The Evaluation of New Generation Cardiovascular Risk Markers in Childhood Obesity

Obesity, as excessive fat accumulation in the body, is a global health problem. The prevalence of obesity and its complications increase due to easy access to high-energy food and decreased physical activity. Cardiovascular diseases (CVDs) constitute a significant part of obesity-related morbidity and mortality. Since the effects of obesity on cardiovascular system may start during childhood without clinical findings, elucidating the mechanisms of cardiovascular changes associated with childhood obesity became more important. In this study, we aimed to investigate some biochemical parameters which may be involved in obesity-related pathologic processes of CVDs. One hundred and seventy-seven children were included in the study, and they were divided into four groups based upon WHO criteria and presence of the metabolic syndrome (MetS): children with normal-BMI, obesity, morbid obesity, and MetS. High-sensitive cardiac troponin T (hs-cTnT), cardiac myosin binding protein C (cMyBP-C), trimethylamine N-oxide (TMAO), soluble tumor necrosis factor-like weak inducer (sTWEAK), chromogranin A (CgA), multimerin-2 levels, and other biochemical parameters were measured in serum samples. Anthropometric measurements and clinical findings of the children were recorded. Statistical analyses were performed. Children with normal-BMI had significantly higher CgA levels than children with obesity, morbid obesity, and MetS (p < 0.05). Cardiac MyBP-C levels of children with MetS were significantly higher than of children with normal-BMI and OB children (p < 0.05). There was no significant difference in hs-cTnT, sTWEAK, TMAO and multimerin-2 between the groups (p>0.05). These results suggested that cMyBP-C and CgA molecules may be involved in the pathogenesis of obesity-related CVDs.

Associations among Fetuin A, Cortisol and Thyroid Hormones in Children with Morbid Obesity and Metabolic Syndrome

Obesity is a disease with an ever-increasing prevalence throughout the world. The metabolic network associated with obesity is very complicated. In metabolic syndrome (MetS), it becomes even more difficult to understand. Within this context, hormones, cytokines, and many others participate in this complex matrix. The collaboration among all of these parameters is a matter of great wonder. Cortisol, as a stress hormone, is closely associated with obesity. Thyroid hormones are involved in the regulation of energy as well as glucose metabolism with all of its associates. Fetuin A has been known for years; however, the involvement of this parameter in obesity discussions is rather new. Recently, it has been defined as one of the new generation markers of obesity. In this study, the aim was to introduce complex interactions among all to be able to make clear comparisons, at least for a part of this complicated matter. Morbid obese (MO) children participated in the study. Two groups with 46 MO children and 43 with MetS were constituted. All children included in the study were above 99th age- and sex-adjusted body mass index (BMI) percentiles according to World Health Organization criteria. Forty-three morbid obese children in the second group also had MetS components. Informed consent forms were filled by the parents of the participants. The institutional ethics committee has given approval for the study protocol. Data as well as the findings of the study were evaluated from a statistical point of view. Two groups were matched for their age and gender compositions. Significantly higher body mass index (BMI), waist circumference, thyrotropin, and insulin values were observed in the MetS group. Triiodothyronine concentrations did not differ between the groups. Elevated levels for thyroxin, cortisol, and fetuin-A were detected in the MetS group compared to the first group (p > 0.05). In MO MetS- group, cortisol was correlated with thyroxin and fetuin-A (p < 0.05). In the MO MetS+ group, none of these correlations were present. Instead, a correlation between cortisol and thyrotropin was found (p < 0.05). In conclusion, findings have shown that cortisol was the key player in severely obese children. The association of this hormone with the participants of thyroid hormone metabolism was quite important. The lack of association with fetuin A in the morbid obese MetS+ group has suggested the possible interference of MetS components in the behavior of this new generation obesity marker. The most remarkable finding of the study was the unique correlation between cortisol and thyrotropin in the morbid obese MetS+ group, suggesting that thyrotropin may serve as a target along with cortisol in the morbid obese MetS+ group. This association may deserve specific attention during the development of remedies against MetS in the pediatric population.

Relationship between Hepatokines and Insulin Resistance in Childhood Obesity

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.

