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Diabetes Core Update
Diabetes Core Update April 2025
00:33:37
Diabetes Core Update is a monthly podcast that presents and discusses the latest clinically relevant articles from the American Diabetes Association’s four science and medical journals – Diabetes, Diabetes Care, Clinical Diabetes, and Diabetes...
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- [00:02]
Dr. John
Welcome to Diabetes Core Update, the American Diabetes Association's official podcast where each month we discuss with you the most important articles to be published on diabetes, obesity and metabolism across the medical literature. This month we have a really fantastic set of articles, beginning with an article on coronary calcium guided primary prevention strategies published in John, where we will be talking with the author of the editorial that was published in JAMA Cardiology. Then an article from Diabetes Care on health related quality of life and health utility after metabolic bariatric surgery versus medical lifestyle intervention in individuals with type 2 diabetes and obesity. Then we're going to discuss an article from the Lancet on suicide and suicide attempts in users of GLP1 receptor agonist. This is a nationwide case time control study. Very important information. Then we're going to discuss a very interesting and important article on self monitored blood glucose and continuous glucose monitoring in youth with type 1 diabetes and and Medicaid insurance. Looking at the question of if you use self monitoring of blood glucose as a criteria for entry to get cgm, does that make sense? This was published in Diabetes Care. And finally we will conclude with an interesting discussion with the author of an invited commentary from JAMA Network Open who discusses the relationship between poor sleep and adverse effects on blood glucose and specifically discusses an article on gestational diabetes progressing to type 2 diabetes and is poor sleep to blame for our first article? This month we'll be discussing a study published in JAMA titled A Third the Effects of Combining Coronary Calcium Score with Treatment on Plaque Progression in Familial Coronary Artery Disease, a Randomized Clinical trial. Joining us to discuss this trial and importantly its implications is Dr. Michael Blaha, who wrote the editorial about this article in Jama Cardiology. Dr. Blaha is a professor of cardiology and epidemiology and presently serves as the Director of Clinical clinical Research for the Johns Hopkins Ciccaroni center for the Prevention of Cardiovascular Disease. Welcome Mike.
- [03:01]
Dr. Michael Blaha
My pleasure to be here. Thank you so much for the invitation.
- [03:04]
Dr. John
Mike, can we start by your giving us some background why they chose to do this article?
- [03:11]
Dr. Michael Blaha
Sure, yeah. I think there's a lot of uncertainty in clinical practice when you have patients that are not clearly low risk but are not clearly high risk, but have what we call a risk enhancing factor. There's a list of risk enhancing factors in our guidelines, but I think the most common one that we talk about is a family history of premature coronary disease. There's always this issue when a patient is not clearly high risk but has a family history of premature coronary disease, what do you do? Do you put that patient on a statin because that family history, do you, do you treat other risk factors aggressively or do you conduct some sort of extra advanced risk stratification to personalize the management? That really is what the background is for this trial.
- [03:56]
Dr. John
Yeah, and this happens a lot in all of our practices. That intermediate risk zone is really a ten year calculated risk of about seven and a half to 20%. And as you said, particularly if you have risk enhancing factors that leans you toward treatment. But ideally we, we'd like to be a little more precise. Can you tell us about what this trial looked at, how they went about looking at this question?
- [04:25]
Dr. Michael Blaha
Yeah, so in our ACCAHA guidelines, and actually the European guidelines would be the same, the National Lipid association says the same thing as well. It says in this scenario where you have an intermediate risk patient, perhaps with a risk enhancing factor like family history, consider doing a coronary artery calcium score. That's a Class 2A recommendation to further refine the risk of that patient and most importantly, the treatment strategy, offering possibilities of being less aggressive with the therapy or more aggressive based on the results. But that hadn't been put to the test. So this trial took just these patients. They had calcium scores done. We'll talk about the methods anyway in a moment, but then randomize them to a calcium score guided approach or a standard of care approach and try to assess. Well, it makes sense to do a calcium score and treat in a personalized way. But does it actually bear out in a clinical trial that it improves some intermediary outcomes.
