Metabolic syndrome and leptin concentrations in obese children
http://www.100md.com
《美国医学杂志》
Endocrinology and Metabolism Research Center, Tehran University of Medical Sciences, Tehran, Iran,
Abstract
Objective. Obesity and its complications including metabolic syndrome has been increased in children and adolescents recently. Leptin is known to play an important role in the pathogenesis of obesity. Methods. The objective of this study was to evaluate the relationship of leptin and metabolic syndrome in obese Iranian children. A cross sectional study was carried out in 65 primary schools in Tehran. The children with waist circumferences equal or above 90th percentile for their height and age were chosen for further evaluations. 505 children aged 7-12 years participated in the study. Anthropometric variables measurements, blood pressure, fasting plasma glucose, triglyceride, high-density lipoprotein cholesterol and serum leptin were obtained from the study sample. Results. Serum leptin levels were significantly higher in girls in comparison to the boys (with median 11.0 Vs 8.25 ng/dl; P value = 0.007). Serum level of leptin were higher in children with metabolic syndrome (median 11.3 Vs 8.9 ng/dl; P value = 0.045). However, after adjustment for sex, this association was removed. Conclusion. Leptin did not appear to have a major role in metabolic syndrome, even though it was strongly associated with obesity parameters. More studies evaluating the relationship between leptin and metabolic syndrome in various ethnic groups are recommended.
Keywords: Leptin; Metabolic syndrome; Childhood obesity
'Metabolic syndrome' is characterized by a clustering of metabolic abnormalities which leads to increased cardiovascular disease and all-causes mortality.[1] The five generally accepted features of metabolic syndrome are obesity, insulin resistance, dyslipidemia [including increased triglycerides and decreased HDL], impaired glucose tolerance, and hypertension.[1] Obesity has a central role in metabolic syndrome.[2] Recent studies suggest that this syndrome may also occur in children.[3] Among children and adolescents, metabolic syndrome is associated with subsequent risk of type 2 diabetes mellitus and cardiovascular diseases in adulthood.[3] Considering recent global rise of childhood obesity prevalence, the overall prevalence of the metabolic syndrome in children and adolescents seems to be higher than what is estimated from previous studies.[3]
Leptin is a peptide produced by differentiated adipocytes.[4] It is thought to be a key hormone in the regulation of body fat stores. This peptide controls energy metabolism at the level of hypothalamus by supporting food intake and stimulating energy expenditure.[4] The relationship between serum leptin and body mass index has been well established.[5] Leptin is also proposed to be associated with insulin resistance and diabetes in human.[6] However, potential relationship between metabolic syndrome and leptin has not been sufficiently addressed in previous studies, particularly in children.[7]
The present study aims to evaluate such a relationship between plasma leptin and metabolic syndrome in Iranian obese children.
Materials and Methods
Participants
This cross-sectional study was carried out on primary school students of the 6th district of Tehran, Iran. All schools in this area were included in the study. Children with a waist circumference equal to or above 90th percentile of their age and height were invited to attend a school-based clinic. The number of children who accepted to participate in the study was 563.
Children who had history of primary hyperlipidemia, diabetes and secondary obesity were excluded from the study. In addition to participants with uncompleted data, any child receiving pharmacological treatment that could affect the metabolic profile was also excluded. 505 children were included in the final analysis. All children had similar lifestyle with no significant physical training program. Before beginning the study, all parents submitted written informed consents and the study was authorized by the ethical investigation committee of Tehran University of Medical science.
Clinical Assessment
Research physicians recorded body weight to the nearest 0.5 Kilograms (kg) using a standard beam balance scale with subjects barefooted and wearing light indoor clothes. Body height was recorded to the nearest 0.5 centimeter (cm). BMI was calculated as the ratio of body weight to body height squared expressed as Kg/m 2sub . Waist circumference was measured at the distal third of the line from the xyphoid process to the umbilicus. Hip circumference was measured 4 cm below the anterior superior process of the iliac spine. Participants were classified to overweight or obese using international sex and age specific BMI cut-offs recommended by the International Obesity Task Force (IOTF).[8] The physicians measured blood pressure (BP) of the right arm in a sitting position after 5 minutes of rest, using an appropriate cuff size. The first and forth Korotkoff sounds were recorded as systolic and diastolic BP. Blood pressure was measured again after 5 minutes of rest and the average was used in the analysis.
