IBD increases type 1 diabetes risk, revealing a bidirectional link between the two conditions

By Hugo Francisco de SouzaReviewed by Susha Cheriyedath, M.Sc.Sep 19 2024

Research uncovers a strong connection between IBD and type 1 diabetes, urging doctors to rethink patient care by screening for both diseases early on, especially in high-risk groups like ulcerative colitis patients.

Study: Bidirectional association between inflammatory bowel disease and type 1 diabetes: a nationwide matched cohort and case-control study. Image Credit: sciencepics / Shutterstock

In a recent study published in the journal The Lancet Regional Health – Europe, researchers used an extensive cohort comprising more than 637,000 participants and two study design methodologies (case-control and cohort) to investigate the bidirectional (risk) associations between inflammatory bowel disease (IBD) and type 1 diabetes (T1D). Their study included ample follow-up time (median = 14 years) and found that 116 IBD patients and 353 baseline healthy controls developed T1D, with IBD significantly increasing T1D risk (aHR = 1.58). This association was found to be partially independent of shared familial factors, as shown in sibling comparison analyses.

Interestingly, patients with IBD were found to have a significantly higher probability of formerly having contracted T1D, validating the bidirectional associations between these comorbidities. The highest risk was observed in patients with ulcerative colitis (aHR = 2.02), highlighting a stronger association with this IBD subtype. These findings remained robust, independent of familial factors and genetics, suggesting a hidden driver of IBD and T1D's relationship.

Additionally, over 70% of the study cohort was followed for more than ten years, reinforcing the robustness of these findings.

Background

Inflammatory bowel disease (IBD) is an umbrella term for a group of chronic conditions that cause inflammation of the digestive tract, often due to autoimmune complications. Characterized by diarrhea, persistent fever, and abdominal pain, this gastrointestinal (GI) disorder is estimated to affect 0.5–1% of individuals globally and, unfortunately, remains incurable. Type 1 diabetes (T1D) is another increasingly prevalence chronic public health concern with shared pathological (autoimmune) underpinnings as IBD. Characterized by lifelong insulin deficiency, T1D is suspected to impact ~0.1% of the world's population, though some regions, such as Sweden, depict a substantially higher prevalence (~0.5%).

A growing body of evidence suggests the association between IBD and T1D, presumably due to their shared pathological pathways. Genome-wide association studies (GWASs) have elucidated particular interest due to their findings suggesting genetic underpinnings for IBD and T1D, which are observable through their frequent co-occurrence. Unfortunately, epidemiological evidence has been both inconclusive (some studies find associations while others cannot) and confounding (ethnicity seems to play a role in patients' susceptibility to IBD-T1D relationships).

Furthermore, suspected bidirectional associations between these diseases have never been formally investigated, leading researchers and clinicians to assume that the leading disease increases the risk of contracting the latter. Elucidating the associations between these potentially devastating public health concerns may evolve the methodology of patient treatment plans moving forward, resulting in a safer, healthier tomorrow.

About the study

The present study is a nationwide matched investigation of the associations between IBD and T1D. It leverages two separate study designs – case-control and matched cohort – to test if patients with IBD were at higher risk of contracting or having been previously diagnosed with T1D. Data for the study was derived from the Epidemiology Strengthened by histoPathology Reports in Sweden (ESPRESSO) and the Swedish National Patient Register (NPR) databases. Data acquisition limitations (ICD code limitations not addressed until ICD-10) restricted the study cohort to participants ≤28 years in 1987.

Study data was collected between 1987 and 2017 and included all patients positively identified as living with IBD (using the International Classification of Disease [ICD] codes). Data collection included Crohn's disease (CD) location, ulcerative colitis (UC) extent, and primary sclerosing cholangitis (PSC) presence/absence. Additionally, demographic data acquired from the Total Population Register (TPR) included IBD diagnosis year, sex, age, country of birth, and county of residence).

For both case-control and cohort studies, relative risk estimates were calculated (hazard ratio [HR] and odds ratio [OR], respectively). A flexible parametric survival model was used to improve HR computation. Conditional logistic regression was used to resolve results from both studies.

Study findings

The present work identified 20,314 (≤28 years) and 87,001 IBD-positive participants for the case-control and cohort studies, respectively. These participants were matched with 99,200 (case-control) and 431,054 baseline healthy reference individuals.

"Patients with IBD had a median age of 20.8 years at index date (33.0% diagnosed <18 years), and females comprised 46.4% of IBD patients. The prevalence of autoimmune diseases other than T1D was higher in IBD patients (9.0%) than in reference individuals (3.8%)," supporting the complexity of autoimmune comorbidities in IBD patients.

During the follow-up period (median = 14 years), 116 IBD cases and 353 reference controls were reported to develop T1D. Cases were found to have significantly higher T1D risk (aHR = 1.58) compared to their control counterparts, with aHR highest for UC patients (2.02).

Similar findings were observed in the backtracking case-control study – 1018 cases (1.2%) and 3,496 controls (0.8%) were found to be previously diagnosed with T1D with the highest risk in the IBD cohort (aOR = 1.36). Males and participants between 18–28 years were at higher risk, reinforcing previously noted gender and age-specific patterns in T1D development.  Even more noteworthy – sibling analysis (wherein one sibling is diagnosed with IBD while the other is not) revealed that the IBD-diagnosed sibling is at significantly higher T1D risk (aHR = 1.44) than their healthy sibling, suggesting that environmental and genetic factors alone may not fully explain this association.

Conclusions

The present study highlights the bidirectional associations between IBD and T1D, using an extensive cohort (n = 637,596), two independent study designs (case-control and cohort), and substantial follow-up (median = 14 years) to validate that the presence of one condition significantly increases the risk of contracting the other.

These findings emphasize the need for additional bidirectional research to avoid reinventing the wheel in favor of killing two birds with one stone. While the study suggests that the absolute risk may not be high enough to warrant routine screening for both conditions, clinicians should still remain aware of the increased co-occurrence risk, especially in high-risk groups. More pressingly, they suggest the need for clinicians to screen for both diseases and tailor long-term patient intervention plans to account for their co-occurrence, given their bidirectional associations.