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: Obesity in children particularly draws attention, because it may threaten the individual’s future life due to many chronic diseases it may lead to. Most of these diseases including obesity itself altogether are related to inflammation. For this reason, inflammation-related parameters gain importance. Within this context, complete blood cell counts, ratios or indices derived from these counts have recently found some platform to be used as inflammatory markers. So far, mostly adipokines were investigated within the field of obesity. Metabolic inflammation is closely associated with cellular dysfunction. In this study, hematologic inflammatory markers and cytokines produced predominantly by the liver (fibroblast growth factor-21 (FGF-21) and fetuin A) were investigated in pediatric obesity. Two groups were constituted from 76 obese children based on World Health Organization criteria. Group 1 was composed of children, whose age- and sex-adjusted body mass index (BMI) percentiles were between 95 and 99. Group 2 consists of children, who are above 99th percentile. The first and the latter groups were defined as obese (OB) and morbid obese (MO). Anthropometric measurements of the children were performed. Informed consent forms and the approval of the institutional ethics committee were obtained. Blood cell counts and ratios were determined by automated hematology analyzer. The related ratios and indexes were calculated. Statistical evaluation of the data was performed by SPSS program. There was no statistically significant difference in terms of neutrophil-to lymphocyte ratio, monocyte-to-high density lipoprotein cholesterol ratio and platelet-to-lymphocyte ratio between the groups. Mean platelet volume and platelet distribution width values were decreased (p < 0.05), total platelet count, red cell distribution width (RDW) and systemic immune inflammation index values were increased (p < 0.01) in MO group. Both hepatokines were increased in the same group, however increases were not statistically significant. In this group, also a strong correlation was calculated between FGF-21 and RDW when controlled by age, hematocrit, iron and ferritin (r = 0.425; p < 0.01). In conclusion, the association between RDW, a hematologic inflammatory marker, and FGF-21, an inflammation-related hepatokine, found in MO group is an important finding discriminating between OB and MO children. This association is even more powerful when controlled by age and iron-related parameters.
Abstract: Obesity is defined as a severe chronic disease characterized by a low-grade inflammatory state. Therefore, inflammatory markers gained utmost importance during the evaluation of obesity and metabolic syndrome (MetS), a disease characterized by central obesity, elevated blood pressure, increased fasting blood glucose and elevated triglycerides or reduced high density lipoprotein cholesterol (HDL-C) values. Some inflammatory markers based upon complete blood cell count (CBC) are available. In this study, it was questioned which inflammatory marker was the best to evaluate the differences between various obesity groups. 514 pediatric individuals were recruited. 132 children with MetS, 155 morbid obese (MO), 90 obese (OB), 38 overweight (OW) and 99 children with normal BMI (N-BMI) were included into the scope of this study. Obesity groups were constituted using age- and sex-dependent body mass index (BMI) percentiles tabulated by World Health Organization. MetS components were determined to be able to specify children with MetS. CBC were determined using automated hematology analyzer. HDL-C analysis was performed. Using CBC parameters and HDL-C values, ratio markers of inflammation, which cover neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), monocyte-to-HDL-C ratio (MHR) were calculated. Statistical analyses were performed. The statistical significance degree was considered as p < 0.05. There was no statistically significant difference among the groups in terms of platelet count, neutrophil count, lymphocyte count, monocyte count, and NLR. PLR differed significantly between OW and N-BMI as well as MetS. Monocyte-to HDL-C value exhibited statistical significance between MetS and N-BMI, OB, and MO groups. HDL-C value differed between MetS and N-BMI, OW, OB, MO groups. MHR was the ratio, which exhibits the best performance among the other CBC-based inflammatory markers. On the other hand, when MHR was compared to HDL-C only, it was suggested that HDL-C has given much more valuable information. Therefore, this parameter still keeps its value from the diagnostic point of view. Our results suggest that MHR can be an inflammatory marker during the evaluation of pediatric MetS, but the predictive value of this parameter was not superior to HDL-C during the evaluation of obesity.
