title: Sfrp5 associates with beta-cell function in humans.
abstract: BACKGROUND
  Secreted frizzled-related protein (Sfrp)5 improves insulin sensitivity, but impairs beta-cell function in rodents. However, the relationship between Sfrp5, insulin sensitivity and secretion in humans is currently unclear. Therefore, the aim of the study was to characterize the associations between serum Sfrp5 and indices of insulin sensitivity and beta-cell function from dynamic measurements using oral glucose tolerance tests (OGTT) in humans.
  
  
  METHODS
  This study enrolled 194 individuals with nonalcoholic fatty liver disease (NAFLD), who were 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 insulin sensitivity 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 adjustment for age, sex and body mass index. Sfrp5 inversely correlated only with QUICKI as a marker of insulin sensitivity in the model adjusted for age and sex (rs = -0·149, P = 0·039). These associations were not influenced by the additional adjustment for hepatic steatosis index.
  
  
  CONCLUSIONS
  The inverse association of serum Sfrp5 with beta-cell function suggests a detrimental role of Sfrp5 for insulin secretion also in humans. The severity of NAFLD does not appear to affect this relationship. The weak association between serum Sfrp5 and insulin sensitivity was partially explained by body mass.
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Carstensen-Kirberg
authors.affiliation: 2nd Department of Internal Medicine, Research Institute and Diabetes Center, Athens University, 'Attikon' University General Hospital, Athens, Greece.
authors.forename: Erifili
authors.initials: E
authors.lastname: Hatziagelaki
authors.affiliation: 2nd Department of Internal Medicine, Research Institute and Diabetes Center, Athens University, 'Attikon' University General Hospital, Athens, Greece.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Tsiavou
authors.affiliation: 4th Department of Internal Medicine, 'Attikon' University General Hospital, Athens, Greece.
authors.forename: Athina
authors.initials: A
authors.lastname: Chounta
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Nowotny
authors.affiliation: Metabolic Unit, CNR Neuroscience Institute, National Research Council, Padova, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pacini
authors.affiliation: 2nd Department of Internal Medicine, Research Institute and Diabetes Center, Athens University, 'Attikon' University General Hospital, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Dimitriadis
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.|Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.|German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D005136:Eye Proteins / Q000097:blood*; D005260:Female; D018149:Glucose Intolerance / Q000097:blood* / Q000150:complications; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000097:blood*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000150:complications; D009765:Obesity / Q000097:blood / Q000150:complications; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001786:Blood Glucose; D002096:C-Peptide; D005136:Eye Proteins; D007328:Insulin; D008565:Membrane Proteins; C118511:SFRP5 protein, human; D000094742:Secreted Frizzled-Related Proteins
keywords: Beta-cell function; Sfrp5; insulin sensitivity; nonalcoholic fatty liver diseases