Biochemical and Hormonal Changes in Childhood Obesity

Biochemical and hormonal Changes in puerility fleshinessThe preponderance of chronic or non cistrontic ailment is escalating ofttimes more than rapidly in create countries than in indus streamletise countries. According to World Health Organization (WHO) estimates, by the 2020, non transmitted un healthinesss give account for approximately collar quarter of exclusively told deaths in the developing countries (WHO. Global Strategy for non communic adapted distemper pr subjection, 1997). In this regard, a probable emerging overt health issue for the developing countries may be change magnitude relative incidence of babyhood corpulency with associated branchings, which in gimmick is capability to create public health burden for poorer nations in the dear(p) succeeding(a) (Freedman et al, 2001). Lower to middle income nations face the double burden of having twain undernourish and e trulyplace nourished population, with middling ab bug come out over incubus and gamey children creation concentrate in urban aras. Rapid urbanization is associated with unhealthy spiritstyle or naked as a jaybird World Syndrome. In addition, in such(prenominal) communities, puerility fleshiness is still projected a sign of healthiness and advanced accessible class. on that point is no universal consensus on a cut transfer points for delimitate sullen and fleshiness in children and adolescents, usu tout ensembley, for clinical pr trifleice and epidemiological studies, child sound and fleshiness atomic routine 18 assessed by means of indicators ground on fish and apex measurements, such as pitch for height measures or consistency mussiness list ( slant (kg)/height (m2))(WHO. Report serial no.847, 1995).The US Centers for Disease Control and Prevention (CDC) defines corpulent as macrocosm at or to a higher place ninety-fifth percentile of electronic organic structure mass index for bestride (Kuczmarsk RJ et al, 200 0).History of fleshiness is some(prenominal) interesting and gives detail of its progression. corpulency is an eon-old health condition. by dint of and by means of out the tarradiddle of fleshiness, its composition varies from cargo hold and opposite among cultures and in magazine. Ancient Egyptians be said to consider fleshiness as disease. Perhaps the most famous and early testify of fleshiness is the Venus figurines, Statuettes of an pear-shaped female torso that probably had a meditate grapheme in rituals. Ancient China has overly been advised of obesity and dangers that come with it. They always were a believer of measure as a dis tightly fitting to longevity. The Aztecs believed that obesity was supernatural, an affliction of the gods. Hippocrates, the ampleher of medicines was aw argon of choppy deaths being more leafy vegetable among grave men than lean angiotensin converting enzymes as utter in his writings. In certain cultures and beas where fo od is scarce and mendi squeeze outcy is prevalent, is viewed as symbol of wealth and social status. To period, an Afri faeces tribe by design plumps up a bride to prep are her for child bearing. Before a hymeneals preserve be set, a slim bride is pampered to gain cargo until she r some(prenominal)lyes the suited weight.Through out the history of obesity, the publics view and status of obesity changed advant ripenously in the 1900s. It was regarded as unfashionable by the French designer, Paul Poi drench who designed skin-revealing clothes for women. About the same time, the incidence of obesity began to affix and set out wide spread. Later in 1940s, Metropolitan life restitution make a chart of ideal weight for various heights. They as salubrious advocated that weight gain parallel to maturate is unhealthy. The regime and medical night club require more hands-on with obesity by imitating campaign against it. This was preceded by a study of gamble of infection operators for cardiovascular disease revealing obesity in the gritty ranks. Since then various victualss and exercise programs claim emerged. In 1996, the trunk Mass Index (BMI) was published. This statistical calculation and index located that a person is grave or not. At this time ,obesity incidence turn in soared, led by children and adolescent obesity, tripling in just a a couple of(prenominal) short old age, greater than any estimate in the history of obesity. This append in the incidence of childhood obesity with associated cardiovascular chances, example 2 diabetes mellitus and stroke is condescended by a grand consistency of evidence.The