Search results for: Morbid obesity.

Authors: Mustafa M. Donma, Orkide Donma

Abstract:

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.

Keywords: children, cortisol, fetuin A, morbid obesity, thyrotropin

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Authors: Orkide Donma, Mustafa M. Donma

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Obesity may lead to growing serious health problems throughout the world. Vitamin D appears to play a role in cardiovascular and metabolic health. Vitamin D deficiency may add to derangements in human metabolic systems, particularly those of children. Childhood obesity is associated with an increased risk of chronic and sophisticated diseases. The aim of this study is to investigate associations as well as possible differences related to parameters affected by obesity and their relations with vitamin D status in obese (OB) and morbid obese (MO) children. This study included a total of 78 children. Of them, 41 and 37 were OB and MO, respectively. WHO BMI-for age percentiles were used for the classification of obesity. The values above 99 percentile were defined as MO. Those between 95 and 99 percentiles were included into OB group. Anthropometric measurements were recorded. Basal metabolic rates (BMRs) were measured. Vitamin D status is determined by the measurement of 25-hydroxy cholecalciferol [25- hydroxyvitamin D3, 25(OH)D] using high-performance liquid chromatography. Vitamin D status was evaluated as deficient, insufficient and sufficient. Values < 20.0 ng/ml, values between 20-30 ng/ml and values > 30.0 ng/ml were defined as vitamin D deficient, insufficient and sufficient, respectively. Optimal 25(OH)D level was defined as ≥ 30 ng/ml. SPSSx statistical package program was used for the evaluation of the data. The statistical significance degree was accepted as p < 0.05. Mean ages did not differ between the groups. Significantly increased body mass index (BMI), waist circumference (C) and neck C as well as significantly decreased fasting blood glucose (FBG) and vitamin D values were observed in MO group (p < 0.05). In OB group, 37.5% of the children were vitamin D deficient, and in MO group the corresponding value was 53.6%. No difference between the groups in terms of lipid profile, systolic blood pressure (SBP), diastolic blood pressure (DBP) and insulin values was noted. There was a severe statistical significance between FBG values of the groups (p < 0.001). Important correlations between BMI, waist C, hip C, neck C and both SBP as well as DBP were found in OB group. In MO group, correlations only with SBP were obtained. In a similar manner, in OB group, correlations were detected between SBP-BMR and DBP-BMR. However, in MO children, BMR correlated only with SBP. The associations of vitamin D with anthropometric indices as well as some lipid parameters were defined. In OB group BMI, waist C, hip C and triglycerides (TRG) were negatively correlated with vitamin D concentrations whereas none of them were detected in MO group. Vitamin D deficiency may contribute to the complications associated with childhood obesity. Loss of correlations between obesity indices-DBP, vitamin D-TRG, as well as relatively lower FBG values, observed in MO group point out that the emergence of MetS components starts during obesity state just before the transition to morbid obesity. Aside from its deficiency state, associations of vitamin D with anthropometric measurements, blood pressures and TRG should also be evaluated before the development of morbid obesity.

Keywords: Children, morbid obesity, obesity, vitamin D.

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Authors: Mustafa M. Donma, Sule G. Kacmaz, Ahsen Yilmaz, Savas Guzel, Orkide Donma

Abstract:

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.

Keywords: biomarker, cardiovascular diseases, children, obesity

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Authors: Mustafa M. Donma, Orkide Donma

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Anthropometric measurements are essential for obesity studies. Waist circumference (WC) is the most frequently used measure and along with hip circumference (HC), it is used in most equations derived for the evaluation of obese individuals. Morbid obesity (MO) is the most severe clinical form of obesity and such individuals may also exhibit some clinical findings leading to metabolic syndrome (MetS). Then, it becomes a requirement to discriminate MO children with MetS (MOMetS+) from MO children without MetS (MOMetS-). Almost all obesity indices can differentiate obese (OB) children from children with normal body mass index (N-BMI). However, not all of them are capable of making this distinction. The aim of this study was to find out the clinical availability of (waist circumference + hip circumference)/2 ((WC+HC)/2) for the differential diagnosis of MOMetS+ and MOMetS- and to compare the possible preponderance of it over some other anthropometric or fat-based obesity indices. 45 MOMetS+ and 45 MOMetS- children were included in the study. Participants have submitted informed consent forms. The study protocol was approved by the Non-interventional Clinical Studies Ethics Committee of Tekirdag Namik Kemal University. Anthropometric measurements were performed. BMI, waist-to-hip circumference (WHR), (WC+HC)/2, trunk-to-leg fat ratio (TLFR), trunk-to-appendicular fat ratio (TAFR), trunk fat+leg fat/2 ((trunk+leg fat)/2), diagnostic obesity notation model assessment index-2 (D2I) and fat mass index (FMI) were calculated for both groups. Study data were analyzed statistically and 0.05 for p value was accepted as the statistical significance degree. Statistically higher BMI, WC, (WC+HC)/2, (trunk+leg fat)/2 values were found in MOMetS+ children than MOMetS- children. No statistically significant difference was detected for WHR, TLFR, TAFR, D2I and FMI between two groups. The lack of difference between the groups in terms of FMI and D2I pointed out the fact that the recently developed fat-based index; (trunk+leg fat)/2 gives much more valuable information during the evaluation of MOMetS+ and MOMetS- children. Upon evaluation of the correlations, (WC+HC)/2 was strongly correlated with D2I and FMI in both MOMetS+ and MOMetS- groups. Neither D2I nor FMI was correlated with W/H. Strong correlations were calculated between (WC+HC)/2 and (trunk+leg fat)/2 in both MOMetS- (r = 0.961; p < 0.001) and MOMetS+ (r = 0.936; p < 0.001) groups. Partial correlations between (WC+HC)/2 and (trunk+leg fat)/2 after controlling the effect of basal metabolic rate were r = 0.726; p < 0.001 in MOMetS- group and r = 0.932; p < 0.001 in MOMetS+ group. The correlation in the latter group was higher than the first group. In conclusion, recently developed anthropometric obesity index (WC+HC)/2 and fat-based obesity index (trunk+leg fat)/2 were of preponderance over the previously introduced classical obesity indices such as WHR, D2I and FMI during the differential diagnosis of MOMetS+ and MOMetS- children.

