title: Fibroblast Growth Factor 21 and Fetuin-A in Obese Adolescents With and Without Type 2 Diabetes.
abstract: BACKGROUND
  Hepatokines such as fetuin-A or fibroblast growth factor 21 (FGF21) are reasonable candidates affecting the pathophysiology of type 2 diabetes mellitus (T2DM). However, studies in humans at the onset of disease are scarce.
  
  
  OBJECTIVE
  The objective of the study was to compare FGF21 and fetuin-A levels between adolescents with and without T2DM.
  
  
  METHODS
  This was a cross-sectional comparison of adolescents with and without T2DM.
  
  
  METHODS
  The study was conducted at diabetes and obesity treatment centers.
  
  
  METHODS
  Seventy-four predominantly Caucasian adolescents with T2DM aged 12-18 years and 74 body mass index (BMI)-, age-, and gender-matched controls participated in the study.
  
  
  METHODS
  There were no interventions.
  
  
  METHODS
  FGF21 and fetuin-A and their correlation to age, BMI, glycated hemoglobin, blood pressure, lipids, adiponectin, and leptin were measured.
  
  
  RESULTS
  Adolescents with T2DM showed significant higher FGF21 serum concentrations compared with obese controls without T2DM [median 277 pg/mL (interquartile range [IQR] 161-586) vs 200 pg/mL (IQR 116-323), respectively, P = .009] and higher fetuin-A serum concentrations (median 0.30 g/L (IQR 0.27-0.33) vs 0.28 g/L (IQR 0.25-0.30), respectively, P = .005). In a multiple linear regression analysis, fetuin-A was positively associated with glycated hemoglobin [β-coefficient 0.005 (95% confidence interval ± 0.004), P = .013], negatively with adiponectin (β-coefficient -0.004 (95% confidence interval ±0.002, P = .006) but not with BMI, age, gender, ethnicity, or leptin. FGF21 was not associated with any parameter in multiple linear regression analysis.
  