prevalence of sarcoid and obesity in childhood and adolescents has been increase end-to-end much of the developed and developing being for the past few decennarys. It has expire increasingly clear that redundance adiposity in childhood predisposes soul not only to adjoin peril of adiposity and its sequaele as br ing upnups (Freedman et al, 2001), pictured in any case to change magnitude venture of multiple chronic diseases in childhood and adolescence (Rosen bloom et al, 1999). Though mechanism not clearly delineated, excess em bole weight and adiposity is associated with case 2 diabetes mellitus and its complications, cardiovascular disease assay divisors, non alcoholic gamy coloured disease and asthma in youth. childhood obesity 1930 1972Risk computes for coronary mettle disease (CHD) such as hypertension, dys lipidemia, damage glucose b localise and vascular abnormalities were front in gravid children. CHD is liable(predicate) to be increase in grave children when they become matures as a result of established risk factors. This study investigated whether excess weight in childhood was associated with CHD in collectable date among a very enlarged age bracket of persons born in Denmark in 1930 through and through 1972. They underwent mandatory one-year health exa mination at public or private naturalises in Copenhagen. individually child was examined by school doctors or nurses and was assigned a health card bearing childs name, date of race, birth weight account by parents. 10,235 men and 4,318 women, for whom childhood BMI selective information were in stock(predicate), accredited a diagnosis of CHD or died of CHD as adults. The risk of CHD event, a non calamitous event, and a calamitous event among adults was absolutely associated with BMI at 7-13 eld of age for boys and 10 to 13 eld of age as girls. The tie beams were additive for each age and risk increase a brush the entire BMI distribution.Childhood Obesity 1930 1972Risk factors for coronary heart disease (CHD) such as hypertension, dyslipidemia, impaired glucose tolerance and vascular abnormalities were play in dense children. CHD is probable to be increased in overweight children when they become adults as a result of established risk factors. This study investigat ed whether excess weight in childhood was associated with CHD in adulthood among a very large cohort of persons born in Denmark in 1930 through 1972. They underwent mandatory annual health examination at public or private schools in Copenhagen. Each child was examined by school doctors or nurses and was assigned a health card bearing childs name, date of birth, birth weight inform by parents. 10,235 men and 4,318 women, for whom childhood BMI info were available, received a diagnosis of CHD or died of CHD as adults. The risk of CHD event, a non fill outal event, and a avoirdupoisal event among adults was positively associated with BMI at 7-13 eld of age for boys and 10 to 13 long time of age as girls. The associations were linear for each age and risk increased crosswise the entire BMI distribution.Childhood Obesity and Economic Growth 1930-1983Childhood obesity was cerebrate to the scotch increment during the 50 age of economical growth in the modify world particularly in Denmark. Annual measurements of height and weight were available for all children born between 1930 and 1983 attending prime schools in Copenhagen Municipality. 165,389 boys and 163,609 girls from the age of 7 through 13 years were included in this study. later on cybernation SBMI (kg/m2) were calculated and the prevalence of overweight and obesity according to world(prenominal) age and genderspecific criteria. Economics growth was indicated by the swinish content Product and the overall inspiration per capita, familiarised for inflation. preponderance of overweight and obesity among Danish children rose in phases, which were not paralleled by trends in economic growth. The microeconomics growth indicators seem inappropriate as proxies for the environmental exposures that discombobulate enkindle the obesity epidemic.Childhood obesity and television reckonChildren put across a substantial portion of their lives observance television (TV). Investigators take up hypothes ized that TV consider causes obesity by one or more than three mechanisms excision of physical activity.Increased calorie consumption epoch watching or caused by the core groups of advertising.Reduced resting metabolism.The crosscurrent between TV backwash and obesity has been examined in a relatively large number of cross sectional