Keywords: Hip circumference, metabolic syndrome, morbid obesity, waist circumference.

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Authors: Mustafa M. Donma, Orkide Donma

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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.

Keywords: Children, inflammation, insulin resistance, metabolic syndrome, obesity.

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Authors: Mustafa M. Donma, Orkide Donma

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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.

Keywords: adropin, fetuin A, fibroblast growth factor-21, insulin resistance, pediatric obesity

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Authors: Mustafa M. Donma, Orkide Donma

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Metabolic syndrome (MetS) is a disease associated with obesity. It is a complicated clinical problem possibly affecting body composition as well as macrominerals. These parameters gain further attention particularly in pediatric population. The aim of this study is to investigate the amount of discrete body composition fractions in groups that differ in the severity of obesity. Also, the possible associations with calcium (Ca), phosphorus (P), magnesium (Mg) will be examined. The study population was divided into four groups. 28, 29, 34 and 34 children were involved in Group 1 (healthy), Group 2 (obese), Group 3 (morbid obese) and Group 4 (MetS), respectively. Institutional Ethical Committee approved the study protocol. Informed consent forms were obtained from the parents of the participants. The classification of obese groups was performed based upon the recommendations of World Health Organization. MetS components were defined. Serum Ca, P, Mg concentrations were measured. Within the scope of body composition, fat mass, fat-free mass, protein mass, mineral mass were determined by body composition monitor using bioelectrical impedance analysis technology. Weight, height, waist circumference, hip circumference, head circumference and neck circumference values were recorded. Body mass index, diagnostic obesity notation model assessment index, fat mass index and fat-free mass index values were calculated. Data were statistically evaluated and interpreted. There was no statistically significant difference among the groups in terms of Ca and P concentrations. Magnesium concentrations differed between Group 1 and Group 4. Strong negative correlations were detected between P as well as Mg and fat mass index as well as diagnostic obesity notation model assessment index in Group 4, which comprised morbid obese children with MetS. This study emphasized unique associations of P and Mg minerals with diagnostic obesity notation model assessment index and fat mass index during the evaluation of morbid obese children with MetS. It was also concluded that diagnostic obesity notation model assessment index and fat mass index were more proper indices in comparison with body mass index and fat-free mass index for the purpose of defining body composition in children.

Keywords: Children, fat mass, fat-free mass, macrominerals, obesity.

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Authors: Mustafa M. Donma, Orkide Donma

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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. 

Keywords: Body mass index, children, D2I index, fat mass index, obesity.

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Authors: Mustafa M. Donma, Orkide Donma, Murat Aydin, Muhammet Demirkol, Burcin Nalbantoglu, Aysin Nalbantoglu, Birol Topcu

