Tuesday , November 21 2017
Home / Therapies / SGLT-2 Therapy Center / Transcript: Dr. Aaron Vinik on What Matters in Studying Bariatric Surgery Outcomes

Transcript: Dr. Aaron Vinik on What Matters in Studying Bariatric Surgery Outcomes

vinik-newExclusive Interview from AACE Orlando

This is a two-part interview. Click here for Part 2.

This interview is also available in video format. Click here to view.
Steve: This is the Diabetes in Control and we’re here with one of our favorite interviewees and he also sits on our board and I’m sure everybody who’s watching this knows Dr. Vinik because we’ve had a number of our prior interviews on our website. And I think we’ll all learn something new every time he shows up, and I would say you’re one of my favorite interviewee’s.  But more importantly the information you come up with is really important to the everyday practice of the medical profession.  So first question is, why are you here at AACE?

Dr. Vinik: I’m here so that you can interview me, basically. If I’m your favorite interviewee, then I’ll come just to be interviewed by you.

Steve: So there’s been a lot of things that were happening here and one of the big things is they’re changing the standard for bariatric surgery, and they’ve changed the criteria, so more people have access to it. But my personal thought is that in most of the studies we’ve seen, that people who go under the knife, eventually, not everyone, but a large majority gain the weight back, maybe not all the weight but certainly gain much of it back. So where does that help, going to major surgery to do something, and then we see that, it almost gets reversed? So, now we’re saying that people that don’t weigh as much as they originally thought, would benefit from this surgery.  So where do we stand with that?

Dr. Vinik: I think that’s really an important question, Steve. So let me tell you where I’m coming from.  I don’t care about the weight loss and I don’t care about the recidivism rate and I don’t care about all those people who’ve gained all the weight back again.  That is of no consequence to me whatsoever.  I use bariatric surgery as a tool and as a tool to find out if it was feasible or possible to reverse the abnormalities in involuntary nervous system function, autonomic nervous system function, because the data shows the following — that if you have a heart rate over 78 beats per minute, and you’ve got impairment or loss of heart , you have a 4.44-fold increased likelihood of dying of a heart attack. And that’s a sudden death, not the heart attack that we’re used to, which is a coronary artery disease death, this is just sudden death out of the blue.  And if you recall, in the Accord Study, there was a 22% increased risk of dying and that death was not a heart attack in the traditional sense.  It was sudden death.  So what is sudden death?  Sudden death is usually an arrhythmia, ok, and a death where the heart just stops beating.  And that is not the traditional coronary artery disease.  So, my question about Guthrie bypass surgery, if it is so good, I mean, there are surgeons who have written to say, is it true that bypass surgery is the cure for diabetes?  Is it true that we can have a permanent cure for obesity?  The answer to both of those is no.  That’s not the question that I’m addressing.  The question I’m addressing is we have given up hope on the ability to stop people having cardiovascular events. We have even changed the way we did studies, so that there were… there was no longer a desire to show that if we used a new drug like an SGLT-2 inhibitor, like an incretin, could we decrease the rate of cardiovascular deaths.  We’ve said as long as it wasn’t worse than placebo, ok, and if it wasn’t worse than placebo, we approved those drugs to know about glucose.  Now the biggest problem of all is that if you look at all the studies that have been done to lower glucose, no single study that has done that has shown that you reduce cardiovascular events.  Now, so now we’re in an interesting situation.  Along comes Empagliflozin, I’m allowed to mention them because they have done the study, and the study shows not that you reduce, you know the traditional heart attacks, it shows that you have a 44/45% reduction in heart failure. You know, a 35% reduction in sudden death. Now that’s interesting, ‘cause I’m hearing the two words I want you to hear. They’re the same as what I’m concerned with; why the increase in sudden death that occurred in the ACCORD study? Why did people die that have autonomic nerve dysfunction, autonomic neuropathy and they died suddenly?  And suddenly we’ve got a drug that’s introduced ostensibly just so that you would pee out the sugar and look what it does. There’s an incredible benefit that is derived from using this drug in terms of heart failure, in terms of sudden death. So I got very excited. I think now, I’ve got to go to see if I can duplicate it, and I want to make it…  Then while we are thinking about this, we get the report that an incretin, a GLP-1 analog, is doing the same thing as an SGLT-2 Inhibitor.  Now you’ve got then ask, well what’s the similarity or dissimilarity between these two and that becomes very important because if it is a similarity then what you’ve got to do is find out what that means and if it means that there’s something in common, you know Bob’s going to be your uncle.

