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 Table of Contents  
REVIEW ARTICLE
Year : 2014  |  Volume : 1  |  Issue : 4  |  Page : 238-244

Metabolic syndrome in pediatric age - A group requiring intensive review


1 Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India
2 Department of Public Health, International Union, IUATLD South Asia Office, Qutub Institutional Area, New Delhi, India

Date of Submission07-Jun-2014
Date of Decision22-Nov-2014
Date of Acceptance27-Nov-2014
Date of Web Publication11-Dec-2014

Correspondence Address:
Vanita L Das
Associate Professor, Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan 342 005
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2347-9906.146803

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  Abstract 

Metabolic syndrome or MS as it is called is a compilation of most of the non-communicable disease components which is a life style disease with strong genetic predisposition, culminating in a morbid adulthood. The increasing number of subjects under the umbrella of MS is alarming. Diabetes mellitus, hypertension is the end result of this insulin resistance as it is sometimes called. Apart from genes, it also has strong inflammatory components that are responsible for early onset of MS. MS is marked by a gamut of inflammatory and non-inflammatory markers. If diagnosed early by screening the population, the percentage of florid cases of this debilitating syndrome can be brought down. Active intervention and constant monitoring of affected or predisposed young subjects will curtail the progress of MS and prevent full blown diabetes and hypertension, thus reducing cardiovascular complications, other morbidity and early mortality. Prevention is always better than cure.

Keywords: Adolescents, genes involved, markers, metabolic syndrome


How to cite this article:
Das VL, Purohit P, Sharma P, Das A. Metabolic syndrome in pediatric age - A group requiring intensive review. J Obes Metab Res 2014;1:238-44

How to cite this URL:
Das VL, Purohit P, Sharma P, Das A. Metabolic syndrome in pediatric age - A group requiring intensive review. J Obes Metab Res [serial online] 2014 [cited 2021 Oct 16];1:238-44. Available from: https://www.jomrjournal.org/text.asp?2014/1/4/238/146803


  Introduction Top


The concept of metabolic syndrome (MS) is much discussed and debated over half a century now. Once mainly found in the adult population, there is this world wide surge of the syndrome X, which we now term as MS is also found in minors (pediatric age group). Gerald Reaven was one who pioneered the definition "as a link between insulin resistance (IR), hypertension, dyslipidemia, impaired glucose tolerance and other metabolic abnormalities associated with an increased risk of atherosclerotic cardiovascular diseases (CVDs) in adults". [1] In the grassroots level, the cause is IR, a phenomenon occurring in obese who have proven resistance to the insulin effect on carbohydrate and fat assimilation. [2] The pathogenesis of IR insulin resistance is clear. It is free fatty acid (FFA) accumulation in the liver, fat cells, pancreas and skeletal muscles of overweight and obese subjects interfere with the normal signaling cascade. FFA accumulation in the liver makes it resistant to insulin's action to be able to produce glucose. There is hyperinsulinemia that causes liver to become a "fat producing factory", further causing hypertriglyceridemia. Adipose tissues being resistant to insulin cause an increase in lipolysis with NEFA increasing in blood. The whole process begins in these subjects in childhood and manifests as CVD with/without hypertension. [3] As a result, pancreas needs to produce insulin production to maintain the normoglycemic state, promoting, in this way, FFA or NEFA accumulation further worsening IR and a vicious cycle ensues. Over the last decade, the concept of MS has evolved and is being defined now as a collection of clinical findings that cluster together with greater frequency than would be expected by random chance and predict the future development of diabetic mellitus (DM) and/CVD. [4],[5]

Insulin resistance was an essential requirement for the diagnosis of MS as defined by WHO in 1998 and European Group for the study of Insulin Resistance (EGIR) 1999. It is no longer a requirement in the more recent definitions used by NCEP/AHA/IDF-consensus 2004 and 2005. Now this has created a problem as MS, as of now, may include several different syndromes with different etiologies and outcomes. This has led to criticisms whether MS, at all is a clinical entity or not?

In contrast, the designation of IR is specific; representing a collection of clinical, biochemical findings that are associated with IR. This IR is a pathophysiologic construct with IR as the core etiological factor while MS is a cluster of interrelated risk factors for diabetes and CVD with no imputation of etiology. IR is recognized to be a possible causative factor at least in many cases.