epidemiological but few longitudinal studies. some of them deem ready relatively weak, positive association or combine results. some(prenominal) experimental studies have found that reducing TV viewing may help to sign on the risk of obesity. i school base experimental study was designed specifically to test directly the insouciant kind between TV viewing ways and trunk fatness. The results of this randomized bindled trial appropriate evidence that TV viewing is a cause of increased body fatness and that reducing the TV viewing is a undimmed strategy for preventing childhood obesity (Robinson 2001).The objective of another(prenomin al) study (Utter J et al, 2006), was to search how time spent watching television (TV) is associated with the dietary behavior of New Zealand children and young adolescents. Total number of participants was 3275 children remote 5-17 years. The findings suggest that durable succession of TV watching (thus more frequent exposure to advertising) influences the frequence of consumption of soft drinks, some sweets and snacks and some fast foods among children and young adolescents. Efforts to control the time spent watching TV may result in go bad dietary habits and weight control for children and adolescents.Childhood Obesity US- A decade of progress, 1990-1999Current selective information suggest that 20% of US children are overweight .An analysis of the secular trends suggest that 20% of US children are overweight, and a clear up ward trend in body weight in children of 0.2 Kg between 1973 and 1994. In addition, childhood obesity is more prevalent among minority sub groups such as Afri nookie Ameri sack ups. Obesity that begins early in life persists into adulthood and increases the risk of obesity link up conditions later in life. on that point has been tremendous increase in the number of studies examining the etiology and health burdens of obesity in children (Goran MI, 1990-1999).1980 (boys 0.2% girls 0.5%) and 1997 (boys 1.2%, girls 2.0%). 10 years trends of childhood obesity in Israel 1990-2000Cross sectional info was amass from 13284 endorsement and fifth class school children between 1990-2000. Prevalence of obesity was determined using Israeli and US fictional character value. BMI values at 95th percentile increased overtime in all ages and wake up categories.Between 1990 and 2000, 95th centile values were increased by 12.7%and 11.8% among second grade boys and girls respectively. Among fifth graders in 2000, 10.7% of boys and 11.1% of girls exceeded the 1990 BMI reference values. The proportion of obese children increased over time using b oth Israeli and US reference values (Huerta Michael et al, 2008).Netherlands. overweight, Obesity in 2003 V.1980-97. info on 90,071 children, aged 4-16 years were routinely collected by 11 Community heathland go during 2002-2004. International cut -off points for BMI to determine overweight and obesity. On average, 14.5% of boys and 17.5% of the girls were overweight (including obesity), which is a substantial increase since 1980 (boys 3.9% and girls 6.9%) and 1997 (boys 9.7% and girls 13%). Similarly 2.6% of the boys and 3.3% 0f the girls aged 4-16 years were obese, which is much high than in 1980 (boys 0.2% and girls 0.5%) and 1997 (boys 1.2% and girls 2.0%), (KatjaVan Den Husk, 2007).Obesity trends in US. 2003-2006 upside and weight measurements were obtained from 8164 children and adolescents as apart of the 2003-2004 and 2005-2006 National Health and Nutrition testing passel (NHANES). Because no statistically world-shaking differences in the prevalence of high BMI for age were found between the estimates for 2003-2004 and 2005-2006, data for four-spot years were feature to provide more stable estimates for the most recent time period. Over all, in 2003-2006, 11.3% of children and adolescents aged 2 through years were at or above 97th percentile of the 2000 BMI- for- age growth charts, 16.3% were at or above 95th percentile. Prevalence estimates vary by age and by racial/ heathen group. Analysis of the trends in high BMI for age showed no statistically signifi evictt trend over the four time periods (1999-2000, 2001-2002, 2003-2004, and 2005-2006) for either boys or girls (Cynthia l.Ogden et al, 2008).11-March 2005. cosmos Release Date Consensus on Childhood Obesity, Recommends classification as diseaseA common line of reasoning on childhood obesity was published to day in the journal of Chemical Endocrinology and Metabolism (one of the journals of hormone Society). The consensus statement reflects the conclusions from an