Abstract: Metabolisms of macrominerals, those of calcium, phosphorus and magnesium, are closely associated with the metabolism of vitamin D. Particularly magnesium, the second most abundant intracellular cation, is related to biochemical and metabolic processes in the body, such as those of carbohydrates, proteins and lipids. The status of each mineral was investigated in obesity to some extent. Their products and ratios may possibly give much more detailed information about the matter. The aim of this study is to investigate possible relations between each macromineral and some obesity-related parameters. This study was performed on 235 children, whose ages were between 06-18 years. Aside from anthropometric measurements, hematological analyses were performed. TANITA body composition monitor using bioelectrical impedance analysis technology was used to establish some obesity-related parameters including basal metabolic rate (BMR), total fat, mineral and muscle masses. World Health Organization body mass index (BMI) percentiles for age and sex were used to constitute the groups. The values above 99th percentile were defined as morbid obesity. Those between 95th and 99th percentiles were included into the obese group. The overweight group comprised of children whose percentiles were between 95 and 85. Children between the 85th and 15th percentiles were defined as normal. Metabolic syndrome (MetS) components (waist circumference, fasting blood glucose, triacylglycerol, high density lipoprotein cholesterol, systolic pressure, diastolic pressure) were determined. High performance liquid chromatography was used to determine Vitamin D status by measuring 25-hydroxy cholecalciferol (25-hydroxy vitamin D3, 25(OH)D). Vitamin D values above 30.0 ng/ml were accepted as sufficient. SPSS statistical package program was used for the evaluation of data. The statistical significance degree was accepted as p < 0.05. The important points were the correlations found between vitamin D and magnesium as well as phosphorus (p < 0.05) that existed in the group with normal BMI values. These correlations were lost in the other groups. The ratio of phosphorus to magnesium was even much more highly correlated with vitamin D (p < 0.001). The negative correlation between magnesium and total fat mass (p < 0.01) was confined to the MetS group showing the inverse relationship between magnesium levels and obesity degree. In this group, calcium*magnesium product exhibited the highest correlation with total fat mass (p < 0.001) among all groups. Only in the MetS group was a negative correlation found between BMR and calcium*magnesium product (p < 0.05). In conclusion, magnesium is located at the center of attraction concerning its relationships with vitamin D, fat mass and MetS. The ratios and products derived from macrominerals including magnesium have pointed out stronger associations other than each element alone. Final considerations have shown that unique correlations of magnesium as well as calcium*magnesium product with total fat mass have drawn attention particularly in the MetS group, possibly due to the derangements in some basic elements of carbohydrate as well as lipid metabolism.
Abstract: Morbid obesity is a health threatening condition particularly in children. Generally, it leads to the development of metabolic syndrome (MetS) characterized by central obesity, elevated fasting blood glucose (FBG), triglyceride (TRG), blood pressure values and suppressed high density lipoprotein cholesterol (HDL-C) levels. However, some ambiguities exist during the diagnosis of MetS in children below 10 years of age. Therefore, clinicians are in the need of some surrogate markers for the laboratory assessment of pediatric MetS. In this study, the aim is to develop an index, which will be more helpful during the evaluation of further risks detected in morbid obese (MO) children. A total of 235 children with normal body mass index (N-BMI), with varying degrees of obesity; overweight (OW), obese (OB), MO as well as MetS participated in this study. The study was approved by the Institutional Ethical Committee. Informed consent forms were obtained from the parents of the children. Obesity states of the children were classified using BMI percentiles adjusted for age and sex. For the purpose, tabulated data prepared by WHO were used. MetS criteria were defined. Systolic and diastolic blood pressure values were measured. Parameters related to glucose and lipid metabolisms were determined. FBG, insulin (INS), HDL-C, TRG concentrations were determined. Diagnostic Obesity Notation Model Assessment Laboratory (DONMALAB) Index [ln TRG/HDL-C*INS] was introduced. Commonly used insulin resistance (IR) indices such as Homeostatic Model Assessment for IR (HOMA-IR) as well as ratios such as TRG/HDL-C, TRG/HDL-C*INS, HDL-C/TRG*INS, TRG/HDL-C*INS/FBG, log, and ln versions of these ratios were calculated. Results were interpreted using statistical package program (SPSS Version 16.0) for Windows. The data were evaluated using appropriate statistical tests. The degree for statistical significance was defined as 0.05. 