Visceral Fat and Cardiometabolic Risk Factors; Autoantibodies and IBD

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of Texas Tech Health El Paso, look at the top medical stories of the week.

This week’s topics include visceral fat and cardiometabolic risk factors, delirium and cognitive decline and hospitalization, caps on insulin price, and factors involved with inflammatory bowel disease (IBD).

Program notes:

0:38 Autoantibodies and IBD

1:39 Looked at 4,900 people with IBD

2:33 Small percentage of adults with condition

3:19 Insulin price caps impact

4:19 Helped those with highest baseline cost

5:21 Aren’t usually just taking one medicine

6:22 Weight loss and distribution with weight regain

7:25 Regain weight but reduction in visceral fat

8:26 Long lasting metabolic benefits

8:36 Delirium, hospitalizations, and cognitive decline

9:36 Several tests over 5 years of follow up

10:50 Does it just identify those who are frail?

11:55 A more comprehensive evaluation may be needed

13:00 End

Transcript:

Elizabeth: How have capped insulin costs impacted Medicare beneficiaries?

Rick: Assessing different fat deposits 5 and 10 years after weight-loss strategies.

Elizabeth: How is delirium related to the ultimate development of cognitive impairment?

Rick: And how autoantibodies can be responsible for inflammatory bowel disease.

Elizabeth: That’s what we’re talking about this week on TTHealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I’m Rick Lange, president of Texas Tech Health El Paso.

Elizabeth: Rick, how about if we turn straight to the New England Journal of Medicine, this idea of autoantibodies and [inflammatory bowel disease]?

Rick: This is the first, established, common, molecular mechanism of inflammatory bowel disease. We’ve known about autoantibodies for over 20 years now. Their role in causing opportunistic infection has been known for a long period of time. This is now a discovery that these autoantibodies can be responsible for inflammatory bowel disease.

There were kids that had inflammatory bowel disease, and there were genetic abnormalities that identified that they did not produce interleukin-10. Interleukin-10 is produced by several different types of white cells, and it’s actually an anti-inflammatory cytokine. It has multiple functions. Its absence from inborn errors of metabolism means that the inflammatory cytokines are increased in the blood, and particularly in the intestine, and responsible for inflammatory bowel disease in kids.

So these investigators said, I wonder if a very similar thing could be happening in adults. To assess this, they looked at over 4,900 patients that had inflammatory bowel disease, looking for autoantibodies that would neutralize interleukin-10. They looked at it in 1,000 controls as well.

And what they discovered is that none of the control patients have the autoantibody, whereas 3.5% of adults with inflammatory bowel disease actually have the autoantibody. They can identify a specific allele that is enriched with this capacity to develop the autoantibody, 35- to 50-fold more likely to develop the autoantibody than people that don’t have the allele. It changes the paradigm that autoantibody is not only responsible for opportunistic infection, but also responsible for an inflammatory condition in the intestine as well, inflammatory bowel disease.

Elizabeth: If you depleted those antibodies, would you have a reduction or cessation of symptoms? Also, this accounts for a very small percentage of the folks who have this condition.

Rick: It is a very small percentage, but again, the first molecular mechanism. Your point’s well taken. Authors that wrote the editorial suggested these patients would benefit from things that deplete B cells that make the autoantibodies, or if you do a plasma cell exchange where you deplete either the autoantibody or the B cells, or you block the receptor to them. Those are all potential ways of addressing this particular condition. It also makes us wonder whether other autoantibodies could be responsible.

Elizabeth: It’s really a great bench-to-bedside kind of an exemplar. And again, I’m wondering for all those folks who have [IBD], gosh, is this really going to be opening a door to understanding why everyone has it?

Rick: I think it will, Elizabeth.

Elizabeth: Let’s turn to JAMA then, and let’s look at something very, very practical.

Some years ago now, insulin, as a part of the Inflation Reduction Act, was capped at out-of-pocket costs at $35 for a 30-day supply for Medicare beneficiaries. And the question is, gosh, how has that impacted utilization — filling one’s prescriptions and actually using the stuff in those folks who are Medicare beneficiaries?

They looked at a study cohort that contained almost 3 million insulin users. They looked at the cost per 30-day supply of insulin before this policy and then afterward. They found out that before it, it was just about $23. Afterwards, it was just over $18, a relative reduction of 48%. They looked at insulin fills, adherence, and persistence to basal insulin, found that it did not increase for the full cohort, but did for those people who had the highest baseline cost for their insulin. Those people had this greater adherence, persistence, and fills for their insulin.

So this Medicare $35 insulin out-of-pocket cap did decrease and stabilize insulin out-of-pocket costs, increased insulin use for people with previously high out-of-pocket cost, and it boosts the insulin among those users. And clearly, we want to be able to boost that insulin because that’s what helps us to avoid a lot of complications of diabetes that are certainly possible.

Rick: Yeah, and Elizabeth, just the cost overall of pharmacologic therapy of insulin has increased substantially. For a lot of reasons, we have newer glucose-lowering agents in addition to insulin, but a lot of different insulins.

The cost, as you mentioned, when it was capped at $35, there are some individuals that were paying under $35 already, so it didn’t matter. Overall, when you look at the total group, it reduced the cost by about $5 per month. For those already under the cap, it didn’t change. For those in the highest level, it was obviously a much greater reduction in 30-day cost.

But also, these individuals aren’t usually just taking glucose-lowering medications. They oftentimes have hyperlipidemia, hypertension. They’re oftentimes on many medications. In fact, the median number of prescriptions for patients with type 2 diabetes is five, and there are 11% taking more than 10 different drugs. So whatever we can do to reduce the cost of medications, and particularly insulin, which was getting out of control, increases the use and increases filling subscriptions.

