Skip to main content

Advertisement

SpringerLink
Log in

Comorbid Diabetes in Inflammatory Bowel Disease Predicts Adverse Disease-Related Outcomes and Infectious Complications

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Diabetes mellitus (DM) and inflammatory bowel diseases (IBD) are chronic systemic illnesses associated with chronic inflammation, dysbiosis, impaired immune function, and infection risk. The impact of DM in modifying disease activity in patients with IBD remains largely unknown.

Aim

To investigate the impact of DM on IBD-related disease outcomes, mortality, and infections in patients with IBD.

Methods

We performed a longitudinal cohort analysis. Using a large institutional database, patients with concurrent IBD and DM (IBD–DM), and IBD without DM (IBD cohort), were identified and followed longitudinally to evaluate for primary (IBD-related) and secondary (mortality and infections) outcomes. Cox proportional hazards models were used to determine the independent effect of DM on each outcome, adjusting for confounding effects of covariates.

Results

A total of 901 and 1584 patients were included in the IBD–DM and DM cohorts. Compared with IBD, IBD–DM had significantly higher risk of IBD-related hospitalization [adjusted hazard ratio (HR) 1.97, 95% confidence interval (1.71–2.28)], disease flare [HR 2.05 (1.75–2.39)], and complication [HR 1.54 (1.29–1.85)]. No significant difference was observed in the incidence of IBD-related surgery. All-cause mortality, sepsis, Clostridioides difficile infection (CDI), pneumonia, urinary tract infection, and skin infection were also more frequent in the IBD–DM than the IBD cohort (all p ≤ 0.05). Subgroup analysis of Crohn’s disease (CD) and ulcerative colitis patients showed similar associations, except with an additional risk of surgery and no association with CDI in the CD–DM cohort.

Conclusion

Comorbid diabetes in patients with IBD is a predictor of poor disease-related and infectious outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Podolsky DK. Inflammatory bowel disease. N Engl J Med. 1991;325:1008–1016. https://doi.org/10.1056/NEJM199110033251406.

    Article  CAS  PubMed  Google Scholar 

  2. Loftus EV Jr. Update on the incidence and prevalence of inflammatory bowel disease in the United States. Gastroenterol Hepatol (N Y). 2016;12:704–707.

    Google Scholar 

  3. Dahlhamer JM, Zammitti EP, Ward BW, Wheaton AG, Croft JB. Prevalence of inflammatory bowel disease among adults aged ≥18 years–United States, 2015. MMWR Morb Mortal Wkly Rep. 2016;65:1166–1169. https://doi.org/10.15585/mmwr.mm6542a3.

    Article  PubMed  Google Scholar 

  4. Kim DH, Cheon JH. Pathogenesis of inflammatory bowel disease and recent advances in biologic therapies. Immune Netw. 2017;17:25–40. https://doi.org/10.4110/in.2017.17.1.25.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Khan I, Ullah N, Zha L, et al. Alteration of gut microbiota in inflammatory bowel disease (IBD): Cause or consequence? IBD treatment targeting the gut microbiome. Pathogens. 2019;. https://doi.org/10.3390/pathogens8030126.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2020. Centers for Disease Control and Prevention, US Department of Health and Human Services, Atlanta, GA. 2020. https://www.cdc.gov/diabetes/data/statistics/statistics-report.html.

  7. Katsarou A, Gudbjornsdottir S, Rawshani A, et al. Type 1 diabetes mellitus. Nat Rev Dis Primers. 2017;3:17016. https://doi.org/10.1038/nrdp.2017.16.

    Article  PubMed  Google Scholar 

  8. Afzali A, Katz S. Inflammatory bowel disease in the baby to baby boomer: pediatric and elderly onset of IBD. Curr Treat Options Gastroenterol. 2018;16:289–305. https://doi.org/10.1007/s11938-018-0188-9.

    Article  PubMed  Google Scholar 

  9. Qin J, Li Y, Cai Z, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature. 2012;490:55–60. https://doi.org/10.1038/nature11450.

    Article  CAS  PubMed  Google Scholar 

  10. Knapp S. Diabetes and infection: is there a link? A mini-review. Gerontology. 2013;59:99–104. https://doi.org/10.1159/000345107.