Blood Sampling and Analysis
After overnight fasting, blood samples were collected from a vein in the antecubital fossa without venous occlusion. All collections were made between 8:00 and 9:00 am. The samples were immediately centrifuged for serum separation and stored at -20 degrees centigrade. Glucose were measured through calorimetric assays (Pars Azmoon kit; Iran) using automatic serum auto analyzer (Hitachi 902; Boehringer Manneheim, Germany). Serum leptin was measured by a commercial ELISA kit (ALEXIS San Diego, USA).
Diagnosis of metabolic syndrome was established when three or more of the following was presented: glucose levels greater than 100 mg/dl or 5.5 mmol/l according to American Diabetes Association recommendations (which is the same for children and adolescents),[9] at least one of the systolic or diastolic blood pressures above the 90th percentile for age and sex,[9] waist circumference above the 90th percentile for age and gender according to data from NHANES III,[9] triglyceride levels above the 95th percentile, and HDL levels below the 5th percentile for age and gender.[10]
Statistical Analysis
As leptin levels in our sample did not follows a normal distribution, we used non-parametric statistical tests (Mann-Whitney U test) to compare leptin levels between two groups of metabolic and non-metabolic syndrome participants. All data are expressed as mean ± standard deviations, except for leptin that is expressed as median (inter-quartile range). Multivariate logistic regression analyses were performed to evaluate the association of leptin levels with other metabolic variables. P value of 0.05 or less was considered as statistically significant. All statistical analyses were conducted using SPSS package (Version 11.5, Chicago, IL).
Results
The anthropometric and biochemical characteristics of the participants are summarized in table1. Of the 505 participants, 51.1% were boys and 48.9% were girls with the mean age of 9.5 ± 1.2. The number of children with metabolic syndrome was 105 (20.8 %). Waist, BMI and systolic blood pressure were significantly higher in boys comparing to girls (P < 0.05). Serum leptin level was significantly higher in girls in comparison to the boys
(P = 0.007).
The mean levels of biochemical and anthropometric variables of children with and without metabolic syndrome are summarized in table2. Children with metabolic syndrome were significantly more obese than others. HDL cholesterol levels were not different between two groups table2.
Median level of leptin was 11.3 in children with metabolic syndrome and 8.9 in children without metabolic syndrome. The difference was significant in Mann-Whitney U test (P: 0.045). After adjustment for BMI and sex in multivariable logistic regression analysis, there was no significant association between leptin and metabolic syndrome status (Odds Ratio: 0.949, 95% CI: 0.582-1.547). The correlation matrix between the study variables are presented in table3. There were significant correlations between leptin levels and systolic and diastolic blood pressures and triglyceride levels (P<0.05).
Discussion
Metabolic syndrome, a well-recognized constellation of risk factors for type 2 diabetes and atherosclerotic cardiovascular diseases, has its roots in childhood. Autopsy studies have revealed that early evidence of disease processes can be found in childhood [11]. Many studies showed that weight gain has a potent role in this syndrome.[4] With recent marked increase in childhood obesity prevalence, questions regarding the role of obesity-related factors such as leptin in children have increased in importance.[4]
Leptin is a product of ob gene and is expressed only in adipose tissues.[12] It circulates in plasma in a free or bound to leptin-binding proteins.[12] Leptin levels reflect not only the amount of fat stored in the adipose tissues, but also energy imbalance; prolonged fasting, for instance, substantially decreases leptin levels, whereas overfeeding greatly increases them.[12] The role of leptin in the pathophysiology of obesity and related disorders has been reviewed systematically.[12] Although the number of relevant publications shows a great rise in recent years, but most of these studies are about adult subjects and lower attention has been paid to childhood obesity and the role of leptin.