The Association of Vitamin B₁₂ with Body Weight-and Fat-Based Indices in Childhood Obesity

Vitamin deficiencies are common in obese individuals. Particularly, the status of vitamin B12 and its association with vitamin B9 (folate) and vitamin D is under investigation in recent time. Vitamin B12 is closely related to many vital processes in the body. In clinical studies, its involvement in fat metabolism draws attention from the obesity point of view. Obesity, in its advanced stages and in combination with metabolic syndrome (MetS) findings, may be a life-threatening health problem. Pediatric obesity is particularly important, because it may be a predictor of the severe chronic diseases during adulthood period of the child. Due to its role in fat metabolism, vitamin B12 deficiency may disrupt metabolic pathways of the lipid and energy metabolisms in the body. The association of low B12 levels with obesity degree may be an interesting topic to be investigated. Obesity indices may be helpful at this point. Weight- and fat-based indices are available. Of them, body mass index (BMI) is in the first group. Fat mass index (FMI), fat-free mass index (FFMI) and diagnostic obesity notation model assessment-II (D2I) index lie in the latter group. The aim of this study is to clarify possible associations between vitamin B12 status and obesity indices in pediatric population. The study comprises a total of 122 children. 32 children were included in the normal-body mass index (N-BMI) group. 46 and 44 children constitute groups with morbid obese children without MetS and with MetS, respectively. Informed consent forms and the approval of the institutional ethics committee were obtained. Tables prepared for obesity classification by World Health Organization were used. MetS criteria were defined. Anthropometric and blood pressure measurements were taken. BMI, FMI, FFMI, D2I were calculated. Routine laboratory tests were performed. Vitamin B9, B12, D concentrations were determined. Statistical evaluation of the study data was performed. Vitamin B9 and vitamin D levels were reduced in MetS group compared to children with N-BMI (p > 0.05). Significantly lower values were observed in vitamin B12 concentrations of MetS group (p < 0.01). Upon evaluation of blood pressure as well as triglyceride levels, there exist significant increases in morbid obese children. Significantly decreased concentrations of high-density lipoprotein cholesterol were observed. All of the obesity indices and insulin resistance index exhibit increasing tendency with the severity of obesity. Inverse correlations were calculated between vitamin D and insulin resistance index as well as vitamin B12 and D2I in morbid obese groups. In conclusion, a fat-based index, D2I, was the most prominent body index, which shows strong correlation with vitamin B12 concentrations in the late stage of obesity in children. A negative correlation between these two parameters was a confirmative finding related to the association between vitamin B12 and obesity degree. 

Body Mass Index, Components of Metabolic Syndrome and Hyperuricemia among Women in Postmenopausal Period

In recent years, the problem of hyperuricemia is getting a particular importance due to its increased incidence in the world population. The aim of this study was to determine uriс acid level in blood serum, incidence of hyperuricemia among women in postmenopausal period and their association with body mass index and some components of metabolic syndrome (triglyceride, cholesterol, systolic and diastolic pressure). We examined 412 women in postmenopausal period. They were divided in to the following groups: I group (BMI = 18,5-24,9), II group (BMI = 25,0-29,9), III group (BMI = 30,0-34,9), IV group (BMI > 35). We determined uric acid level among women during postmenopausal period depending on their body mass index. The higher level of uric acid was found in patients with the maximal body mass index (BMI > 35). In the I group it was 277,52 ± 8,40; in the II group – 286,81 ± 7,79; in the III group – 291,81 ± 7,56; in the IV group – 327,17 ± 12,17. Incidence of hyperuricemia among women in the I group was 10,2%, in the II group – 15,9%; in the III group – 21,2%, in the IV group – 34,2%. We found an interdependence between an uric acid level and BMI in the examined women (r = 0,21, p < 0,05). We determined that the highest level of triglyceride (F = 18,62, p < 0,05), cholesterol (F = 3,64, p < 0,05), atherogenic coefficient (F = 22,64, p < 0,05), systolic (F = 10,5, p < 0,05) and diastolic pressure (F = 4,30, p < 0,05) was among women with hyperuricemia. It was an interdependence between an uric acid level and triglyceride (r = 0,26, p < 0,05), atherogenic coefficient (r = 0,24, p < 0,05) among women in postmenopausal period.

The Evaluation of Complete Blood Cell Count-Based Inflammatory Markers in Pediatric Obesity and Metabolic Syndrome

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.