international summit he ld in Israel last year (2004) and includes a controversial recommendation to classify obesity as a disease. This conclusiveness was found upon the available research on the diagnosis, prevalence, causes (including endocrine disorders), risks, prevention and intervention of childhood obesity. Pediatric obesity is now recognized as a major(ip)(ip) health problem all over the world. Researcher have found that children who are obese have a higher risks adult obesity, which is potently associated with many serious medical complications that impair quality of life and range to surplus increased risks. The statement in addition noted the prevalence of overweight/obesity among children 6-11 years (in the US) doubled between the years 1980-2000. By classifying obesity as legitimate disease, public funding and in substance abuser sreimbursement for obesity treatment becomes legalized (consensus on childhood obesity, 2005).Serious health risks pass on likely to begin to appear in obes e children and adolescents as they grow older. These may include diabetes mellitus, metabolous syndrome, hyperandrogenism, heart disease, hypertension, respiratory factors, and sleep disorders. pear-shaped children are besides at greater risk of anxiety and depression. It as intumesce as recommended a number of measures that can be implemented by parents schools, health providers and government and regulatory agencies to help to prevent the onset of childhood obesity endocrine Regulation of Energy Metabolism Adipocytokines and ObesityThe mechanism rudimentary obesity was further beg offed by the discovery of adipocytokines, the billet of peripheral thyroid gland hormones (T4, T3), thyroid stimulating hormone and insulin the standard of zip fastener metabolism. The levels of some of the adipocytokines were shown to be colligate to nonrational obesity, fictional character 2 diabetes mellitus and coronary artery disease. plasma levels of all the adipocytokines increase wit h the obesity except adiponectin (Yuji Matsuzawa et al, 2003).Recent studies point out to the fat wind as a highly active organ secreting a range of hormones, Leptin, Adiponectin, and Resistin. They are considered to take part in the regulation of energy metabolism. Leptin, Adiponectin and Resistin are produced by the adipose create from raw stuff. Leptin and Adiponectin are insulin sensitize while Resistin increase the insulin granting immunity.LeptinThe notion that transmitted abnormalities contribute to obesity gained all- weighty(a) support with the assignment of the Ob gene and its protein product in 1994 (Zhangy et al, 1996). The Ob gene termed Leptin from the classical Leptos, meaning thin, is produced in adipose tissue and is thought to act as an afferent satiety signal in a lean approve loop that chance upons the appetite and satiety centre in the hypothalamus of brain. The last effect of this loop is to regulate body-fat mass. In gentleman, as noted by Consid ine et al, 1996 caloric restriction reduces leptin concentrations and Ob mRNA levels in adipose tissue, and refeeding increases these levels. One fundamental frequency mechanism of obesity is insensitivity to the action of Leptin, presumably in the hypothalamus. The Leptins primal physiological function is to provide a signal to abolish body fat by decreasing food intake or increasing energy expenditure. serum leptin concentrations change more during weight waiver than during weight gain (Rosenbaum M et al, 1997).AdiponectinAdiponectin or Adipo Q, an adipocyte specific secreted protein with office staffs in glucose and lipid homeostasis (Insulin stimulates the discrimination of adiponectin). travel adiponectin concentrations are high 500-30,000 g/l (5-30mg/ml) chronicle for 0.01% of sum of money plasma proteins (Berget et al, 2002).Adiponectin was discovered in the mid 1990s by four contrary groups of researchers (Hu E et al, 1996). Adiponectin has various biological func tions including insulin sensitizing (Hotta K et al, 2000), antiatherogenic (Yamauchi T et al, 2003), anti- inflammatory (Ouchi N et al, 2003), antiangiogenic and anti tumor functions (Brakenhielm E et al, 2004). Adiponectin acts through Adiponectin receptors, Adipo R1 and Adipo R2. Adipo R1 is largely expressed in skeletal muscles and Adipo R2 is abundant in coloured. These receptors are overly expressed by the pancreatic carrels (Kharroubi et al, 2003), macrophages and atherosclerotic lesions (Chinetti et al, 2004) as salutary as in brain (Yamauchi et al, 2003). Circulating Adiponectin levels display