35 N, 20 OW, 47 OB, 97 MO children and 36 with MetS were investigated. Mean ± SD values of TRG/HDL-C were 1.27 ± 0.69, 1.86 ± 1.08, 2.15 ± 1.22, 2.48 ± 2.35 and 4.61 ± 3.92 for N, OW, OB, MO and MetS children, respectively. Corresponding values for the DONMALAB index were 2.17 ± 1.07, 3.01 ± 0.94, 3.41 ± 0.93, 3.43 ± 1.08 and 4.32 ± 1.00. TRG/HDL-C ratio significantly differed between N and MetS groups. On the other hand, DONMALAB index exhibited statistically significant differences between N and all the other groups except the OW group. This index was capable of discriminating MO children from those with MetS. Statistically significant elevations were detected in MO children with MetS (p < 0.05). Multiple parameters are commonly used during the assessment of MetS. Upon evaluation of the values obtained for N, OW, OB, MO groups and for MO children with MetS, the [ln TRG/HDL-C*INS] value was unique in discriminating children with MetS.
Abstract: Obesity is known to be associated with many clinically important diseases including metabolic syndrome (MetS). Vitamin B12 plays essential roles in fat and protein metabolisms and its cooperation with vitamin B9 is well-known. The aim of this study is to investigate the possible contributions as well as associations of these micronutrients upon obesity and MetS during childhood. A total of 128 children admitted to Namik Kemal University, Medical Faculty, Department of Pediatrics Outpatient Clinics were included into the scope of this study. The mean age±SEM of 92 morbid obese (MO) children and 36 with MetS were 118.3±3.8 months and 129.5±6.4 months, respectively (p > 0.05). The study was approved by Namık Kemal University, Medical Faculty Ethics Committee. Written informed consent forms were obtained from the parents. Demographic features and anthropometric measurements were recorded. WHO BMI-for age percentiles were used. The values above 99 percentile were defined as MO. Components of MetS [waist circumference (WC), fasting blood glucose (FBG), triacylglycerol (TRG), high density lipoprotein cholesterol (HDL-Chol), systolic pressure (SP), diastolic pressure (DP)] were determined. Routine laboratory tests were performed. Serum vitamin B12 concentrations were measured using electrochemiluminescence immunoassay. Vitamin B9 was analyzed by an immunoassay analyzer. Values for vitamin B12 < 148 pmol/L, 148-221 pmol/L, > 221 pmol/L were accepted as low, borderline and normal, respectively. Vitamin B9 levels ≤ 4 mcg/L defined deficiency state. Statistical evaluations were performed by SPSSx Version 16.0. p≤0.05 was accepted as statistical significance level. Statistically higher body mass index (BMI), WC, hip circumference (C) and neck C were calculated in MetS group compared to children with MO. No difference was noted for head C. All MetS components differed between the groups (SP, DP p < 0.001; WC, FBG, TRG p < 0.01; HDL-Chol p < 0.05). Significantly decreased vitamin B9 and vitamin B12 levels were detected (p < 0.05) in children with MetS. In both groups percentage of folate deficiency was 5.5%. No cases were below < 148 pmol/L. However, in MO group 14.3% and in MetS group 22.2% of the cases were of borderline status. In MO group B12 levels were negatively correlated with BMI, WC, hip C and head C, but not with neck C. WC, hip C, head C and neck C were all negatively correlated with HDL-Chol. None of these correlations were observed in the group of children with MetS. Strong positive correlation between FBG and insulin as well as strong negative correlation between TRG and HDL-Chol detected in MO children were lost in MetS group. Deficiency state end-products of both B9 and B12 may interfere with the expected profiles of MetS components. In this study, the alterations in MetS components affected vitamin B12 metabolism and also its associations with anthropometric body measurements. Further increases in vitamin B12 and vitamin B9 deficiency in MetS associated with the increased vitamin B12 as well as vitamin B9 deficiency metabolites may add to MetS parameters.