Steve: I always thought that the ACCORD study the reason for the increase in deaths was because we were taking patients that all have some kind of cardiovascular disease, they’ve all had diabetes for many years, they all have A1C elevations, they were all on 10 drugs, and then we tried to lower their blood sugars dramatically. If your blood sugars have been high for 25 years and all the sudden you bring them down drastically, obviously the body is going to react.

Dr. Vinik: Ok, so you picked a lot of the right things. These were people with advanced disease. These are people, like you’re quoting, and these are people on many drugs, and then we were aggressive in trying lower glucose, but you left out one thing.  The thing is what is characteristic about that person that is going to die a sudden death? And the characteristic is that they have an increased risk in heart rate, above 78 beats per minute, and they have lost heart rate variability so I think about the future.  The future says if we can identify the people that have those risk factors, then we’re not going to go fast on the pedal of glycemic control, we’ve going to back off.  We’re going say, that’s not the right thing to be doing.  So, you would then argue with me and say that, “Is there any evidence that I can reverse the autonomic dysfunction?” That’s why we chose gastric bypass.  It is the quickest way for me to prove that I can reverse it, and I did, 4 months totally reversible.  Now we got clean slates, now we can choose those people to put them into any kind of study we like because their autonomic function is intact. And now I know I’m safe to do that, and that’s what I’ve learnt from this, I mean for me it’s very exciting.  That we can do it. And so what I have I proposed? I’ve proposed a new system for looking at people’s risk and if a person’s got high potential of dyslipidemia, all that. So a long-term risk of a macrovascular vein.  But if a person has got a static heart rate, numb feet, and loss of heart rate variability, there’s no way in the world that you must be aggressive with that person for glycemic control, because you’re not going to save his life, you’re going to kill him.

Steve: So, when you talk about, it’s important to know the factors, the risk factors going in, so you mentioned numb feet, you mentioned heart rate, how do you see there’s retinopathy, there’s kidney issues…if we were to make a list of the things that we should be aware of that would determine how we would treat a patient, and that’s completely different than what we do today, from what you’re saying, it wouldn’t be that difficult to come up with a risk factor, put a number on it, and then basically, this is how you treat it. If a person has a score of 10, this might be the way to go. If a person has a score of 4 this may be the way to go.  Because we have so many combinations now that a family practitioner really needs help. I mean, where do you start? We have 11,000 possible combinations.  OK, the ADA says we start with Metformin. A patient can’t take Metformin, what do we do next? SGLT-2s? Or a GLP-1? Or a DPP-4? Or let’s combine the DPP-4 with the insulin? It really becomes very confusing for a family practitioner, not so much for endos, on the best way to treat that, so if we had a scale, where so many risk factors you don’t use this drug, or with kidney issues you can’t use this drug.  It would be kind of easy for a family practitioner to at least give him some help in deciding the best treatments, certainly use his own personal judgment, but it would give a starting point.  It sounds so simple. Sometimes I think of things and I say, why hasn’t anybody else thought of this. And I’m sure they have.