We found that the girls had higher plasma leptin levels comparing to the boys. This finding is in line with the hypothesis that there are gender differences in leptin synthesis, transport or clearance rates.[2] In normal children, leptin levels increase before puberty as body fat mass increases and reach their peak at the onset of puberty, suggesting that leptin may trigger puberty in humans. The difference in genders may be explained by later puberty development among boys and to greater accretion of fat mass in girls in contrast to the greater increase in lean mass in boys during adolescence.[2]
Leptin concentration in our study is significantly higher in obese children than non-obese, which is similar to previous studies.[13], [14] These finding suggests that BMI is the main determinants for the variations of leptin. In addition, it also suggests that resistance to the effects of leptin may start in early childhood.[13], [14]
The results of our study are also consistent with other studies that have shown relationships between leptin levels and serum lipid concentrations.[15], [16] The significant correlation between triglyceride and leptin are similar to other studies that have shown leptin is related to the levels of triglycerides. One study has suggested that triglyceride levels explain 38% of the variation in leptin.[13] However, some studies believe that this association was dependent on adiposity and total body fatness.[4]
Similar to other studies, we found that hypertension is related to high levels of leptin.[7],[17] This phenomenon may be due to potential vaso-constrictive effects of leptin as a result of increased sympathetic activity.[17] In addition, leptin may act through indirect pathways such as rennin, aldosterone, and angiotensinogen. Despite these suggestions, the mechanisms underlying the relationship between leptin and blood pressure are still unclear.[18]
Development of hyperinsulinemia and metabolic syndrome is suggested to be a consequence of hyperleptinemia in obese subjects.[12], [17] In our study, we found higher concentrations of plasma leptin in children with metabolic syndrome. However, this association disappeared after adjustment for BMI and sex in regression analysis. Although some studies have proposed leptin an independent predictor of insulin resistance and metabolic syndrome in children, our results did not confirm this finding.[2] Chu et al. showed that BMI and leptin are the predictor markers of hyperinsulinemia and metabolic syndrome among school children in Taiwan. Meanwhile, similar to our results, Park et al. showed that leptin have no major role in linking various components of the metabolic syndrome.[16] A possible explanation for such inconsistency is that the relationship between leptin and metabolic syndrome might be different in different ethnic groups. Future studies can verify this hypothesis.[16]
The main limitation of our study was lack of measurement of insulin and insulin resistance index. Therefore, we could not evaluate the relationship between leptin, hyperinsulinemia and metabolic syndrome. Based on the results of some studies in children and adolescents, leptin is an independent predictor of basal insulin and children with high plasma leptin levels have higher insulin levels.[17] However, Sudi et al. revealed that in the state of childhood and adolescent obesity, total adiposity but not insulin is the main determinant for leptin concentrations.[13]
In summary, this study has confirmed the significant difference in leptin levels between boys and girls as well as obese and non-obese children. There was a marginal difference in leptin levels between metabolic and non-metabolic syndrome children that was removed after adjustment for sex and BMI. Although leptin was strongly associated with obesity indices in this study, it did not appear to have a major role in metabolic syndrome. Further studies to evaluate such relationship in different ethnic groups are warranted.[19]
References
1. Moreno LA, Pineda I, Rodriguez G et al. Leptin and metabolic syndrome in obese and non-obese children. Horm Metab Res 2002; 34 : 394-399.
2. Chu NF, Wang DJ, Shieh SM et al . Plasma leptin concentrations and obesity in relation to insulin resistance syndrome components among school children in Taiwan-The Taipi Children Heart Study. Int J Obesity 2000; 24 : 1265-1271.
3. Weiss R, Dziura J, Burget TS et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004; 350: 2362-2374.
4. Steinberger J, Steffen L, Jacobs DR et al. Relation of leptin to insulin resistance syndrome in children. Obes Res 2003; 11: 1124-1130.
5. Erturk E, Kuru N, Savci V et al. Serum leptin levels correlate with obesity parameters but not with hyperinsulinism in women with polycystic ovary syndrome. Fertil Steril 2004;82 : 1364-1368.
6. Christos S, Mantzoros. The role of leptin in human obesity and disease: A review of current evidence. Ann Intern Med 1999; 130: 671-680.
7. Valle M, Gascon F, Martos R et al. Relationship between high plasma leptin concentrations and metabolic syndrome in obese pre-pubertal children. Int J Obesity 2003; 27 : 13-18 .
8. Cole TJ, Blezzi MC, Flegal KM et al. Establishing a standard definition for child overweight and obesity worldwide: International survey. BMJ 2000; 320 : 1240-1243.