All definitions differ by the degree or cut off points of dyslipidemia triglycerides (TG and high density lipoprotein cholesterol [HDL-C]), blood pressure (BP) and glucose concentration, [4],[5],[6] whether to use waist circumference (WC) or body mass index (BMI) as the measure of obesity, and to include IR or microalbuminuria as its components. [7]

In spite of the difficulty in translating the MS definition from adult to children, MS in children is commonly defined as the co-occurrence of three or more of the following features: Severe obesity (WC > than ninetieth gender and age specific percentile), dyslipidemia (increase in TG and decrease in HDL), hypertension and altered glucose metabolism as IGT and T2DM. [8],[9],[10],[11] Recent studies show that MS is far more common among children and adolescents than previously reported, and its prevalence increases directly with obesity. [12]

Recently, to overcome the conflicts arising from different definitions, the International Diabetes Federation consensus group has come up with an easy definition that can be easily applied in a clinical set up [Table 1]. The confounding definitions now used make it difficult to follow MS in pediatric age group. Studies nine have clearly concluded how the prevalence of MS is dramatically influenced by changes in defining criteria (15-50%). Also, MS and Obesity are strongly interlinked but never the same. Ethnicity has also to be a serious concern while evaluating and defining as caucasians are more insulin resistant than African-American and Hispanics. Definition of MS is difficult as compared to adults as normal reference range of HDL, TG, WC and BP are lacking in children age group worldwide. Although we do not have consensus to define and diagnose MS in adult and children, MS is associated with 1.5 fold increase in overall mortality and 2.5 fold increase in cardiovascular mortality. [13] To determine the prevalence of MS in children and adolescents, either the adult criteria are modified for pediatrics reference values or a specific cut off points are used. Some studies suggest cut off points corresponding to 95 th percentile of each variable by sex, age and height percentile when including BP. However, the lack of consensus prevalence of this syndrome is markedly different in different studies.
Table 1: International diabetic federation criteria for metabolic syndrome in children


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International Diabetes Federation Criteria for MS in Children. (Supported by WHO, NCEPATP III, EGSIR) requires Mandatory central/truncal obesity any two the given criteria.

Metabolic syndrome cannot be diagnosed <6 years of age but should be strictly monitored. Different reference range is also needed for different ethnicity. [7]

Earliest identification of MS in youth so as to intervene is of utmost importance. These subjects will be prevented from developing CVD or other metabolic issues in their adulthood. It is because of this advantage that several studies have been conducted on clinical parameters as predictors of MS and demonstrating a strong link between changes of risk variables as BMI, WC, HDL, TG, Glucose and Insulin from childhood to early adulthood and CVD later in their lifetime. Therefore, MS in Pediatrics Age Group has to be earmarked. Corner stone remains-agree or disagree, in spite of above limitations definitions still stand and need to be identified by the pediatricians. CDC and International Obesity Task Force have recognized BMI as the coronary artery risk. Higher than 85 th percentile is the cut off limit of "at risk overweight" and Children with BMI higher than 95 th percentile as overweight. [13],[14],[15] MS and Obesity - prevalence and severity wise are strongly associated. [9] However, obesity per se is not the only predictor sufficient for identifying children at risk for MS and consequently CAD. Fat distribution is one that plays an important in influencing the occurrence of metabolic complications consequent to obesity. Visceral fat distribution is strongly associated with MS in childhood. [16] and CAD later in life. WCis recognized as the best clinical predictor of visceral fat accumulation. [17] Although reference values for WC do exist for few countries like USA, [18] Canada, [19] UK [20] Italy, [21] but no organization has endorsed a WCcut off for children.