Dr. Vinik: Steve, I think your question is along the lines of what I’m trying to say. And they are the following: you can’t give people long compendia of things to look at.  Even when you look at today, the primary care doc and he goes to look at the AACE guidelines for diabetes management.  He gets on to the first line, and by the second line he’s tired, by the third line he’s gone to sleep and it’s over. And you can’t do that with primary care docs.  Primary care docs tell you the following, they say, “Tell us what to look for and what you must do.  That’s all we want. Two questions.  Tell us what to look for. Tell us what to do.” They don’t say give us a long list, a laundry list of things that they must look for. They won’t do that.  But did you hear that I do mean to tell them to take their shoes off, I say if they’ve got numb feet.  I ask the question. And the first thing I would do when I see that person is I would take their pulse rate, and then I would just say, just breathe deeply in and out and while I’m doing that in the nice old-fashioned way of us old doctors and just feel for whether the heart rate is moving up and down.  Now I’ve got the chair.  If he’s missing all those things, he’s got a 444% chance of dying by intense … control, so I must use drugs that will not produce a drop in blood-glucose; not produce a marked increase secretion of insulin, and I must use drugs that act by alternate mechanisms that are safe and have been shown to be safe.  Like we’ve now got these polarized drugs.  Metformin’s a wonderful drug, it helps people because it stops them eating, it gives them a metallic taste in the mouth, they get diarrhea, it’s a wonderful drug.  But does Metformin, there’s only one study ever that Metformin was shown to reduce cardiovascular events.  In a very small subset of people in the UKPDS, that’s all. Ok. And everybody says, yes it must be our first-time drug (repeats), but nobody’s asking the question, now, that we’ve learned, the beauty of the introduction of these new studies of the new drugs is by accident.  We’ve stumbled across a new physiology of pathophysiology, so don’t let’s be blind to it. Let’s welcome it, you know, get our arms around it and hug it and say “Well, now we’ve got a nice way to go.”  Simplify the risk profile, if the Wusin who wrote the paper from the Framingham Study, W-U-S-I-N, who wrote this paper, New England Journal of Medicine who said, “For years now we’ve used the Framingham Risk Score for heart attacks. I want to tell you all that he made a mistake.” We just have to have the resting heart rate and heart rate variability and we got it. It’s the best predictor we have. And I’m saying ask about numb feet.

Steve:I think the last time we spoke you had mentioned that we’re kind of coming into a new paradigm on a way to treat diabetes. Maybe it’s not so much about reducing A1C because you don’t die from a reduction of A1C, you die from cardiovascular problems. Heart attacks, you know, sudden heart attacks, and now we have drugs and we’re learning more because we thought it was one, now it is two, and it could be 3, actually it is 3, I believe.

Dr. Vinik: It’s 3, right.

Steve: …drugs that can actually prevent death. So is it more important to lower blood-sugar or prevent you from dying? So it’s kind of easy to figure out even though we still have to look at blood sugars.

Dr. Vinik: Wait a second, don’t make that mistake. The reason we’ve got to look at blood sugars is because of microvascular disease. You lower the blood sugar and you do it very gently. Now if you want to prevent retinopathy, nephropathy, neuropathy, there’s no doubt about that, that microvascular disease responds to glycemic control.  And that’s the only reason you must do it, not to reduce heart attacks, not to reduce sudden death, not to reduce cardiac failure. None of those. And that’s what’s hurting. I mean if you look at the statistics to date of people with type 2 diabetes, 44% of those people end up in heart failure. So why aren’t we saying let’s do what’s appropriate?  This organization that I belong to they’re still hanging onto that notion. They say what’s you’re A1C, what’s your A1C, what’s your A1C? And they say you’re going to die of a heart attack. In one of the presentation here, they presented an older woman with a hemoglobin A1C of 7.5, and she had two previous bypasses, cabbages, that she’s had.  She’s hypertensive and dyslipidemic, but she also had lost heart rate variability and she had peripheral neuropathy. And they said what can we do to bring her blood glucose down? I said you do nothing. You do the worst thing in the world, is if you lower that person’s glucose, that person will die.  That person ended up in the hospital and died.  Because they were told that they had to lower the glucose, because her A1C was too high. Is that good?

Steve: That really comes from knowledge of the physician and his learning capabilities. You had mentioned that heart rate of 78, was that a resting heart rate?

Dr. Vinik: Yes, resting heart rate and that’s not my number actually it’s cropped up 3 times that same crazy number, you know, has pitched up in 3 major studies. 35,000 people in a study where they look for prospectively, a heart rate prediction. If you can get your heart rate below 58 beats per minute, good place to be, that’s why you’ve got to work out every day, like me, even with my cane. I’ve got to get that heart rate down, got to get it down, not too much coffee.  But if you have a heart rate over 78 beats per minute, you’re at risk.  If you have a heart rate of 58 and you do well and then you become slothful and become lazy and sitting on the couch, you’re watching TV and never standing up, and it increases from 58 to 78 you have a 90% increase likelihood of an event. So…and it’s simple.

