UEG Journal podcast Episode 13: Beyond the Gut-Metabolic and Systemic Connections in GI Diseases

00:00:06: Hello and welcome back to UEG Journal podcast.

00:00:09: You will quick

00:00:10: dive into the latest, most impactful research in gastroenterology.

00:00:15: I am Dr Mohsen Subani, associate editor with UEG journal And a Gastroenterologist

00:00:21: based

00:00:21: at Nottingham University Hospital UK.

00:00:32: Today we are back with the latest episode and so let's grab a coffee, join us for our first and focus roundup of what's new in GI.

00:00:41: Our first article today is titled Fatty pancreas and risk of Diabetes, Chronic kidney disease and cardiovascular event.

00:00:49: study was conducted by Nicola Pugilis & Colleague and it was published.

00:00:57: So fatty pancreas has gained increased attention as an ectopic fat depot link to metabolic dysfunction.

00:01:04: However, other previous studies have used inconsistent definitions making it quite difficult to compare findings.

00:01:12: This study is among the first to evaluate fatty pancreates using new twenty-twenty six international consensus that uses MRI based thresholds and examines its relationship with major cardiometabolic outcomes.

00:01:27: Investigators analyzed over nineteen thousand participants of European ancestry from UK Biome Bank with imaging cohort.

00:01:37: Pincartic fat was quantified using MRI proton density, fat fraction or PDFF and classified as normal, mild.

00:01:47: fatty pancreas are moderate to severe fatty pancreates.

00:01:51: Participants were followed up from median for four point eight years to evaluate development of any cardio metabolic outcomes such that two diabetes chronic kidney disease or any cardiovascular events.

00:02:03: The strongest

00:02:04: findings related to diabetes.

00:02:07: compared with participants with normal pancreatic fat Those with moderate to severe fatty pancreas had more than a three-fold auger odd of prevalent type II diabetes and the two point seven full higher risk of developing diabetes during fallout.

00:02:22: And also, even mild fatty pancreates was associated with more then double the risks of type II Diabetes.

00:02:29: And reportedly every five percent increase in pancreatic fat was associated.

00:02:39: Manila, this is alarming.

00:02:41: So specifically for kidney outcomes moderate to severe fatty pancreas was associated as high as eighty-two percent incident of chronic kidney disease while each five per cent increase in pancreatic fat increased the risk of chronic Kidney Disease by eleven Percent.

00:02:57: The association with cardiovascular events Was a bit more modest.

00:03:02: However both mild and moderate to Severe Fatty Pancreas were Associated With about thirty percent high risk of major advanced cardiovascular events, although these findings were less consistent in sensitivity analysis than those that we have already talked about for diabetes and kidney disease.

00:03:20: Overall the study suggests that fat pancreas is not simply an incidental imaging finding.

00:03:26: In fact ,the newly established consensus MRI threshold The authors demonstrate that pancreatic fat independently predict future risk after two diabetes chronic kidney disease and a weakly association with cardiovascular events.

00:03:42: So, as I take home message i would say that this finding support incorporating fatty pancreas into the cardiovascular kidney metabolic framework and allow its potential role in improving cardiometabolic risk assessments when abdominal MRI is already available.

00:03:58: Amazing!

00:03:59: so let's move on to our next study where we'll be discussing eucenophilic esophagitis an association in autoimmune thyroid disease, a population-based study by Surin Kozog and colleagues published.

00:04:32: This nationwide Swedish study aimed to assess whether patients with EOE are at a higher risk of developing autoimmune thyroid disease or rather, thyroid disease is already present before the diagnosis of EOe.

00:04:49: Indeed!

00:04:50: So using nationwide espresso cohort that investigators identified over diagnosed between two thousand six to two thousand three, so it's very robust cohort.

00:05:06: Each patient was matched up with upto five population control cohort and a sibling comparison was also performed to account for any shared genetics an environmental factor.

00:05:18: Yes Muzan And the primary finding here is that EOE was not associated with significantly hardware risk of developing autoimmune thyroid disease during follow-up.

00:05:28: The other ratio was one point which was not statistically significant and also similar findings were observed after adjustment for multiple confounders, as well in the sibling analysis that you have just referred.