    Article  CAS  PubMed  Google Scholar 

  11. Abu-Ashour W, Twells L, Valcour J, et al. The association between diabetes mellitus and incident infections: a systematic review and meta-analysis of observational studies. BMJ Open Diabetes Res Care. 2017;5:e000336. https://doi.org/10.1136/bmjdrc-2016-000336.

    Article  PubMed  PubMed Central  Google Scholar 

  12. McConachie SM, Wilhelm SM, Bhargava A, Kale-Pradhan PB. Biologic-induced infections in inflammatory bowel disease: the TNF-alpha antagonists. Ann Pharmacother. 2018;52:571–579. https://doi.org/10.1177/1060028018754896.

    Article  CAS  PubMed  Google Scholar 

  13. Ananthakrishnan AN, Cagan A, Cai T, et al. Diabetes and the risk of infections with immunomodulator therapy in inflammatory bowel diseases. Aliment Pharmacol Ther. 2015;41:1141–1148. https://doi.org/10.1111/apt.13195.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bhakta A, Tafen M, Glotzer O, et al. Increased incidence of surgical site infection in IBD patients. Dis Colon Rectum. 2016;59:316–322. https://doi.org/10.1097/DCR.0000000000000550.

    Article  PubMed  Google Scholar 

  15. Coakley BA, Divino CM. Identifying factors predictive of surgical-site infections after colectomy for fulminant ulcerative colitis. Am Surg. 2012;78:481–484.

    Article  PubMed  Google Scholar 

  16. Kumar A, Kim M, Lukin DJ. Helicobacter pylori is associated with increased risk of serrated colonic polyps: analysis of serrated polyp risk factors. Indian J Gastroenterol. 2018;37:235–242. https://doi.org/10.1007/s12664-018-0855-8.

    Article  PubMed  Google Scholar 

  17. Francischetti IMB, Szymanski J, Rodriguez D, Heo M, Wolgast LR. Laboratory and clinical predictors of 30-day survival for patients on extracorporeal membrane oxygenation (ECMO): 8-year experience at Albert Einstein College of Medicine, Montefiore Medical Center. J Crit Care. 2017;40:136–144. https://doi.org/10.1016/j.jcrc.2017.03.027.

    Article  PubMed  Google Scholar 

  18. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40:373–383. https://doi.org/10.1016/0021-9681(87)90171-8.

    Article  CAS  PubMed  Google Scholar 

  19. Harper JW, Welch MP, Sinanan MN, Wahbeh GT, Lee SD. Co-morbid diabetes in patients with Crohn’s disease predicts a greater need for surgical intervention. Aliment Pharmacol Ther. 2012;35:126–132. https://doi.org/10.1111/j.1365-2036.2011.04915.x.

    Article  CAS  PubMed  Google Scholar 

  20. Choi JK, Kim DW, Shin SY, Park EC, Kang JG. Effect of ulcerative colitis on incidence of colorectal cancer: results from the nationwide population-based cohort study (2003–2013). J Cancer. 2016;7:681–686. https://doi.org/10.7150/jca.14264.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Fitzmorris PS, Colantonio LD, Torrazza Perez E, Smith I, Kakati DD, Malik TA. Impact of metabolic syndrome on the hospitalization rate of Crohn’s disease patients seen at a tertiary care center: a retrospective cohort study. Digestion. 2015;91:257–262. https://doi.org/10.1159/000380763.

    Article  CAS  PubMed  Google Scholar 

  22. Click B, Ramos Rivers C, Koutroubakis IE, et al. Demographic and clinical predictors of high healthcare use in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2016;22:1442–1449. https://doi.org/10.1097/MIB.0000000000000763.

    Article  PubMed  Google Scholar 

  23. Nwaneri C, Cooper H, Bowen-Jones D. Mortality in type 2 diabetes mellitus: magnitude of the evidence from a systematic review and meta-analysis. Br J Diabetes Vasc Dis. 2013;13:192–207. https://doi.org/10.1177/1474651413495703.

    Article  Google Scholar 

  24. Bewtra M, Kaiser LM, TenHave T, Lewis JD. Crohn’s disease and ulcerative colitis are associated with elevated standardized mortality ratios: a meta-analysis. Inflamm Bowel Dis. 2013;19:599–613. https://doi.org/10.1097/MIB.0b013e31827f27ae.

    Article  PubMed  Google Scholar 

  25. Rodemann JF, Dubberke ER, Reske KA, Seo DH, Stone CD. Incidence of Clostridium difficile infection in inflammatory bowel disease. Clin Gastroenterol Hepatol. 2007;5:339–344. https://doi.org/10.1016/j.cgh.2006.12.027.

