Diabetes Core Update Oct 2025

Summary

Diabetes Core Update – October 2025

Podcast: Diabetes Core Update
Release Date: October 3, 2025
Hosts: Dr. Neil Skolnik & Dr. John J. Russell
Special Guest: Dr. Rebecca Graves (segment one)

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Overview

This episode provides a concise, insightful review of newly published research from major diabetes journals, with a focus on clinically relevant evidence that can inform practice for providers treating diabetes and related metabolic conditions. Topics explored include the impact of ultra-processed foods on women with gestational diabetes, mortality risk reduction from plant-based diets, novel pharmacotherapy in chronic kidney disease and type 2 diabetes, risk of phimosis with SGLT2 inhibitors, and ocular safety signals with GLP-1 receptor agonists.

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Key Discussion Points & Insights

1. Ultra-Processed Foods, Diet Quality, and Type 2 Diabetes Risk in Gestational Diabetes Survivors

(Diabetes Care)
Featuring: Dr. Rebecca Graves ([00:03]–[10:07])

• Background:

  • Women with gestational diabetes (GDM) are at higher subsequent risk for type 2 diabetes.
  • Ultra-processed food (UPF) consumption is increasingly scrutinized for its metabolic impact.

• Study Design:

  • Nurses’ Health Study II cohort; n=4,207 women with history of GDM; ~30-year longitudinal follow-up.
  • Used NOVA classification for UPFs and Alternate Healthy Eating Index (AHEI) for diet quality.

• Findings:

  • Strong dose-response: Higher UPF intake linked with increased weight gain and higher T2D risk.
  • “Increased habitual consumption of ultra processed food led to diabetes, basically to type 2 diabetes. Even if that person has a higher healthy consumption score.” — Dr. Graves [04:47]
  • Weight gain difference relatively modest (1 kg more over 30 years for highest UPF quartile), but diabetes risk increase substantial: 20–25% elevation in highest vs. lowest UPF groups.

• Clinical Implications:

  • UPF intake should be a central component in dietary counseling for women after GDM.
  • Substitution effect: “The consumption of ultra processed foods often substitutes the consumption of healthy foods.” — Dr. Graves [07:59]
  • Additional concerns: UPF packaging (plastics/chemicals linked to endocrine disruption), non-nutritive food burden, impacts on gut microbiome.

• Memorable Quotes:

  • “UPF [ultra processed food] consumption is a critical factor in assessing diet quality for optimal cardiometabolic health.” — Dr. Graves [06:14]
  • “Most ultra processed foods are often non-nutritive, they often have zero nutritional contribution to our diets.” — Dr. Graves [08:49]

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2. Plant-Based Diets and Mortality in Diabetes

(Diabetes Care)
Summary by hosts ([10:10]–[11:58])

• Study Overview:

  • UK Biobank cohort, >4,800 T2D patients, >11 years median follow-up.
  • Assessed “Plant Diet Index” (PDI), healthy PDI, and unhealthy PDI.

• Major Results:

  • Highest adherence to healthy PDI: 21% lower all-cause mortality; unhealthy PDI: 24% higher risk.
  • Effects even greater in patients with poor glycemic control, central adiposity, early-onset, or long-duration diabetes.

• Clinical Perspective:

  • “We’re looking at mortality, all cause mortality as the major endpoint and seeing a 20% difference over 11 years. That is...really big and important.” — Dr. Skolnik [11:58]
  • Plant-based healthy diets should be an aspirational goal in diabetes care, though dietary adherence remains challenging in today’s food environment.

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3. Combination Therapy: Finerenone with Empagliflozin in T2D and CKD

(New England Journal of Medicine)
Summary by hosts ([11:58]–[15:49])

• Study Details:

  • Randomized trial; patients with T2D, CKD, albuminuria, on background renin-angiotensin system inhibition.
  • Compared finerenone, empagliflozin, and their combination (180-day outcome: UACR reduction).

• Outcomes:

  • Combination decreased urinary albumin-to-creatinine ratio by 29–32% more than either agent alone.
  • Adverse events (hypotension, AKI, hyperkalemia) were rare and comparable between groups.