9. Cruz ML, Goran MI. The metabolic syndrome in children and adolescents. Curr Diabetes Reports 2004; 4 : 53-62.
10. Lipid Research Clinivs: Population Studies Data Book, Vol 1. The prevalence study. Bethesda, MD, Department of Health and human services, Publication (NIH) 80-1527.
11. Chen W, Srinivasan SR, Li S . Metabolic syndrome variables at low levels in childhood are beneficially associated with adulthood cardiovascular risk. Diabetes Care 2005; 28 : 126-131.
12. Remesar X, Rafecas I, Fernandez-Lopez JA et al . Is leptin an insulin counter-regulatory hormone FEBS letters 1997; 402 : 9-11.
13. Sudi K, Gallistl S, Trobunger M et al. Insulin and insulin resistance index are not independent determinants for the variation in leptin in obese children and adolescents. J Pediatr Endocrinol Metab 2000; 13 : 923-932.
14. Zimmet P, Hodge A, Nicolson M et al. Serum leptin concentration, obesity, and insulin resistance in Western Samoas: cross sectional study. BMJ 1996; 13 : 965-969.
15. Shimabukuro M, Koyama K, Chen G et al. Direct antidiabetic effect of leptin through triglyceride depletion of tissue. Proc Natl Acad Sci USA 1997; 94 : 4637-4641.
16. Park HS, Lee MS, Park JY. Leptin and the metabolic syndrome in Korean adolescents: Factor analysis. Ped Int 2004; 46 : 697-703.
17. Nishina M, Kikuchi T, Yamazaki H et al . Relationship among systolic blood pressure, serum insulin and leptin,and visceral fat accumulation in obese children. Hypertens Res 2003; 26 : 281-288.
18. Chu NF, Wang DJ, Shieh SM. Obesity, leptin and blood pressure among children in Taiwan: The Taipei children's heart study. AJH 2001; 14 : 135-140.
19. Leyva F, Godsland IF, Ghatei M et al Hyperleptinemia as a component of a metabolic syndrome of cardiovascular risk. ArtheriosclerThromb Vasc Biol 1998; 18 : 928-933.(Hamidi Anahita, Fakhrzade)
Abstract
Objective. Obesity and its complications including metabolic syndrome has been increased in children and adolescents recently. Leptin is known to play an important role in the pathogenesis of obesity. Methods. The objective of this study was to evaluate the relationship of leptin and metabolic syndrome in obese Iranian children. A cross sectional study was carried out in 65 primary schools in Tehran. The children with waist circumferences equal or above 90th percentile for their height and age were chosen for further evaluations. 505 children aged 7-12 years participated in the study. Anthropometric variables measurements, blood pressure, fasting plasma glucose, triglyceride, high-density lipoprotein cholesterol and serum leptin were obtained from the study sample. Results. Serum leptin levels were significantly higher in girls in comparison to the boys (with median 11.0 Vs 8.25 ng/dl; P value = 0.007). Serum level of leptin were higher in children with metabolic syndrome (median 11.3 Vs 8.9 ng/dl; P value = 0.045). However, after adjustment for sex, this association was removed. Conclusion. Leptin did not appear to have a major role in metabolic syndrome, even though it was strongly associated with obesity parameters. More studies evaluating the relationship between leptin and metabolic syndrome in various ethnic groups are recommended.
Keywords: Leptin; Metabolic syndrome; Childhood obesity
'Metabolic syndrome' is characterized by a clustering of metabolic abnormalities which leads to increased cardiovascular disease and all-causes mortality.[1] The five generally accepted features of metabolic syndrome are obesity, insulin resistance, dyslipidemia [including increased triglycerides and decreased HDL], impaired glucose tolerance, and hypertension.[1] Obesity has a central role in metabolic syndrome.[2] Recent studies suggest that this syndrome may also occur in children.[3] Among children and adolescents, metabolic syndrome is associated with subsequent risk of type 2 diabetes mellitus and cardiovascular diseases in adulthood.[3] Considering recent global rise of childhood obesity prevalence, the overall prevalence of the metabolic syndrome in children and adolescents seems to be higher than what is estimated from previous studies.[3]
Leptin is a peptide produced by differentiated adipocytes.[4] It is thought to be a key hormone in the regulation of body fat stores. This peptide controls energy metabolism at the level of hypothalamus by supporting food intake and stimulating energy expenditure.[4] The relationship between serum leptin and body mass index has been well established.[5] Leptin is also proposed to be associated with insulin resistance and diabetes in human.[6] However, potential relationship between metabolic syndrome and leptin has not been sufficiently addressed in previous studies, particularly in children.[7]
The present study aims to evaluate such a relationship between plasma leptin and metabolic syndrome in Iranian obese children.