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Childhood obesity is an ever increasing global health problem, affecting both developed and developing countries. Accurate evaluation of obesity in children requires difficult and detailed investigation. In our study, obesity in children was evaluated using new body fat ratios and indices. Assessment of anthropometric measurements, as well as some ratios, is important because of the evaluation of gender differences particularly during the late periods of obesity. A total of 239 children; 168 morbid obese (MO) (81 girls and 87 boys) and 71 normal weight (NW) (40 girls and 31 boys) children, participated in the study. Informed consent forms signed by the parents were obtained. Ethics Committee approved the study protocol. Mean ages (years)±SD calculated for MO group were 10.8±2.9 years in girls and 10.1±2.4 years in boys. The corresponding values for NW group were 9.0±2.0 years in girls and 9.2±2.1 years in boys. Mean body mass index (BMI)±SD values for MO group were 29.1±5.4 kg/m² and 27.2±3.9 kg/m² in girls and boys, respectively. These values for NW group were calculated as 15.5±1.0 kg/m² in girls and 15.9±1.1 kg/m² in boys. Groups were constituted based upon BMI percentiles for age-and-sex values recommended by WHO. Children with percentiles >99 were grouped as MO and children with percentiles between 85 and 15 were considered NW. The anthropometric measurements were recorded and evaluated along with the new ratios such as trunk-to-appendicular fat ratio, as well as indices such as Index-I and Index-II. The body fat percent values were obtained by bio-electrical impedance analysis. Data were entered into a database for analysis using SPSS/PASW 18 Statistics for Windows statistical software. Increased waist-to-hip circumference (C) ratios, decreased head-to-neck C, height ‘to’ ‘two’-‘to’-waist C and height ‘to’ ‘two’-‘to’-hip C ratios were observed in parallel with the development of obesity (p≤0.001). Reference value for height ‘to’ ‘two’-‘to’-hip ratio was detected as approximately 1.0. Index-II, based upon total body fat mass, showed much more significant differences between the groups than Index-I based upon weight. There was not any difference between trunk-to-appendicular fat ratios of NW girls and NW boys (p≥0.05). However, significantly increased values for MO girls in comparison with MO boys were observed (p≤0.05). This parameter showed no difference between NW and MO states in boys (p≥0.05). However, statistically significant increase was noted in MO girls compared to their NW states (p≤0.001). Trunk-to-appendicular fat ratio was the only fat-based parameter, which showed gender difference between NW and MO groups. This study has revealed that body ratios and formula based upon body fat tissue are more valuable parameters than those based on weight and height values for the evaluation of morbid obesity in children.

Keywords: Anthropometry, childhood obesity, gender, Morbid obesity.

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Authors: Mustafa M. Donma, Orkide Donma

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The number of indices developed for the evaluation of obesity and metabolic syndrome (MetS) both in adults and pediatric population is ever increasing. These indices can be weight-dependent or weight–independent. Some are extremely sophisticated equations and their clinical utility is questionable in routine clinical practice. The aim of this study was to compare presently available obesity indices and find the most practical one. Their associations with MetS components were also investigated to determine their capacities in differential diagnosis of morbid obesity with and without MetS. Children with normal body mass index (N-BMI) and morbid obesity were recruited for this study. Three groups were constituted. Age- and sex-dependent BMI percentiles for morbid obese (MO) children were above 99 according to World Health Organization tables. Of them, those with MetS findings were evaluated as MetS group. Children, whose values were between 85 and 15, were included in N-BMI group. The study protocol was approved by the Ethics Committee of Tekirdag Namik Kemal University, Faculty of Medicine. Parents filled out informed consent forms to participate in the study. Anthropometric measurements and blood pressure values were recorded. BMI, hip index (HI), conicity index (CI), triponderal mass index (TPMI), body adiposity index (BAI), body shape index (BSI), body roundness index (BRI), abdominal volume index (AVI), waist-to-hip ratio (WHR) and [waist circumference (WC) + hip circumference (HC)]/2 were the formulas examined in this study. Routine biochemical tests including fasting blood glucose (FBG), insulin (INS), blood lipids were performed. Statistical program SPSS was used for the evaluation of study data; p < 0.05 was accepted as the statistical significance degree. HI did not differ among the groups. A statistically significant difference was noted between N-BMI and MetS groups in terms of ABSI. All the other indices were capable of making discrimination between N-BMI-MO, N-BMI- MetS and MO-MetS groups. No correlation was found between FBG and any obesity indices in any groups. The same was true for INS in N-BMI group. Insulin was correlated with BAI, TPMI, CI, BRI, AVI and (WC+HC)/2 in MO group without MetS findings. In the MetS group, the only index, which was correlated with INS, was (WC+HC)/2. These findings have pointed out that complicated formulas may not be required for the evaluation of the alterations among N-BMI and various obesity groups including MetS. The simple easily computable weight-independent index, (WC+HC)/2, was unique, because it was the only index, which exhibits a valuable association with INS in MetS group. It did not exhibit any correlation with other obesity indices showing associations with INS in MO group. It was concluded that (WC+HC)/2 was pretty valuable practicable index for the discrimination of MO children with and without MetS findings.

Keywords: Fasting blood glucose, insulin, metabolic syndrome, obesity indices.

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Authors: Mustafa M. Donma, Orkide Donma

