Episode 65: Statins Help Patients with Diabetes

Mike: This is BACON, brief ACO news from the MaineHealth Accountable Care Organization. A monthly podcast for health care providers. I'm Mike Clark.

Heather: And I'm Heather Ward. Mike and I are practicing physicians and participants in the MaineHealth ACO. This month we explore the science behind one of the ACO's Quality Heat Map measures: Statin use among patients with diabetes.

Mike: Yes, and to do so, we welcome a special guest to guide us through. So let's get started.

Heather: The use of statins among patients with diabetes is one of the ten clinical quality measures that the ACO tracks most closely. This year, the goal is to have at least 78.9% of these patients on a statin.

Mike: But wait a minute, Heather. Why is statin use indicated for diabetes? Statins? You know, after all, they're primarily used for treating high cholesterol, right?

Heather: Well, there's a pretty compelling case for statin use in diabetes. And luckily, today we have a special guest to help us understand this. Doctor Stephen Babirak is a leading endocrinologist here in Maine with more than 30 years of experience in the field. He's board certified in internal medicine and endocrinology, diabetes and metabolism. He's also directed or co-directed a number of endocrinology and diabetes programs throughout his career, including Maine Medical Center's Diabetes Division. Doctor Babirak current practice is metabolic leader. It's a diabetes center of excellence and subspecializes in lipoprotein disorders.

Mike: Doctor Babirak, we are thrilled. Welcome to the show. Thank you so much for joining us.

Stephen: Thank you both. It's great to be here and talk about one area that is interesting to me for many decades.

Heather: We are so excited to have you here. So you have researched the impact of statins on diabetes outcomes for a long time, and I am hoping that you can start us off with some of the basics. Really, as a primary care physician, talking to patients about this all the time, I just want to understand why is it important for a patient with diabetes who has normal cholesterol to be on a statin?

Stephen: Well, this question has a lot of research behind it, but the real reason why we are most interested in taking care of diabetics with statins or other lipid lowering drugs is the basic reason that the vast majority of people with diabetes die from cardiovascular disease. We do know that cardiovascular disease is the major cause of death, disability, and it is the major leading cost for diabetes. If you include just stroke and heart attack, it accounts for about 66% of all diabetic deaths. If you include heart failure and peripheral artery disease, it accounts for about 80% of all the death in people with diabetes. That's four times more than every other reason put together in diabetes. And I'll explain in a little bit more detail why statin use has come to be the drug of choice, based on all the scientific data that is available now to reduce cardiovascular outcomes in people with diabetes.

Mike: Wow. That that is an incredible statistic. And it's such a significant burden of the morbidity and mortality that our diabetic patients carry. I would love to hear a little bit more about the physiology as you alluded to and how this improves outcomes in our patients with diabetes.

Stephen: Well, the research goes back, at least in my history, back to about 50 years. You know, for many years we've been trying to understand why. As mentioned earlier, people with relatively normal cholesterol have rates of death that are equal to somebody with familial hypercholesterolemia, whose LDL cholesterol is two, three, four, or five times the normal range. How can it be? So my research started about 50 years ago looking at triglyceride metabolism. And it has evolved over the years by a number of investigators. We first showed in 1980 to 1989 a trial called the Familial Atherosclerosis Treatment Study, where in this study, we took people in, some with diabetes that already had heart disease, so it was secondary prevention, and we showed with lipid lowering therapy a 90% reduction in recurrent heart attack, stroke or death. And so secondary prevention became a huge tool for clinicians way back in the time frame where nobody thought that cholesterol had any meaningful impact for people with diabetes.

Stephen: In 1993 and 1994, other studies were published, the 4S Trial, for example, and AFCAPS/TexCAPS Trial in primary prevention. I participated in that trial in a large diabetes clinic I was in during the Air Force, and again, we showed the majority of heart attack, stroke and death was diminished by aggressive lipid lowering. Followed serially by other investigators, the Heart Protection Study was the first study ever to show a reduction in death in diabetes with a drug that had nothing to do with diabetes control. Again, statin use in these trials was either statin in the form of lovastatin, which was the first statin ever designed, and it had reductions in clinical events similar to what we saw in patients with very, very high cholesterol levels.