The Potential Involvement of Platelet Indices in Insulin Resistance in Morbid Obese Children

Association between insulin resistance (IR) and hematological parameters has long been a matter of interest. Within this context, body mass index (BMI), red blood cells, white blood cells and platelets were involved in this discussion. Parameters related to platelets associated with IR may be useful indicators for the identification of IR. Platelet indices such as mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT) are being questioned for their possible association with IR. The aim of this study was to investigate the association between platelet (PLT) count as well as PLT indices and the surrogate indices used to determine IR in morbid obese (MO) children. A total of 167 children participated in the study. Three groups were constituted. The number of cases was 34, 97 and 36 children in the normal BMI, MO and metabolic syndrome (MetS) groups, respectively. Sex- and age-dependent BMI-based percentile tables prepared by World Health Organization were used for the definition of morbid obesity. MetS criteria were determined. BMI values, homeostatic model assessment for IR (HOMA-IR), alanine transaminase-to-aspartate transaminase ratio (ALT/AST) and diagnostic obesity notation model assessment laboratory (DONMA-lab) index values were computed. PLT count and indices were analyzed using automated hematology analyzer. Data were collected for statistical analysis using SPSS for Windows. Arithmetic mean and standard deviation were calculated. Mean values of PLT-related parameters in both control and study groups were compared by one-way ANOVA followed by Tukey post hoc tests to determine whether a significant difference exists among the groups. The correlation analyses between PLT as well as IR indices were performed. Statistically significant difference was accepted as p-value < 0.05. Increased values were detected for PLT (p < 0.01) and PCT (p > 0.05) in MO group compared to those observed in children with N-BMI. Significant increases for PLT (p < 0.01) and PCT (p < 0.05) were observed in MetS group in comparison with the values obtained in children with N-BMI (p < 0.01). Significantly lower MPV and PDW values were obtained in MO group compared to the control group (p < 0.01). HOMA-IR (p < 0.05), DONMA-lab index (p < 0.001) and ALT/AST (p < 0.001) values in MO and MetS groups were significantly increased compared to the N-BMI group. On the other hand, DONMA-lab index values also differed between MO and MetS groups (p < 0.001). In the MO group, PLT was negatively correlated with MPV and PDW values. These correlations were not observed in the N-BMI group. None of the IR indices exhibited a correlation with PLT and PLT indices in the N-BMI group. HOMA-IR showed significant correlations both with PLT and PCT in the MO group. All of the three IR indices were well-correlated with each other in all groups. These findings point out the missing link between IR and PLT activation. In conclusion, PLT and PCT may be related to IR in addition to their identities as hemostasis markers during morbid obesity. Our findings have suggested that DONMA-lab index appears as the best surrogate marker for IR due to its discriminative feature between morbid obesity and MetS.

Associations between Surrogate Insulin Resistance Indices and the Risk of Metabolic Syndrome in Children

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.

Association of Brain Derived Neurotrophic Factor with Iron as well as Vitamin D, Folate and Cobalamin in Pediatric Metabolic Syndrome

The impact of metabolic syndrome (MetS) on cognition and functions of the brain is being investigated. Iron deficiency and deficiencies of B9 (folate) as well as B12 (cobalamin) vitamins are best-known nutritional anemias. They are associated with cognitive disorders and learning difficulties. The antidepressant effects of vitamin D are known and the deficiency state affects mental functions negatively. The aim of this study is to investigate possible correlations of MetS with serum brain-derived neurotrophic factor (BDNF), iron, folate, cobalamin and vitamin D in pediatric patients. 30 children, whose age- and sex-dependent body mass index (BMI) percentiles vary between 85 and 15, 60 morbid obese children with above 99th percentiles constituted the study population. Anthropometric measurements were taken. BMI values were calculated. Age- and sex-dependent BMI percentile values were obtained using the appropriate tables prepared by the World Health Organization (WHO). Obesity classification was performed according to WHO criteria. Those with MetS were evaluated according to MetS criteria. Serum BDNF was determined by enzyme-linked immunosorbent assay. Serum folate was analyzed by an immunoassay analyzer. Serum cobalamin concentrations were measured using electrochemiluminescence immunoassay. Vitamin D status was determined by the measurement of 25-hydroxycholecalciferol [25-hydroxy vitamin D3, 25(OH)D] using high performance liquid chromatography. Statistical evaluations were performed using SPSS for Windows, version 16. The p values less than 0.05 were accepted as statistically significant. Although statistically insignificant, lower folate and cobalamin values were found in MO children compared to those observed for children with normal BMI. For iron and BDNF values, no alterations were detected among the groups. Significantly decreased vitamin D concentrations were noted in MO children with MetS in comparison with those in children with normal BMI (p ≤ 0.05). The positive correlation observed between iron and BDNF in normal-BMI group was not found in two MO groups. In THE MetS group, the partial correlation among iron, BDNF, folate, cobalamin, vitamin D controlling for waist circumference and BMI was r = -0.501; p ≤ 0.05. None was calculated in MO and normal BMI groups. In conclusion, vitamin D should also be considered during the assessment of pediatric MetS. Waist circumference and BMI should collectively be evaluated during the evaluation of MetS in children. Within this context, BDNF appears to be a key biochemical parameter during the examination of obesity degree in terms of mental functions, cognition and learning capacity. The association observed between iron and BDNF in children with normal BMI was not detected in MO groups possibly due to development of inflammation and other obesity-related pathologies. It was suggested that this finding may contribute to mental function impairments commonly observed among obese children.

