@article{wagner_pancreatic_2020,
	title = {Pancreatic Steatosis Associates With Impaired Insulin Secretion in Genetically Predisposed Individuals},
	volume = {105},
	issn = {0021-972X, 1945-7197},
	url = {https://academic.oup.com/jcem/article/doi/10.1210/clinem/dgaa435/5877700},
	doi = {10.1210/clinem/dgaa435},
	abstract = {Abstract
            
              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}], {HbA}1c \<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.},
	pages = {dgaa435},
	number = {11},
	journaltitle = {The Journal of Clinical Endocrinology \& Metabolism},
	author = {Wagner, Róbert and Jaghutriz, Benjamin Assad and Gerst, Felicia and Barroso Oquendo, Morgana and Machann, Jürgen and Schick, Fritz and Löffler, Markus W and Nadalin, Silvio and Fend, Falko and Königsrainer, Alfred and Peter, Andreas and Siegel-Axel, Dorothea and Ullrich, Susanne and Häring, Hans-Ulrich and Fritsche, Andreas and Heni, Martin},
	urldate = {2020-11-19},
	date = {2020-11-01},
	langid = {english},
	keywords = {{WP}5},
}