- [05:28]
Dr. John
That'S so important. Can you tell us how they went about looking at this?
- [05:33]
Dr. Michael Blaha
Yeah. So this is an Australian trial called the Cotton Cad trial. And the, the rationale once again is these patients with family history. Now in Australia, they use statins a little less aggressively than we do in the United States. So there's quite a bit of equipoise here, even up to, like you said, these higher intermediate risk patients. So generally speaking, they took middle aged intermediate risk patients with a family history and they did a calcium score. And if the calcium score was zero, which occurred in 56 to 58% of patients, those patients did not get in the trial. And they also took patients with very high calcium scores above 400 and did not put those in the trial. But the other ones they put into a trial, the trial was a randomization to being told the calcium score and having an education program around that calcium score with treatment based on the calcium score results or in the other arm binding to the calcium score and usual care. So the clinicians were unaware whether these patients were high risk or low risk and treated as we would in clinical practice when we were not guided by imaging and the other arm specific teaching based on the imaging, they were shown their scores and talked about their implications and offered statin therapy accordingly.
- [06:51]
Dr. John
Yeah. Now, at baseline, what was the calculated 10 year risk of. Of people?
- [06:58]
Dr. Michael Blaha
Yeah, their risk was about 7%. So in the US guidelines, that would put them distinctly in that borderline risk zone or approaching that intermediate risk zone. So very much in that uncertain zone where the guidelines do not have a strong recommendation for statins, but a moderate level of evidence to consider a moderate intensity statin. So you're going to see a lot of variability in practice whether these patients get treated or not.
- [07:25]
Dr. John
Yeah, so it was really fascinating. So can you tell us about what the treatment ended up being? In the group with coronary scores done and in the group that did not have that done?
- [07:38]
Dr. Michael Blaha
Yeah. So in the group with the coronary scores done, of course, all these patients were then determined to have a calcium score or have plaque in their arteries based on the calcium score. Many more of these patients were treated with the statin compared to the usual care arm where clinicians didn't have any extra information. So they knew this was a borderline patient with a family history and they may or may not have treated the patient, but ended up overall much less patients being treated in that arm of the trial. So there was more aggressive LDL control in the calcium score and formed arm.
- [08:14]
Dr. John
Yeah, and that was so important. I was so happy in your editorial that you pointed out that over 50% of the people had calcium scores of zero, so actually fell out of the trial and didn't get a statin at all. So now we're just looking at the people for whom there was a calcium score greater than zero and less than 400. Right. And they all received statins, I think a Tor of a 40. What did the results show?
- [08:41]
Dr. Michael Blaha
Yes, so the results in this study was not hard cardiovascular outcomes, but it was plaque progression. So at the time of that baseline CT scan where the calcium score was determined, they had a CT angiogram as well to look for plaque. And then at the end of the study, they also had another CT angiogram. So plaque progression could be quantified, including total plaque progression, non calcified plaque progression, and several other iterations of plaque progression. So what they're able to show is in that group that had they were informed of their calcium scores, as you said, were treated much more likely to be treated and adhere to their statins compared to the other group where they were treated less and adhered to those treatment less. There was significantly more plaque regression or slowed plaque progression in the calcium score informed arm, and there was less slowing of plaque progression in the usual care arm. This has been shown in other studies, this plaque progression metric to correspond to outcomes. And it's being accepted increasingly as a valid surrogate. So it suggests that we're having more of an impact on atherosclerosis in that personalized treatment arm where patients were informed of the calcium score and then treated with the statin accordingly.
- [09:54]
Dr. John
So this is a big deal because it lets us in over half of the people not use a statin, but in the people who are at higher risk actually use a statin. And this trial showed that it decreased progression of atherosclerosis. What do you see as the clinical implications of the trial?