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Metabolic syndrome (MetS) is a severe health problem caused by morbid obesity, the severest form of obesity. The components of MetS are rather stable in adults. However, the diagnosis of MetS in morbid obese (MO) children still constitutes a matter of discussion. The aim of this study was to develop a formula, which facilitated the diagnosis of MetS in MO children and was capable of discriminating MO children with and without MetS findings. The study population comprised MO children. Age and sex-dependent body mass index (BMI) percentiles of the children were above 99. Increased blood pressure, elevated fasting blood glucose (FBG), elevated triglycerides (TRG) and/or decreased high density lipoprotein cholesterol (HDL-C) in addition to central obesity were listed as MetS components for each child. Two groups were constituted. In the first group, there were 42 MO children without MetS components. Second group was composed of 44 MO children with at least two MetS components. Anthropometric measurements including weight, height, waist and hip circumferences were performed during physical examination. BMI and homeostatic model assessment of insulin resistance (HOMA-IR) values were calculated. Informed consent forms were obtained from the parents of the children. Institutional Non-Interventional Clinical Studies Ethics Committee approved the study design. Routine biochemical analyses including FBG, insulin (INS), TRG, HDL-C were performed. The performance and the clinical utility of Diagnostic Obesity Notation Model Assessment Metabolic Syndrome Index (DONMA MetS index) [(INS/FBG)/(HDL-C/TRG)*100] was tested. Appropriate statistical tests were applied to the study data. p value smaller than 0.05 was defined as significant. MetS index values were 41.6 ± 5.1 in MO group and 104.4 ± 12.8 in MetS group. Corresponding values for HDL-C values were 54.5 ± 13.2 mg/dl and 44.2 ± 11.5 mg/dl. There was a statistically significant difference between the groups (p < 0.001). Upon evaluation of the correlations between MetS index and HDL-C values, a much stronger negative correlation was found in MetS group (r = -0.515; p = 0.001) in comparison with the correlation detected in MO group (r = -0.371; p = 0.016). From these findings, it was concluded that the statistical significance degree of the difference between MO and MetS groups was highly acceptable for this recently introduced MetS index. This was due to the involvement of all of the biochemically defined MetS components into the index. This is particularly important because each of these four parameters used in the formula is a cardiac risk factor. Aside from discriminating MO children with and without MetS findings, MetS index introduced in this study is important from the cardiovascular risk point of view in MetS group of children.

Keywords: Fasting blood glucose, high density lipoprotein cholesterol, insulin, metabolic syndrome, morbid obesity, triglycerides.

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Authors: Orkide Donma, Mustafa M. Donma

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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.

Keywords: Children, insulin resistance, metabolic syndrome, plateletcrit, platelet indices.

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Authors: Orkide Donma, Mustafa M. Donma

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 (DONMA_LAB) 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 DONMA_LAB 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, DONMA_LAB 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.

Keywords: Children, index, laboratory, metabolic syndrome, obesity.

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Authors: Orkide Donma, Mustafa M. Donma

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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. 15^th-to-85^th 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.

Keywords: Children, lipid ratios, metabolic syndrome, obesity indices.

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Authors: Orkide Donma, Mustafa M. Donma

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Basal metabolic rate is questioned as a risk factor for weight gain. The relations between basal metabolic rate and body composition have not been cleared yet. The impact of fat mass on basal metabolic rate is also uncertain. Within this context, indices based upon total body mass as well as total body fat mass are available. In this study, the aim is to investigate the potential clinical utility of these indices in the adult population. 287 individuals, aged from 18 to 79 years, were included into the scope of the study. Based upon body mass index values, 10 underweight, 88 normal, 88 overweight, 81 obese, and 20 morbid obese individuals participated. Anthropometric measurements including height (m), and weight (kg) were performed. Body mass index, diagnostic obesity notation model assessment index I, diagnostic obesity notation model assessment index II, basal metabolic rate-to-weight ratio were calculated. Total body fat mass (kg), fat percent (%), basal metabolic rate, metabolic age, visceral adiposity, fat mass of upper as well as lower extremities and trunk, obesity degree were measured by TANITA body composition monitor using bioelectrical impedance analysis technology. Statistical evaluations were performed by statistical package (SPSS) for Windows Version 16.0. Scatterplots of individual measurements for the parameters concerning correlations were drawn. Linear regression lines were displayed. The statistical significance degree was accepted as p < 0.05. The strong correlations between body mass index and diagnostic obesity notation model assessment index I as well as diagnostic obesity notation model assessment index II were obtained (p < 0.001). A much stronger correlation was detected between basal metabolic rate and diagnostic obesity notation model assessment index I in comparison with that calculated for basal metabolic rate and body mass index (p < 0.001). Upon consideration of the associations between basal metabolic rate-to-weight ratio and these three indices, the best association was observed between basal metabolic rate-to-weight and diagnostic obesity notation model assessment index II. In a similar manner, this index was highly correlated with fat percent (p < 0.001). Being independent of the indices, a strong correlation was found between fat percent and basal metabolic rate-to-weight ratio (p < 0.001). Visceral adiposity was much strongly correlated with metabolic age when compared to that with chronological age (p < 0.001). In conclusion, all three indices were associated with metabolic age, but not with chronological age. Diagnostic obesity notation model assessment index II values were highly correlated with body mass index values throughout all ranges starting with underweight going towards morbid obesity. This index is the best in terms of its association with basal metabolic rate-to-weight ratio, which can be interpreted as basal metabolic rate unit.

Keywords: Basal metabolic rate, body mass index, children, diagnostic obesity notation model assessment index, obesity.

