{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:50:34Z","timestamp":1791521434240,"version":"4.3.4"},"reference-count":30,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T00:00:00Z","timestamp":1595980800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"German Center for Diabetes Research","award":["01GI0925"],"award-info":[{"award-number":["01GI0925"]}]},{"name":"European Union\u2019s Seventh Framework Program","award":["FP7\/2007\u20132013"],"award-info":[{"award-number":["FP7\/2007\u20132013"]}]},{"name":"Swiss State Secretariat for Education\u201a Research and Innovation","award":["115881"],"award-info":[{"award-number":["115881"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Pancreatic steatosis leading to beta-cell failure might be involved in type 2 diabetes (T2D) pathogenesis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We hypothesized that the genetic background modulates the effect of pancreatic fat on beta-cell function and investigated genotype \u00d7 pancreatic fat interactions on insulin secretion.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Two observational studies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>University hospital.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients or participants<\/jats:title>\n                  <jats:p>A total of 360 nondiabetic individuals with elevated risk for T2D (Tuebingen Family Study [TUEF]), and 64 patients undergoing pancreatectomy (Pancreas Biobank [PB], HbA1c &amp;lt;9%, no insulin therapy).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Main Outcome Measures<\/jats:title>\n                  <jats:p>Insulin secretion calculated from 5-point oral glucose tolerance test (TUEF) and fasting blood collection before surgery (PB). A genome-wide polygenic score for T2D was computed from 484,788 genotyped variants. The interaction of magnetic resonance imaging-measured and histologically quantified pancreatic fat with the polygenic score was investigated. Partitioned risk scores using genome-wide significant variants were also computed to gain insight into potential mechanisms.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Pancreatic steatosis interacted with genome-wide polygenic score on insulin secretion (P = 0.003), which was similar in the replication cohort with histological measurements (P = 0.03). There was a negative association between pancreatic fat and insulin secretion in participants with high genetic risk, whereas individuals with low genetic risk showed a positive correlation between pancreatic fat and insulin secretion. Consistent interactions were found with insulin resistance-specific and a liver\/lipid-specific polygenic scores.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>The associations suggest that pancreatic steatosis only impairs beta-cell function in subjects at high genetic risk for diabetes. Genetically determined insulin resistance specifically renders pancreatic fat deleterious for insulin secretion.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa435","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T09:18:54Z","timestamp":1596014334000},"page":"3518-3525","source":"Crossref","is-referenced-by-count":69,"title":["Pancreatic Steatosis Associates With Impaired Insulin Secretion in Genetically Predisposed Individuals"],"prefix":"10.1210","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6120-0191","authenticated-orcid":false,"given":"R\u00f3bert","family":"Wagner","sequence":"first","affiliation":[{"name":"Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"German Center for Diabetes Research (DZD e.V.)"},{"name":"Department of Internal Medicine, Division of Diabetology, Endocrinology and Nephrology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin Assad","family":"Jaghutriz","sequence":"additional","affiliation":[{"name":"Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"German Center for Diabetes Research (DZD e.V.)"},{"name":"Department of Internal Medicine, Division of Diabetology, Endocrinology and Nephrology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia","family":"Gerst","sequence":"additional","affiliation":[{"name":"Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"German Center for Diabetes Research (DZD e.V.)"},{"name":"Department of Internal Medicine, Division of Diabetology, Endocrinology and Nephrology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgana","family":"Barroso Oquendo","sequence":"additional","affiliation":[{"name":"Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"German Center for Diabetes Research (DZD e.V.)"},{"name":"Department of Internal Medicine, Division of Diabetology, Endocrinology and Nephrology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4458-5886","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Machann","sequence":"additional","affiliation":[{"name":"Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"German Center for Diabetes Research (DZD e.V.)"},{"name":"Section on Experimental Radiology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fritz","family":"Schick","sequence":"additional","affiliation":[{"name":"Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"German Center for Diabetes Research (DZD e.V.)"},{"name":"Section on Experimental Radiology, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2513-1317","authenticated-orcid":false,"given":"Markus W","family":"L\u00f6ffler","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplant Surgery, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Interfaculty Institute for Cell Biology, Department of Immunology, 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