Abstract: Obesity is a low-grade inflammatory disease and may lead to health problems such as hypertension, dyslipidemia, diabetes. It is also associated with important risk factors for cardiovascular diseases. This requires the detailed evaluation of obesity, particularly in children. The aim of this study is to enlighten the potential associations between lipid ratios and obesity indices and to introduce those with discriminating features among children with obesity and metabolic syndrome (MetS). A total of 408 children (aged between six and eighteen years) participated in the scope of the study. Informed consent forms were taken from the participants and their parents. Ethical Committee approval was obtained. Anthropometric measurements such as weight, height as well as waist, hip, head, neck circumferences and body fat mass were taken. Systolic and diastolic blood pressure values were recorded. Body mass index (BMI), diagnostic obesity notation model assessment index-II (D2 index), waist-to-hip, head-to-neck ratios were calculated. Total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDLChol), low-density lipoprotein cholesterol (LDLChol) analyses were performed in blood samples drawn from 110 children with normal body weight, 164 morbid obese (MO) children and 134 children with MetS. Age- and sex-adjusted BMI percentiles tabulated by World Health Organization were used to classify groups; normal body weight, MO and MetS. 15th-to-85th percentiles were used to define normal body weight children. Children, whose values were above the 99th percentile, were described as MO. MetS criteria were defined. Data were evaluated statistically by SPSS Version 20. The degree of statistical significance was accepted as p≤0.05. Mean±standard deviation values of BMI for normal body weight children, MO children and those with MetS were 15.7±1.1, 27.1±3.8 and 29.1±5.3 kg/m2, respectively. Corresponding values for the D2 index were calculated as 3.4±0.9, 14.3±4.9 and 16.4±6.7. Both BMI and D2 index were capable of discriminating the groups from one another (p≤0.01). As far as other obesity indices were considered, waist-to hip and head-to-neck ratios did not exhibit any statistically significant difference between MO and MetS groups (p≥0.05). Diagnostic obesity notation model assessment index-II was correlated with the triglycerides-to-HDL-C ratio in normal body weight and MO (r=0.413, p≤0.01 and r=0.261, (p≤0.05, respectively). Total cholesterol-to-HDL-C and LDL-C-to-HDL-C showed statistically significant differences between normal body weight and MO as well as MO and MetS (p≤0.05). The only group in which these two ratios were significantly correlated with waist-to-hip ratio was MetS group (r=0.332 and r=0.334, p≤0.01, respectively). Lack of correlation between the D2 index and the triglycerides-to-HDL-C ratio was another important finding in MetS group. In this study, parameters and ratios, whose associations were defined previously with increased cardiovascular risk or cardiac death have been evaluated along with obesity indices in children with morbid obesity and MetS. Their profiles during childhood have been investigated. Aside from the nature of the correlation between the D2 index and triglycerides-to-HDL-C ratio, total cholesterol-to-HDL-C as well as LDL-C-to- HDL-C ratios along with their correlations with waist-to-hip ratio showed that the combination of obesity-related parameters predicts better than one parameter and appears to be helpful for discriminating MO children from MetS group.
