Sfrp5 associates with beta-cell function in humans

Background Secreted frizzled-related protein (Sfrp)5 improves insulin sensitivity, but impairs beta-cell functionin rodents. However, the relationship between Sfrp5, insulin sensitivity and secretion in humans is currentlyunclear. Therefore, the aim of the study was to characterize the associations between serum Sfrp5 and indicesof insulin sensitivity and beta-cell function from dynamic measurements using oral glucose tolerance tests(OGTT) in humans.Material and methods This study enrolled 194 individuals with nonalcoholic fatty liver disease (NAFLD), whowere diagnosed based on ultrasound and liver transaminases and underwent a frequent sampling 75-g OGTT.Fasting serum Sfrp5 was measured by ELISA. Associations were assessed with several indices of insulinsensitivity and beta-cell function derived from glucose, insulin and C-peptide concentrations during the OGTT.Results Circulating Sfrp5 associated inversely with the insulinogenic index based on C-peptide (rs= ?0?244,P = 0?001), but not with the insulinogenic index based on insulin levels (rs= ?0?007, P = 0?926) after adjust-ment for age, sex and body mass index. Sfrp5 inversely correlated only with QUICKI as a marker of insulinsensitivity in the model adjusted for age and sex (rs= ?0?149, P = 0?039). These associations were not influ-enced by the additional adjustment for hepatic steatosis index.Conclusions The inverse association of serum Sfrp5 with beta-cell function suggests a detrimental role ofSfrp5 for insulin secretion also in humans. The severity of NAFLD does not appear to affect this relationship. Theweak association between serum Sfrp5 and insulin sensitivity was partially explained by body mass.