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Diabetes Mellitus in Children with Acute Recurrent and Chronic Pancreatitis

Data From the INternational Study Group of Pediatric Pancreatitis

In Search for a CuRE Cohort

Bellin, Melena D.*; Lowe, Mark; Zimmerman, M. Bridget; Wilschanski, Michael§; Werlin, Steven||; Troendle, David M.; Shah, Uzma#; Schwarzenberg, Sarah J.*; Pohl, John F.**; Perito, Emily††; Ooi, Chee Yee‡‡; Nathan, Jaimie D.§§; Morinville, Veronique D.||||; McFerron, Brian A.¶¶; Mascarenhas, Maria R.##; Maqbool, Asim##; Liu, Quin***; Lin, Tom K.§§; Husain, Sohail Z.†††; Himes, Ryan‡‡‡; Heyman, Melvin B.††; Gonska, Tanja§§§; Giefer, Matthew J.||||||; Gariepy, Cheryl E.¶¶¶; Freedman, Steven D.###; Fishman, Douglas S.‡‡‡; Barth, Bradley; Abu-El-Haija, Maisam§§; Uc, Aliye

Journal of Pediatric Gastroenterology and Nutrition: November 2019 - Volume 69 - Issue 5 - p 599–606
doi: 10.1097/MPG.0000000000002482
Original Article: Pancreatology
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Objectives: Adults with chronic pancreatitis (CP) have a high risk for developing pancreatogenic diabetes mellitus (DM), but little is known regarding potential risk factors for DM in children with acute recurrent pancreatitis (ARP) or CP. We compared demographic and clinical features of children with ARP or CP, with and without DM, in the INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE (INSPPIRE) registry.

Methods: We reviewed the INSPPIRE database for the presence or absence of physician-diagnosed DM in 397 children, excluding those with total pancreatectomy with islet autotransplantation, enrolled from August 2012 to August 2017. Patient demographics, BMI percentile, age at disease onset, disease risk factors, disease burden, and treatments were compared between children with DM (n = 24) and without DM (n = 373).

Results: Twenty-four children (6% of the cohort) had a diagnosis of DM. Five of 13 tested were positive for beta cell autoantibodies. The DM group was 4.2 years [95% confidence interval (CI) 3–5.4] older at first episode of acute pancreatitis, and tended to more often have hypertriglyceridemia [odds ratio (OR) 5.21 (1.33–17.05)], coexisting autoimmune disease [OR 3.94 (0.88–13.65)] or pancreatic atrophy [OR 3.64 (1.13, 11.59)].

Conclusion: Pancreatic atrophy may be more common among children with DM, suggesting more advanced exocrine disease. However, data in this exploratory cohort also suggest increased autoimmunity and hypertriglyceridemia in children with DM, suggesting that risk factors for type 1 and type 2 DM, respectively may play a role in mediating DM development in children with pancreatitis.

*Pediatrics, University of Minnesota, Minneapolis, MN

Washington University, St. Louis, MO

University of Iowa, Iowa City, IA

§Hadassah Hebrew University Hospital, Jerusalem, Israel

||The Medical College of Wisconsin, Milwaukee, WI

UT Southwestern Medical Center, Dallas, TX

#Massachusetts General Hospital for Children, Boston, MA

**University of Utah, Salt Lake City, UT

††University of California San Francisco (UCSF), San Francisco, CA

‡‡School of Women's & Children's Health, Medicine, University of New South Wales, Sydney, New South Wales, Australia

§§Cincinnati Children's Hospital Medical Center, Cincinnati, OH

||||Montreal Children, Montreal, QC, Canada

¶¶Indiana University Riley Hospital for Children, Indianapolis, IN

##The Children's Hospital of Philadelphia, Philadelphia, PA

***Cedars-Sinai Medical Center, Los Angeles, CA

†††University of Pittsburgh and the UPMC Children's Hospital of Pittsburgh, Pittsburgh, PA

‡‡‡Texas Children's Hospital, Houston, TX

§§§The Hospital for Sick Children, Toronto, Ontario, Canada

||||||Seattle Childrens Hospital, Seattle, WA

¶¶¶Nationwide Children's Hospital, Columbus, OH

###Beth Israel Deaconess Medical Center, Boston, MA.

Address correspondence and reprint requests to Melena D. Bellin, MD, University of Minnesota Masonic Children's Hospital, East Building Room MB 671, 2450 Riverside Avenue S, Minneapolis, MN 55454 (e-mail: bell0130@umn.edu).

Received 3 December, 2018

Accepted 2 August, 2019

Research reported in this publication was supported by National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award numbers R21 DK096327 (A.U.), U01 DK108334 (A.U.).

M.L. is on the Board of Directors of the National Pancreas Foundation; receives royalties from Millipore Inc and UpToDate. T.G. and M.W. received a research grant from Vertex Pharmaceuticals. S.H. owns equity in PrevCon. J.P. is on the speaker's bureau for Medical Education Resources, Inc.; M.B. has served as a consultant for AbbVie Inc, NovoNordisk, and ARIEL Precision Medicine, and receives research funding from ViaCyte. A.U. is a member of American Board of Pediatrics, Subboard of Pediatric Gastroenterology.

The other authors report no conflicts of interest.

© 2019 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,