• Practice Takeaway:

  • Early interventions in CKD3/CKD4 stages are pivotal to altering the course of kidney disease and its cardiac consequences.
  • “Protecting the kidneys is a cardiac event…has effects on the heart which everyone can see outcomes and mortality with that.” — Dr. Russell [15:49]

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4. Phimosis Risk with SGLT2 Inhibitors vs. GLP-1 RA

(Diabetes Care)
Summary by hosts ([15:49]–[20:14])

• Study Recap:

  • Danish cohort, men starting SGLT2 inhibitors or GLP-1RAs (all metformin users).
  • SGLT2s: 32,000+ users; GLP-1: ~15,000. Median 4-year follow-up.

• Key Results:

  • SGLT2 inhibitors had higher risk: 1-year risk of phimosis 0.9% vs. 0.5%; 8-year risk ~4.8% vs. 3.6% (RR 1.36).
  • Penile cancer numerically higher (not significant) in SGLT2 group.

• Population Considerations:

  • Risk more pertinent in countries with lower circumcision prevalence (e.g., Denmark ~5–10% vs. US ~80%).

• Commentary:

  • “These are significant increases in risk and an absolute incidence of close to 5% over five years is real and important.” — Dr. Skolnik [20:14]

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5. GLP-1 Receptor Agonists and Sight-Threatening Eye Complications in Type 2 Diabetes

(JAMA Network Open)
Summary by hosts ([20:14]–[26:25])

• Study Recap:

  • Retrospective cohort, >185,000 adults with T2D (US Trinex database, 2015–2022).
  • GLP-1 RA use associated with:
    • Slight increase in diabetic retinopathy diagnosis (HR 1.07).
    • In existing retinopathy cases, no increase in progression to proliferative retinopathy or macular edema, but reduction in vitreous hemorrhage (HR 0.70), neovascular glaucoma (HR 0.78), and blindness (HR 0.77).

• Expert Take:

  • “Science is not static. Science kind of evolves and we have to continue to look to things to make care better and make care safer.” — Dr. Russell [23:11]
  • The clinical significance of small, statistically marginal safety signals must be weighed against overall cardiovascular and glycemic benefits, especially in the context of broadening GLP-1 RA use (e.g., non-diabetic populations).

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Notable Quotes & Memorable Moments

• “[Ultra processed food] consumption is a critical factor in assessing diet quality for optimal cardiometabolic health.” — Dr. Rebecca Graves [06:14]
• “Here we’re looking at mortality, all cause mortality as the major endpoint and seeing a 20% difference over 11 years. That is...really big and important.” — Dr. Neil Skolnik [11:58]
• “Protecting the kidneys is a cardiac event…has effects on the heart which everyone really can linear see the outcomes and mortality with that.” — Dr. John Russell [15:49]
• “Science is not static...we have to continue to look to things to make care better and make care safer.” — Dr. John Russell [23:11]

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Timestamps for Major Segments

| Segment/Article | Timestamps | |---------------------------------------------------------------------------------------|--------------| | Ultra-Processed Foods in Gestational Diabetes (Graves interview) | 00:03–10:07 | | Plant-Based Diet & Mortality in T2D | 10:10–11:58 | | Finerenone + Empagliflozin in T2D & CKD | 11:58–15:49 | | Phimosis risk: SGLT2i vs. GLP-1s | 15:49–20:14 | | GLP-1 RAs and Eye Complications | 20:14–26:25 | | Rebranding Announcement & Closing | 26:25–27:31 |

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Podcast Update

Announcement: Starting next month, the podcast will be rebranded as "Diabetes, Obesity and Cardiometabolic Update" (Doc Update) to reflect the expanded focus on the full spectrum of cardiometabolic health. Same format, broader scope.

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For full articles and more resources, visit diabetesjournals.org.