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Authors: Mustafa M. Donma, Orkide Donma

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Spexin, expressed in the central nervous system, has attracted much interest in feeding behavior, obesity, diabetes, energy metabolism and cardiovascular functions. Fetuin A is known as the negative acute phase reactant synthesized in the liver. Eosinophils are early indicators of cardiometabolic complications. Patients with elevated platelet count, associated with hypercoagulable state in the body, are also more liable to cardiovascular diseases (CVDs). In this study, the aim is to examine the profiles of spexin and fetuin A concomitant with the course of variations detected in eosinophil as well as platelet counts in morbid obese children. 34 children with normal-body mass index (N-BMI) and 51 morbid obese (MO) children participated in the study. Written-informed consent forms were obtained prior to the study. Institutional ethics committee approved the study protocol. Age- and sex-adjusted BMI percentile tables prepared by World Health Organization were used to classify healthy and obese children. Mean age ± SEM of the children were 9.3 ± 0.6 years and 10.7 ± 0.5 years in N-BMI and MO groups, respectively. Anthropometric measurements of the children were taken. BMI values were calculated from weight and height values. Blood samples were obtained after an overnight fasting. Routine hematologic and biochemical tests were performed. Within this context, fasting blood glucose (FBG), insulin (INS), triglycerides (TRG), high density lipoprotein-cholesterol (HDL-C) concentrations were measured. Homeostatic model assessment for insulin resistance (HOMA-IR) values were calculated. Spexin and fetuin A levels were determined by enzyme-linked immunosorbent assay. Data were evaluated from the statistical point of view. Statistically significant differences were found between groups in terms of BMI, fat mass index, INS, HOMA-IR and HDL-C. In MO group, all parameters increased as HDL-C decreased. Elevated concentrations in MO group were detected in eosinophils (p < 0.05) and platelets (p > 0.05). Fetuin A levels decreased in MO group (p > 0.05). However, decrease was statistically significant in spexin levels for this group (p < 0.05). In conclusion, these results have suggested that increases in eosinophils and platelets exhibit behavior as cardiovascular risk factors. Decreased fetuin A behaved as a risk factor suitable to increased risk for cardiovascular problems associated with the severity of obesity. Along with increased eosinophils, increased platelets and decreased fetuin A, decreased spexin was the parameter, which reflects best its possible participation in the early development of CVD risk in MO children.

Keywords: Cardiovascular diseases, eosinophils, fetuin A, pediatric morbid obesity, platelets, spexin.

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Authors: Mustafa M. Donma, Orkide Donma

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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.

Keywords: Blood pressure, children, index, metabolic syndrome, obesity.

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Authors: Orkide Donma, Mustafa M. Donma

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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<0.05 was accepted as the degree for statistical significance. The mean ages±SD values of Group 1 and Group 2 were 9.9±3.1 years and 10.8±3.2 years, respectively. Body mass index (BMI) values were calculated as 27.4±5.9 kg/m² and 30.6±8.1 kg/m², successively. There were no statistically significant differences between the ages and BMI values of the groups. Insulin levels were statistically significantly increased in MetS in comparison with the levels measured in MO children. There was not any difference between MO children and those with MetS in terms of cortisol, T₃, T₄ and TSH. However, T₄ levels were positively correlated with cortisol and negatively correlated with insulin. None of these correlations were observed in MO children. Cortisol levels in both MO as well as MetS group were significantly correlated. Cortisol, insulin, and thyroid hormones are essential for life. Cortisol, called the control system for hormones, orchestrates the performance of other key hormones. It seems to establish a connection between hormone imbalance and inflammation. During an inflammatory state, more cortisol is produced to fight inflammation. High cortisol levels prevent the conversion of the inactive form of the thyroid hormone T₄ into active form T₃. Insulin is reduced due to low thyroid hormone. T₃, which is essential for blood sugar control- requires cortisol levels within the normal range. Positive association of T₄ with cortisol and negative association of it with insulin are the indicators of such a delicate balance among these hormones also in children with MetS.

Keywords: Children, cortisol, insulin, metabolic syndrome, thyroid hormones.

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Authors: Mustafa M. Donma, Orkide Donma