Importance of Macromineral Ratios and Products in Association with Vitamin D in Pediatric Obesity Including Metabolic Syndrome

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.

Links between Inflammation and Insulin Resistance in Children with Morbid Obesity and Metabolic Syndrome

Obesity is a clinical state associated with low-grade inflammation. It is also a major risk factor for insulin resistance (IR). In its advanced stages, metabolic syndrome (MetS), a much more complicated disease which may lead to life-threatening problems, may develop. Obesity-mediated IR seems to correlate with the inflammation. Human studies performed particularly on pediatric population are scarce. The aim of this study is to detect possible associations between inflammation and IR in terms of some related ratios. 549 children were grouped according to their age- and sex-based body mass index (BMI) percentile tables of WHO. MetS components were determined. Informed consent and approval from the Ethics Committee for Clinical Investigations were obtained. The principles of the Declaration of Helsinki were followed. The exclusion criteria were infection, inflammation, chronic diseases and those under drug treatment. Anthropometric measurements were obtained. Complete blood cell, fasting blood glucose, insulin, and C-reactive protein (CRP) analyses were performed. Homeostasis model assessment of insulin resistance (HOMA-IR), systemic immune inflammation (SII) index, tense index, alanine aminotransferase to aspartate aminotransferase ratio (ALT/AST), neutrophils to lymphocyte (NLR), platelet to lymphocyte, and lymphocyte to monocyte ratios were calculated. Data were evaluated by statistical analyses. The degree for statistical significance was 0.05. Statistically significant differences were found among the BMI values of the groups (p < 0.001). Strong correlations were detected between the BMI and waist circumference (WC) values in all groups. Tense index values were also correlated with both BMI and WC values in all groups except overweight (OW) children. SII index values of children with normal BMI were significantly different from the values obtained in OW, obese, morbid obese and MetS groups. Among all the other lymphocyte ratios, NLR exhibited a similar profile. Both HOMA-IR and ALT/AST values displayed an increasing profile from N towards MetS3 group. BMI and WC values were correlated with HOMA-IR and ALT/AST. Both in morbid obese and MetS groups, significant correlations between CRP versus SII index as well as HOMA-IR versus ALT/AST were found. ALT/AST and HOMA-IR values were correlated with NLR in morbid obese group and with SII index in MetS group, (p < 0.05), respectively. In conclusion, these findings showed that some parameters may exhibit informative differences between the early and late stages of obesity. Important associations among HOMA-IR, ALT/AST, NLR and SII index have come to light in the morbid obese and MetS groups. This study introduced the SII index and NLR as important inflammatory markers for the discrimination of normal and obese children. Interesting links were observed between inflammation and IR in morbid obese children and those with MetS, both being late stages of obesity.

Understanding the Nature of Blood Pressure as Metabolic Syndrome Component in Children