Why measuring WC is important? Many multiracial cohort studies in pediatric age group have shown that subjects within a given BMI category with high circumference values are more likely to have increased CAD risk factors compared to low WC. [22] This shows that amongst the two, WC is a better predictor of MS as compared to BMI. In reality, as in the Adults [23],[24],[25],[26],[27] in children an increased WC has been correlated with abnormal systolic and diastolic BP, elevated level of serum cholesterol, high low-density lipoproteins (LDL), TG, insulin and low HDL concentrations. [28],[29],[30] The association between the clustering of cardiovascular risk factors and WC is not only a reflection of the degree of obesity but has a psychopathologic background. Visceral Obesity is the main risk factor for the development of IR, DM, hypertension, CVD. [31],[32] Visceral fat produces local tissue derived hormones and cytokines such as TNF-alpha, leptin, adiponectin and resistin. There is impaired hepatic glucose production, [33] increased portal efflux of NEFA/FFA and production of glycerol (viscous trihydric alcohol) by adipose tissues. [34] Some researchers have shown that removal of visceral fat abolishes IR and other consequent metabolic complications. Removal was added with increased hepatic insulin action. [35],[36] Family history needs to be deeply investigated as the heritability for MS has been well demonstrated, [37],[38] apart from anthropometric measurements obtained during the physical examination such a BMI and WC. It can enrich or strengthen the data collected. In fact, heritability for obesity ranges from 60% to 80% and heritability for BP varies from 11% to 37%. Lipid profile inheritance varies from 43% to 54%. Moreover, a recent study by Weiss et al. shows that those children who do not show MS early on childhood are less prone to develop it later, further supporting, indirectly, a strong genetic component in the development of MS. [39] Fetal malnutrition is now attributed to be the possible cause of MS. LBW and low birth at 1 year of age correlate with type 2 DM four to five decades later. A similar relationship with LBW has been shown for hypertension, visceral obesity, dyslipidemia, procoagulant state and coronary artery disease (CAD). The thrifty phenotype hypothesis that focuses on impaired fetal growth, induced by insufficient maternal nutrition or placental dysfunction has been associated with increased risk of developing MS. [40] Those that are growth restricted during fetal life, but subsequently grow rapidly and achieve a higher body weight are the most affected children and show increased adiposity in childhood and later adult life associated with IR. [41] Aside from genetic defects, which typically produce severe early onset obesity, more subtle alterations such as the nutritional level experienced in early life have been shown to result in impaired energy balance regulation, and are associated with development of a florid case of MS. [42] It is suggested that fetal malnutrition leads to MS later in life, but mechanisms are unknown. Phillips et al. have shown that fasting plasma cortisol concentration in men are inversely correlated with birth weight and positively correlated with systolic BP, fasting and 2 h plasma glucose concentrations during the oral glucose challenge, plasma TG and IR. They have speculated that fetal malnutrition is thought to lead to deficient B-cell development which predetermines B cell failure later in life. [43]

Metabolic phenotype of children and adolescents with MS has been studied. [44] All patients should be investigated for IR as it is the hallmark or pathogenic primers for the development of MS. Weiss et al. have demonstrated how the increase in IR parallels the risk of MS in obese children and adolescents. In this latter study, a strong correlation of IR to obesity and glucose metabolism and moderate correlation to dyslipidemia has been shown. Some studies suggest that hyperinsulinemia causes these alterations.

Insulin resistance is commonly referred to as MS. IR can be defined as the inability of insulin to produce its usual biological actions at circulating concentrations that are effective in normal subjects. In terms of glucose metabolism IR leads to impaired suppression of endogenous glucose production, under basal conditions as well as after eating when the physiological rise in insulin in response to glucose entry from the gut normally shuts down glucose production by the liver, and to reduced peripheral uptake of Glucose. This alterations result in hyperglycemia and a compensatory increase in insulin secretion. Resistance to the ability of insulin to suppress very low density lipoproteins (VLDL) production by the liver increases circulating serum which in turn leads to a decrease in HDL-C and formation of atherogenic, small dense, LDL particles. Resistance in adipose tissues increases the efflux of FFA both to the liver and the skeletal muscles, impairing the action of insulin on glucose metabolism in these tissues. [1] Resistance to other actions of insulin vasodilator and anti-platelet aggregation effects, also characterize IR in patients with type 2 DM.

The risk of death from CVD in these subjects is twofold as compared to those not meeting IDF criteria. Subjects meeting this criterion have 5 times greater risk of developing type 2 DM. Inflammatory markers are well investigated, and C-reactive protein (CRP) has been used as the hallmark of this proinflammatory state. CRP is a risk parameter for NIDDM and CVDs. CRP is an acute phase reactant and has been used for decades in the diagnosis and monitoring of acute infections and chronic inflammatory diseases. Some of the newer epidemiological studies have shown that increase in CRP concentrations, even when within the reference values can predict the development of type II diabetes, and CVDs, in an otherwise healthy population group. It is definitely a powerful risk marker, and some evidence suggests that CRP directly promotes atherosclerotic processes. [45] In adults plasma, CRP plasma concentrations are significantly associated with body fat as well as with specific components of MS including systolic BP and plasma concentrations and plasma concentrations of insulin, TG and HDL-C in the fasting state . [46]