00:05:44: However on further exploration you will find that patients with eucenophilic center for dieters are twenty per nine percent more likely to had a diagnosis of auto-mean thyroid disease before their UAE was diagnosed.

00:06:00: More than ninety percent of these thyroid disorders were autoimmune hypothyroidism, including Hashimoto thyroiditis.

00:06:08: Yes and that's another interesting finding here was the age-specific effects.

00:06:12: Children diagnosed with EOE had a much stronger association without an immunotherapy disease then adults.

00:06:19: Childhood onset EOe was associated more than twofold higher risk for developing autoimmune diseases having other ratio to point five and HALMOS-V full higher odds of having preexisting autoimmune thyroid disease with an odds ratio of HALMS V.

00:06:38: So, interestingly Manila taking these findings into account also suggests that this stronger association in children may reflect differences in immune activity greater clinical surveillance and shared immune mechanism.

00:06:52: although observational design cannot establish visuality the finding highlight a distinct subgroup of patient who may want closer clinical attention.

00:07:01: Yes, so TECO messages here are that adults with EOE do not appear to have a substantially increased future risk of autoimmune thyroid disease.

00:07:12: however Autoimmune thyroid diseases is more common at the time of EOe diagnosis particularly in patients with childhood onset EOEs.

00:07:21: So as clinicians we should remain alert to symptoms suggestive of thyroid dysfunction especially in patients that are diagnosed with EOE at an younger age.

00:07:32: So let's move on to a very topical article which we're going to discuss about GLP-I analogs, which is quite a lot of debate ongoing.

00:07:43: so In this specific study the authors look into risk of call stones and really complication related to use of glucagon like peptide I receptor agonist for type II diabetes included Mohamed Aldoussouke and colleagues.

00:07:59: And this was published in recent issue of UG Journal.

00:08:02: Yes, as you have just alluded GLP-I receptor agonies seven years transformed the management of patients with type two diabetes but also obesity which proved benefits in leachemic control with loss and cardiovascular outcomes.

00:08:16: However there remain several concerns regarding the potential association with blood weather and biliary diseases that haven't yet been completely uncovered.

00:08:25: So the aim of this real-world study was specifically to quantify those risks in our everyday routine clinical practice.

00:08:33: So authors actually looked into a database by name of Trinite X, which is US based research network investigated A big cohort of patients included over hundred and fifty thousand adults with type two diabetes.

00:08:47: The cohorts were propensity score matched four hundred thousand patients receiving GLP-I receptor agonist compared with equal number of mesh controls, receiving other glucose lowering treatments.

00:09:02: With followup extended to three years.

00:09:04: The

00:09:05: main finding here was a modest but significant increase in goldbladder related complications at three years.

00:09:12: GLP receptor agonist use was associated with a forty-three percent higher risk of gallstones, or common bile duct stones.

00:09:20: and the forty five high risk of acute colostoitis.

00:09:23: And also a fifty four percent higher likelihood of requiring colostectomy.

00:09:29: Yes Manola but while looking into this finding we should look in to absolute even traits that remain very low.

00:09:38: only about one point three percent of GLP One user developed gallstones, and over .

00:09:43: four percent valcolysis titers.

00:09:45: And just point three per cent actually underwent valcolysysctomy for three

00:09:48: years.".

00:09:49: Yes so perhaps the most reassuring finding was what to study did not show?

00:09:54: GLP-I receptor agonists were NOT associated with an increased risk of acute pancreatitis or need for ERCP addressing two important complications that have generated considerable concern in our clinical practice.

00:10:08: The risk also differed between individual agents, semi-glutide and gluglutide were associated with significantly higher pairs of gallstone.

00:10:18: An overall biliary complication whereas lyroglutides and exenotides didn't show any significant increase in the risks.

00:10:25: The authors also identified obesity, steatotic liver disease or alcohol use as an independent predictor of biliary even suggesting that patient characteristics remain important determinant these conditions.

00:10:40: Yeah, so the take home message here is that GLP-I receptor agonists are effective as we know but they also have a quite favorable safety profile.

00:10:50: however clinicians need to be aware of the modest increase in gallbladder disease particularly long term treatment and patients with obesity or fatty liver diseases.