Stephen: In 2001, the ATP thought it was so significant that they put diabetes as top of the list for lipid lowering therapy in prevention for coronary artery disease and stroke. So, both secondary and primary prevention studies have changed the whole history of diabetes and again lowered the major cause of death, disability and cost of diabetes. Again, a drug that had nothing to do with blood sugar. It was the first drug ever to reduce death in diabetes.

Heather: That is really just impressive information and a powerful argument for the use of statins in diabetes. I think for me, hearing you say that heart disease is the leading cause of death in people with diabetes is argument in and of itself to use statins and diabetes. But for some people, my patients in particular, who have been reading things in perhaps lay literature, there are a lot of misconceptions that go along with statins. And if you don't mind, I'd really like to just take this opportunity to dispel some of those myths if it's okay. So, first myth ready? Lowering cholesterol causes dementia. What do you say to that?

Stephen: Well, it is something, Heather, that was first on the top of the list when lipid lowering therapy hit the market in the United States with statin use in 1987, Lovastatin was the first drug out, and a number of concerns came to the forefront to clinicians. And one of them was neurologic function. We do know that if you actually look at nerve cells, the majority of a nerve cell is actually cholesterol. And cholesterol is essential for nerve function, proper nerve function. And we did know from genetic studies decades before that if you had no cholesterol in your bloodstream that you died young. One of the complications was neurologic related to peripheral neuropathy. But one of the biggest concerns initially was that it would affect neurologic function in the brain. And so, a number of studies were done, and it was heightened awareness regarding the effect of statins on neurologic function. Fortunately, none of the studies really showed a consistent relationship between neurologic function, cognition, dementia, memory, or any neurologic event. Now, there had been some reports that memory in some studies can be affected. Three randomized clinical trials showed no effect on cognition. The FDA did a post-marketing analysis and did an entire look at this in addition and again showed no decline in any neurologic function. Now we worried about this. But in another potential benefit is to reduce cardiovascular induced dementia. And so other studies have been published to show that vascular risk factor reduction can actually improve outcomes of cognitive function in people with diabetes. We do know that the vascular risk factors such as hyperlipidemia, diabetes, metabolic syndrome, cardiovascular disease, hypertension, obesity and smoking are all related to dementia, Alzheimer's disease, and vascular dementia. So the next question was does improving lipids actually improve memory and improve cognitive function, and the results really have been plus and minus. There's been no consistent finding, and therefore it is not a reason not to use lipid lowering therapy in people with diabetes. And again there may be some benefit.

Heather: That's great. Also, I'm seeing more from our neurologists as well pushing us to use statins more aggressively just to help reduce that vascular risk. Awesome. Okay. So myth number two. Statins cause diabetes.

Stephen: Well, this was proposed as a potential problem with risks of statins. And it indeed has been shown that it is a rare consequence of statin use. We're trying to understand the pathophysiology of how it happens. But we know it's rare. So large clinical trials, as well as multi-centered analysis, have looked at the potential risk of getting diabetes incident diabetes in patients on statin drugs. So we do know that from these large meta analysis, about one in every 250 people or more, more likely one out of every 500 people that go on a statin that don't have diabetes may develop incident diabetes. It's suggested that the rationale for this is that genetic studies looking at people with low levels of HMG-CoA reductase, which is the rate limiting enzyme for cholesterol formation, which on which a statin actually lowers it, that in these patients with a genetic cause of low HMG-CoA reductase, that it is associated with mild hypoglycemia. We do know that the incidence of diabetes in the general population is about 10% in Maine. And we do know that if it is true that hypoglycemia develops, it tends to develop in people who are at high risk of developing diabetes, who are at risk of getting diabetes in the first place.