- [10:14]
Dr. Michael Blaha
Yet? This falls in line with what we've been saying for a long time, in fact way that our guidelines are written, but without this benefit of this trial, which is we can personalize the care of these patients that are borderline risk or early intermediate risk patients with a family history, because we know they're all not created equal. Right? We know this from practice. Some of them turn out to be high risk patients, Some of them, for whatever reason, just haven't inherited that risk from their father who might have had a heart attack. And they're actually a low risk patient. So what this tells us, the implication is that we can successfully personalize therapy, find almost three out of five patients who don't have any calcium in their arteries and potentially treat them more conservatively. Of course we're treating them still, but we're emphasizing lifestyle therapy and things that benefit over the decades of the remainder of their life, and emphasizing aggressive treatment on the patients with identified atherosclerosis and maybe treat those even to aggressive LDL targets. So it's not one size fits all. In fact, it's not everyone needs a therapy, but some people need aggressive therapy. And then we can actually impact the natural history of plaque and plaque progression with our interventions in these patients. So it's really important. It tells us what I think, what patients are asking for. What the patients ask me a lot is do I have plaque and what can we do about it? And what's the rationale for me to take this drug for the rest of my life? And I could say, well, I know what the rationale is in this case. You have plaque in your arteries. In fact, you might have substantial plaque in your arteries. This is likely to be the substrate that your father or mother had before their event. And we're going to try to get on top of this now.
- [11:53]
Dr. John
So important. And this was in patients what ages, beginning at age 40, was it?
- [11:59]
Dr. Michael Blaha
Yeah, that's right. And I think the mean age falls kind of right there in the middle age group, I think in the, in the 50s. That's, that's the commonly the patient that I see in my practice, you know, in that 50 zone, starts to be aware of their potential risk and comes in for what I would call a personalized risk assessment visit. They're open to therapy, but they're not saying to me, well, I just want to take everything I can. They say, well, I want to know my risk before I make my decisions about what I want to take for preventive care. And I enjoy those discussions with patients.
- [12:33]
Dr. John
These are great discussions. And this takes us one step closer to really the holy grail in medicine, which is personalized risk management, treating the right patient with the right drug at the right time. Dr. Michael Blaha, thank you so much for joining us.
- [12:49]
Dr. Michael Blaha
Oh, my pleasure. Thank you so much.
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Dr. John
For our next article, we're going to discuss an article from Diabetes Care titled health related quality of life and health utility after metabolic bariatric surgery versus medical lifestyle interventions in individuals with type 2 diabetes and obesity. The ARMS T2D study Type 2 diabetes and obesity are associated with reduced health related quality of life. We know that, but long term effects of metabolic and bariatric surgery compared with those of medical lifestyle intervention on these outcomes are unclear. The authors studied 228 individuals with type 2 diabetes and obesity randomly assigned to metabolic bariatric surgery and that included Roux En Y, gastric bypass, sleeve gastrectomy or gastric band or medical and lifestyle interventions. In the ARMS T2D study, health related quality of life was measured with a 36 item health survey that is a standard one including physical component score and mental component score and these were measured annually for up to to 12 years. The mean age on entry was a little over 49 years. 68% of people were women. The average BMI was 36.3 and the mean A1C was 8.7 with quite a range. 1.6% physical component score improved significantly more in the metabolic and bariatric surgery group versus the medical lifestyle group over 12 years. Metabolic bariatric surgery was associated with better general health and these P values by the way, were impressive. P less than 0.001 for everything I'm reading. Physical function and vitality reduction in BMI was greater after metabolic bariatric surgery than after medical and lifestyle interventions, and that correlated with improved physical physical component scores. The mental component score changed minimally from baseline and was similar between the two groups.
