title: An extended fatty liver index to predict non-alcoholic fatty liver disease.
abstract: BACKGROUND
  In clinical practice, there is a strong interest in non-invasive markers of non-alcoholic fatty liver disease (NAFLD). Our hypothesis was that the fold-change in plasma triglycerides (TG) during a 2-h oral glucose tolerance test (fold-change TGOGTT) in concert with blood glucose and lipid parameters, and the rs738409 C>G single nucleotide polymorphism (SNP) in PNPLA3 might improve the power of the widely used fatty liver index (FLI) to predict NAFLD.
  
  
  METHODS
  The liver fat content of 330 subjects was quantified by1H-magnetic resonance spectroscopy. Blood parameters were measured during fasting and after a 2-h OGTT. A subgroup of 213 subjects underwent these measurements before and after 9 months of a lifestyle intervention.
  
  
  RESULTS
  The fold-change TGOGTTwas closely associated with liver fat content (r=0.51, P<0.0001), but had less power to predict NAFLD (AUROC=0.75) than the FLI (AUROC=0.79). Not only was the fold-change TGOGTTindependently associated with liver fat content and NAFLD, but so also were the 2-h blood glucose level and rs738409 C>G SNP in PNPLA3. In fact, a novel index (extended FLI) generated from these and the usual FLI parameters considerably increased its power to predict NAFLD (AUROC=0.79-0.86). The extended FLI also increased the power to predict changes in liver fat content with a lifestyle intervention (n=213; standardized beta coefficient: 0.23-0.29).
  
  
  CONCLUSIONS
  This study has provided novel data confirming that the OGTT-derived fold-change TGOGTTand 2-h glucose level, together with the rs738409 C>G SNP in PNPLA3, allow calculation of an extended FLI that considerably improves its power to predict NAFLD.
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller Street 10, 72076 Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Centre Munich, University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Kantartzis
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller Street 10, 72076 Tübingen, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Rettig
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller Street 10, 72076 Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Centre Munich, University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Staiger
authors.affiliation: German Center for Diabetes Research (DZD), Neuherberg, Germany; Section on Experimental Radiology, University of Tübingen, Tübingen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Machann
authors.affiliation: German Center for Diabetes Research (DZD), Neuherberg, Germany; Section on Experimental Radiology, University of Tübingen, Tübingen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Schick
authors.affiliation: Department of Biochemistry and Molecular Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Scheja
authors.affiliation: Institute of Clinical Physiology National Research Council, Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Gastaldelli
authors.affiliation: Division of Gastroenterology, Department of Medical Sciences, University of Torino, Torino, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Bugianesi
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller Street 10, 72076 Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Centre Munich, University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Peter
authors.affiliation: German Center for Diabetes Research (DZD), Neuherberg, Germany; Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
authors.forename: M B
authors.initials: MB
authors.lastname: Schulze
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller Street 10, 72076 Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Centre Munich, University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Fritsche
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller Street 10, 72076 Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Centre Munich, University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
authors.forename: H-U
authors.initials: HU
authors.lastname: Häring
authors.affiliation: Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Otfried-Müller Street 10, 72076 Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Centre Munich, University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany. Electronic address: norbert.stefan@med.uni-tuebingen.de.
authors.forename: N
authors.initials: N
authors.lastname: Stefan
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology* / Q000503:physiopathology; D011237:Predictive Value of Tests; D012372:ROC Curve; D014280:Triglycerides / Q000097:blood
chemical_list: D014280:Triglycerides
keywords: Fatty liver; Lifestyle intervention; NAFLD; OGTT; Prediction; Triglycerides