Stephen: So, it's been shown that it may be related. This incidence may be an increased incidence of hypoglycemia, may be related to people who are already at risk of getting diabetes. So clearly the risk of getting diabetes is much more common than 1 in 250 or 1 in 500 patients. And we do know that the benefits of lipid lowering therapy in people with diabetes or without diabetes exceeds the risk of getting diabetes, for example, a study was done that showed that the overall absolute risk is small of getting diabetes in the general population. Without statin, it's 1.2%. If you look at people on statin, it's 1.5%. And the risk reduction in heart attack, stroke and death, which is the leading killer in people without diabetes and by far the leading killer in diabetes, is huge. So to prevent one case of diabetes in 255 people, for example, you would have to give up 5.4 cardiovascular events in the 255 people. So the American Heart Association, the American Diabetes Association, and every major international organization support the use of statin irregardless if they may get diabetes in somebody who is already predisposed to get diabetes.

Heather: Yeah. Well, that makes that makes a lot of sense. And that clarification is really helpful. Okay. The next one is statins are too expensive.

Stephen: Well, it initially was very true. Just like any new drug that hit the market. Statins were very expensive to start with. Certainly not as expensive as some of the other drugs we currently use. But statins initially were very expensive, and insurance companies were unlikely to accept that. But over the course of the last 30 years, the price of statins are now generic, and many of the current insurance companies and pharmacies themselves the charge for generic statins, such as rosuvastatin, which is probably the most commonly used one in people with diabetes, is very affordable and commonly it's free under many insurance programs, including Medicare. At least in my Medicare program.

Heather: Awesome. Well, that is super helpful. Okay. I have one more. And this is a common concern among some of my male patients. The last myth is cholesterol lowering medications lower the cholesterol needed to make testosterone. Well, is this true?

Stephen: It is not true. You know, the availability of steroid production related to steroid synthesis is, is totally unfounded that it would interfere with the synthesis. Every cell in your body can make cholesterol, and a cholesterol inhibitor such as a statin does not inhibit, absolutely, cholesterol formation in any tissue. It does reduce cholesterol synthesis, mainly in the liver, but it does not inhibit the cholesterol needed for testosterone production, for adrenal hormone production, or any steroid production for that matter. This has been well studied, and this is a myth in the literature that is totally unfounded.

Heather: That is fantastic. It's a nice reminder of our basic pathophysiology from med school. Two different compartments. And all those cells can make the cholesterol that they need. That. That's great. Thank you for the myth busting.

Stephen: Oh, I don't know if I did it, but there's many things that we have to face as clinicians. And certainly, in the lipid clinic here, we face a lot of these problems. And I think probably one of the most important things is that that we need to emphasize that the patients, that they're not going to die from a high blood sugar, although that's what we've been focusing on from 1929 all the way until now and even before 1921.

Heather: Yeah.

Stephen: And that lowering blood sugar has nothing to do with reducing their death or their stroke or their heart attack, or their amputation from peripheral artery disease. That clearly quality of life has improved dramatically with statin therapy. And it is true that there are some patients we have to be careful about using statins in. There's no doubt like any other drug, it can be a double edged sword. But the reality is, is that they're going to die more than likely from a cardiovascular event than they're going to die from a high blood sugar.

Mike: That's excellent. Thank you so much, Doctor Babirak. It's great to have tools in our toolbox as we sit down and have these important conversations with our patients. And often it's more than one conversation, right? We've got to keep revisiting these with our patients as we advocate for their best health outcomes.

Mike: I'm curious also is is this understanding, this led to consensus among medical societies? Is there really any controversy left out there among the professional societies around this recommendation of statin use in our diabetic population?

Stephen: There is no controversy at all anymore. It is, again, one of the most important things to reduce the major cause of death. And I showed back in 1993 the major cause of disability and the major cause of diabetes. So when you look at the benefit, it's it's a win win win for everybody. It's a win for the medical system. It's it's a win for the physician to prevent the major problem that does occur in diabetics. And it's a win for the patient. So the way I think everybody has placed this, the ADA has certainly taken a primary role in trying to educate people. But so did the American College of Cardiology, the American College of Endocrinology, of every major international organization, all recommends the same thing. And now the goals of therapy have reduced way down to lower levels than we've ever seen before for LDL or non-HDL cholesterol. So, because of the pathophysiology of why diabetics get such rapid head to toe atherosclerosis, is really well known that the statins attack that it's not like FH, where LDL is the major cause of their blockages in the heart or blockages in the cerebral vascular system. But what we do know that aggressive lipid lowering lowers the major atherogenic lipoproteins that are circulating in a diabetic. And we need to be very aggressive. So the new recommendations are seem to be extreme to most clinicians, but every single study that's ever been done on lipid lowering all showed the same thing, whether it's in this country or out of this country worldwide. It is very well recognized now that if a diabetic has cardiovascular disease, and that can be defined in a number of ways, that that the LDL target is 55 or lower, or a non-HDL of 80 or lower in people without cardiovascular disease and diabetes, the LDL reduction is to 70 or lower with a non-HDL of greater less than 100.