  
  CONCLUSIONS
  Increased FGF21 serum levels in obese adolescents with T2DM compared with obese adolescents without T2DM suggest a FGF21-resistant state in T2DM because FGF21 improves insulin sensitivity. The increase of fetuin-A levels in obese adolescents with T2DM supports the hypothesis that fetuin-A is involved in the pathogenesis of T2DM because this hepatokine leads to insulin resistance.
authors.affiliation: Department of Pediatric Endocrinology, Diabetes, and Nutrition Medicine (T.R.), Vestische Hospital for Children and Adolescents Datteln, University of Witten/Herdecke, D-45711 Datteln, Germany; Division of Pediatric Endocrinology (J.W.), Children's Hospital, University of Bonn, D-53117 Bonn, Germany; Department of Pediatric Endocrinology and Diabetes (S.W.), Charité Children's Hospital Universitätsmedizin Berlin, D-10117 Berlin, Germany; Division of Endocrinology and Diabetes (B.K.), Medical Faculty, Rhine-Westphalia Technical University, German Center for Diabetes Research, Aachen University, D-52062 Aachen, Germany; Department of General Pediatrics, Neonatology, and Pediatric Cardiology (T.M.), University Children's Hospital Düsseldorf, D-40225 Düsseldorf, Germany; Department for Pediatrics and Adolescent Medicine (M.F.), Medical University of Vienna, A-1090 Vienna, Austria; and Institute of Epidemiology and Medical Biometry (R.W.H.), Central Institute for Epidemiology and Medical Biometrics, German Center for Diabetes Research, University of Ulm, 89081 Ulm, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reinehr
authors.affiliation: Department of Pediatric Endocrinology, Diabetes, and Nutrition Medicine (T.R.), Vestische Hospital for Children and Adolescents Datteln, University of Witten/Herdecke, D-45711 Datteln, Germany; Division of Pediatric Endocrinology (J.W.), Children's Hospital, University of Bonn, D-53117 Bonn, Germany; Department of Pediatric Endocrinology and Diabetes (S.W.), Charité Children's Hospital Universitätsmedizin Berlin, D-10117 Berlin, Germany; Division of Endocrinology and Diabetes (B.K.), Medical Faculty, Rhine-Westphalia Technical University, German Center for Diabetes Research, Aachen University, D-52062 Aachen, Germany; Department of General Pediatrics, Neonatology, and Pediatric Cardiology (T.M.), University Children's Hospital Düsseldorf, D-40225 Düsseldorf, Germany; Department for Pediatrics and Adolescent Medicine (M.F.), Medical University of Vienna, A-1090 Vienna, Austria; and Institute of Epidemiology and Medical Biometry (R.W.H.), Central Institute for Epidemiology and Medical Biometrics, German Center for Diabetes Research, University of Ulm, 89081 Ulm, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Karges
authors.affiliation: Department of Pediatric Endocrinology, Diabetes, and Nutrition Medicine (T.R.), Vestische Hospital for Children and Adolescents Datteln, University of Witten/Herdecke, D-45711 Datteln, Germany; Division of Pediatric Endocrinology (J.W.), Children's Hospital, University of Bonn, D-53117 Bonn, Germany; Department of Pediatric Endocrinology and Diabetes (S.W.), Charité Children's Hospital Universitätsmedizin Berlin, D-10117 Berlin, Germany; Division of Endocrinology and Diabetes (B.K.), Medical Faculty, Rhine-Westphalia Technical University, German Center for Diabetes Research, Aachen University, D-52062 Aachen, Germany; Department of General Pediatrics, Neonatology, and Pediatric Cardiology (T.M.), University Children's Hospital Düsseldorf, D-40225 Düsseldorf, Germany; Department for Pediatrics and Adolescent Medicine (M.F.), Medical University of Vienna, A-1090 Vienna, Austria; and Institute of Epidemiology and Medical Biometry (R.W.H.), Central Institute for Epidemiology and Medical Biometrics, German Center for Diabetes Research, University of Ulm, 89081 Ulm, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Meissner
authors.affiliation: Department of Pediatric Endocrinology, Diabetes, and Nutrition Medicine (T.R.), Vestische Hospital for Children and Adolescents Datteln, University of Witten/Herdecke, D-45711 Datteln, Germany; Division of Pediatric Endocrinology (J.W.), Children's Hospital, University of Bonn, D-53117 Bonn, Germany; Department of Pediatric Endocrinology and Diabetes (S.W.), Charité Children's Hospital Universitätsmedizin Berlin, D-10117 Berlin, Germany; Division of Endocrinology and Diabetes (B.K.), Medical Faculty, Rhine-Westphalia Technical University, German Center for Diabetes Research, Aachen University, D-52062 Aachen, Germany; Department of General Pediatrics, Neonatology, and Pediatric Cardiology (T.M.), University Children's Hospital Düsseldorf, D-40225 Düsseldorf, Germany; Department for Pediatrics and Adolescent Medicine (M.F.), Medical University of Vienna, A-1090 Vienna, Austria; and Institute of Epidemiology and Medical Biometry (R.W.H.), Central Institute for Epidemiology and Medical Biometrics, German Center for Diabetes Research, University of Ulm, 89081 Ulm, Germany.
authors.forename: Susanna
authors.initials: S
authors.lastname: Wiegand
authors.affiliation: Department of Pediatric Endocrinology, Diabetes, and Nutrition Medicine (T.R.), Vestische Hospital for Children and Adolescents Datteln, University of Witten/Herdecke, D-45711 Datteln, Germany; Division of Pediatric Endocrinology (J.W.), Children's Hospital, University of Bonn, D-53117 Bonn, Germany; Department of Pediatric Endocrinology and Diabetes (S.W.), Charité Children's Hospital Universitätsmedizin Berlin, D-10117 Berlin, Germany; Division of Endocrinology and Diabetes (B.K.), Medical Faculty, Rhine-Westphalia Technical University, German Center for Diabetes Research, Aachen University, D-52062 Aachen, Germany; Department of General Pediatrics, Neonatology, and Pediatric Cardiology (T.M.), University Children's Hospital Düsseldorf, D-40225 Düsseldorf, Germany; Department for Pediatrics and Adolescent Medicine (M.F.), Medical University of Vienna, A-1090 Vienna, Austria; and Institute of Epidemiology and Medical Biometry (R.W.H.), Central Institute for Epidemiology and Medical Biometrics, German Center for Diabetes Research, University of Ulm, 89081 Ulm, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Fritsch
authors.affiliation: Department of Pediatric Endocrinology, Diabetes, and Nutrition Medicine (T.R.), Vestische Hospital for Children and Adolescents Datteln, University of Witten/Herdecke, D-45711 Datteln, Germany; Division of Pediatric Endocrinology (J.W.), Children's Hospital, University of Bonn, D-53117 Bonn, Germany; Department of Pediatric Endocrinology and Diabetes (S.W.), Charité Children's Hospital Universitätsmedizin Berlin, D-10117 Berlin, Germany; Division of Endocrinology and Diabetes (B.K.), Medical Faculty, Rhine-Westphalia Technical University, German Center for Diabetes Research, Aachen University, D-52062 Aachen, Germany; Department of General Pediatrics, Neonatology, and Pediatric Cardiology (T.M.), University Children's Hospital Düsseldorf, D-40225 Düsseldorf, Germany; Department for Pediatrics and Adolescent Medicine (M.F.), Medical University of Vienna, A-1090 Vienna, Austria; and Institute of Epidemiology and Medical Biometry (R.W.H.), Central Institute for Epidemiology and Medical Biometrics, German Center for Diabetes Research, University of Ulm, 89081 Ulm, Germany.
authors.forename: Reinhard W
authors.initials: RW
authors.lastname: Holl
authors.affiliation: Department of Pediatric Endocrinology, Diabetes, and Nutrition Medicine (T.R.), Vestische Hospital for Children and Adolescents Datteln, University of Witten/Herdecke, D-45711 Datteln, Germany; Division of Pediatric Endocrinology (J.W.), Children's Hospital, University of Bonn, D-53117 Bonn, Germany; Department of Pediatric Endocrinology and Diabetes (S.W.), Charité Children's Hospital Universitätsmedizin Berlin, D-10117 Berlin, Germany; Division of Endocrinology and Diabetes (B.K.), Medical Faculty, Rhine-Westphalia Technical University, German Center for Diabetes Research, Aachen University, D-52062 Aachen, Germany; Department of General Pediatrics, Neonatology, and Pediatric Cardiology (T.M.), University Children's Hospital Düsseldorf, D-40225 Düsseldorf, Germany; Department for Pediatrics and Adolescent Medicine (M.F.), Medical University of Vienna, A-1090 Vienna, Austria; and Institute of Epidemiology and Medical Biometry (R.W.H.), Central Institute for Epidemiology and Medical Biometrics, German Center for Diabetes Research, University of Ulm, 89081 Ulm, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Woelfle
mesh_terms: D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D063766:Pediatric Obesity / Q000097:blood* / Q000150:complications; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D005346:Fibroblast Growth Factors; D006442:Glycated Hemoglobin; D060749:alpha-2-HS-Glycoprotein; C556354:AHSG protein, human; C414620:fibroblast growth factor 21; C517652:hemoglobin A1c protein, human