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Cardiovascular (CV) pathology is one of the expected consequences of excessive fat gain. The role of zinc (Zn) in thyroid hormone metabolism (THM) is a matter of debate. Both thyroid stimulating hormone (TSH) and Zn levels are subject to variation in obese individuals. Zn participates in THM. It is closely related to TSH. Since thyroid hormones are required for Zn absorption, hypothyroidism can lead to Zn deficiency and vice versa. Zn exhibits protective effects on CV health and it is inversely correlated with CV markers in childhood obesity. The association between subclinical hypothyroidism (SCHT) and metabolic disorders is under investigation due to its clinical importance. SCHT is defined as the elevated serum TSH levels in the presence of normal free thyroxin (T4) concentrations. The aim of this study is to evaluate the associations between TSH levels and Zn concentrations in SCHT cases detected in morbid obese (MO) children with and without metabolic syndrome (MetS) [(MOMetS+ and MOMetS-)], respectively. 42 children were present in each study group. Informed consent forms were obtained. Tekrdag Namik Kemal University Faculty of Medicine Non-Interventional Clinical Investigations Ethical Committee approved the study protocol. World Health Organization criteria were used for obesity classification. Children with age and sex-dependent body mass index percentile values above 99 were defined as MO. Children exhibiting at least two of MetS criteria were included in MOMetS+ group. Elevated fasting blood glucose, elevated triglycerides (TRG)/decreased high density lipoprotein-cholesterol (HDL-C) concentrations, elevated blood pressure values in addition to central obesity were listed as MetS criteria. Anthropometric measures were recorded. Routine biochemical analyses were performed. In MOMetS- group 13, in MOMetS+ group 15 children were with SCHT. Statistical analyses were performed. p < 0.05 was accepted as statistically significant. In MOMetS- and MOMetS+ groups, TSH levels were 4.1 ± 2.9 mU/L and 4.6 ± 3.1 mU/L, respectively. Corresponding values for SCHT cases were 7.3 ± 3.1 mU/L and 8.0 ± 2.7 mU/L. Free T4 levels were within normal limits. Zn concentrations were negatively correlated with TSH levels in both groups. Significant negative correlation calculated in MOMetS+ group (r = -0.909; p < 0.001) was much stronger than that found in MOMetS- group (r = -0.706; p < 0.05). This strong correlation (r = -0.909; p < 0.001) calculated for cases with SCHT in MOMetS+ group was much lower in the same group (r = -0.793; p < 0.001) when all cases were considered. In conclusion, the presence of strong correlations between TSH and Zn in SCHT in both MOMetS- and MOMetS+ groups have pointed out that MO children were under the threat of CV pathologies. The detection of the much stronger correlation in MOMetS+ group in comparison with the correlation found in MOMetS- group was the indicator of greater CV risk due to the presence of MetS. In MOMetS+ group, correlation in SCHT cases found higher than correlation calculated for all cases confirmed much higher CV risk due to the contribution of SCHT.

Keywords: Cardiovascular risk, child morbid obesity, subclinical hypothyroidism, zinc.

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Authors: Orkide Donma, Mustafa M. Donma

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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.

Keywords: Children, complete blood count, gender, metabolic syndrome.

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Authors: Mustafa M. Donma, Orkide Donma

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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.

Keywords: Children, insulin resistance indices, metabolic syndrome, obesity.

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Authors: Mustafa M. Donma, Orkide Donma

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Obesity is a low-grade inflammatory state. Childhood obesity is a multisystem disease, which is associated with a number of complications as well as potentially negative consequences. Gender is an important universal risk factor for many diseases. Hematological indices differ significantly by gender. This should be considered during the evaluation of obese children. The aim of this study is to detect hematologic indices that differ by gender in morbid obese (MO) children. A total of 134 MO children took part in this study. The parents filled an informed consent form and the approval from the Ethics Committee of Namik Kemal University was obtained. Subjects were divided into two groups based on their genders (64 females aged 10.2±3.1 years and 70 males aged 9.8±2.2 years; p ≥ 0.05). Waist-to-hip as well as head-to-neck ratios and body mass index (BMI) values were calculated. The children, whose WHO BMI-for age and sex percentile values were > 99 percentile, were defined as MO. Hematological parameters [haemoglobin, hematocrit, erythrocyte count, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, red blood cell distribution width, leukocyte count, neutrophil %, lymphocyte %, monocyte %, eosinophil %, basophil %, platelet count, platelet distribution width, mean platelet volume] were determined by the automatic hematology analyzer. SPSS was used for statistical analyses. P ≤ 0.05 was the degree for statistical significance. The groups included children having mean±SD value of BMI as 26.9±3.4 kg/m² for males and 27.7±4.4 kg/m² for females (p ≥ 0.05). There was no significant difference between ages of females and males (p ≥ 0.05). Males had significantly increased waist-to-hip ratios (0.95±0.08 vs 0.91±0.08; p=0.005) and mean corpuscular hemoglobin concentration values (33.6±0.92 vs 33.1±0.83; p=0.001) compared to those of females. Significantly elevated neutrophil (4.69±1.59 vs 4.02±1.42; p=0.011) and neutrophil-to-lymphocyte ratios (1.70±0.71 vs 1.39±0.48; p=0.004) were detected in females. There was no statistically significant difference between groups in terms of C-reactive protein values (p ≥ 0.05). Adipose tissue plays important roles during the development of obesity and associated diseases such as metabolic syndrom and cardiovascular diseases (CVDs). These diseases may cause changes in complete blood cell count parameters. These alterations are even more important during childhood. Significant gender effects on the changes of neutrophils, one of the white blood cell subsets, were observed. The findings of the study demonstrate the importance of considering gender in clinical studies. The males and females may have distinct leukocyte-trafficking profiles in inflammation. Female children had more circulating neutrophils, which may be the indicator of an increased risk of CVDs, than male children within this age range during the late stage of obesity. In recent years, females represent about half of deaths from CVDs; therefore, our findings may be the indicator of the increasing tendency of this risk in females starting from childhood.

Keywords: Children, gender, morbid obesity, neutrophil-to-lymphocyte ratio.

