{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T15:04:06Z","timestamp":1779894246723,"version":"3.53.1"},"posted":{"date-parts":[[2026,5,25]]},"group-title":"Endocrinology (including Diabetes Mellitus and Metabolic Disease)","reference-count":19,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["NIH P30DK116074"],"award-info":[{"award-number":["NIH P30DK116074"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"crossref","award":["R03 DK 131156"],"award-info":[{"award-number":["R03 DK 131156"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,5,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Acute pancreatitis (AP) is an established risk factor for diabetes, with approximately 20% of children developing either prediabetes or diabetes within one year of their first episode. Little is known about the diabetes pathophysiology or which individuals are at highest risk. We aimed to evaluate whether genetic risk scores (GRS) for type 1 (T1D) and polygenic risk scores (PRS) type 2 diabetes (T2D) are associated with progression to dysglycemia following AP.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Clinical data were available for 123 children (mean age (IQR), 12 (8-15) years; mean body mass index (BMI), 21.8) with AP who were followed for &gt;1 year. Array genotyping coupled with imputation using the TOPMed reference panel was performed. Genetic ancestry was predicted using a random forest classifier. GRS for T1D and T2D were calculated using either an ancestry-appropriate (T1D-GRS) or a multi-ancestry (T2D-PRS) weighted framework. To evaluate risk compared to the population we used predefined GRS thresholds from UK Biobank.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among the 123 subjects, 24 developed dysglycemia (5 with diabetes and 19 with prediabetes). The majority (75.6%, n=93) of children were of European ancestry. Comparison of the T1D-GRS burden with the UK BioBank showed numerically higher proportions for any given threshold. At the top 5% threshold, 9.7% of our cohort were classified as high-risk compared to 5% in UK Biobank (p&lt;0.05). The elevated T1D-GRS could be primarily attributed to non-HLA variants and was more enriched in those testing positive for \u22651 islet-autoantibody. The T2D-PRS was also elevated in the dysglycemic group but only reached statistical significance in those who were obese.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>These findings highlight the potential role of both T1D-GRS and T2D-PRS in investigating diabetes susceptibility following AP.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.05.23.26353958","type":"posted-content","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:20:46Z","timestamp":1779754846000},"source":"Crossref","is-referenced-by-count":0,"title":["Role of genetic risk on progression to diabetes in children with acute pancreatitis"],"prefix":"10.64898","author":[{"given":"Lu","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Stanford School of Medicine, Stanford University, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faizan","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth A.","family":"Sharp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford School of Medicine, Stanford University, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford School of Medicine, Stanford University, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swaraj","family":"Thaman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford School of Medicine, Stanford University, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive H.","family":"Wasserfall","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology, and Laboratory, Medicine, University of Florida, FL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1205-1844","authenticated-orcid":false,"given":"Anna L.","family":"Gloyn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford School of Medicine, Stanford University, CA, USA"},{"name":"Department of Genetics, Stanford School of Medicine, Stanford University, CA, USA"},{"name":"Stanford Diabetes Research Center, Stanford School of Medicine, Stanford University, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maisam","family":"Abu-El-Haija","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH, USA"},{"name":"Department of Pediatrics, College of Medicine, University of Cincinnati, Cincinnati, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"issue":"10","key":"2026052707100960000_2026.05.23.26353958v1.1","doi-asserted-by":"crossref","first-page":"2033","DOI":"10.1016\/j.cgh.2024.05.039","article-title":"The Role of Pancreatitis Risk Genes in Endocrine Insufficiency Development After Acute Pancreatitis in Children","volume":"22","year":"2024","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"4","key":"2026052707100960000_2026.05.23.26353958v1.2","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1053\/j.gastro.2025.04.001","article-title":"Acute Pancreatitis in Children: It\u2019s Not Just a Simple Attack","volume":"169","year":"2025","journal-title":"Gastroenterology"},{"issue":"9","key":"2026052707100960000_2026.05.23.26353958v1.3","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1038\/s41574-025-01132-w","article-title":"Diabetes mellitus polygenic risk scores: heterogeneity and clinical translation","volume":"21","year":"2025","journal-title":"Nat Rev Endocrinol"},{"issue":"8","key":"2026052707100960000_2026.05.23.26353958v1.4","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S2213-8587(22)00159-0","article-title":"Type 1 diabetes in diverse ancestries and the use of genetic risk scores","volume":"10","year":"2022","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"6","key":"2026052707100960000_2026.05.23.26353958v1.5","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1097\/MPG.0000000000001583","article-title":"Classification of Acute Pancreatitis in the Pediatric Population: Clinical Report From the NASPGHAN Pancreas Committee","volume":"64","year":"2017","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"2026052707100960000_2026.05.23.26353958v1.6","doi-asserted-by":"crossref","unstructured":"Tatum JD , Hornung L , Bellin MD , Elder DA , Thompson T , Vitale DS , Wasserfall CH , Shah AS , Abu-El-Haija M . 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