Patients With IBD More Likely to Develop, or Have Prior, T1D

VIENNA — Researchers have determined a bidirectional relationship between inflammatory bowel disease (IBD) and type 1 diabetes (T1D), using both a cohort and case-control approach to analysis.

Their findings showed that patients with IBD had a moderately increased risk for T1D and higher odds of having prior T1D than the general population. These bidirectional associations were partially independent of shared familial factors.

Although the absolute risk for T1D is low in patients with IBD, these findings suggest that if there are nonspecific symptoms, such as weight loss and fatigue, which are typical of T1D but not of IBD, then it might be reasonable to test for diabetes, lead researcher Jiangwei Sun, PhD, postdoctoral researcher at the Karolinska Institutet, Stockholm, Sweden, told Medscape Medical News.

“Patients with IBD and T1D also tend to have worse disease outcomes for both diseases, but these two diseases are not recognized as comorbidities in the clinical guidelines,” he said.

Anecdotally, “many clinicians believe there is a higher risk of autoimmune disease in patients with IBD but not much attention is paid to type 1 diabetes,” he added.

Sun presented the study at United European Gastroenterology (UEG) Week 2024. It was also published recently in The Lancet.

Exploring the Bidirectional Relationship 

Prior research in the form of a systematic review found no association between IBD and T1D, which was surprising, Sun said. Further studies found an association between IBD and incident T1D; however, these studies did not explore bidirectionality between the two diseases.

These studies also did not take shared genetic and environmental factors into consideration, though “there is known to be familial co-aggregation of IBD and T1D based on previous findings,” he said.

In this current study, Sun and colleagues compared patients with IBD with the general population, as well as with siblings without IBD to consider the potential influence of shared genetics and earlier environmental factors. 

The research used two approaches to look for a bidirectional association: A nationwide matched cohort study (IBD and incident T1D) and a case-control study (IBD and prior T1D).

The cohort study included 20,314 patients with IBD aged ≤ 28 years, who were identified between 1987 and 2017. Of these, 7277 had Crohn’s disease, 10,112 had ulcerative colitis, and 2925 had unclassified IBD. There were 99,200 individually matched reference individuals.

The case-control study included 87,001 patients with IBD (without age restriction) and 431,054 matched control individuals.

Risk ratios were calculated using an adjusted hazard ratio (aHR) of incident T1D in the cohort study and an adjusted odds ratio (aOR) of prior T1D in the case-control study.

In the cohort study, the median follow-up was 14 years. Over that time, 116 patients with IBD and 353 reference individuals developed T1D. The aHR for a patient with IBD developing T1D was 1.58 (95% CI, 1.27-1.95). For patients with ulcerative colitis, the aHR of developing T1D increased to 2.02 (95% CI, 1.51-2.70); however, the association was not found for Crohn’s disease or unclassified IBD possibly due to the sample size of these latter categories, noted Sun.

In the case-control study, Sun and colleagues identified 1018 (1.2%) patients with IBD and 3496 (0.8%) control individuals who had been previously diagnosed with T1D. Patients with IBD had higher odds of having prior T1D than those without IBD (aOR, 1.36; 95% CI, 1.26-1.46). This positive association was observed in all IBD subtypes, said Sun, who added that the sample size was larger in this analysis than in the cohort analysis.

Upon comparing patients with IBD with their siblings without IBD, analyses showed similar associations between IBD and T1D; the aHR was 1.44 (95% CI, 0.97-2.15) for developing T1D, and the aOR was 1.32 (95% CI, 1.18-1.49) for prior T1D.

That these positive associations between IBD and T1D exist even when comparing patients with IBD with their siblings without IBD suggests genetics and shared environmental factors do not fully explain the association, and that later environmental factors might play a role, said Sun.

“I’m not surprised with these results,” he added. “They make sense because we know that both IBD and T1D are immunity-related diseases and have some shared pathways.”

Commenting on the study, Tine Jess, MD, director, Center for Molecular Prediction of Inflammatory Bowel Disease, PREDICT, Aalborg University in Copenhagen, Copenhagen, Denmark, said, “The really interesting finding here is that type 1 diabetes may precede IBD, which points toward common etiologies rather than one disease leading to the other.”

“This is in line with mounting evidence that IBD is measurable at the molecular level years prior to diagnosis,” she added.

Awareness of the bidirectional association may facilitate early detection of both conditions, Sun and his colleagues noted.

Sun reported no relevant financial relationships. Jess reported receiving consultancy fees from Ferring and Pfizer.