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.