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Observational Study
. 2024 Oct;22(10):2033-2043.e2.
doi: 10.1016/j.cgh.2024.05.039. Epub 2024 Jun 12.

The Role of Pancreatitis Risk Genes in Endocrine Insufficiency Development After Acute Pancreatitis in Children

Maisam Abu-El-Haija  1 , Wenying Zhang  2 , Rebekah Karns  3 , Gila Ginzburg  4 , David S Vitale  5 , Peter Farrell  5 , Alexander Nasr  3 , Sherif Ibrahim  3 , Melena D Bellin  6 , Tyler Thompson  3 , Vineet Garlapally  3 , Jessica G Woo  7 , Sohail Z Husain  8 , Lee A Denson  5
Affiliations
Observational Study

The Role of Pancreatitis Risk Genes in Endocrine Insufficiency Development After Acute Pancreatitis in Children

Maisam Abu-El-Haija et al. Clin Gastroenterol Hepatol. 2024 Oct.

Abstract

Background & aims: Acute pancreatitis (AP) is increasingly recognized as a risk factor for diabetes mellitus (DM). We aimed to study the association of pancreatitis genes with pancreatic endocrine insufficiency (pre-DM and DM) development post-AP in children.

Methods: This was an observational cohort study that enrolled subjects ≤21 years with their first episode of AP and followed them for 12 months for the development of pancreatic endocrine insufficiency. Pancreatitis risk genes (CASR, CEL, CFTR, CLDN2, CPA1, CTRC, PRSS1, SBDS, SPINK1, and UBR1) were sequenced. A genetic risk score was derived from all genes with univariable P < .15.

Results: A total 120 subjects with AP were genotyped. Sixty-three subjects (52.5%) had at least 1 reportable variant identified. For modeling the development of pancreatic endocrine insufficiency at 1 year, 6 were excluded (2 with DM at baseline, 3 with total pancreatectomy, and 1 death). From this group of 114, 95 remained normoglycemic and 19 (17%) developed endocrine insufficiency (4 DM, 15 pre-DM). Severe AP (58% vs 20%; P = .001) and at least 1 gene affected (79% vs 47%; P = .01) were enriched among the endocrine-insufficient group. Those with versus without endocrine insufficiency were similar in age, sex, race, ethnicity, body mass index, and AP recurrence. A model for pre-DM/DM development included AP severity (odds ratio, 5.17 [1.66-16.15]; P = .005) and genetic risk score (odds ratio, 4.89 [1.83-13.08]; P = .002) and had an area under the curve of 0.74.

Conclusions: In this cohort of children with AP, pancreatitis risk genes and AP disease severity were associated with pre-DM or DM development post-AP.

Keywords: Children; Diabetes; Genetic Risks; Pancreatitis.

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Conflict of interest statement

Conflict of Interest Statement:

MDB receives research support from Dexcom and Viacyte; and discloses consulting for Ariel Precision Medicine and Vertex. All other authors report no conflicts of interest.

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