Transcript

[A]

We have another great issue this month, beginning with an article focusing on follow up of women with gestational diabetes and looking at the relationship of ultra processed food consumption and diet quality with long term weight change and progression from gestational diabetes to type 2 diabetes over time. The then another article focused on diet looking at plant based dietary patterns associated with reduced risk of all cause mortality in people with diabetes. Both of these articles are from Diabetes Care. Then an article from the New England Journal on phenarinon with empagliflozin in people with type 2 diabetes and chronic kidney disease, followed by a discussion of an article from Diabetes Care on the risk of phimosis associated with SGLT2 inhibitors versus GLP1 receptor agonists. And then finally an article from JAMA network open on GLP1 receptor agonists and site threatening ophthalmologic complications in people with type 2 diabetes. For our first article today we'll be discussing an article titled Ultra Processed Foods and Diet Quality in Association with Long Term Weight Change and Progression to type 2 diabetes among individuals with a History of Gestational Diabetes. A prospective study and this article was published in Diabetes Care. It's an important one. And joining us to discuss this article is Dr. Rebecca Graves, who is an associate professor and director of Special Projects and Evaluation in the College of Nursing at the University of South Alabama Health Sciences in Mobile, Alabama. Rebecca, welcome to our podcast.

[B]

Thank you so much for your warm welcome and I'm happy to be here and to be participating in this.

[A]

Rebecca, can you give us some insight into the background for this article and why they chose to study both ultra processed foods and this population, women with gestational diabetes.

[B]

We know that women with gestational diabetes have a greater risk of developing type 2 diabetes and we're beginning to learn that ultra processed foods play a role in the onset of type 2 diabetes. I feel like ultra processed foods is a buzzword that maybe we're starting to hear a lot more about now and we're learning more about how to shape our diets away from this. But as healthcare providers, we're learning how to teach our patients about healthful diets or healthful foods. Really. There were two scales in the in this study, the NOVA classification was looking at how they determine ultra processed foods, how they measure almost the degree of processing in the foods. And then the alternate healthy eating index 2010 is basically the higher the AHEI score is, the more healthful a person's diet is.

[A]

And so they looked at these diets over what like 30 years, is that right?

[B]

Yeah, so about 30 years. It's a really good longitudinal sample. It's the Nurses Health Study too. So they were able to look at a really large number of women. The sample of women who had gestational diabetes that was 4207, which is a very nice, robust study. So they were looking at the women who'd had a history of gestational diabetes as a very robust sample size.

[A]

So what did they look at when it came to looking at ultra processed foods?

[B]

They looked at the total number of calories per day that were ultra processed, of foods that were ultra processed, the percentage, the servings of ultra processed foods per day, the percentage of calories per day that were ultra processed, and then the percentage of grams per day of ultiprosis.

[A]

And let's jump ahead now to the results. Because of these, 4,200 women, over 1,000 over time developed type 2 diabetes. So this is clearly a high risk group. We know that women with gestational diabetes are at high risk of eventually developing diabetes, but what do they find with regard to the relationship between ultra processed food consumption and that outcome?

[B]

Yes, it comes as no surprise, but the greater the intake of ultra processed foods, the greater risk of converting to type 2 diabetes. There were four quartiles, so that one group with a healthy diet, low ultra processed foods, were the only ones that didn't have a significant weight gain over the years that they were really looking at this. So if they had any high or increased consumption of ultra processed food, there was weight gain. And increased habitual consumption of ultra processed food led to diabetes, basically to type 2 diabetes. Even if that person has a higher healthy consumption score.

[A]

Yeah, I found it fascinating when they looked at weight gain comparing the ultra processed food consumption in the lowest quartile versus the highest quartile. Not surprising. There was higher weight gain, but it was only about 1 kilo more over the large amount of time they followed people. But the difference in diabetes rates were in the range lowest to highest consumption, in the range of 20 to 25% increase in diabetes risk. And that was pretty impressive. What do you think the implications of this are? How do we use this information in practice?

[B]

There was a very interesting statement in the article that basically said that this is a very poignant point of education in diabetes education. What we don't know can hurt us and what we don't realize is that things that we're consuming every day can really interfere with our cardiometabolic health. Okay, this is, this was the quote that I Thought was very interesting. UPF ultra processed food consumption is a critical factor in assessing diet quality for optimal cardiometabolic health. That's the big take home for that, is that this is, we need to consider this and look at it and as providers, I don't know really that we do that very often.

[A]

Yeah, I agree with you Rebecca. I think when I see a woman in follow up after she's had a child and in our practice we often care for the child as well as the mom. I will talk a lot about how things are going in the family system. I'll also remind moms to exercise whether or not they had gestational diabetes. But I, I'm not sure I'm as attentive to their diabetes risk as I should be both with regard to emphasis on exercise and emphasis on diet. And the idea that ultra processed foods can increase their eventual diabetes risk BY up to 25% is meaningful. And for me probably changes the way I have these discussions with moms in that year, two years and five to 10 years after their pregnancy.