Pediatric overweight and obesity need attention because they may cause morbid obesity, which may develop metabolic syndrome (MetS). Criteria used for the definition of adult MetS cannot be applied for pediatric MetS. Dynamic physiological changes that occur during childhood and adolescence require the evaluation of each parameter based upon age intervals. The aim of this study is to investigate the distribution of blood pressure (BP) values within diverse pediatric age intervals and the possible use and clinical utility of a recently introduced Diagnostic Obesity Notation Model Assessment Tension (DONMA tense) Index derived from systolic BP (SBP) and diastolic BP (DBP) [SBP+DBP/200]. Such a formula may enable a more integrative picture for the assessment of pediatric obesity and MetS due to the use of both SBP and DBP. 554 children, whose ages were between 6-16 years participated in the study; the study population was divided into two groups based upon their ages. The first group comprises 280 cases aged 6-10 years (72-120 months), while those aged 10-16 years (121-192 months) constituted the second group. The values of SBP, DBP and the formula (SBP+DBP/200) covering both were evaluated. Each group was divided into seven subgroups with varying degrees of obesity and MetS criteria. Two clinical definitions of MetS have been described. These groups were MetS3 (children with three major components), and MetS2 (children with two major components). The other groups were morbid obese (MO), obese (OB), overweight (OW), normal (N) and underweight (UW). The children were included into the groups according to the age- and sex-based body mass index (BMI) percentile values tabulated by WHO. Data were evaluated by SPSS version 16 with p < 0.05 as the statistical significance degree. Tension index was evaluated in the groups above and below 10 years of age. This index differed significantly between N and MetS as well as OW and MetS groups (p = 0.001) above 120 months. However, below 120 months, significant differences existed between MetS3 and MetS2 (p = 0.003) as well as MetS3 and MO (p = 0.001). In comparison with the SBP and DBP values, tension index values have enabled more clear-cut separation between the groups. It has been detected that the tension index was capable of discriminating MetS3 from MetS2 in the group, which was composed of children aged 6-10 years. This was not possible in the older group of children. This index was more informative for the first group. This study also confirmed that 130 mm Hg and 85 mm Hg cut-off points for SBP and DBP, respectively, are too high for serving as MetS criteria in children because the mean value for tension index was calculated as 1.00 among MetS children. This finding has shown that much lower cut-off points must be set for SBP and DBP for the diagnosis of pediatric MetS, especially for children under-10 years of age. This index may be recommended to discriminate MO, MetS2 and MetS3 among the 6-10 years of age group, whose MetS diagnosis is problematic.

Coalescence of Insulin and Triglyceride/High Density Lipoprotein Cholesterol Ratio for the Derivation of a Laboratory Index to Predict Metabolic Syndrome in Morbid Obese Children

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.

The Role of Chemerin and Myostatin after Physical Activity

Obesity and overweight is one of the most common metabolic disorders in industrialized countries and in developing countries. One consequence of pathological obesity is cardiovascular disease and metabolic syndrome. Chemerin is an adipocyne that plays a role in the regulation of the adipocyte function and the metabolism of glucose in the liver and musculoskeletal system. Most likely, chemerin is involved in obesity-related disorders such as type 2 diabetes and cardiovascular disease. Aerobic exercises reduce the level of chemerin and cause macrophage penetration into fat cells and inflammatory factors. Several efforts have been made to clarify the cellular and molecular mechanisms of hypertrophy and muscular atrophy. Myostatin, a new member of the TGF-β family, is a transforming growth factor β that its expression negatively regulates the growth of the skeletal muscle; and the increase of this hormone has been observed in conditions of muscular atrophy. While in response to muscle overload, its levels decrease after the atrophy period, TGF-β is the most important cytokine in the development of skeletal muscle. Myostatin plays an important role in muscle control, and animal and human studies show a negative role of myostatin in the growth of skeletal muscle. Separation of myostatin from Golgi begins on the ninth day of the onset period and continues until birth at all times of muscle growth. Higher levels of myostatin are found in obese people. Resistance training for 10 weeks could reduce levels of plasma myostatin.

Cobalamin, Folate and Metabolic Syndrome Parameters in Pediatric Morbid Obesity and Metabolic Syndrome

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.

The Valuable Triad of Adipokine Indices to Differentiate Pediatric Obesity from Metabolic Syndrome: Chemerin, Progranulin, Vaspin

