Thomas Reinehr1, Beate Karges1, Thomas Meissner1, Susanna Wiegand1, Maria Fritsch1, Reinhard W Holl1, Joachim Woelfle1. 1. 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.
Abstract
CONTEXT: 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. DESIGN: This was a cross-sectional comparison of adolescents with and without T2DM. SETTING: The study was conducted at diabetes and obesity treatment centers. PATIENTS: 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. INTERVENTION: There were no interventions. MAIN OUTCOME MEASURES: 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.
CONTEXT: 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. DESIGN: This was a cross-sectional comparison of adolescents with and without T2DM. SETTING: The study was conducted at diabetes and obesity treatment centers. PATIENTS: 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. INTERVENTION: There were no interventions. MAIN OUTCOME MEASURES: 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: Julia Seyfarth; Thomas Reinehr; Annika Hoyer; Christina Reinauer; Christina Bächle; Beate Karges; Ertan Mayatepek; Michael Roden; Sabine E Hofer; Susanna Wiegand; Joachim Woelfle; Wieland Kiess; Joachim Rosenbauer; Reinhard W Holl; Thomas Meissner Journal: J Inherit Metab Dis Date: 2017-10-13 Impact factor: 4.982