Abstract: Obesity, a disease associated with a low-grade inflammation, is a risk factor for the development of metabolic syndrome (MetS). So far, MetS risk factors such as parameters related to glucose and lipid metabolisms as well as blood pressure were considered for the evaluation of this disease. There are still some ambiguities related to the characteristic features of MetS observed particularly in pediatric population. Hormonal imbalance is also important, and quite a lot information exists about the behaviour of some hormones in adults. However, the hormonal profiles in pediatric metabolism have not been cleared yet. The aim of this study is to investigate the profiles of cortisol, insulin, and thyroid hormones in children with MetS. The study population was composed of morbid obese (MO) children without (Group 1) and with (Group 2) MetS components. WHO BMI-for age and sex percentiles were used for the classification of obesity. The values above 99 percentile were defined as morbid obesity. Components of MetS (central obesity, glucose intolerance, high blood pressure, high triacylglycerol levels, low levels of high density lipoprotein cholesterol) were determined. Anthropometric measurements were performed. Ratios as well as obesity indices were calculated. Insulin, cortisol, thyroid stimulating hormone (TSH), free T3 and free T4 analyses were performed by electrochemiluminescence immunoassay. Data were evaluated by statistical package for social sciences program. p
Abstract: Childhood obesity, which may lead to increased risk for heart diseases in children as well as adults, is one of the most important health problems throughout the world. Prevalences of morbid obesity and metabolic syndrome (MetS) are being increased during childhood age group. MetS is a cluster of metabolic and vascular abnormalities including hypercoagulability and an increased risk of cardiovascular diseases (CVDs). There are also some relations between some components of MetS and leukocytes. The aim of this study is to investigate complete blood cell count parameters that differ between morbidly obese boys and girls with MetS diagnosis. A total of 117 morbid obese children with MetS consulted to Department of Pediatrics in Faculty of Medicine Hospital at Namik Kemal University were included into the scope of the study. The study population was classified based upon their genders (60 girls and 57 boys). Their heights and weights were measured and body mass index (BMI) values were calculated. WHO BMI-for age and sex percentiles were used. The values above 99 percentile were defined as morbid obesity. Anthropometric measurements were performed. Waist-to-hip and head-to-neck ratios as well as homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. Components of MetS (central obesity, glucose intolerance, high blood pressure, high triacylglycerol levels, low levels of high density lipoprotein cholesterol) were determined. Hematological variables were measured. Statistical analyses were performed using SPSS. The degree for statistical significance was p ≤ 0.05. There was no statistically significant difference between the ages (11.2±2.6 years vs 11.2±3.0 years) and BMIs (28.6±5.2 kg/m2 vs 29.3±5.2 kg/m2) of boys and girls (p ≥ 0.05), respectively. Significantly increased waist-to-hip ratios were obtained for boys (0.94±0.08 vs 0.91±0.06; p=0.023). Significantly elevated values of hemoglobin (13.55±0.98 vs 13.06±0.82; p=0.004), mean corpuscular hemoglobin concentration (33.79±0.91 vs 33.21±1.14; p=0.003), eosinophils (0.300±0.253 vs 0.196±0.197; p=0.014), and platelet (347.1±81.7 vs 319.0±65.9; p=0.042) were detected for boys. There was no statistically significant difference between the groups in terms of neutrophil/lymphocyte ratios as well as HOMA-IR values (p ≥ 0.05). Statistically significant gender-based differences were found for hemoglobin as well as mean corpuscular hemoglobin concentration and hence, separate reference intervals for two genders should be considered for these parameters. Eosinophils may contribute to the development of thrombus in acute coronary syndrome. Eosinophils are also known to make an important contribution to mechanisms related to thrombosis pathogenesis in acute myocardial infarction. Increased platelet activity is observed in patients with MetS and these individuals are more susceptible to CVDs. In our study, elevated platelets described as dominant contributors to hypercoagulability and elevated eosinophil counts suggested to be related to the development of CVDs observed in boys may be the early indicators of the future cardiometabolic complications in this gender.