 and welcome to the latest edition of Telehealth in Hawaii. I'm your host, Vikram Acharya. I'm the Chief Executive Officer of Cloudwell Health and all virtual telemedicine-based provider located in Hawaii. We have an excellent show for you today. We have two physicians that are leaders, researchers, and authors, Dr. Sanjeev Chopra and Dr. Martin Abramson. How are you both today? Hi, thank you for inviting us on the show. Oh, Vikram, I'm on top of the world. Well, thank you for being on the show. Absolutely, I'm honored to be on the show. Dr. Chopra and Dr. Abramson are the authors of Conquer Your Diabetes, a wonderful book around the prevention, control, and remission of diabetes. To get things started, Dr. Chopra, tell me a little bit about yourself, where you're from, your role at Harvard Medical School, and we'll go from there. So I'm a hepatologist, specialist in liver disease, a professor of medicine at Harvard Medical School, and I had the privilege of serving as the faculty dean for continuing medical education at Harvard Medical School for 12 years. I was born in India, schooled by Irish Christian brothers, and then did medical school at the All-India Institute of Medical Sciences in New Delhi, and then came with my wife, who was my classmate, to America in 1972, and I've been in Boston since 1973. I'm passionate about teaching and writing and speaking, and I'm also privileged to serve as the editor-in-chief of the hepatology section of Up to Date, the largest electronic textbook to subscribe to by 1.5 million physicians in 195 countries. I've lived in Boston since 1973. I have a beautiful family, and I'll have two incredible inspiring granddaughters who live in New York. Excellent, excellent. Dr. Abranson, walk me through your background. Yeah, so like Sanjeev, I'm born outside of the United States. I was actually born in a little city called Bulawaya, which is in Zimbabwe, and I did all my schooling there before leaving Bulawaya to go to Cape Town, South Africa to study medicine. I studied medicine there, did my residency fellowship training and research training in Cape Town, and then was head of the endocrine unit at the University of Cape Town and Crutuscure Hospital before I was recruited to what was the Beth Israel Hospital in Boston in 1992. And I came here to set up a program in diabetes for the hospital. I trained as an endocrinologist and then focused more of my efforts on managing people with diabetes and developing diabetes programs for people. Beth Israel and the Deaconess Hospital subsequently merged and that merger led to a relationship with the Jocelyn Diabetes Center, which is a prominent diabetes center, probably the most prominent in the world. Started, it's the oldest one, started by Elliot Jocelyn in the late 19th century before insulin was available as a treatment for diabetes. And because of that merger with the Deaconess and the relationship with Jocelyn, I transitioned into the Jocelyn Diabetes Center where I was first the head of the adult diabetes section and then I was the chief medical officer for just over 10 years before transitioning out of that role and coming back to Beth Israel Deaconess Medical Center where I continued to see patients with diabetes. And for 25 years, Sanjiv and I have worked together. We've run the Division of Continuing Medical Education in the Department of Medicine at Beth Israel Deaconess Hospital. We've become close friends, brothers, colleagues. And this opportunity came really when COVID struck. In all credit to Sanjiv, he said, Martin, let's try to book on diabetes. I'm a diabetes physician. He's a hepatologist. We both like to teach. We're passionate about teaching. We're passionate about lecturing and we're passionate about the things that we do. So it was a natural fit that the two brothers worked together to develop this book. Actually, Vikram, Martin and I together with another colleague, Richard Beezer, could have an annual Howard Medical School CME course on diabetes and its complications. Martin gives several talks, Richard gives several talks. I give a keynote on microbiome, man in medicine and then talk about non-alcoholic fatty liver disease which often related to type two diabetes and obesity and afflicts an estimated 70 to 100 million Americans. Very impressive. So we have Dr. Chopra is a hepatologist, a liver doctor. Dr. Abramson is an endocrinologist. How is diabetes for the non-clinical audience linked between endocrinology and the liver? We'll start with that. So there are a number of liver conditions leading to cirrhosis, chronic hepatitis C which afflicts 170 million people in the world, non-alcoholic fatty liver disease which we think may afflict up to a billion people in the world, alcoholic cirrhosis which is a very prevalent disorder throughout the world and then a condition that's called celiac disease