But how does adiposity independently contribute to variations in the CRP? Some studies have shown that chronic simmering low-grade inflammation might be an early event in the development of IR and MS. [47] However, some studies have demonstrated that in some females who are obese but seemingly healthy, CRP levels were markedly increased among those insulin resistant and relationship between CRP and insulin resistant was independent of obesity suggesting that IR and/or other abnormalities associated with MS might induce inflammatory response. [48] Although the data are limited in children and adolescent age groups nevertheless association between CRP concentrations and cardiovascular risk factors have been observed to very similar with that of adults. [49],[50] Studies in children show a direct relationship as it has less likely confounding factors like chronic ailments: Bronchitis, arthritis, atherosclerosis and other undetected chronic diseases. Therefore, pediatric age group may help improve our concepts of relationship between obesity, inflammation, IR and MS. [51] In addition because CRP in youth, for a persistent time, may provide an early warning for later risk of developing cardiovascular diseases, it is important to precisely characterize the relationship between CRP values, excess weight add CVD risk factors in the young age-group and adolescents. [52] Each element of the syndrome worsens with increasing obesity, an association that is independent of age, sex and pubertal status. IR in obese children is strongly associated with specific adverse metabolic factor Reactive proteins and interleukin 6 (IL-6) levels, which are putative biomarkers of inflammation and potential predictors of adverse cardiovascular outcomes, rose with the diagnosis of obesity, whereas the levels of adiponectin, a biomarker of insulin sensitivity, decreased. [53] The degree of obesity in children and adolescents has important implications because the risk of deaths from all causes among adults with severe obesity is twice that among moderately obese adults.

There is a proven deleterious effect of increasing BMI among the children and adolescent age group. The influence of BMI on CRP (Z score) and IL-6 (a low grade inflammation marker) may increase as children become more obese. [54] Underlying inflammation is an additional factor contributing to adverse long-term cardiovascular outcomes in this age group.

IL-6, a well-known regulator of hepatic production of CRP, increases with obesity. Adiponectin, a biomarker for insulin sensitivity, has been implicated as having an important role in preventing athermanous plaques. [55] In contrast to CRP levels, Adiponectin levels drops with an increase in Z score of BMI. MS phenotype tends to persist over time and tends to progress clinically. However, a dramatic increase in the incidence of type II diabetes may represent only the tip of the iceberg and may herald the convergence of an epidemic of advanced CVD due to synergistic effects of other components of MS as well as chronic low-grade inflammation, as obese adolescents become obese young adults. CRP is a risk parameter for NIDDM and CVDs. CRP is an acute phase reactant and has been used for decades in the diagnosis and monitoring of acute infections and chronic inflammatory diseases. [56] Some of the newer epidemiological studies have shown that the increase in CRP concentrations, even when within the reference values can predict the development of type II diabetes and CVDs in an otherwise healthy population group. It is definitely a powerful risk marker, and some evidence suggests that CRP directly promotes atherosclerotic processes. In adult's plasma, CRP plasma concentrations are significantly associated with body fat as well as with specific components of MS including systolic BP.

Obesity component of MS is associated with chronic low-grade inflammation. Apart from the much studied factors described high mobility group box× 1 protein (HMGB1) play a key role in inflammation, immune stimulatory, and chemotactic processes. [57] It is a peptide marker for MS, and one of the studies showed a good correlation with homeostatic model assessment-IR (HOMA-IR), lipid profile, IL-18, IL-6, resistin levels while adiponectin levels is lowered. [58] Subclinical atherosclerosis, independent of classical risk factors for cardiovascular disease, as can be detected by serum markers in many patients of vasculitis can be caused by disease-related endothelial activation. [59] Adiponectin as a biomarker of MS in children and adolescents showed a negative correlation. [60] At multivariate analysis, HMGB1 independently correlated with BMI, free T3, HDL, and HOMA IR. At receiver operating characteristic analysis, HMGB1 showed a higher sensitivity and specificity than IL-6 and adiponectin. [61] Adipsin, visfatin are other biologically active molecules produced by the adipose tissue. The pro-inflammatory cytokines act through NF Kappa B and JNK systems. There is macrophage infiltration of adipose tissues and increase in the number of M1 or classically active macrophages. Macrophages have been described as the primary source of many circulating inflammatory molecules dealt above. But what causes this infiltration is not yet clear. Theories include altered signaling by adipocytes, nutritional induction of metabolic endotoxemia or reduced angiogenesis and local tissue hypoxia. PPAR gamma agonists have been shown to alter macrophage phenotype to M2 or an alternatively activated anti anti-inflammatory phenotype and may induce macrophage specific cell death. [62] This lipid disorder consists of elevations of serum TG, apolipoprotein B (apo B) and small (LDL) particles, and low levels of HDL. [63] It can be differentiated from elevated LDL cholesterol, which is the major lipid risk factor for CVD. Many controlled clinical trials show that the LDL-lowering therapy reduces the risk for CVD. [64] The connection between atherogenic dyslipidemia and CVD risk is more complicated than for LDL cholesterol; the multiple lipid abnormalities of atherogenic dyslipidemia make it difficult to dissect the contributions of each abnormality to CVD. These multiple abnormalities almost certainly promote the development of atherosclerosis. An important point to make, however, is that elevated total apo B overlaps with LDL cholesterol. In normal persons, apo B is mainly carried in LDL, whereas only small amounts are present in VLDL. When TG is elevated, however, a somewhat greater portion of apo B is found in VLDL. With atherogenic dyslipidemia, the LDL cholesterol level in the LDL fraction underestimates the number of LDL particles present, because these particles are partially depleted of cholesterol. In atherogenic dyslipidemia, the total apo B level frequently is abnormally elevated. There is growing evidence that all apo B-containing lipoproteins are atherogenic. Whether the different types of lipoproteins that carry apo B i.e., VLDL, large LDL, and small LDL have the same or different atherogenic potential is uncertain. Suggestive evidence points to small LDL particles being particularly atherogenic, but the evidence is not unequivocal. Some of the apparently higher atherogenicity of small LDL may be related to an increased number of LDL particles in the LDL fraction. [61],[65] The apparent relationship of atherogenic dyslipidemia to CVD risk raises a fundamental question: do elevated LDL cholesterol and atherogenic dyslipidemia carry a common denominator, namely, an increased number of apo B-containing lipoproteins in the circulation? If so, is the difference between the two conditions only apparent rather than real?