00:11:02: As clinicians we need to be aware that if our patients develop persistent right upper quadrant pain, fever or jodis of course they need to evaluated promptly for biliary complications.

00:11:13: Quite rightly so.

00:11:15: taking these findings into account the properties of GLP receptor organist also warrant a right indication.

00:11:23: absolute riskability complication is low.

00:11:26: there was no increase in scapancotitis at ERCP for most patients and a proven metabolic and cardiovascular benefit of these agents are likely out with relative small increase in risk of gall bladder disease.

00:11:39: Yeah, thank you Mohsen!

00:11:41: And now we move to our final article that explores the topic as becoming increasingly relevant in clinical practice – The impact of metabolic syndrome on patients with IBD.

00:11:52: So traditionally we think patients with an IBD has underweight or malnourished but that's no longer the reality.

00:12:01: But disease control, changing lifestyle and rising obesity rates mean that metabolic disease is now an important part of IBD

00:12:10: landscape.".

00:12:12: So using the Trinet X electronic health record, the investigators analyzed nearly one million patients with Crohn's disease and ulcerative colitis between.

00:12:23: The major finding of this study was the dramatic rise in cardiometabolic disease.

00:12:28: For example, hypertension nearly tripled, diabetes more than tripled.

00:12:33: Obesity increased almost six-fold and metabolic dysfunction associated with seatotic liver disease increased almost ten-fold.

00:12:43: That's worrying!

00:12:44: The key question is whether metabolic syndrome simply coexists with IBD or if it affects outcome?

00:12:52: Compared with patients who had IBD alone, those with metabolic syndrome had approximately double the risk of major cardiovascular events.

00:13:00: Heart failure, chronic kidney disease and mast T. They were also experienced high rates of hospitalization, cardiac stride use and IBD related surgery in patient with IBD and coexisting metabolic syndrome.

00:13:17: Yes!

00:13:17: And that's very important because this suggests that metabolic syndrome may need more than just a conmorbidity, as it might also be the marker of severe disease presentation in patients with IBD.

00:13:29: However while this observational study cannot prove causality –as we all know– there are plausible biological mechanisms that help us to understand these more deeply.

00:13:39: For example We knew that visceral adipose tissue promotes chronic inflammation through cytokines like TNF-alpha and interlegal pin six and these contribute to insulin resistance, and thus alter our gut microbiome.

00:13:53: On the other hand corticosteroids may further worsen metabolic dysfunction And all this creates like a vicious cycle.

00:14:01: Importantly These findings build on previous studies showing that one in five patients in IBD already has metabolic syndrome.

00:14:09: What does study add is long student perspective demonstrating that burden of metabolic disease is increasing and associated with poor clinical outcomes across multi-organ systems.

00:14:21: And as we did in real world database studies, of course we are dealing some limitations.

00:14:26: Diagnosis relies on electronic health record coding, metabolic syndrome was defined using diagnostic codes rather than formal criteria, and detailed information on disease activity, inflammatory markers diet... ...and also for example body composition wasn't available.

00:14:42: Nevertheless the consistency of these findings and also cross diseases, as we have already said makes the overall message quite compelling.

00:14:51: So my take on messages that modern IBD is no longer just a disease of intestinal inflammation.

00:14:58: metabolic has become an important determinant of patients outcomes.

00:15:02: alongside controlling the inflammation clinicians should actively assess and manage obesity diabetes hypertension dyslipidemia and fat liver disease and a multidisciplinary approach might be warranted.

00:15:16: So this study does improve that metabolic syndrome causes worse IBD, but it provides strong real-world evidence that patients who have both conditions, IBD and metabolic syndrome experience substantially poorer outcomes.

00:15:30: so as gastroenterologists we increasingly need to treat the whole patient not just gut and pay attention these very important comorbidities factors of disease activity.

00:15:42: So with this end, thank you very much for joining us on the latest episode of UAG General Podcast.

00:15:48: Today's studies reminded that gastroenterology is increasingly connected to a broad aspect health from metabolism and immunity to long-term patient outcome.

00:15:58: We hope you enjoyed this quick review of latest research from UAG Journal And I hope that you will join us in further episodes.

00:16:07: Up till then, please stay tuned and don't forget to subscribe and share UUG protocols.

00:16:14: Thank

00:16:25: you!