Stephen: Now these endpoint targets are hard to achieve and sometimes impossible to achieve with our current medical armamentarium of drugs. We do know that the newer drugs, which are non statin drugs such as Pcsk9 inhibitor, and I published some of this work in diabetes a number of years ago And in other work with Ossetia, which is less profound in its cardiovascular risk reduction that other non-statin drugs are needed to add to statin drugs to get to these endpoints. And sometimes even those drugs won't get us to the endpoints. And we are at metabolic leader do LDL apheresis, which is the treatment of last resort for people with established cardiovascular disease and hyperlipidemia. And many of the patients we see have diabetes, where we actually remove the atherogenic lipoproteins from their blood and give them the blood back. It's a relatively benign procedure in which it takes about four hours, and we are the second largest in the United States, a center that that does this on a regular basis. And so, we have this resource in Maine for clinicians. And it is underused by far. There are many people with diabetes who are way undertreated. And we are a center for that kind of approach to people who are very difficult to control.

Heather: Well, this has been so enlightening. And I can't thank you enough for coming here and spending your time with us today. I'm wondering if you have any final words of wisdom for primary care providers, in particular, who are treating patients with diabetes?

Stephen: Well, you know, as I mentioned, the threat to a diabetic and their outcome is really related to their cardiovascular disease and the perceived threat of cardiovascular disease is minimized, I think, in people with diabetes. We need to be strong advocates for cardiovascular risk reduction. And there's many ways lipid lowering is one of them. Lipid lowering was the first, as I mentioned in the history of diabetes, to show a reduction in the major threat, which is heart attack or stroke, or other forms of cardiovascular disease also have been highlighted. We need to be clear in communicating this to patients to say that, you know, you're not going to die from a high blood sugar. Look, we spend all our time talking about blood sugar, but really, the major cause of what's going to either kill you or disable you is really cardiovascular disease. And the treatment is very important. If you have a diabetic who's already had a cardiovascular event, their rates of death are equal to somebody with metastatic colon carcinoma. Now look what we do to people with metastatic colon carcinoma. We do surgery. We do radiation. We do chemotherapy. That almost kills them. You know, a statin therapy is not anywhere near any of that in severity as far as treatment goes. And it has better outcomes than most chemotherapy in patients with metastatic colon carcinoma. So, and when you look at the simplicity of what it is that kills them and the simplicity of what the treatment is, for most people with diabetes, it is a no brainer to go on a statin drug. And again, we need to highlight that there are barriers. There's misunderstandings and costs. There's misunderstanding and side effects. But we need to reinforce the benefits at each office visit.

Heather: Yeah.

Mike: Wow. Thank you. Wow. Doctor Babirak, thank you so much. Just to really give us that context and help us, really as frontline primary care docs to really grasp the urgency of this very accessible intervention that can make such a huge impact in our patients lives. This has been such a valuable conversation. Thank you. Thank you, doctor Babirak, so much for your insights today. It has been a pleasure.

Stephen: Well, thank you for letting me join. And it is obviously an obviously a passion of mine for a number of decades, and really anything I can do to help. I am more than willing. But thank you for the opportunity to be here.

Heather: Thank you so much.

Heather: Thanks for listening to BACON this month. You can find all our episodes on your podcast app and at our web page, MaineHealthACO.org/BACON. And if you have questions, comments or suggestions, we'd love to hear from you. Please email us at bacon@mainehealth.org. That's Bacon@mainehealth.org.

Mike: BACON is produced by the MaineHealth Accountable Care Organization. Thanks for joining us. See you next time.

Heather: See you next time.