- [15:18]
Dr. Neil
John so Neil, I find this a very interesting article and when you think in our clinical time, what percentage of our work week we are now talking about obesity and medicines and does someone qualify, et cetera. So I find this to be very interesting thinking about the medications that we use for obesity. Certainly in 2025 we have really seen a lot more pushback from insurance companies for paying for these medications for patients. And I think if you could say that the data was a complete draw, it would be much easier to say you're not changing someone's body, et cetera. Why not just do the medications? But at least in this study, it's not. It doesn't answer every question. But clearly in the study people did better in the surgical arm versus the medication arm. And certainly there are impacts on Mace and other things. But if we take that aside and we just kind of look at kind of quality of life type thing, people are doing better in the bariatric surgery arm than the medication arm. So again, a study that's been going on for 12 years has not seen the advent of some of our newer medications. Again, that said, I find this to be interesting. Taking a deeper dive. There was a paper in 2024 out in Northwestern that actually just looked at costs and looked at cost of having bariatric surgery. And bariatric surgery for the most part is going to be roughly an $18,000 one off expense. If you look at some of the medications we're going to use, we're looking about $1,200 a month. Again, there are deals and all kinds of stuff, but if someone was paying retail about $14,000 a year. So at some point and the studies are saying to us, hey, we're going to put you on these medications and you're going to have to be on these medications the rest of your life. And if we're looking at two out of five people in the United States are going to qualify as having obesity, that we're going to have put people on medications for life, maybe that we really have to have a little bit of a paradigm shift. Looking back at bariatric surgery again, maybe our insurance companies will say, hey, we're not going to pay for medications, but we would pay for surgery, which really seems so obtuse and so backwards for everything we've ever done. But I think this paper would lend some credence for someone at an insurance company to say, have you talked to your surgeon yet? So our next article is from the Lancet and it looked at suicide and suicide attempt in users of GLP1 receptor agonists. A nation case time control study so this was a study study that was done out of France and it looked at patients who were over 18 years of age who died by suicide or were hospitalized for a suicide attempt between the years 2013 and 2021 who had at least one GLP1 receptor agonist dispensing within the 180 days prior to that. In the French National Health Data System, a case time control design compared for each patient GLP1 exposure in the 30 days preceding the outcome to 3 day earlier 30 day reference periods potential exposure 10 bias was controlled up to 5 time controls matched on age, sex, psychiatric history, obesity and calendar time. Analyses were adjusted for time varying confounders. And finally the DPP4 inhibitors were studied as a negative control for for some of these potential biases. The study included over 1,100 cases and over 5,400 controls. The mean case age was around 57 years of age. Around 45% of the patients were male. Two thirds had a recent psychiatric history and over 50% had obesity. The use of a GLP1 receptor agonist was not associated with an increased risk of suicide or a suicide attempt. With odds ratio of 0.62 with consistent results for DPP4 with an odds ratio of 0.75. Results obtained according to recent psychiatric history and obesity were comparable.
- [19:53]
Dr. John
Neil John, this is a powerful study. Case control design allows you to detect rare events that occur. And even with this really well carried out very large case control study, no increase and no suggestion of any increase in suicide or suicide risk. They did an excellent control as well looking at DPP4s and this adds to the data that's already out there. In January of 24 the FDA issued an official update. They had looked at their adverse event reporting system and they said and this is a quote from their top line, preliminary evaluation does not suggest a causal link. Just a few months ago JAMA in September there were two different articles. One was a cohort study of almost 300,000 individuals initiating GLP1s or SGLT2s and this was out of Sweden and Denmark. The incidence rates of suicide death were low and those initiating GLP1s did not experience an increased risk. The Other article in JAMA that September was a look at prospective trial step 1, 2, 3 and 5. Over 3,600 patients, no increase in depression or suicide. Our current article from the Lancet again, large powerful studies specifically looking does it increase risk in people who have psychiatric issues? It does not. I think, I think we can finally put this issue to rest. I don't think there is any suggestion of an increased risk. We can be very reassured as we are prescribing and we can reassure patients if they ask. Our next article from Diabetes Care is on the association between self monitored blood glucose and continuous glucose monitoring in youth with type 1 diabetes and Medicaid insurance. Turns out that youth with type 1 diabetes who have Medicaid in most states must demonstrate that they have self monitored their blood glucose level at least four times daily to receive CGMs. A new California Medicaid policy eliminated this requirement and so CGM access increased. And what the study did was they looked at whether infrequent baseline self monitoring of blood glucose resulted in suboptimal outcomes or non adherence with CGM use. I think we all are guessing already what this article shows and we'll be happy to see it. So this retrospective study included youth with type 1 diabetes and Medicaid who started CGM after January 2019. In in two large healthcare systems patients were stratified by data on baseline self monitoring blood glucose frequency less than or greater than or equal to four checks daily. That data was collected at the clinic visit prior to starting cgm and then they looked how they all did over time. They followed 78 youth for six months. CGM adherence was similar between the self monitoring frequency groups at three months and it was sustained at six months. No significant difference between the groups. A1C values improved in both groups at three months with a larger improvement in those who self monitored less than four checks daily. 1.3% improvement in A1C versus 0.4 and those values were sustained at six months.