    Article  PubMed  Google Scholar 

  26. Balram B, Battat R, Al-Khoury A, et al. Risk factors associated with Clostridium difficile infection in inflammatory bowel disease: a systematic review and meta-analysis. J Crohns Colitis. 2019;13:27–38. https://doi.org/10.1093/ecco-jcc/jjy143.

    Article  PubMed  Google Scholar 

  27. Carey IM, Critchley JA, DeWilde S, Harris T, Hosking FJ, Cook DG. Risk of infection in type 1 and type 2 diabetes compared with the general population: a matched cohort study. Diabetes Care. 2018;41:513–521. https://doi.org/10.2337/dc17-2131.

    Article  PubMed  Google Scholar 

  28. Shah ED, Farida JP, Siegel CA, Chong K, Melmed GY. Risk for overall infection with anti-TNF and anti-integrin agents used in IBD: a systematic review and meta-analysis. Inflamm Bowel Dis. 2017;23:570–577. https://doi.org/10.1097/MIB.0000000000001049.

    Article  PubMed  Google Scholar 

  29. Gong SS, Fan YH, Han QQ, Lv B, Xu Y. Nested case-control study on risk factors for opportunistic infections in patients with inflammatory bowel disease. World J Gastroenterol. 2019;25:2240–2250. https://doi.org/10.3748/wjg.v25.i18.2240.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Din H, Anderson AJ, Ramos Rivers C, et al. Disease characteristics and severity in patients with inflammatory bowel disease with coexistent diabetes mellitus. Inflamm Bowel Dis. 2020;. https://doi.org/10.1093/ibd/izz305.

    Article  PubMed  Google Scholar 

  31. Calle MC, Fernandez ML. Inflammation and type 2 diabetes. Diabetes Metab. 2012;38:183–191. https://doi.org/10.1016/j.diabet.2011.11.006.

    Article  CAS  PubMed  Google Scholar 

  32. Jurjus A, Eid A, Al Kattar S, et al. Inflammatory bowel disease, colorectal cancer and type 2 diabetes mellitus: the links. BBA Clin. 2016;5:16–24. https://doi.org/10.1016/j.bbacli.2015.11.002.

    Article  PubMed  Google Scholar 

  33. Nishida A, Inoue R, Inatomi O, Bamba S, Naito Y, Andoh A. Gut microbiota in the pathogenesis of inflammatory bowel disease. Clin J Gastroenterol. 2018;11:1–10. https://doi.org/10.1007/s12328-017-0813-5.

    Article  PubMed  Google Scholar 

  34. Kumar A, Lukin DJ. Incident heart failure is a predictor of adverse outcomes in inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2020;32:205–215. https://doi.org/10.1097/MEG.0000000000001648.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Gastroenterology, Jill Roberts Center for Inflammatory Bowel Disease, Weill Cornell Medical College, 1315 York Avenue, Mezzanine SM1A15, New York, NY, 10021, USA

    Anand Kumar & Dana J. Lukin

  2. Division of Gastroenterology, Department of Medicine, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA

    Anand Kumar, Tatiana Teslova & Dana J. Lukin

  3. Division of Endocrinology and Metabolism, Department of Medicine, Renaissance School of Medicine at Stony Brook, Stony Brook, NY, USA

    Erin Taub & Joshua D. Miller

Authors
  1. Anand Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tatiana Teslova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Erin Taub
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joshua D. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dana J. Lukin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dana J. Lukin.

Ethics declarations

Conflict of interest

Anand Kumar, Tatiana Teslova, and Erin Taub have no financial interests to disclose. Joshua D. Miller has received consulting fees from Joslin Diabetes Center. Dana J. Lukin has received consulting fees from Abbvie, Abgenomics, Pfizer, Prometheus, and Takeda and Grant Support from Abbvie, Kenneth Rainin Foundation, and Takeda. The authors have no non-financial competing interests to disclose.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kumar, A., Teslova, T., Taub, E. et al. Comorbid Diabetes in Inflammatory Bowel Disease Predicts Adverse Disease-Related Outcomes and Infectious Complications. Dig Dis Sci 66, 2005–2013 (2021). https://doi.org/10.1007/s10620-020-06439-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-020-06439-4

Keywords

Search

Navigation