Abstract: Childhood obesity is an important clinical problem, because it may lead to chronic diseases during the adulthood period of the individual. Obesity is a metabolic disease associated with low-grade inflammation. The liver occurs at the center of metabolic pathways. Adropin, fibroblast growth factor-21 (FGF-21) and fetuin A are hepatokines. Due to the immense participation of the liver in glucose metabolism, these liver derived factors may be associated with insulin resistance (IR), which is a phenomenon discussed within the scope of obesity problems. The aim of this study is to determine the concentrations of adropin, FGF-21 and fetuin A in childhood obesity, to point out possible differences between the obesity groups and to investigate possible associations among these three hepatokines in obese and morbid obese children. A total of 132 children were included in the study. Two obese groups were constituted. The groups were matched in terms of mean±SD values of ages. Body mass index values of the obese and morbid obese groups were 25.0±3.5 kg/m2 and 29.8±5.7 kg/m2, respectively. Anthropometric measurements including waist circumference, hip circumference, head circumference, and neck circumference were recorded. Informed consent forms were taken from the parents of the participants and the Ethics Committee of the institution approved the study protocol. Blood samples were obtained after an overnight fasting. Routine biochemical tests including glucose- and lipid-related parameters were performed. Concentrations of the hepatokines (adropin, FGF-21, fetuin A) were determined by enzyme-linked immunosorbent assay. Insulin resistance indices such as homeostasis model assessment for IR (HOMA-IR), alanine transaminase-to aspartate transaminase ratio (ALT/AST), diagnostic obesity notation model assessment laboratory index, diagnostic obesity notation model assessment metabolic syndrome index as well as obesity indices such as diagnostic obesity notation model assessment-II index, and fat mass index were calculated using the previously derived formulas. Statistical evaluation of the study data as well as findings of the study were performed by SPSS for Windows. Statistical difference was accepted significant when p < 0.05. Statistically significant differences were found for insulin, triglyceride, high density lipoprotein cholesterol levels of the groups. A significant increase was observed for FGF-21 concentrations in the morbid obese group. Higher adropin and fetuin A concentrations were observed in the same group in comparison with the values detected in the obese group (p > 0.05). There was no statistically significant difference between the ALT/AST values of the groups. In all of the remaining IR and obesity indices, significantly increased values were calculated for morbid obese children. Significant correlations were detected between HOMA-IR and each of the hepatokines. The highest one was the association with fetuin A (r = 0.373, p = 0.001). In conclusion, increased levels observed in adropin, FGF-21 and fetuin A have shown that these hepatokines possess increasing potential going from the obese to morbid obese state. Out of the correlations found with IR index, the most affected hepatokine was fetuin A, the parameter possibly used as the indicator of the advanced obesity stage.
Abstract: A well-defined insulin resistance (IR) is one of the requirements for the good understanding and evaluation of metabolic syndrome (MetS). However, underlying causes for the development of IR are not clear. Endothelial dysfunction also participates in the pathogenesis of this disease. IR indices are being determined in various obesity groups and also in diagnosing MetS. Components of MetS have been well established and used in adult studies. However, there are some ambiguities particularly in the field of pediatrics. The aims of this study were to compare the performance of fasting blood glucose (FBG), one of MetS components, with some other IR indices and check whether FBG may be replaced by some other parameter or ratio for a better evaluation of pediatric MetS. Five-hundred and forty-nine children were involved in the study. Five groups were constituted. Groups 109, 40, 100, 166, 110, 24 children were included in normal-body mass index (N-BMI), overweight (OW), obese (OB), morbid obese (MO), MetS with two components (MetS2) and MetS with three components (MetS3) groups, respectively. Age and sex-adjusted BMI percentiles tabulated by World Health Organization were used for the classification of obesity groups. MetS components were determined. Aside from one of the MetS components-FBG, eight measures of IR [homeostatic model assessment of IR (HOMA-IR), homeostatic model assessment of beta cell function (HOMA-%β), alanine transaminase-to-aspartate transaminase ratio (ALT/AST), alanine transaminase (ALT), insulin (INS), insulin-to-FBG ratio (INS/FBG), the product of fasting triglyceride and glucose (TyG) index, McAuley index] were evaluated. Statistical analyses were performed. A p value less than 0.05 was accepted as the statistically significance degree. Mean values for BMI of the groups were 15.7 kg/m2, 21.0 kg/m2, 24.7 kg/m2, 27.1 kg/m2, 28.7 kg/m2, 30.4 kg/m2 for N-BMI, OW, OB, MO, MetS2, MetS3, respectively. Differences between the groups were significant (p < 0.001). The only exception was MetS2-MetS3 couple, in spite of an increase detected in MetS3 group. Waist-to-hip circumference ratios significantly differed only for N-BMI vs, OB, MO, MetS2; OW vs MO; OB vs MO, MetS2 couples. ALT and ALT/AST did not differ significantly among MO-MetS2-MetS3. HOMA-%β differed only between MO and MetS2. INS/FBG, McAuley index and TyG were not significant between MetS2 and MetS3. HOMA-IR and FBG were not significant between MO and MetS2. INS was the only parameter, which showed statistically significant differences between MO-MetS2, MO-MetS3, and MetS2-MetS3. In conclusion, these findings have suggested that FBG presently considered as one of the five MetS components, may be replaced by INS during the evaluation of pediatric morbid obesity and MetS.