- [23:51]
Dr. Neil
John so Neil, a study that I don't think is surprising to anyone, just hearing the title and kind of thinking about the logic of this and it speaks to the sometimes the non logic in the system, right, that someone has to cross a certain kind of arbitrary threshold for someone to think that something's not worth doing and we're talking about children with diabetes and CGM are so widespread now. I recently sat in a meeting next to a doctor who had a 12 pack who was trying to turn his life around with a CGM on. I'm like probably the last person who needs a CGM on, I get it. If insurance wants to draw the line on that or that patient who just takes metformin and they have type 2 diabetes and they don't check, I see lots of reasons not to give a CGM to everyone. But I don't see a reason for someone who has type 1 diabetes. I don't see a reason for anyone who's ever had dka. I don't see a reason for anyone who is on insulin and has had an admission for hypoglycemia overall. If, if, and this is insurance companies talking, if you look at outcomes and outcomes linked to lower A1Cs cost, people cost the society a lot less Money if people's A1C are in better control. A study out of Europe talked about €450 a year associated with some modest decrease in a 1Cs just going back to self monitor blood glucose. That's worth probably about a half a point on a 1C. I think California is leading the way. I think it's really hard for someone to say that a child with type 1 diabetes needs to be willing to prick their finger four times a day. A painful thing. Part of the reason for doing CGM is because they that doesn't work.
- [26:02]
Dr. John
And for our final article of this issue, we are fortunate to have Dr. Marie Pierre St. Orange joining us. Dr. St. Orange is an Associate professor of Nutritional Medicine in Medicine and the Institute of Human Nutrition at Columbia University Medical center in New York City and Director, center of Excellence for Sleep and circadian research. Dr. St. Orange wrote the invited commentary in JAMA Network Open titled From Gestational Diabetes to Type 2 Diabetes is Poor Sleep to Blame? This was a commentary on an article in the same issue titled Sleep Characteristics and Long Term risk of type 2 diabetes among women with Gestational Diabetes. Welcome, Marie Pierre.
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Dr. Michael Blaha
Thank you.
- [26:55]
Dr. John
This was such a wonderful commentary and as a clinician I came away feeling I learned a lot and have a lot that I need to start doing with my patients. Can you share with us some of what you talked about in that commentary, the background on the importance of sleep with regard to diabetes and what this new study adds.
- [27:21]
Dr. Marie Pierre St. Orange
So we already know that having short sleep duration, having poor quality sleep is a risk factor for type 2 diabetes. And this study now looks at women who have had an experience of gestational diabetes and what's their sleep experience and how does that influence their risk of developing type 2 diabetes. And I'll get to the findings right away. The final message is really that having short sleep or Snoring, having had digestational diabetes exacerbates that risk of developing type 2 diabetes over follow up. And these people were followed up for about 17 years.
- [28:01]
Dr. John
That's amazing. And I guess we've known that it increases the risk. But what was amazing to me, a couple of things. One, the degree of increase in risk. Can you share a little bit about that?