where there is an association between type one diabetes and celiac disease. There's also a condition called hemochromatosis which is the most common genetic disorder known to man. Most physicians or medical students when asked what's the most common genetic disorder and probably say cystic fibrosis. In reality, it's hemochromatosis, a genetic disorder in which there is avid absorption of iron from the gut and then it gets deposited in the liver, the pancreas, the brain, the heart, the skin and it leads to in advanced stages diabetes cirrhosis, very high risk of primary liver cancer. This condition is sometimes called bronzed diabetes. So four or five links between liver disease and diabetes. There's other links because the liver is the source of glucose storage and glucose production. And so under normal circumstances, we all know that if we don't eat, our blood glucose levels will not drop too low. The reason for that is the liver has taken the glucose in that is available and distorted as glycogen which is long chains of glucose. And if you don't eat, the glycogen gradually breaks down to maintain blood glucose levels in the normal range. Similarly, when we do eat proteins and amino acids proteins and amino acids in the liver are changed to glucose and then glycogen. So the liver is a hugely important organ in terms of maintaining glucose levels in the normal range. In type two diabetes, which is the commonest form of diabetes affects 95% of people with diabetes. There is a condition called insulin resistance. Whereby the insulin that is produced in the pancreas is just not effective enough to do its job. And the job of insulin is to push glucose that is in the blood into the cells where it's used for energy. So under normal circumstances, if you eat a meal all the carbohydrates get broken down ultimately into glucose, which is in the blood it begins to rise, the pancreas produces insulin which then takes that glucose and pushes it into the cells where it's used for energy. The liver is a site of what we call insulin resistance. And interestingly enough, paradoxically enough when people in people with type two diabetes the liver thinks that the body is devoid of glucose. And there is an increased production of glucose by the liver even when you don't eat even in the fasting state the liver overproduces glucose and that leads to high fasting sugars. So physiology is intricately linked in terms of glucose control, the deposition of glycogen the ability of what's called gluconeogenesis but it's also fascinating that the most common general surgical procedure right now and it's a sad commentary but it is bariatric surgery for weight loss. And people who want to go bariatric surgery can have remission of their diabetes. It's the one surgical procedure that's linked to longevity. Two years out after bariatric surgery patients are taking many, many less medications or low doses and it pays off. Two years later it pays off for the cost of the bariatric surgery. So that's in terms of the diabetes. What happens to the liver disease? One of these people have significant fibrosis or scarring of the liver or even cirrhosis of the liver. And two thirds, the liver fibrosis including early cirrhosis is reversed after bariatric surgery. It's an incredible story. We should get there to the stage where we need bariatric surgery. And one of the game changers will be a new medication which in recent studies in a phase three study patients on the high dose lost 52 pounds. And even on the lower level, 52 pounds. Yeah. You know drugs that cause six, eight pound weight loss, 52 pounds and with the intermediate dose it was like 45 pounds. And with the lowest dose it was like 33 pounds. Phenomenal. Let me just add into that because what Sanjeev is saying is absolutely correct. But let me tell the people listening here that if you lose weight absent of bariatric surgery and it's not easy, but if you do lose weight, weight loss is what drives the improvement in the liver scarring and the fibrosis and so on. Now this new drug that Sanjeev mentions is a sort of one step up, slight step up of a drug that is already available. And they belong to the class of drugs called GLP1 receptor agonists or incrotons. These are newer drugs that came about. So it's a fascinating story how these drugs came about because the first of these drugs that came about came about through a discovery that the saliva of a healer monster, which is basically a lizard that lives primarily in Arizona and parts of California too, contains an enzyme, contained a product that actually stimulated insulin secretion in human beings. And this was almost a serendipitous discovery. And then they then discovered that if you take what is called an analog of this enzyme, you can actually lower glucose levels through stimulating insulin secretion, through blocking