[B]

Right, I agree and I think that it's as we're saying, this person's already at an increased risk. So what a prudent healthcare provider would do is to do whatever we can do to decrease that risk. And we're learning through this study and others that the consumption of ultra processed foods is increasing that risk significantly. That's substantial. One other thing that I took from this I thought was very interesting and we need to remember this and teach this to our patients is that the consumption of ultra processed foods often substitutes the consumption of healthy foods. So the more ultra processed foods that we are consuming, we only eat so much a day. So we're not eating those healthy fruits and vegetables and the whole foods and the fresh fish and those types of things. Okay, so that's, that was one take home I thought was interesting. The other thing is that most of we know this, but this is something important to remember. The ultra processed foods are often non nutritive, they often have zero nutri nutritional contribution to our diets. So while they fill us up while they're convenient, they're on the go, they're really not, they're not worth anything basically. And then all the other thing, and this is something I've included in some of my talks on, on looking at obesity and prevention of obesity, is that we have to think about the internal and external environment because most of the time these ultra processed foods are packaged in plastics which can then. And they're also treated with chemicals and these can be those EDCs, the endocrine disrupting chemicals which can lead to diabetes, can lead to OBEs and then also the gut microbiome. So that can impair that as well. So those are just things to remember about that.

[A]

Those are really critically important points about an article that I think has large impact in the way we advise women Beginning our next office session. Dr. Rebecca Graves, thank you so much for joining us.

[B]

Thank you so much for having me. It was a pleasure.

[C]

Our next article is on plant based dietary patterns associated with reduced risk of all cause mortality in diabetes subgroups. This was a prospective cohort study from the UK Biobank, so this study included over 4800 UK Biobank participants who had type 2 diabetes and at least two 24 hour dietary recalls. The researchers generated overall healthy and unhealthy scores, multivariable Cox regression, estimated hazard ratio and 95% confidence interval for odds cause mortality comparing the highest tertile and the lowest tertile of adherence to a plant diet index, a healthy plant diet index and an unhealthy plant diet index. The interaction between PDI adherence and diabetes subgroup looking at a 1C weight, circumference, age of diagnosis, diabetes duration were assessed by two dimensional B splines and by including product terms into the model. They follow these patients for mean follow up of over 11 years. There were 679 deaths that occurred. Individuals with the highest PDI adherence compared to those with the lowest were at the lowest risk of all cause cause mortality with a hazard ratio of 0.79 or a 21% lower chance of mortality in a similar direction were observed for those with a healthy PDI 0.82 or 18% reduction. Unhealthy PDI was associated with increased mortality risk and a 24% higher risk. So a confidence interval of or hazard ratio of 1.24. The associations of PDI, healthy PDI and unhealthy PDI with odds cause mortality were more pronounced for those with poor glycemic control, higher waist circumference, diagnosis early in life and longer diabetes duration.

[A]