- [28:14]
Dr. Marie Pierre St. Orange
Yes. So if people frequently snored and had short sleep, so less than seven hours per night, they had double the risk of developing type 2 diabetes than if they didn't snore and had adequate sleep duration. So really showing that achieving adequate sleep duration, the nadir here was seven hours, seven to eight hours was the optimal sleep duration that they found to be protective or reducing the risk of developing type 2 diabetes.
- [28:42]
Dr. Michael Blaha
Yeah.
- [28:43]
Dr. John
And it's interesting. We've known for a long time the issue of gestational diabetes increasing future risk. And we know those are people to pay attention to, regularly screen for diabetes, to counsel about diet and exercise. But this adds another thing that I'm not sure we're usually counseling about. What do you see as the clinical implications of this?
- [29:08]
Dr. Marie Pierre St. Orange
My background is nutrition. When we talk about type 2 diabetes, gestational diabetes, reducing the risk of developing type 2 diabetes, we're very concerned about diet. Right. We talk about nutrition with our patients. But I think that now we also need to talk about sleep because in the context of short sleep, diet changes too. We've shown that individuals who are sleep restricted don't get enough sleep or don't get good quality sleep. Sleep also don't get good quality diet. They don't choose healthy foods, they tend to eat more, they tend to gain weight from sleep restriction. All of this really ties into the exacerbated risk of type 2 diabetes. When you're compounding that with gestational diabetes.
- [29:57]
Dr. John
That's interesting. So there's more difficulty with food choices. Is there any information that suggests, is it that when we're tired we have less self control or is it that the food signaling is different when we don't get enough sleep?
- [30:13]
Dr. Marie Pierre St. Orange
Yeah, I think it's a little bit of both. So we've done research to look at brain activation in response to sleep restriction and shown that the reward centers of the brain tend to be activated to a greater extent from sleep restriction relative to having adequate sleep. This is also seen in response to unhealthy foods, more so than healthier food options. But we have also shown that in women, interestingly, following sleep restriction, GLP1 is reduced.
- [30:46]
Dr. John
Wow.
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Dr. Marie Pierre St. Orange
Homeostatic and reward hedonic system, both of those are involved.
- [30:54]
Dr. John
And that so fits with what we've learned about obesity in general, because in the old days, we used to think about it as a lack of control. We now know that's not the case. It has to do with changes in hormone levels like GLP1s, as well as signaling in the brain, higher responses to food stimuli. And it sounds like sleep is one of the things that triggers that.
- [31:23]
Dr. Marie Pierre St. Orange
Yes, and we often hear about ghrelin, too, and I didn't mention ghrelin here because in our study where we found alterations in appetite regulating hormones, ghrelin was increased in men, not in women. It was GLP1 that was reduced in women and not in men. So there seems to be some sex differences there.
- [31:43]
Dr. John
Absolutely fascinating. And this is a big one. This has direct implications to what people like myself, practicing clinicians, talk to our patients about in the office, particularly those who have a history of gestational diabetes, that it's not just food, it's not just exercise, as if that's not enough.
- [32:06]
Dr. Michael Blaha
But now it's because if you don't.
- [32:09]
Dr. Marie Pierre St. Orange
Get adequate sleep, you're not going to be able to make healthy choices at all. We know that insufficient sleep alters decision making. And to me, decision making implies all aspects of life, lifestyle, behaviors as well. So choosing what to eat, are you having a side salad or French fries with that sandwich? Choosing to take the stairs rather than the escalator. All of this is also relevant when we're talking with our patients about healthy diet, adequate food.
- [32:38]
Dr. John
So helpful. Marie Pierre what people can't see who are listening to this podcast. And one of the reasons I'm smiling is your bike that you take to work every day that is hanging on your wall in the background. You are really living what you speak. Dr. Marie Pierre St. Orange, thank you so much for joining us.
- [33:05]
Dr. Marie Pierre St. Orange
And thank you for having me.
- [33:06]
Dr. Michael Blaha
It's been a pleasure.
- [33:10]
Dr. John
For more information and links to the articles that we discussed in this issue, just go to diabetesjournal.org until next month. Keep listening and keep learning.