Materials and Methods
Participants
This cross-sectional study was carried out on primary school students of the 6th district of Tehran, Iran. All schools in this area were included in the study. Children with a waist circumference equal to or above 90th percentile of their age and height were invited to attend a school-based clinic. The number of children who accepted to participate in the study was 563.
Children who had history of primary hyperlipidemia, diabetes and secondary obesity were excluded from the study. In addition to participants with uncompleted data, any child receiving pharmacological treatment that could affect the metabolic profile was also excluded. 505 children were included in the final analysis. All children had similar lifestyle with no significant physical training program. Before beginning the study, all parents submitted written informed consents and the study was authorized by the ethical investigation committee of Tehran University of Medical science.
Clinical Assessment
Research physicians recorded body weight to the nearest 0.5 Kilograms (kg) using a standard beam balance scale with subjects barefooted and wearing light indoor clothes. Body height was recorded to the nearest 0.5 centimeter (cm). BMI was calculated as the ratio of body weight to body height squared expressed as Kg/m 2sub . Waist circumference was measured at the distal third of the line from the xyphoid process to the umbilicus. Hip circumference was measured 4 cm below the anterior superior process of the iliac spine. Participants were classified to overweight or obese using international sex and age specific BMI cut-offs recommended by the International Obesity Task Force (IOTF).[8] The physicians measured blood pressure (BP) of the right arm in a sitting position after 5 minutes of rest, using an appropriate cuff size. The first and forth Korotkoff sounds were recorded as systolic and diastolic BP. Blood pressure was measured again after 5 minutes of rest and the average was used in the analysis.
Blood Sampling and Analysis
After overnight fasting, blood samples were collected from a vein in the antecubital fossa without venous occlusion. All collections were made between 8:00 and 9:00 am. The samples were immediately centrifuged for serum separation and stored at -20 degrees centigrade. Glucose were measured through calorimetric assays (Pars Azmoon kit; Iran) using automatic serum auto analyzer (Hitachi 902; Boehringer Manneheim, Germany). Serum leptin was measured by a commercial ELISA kit (ALEXIS San Diego, USA).
Diagnosis of metabolic syndrome was established when three or more of the following was presented: glucose levels greater than 100 mg/dl or 5.5 mmol/l according to American Diabetes Association recommendations (which is the same for children and adolescents),[9] at least one of the systolic or diastolic blood pressures above the 90th percentile for age and sex,[9] waist circumference above the 90th percentile for age and gender according to data from NHANES III,[9] triglyceride levels above the 95th percentile, and HDL levels below the 5th percentile for age and gender.[10]
Statistical Analysis
As leptin levels in our sample did not follows a normal distribution, we used non-parametric statistical tests (Mann-Whitney U test) to compare leptin levels between two groups of metabolic and non-metabolic syndrome participants. All data are expressed as mean ± standard deviations, except for leptin that is expressed as median (inter-quartile range). Multivariate logistic regression analyses were performed to evaluate the association of leptin levels with other metabolic variables. P value of 0.05 or less was considered as statistically significant. All statistical analyses were conducted using SPSS package (Version 11.5, Chicago, IL).
Results
The anthropometric and biochemical characteristics of the participants are summarized in table1. Of the 505 participants, 51.1% were boys and 48.9% were girls with the mean age of 9.5 ± 1.2. The number of children with metabolic syndrome was 105 (20.8 %). Waist, BMI and systolic blood pressure were significantly higher in boys comparing to girls (P < 0.05). Serum leptin level was significantly higher in girls in comparison to the boys
(P = 0.007).