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Authors: Mustafa M. Donma, Orkide Donma

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A growing list of cancers might be influenced by obesity. Obesity is associated with an increased risk for the occurrence and development of some cancers. Inflammation can lead to cancer. It is one of the characteristic features of cancer and plays a critical role in cancer development. C-reactive protein (CRP) is under evaluation related to the new and simple prognostic factors in patients with metastatic renal cell cancer. Obesity can predict and promote systemic inflammation in healthy adults. BMI is correlated with hs-CRP. In this study, SII index and CRP values were evaluated in children with normal BMI and those within the range of different obesity grades to detect the tendency towards cancer in pediatric obesity. A total of one hundred and ninety-four children; thirty-five children with normal BMI, twenty overweight (OW), forty-seven obese (OB) and ninety-two morbid obese (MO) participated in the study. Age- and sex-matched groups were constituted using BMI-for age percentiles. Informed consent was obtained. Ethical Committee approval was taken. Weight, height, waist circumference (C), hip C, head C and neck C of the children were measured. The complete blood count test was performed. C-reactive protein analysis was performed. Statistical analyses were performed using SPSS. The degree for statistical significance was p≤0.05. SII index values were progressively increasing starting from normal weight (NW) to MO children. There is a statistically significant difference between NW and OB as well as MO children. No significant difference was observed between NW and OW children, however, a correlation was observed between NW and OW children. MO constitutes the only group, which exhibited a statistically significant correlation between SII index and CRP. Obesity-related bladder, kidney, cervical, liver, colorectal, endometrial cancers are still being investigated. Obesity, characterized as a chronic low-grade inflammation, is a crucial risk factor for colon cancer. Elevated childhood BMI values may be indicative of processes leading to cancer, initiated early in life. Prevention of childhood adiposity may decrease the cancer incidence in adults. To authors’ best knowledge, this study is the first to introduce SII index values during obesity of varying degrees of severity. It is suggested that this index seems to affect all stages of obesity with an increasing tendency and may point out the concomitant status of obesity and cancer starting from very early periods of life.

Keywords: Children, c- reactive protein, systemic immune-inflammation index, obesity.

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Authors: Orkide Donma, Mustafa M. Donma, Muhammet Demirkol, Murat Aydin, Tuba Gokkus, Burcin Nalbantoglu, Aysin Nalbantoglu, Birol Topcu

Abstract:

Obesity in childhood establishes a ground for adulthood obesity. Especially morbid obesity is an important problem for the children because of the associated diseases such as diabetes mellitus, cancer and cardiovascular diseases. In this study, body mass index (BMI), body fat ratios, anthropometric measurements and ratios were evaluated together with different laboratory indices upon evaluation of obesity in morbidly obese (MO) children. Children with nutritional problems participated in the study. Written informed consent was obtained from the parents. Study protocol was approved by the Ethics Committee. Sixty-two MO girls aged 129.5±35.8 months and 75 MO boys aged 120.1±26.6 months were included into the scope of the study. WHO-BMI percentiles for age-and-sex were used to assess the children with those higher than 99^th as morbid obesity. Anthropometric measurements of the children were recorded after their physical examination. Bio-electrical impedance analysis was performed to measure fat distribution. Anthropometric ratios, body fat ratios, Index-I and Index-II as well as insulin sensitivity indices (ISIs) were calculated. Girls as well as boys were binary grouped according to homeostasis model assessment-insulin resistance (HOMA-IR) index of <2.5 and >2.5, fasting glucose to insulin ratio (FGIR) of <6 and >6 and quantitative insulin sensitivity check index (QUICKI) of <0.33 and >0.33 as the frequently used cut-off points. They were evaluated based upon their BMIs, arms, legs, trunk, whole body fat percentages, body fat ratios such as fat mass index (FMI), trunk-to-appendicular fat ratio (TAFR), whole body fat ratio (WBFR), anthropometric measures and ratios [waist-to-hip, head-to-neck, thigh-to-arm, thigh-to-ankle, height/2-to-waist, height/2-to-hip circumference (C)]. SPSS/PASW 18 program was used for statistical analyses. p≤0.05 was accepted as statistically significance level. All of the fat percentages showed differences between below and above the specified cut-off points in girls when evaluated with HOMA-IR and QUICKI. Differences were observed only in arms fat percent for HOMA-IR and legs fat percent for QUICKI in boys (p≤ 0.05). FGIR was unable to detect any differences for the fat percentages of boys. Head-to-neck C was the only anthropometric ratio recommended to be used for all ISIs (p≤0.001 for both girls and boys in HOMA-IR, p≤0.001 for girls and p≤0.05 for boys in FGIR and QUICKI). Indices which are recommended for use in both genders were Index-I, Index-II, HOMA/BMI and log HOMA (p≤0.001). FMI was also a valuable index when evaluated with HOMA-IR and QUICKI (p≤0.001). The important point was the detection of the severe significance for HOMA/BMI and log HOMA while they were evaluated also with the other indices, FGIR and QUICKI (p≤0.001). These parameters along with Index-I were unique at this level of significance for all children. In conclusion, well-accepted ratios or indices may not be valid for the evaluation of both genders. This study has emphasized the limiting properties for boys. This is particularly important for the selection process of some ratios and/or indices during the clinical studies. Gender difference should be taken into consideration for the evaluation of the ratios or indices, which will be recommended to be used particularly within the scope of obesity studies.