Neil John, let me share a few thoughts. First, just to level set, we know what a plant based diet is here. When they were talking about a healthy diet that meant people who were not drinking so much sodas and eating a lot of processed foods. When you stand back and think about it and I recognize this is an observational trial, not a randomized prospective trial, but we've talked about many prospective trials over the years that use maces and endpoint major adverse cardiac events and we get very appropriately excited about a statistically significant improvement in MACE over three to five years. Most of those trials don't achieve a mortality difference. Some have, but most don't. Here we're looking at mortality, all cause mortality as the major endpoint and seeing a 20% difference over 11 years. That is, I'll just say it. That is really big and important. There is very little doubt. And here we focused on people with diabetes. We see effects in populations whether people have diabetes or not. And here we saw a greater degree of effect in the people who are at greatest risk, those who had diabetes the longest, those whose A1Cs were the worst. What do we do with that information? I think there's no question. One thing that we need to do is emphasize this as we talk to patients. I think diet is complicated. It's hard to understand. And even when we emphasize it, the challenge here is it's even harder to follow. We are filled with stimuli in a toxic food environment that promote the eating of unhealthy foods, whether it's advertisements or just walking through the aisles of a supermarket. Nonetheless, this really is informative and shows that a plant based healthy diet is something that we can share with our patients and have as an aspirational goal. Our next article from the New England Journal of Medicine is on phenerinone with empagliflozin in chronic kidney disease and type 2 diabetes. The authors randomly assigned participants with ckd and an EGFR 30 to 90 as well as albuminuria, a urinary albumin to creatinine ratio between 100 and less than or equal to 5000 who also had type 2 diabetes and who were already on a renin angiotensin system inhibitor in a one to one ratio to receive received phenerinon with an empamaxion placebo. Dose of phenerin was either 10 or 20 depending on someone's EGFR empagliflozin at a dose of 10 milligrams a day with phenerinone matching placebo or a combination of the two. The primary outcome was the relative change in the log transformed mean urinary albumin to creatinine ratio from baseline to 180 days as well as assessing safety at baseline, the UACR was similar among all the participants in the three groups with a median value of approximately 580. At day 180, the reduction in UACR with combination therapy was 29% greater than it was with phenuron alone and it was 32% greater than than with EMPA alone. Neither agent alone or in combination led to unexpected adverse events. Symptomatic hypotension, acute kidney injury and hyperkalemia leading to drug discontinuation were uncommon.

[C]

John so Neil, I think we're on the precipice of some different things in care and primary care. So if you look at people who have CKD5, the lifespan without having a kidney transplant is about five years. All comers, regardless of the age, when you enter into CKD5 really hasn't changed a ton short of some of the transplant advancements. You and I can't make a whole lot of difference for our patients who are in CKD5. We sure as heck fire might be able to make a difference in our patients who have CKD3 or CKD4 that they never get into CKD5. So I think one of the things, and I think the first paradigm, and I think we've been living it for a little bit, is starting to see can we stop the line, can we slow the descent when someone's in CKD3? And we've been doing that with the SGLT2s for a couple of years now. We're kind of looking at using some combination agents to really pull on the emergency brake a little harder. And this study shows that the truth is for that average patient and if you said, okay, Your GFR is 45 and your urine microalbumin is 45, what's the chance that you're going to go on to kidney failure? And there's a nice calculator called kidney failurerisk.com that you can put in someone's numbers and when you put in those numbers, it's relatively low and it'll give you a two year and a five year old output and might, and you might say to a patient, geez, your chance in five years of being needing a transplant or being on dialysis is 4%. And maybe for an older person that really doesn't resonate all that much. So we're doing all these things in the kidney space because it's the number one cause of kidney failure in the United States, et cetera. The thing we are now entering into is now the development of this cardiac kidney metabolic syndrome. And the AHA had a guideline last year to start looking at this. And when you look at the people who are dying from kidney disease, they're not really dying from hyperkalemia, they're not necessarily dying from uremia, they're dying from an increased rate of having cardiovascular output events. When people's kidneys get worse, you have less positive effect from statins and a lot of the things that we've come to really help hold back that, that tsunami. So I think we're going to start seeing now that actually protecting the kidneys is a cardiac event and there's a calculator that you can see the prevent trial that looks at all that. So I think we're going to be talking more and more about how protecting the kidney is wonderful for the kidney but it's also, you know, has effects on the heart which everyone really can linear see the outcomes and mortality with that. Our next article is from Diabetes Care and it looked at risk of phimosis associated with SGLT2 versus GLP1, a Danish cohort study. So this was a population based active comparator new user cohort study emulating a target trial. The study included all adult male metformin users in Denmark initiating either an SGLT2 or GLP1 between the years of 2016 and 2021. The researchers used inverse probability of treatment weighing to balance the distribution of potential co founders. They estimated weighted intention to treat and risk ratios of phimosis identified from population based medical databases. So in this study they included over 32,000 SDLT2 inhibitor initiators and close to 15,000 GLP1 inhibitor initiators. With a median follow up of 4 years, a maximum being 8 years. The risk of phibosis was elevated among SGLT2 users. The 1 year risk of phibosis was 0.9% among new SGLT users and 0.5% among new GLP1 users, corresponding to a 1 year risk ratio of 1.88. During 8 years of follow up, the risk of phibnosis accumulated up to 4.8% in SCLT users and 3.6 in GLP1 users with an 8 year risk ratio of 1.36.