Another important component of atherogenic dyslipidemia is a low level of HDL-C. This reduced level may raise the risk for CVD; however, if so, what is the mechanism? At least three possibilities exist. [2] First, HDL may protect directly against the development of atherosclerosis. Second, low HDL level may indicate the presence of increases in atherogenic apo B-containing lipoproteins. Third, a low HDL commonly associates with the nonlipid risk factors of the MS. A low HDL also may be directly atherogenic because of a deficit in the protective effect of HDL. [66] Despite the traditional focus on LDL and CVD risk, a portion of the connection between blunted insulin signaling, abnormal lipid metabolism, and atherosclerosis appears to be mediated by aberrations in triglyceride/very low-density lipoprotein and HDL levels instead of LDL. [67] Derangements in adipocyte and hepatocyte function play a central role in these abnormalities. [68],[69]

 
  References Top

1.
Reaven GM. Banting Lecture 1988. Role of insulin resistance in human disease 1988. Nutrition 1997;13:65.  Back to cited text no. 1
    
2.
McGarry JD. Banting lecture 2001: Dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 2002;51:7-18.  Back to cited text no. 2
    
3.
Nathan BM, Moran A. Metabolic complications of obesity in childhood and adolescence: More than just diabetes. Curr Opin Endocrinol Diabetes Obes 2008;15:21-9.  Back to cited text no. 3
    
4.
Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005;365:1415-28.  Back to cited text no. 4
    
5.
Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome, an American Heart Association/National Heart, Lung and Blood Institute Scientific Statement. Circulation 2005;112:2735-52.  Back to cited text no. 5
    
6.
AlbertiK GM, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome. Circulation 2009;120:1640-5.  Back to cited text no. 6
    
7.
Zimmet P, Alberti KG, Kaufman F, Tajima N, Silink M, Arslanian S, et al. The metabolic syndrome in children and adolescents - An IDF consensus report. Pediatr Diabetes 2007;8:299-306.  Back to cited text no. 7
    
8.
Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH. Prevalence of a metabolic syndrome phenotype in adolescents: Findings from the third National Health and Nutrition Examination Survey, 1988-1994. Arch Pediatr Adolesc Med 2003;157:821-7.  Back to cited text no. 8
    
9.
Cruz ML, Weigensberg MJ, Huang TT, Ball G, Shaibi GQ, Goran MI. The metabolic syndrome in overweight Hispanic youth and the role of insulin sensitivity. J Clin Endocrinol Metab 2004;89:108-13.  Back to cited text no. 9
    
10.
Ford ES, Ajani UA, Mokdad AH, National Health and Nutrition Examination. The metabolic syndrome and concentrations of C-reactive protein among U.S. youth. Diabetes Care 2005;28:878-81.  Back to cited text no. 10
    
11.
de Ferranti SD, Gauvreau K, Lugwig DS, et al. Prevalence of MS in American Adolescents finding from 3 rd national health and nurtrition examination survey. Circulation 2004;110:2494-7.  Back to cited text no. 11
    