The mean levels of biochemical and anthropometric variables of children with and without metabolic syndrome are summarized in table2. Children with metabolic syndrome were significantly more obese than others. HDL cholesterol levels were not different between two groups table2.
Median level of leptin was 11.3 in children with metabolic syndrome and 8.9 in children without metabolic syndrome. The difference was significant in Mann-Whitney U test (P: 0.045). After adjustment for BMI and sex in multivariable logistic regression analysis, there was no significant association between leptin and metabolic syndrome status (Odds Ratio: 0.949, 95% CI: 0.582-1.547). The correlation matrix between the study variables are presented in table3. There were significant correlations between leptin levels and systolic and diastolic blood pressures and triglyceride levels (P<0.05).
Discussion
Metabolic syndrome, a well-recognized constellation of risk factors for type 2 diabetes and atherosclerotic cardiovascular diseases, has its roots in childhood. Autopsy studies have revealed that early evidence of disease processes can be found in childhood [11]. Many studies showed that weight gain has a potent role in this syndrome.[4] With recent marked increase in childhood obesity prevalence, questions regarding the role of obesity-related factors such as leptin in children have increased in importance.[4]
Leptin is a product of ob gene and is expressed only in adipose tissues.[12] It circulates in plasma in a free or bound to leptin-binding proteins.[12] Leptin levels reflect not only the amount of fat stored in the adipose tissues, but also energy imbalance; prolonged fasting, for instance, substantially decreases leptin levels, whereas overfeeding greatly increases them.[12] The role of leptin in the pathophysiology of obesity and related disorders has been reviewed systematically.[12] Although the number of relevant publications shows a great rise in recent years, but most of these studies are about adult subjects and lower attention has been paid to childhood obesity and the role of leptin.
We found that the girls had higher plasma leptin levels comparing to the boys. This finding is in line with the hypothesis that there are gender differences in leptin synthesis, transport or clearance rates.[2] In normal children, leptin levels increase before puberty as body fat mass increases and reach their peak at the onset of puberty, suggesting that leptin may trigger puberty in humans. The difference in genders may be explained by later puberty development among boys and to greater accretion of fat mass in girls in contrast to the greater increase in lean mass in boys during adolescence.[2]
Leptin concentration in our study is significantly higher in obese children than non-obese, which is similar to previous studies.[13], [14] These finding suggests that BMI is the main determinants for the variations of leptin. In addition, it also suggests that resistance to the effects of leptin may start in early childhood.[13], [14]
The results of our study are also consistent with other studies that have shown relationships between leptin levels and serum lipid concentrations.[15], [16] The significant correlation between triglyceride and leptin are similar to other studies that have shown leptin is related to the levels of triglycerides. One study has suggested that triglyceride levels explain 38% of the variation in leptin.[13] However, some studies believe that this association was dependent on adiposity and total body fatness.[4]
Similar to other studies, we found that hypertension is related to high levels of leptin.[7],[17] This phenomenon may be due to potential vaso-constrictive effects of leptin as a result of increased sympathetic activity.[17] In addition, leptin may act through indirect pathways such as rennin, aldosterone, and angiotensinogen. Despite these suggestions, the mechanisms underlying the relationship between leptin and blood pressure are still unclear.[18]
Development of hyperinsulinemia and metabolic syndrome is suggested to be a consequence of hyperleptinemia in obese subjects.[12], [17] In our study, we found higher concentrations of plasma leptin in children with metabolic syndrome. However, this association disappeared after adjustment for BMI and sex in regression analysis. Although some studies have proposed leptin an independent predictor of insulin resistance and metabolic syndrome in children, our results did not confirm this finding.[2] Chu et al. showed that BMI and leptin are the predictor markers of hyperinsulinemia and metabolic syndrome among school children in Taiwan. Meanwhile, similar to our results, Park et al. showed that leptin have no major role in linking various components of the metabolic syndrome.[16] A possible explanation for such inconsistency is that the relationship between leptin and metabolic syndrome might be different in different ethnic groups. Future studies can verify this hypothesis.[16]
The main limitation of our study was lack of measurement of insulin and insulin resistance index. Therefore, we could not evaluate the relationship between leptin, hyperinsulinemia and metabolic syndrome. Based on the results of some studies in children and adolescents, leptin is an independent predictor of basal insulin and children with high plasma leptin levels have higher insulin levels.[17] However, Sudi et al. revealed that in the state of childhood and adolescent obesity, total adiposity but not insulin is the main determinant for leptin concentrations.[13]
In summary, this study has confirmed the significant difference in leptin levels between boys and girls as well as obese and non-obese children. There was a marginal difference in leptin levels between metabolic and non-metabolic syndrome children that was removed after adjustment for sex and BMI. Although leptin was strongly associated with obesity indices in this study, it did not appear to have a major role in metabolic syndrome. Further studies to evaluate such relationship in different ethnic groups are warranted.[19]
References
1. Moreno LA, Pineda I, Rodriguez G et al. Leptin and metabolic syndrome in obese and non-obese children. Horm Metab Res 2002; 34 : 394-399.
