ESPE Abstracts (2019) 92 P1-60

The Effect of Improved Metabolic Risk Factors and Metformin Therapy on Circulating Hepatokines in Obese, Insulin-Resistant Adolescents

Suna Kılınç1, Ayşegül Kırankaya2, Zeynep Atay3


1University of Health Science Bağcılar Training and Research Hospital, Department of Pediatric Endocrinology, Istanbul, Turkey. 2University of Health Science Bağcılar Training and Research Hospital, Biochemistry, Istanbul, Turkey. 3Medipol University, Fakulty of Medicine, Department of Pediatric Endocrinology, Istanbul, Turkey


Introduction: The molecular mechanisms underlying insulin resistance (IR) is complex and has not been fully elucidated yet. The experimental studies point out the role of liver-derived proteins, called hepatokines.

Aims: To compare metabolic parameters and hepatokines levels in obese adolescents and healthy controls and to assess the effect of metformin therapy on plasma hepatokines levels in obese, insulin-resistant adolescents.

Material and Methods: Sixty-nine subjects (38 girls, 31 boys) aged between 12-18 years were included. Participants were categorized into two groups. The first-group comprised obese adolescents with a body mass index (BMI) >95th percentile and the second-group comprised healthy controls with a BMI between the 5th and 85th percentile. Anthropometric and biochemical (glucose, insulin, lipid profile, Fetuin-A, fibroblast growth factor-21 (FGF-21), angiopoietin-related growth factor (AGF), leukocyte-derived chemotaxin 2 (LECT2) and Selenoprotein-P (SEPP1)) parameters were evaluated. Firstly, metabolic parameters and hepatokines levels were compared in obese group and healthy controls. Secondly all obese patients underwent a standard oral glucose tolerance test (OGTT). Patients diagnosed with IR at OGTT were started metformin (2g/day, 2 doses) therapy for 6-months. Then the differences in the biochemical characteristics and hepatokines levels analyzed between pre- and post-treatment. Plasma hepatokines levels were determined using an enzyme-linked immunosorbent assay (ELISA) method (Abbkine, Inc. China).

Results: Study included 44 obese (21 males, 23 females; mean age: 13.1±1.9 years) and 25 healthy non-obese children (10 males, 15 females; mean age: 13.5±1.9 years). Glucose, insulin, HbA1c, Fetuin-A, LECT2 and SEPP1 levels were significantly higher in obese patients (P<0.05); FGF-21 and AGF levels were not significantly different between the two groups (P=0.776, P=0.214). There was a statistically significant decrease in serum glucose, insulin, HbA1c, total cholesterol, triglyceride and LECT2 levels and a statistically significant increase in serum HDL-cholesterol levels after 6-months of metformin therapy. There was no statistically significant difference in Fetuian-A, FGF-21, AGF and SEPP1 levels after treatment (P>0.05).

Conclusion: Plasma levels of Fetuin-A, LECT2 and SEPP1, which are thought to be effective in insulin signaling pathways, were significantly higher in obese patients. Six-months of metformin therapy also found to be effective in decreasing serum LECT2 levels.

Keywords: Childhood-obesity, insulin resistance, metformin, hepatokines, fetuin-A, FGF21, AGF,LECT2, SEPP1

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