12.
Ogden CL, Flegal KM, Carroll MD, Johnson CL. Prevalence and trends in overweight among US children and adolescents, 1999-2000. JAMA 2002;288:1728-32.  Back to cited text no. 12
    
13.
Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: International survey. BMJ 2000;320:1240-3.  Back to cited text no. 13
    
14.
Himes JH, Dietz WH. Guidelines for overweight in adolescent preventive services: Recommendations from an expert committee. The expert committee on clinical guidelines for overweight in adolescent preventive services. Am J Clin Nutr 1994;59:307-16.  Back to cited text no. 14
    
15.
Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, Mei Z, et al. 2000 CDC Growth Charts for the United States: Methods and development. Vital Health Stat 11 2002;1-190.  Back to cited text no. 15
    
16.
Fernández JR, Redden DT, Pietrobelli A, Allison DB. Waist circumference percentiles in nationally representative samples of African-American, European-American, and Mexican-American children and adolescents. J Pediatr 2004;145:439-44.  Back to cited text no. 16
    
17.
Pouliot MC, Després JP, Lemieux S, Moorjani S, Bouchard C, Tremblay A, et al. Waist circumference and abdominal sagittal diameter: Best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women. Am J Cardiol 1994;73:460-8.  Back to cited text no. 17
    
18.
St-Pierre J, Lemieux I, Perron P, Brisson D, Santuré M, Vohl MC, et al. Relation of the "hypertriglyceridemic waist" phenotype to earlier manifestations of coronary artery disease in patients with glucose intolerance and type 2 diabetes mellitus. Am J Cardiol 2007;99:369-73.  Back to cited text no. 18
    
19.
Katzmarzyk PT. Waist circumference percentiles for Canadian youth 11-18y of age. Eur J Clin Nutr 2004;58:1011-5.  Back to cited text no. 19
    
20.
McCarthy HD, Jarrett KV, Crawley HF. The development of waist circumference percentiles in British children aged 5.0-16.9 y. Eur J Clin Nutr 2001;55:902-7.  Back to cited text no. 20
    
21.
Zannolli R, Morgese G. Waist percentiles: A simple test for atherogenic disease? Acta Paediatr 1996;85:1368-9.  Back to cited text no. 21
    
22.
Pouliot MC, Després JP, Lemieux S, Moorjani S, Bouchard C, Tremblay A, et al. Waist circumference and abdominal sagittal diameter: Best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women. Am J Cardiol 1994; 73:460-8.  Back to cited text no. 22
    
23.
Dobbelsteyn CJ, Joffres MR, MacLean DR, Flowerdew G. A comparative evaluation of waist circumference, waist-to-hip ratio and body mass index as indicators of cardiovascular risk factors. The Canadian heart health surveys. Int J Obes Relat Metab Disord 2001;25:652-61.  Back to cited text no. 23
    
24.
Janssen I, Katzmarzyk PT, Ross R. Body mass index, waist circumference, and health risk: Evidence in support of current National Institutes of Health guidelines. Arch Intern Med 2002;162:2074-9.  Back to cited text no. 24
    
25.
Janssen I, Heymsfield SB, Allison DB, Kotler DP, Ross R. Body mass index and waist circumference independently contribute to the prediction of nonabdominal, abdominal subcutaneous and visceral fat. Am J Clin Nutr 2002;75:683-8.  Back to cited text no. 25
    
26.
Thompson CJ, Ryu JE, Craven TE, Kahl FR, Crouse JR 3 rd . Central adipose distribution is related to coronary atherosclerosis. Arterioscler Thromb 1991;11:327-33.  Back to cited text no. 26
    
27.
Van Pelt RE, Evans EM, Schechtman KB, Ehsani AA, Kohrt WM. Waist circumference vs body mass index for prediction of disease risk in postmenopausal women. Int J Obes Relat Metab Disord 2001;25:1183-8.  Back to cited text no. 27
    
28.
Maffeis C, Pietrobelli A, Grezzani A, Provera S, Tatò L. Waist circumference and cardiovascular risk factors in prepubertal children. Obes Res 2001;9:179-87.  Back to cited text no. 28
    
29.
Freedman DS, Serdula MK, Srinivasan SR, Berenson GS. Relation of circumferences and skinfold thicknesses to lipid and insulin concentrations in children and adolescents: The Bogalusa heart study. Am J Clin Nutr 1999;69:308-17.  Back to cited text no. 29
    