Elizabeth: The study notes that this act actually has saved insulin users in the United States $170 million in out-of-pocket costs in 2024. This is their basal insulin, and as we know, there are a number of different types of insulins. And I, for one, would be in favor of price caps on all of them.

Rick: Right. And Elizabeth, it’s the other medications besides the basal insulin that are really very expensive. It would be nice to be able to reduce the cost of all of these drugs, especially for individuals that are on five or 10 different drugs.

Let’s talk about the next one, and this is an article that was published in Circulation this week. It talks about lifestyle interventions that reduce weight. When we reduce weight, we can also greatly reduce abdominal adipose or fat deposition. And this includes visceral adipose tissue that is around organs, deep subcutaneous adipose tissue, and superficial adipose tissue. In addition, what are called ectopic fat depositions. That’s fat in the liver and fat around the pancreas. And we know that when you reduce your weight using lifestyle interventions, you reduce these fat deposits, you have improvements in insulin resistance, cholesterol, your lipid status.

OK, what happens 5 and 10 years later? Many individuals regain weight. Does the fat deposition stay the same and is there any cardiometabolic consequences?

So there were two large studies — one conducted from 2012 to 2014, one from 2017 to 2018 — that evaluated different dietary patterns in which individuals did have weight loss, and then they followed them for 5 or 10 years later. And specifically, they did MRI scans that could evaluate where the fat was distributed before, and then 5 and 10 years after a follow-up.

When people have lifestyle interventions, that is diet and physical activity that lowered their fat, even though they regained weight later, there were still long-term improvements in cardiometabolic measures, despite the fact they had regained weight. Specifically, there was a continued reduction in visceral fat, even though there was an increase in fat in the liver and around the pancreas. If there was a 10% reduction in visceral fat, it reduced the risk of future type 2 diabetes by nearly 30%. So this suggests that visceral fat loss, rather than weight loss, is a key target for having durable cardiometabolic health.

Elizabeth: Of course, it would be nice if we could somehow target that particular area of fat deposition for weight loss. I don’t think we’re there yet.

Rick: Even when they regained weight, there was still decreased visceral fat. When you’re losing weight, it happens throughout the body. But it’s nice to know that these lifestyle-induced, moderate weight loss can yield long-lasting metabolic benefits.

Elizabeth: It’s worth trying it, even if it’s not something that you’re able to sustain over the long haul.

Let’s turn to JAMA Internal Medicine. Rehospitalization, postoperative delirium, and cognitive decline in older adults. Delirium, of course, frequently seen in these postoperative states for older people and predicts cognitive decline. What they wanted to examine in this study is whether recurrent hospitalizations are kind of the mechanism by which there is delirium and subsequent cognitive decline.

They looked at a prospective cohort in community-dwelling, older adults enrolled with 5 years of follow-up data in the Successful Aging after Elective Surgery longitudinal study. They examined incident delirium following their major elective surgery with and without rehospitalization, and by type. And that would be rehospitalization alone, rehospitalization with an [intensive care unit] stay, or with a post-acute care stay. And they looked at long-term cognitive decline measured by a scale that’s called the General Cognitive Performance score, which is a composite measure of several tests. And they repeated these 10 times over 5 years. Five hundred and sixty older adult participants with their cognitive score measured at baseline. And then they looked at each rehospitalization.

They did see a decline of about 0.19 units per year. When delirium was experienced, there was a more marked cognitive decline. They noted that rehospitalizations were more common among patients who developed delirium. However, adjustment for combined rehospitalizations for each type of rehospitalization only showed a minimal change that was not statistically significant. So contrary to their central hypothesis, rehospitalization did not mediate the association between delirium and long-term cognitive decline. So we got to kind of go back to the drawing board and find out, well, what is that association? It’s not rehospitalization that’s doing it.

Rick: We’re trying to decide, does delirium contribute to later cognitive decline, or does it just identify people that are frail that are going to be rehospitalized, and that’s the reason that there’s later cognitive decline. And what this study showed is clearly when people are hospitalized, there’s some cognitive impairment, but that’s usually short-acting. But people with delirium have advanced cognitive decline even in the absence of hospitalization. What that implies is we’ve got to prevent delirium. We know there are a lot of different ways to address delirium in the hospital. That’s where we need to focus our attention.

Elizabeth: Even in circumstances where those preventive strategies are employed, delirium still occurs.

Rick: We can prevent delirium 30% to 40% of the time. But if delirium is the cause of later cognitive decline, then decreasing that at 30% to 40% should have a significant impact.

Elizabeth: Absolutely. The editorialist points out that this finding — that’s the absence of mediation through rehospitalization — might simply mean that rehospitalization is too narrow a definition to employ with relationship to the development of cognitive decline.

Rick: Right. I mean, they use rehospitalization as an indication of how frail the person is. A more comprehensive evaluation could be important.

Elizabeth: You pointed out, of course, that there are strategies to try to prevent the development of delirium a priori. The editorialist also points out, and I think this is an important conclusion also, that we need to figure out how to reduce readmissions, improve care transitions, promote early mobilization, simplify medication regimens, and pay closer attention to post-acute care, because those things are also important in this whole lash-up that results in long-term cognitive impairment.

Rick: Exactly, Elizabeth. And you won’t have delirium if you don’t have hospitalization. And when the patients are hospitalized, trying to prevent it in the methods that you described is incredibly important.

Elizabeth: On that note then, that’s a look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.