Keywords: Anthropometry, childhood obesity, gender, insulin sensitivity index.

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Authors: Mustafa M. Donma, Orkide Donma

Abstract:

Alterations in lipid parameters as well as in the fat distribution of the body are noteworthy during the evaluation of obesity stages. Total cholesterol (TC), triglycerides (TRG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C) are basic lipid fractions. Fat deposited in trunk and extremities may give considerable amount of information. Ratios such as trunk-to-leg fat ratio (TLFR) and trunk-to-appendicular fat ratio (TAFR) are derived from distinct fat distribution in these areas. In this study, lipid fractions and TLFR as well as TAFR were evaluated and the distinctions among healthy, obese (OB) and morbid obese (MO) groups were investigated. Three groups [normal body mass index (N-BMI), OB, MO] were constituted. Ages and sexes of the groups were matched. The study protocol was approved by the Non-interventional Ethics Committee of Tekirdag Namik Kemal University. Written informed consent forms were obtained from the parents of the participants. Anthropometric measurements (height, weight, waist circumference, hip circumference, head circumference, neck circumference) were recorded during the physical examination. BMI values were calculated. Total, trunk, leg and arm fat mass values were obtained by TANITA Bioelectrical Impedance Analysis. These values were used to calculate TLFR and TAFR. Systolic (SBP) and diastolic blood pressures (DBP) were measured. Routine biochemical tests including lipid fractions were performed. Data were evaluated using SPSS software. p value smaller than 0.05 was accepted as significant. There was no difference among the age values and gender ratios of the groups. Any statistically significant difference was not observed in terms of DBP, TLFR as well as serum lipid fractions. Higher SBP values were measured both in OB and MO children than those with N-BMI. TAFR showed a significant difference between N-BMI and OB groups. Statistically significant increases were detected between insulin values of N-BMI group and OB as well as MO groups. There were bivariate correlations between LDL and TLFR as well as TAFR values in MO group. When adjusted for SBP and DBP, partial correlations were calculated for LDL-TLFR as well as LDL-TAFR. Much stronger partial correlations were obtained for the same couples upon controlling for TRG and HDL-C. Much stronger partial correlations observed in MO children emphasize the potential transition from morbid obesity to metabolic syndrome. These findings have concluded that LDL-C may be suggested as a discriminating parameter between OB and MO children.

Keywords: Children, lipid parameters, obesity, trunk-to-leg fat ratio, trunk-to-appendicular fat ratio.

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Authors: Mustafa M. Donma, Orkide Donma

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.

Keywords: Children, complete blood cell count, high density lipoprotein cholesterol, metabolic syndrome, obesity.

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Authors: Martina Kanciruk, Jac W. Andrews, Tyrone Donnon

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The purpose of this study was to determine the significance of history of obesity for the development of childhood overweight and/or obesity. Accordingly, a systematic literature review of English-language studies published from 1980 to 2012 using the following data bases: MEDLINE, PsychINFO, Cochrane Database of Systematic Reviews, and Dissertation Abstracts International was conducted. The following terms were used in the search: pregnancy, overweight, obesity, family history, parents, childhood, risk factors. Eleven studies of family history and obesity conducted in Europe, Asia, North America, and South America met the inclusion criteria. A meta-analysis of these studies indicated that family history of obesity is a significant risk factor of overweight and /or obesity in offspring; risk for offspring overweight and/or obesity associated with family history varies depending of the family members included in the analysis; and when family history of obesity is present, the offspring are at greater risk for developing obesity or overweight. In addition, the results from moderator analyses suggest that part of the heterogeneity discovered between the studies can be explained by the region of world that the study occurred in and the age of the child at the time of weight assessment.

Keywords: Childhood obesity, overweight, family history, risk factors, meta-analysis.

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Authors: Mustafa M. Donma, Orkide Donma

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.

Keywords: Children, cobalamin, folate, metabolic syndrome, obesity.

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Authors: A. Chennaf, M. Yahia, W. Bouafia, S. Benbia, D. Khellaf

Abstract:

Our study was designed to highlight changes in  certain biochemical parameters (CH, TG, HDL, GOT, GPT, LDL and  CRP), obese women infertile fertile witnesses and research potential  pathophysiological link between obesity and infertility in this  population of women. This practical work was focused on a  population of 24 obese women infertile, compared to controls,  subjects without any pathology causing disruption of parameters to  be studied to determine the contribution of obesity in the etiology of  infertility. The assay results revealed a highly significant difference  between the two groups in serum CH, TG, HDL, TGO and TGP (P  <0.0001) and in the rate of LDL (p = 0.0017) and CRP (p = 0.02).  The present study indicates that obesity is associated with infertility,  but no direct pathophysiological link between obesity and infertility  has been determined. Further in-depth studies are needed to  determine the exact mechanism by which overweight leads to female  infertility.

 

Keywords: Obesity, fertility, infertility, biochemical, women.

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Authors: Sh. Khoshemehry, M. J. Pourvaghar, M. E. Bahram

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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.

Keywords: Disease, leptin, obesity, physical activity.

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