2. Chu NF, Wang DJ, Shieh SM et al . Plasma leptin concentrations and obesity in relation to insulin resistance syndrome components among school children in Taiwan-The Taipi Children Heart Study. Int J Obesity 2000; 24 : 1265-1271.
3. Weiss R, Dziura J, Burget TS et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004; 350: 2362-2374.
4. Steinberger J, Steffen L, Jacobs DR et al. Relation of leptin to insulin resistance syndrome in children. Obes Res 2003; 11: 1124-1130.
5. Erturk E, Kuru N, Savci V et al. Serum leptin levels correlate with obesity parameters but not with hyperinsulinism in women with polycystic ovary syndrome. Fertil Steril 2004;82 : 1364-1368.
6. Christos S, Mantzoros. The role of leptin in human obesity and disease: A review of current evidence. Ann Intern Med 1999; 130: 671-680.
7. Valle M, Gascon F, Martos R et al. Relationship between high plasma leptin concentrations and metabolic syndrome in obese pre-pubertal children. Int J Obesity 2003; 27 : 13-18 .
8. Cole TJ, Blezzi MC, Flegal KM et al. Establishing a standard definition for child overweight and obesity worldwide: International survey. BMJ 2000; 320 : 1240-1243.
9. Cruz ML, Goran MI. The metabolic syndrome in children and adolescents. Curr Diabetes Reports 2004; 4 : 53-62.
10. Lipid Research Clinivs: Population Studies Data Book, Vol 1. The prevalence study. Bethesda, MD, Department of Health and human services, Publication (NIH) 80-1527.
11. Chen W, Srinivasan SR, Li S . Metabolic syndrome variables at low levels in childhood are beneficially associated with adulthood cardiovascular risk. Diabetes Care 2005; 28 : 126-131.
12. Remesar X, Rafecas I, Fernandez-Lopez JA et al . Is leptin an insulin counter-regulatory hormone FEBS letters 1997; 402 : 9-11.
13. Sudi K, Gallistl S, Trobunger M et al. Insulin and insulin resistance index are not independent determinants for the variation in leptin in obese children and adolescents. J Pediatr Endocrinol Metab 2000; 13 : 923-932.
14. Zimmet P, Hodge A, Nicolson M et al. Serum leptin concentration, obesity, and insulin resistance in Western Samoas: cross sectional study. BMJ 1996; 13 : 965-969.
15. Shimabukuro M, Koyama K, Chen G et al. Direct antidiabetic effect of leptin through triglyceride depletion of tissue. Proc Natl Acad Sci USA 1997; 94 : 4637-4641.
16. Park HS, Lee MS, Park JY. Leptin and the metabolic syndrome in Korean adolescents: Factor analysis. Ped Int 2004; 46 : 697-703.
17. Nishina M, Kikuchi T, Yamazaki H et al . Relationship among systolic blood pressure, serum insulin and leptin,and visceral fat accumulation in obese children. Hypertens Res 2003; 26 : 281-288.
18. Chu NF, Wang DJ, Shieh SM. Obesity, leptin and blood pressure among children in Taiwan: The Taipei children's heart study. AJH 2001; 14 : 135-140.
19. Leyva F, Godsland IF, Ghatei M et al Hyperleptinemia as a component of a metabolic syndrome of cardiovascular risk. ArtheriosclerThromb Vasc Biol 1998; 18 : 928-933.(Hamidi Anahita, Fakhrzade)