another hormone called glucagon, which opposes the action of insulin also produced in the pancreas, by actually slowing the emptying of the stomach and also blocking or suppressing the overproduction of glucose by the liver, which is what happens when people are insulin resistant. And we've seen advances in this original product to medications that can now be taken by injection once a week that have significant impact on weight loss. These drugs can cause significant weight loss. And this new one that Sanjeev mentions is actually what we call an analog of two natural hormones produced in the intestine of humans when food enters the stomach. One is called glucagon-like peptide and the one is called glucose and insulinotropic peptide, GIP and one is GLP-1's GIP for short. And this new drug has actually got both of those hormones in one, which is, it's a drug called tizepotide, which is approved by the FDA but will be on the market very soon. But other drugs that are just GLP-1s can cause significant weight loss and there are a number of those on the market already. I think it's also important for the listener, especially our patients, to appreciate that they don't need to lose all that excess weight. And if they lose five to 9% of excess weight, they can be marked improvement in their diabetes, in their liver disease, in their blood pressure control, in their triglycerides, cholesterol, all of those metabolic parameters can improve remarkably. That is true. Over the course of the pandemic, you mentioned you wrote the book during the course of the pandemic. Are you seeing many more patients with onset of diabetes during the post pandemic at this point in time, because a lot of people have not gone to the doctor, they haven't been as active. You're seeing increased rates of this in your practices? Well, the prevalence of diabetes has continued to increase. So in the United States, in the world, we're now seeing that 13, 14% of the adult population now has diabetes. That's been an increase over, it's been a continuous rise over the past 10, 20 years. I can't say that if in the last year there's been a blip up even further, but certainly we've seen increasing prevalence of diabetes continuously for at least 20 years now. So Vikram, that's an excellent question. I think what did happen during the pandemic, speaking as a liver specialist, is that there was a significant increase in alcoholic hepatitis and alcoholic cirrhosis, and also in worsening of non-alcoholic fatty liver disease. I think for many of us, unfortunately, food is comforting. And if you're sitting at home and you're stressed and you're not traveling and you're not going to the gym, maybe we're eating too much and we're eating the wrong foods and we're drinking a little bit too much alcohol. We had an incredible surge in people on the liver transplant list in our country. And now non-alcoholic steatohepiditis with cirrhosis and liver failure and alcoholic cirrhosis are the one and two indications for liver transplantation in our country. It used to be chronic hepatitis C, but we now have miraculous drugs. You take them by mouth and we have a 95 to 100% cure rate for chronic hepatitis C with pills taken for eight to 12 weeks. And it doesn't matter if they have cirrhosis. It doesn't matter if they have co-infection with HIV. It's really remarkable. It's the only chronic viral infection in human beings where we can use the radical term cure. There's no trace of the virus in the blood. There's no trace of the virus in the liver 20 years after you've eradicated the virus from the blood. So very remarkable, but sadly alcoholic liver disease and non-alcoholic fatty liver disease are on the rise. We have three year olds in our country with fatty liver. We have 16 year olds with fibrosis with scarring. We have 25 and 30 year olds on a liver transplant list with non-alcoholic fatty liver disease cirrhosis and end stage liver and complication. Go ahead, Doctor. Vikram, now you carry on. Now, if I want to check my liver and you mentioned some of these conditions, if I want to see if my liver function is okay, what types of tests can I get? Where can I go? Who can I speak to around this as well as diabetes? Check it out. Very good question, Vikram. I think the primary care physicians routinely will check what are called under the rubric liver function tests, LFTs. And we measure two liver enzymes that deal with liver necrosis. So if there's significant injury to the liver, these two liver enzymes go up in the blood. They're called ALT and AST. Then we check the bilirubin. We check something called alkaline phosphatase. We check albumin, which is a protein made by the liver. And we check the platelet count and something called prothrombin time. Sometimes INR in people on anticoagulation liver disease, we prefer protime. So the liver is the factory