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Wagner, R. ; Jaghutriz, B.A. ; Gerst, F. ; Barroso Oquendo, M. ; Machann, J. ; Schick, F. ; Löffler, M.* ; Nadalin, S.* ; Fend, F.* ; Königsrainer, A.* ; Peter, A. ; Siegel-Axel, D. ; Ullrich, S. ; Häring, H.-U. ; Fritsche, A. ; Heni, M.

Pancreatic steatosis associates with impaired insulin secretion in genetically predisposed individuals.

J. Clin. Endocrinol. Metab. 105:dgaa435 (2020)
Verlagsversion DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
CONTEXT: Pancreatic steatosis leading to beta-cell failure might be involved in type 2 diabetes (T2D) pathogenesis. OBJECTIVE: We hypothesized that the genetic background modulates the effect of pancreatic fat on beta-cell function and investigated genotype × pancreatic fat interactions on insulin secretion. DESIGN: Two observational studies. SETTING: University hospital. PATIENTS OR PARTICIPANTS: A total of 360 nondiabetic individuals with elevated risk for T2D (Tuebingen Family Study [TUEF]), and 64 patients undergoing pancreatectomy (Pancreas Biobank [PB], HbA1c <9%, no insulin therapy). MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Beta Cell Function ; Insulin Secretion ; Non-alcoholic Fatty Pancreas Disease ; Pancreatic Steatosis ; Prediabetes ; Type 2 Diabetes; Beta-cell Function; Fatty Pancreas; Glucose-tolerance; Accuracy; Risk
ISSN (print) / ISBN 0021-972X
e-ISSN 1945-7197
Quellenangaben Band: 105, Heft: 11, Seiten: , Artikelnummer: dgaa435 Supplement: ,
Verlag Endocrine Society
Verlagsort Bethesda, Md.
Begutachtungsstatus Peer reviewed
Förderungen Swiss State Secretariat for Education, Research and Innovation (SERI)
EFPIA
European Union
Federal Ministry of Education and Research (BMBF)