It’s not something he just came up with on his own. The American Diabetes Association asked him to do this to see if he could come up with a better classification than Type 1 and Type 2, Type 1 1/2, Type 3. So Dr. Schwartz, maybe it’s confusing enough, Type 1, Type 2, Type 3, all these different types of diabetes. The late onset type of diabetes, to make it simpler, they’re talking about a new way to classify a person with diabetes that would help not only just classify but help in determining what type of treatment might be best for that patient. So maybe you could give us a little information about this whole new concept?

Dr. Schwartz: Well, the ADA was interesting. They asked me how you diagnose diabetes in the adult, Type 1, Type 2. This was about two and half years ago. What we quickly realized is that we know so much more than we did many years ago when we came up with the current classifications. It was clear at that time Type 1: immune destruction, Type 2: it’s insulin resistance. Fine, that was what we knew. Now we know so much more. There are multiple mechanisms of damage to the beta cell. So the basic principle is that we have genetic factors, we have environmental factors, we have immune dysregulation and inflammatory factors. We have insulin resistance. All these go to the beta cell, affect its function– the beta cell is now the one core defect. The final common denominator for all these mechanisms. The logic then says take the patient in front of you and figure out what’s going on in that particular patient, so you can define better therapy. So, we then follow through with that overriding picture, that umbrella, and say there are at least six specific mechanisms of damage to the beta cell; that’s going to be your insulin resistance organs- muscle, liver, fat-, your brain because you have reduced surge of dopamine in the suprachiasmatic nucleus, the biologic clock- associated with the increase of sympathetic tone, increased appetite, you have the colon abnormalities-, the gut biome story, you have inflammatory immune mechanisms. There you have six mechanisms with damage to the beta cell, and once you damage the beta cell, you have reduced insulin, you have increased glucagon, you have increased GLP-1 resistance, and you have reduced amylin which speeds up the stomach, so there’s another organ. All of those end up causing hyperglycemia, and the most modest hyperglycemia up regulates the SGLT-2 protein in the kidney, which means the sugar stays higher, so you bring the kidney into the equation. Six mechanisms of damage to the beta cell, five downstream events. My simple statement is we have drug therapies even now that can treat all those mechanisms, some of the drugs we have treat multiple mechanisms. GLP-1 has 8 affecting hyperglycemia. The insulin sensitizers like Pioglitazone reduces muscles, liver, fat but it also improves beta cell function. SGLT-2 inhibitors improve kidney, but by losing weight they reduce muscle, liver and fat, they improve beta cell function. So you can then take the least number of drugs that treat the most number of mechanisms of hyperglycemia and then you have a therapeutic regimen for that patient. Right now a lot of our supposition of what’s causing diabetes, the beta cell dysfunction, in that particular patient, are guesses, they’re empiric, based on their family history, based on simple lab tests that we have. So I predict in the future you’re going to have a genomics chips, what genes are found in beta cell dysfunction. By the way a corollary there is that you’ll have genes identified that make you more or less likely to be susceptible to benefit by specific drugs, that’s pharmacogenetics. You’ll have a chip for proteins, proteomic chip, and then you’ll have a chip for metabolic issues, metabolomics. We heard that here at AACE meetings yesterday, how a branch chain of amino acids increased the risk of developing diabetes and progressing diabetes. So you can think of in the future, having three chips, drop of blood on it, it gets back your answer, it will spit out not only what’s going on, it will spit out what the best drugs are for that patient. That’s what’s so exciting and what people have told me in our thinking has been so beneficial and makes them look at the same information in a completely different way. Now, of interest, which goes back to your question, Bob Ratner, the chief scientific officer for ADA is not convinced that it’s going to be easy, if nothing else in a political way, to change Type 1, Type 2, a lot of designations, so be it. We’ll have the patient, specify them however you want, however the ICD-9 people want you to do it, whatever. But we can still tie the same principles to the old classification. Or, ultimately, maybe they’ll change it, the new classification will be diabetes=hyperglycemia, here are mechanisms involved in that patient, here’s the best therapy for that patient. That’s the easiest way I can summarize really in five minutes what the importance that I see in this new approach.

Steve Freed: Well Type 1 and Type 2 have been around for at least a number of years. It’s always very difficult to make changes because the connotation of Type 1 and Type 2 are worldwide. It’s not just the United States. So now to get it changed, to make any significant change it has to be done through the organizations, the EASD.

Dr. Schwartz: So, ideally, you want the EASD, the ADA, World Health Organization, IDF, all these organizations to come together. Practically speaking I can see, and Ratner sees this all the time because in his position he has a political realistic worldview that says, yes we can try over time, maybe we will never succeed, but it doesn’t preclude, and he said this yesterday at a meeting here, it doesn’t preclude applying these principles even to the patients classified in the old way.

Steve Freed: How does prediabetes fit into this?

Dr. Schwartz:  Well all the mechanisms that I said that can damage the kidney occur “early”. They may actually cause the early damage. The downstream effect of abnormal insulin production by the beta cell feedback because hyperglycemia makes the beta cell function even worse. So, all these things happen early. My logic says we should be identifying these people early, even just before they get diabetes, right after they have prediabetes and initiate therapy then. We have this conundrum again, a societal-political one. The CDC says lets prevent diabetes, catch it early, treat it early but the FDA does not give us permission to use drugs in prediabetes. That’s a disconnect, let’s fix it.

Steve Freed: Have you had any connection with EASD as far as putting out feelers?

Dr. Schwartz: Only in the sense that Dr. Ratner and the ADA were kind enough to invite me to a meeting last August in Miami, where we had about 20, 30 physicians representing ADA, EASD, JDRF, and AACE in one place where I presented the ideas. The first response, because you’re going against the grain is, well this is interesting, but…!!   By the end of the second day, all of them were saying you know what Schwartz is saying is more than interesting and there’s things we are going to have to figure out how to deal with. But as of scientific logic, as a pathophysiology, as a method of changing how we approach patients, they all came around and were very intrigued. That was very gratifying to me personally, but more important to all our patients with diabetes, because that’s where all our heads are. How can we improve the care of our patients with diabetes?

Steve Freed: You see this as a huge benefit for the family practitioner making it easier for him to diagnose and treat?

Dr. Schwartz:  Well, right now, it’s unfortunately still empiric, but it’s easier for the physician because you’ll understand that using these drugs that don’t cause hypoglycemia, weight gain, or damage of the beta cell, should be combined early on to succeed in that regard. The least number of drugs treat the most number of causes of hyperglycemia and delay insulin use, which has its detrimental effects. Insulin  causes hypoglycemia, weight gain, and if you’re gaining weight contributes to insulin resistance, which result in increased  triglycerides, and cytokines that will damage beta cells. Primary care can get the benefit of this in realizing early combination therapy is very valuable in  prediabetes/ overt diabetes, and they can learn how to do this.


Dr. Schwartz:  Well, that’s what I did before. That’s the Egregious Eleven. The center of the slide on top a little bit is the beta cell final common denominator to these six organs that are damaging the beta cell. Muscle, liver, fat, brain, colon, immune issues, and inflammatory issues. And then the five things below are the results of damage to the beta cell, insulin, glucagon, GLP-1, stomach, and kidney. It’s there. Even though it’s eleven mechanisms of hyperglycemia, more than the Ominous Octet, there’s a logic to its organization that makes it easier to understand. Damage processes, results of the damage processes, let’s combine drugs that treat as many of those mechanisms as possible.

Continue to Part 2.