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Stanley Schwartz Part 4, Beta Cell Markers in Diabetes

In part 4 of this Exclusive Interview, Stanley Schwartz talks with Diabetes in Control Publisher Steve Freed during the AACE 2018 convention in Boston about precision medicine, which is identifying beta cell markers in diabetes patients in order to determine the best medications to use.

Stanley Schwartz, MD, FACP, FACE is an Emeritus Associate Professor of Medicine at the University of Pennsylvania.

Transcript of this video segment:

Freed: What is the logic of precision medicine?

Schwartz: It’s to find out the specific cause of the beta cell destruction. For that matter, other things, the specific risk they have of complications of diabetes. And that would be to identify markers in each individual patient that tell you then which drugs. Guess what? We’re doing that today in breast cancer, right. They have a genomic ChIP, put a drop, tells which genes are involved, and the readout tells them, “This is the drug you should be using.” We should use the same process of care for patients with diabetes; the genomic ChIP, a metabolomic ChIP, a proteomic ChIP. What are the markers in that individual patient that identify the processes of pathophysiology of destroying beta cells, putting at risk for complications, and figure out the right drugs that treat those complications, and treat the mechanisms that are damaging the beta cells.

Freed: So, what is the value of recognizing the same mechanisms that damage beta cells that are responsible for complication risk?

Schwartz: Well, to go back to when I was in medical school the original thought was, “Are the complications of diabetes a given?” You know, an independent genetic factor that is inherited and completely different from diabetes per se. And there was a gentleman, Marvin Siperstein, quality guy, but he believed that they were two separate diseases; diabetes and the complications of diabetes, and they were completely different. And then, what happened was a gentleman out of Britain, Harry Keen, came up with something that was proven to be more logical. He says, “Diabetes has an abnormal metabolic environment,” right, creates an abnormal metabolic environment; high sugar, high lipids. And you wanted to explain why did some people with the same degree of abnormal metabolic environment, some get complications and some don’t. So, he said, “Well, guess what? Some people are more or less susceptible to damage by the metabolic environment,” so there’s your genetic component. But by the way, some people have other confounding issues; hypertension, hyperlipidemia. Maybe some environmental issues; diet, exercise. And so, your risk of actually getting a complication depends on which genes you have and which comorbidities you have. And then, at some point you’ll get complications, some of them are reversible. And at some point, there may be enough damage to a tissue that it’s irreversible. And that’s the value of recognizing which pathophysiological mechanisms of both diabetes and its complications are going on in a specific way in any individual. So, you can define precise care, there’s where the word precision medicine comes from, for each individual patient.

Freed: Recently, in fact, this morning, I read an article that diabetes increases your risk for liver cancer. We know it basically increases your risk for every disease known to man; dry skin, wrinkles, hearing, eyes, circulation. I can’t think of a disease that somehow is not affected indirectly or directly by elevated blood sugars. And so, maybe you can kind of explain what’s the value of recognizing the mechanisms that damage beta cells that are responsible for malignancy risk and why certain meds can actually treat cancer.

Schwartz: So, this was another 3 AM epiphany I had. (Laughs) And I’m in the process of writing the article. I was asked to review an article. There had been other articles before, so I’m not violating any issues. But the basic principle was there was a clear association of diabetes with malignancy, especially in those patients who were obese and had insulin resistance, and by definition hyperinsulinemia. And you could correlate this increased risk, especially in pancreatic cancer, liver cancer, and endometrial cancer to the greatest degree, and then some other cancers to a lesser degree. And they were the same cancers in “type 1, type 2,” that’s why we should get away from using those designations. And it seems to be related to insulin resistance. And the reason I want to emphasize the type 1 story here, because people say, “Oh, we just said obesity has resistance and so forth,” but guess what, 30% to 50% of type 1 patients have insulin resistance. So, they’re at the same epidemiologic now proven risk of cancer as the type 2s. And not for all cancers, but especially for the three that I mentioned. And it seems to be related to hyperinsulinemia, and the inflammation that can result from it, and over-nutrition, high nutrient states. Because it turns out high nutrient states will lead to biologic pathways that increase the risk of developing cancer and progression of cancer. So, think about it, the same pathophysiological mechanisms that are involved with damaging beta cells, its resistance, inflammation genes, and viral factors put you at risk for complication — could put you at risk for damaged beta cells, put you at risk for complications. And now, seem to put you at risk for developing at least some malignancies. And the correlate not only for stimulating more research but the valuable clinician correlate is it says, “Well, guess what? There are some medicines that we use for diabetes, treating the hyperglycemia that might, in fact, help cardiovascular disease.” I didn’t make that connection before. But guess what? Now, we have the SGLT2s. We have the GLP-1s. We have the bromocriptine quick release, that seem to reduce cardiovascular outcomes. Metformin, 20 years later has that effect, right. And guess what? Now, they’re seeing articles — remember, the same pathophysiological processes are involved and diabetes complications are now involved or been associated with, not proven, with cancer. Guess what? There’s data that now that says, “Metformin might prevent cancer, might treat cancer.” And now, there’s early data suggesting that may be the case with GLP-1s and with SGLT2s. And maybe surprise, turns out that statins might have a benefit that would affect the inflammation story. Turns out some tea leaves. Certain kinds of tea leaves. I don’t know what it’s called. Maybe it’s a fruit, bitter lemon. Both of those, the teas, the bitter lemon, treat sugar and they may be ways to prevent or treat diabetes — treat the cancer related to diabetes. So, it all fits together. But you want to be precision medicine, so you find out the factors affecting each of these issues in each individual patient and then define the right pharmacologic therapy for each of these patients.

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