[A]

Neal John, this is interesting, important and at the same time needs to be put in perspective because it probably has a different meaning depending on the ambient rate of circumcision in the population that you take care of. So these are significant increases in risk and an absolute incidence of close to 5% over five years is real and important. The other outcome they looked at, though it didn't reach statistical significance, was penile cancer, which was higher in the SGLT2 group because there might be a relationship here as well. It's important though to also put this in population perspective. So in Denmark, the estimated rate of circumcision is somewhere around 5 to 10%. And that contrasts to the rate in the United States, which is estimated to be about 80% of the adult population. And so phimosis is going to be far more common in an uncircumcised population. How much of an effect is this going to have on our decisions about prescribing? I think that will be up to the individual practitioner and the individual patient and will depend on the population that they take care of. Our next article is from JAMA network open titled GLP1 receptor agonists and Sight Threatening Ophthalmic Complications in patients with type 2 diabetes the investigators here did a retrospective cohort study of adults with type 2 diabetes between 2015 and 2022 using the Trinex database. The cohort was divided into two groups adjusted for baseline characteristics and what they found in over 185,000 individuals prescribed GLP1 receptor agonists was that the use of GLP1s was associated with an increased incidence of diabetic retinopathy with a hazard ratio of 1.07. There was no statistically significant difference in non arteretic anterior ischemic optic. In a subgroup analysis of over 35,000 individuals with pre existing diabetic retinopathy, GLP1s were not associated with progression to proliferative diabetic retinopathy or diabetic macular edema, but they were associated with a lower occurrence of vitreous hemorrhages with a hazard ratio of 0.7, neovascular glaucoma has a ratio of 0.78 or blindness with a has a ratio of 0.77.

[C]

John so I love a lot of things about this article and what it says about science. So we have come in all of this discourse that science is a stop point, right? So you do a study, the study ends and then there's truth or non truth. And the truth is science continues to evolve, right? We have post release safety studies that go on with drugs to say hey, you studied this drug in 6,000 people and it showed great results. For your primary objective, when a million people are taking this, what are some of the side effects that kind of pop out about things and what are some things that we need to know? And every individual that we talk with, we talk about the risks and benefits of taking any medicines in taking this away, the use of GLP1s in our patients with diabetes and classically that was one of the first things we knew about preventing microvascular disease by having better glycemic control. The people already had diabetic retinopathy in the study when they were put on a GLP1, they actually did better with regard to some of their aspects of retinopathy. When it talks about maybe increasing the rate of retinopathy, it's a pretty low number that's pretty close to that confidence interval. So I might not bet a whole lot on that. But when we think about diabetes and eye disease, it's a top five cause of blindness in the United States. And if we can slow down the progression of eye disease in people with diabetes, if we can have people have better glycemic control and have less of all the other Folter, all that goes along with having less well controlled diabetes and GLP1s do a really nice job with that. But I think the other takeaway point is we now have a whole kind of subculture. If you watch TV for a couple hours, you're going to see direct to marketing things for people who seem a lot more fit than I am, who are being direct to consumer marketed to take GLP1s. And I think if there's a little bit of a signal that has a little less of a safety thing and someone who doesn't already is not already on a path to have some eye disease that you might make better, then maybe people taking a medicine that they don't necessarily need, potentially is it worth it. And I think that's one of the reasons, as you expand the scope of medicines into populations they weren't initially intended for. I am talking about that kind of casual person who sees a famous athlete giving themselves a shot of a GLP1 to lose a little bit of weight. So I think these studies are real important. And I think those of us who are in science, those of us who are talking about P values and confidence intervals in this, need to let people realize that science is not static. Science kind of evolves and we have to continue to look to things to make care better and make care safer.

[A]

John, before we close, I want to share some important news with our listeners. As you know, in addition to diabetes, we've been covering the full range of cardiometabolic conditions. And so our name is going to be changing to meet that consistent mission. Our podcast will be rebranded as Diabetes, Obesity and Cardiometabolic Update. I know, I know you're already thinking and you're right. The new name is Doc Update Diabetes, Obesity and Cardiometabolic Update. You'll notice this when the change is made on your subscriber feedback will have a new title and branding Same great information. 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.

[C]

Sam.