Steve: So what is the risk factor at 78 resting heart beat?

Dr. Vinik: The resting heart rate of a 78? … Unfortunately the risk calculation, use that plus the um… heart rate variability.  So it’s 4.44, so it’s 444% increase.  Now, the study that we’ve just completed, is we show, beautifully, that we can get your resting heart rate down with a bypass, and we can improve your heart rate variability, there is a 40% increase in your heart rate variability, so we know that the bypass, and now I’ll finish my answer to you, and that is, it is totally unrelated to weight loss.  Totally unrelated to obesity.

Steve: And the best way to get that heart rate down?

Dr. Vinik: Exercise, physical activity.

Steve: I just bought a stand up desk.

Dr. Vinik: That’s exactly what I spoke about, not sitting down, you’ve got to stand. Even standing gives you that little bit of an edge. So it’s a very good idea to stand, or like what I like to do, I like to go and see the patients, and I go up and down the stairs. So I go see a patient, and walk back up to my office, go back down, walk back up… You know that’s what I do.

Steve: Then explain to me, that when there’s a meeting like this. Mostly endocrinologists. And there’s stairs and an escalator right there.  Why is it the endocrinologists wait in line to get on the escalator and nobody takes the stairs.

Dr. Vinik: Well, you know have you gone to these new gyms that are cropping up everywhere in town?

Steve: The what?

Dr. Vinik: Gymnasiums or gyms. And do you notice that they are usually on the second floor, and then you notice that they’ve got an escalator up to them.  So that people go on an escalator and then jump onto the treadmill.

Steve: Those people are endocrinologists.

Dr. Vinik: Yeah, oh sure, that’s what they do, that’s what they get in their car to drive a 100 yards to get to the treadmill and then carry out their exercise.  They don’t use, and I said to Etta, Etta’s my wife, so I said to Etta, she came in from Washington, from a meeting, and that our room that we’ve got here is way out of the far end of this Shingled Creek Hotel so she says why didn’t you ask me to get me a room right next to the elevator. I said that’s what I didn’t want to do, and so now you and I, we’ll go and work out in the morning but we’ll walk all the way down, and all the way back, and all the way down and all the way back… that’s what we’ll do.

Steve: I did a presentation once for the electric company and I did three presentations every 8 hours, they had three 8-hour shifts.  And during one of the presentations they gave out awards.  They gave out awards of the closest parking spots right in front to their best employees. So, I got up there and said why do you want to kill your best employees.

Dr. Vinik: That’s right.

Steve: Why do surgeons have parking spaces right in front of the hospital?  You know, that’s setting a very poor example. Getting back, one of the things I’ve found is when it comes to Empagliflozin and the other SGLT-2s is that recently there’s been a huge amount of publicity of DKA for type 2s. And I just talked to a physician, an endocrinologist who said you know, he’s had 1 patient in 33 years with DKA with blood sugars of around 250, he says he doesn’t see any patients on the new drugs, basically, that have DKA that has to be treated. But when you see the headlines and all the newspapers and magazines that these new drugs are causing DKA, it scares physicians off and they don’t prescribe the drug and yet this is the only drug that I’m aware of that reduces blood pressure, reduces weight, reduces… let’s see you’ve got blood pressure, you got weight, what else, I’m trying to think…

Dr. Vinik: It also improves the heart rate and decreases sympathetic tone.

Steve: So it does so many different things and it takes 5 years before a physician feels comfortable, in writing for it.