30.
Savva SC, Tornaritis M, Savva ME, Kourides Y, Panagi A, Silikiotou N, et al. Waist circumference and waist-to-height ratio are better predictors of cardiovascular disease risk factors in children than body mass index. Int J Obes Relat Metab Disord 2000;24:1453-8.  Back to cited text no. 30
    
31.
Ferrannini E, Natali A, Capaldo B, Lehtovirta M, Jacob S, Yki-Järvinen H. Insulin resistance, hyperinsulinemia, and blood pressure: Role of age and obesity. European Group for the Study of Insulin Resistance (EGIR). Hypertension 1997;30:1144-9.  Back to cited text no. 31
    
32.
Fujimoto WY, Bergstrom RW, Boyko EJ, Chen KW, Leonetti DL, Newell-Morris L, et al. Visceral adiposity and incident coronary heart disease in Japanese-American men. The 10-year follow-up results of the Seattle Japanese-American Community Diabetes study. Diabetes Care 1999;22:1808-12.  Back to cited text no. 32
    
33.
O'Shaughnessy IM, Myers TJ, Stepniakowski K, Nazzaro P, Kelly TM, Hoffmann RG, et al. Glucose metabolism in abdominally obese hypertensive and normotensive subjects. Hypertension 1995;26:186-92.  Back to cited text no. 33
    
34.
Williamson JR, Kreisberg RA, Felts PW. Mechanism for the stimulation of gluconeogenesis by fatty acids in perfused rat liver. Proc Natl Acad Sci U S A 1966;56:247-54.  Back to cited text no. 34
    
35.
Barzilai N, She L, Liu BQ, Vuguin P, Cohen P, Wang J, et al. Surgical removal of visceral fat reverses hepatic insulin resistance. Diabetes 1999;48:94-8.  Back to cited text no. 35
    
36.
Kim YW, Kim JY, Lee SK. Surgical removal of visceral fat decreases plasma free fatty acid and increases insulin sensitivity on liver and peripheral tissue in monosodium glutamate (MSG)-obese rats. J Korean Med Sci 1999;14:539-45.  Back to cited text no. 36
    
37.
Terán-García M, Bouchard C. Genetics of the metabolic syndrome. Appl Physiol Nutr Metab 2007;32:89-114.  Back to cited text no. 37
    
38.
Kraja AT, Hunt SC, Pankow JS, Myers RH, Heiss G, Lewis CE, et al. An evaluation of metabolic syndrome in hyper GEN study. Nutr Metab 2005;2:2.  Back to cited text no. 38
    
39.
Hales CN, Barker DJ. The thrifty phenotype hypothesis. Br Med Bull 2001;60:5-20.  Back to cited text no. 39
    
40.
Forsén T, Eriksson J, Tuomilehto J, Reunanen A, Osmond C, Barker D. The fetal and childhood growth of persons who develop type 2 diabetes. Ann Intern Med 2000;133:176-82.  Back to cited text no. 40
    
41.
Yajnik C. Interactions of perturbations in intrauterine growth and growth during childhood on the risk of adult-onset disease. Proc Nutr Soc 2000;59:257-65.  Back to cited text no. 41
    
42.
Ong KK, Loos RJ. Rapid infancy weight gain and subsequent obesity: Systematic reviews and hopeful suggestions. Acta Paediatr 2006;95:904-8.  Back to cited text no. 42
    
43.
Troiano RP, Flegal KM. Overweight children and adolescents: Description, epidemiology, and demographics. Pediatrics 1998;101:497-504.  Back to cited text no. 43
    
44.
Weiss R, Shaw M, Savoye M, Caprio S. Obesity dynamics and cardiovascular risk factor stability in obese adolescents. Pediatr Diabetes 2009;10:360-7.  Back to cited text no. 44
    
45.
van Dielen FM, Buurman WA, Hadfoune M, Nijhuis J, Greve JW. Macrophage inhibitory factor, plasminogen activator inhibitor-1, other acute phase proteins, and inflammatory mediators normalize as a result of weight loss in morbidly obese subjects treated with gastric restrictive surgery. J Clin Endocrinol Metab 2004;89:4062-8.  Back to cited text no. 45
    
46.
Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Low-grade systemic inflammation in overweight children. Pediatrics 2001;107:E13.  Back to cited text no. 46
    
47.
Laws A, King AC, Haskell WL, Reaven GM. Relation of fasting plasma insulin concentration to high density lipoprotein cholesterol and triglyceride concentrations in men. Arterioscler Thromb 1991;11:1636-42.  Back to cited text no. 47
    