Obesity is associated with cardiovascular disease risk factors and metabolic syndrome (MetS). In this study, associations between adipokines and adipokine as well as obesity indices were evaluated. Plasma adipokine levels may exhibit variations according to body adipose tissue mass. Besides, upon consideration of obesity as an inflammatory disease, adipokines may play some roles in this process. The ratios of proinflammatory adipokines to adiponectin may act as highly sensitive indicators of body adipokine status. The aim of the study is to present some adipokine indices, which are thought to be helpful for the evaluation of childhood obesity and also to determine the best discriminators in the diagnosis of MetS. 80 prepubertal children (aged between 6-9.5 years) included in the study were divided into three groups; 30 children with normal weight (NW), 25 morbid obese (MO) children and 25 MO children with MetS. Physical examinations were performed. Written informed consent forms were obtained from the parents. The study protocol was approved by Ethics Committee of Namik Kemal University Medical Faculty. Anthropometric measurements, such as weight, height, waist circumference (C), hip C, head C, neck C were recorded. Values for body mass index (BMI), diagnostic obesity notation model assessment Index-II (D2 index) as well as waist-to-hip, head-to-neck ratios were calculated. Adiponectin, resistin, leptin, chemerin, vaspin, progranulin assays were performed by ELISA. Adipokine-to-adiponectin ratios were obtained. SPSS Version 20 was used for the evaluation of data. p values ≤ 0.05 were accepted as statistically significant. Values of BMI and D2 index, waist-to-hip, head-to-neck ratios did not differ between MO and MetS groups (p ≥ 0.05). Except progranulin (p ≤ 0.01), similar patterns were observed for plasma levels of each adipokine. There was not any difference in vaspin as well as resistin levels between NW and MO groups. Significantly increased leptin-to-adiponectin, chemerin-to-adiponectin and vaspin-to-adiponectin values were noted in MO in comparison with those of NW. The most valuable adipokine index was progranulin-to-adiponectin (p ≤ 0.01). This index was strongly correlated with vaspin-to-adiponectin ratio in all groups (p ≤ 0.05). There was no correlation between vaspin-to-adiponectin and chemerin-to--adiponectin in NW group. However, a correlation existed in MO group (r = 0.486; p ≤ 0.05). Much stronger correlation (r = 0.609; p ≤ 0.01) was observed in MetS group between these two adipokine indices. No correlations were detected between vaspin and progranulin as well as vaspin and chemerin levels. Correlation analyses showed a unique profile confined to MetS children. Adiponectin was found to be correlated with waist-to-hip (r = -0.435; p ≤ 0.05) as well as head-to-neck (r = 0.541; p ≤ 0.05) ratios only in MetS children. In this study, it has been investigated if adipokine indices have priority over adipokine levels. In conclusion, vaspin-to-adiponectin, progranulin-to-adiponectin, chemerin-to-adiponectin along with waist-to-hip and head-to-neck ratios were the optimal combinations. Adiponectin, waist-to-hip, head-to-neck, vaspin-to-adiponectin, chemerin-to-adiponectin ratios had appropriate discriminatory capability for MetS children.

An Indispensable Parameter in Lipid Ratios to Discriminate between Morbid Obesity and Metabolic Syndrome in Children: High Density Lipoprotein Cholesterol

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.

The Cooperation among Insulin, Cortisol and Thyroid Hormones in Morbid Obese Children and Metabolic Syndrome

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

Associations between Metabolic Syndrome and Bone Mineral Density and Trabecular Bone Score in Postmenopausal Women with Non-Vertebral Fractures

Medical, social, and economic relevance of osteoporosis is caused by reducing quality of life, increasing disability and mortality of the patients as a result of fractures due to the low-energy trauma. This study is aimed to examine the associations of metabolic syndrome components, bone mineral density (BMD) and trabecular bone score (TBS) in menopausal women with non-vertebral fractures. 1161 menopausal women aged 50-79 year-old were examined and divided into three groups: A included 419 women with increased body weight (BMI - 25.0-29.9 kg/m2), B – 442 females with obesity (BMI >29.9 kg/m2)i and C – 300 women with metabolic syndrome (diagnosis according to IDF criteria, 2005). BMD of lumbar spine (L1-L4), femoral neck, total body and forearm was investigated with usage of dual-energy X-ray absorptiometry. The bone quality indexes were measured according to Med-Imaps installation. All analyses were performed using Statistical Package 6.0. BMD of lumbar spine (L1-L4), femoral neck, total body, and ultradistal radius was significant higher in women with obesity and metabolic syndrome compared to the pre-obese ones (p

The Effect of Physical Activity and Responses of Leptin

In modern life, daily physical activity is relatively reduced, which is why the incidence of some diseases associated with overweight and obesity, such as hypertension, diabetes and other chronic illnesses, even in young people are observed. Obesity and overweight is one of the most common metabolic disorders in industrialized countries and in developing countries. One consequence of pathological obesity is cardiovascular disease and metabolic syndrome. In the past, it was believed that adipose tissue was ineffective and served only for storing triglycerides. In this review article, it was tried to refer to the esteemed scientific sources about physical activity and responses of leptin.