that makes all the clotting proteins. So if there's significant liver disease, the protime will go up. If there's significant liver disease, it's a synthetic factory making clotting proteins, but also albumin. The albumin will go down. The platelet count goes down because the spleen on the other side, the liver's on the right side, the spleen on the left gets enlarged and it shoots up the platelets. But also thrombopoitin, which stimulates the production of platelets is made in the liver. So it's a very simple panel of tests that is routinely done. The only plea, and it's happening slowly, is that the upper limit of ALT, which in most laboratories is 40, and AST also 40, needs to come down in men. And if it's 36 or 37, it's not normal. Even though it may look normal under the range. And those patients can have significant liver disease. And in women, it needs to come down even lower. When you see an ALT and AST of 22, 24 in a woman, it's fine. In a man, 28, 30, 32, it's fine. But if it's in the so-called upper limit of normal, it's not normal. And the majority of those patients will turn out to have non-alcoholic fatty liver disease because it's the most prevalent chronic liver disorder. And then what can we do? We can encourage them to lose weight. We can tell them to get vaccinated for hepatitis A and B if they don't have protective antibody. We encourage them to drink coffee. Coffee drinkers have the least amount of scarring with naffin. We tell them it's appropriate to take a statin. Most people say, oh, you have liver disease. You can't take a statin. In reality, that's not true. I'll have a greater proclivity for getting liver disease and short-term statin use, multiple studies, all the statins who know the risk of developing primary liver cancer. And then we can encourage them to enroll in clinical trials. So 12 years ago, there were 12 clinical trials in our country. This year in 2022, we have 435 clinical trials going on on non-alcoholic fatty liver disease. So the majority of these people will do well, but we can intervene at a point in time before they progress to get cirrhosis and complication. Dr. Abramson, if I wanted to, as Dr. Chopra articulated around liver function test, for diabetes, what types of preventive measures can I take? So first of all, I wanna tell people listening that if you have diabetes, there's a lot you can do to improve your glucose control to potentially go into remission if you have type 2 diabetes. And there's been huge advances, not only in the diagnosis of diabetes in terms of the ease of diagnosis, but also many, many advances in treatment, notwithstanding the fact that a healthy diet, especially limiting carbohydrates and exercise, go a long way towards maintaining good control and facilitate weight loss. But to diagnose diabetes, all you need is one test called a hemoglobin A1C. And the hemoglobin A1C is a test that can be done at any time of the day, because it's a test that reflects your average glucose over the preceding three months. It was a test originally developed in the 1970s to assess adequacy of glucose control in people who already had diabetes. And it was used then to monitor people every three months and determine how well they were doing with regard to their glucose control. Because it's become a much more standardized test now, we have used, we can now use this test to define or to diagnose prediabetes and diabetes. And hemoglobin A1C level of less than 5.7% is considered normal. Anything between 5.7 and 6.4 is considered prediabetes and 6.5% or higher is considered diabetes. In addition to that, you can do a glucose test, a laboratory glucose test from a blood sample. And we have criteria for what is normal, what is prediabetes and what is diabetes. And that should be done either in the fasting state or sometimes we even do it after giving somebody a glucose load, which is what we call a glucose tolerance test. Those tests are very rarely used today for routine diagnosis of diabetes. They are very commonly used and it's part of routine practice to screen women who are pregnant for a condition called gestational diabetes, which is defined as diabetes developing during pregnancy and which usually goes away after pregnancy but identifies a woman who is at risk for the development of type II diabetes and also a woman who is at higher risk for the development of cardiovascular disease later in life. So those are the simple tests to diagnose diabetes. It is now recommended that anyone 35 or older should be screened for diabetes and the screening should be started at any age if you have risk factors, if you are overweight or obese and have additional risk factors for diabetes, such as a family history of type II diabetes, a history of gestational diabetes, as I said, a woman who has a condition called polycystic ovarian syndrome, people who