48.
Gelaye B, Revilla L, Lopez T, Suarez L, Sanchez SE, Hevner K, et al. Association between insulin resistance and c-reactive protein among Peruvian adults. Diabetol Metab Syndr 2010;2:30.  Back to cited text no. 48
    
49.
Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000;102:2165-8.  Back to cited text no. 49
    
50.
Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO 3 rd , Criqui M, et al. Markers of inflammation and cardiovascular disease: Application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003;107:499-511.  Back to cited text no. 50
    
51.
Steinberger J, Daniels SR, Eckel RH, Hayman L, Lustig RH, McCrindle B, et al. Progress and challenges in metabolic syndrome in children and adolescents: A scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular Nursing; and Council on Nutrition, Physical Activity, and Metabolism. Circulation 2009;119:628-47.  Back to cited text no. 51
    
52.
Rutter MK, Meigs JB, Sullivan LM, D'Agostino RB Sr, Wilson PW. C-reactive protein, the metabolic syndrome, and prediction of cardiovascular events in the Framingham Offspring Study. Circulation 2004;110:380-5.  Back to cited text no. 52
    
53.
Meier U, Gressner AM. Endocrine regulation of energy metabolism: Review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem 2004;50:1511-25.  Back to cited text no. 53
    
54.
Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW, et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004;350:2362-74.  Back to cited text no. 54
    
55.
Shimada K, Miyazaki T, Daida H. Adiponectin and atherosclerotic disease. Clin Chim Acta 2004;344:1-12.  Back to cited text no. 55
    
56.
Ridker PM, Cannon CP, Morrow D, Rifai N, Rose LM, McCabe CH, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med 2005;352:20-8.  Back to cited text no. 56
    
57.
Arrigo T, Chirico V, Salpietro V, Munafò C, Ferraù V, Gitto E, et al. High-mobility group protein B1: A new biomarker of metabolic syndrome in obese children. Eur J Endocrinol 2013;168:631-8.  Back to cited text no. 57
    
58.
Gil-Campos M, Cañete RR, Gil A. Adiponectin, the missing link in insulin resistance and obesity. Clin Nutr 2004;23:963-74.  Back to cited text no. 58
    
59.
Zycinska K, Wardyn KA, Piotrowska E, Zielonka TM, Zycinski H, Bogaczewicz A, et al. Rhinologic and sinonasal changes in PR3 ANCA pulmonary vasculitis. Eur J Med Res 2010;15 Suppl 2:241-3.  Back to cited text no. 59
    
60.
Arrigo T, Chirico V, Salpietro V, Munafò C, Ferraù V, Gitto E, et al. High-mobility group protein B1: A new biomarker of metabolic syndrome in obese children. Eur J Endocrinol 2013;168:631-8.  Back to cited text no. 60
    
61.
Heilbronn LK, Campbell LV. Adipose tissue macrophages, low grade inflammation and insulin resistance in human obesity. Curr Pharm Des 2008;14:1225-30.  Back to cited text no. 61
    
62.
Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: A meta-analysis of population-based prospective studies. J Cardiovasc Risk 1996;3:213-9.  Back to cited text no. 62
    
63.
Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E. Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation 1999;100:230-5.  Back to cited text no. 63
    
64.
Grundy SM. Small LDL, atherogenic dyslipidemia, and the metabolic syndrome. Circulation 1997;95:1-4.  Back to cited text no. 64
    
65.
Reaven GM, Chen YD, Jeppesen J, Maheux P, Krauss RM. Insulin resistance and hyperinsulinemia in individuals with small, dense low density lipoprotein particles. J Clin Invest 1993;92:141-6.  Back to cited text no. 65
    
66.
Wellen KE, Hotamisligil GS. Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 2003;112:1785-8.  Back to cited text no. 66
    
67.
Wilson PW, D'Agostino RB, Parise H, Sullivan L, Meigs JB. Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation 2005;112:3066-72.  Back to cited text no. 67
    
68.
Larsson B, Svärdsudd K, Welin L, Wilhelmsen L, Björntorp P, Tibblin G. Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13 year follow up of participants in the study of men born in 1913. Br Med J (Clin Res Ed) 1984;288:1401-4.  Back to cited text no. 68
    
69.
Goodpaster BH, Kelley DE, Wing RR, Meier A, Thaete FL. Effects of weight loss on regional fat distribution and insulin sensitivity in obesity. Diabetes 1999; 48:839-47.  Back to cited text no. 69
    



 
 
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