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. 2024 Aug 31:46:101056.
doi: 10.1016/j.lanepe.2024.101056. eCollection 2024 Nov.

Bidirectional association between inflammatory bowel disease and type 1 diabetes: a nationwide matched cohort and case-control study

Jiangwei Sun  1 , Jialu Yao  1 , Ola Olén  2   3   4 , Jonas Halfvarsson  5 , David Bergman  1 , Fahim Ebrahimi  1   6 , Sofia Carlsson  7 , Johnny Ludvigsson  8   9 , Jonas F Ludvigsson  1   10   11
Affiliations

Bidirectional association between inflammatory bowel disease and type 1 diabetes: a nationwide matched cohort and case-control study

Jiangwei Sun et al. Lancet Reg Health Eur. .

Abstract

Background: Co-occurrence of inflammatory bowel disease (IBD) and type 1 diabetes (T1D) has been linked to poor clinical outcomes, but evidence on their bidirectional associations remain scarce. This study aims to investigate their bidirectional associations.

Methods: A nationwide matched cohort and case-control study with IBD patients identified between 1987 and 2017. The cohort study included 20,314 IBD patients (≤28 years; Crohn's disease [CD, n = 7277], ulcerative colitis [UC, n = 10,112], and IBD-unclassified [IBD-U, n = 2925]) and 99,200 individually matched reference individuals, with a follow-up until December 2021. The case-control study enrolled 87,001 IBD patients (no age restriction) and 431,054 matched controls. We estimated adjusted hazard ratio (aHR) of incident T1D in the cohort study with flexible parametric survival model and adjusted odds ratio (aOR) of having a prior T1D in the case-control study with conditional logistic regression model, with 95% confidence intervals (CI).

Findings: During a median follow-up of 14 years, 116 IBD patients and 353 reference individuals developed T1D. Patients with IBD had a higher hazard of developing T1D (aHR = 1.58 [95% CI = 1.27-1.95]). The hazard was increased in UC (aHR = 2.02 [1.51-2.70]) but not in CD or IBD-U. In the case-control study, a total of 1018 (1.2%) IBD patients and 3496 (0.8%) controls had been previously diagnosed with T1D. IBD patients had higher odds of having prior T1D (aOR = 1.36 [1.26-1.46]). Such positive association was observed in all IBD subtypes. The sibling comparison analyses showed similar associations between IBD and T1D (aHR = 1.44 [0.97-2.15] and aOR = 1.32 [1.18-1.49]).

Interpretation: Patients with IBD had a moderately increased hazard of developing T1D and higher odds of having prior T1D. Their bidirectional associations may be partially independent of shared familial factors.

Funding: European Crohn's and Colitis Organisation, Stiftelsen Professor Nanna Svartz Fond, SSMF (project#: PG-23-0315-H-02), Ruth and Richard Julin Foundation; and FORTE (project#: 2016-00424).

Keywords: Case–control; Cohort; Inflammatory bowel disease; Nationwide; Type 1 diabetes.

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Conflict of interest statement

All authors have completed the ICMJE uniform disclosure form and declare: OO has been PI on projects at Karolinska Institutet financed by grants from Janssen, Pfizer, AbbVie, Takeda, Galapagos/Alfasigma, Ferring, and Bristol Myer Squibb. JH served as speaker and/or advisory board member for AbbVie, BMS, Celltrion, Eli Lilly, Ferring, Galapagos, Gilead, Index Pharma, Janssen, Medtronic, Merck, MSD, Novartis, Pfizer, Sandoz, Shire, Takeda, Thermo Fisher Scientific, Tillotts Pharma, and Vifor Pharma and received grant support from Takeda, Janssen, and MSD. FE has served as an advisory board member for Boehringer Ingelheim. JFL has coordinated a study on behalf of the Swedish IBD quality register (SWIBREG). That study received funding from Janssen Corporation. JFL has also received financial support from MSD developing a paper reviewing national healthcare registers in China. JFL has a research collaboration on celiac disease with Takeda. The other authors report no disclosures relevant to the manuscript.

Figures

Fig. 1
Fig. 1
Diagram of the study design for the bidirectional association between inflammatory bowel disease (IBD) and type 1 diabetes (T1D). ESPRESSO: Epidemiology Strengthened by histoPathology Reports in Sweden.
Fig. 2
Fig. 2
Incidence rate (IR) and hazard ratios for incident type 1 diabetes (T1D) in patients with inflammatory bowel disease (IBD), compared with their matched reference individuals (A) and full siblings (B), with 95% confidence interval (CI). The hazard ratio was estimated from the flexible parametric survival model in Model 2. CD: Crohn’s disease; IBD-U: IBD-unclassified; and UC: ulcerative colitis.
Fig. 3
Fig. 3
Odds ratios for prior type 1 diabetes (T1D) in patients with inflammatory bowel disease (IBD), compared with their matched reference individuals (A) and full siblings (B), with 95% confidence interval (CI). The odds ratio was estimated from the conditional logistic regression model in Model 2. CD: Crohn’s disease; IBD-U: IBD-unclassified; and UC: ulcerative colitis.
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