have high blood pressure, people who have abnormal cholesterol levels and people who are in certain ethnic groups because there are certain ethnic groups in this country where there's an even higher prevalence of diabetes. African-Americans, American Indians, Asian-Americans as an example. And the Hispanic population. And the Hispanic population. It's mentioning that the hemoglobin A1C is a really remarkable blood test. It gives average of the blood sugar. It represents the average of the blood sugar over the preceding three months. Right, Martin? Three months? That's correct. It's a three-month test measure. And as I say, that was originally developed in the 1970s to as a way of telling people how well their glucose control has been on average because of blood sugar at only one point in time, only tells you what your sugar is then. Nobody really, now we've got things that measure your glucose 24 hours a day without having to prick your finger. They are these continuous glucose monitoring devices which have transformed the way people look after themselves. And I think altogether another topic for another discussion on another day. But the one other limitation of hemoglobin A1C is in people with hemoglobinopathies, for example, sickle cell disease. We wrote the book because we believe in the three eyes that when we have patients, we need to inform them or doctors or colleagues, inform, inspire, and integrate. Three eyes, form, inspire, integrate. And there are amazing stories in the book about people who have conquered their diabetes, lived to the age of 92 years, taken 120,000 injections of insulin during their life. It's just unbelievable. Pilots who lost their license because of type two diabetes and they were taking insulin and they showed working with Martin, one patient in particular that we talk about in the book and he was endorsed the book that he could regulate his blood sugar, tight control, save for him to fly airplanes, commercial airplanes, got his license reinstated. Really remarkable. All the different diets and nutrition, there are at least three patients with type two diabetes who on intermittent fasting have come off insulin, including one patient who had been on insulin for 25 years. So we incorporate a lot of stories. We have checklists with a list of vaccines, the promise of stem cells. There are a couple of patients now who with stem cells appear to have been cured of type one diabetes. So, you know, Walter, the French philosopher once said, every man is guilty of all the good he did not do. And so Martin, I felt, you know, this is an amazing time we live in. It's the 100th anniversary of the first dose of insulin given to a young boy, Leonard Thompson in Canada. Let's write this book. Let's inform, inspire and help people integrate this new knowledge and wisdom. There's one more I, there's one more I that I always add to Sanjeev's three and that's improve the lives of people with diabetes. And this book is intended to improve the lives of people with diabetes as well because there's a lot of positive vibe in the book and it's all true stories. So people with diabetes don't, you should never give up hope. There's always ways that you can look after yourselves, improve your lives and you'll feel so much better for it. That's the important thing. So our patients inspire us and we wanted to pass that message on to the rest of the world. Absolutely. Someone may get diabetes, but there are ways to manage it. There's ways to control it so you can live a healthy and normal life. And throughout this discussion and the book, our audience can learn about it and adapt their lifestyles. If they have diabetes or if they're pre-diabetic, the living a fulfilling life. And it's very unique to have physicians, physician leaders, authors, researchers beyond the show. And I can't thank Dr. Chopra, Dr. Abramson enough for being on the show and contributing and improving the health and wellbeing of the population. I thank you both for being on the show. 30 minutes is not, definitely not enough and we need to have it back. We'll have to do another 30 minutes another time. We're going to do that really soon. The medications and the insulins and the monitoring systems and all sorts of other things and ways in which people can live a healthy life. Yep, coffee drinkers have a low risk of developing diabetes. That's the next subject we're going to get into fairly soon. But for now, I thank you both. Thank you for being on the show. Thank you, Vikram. We're going to do it again soon. I look forward to it. Thank you. Thank you. Thank you so much for watching Think Tech Hawaii. If you like what we do, please like us and click the subscribe button on YouTube and the follow button on Vimeo. You can also follow us on Facebook, Instagram, Twitter and LinkedIn and donate to us at thinktechhawaii.com. Mahalo.