Wagner R, Jaghutriz BA, Gerst F, et al. - In the present study, the researchers tested the assumption that the genetic background modulates the impact of pancreatic fat on beta-cell function and examine genotype x pancreatic fat interactions on insulin secretion. Participants in the study were 360 non-diabetic people with elevated risk for T2D (Tuebingen Family Study, TUEF), and 64 patients undergoing pancreatectomy (Pancreas Biobank, PB, HbA1c < 9%, no insulin therapy). A negative correlation was found between pancreatic fat and insulin secretion in candidates with high genetic risk, whereas people with low genetic risk exhibited a positive association between pancreatic fat and insulin secretion. Among individuals at high genetic risk for diabetes, the findings indicate that pancreatic steatosis only impairs beta-cell function. In particular, genetically determined insulin resistance makes pancreatic fat deleterious for insulin secretion.