Vinik:  If you look at what happened to the physicians, endocrinologists and cardiologists, Rosiglitazone hurt them, and they realized they were making a mistake. Along came Pioglitazone, we thought we had it made.  That was going to do… we didn’t have any other problems, and then we come up with a terrible scare of bladder cancer, and a terrible scare of what it was doing to the liver, as well, and then the fractures, and so that’s why physicians are terrified to use these drugs until they’ve had a good run. I come from Africa originally, and you know what Albert Schweitzer said.  He says, “We are not going to use INH for the treatment of tuberculosis until we’ve had a 20-year trial.” And all the people were dying of tuberculosis.  So that’s what happens, people are afraid of it, because they see all these things that emerge. When Empa came around and it was an SGLT-2 inhibitor, the only thing we feared was that poor old woman who was susceptible to monilia, to fungal infections.  We’re going to get a massive increase in fungal infections. And men were going to get balanitis, and so we thought, that’s such a terrible thing, and we had to find out about the susceptibility to that, and then you found that there were a quadrant of people that you could do pretty well in if you added a little anti-fungal agent on the side you were doing fine.  But not that we were going to run into other things like the possibility of bladder cancer, or the marrow toxicity possibility of it.  And then, the other day, amputations: toes, ok, so you say what the hell is happening here? And then, exactly that is ketoacidosis, Euglycemic ketoacidosis. So here a whole new pathophysiology arises and you know what the beauty of that is? When you get a drug, a new drug, that is working on a system that you haven’t thought of before, everybody says, it’s only going to do one thing, it’s going to cause sugar to go out in the urine and lo and behold, it drops blood pressure. OK? It decreases vascular resistance, it decreases the strain on the heart, and then the heart can relax and it doesn’t go into failure.  All these things come up. Now, you pay a little price. What’s the little price? If you dehydrate, and you will, if you pee out sugar, you’ll dehydrate. And if you’ve got hypertension and ischemic heart disease, and you got microvascular disease, you’re going to lose a toe unless you keep hydrated.  And the physicians learn that when you use a drug that causes you to pee a lot, you better drink a lot.  They didn’t, and then they said look what it does! They were being stupid.  I’m sorry to point fingers at people, but they were being stupid if they thought they could do that safely.  The same way as we’ve now known for a long time about when you do those things, and you change the whole sympathetic nervous system, this is what happens.  Sympathetic supply to any adipose tissue, over there is reduced.  The sympathetic nervous system when adipose tissue increases, fatty acids flux.  So now what is happening and also the activation of the sympathetic nervous system acts on the liver and increases glucose output.  So that is one of the reasons why you see ketoacidosis with hyperglycemia.  The glucagon goes up, the epinephrine goes up, the norepinephrine goes up, the growth hormone goes up, so you pour out all the sugar from the liver and you pouring out fatty acids so you get the ketoacidosis, and now we get a drug that changes that.   The input on the fatty acids loads is reduced. So you’ve got, a weaker drive to ketogenesis.  But the other input, the decrease, the changes that you see in glucagon, GLP1, and the other things, are changing the way the liver is functioning, so you’re not getting this pouring out of glucose, and it’s being suggested, two of us suggested this, one was Ralph DeFronso at the AACE Skydance meeting, and one was me, that the nervous system is involved in this.  So now, we sort of talk about the gut talking to the brain, for years, now the kidneys talking to the liver, and the signaling that goes on when you change sugar absorption in the kidney is huge, it’s like a conflagration over there, what’s happening with the nervous system, what’s happening with all these other hormones, and what’s happening with the central nervous system, and after all this kidney has to talk and now it’s talking, it’s saying I’ve got a few surprises for you guys, don’t think it’s just peeing out sugar.

Steve: So, getting dehydrated can be serious when you are on an SGLT-2?

Dr. Vinik: Absolutely, getting dehydrated and the other thing that happens is becoming secure because your sugar is low. And so you cut back on your insulin.  The moment you cut back on your insulin you have an increased pouring of the fatty acids into ketosis, or ketoacids.  That’s what happens. And these people drop, you’ll see in these cases that have been reviewed in the journals, that all the people have dropped their insulin and they’ve stopped drinking fluids.

Steve: So what do you tell your patients that you’re going to put them on an SGLT2?

Dr. Vinik: Never stop their insulin, thinking that it’s ok because my blood sugar is falling. Your blood sugar is falling because we’re driving it all out in the urine.  You keep the insulin going.  Never do that and always be hydrated.  Don’t dry out. That’s simple rules.

Steve: Do you tell them that you should drink so much water?

Dr. Vinik: Oh yeah absolutely. Absolutely.. You know, I mean, I tell them they need a couple of liters a day, if not more.

Steve: That’s actually good information for everybody to make sure your kidneys are functioning properly.

Dr. Vinik: For everybody. For everybody.

Click here for Part 2 of this exclusive interview with Dr. Vinik.

This interview is also available in video format. Click here to view.