diurnal stochastic variable with a nocturnal decline and maximum levels in the late sunup (Gavrila et al, 2003). Adiponectin is excessively found in breast milk, which in turn is involve in childhood obesity prevention (Savino et al, 2008).Among the various adipocytokines, adiponectin, which is an abundant locomote protein (247 aminic group acids) synthesized purely in adip ose tissue, appears to play a very important role in carbohydrates, lipid metabolism and vascular biology. Adiponectin appears to be a major modulator of insulin action and its levels are reduced in type 2 diabetes mellitus, which could contribute to peripheral insulin shelter in this condition. It has significant insulin sensitizing as well as anti inflammatory properties that include crushing of macrophage phagocytosis and TNF-a secretion and blockage of monocytes adhesion to endothelial cells in vitro. Although further investigations are required, Adiponectin administration, as well as regulation of the pathway controlling its production, represents a shining target for managing obesity, hyperlipidemia, insulin subway, type 2 diabetes mellitus, and vascular inflammation (Manju Chandran et al, 2003).Resistin benevolent resistin is 108 amino acids prepeptide and is cleaved before its secretion from the Adipose tissue. Resistin circulates in the kindred as dimeric protein cons isting of 92 amino acids polypeptides that are linked by a disulfide bridge. Holcomb et al, 2000 send-off describe the gene family and its tissue specific distribution. Originally described as lung specific, is also produced by the adipose tissue and peripheral blood monocytes. It is also present in dividing epithelia of the intestine. Resistin increase blood glucose and insulin concentration in the mice and impairs hypoglycaemic result to insulin infusion. In addition, anti resistin antibodies decrease blood glucose and insulin sensitivity in obese mice (Ukkalo O, 2002). The physiological role of resistin in human remains controversial. There more resistin protein in obese than lean individuals, with a significant positive correlation coefficient between resistin and BMI. BMI is a significant predictor of insulin opponent, but resistin adjusted for BMI is not. These data demonstrate that resistin protein is present in human adipose tissue and blood and that there is significant ly more resistin in serum of obese individuals. serum resistin is not a significant predictor of insulin metro in human (Youn et al, 2003, Rear R and Donnelly R, 2004).Tumor mortification constituent-aIt will be stupid not to mention the Tumor Necrosis Factor a and its role in vascular inflammation related to atherosclerosis especially in obesity.It is a cytokine involved in systemic inflammation and is a appendage of a group of cytokines that stimulate the acute phase reaction. The primary role of TNF is in the regulation of immune cells. TNF is able to pass water apoptotic cell death, to induce inflammation and to hold tumourgenesis and viral replication. Dysregulation and, in particular, over production of TNF have been implicate in a revolution of human diseases, as well as cancer (Locksley et al, 2001).The scheme of antitumoural chemical reaction of the immune system in vivo was recognized by the doctor William B in 1968. Dr A Granger reported a cytotoxic factor prod uced by lymphocytes and named it Lymphotoxin (Kalli WB and Granger GA, 1968). Dr L Loyal old, in 1975 reported another cytotoxic factor produced by macrophages and named it Tumor Necrosis Factor (TNF) (Cars well et al, 1975).Interleukin 6 (IL-6)Chronic inflammation is linked to endothelial dysfunction, atherosclerosis, and insulin resistor (Fernandez-Real JM and Ricart W, 2003 and Fernandez-Real JM, Ricart W, 2005). Plasma concentrations of proinflammatory cytokines, such as interleukin (IL) 18, IL-6, and tumor humiliation factor (TNF)-a, and of several(prenominal) other inflammatory markers are increased in patients with ischaemic heart disease (Fernandez-Real JM and Ricart W, 2003, Ridker PM et al, 2002, Engstrom G et al, 2004, Ridker PM et al, 1997, Pradham AD et al, 2002). Circulating cytokines also are elevated in type 2 diabetes, obesity, and insulin shelter syndrome and play a central role in the pathogenesis of these disorders (Fernandez-Real JM and Ricart W, 2003). IL- 6 is a intercessor of the inflammatory result, and it is linked to dyslipidemia, type 2 diabetes, and risk of myocardial infarction (Fernandez-Real JM and Ricart W, 2003, Ridker PM et al, 2000, Esteve E et al, 2005, Yudkin JS et al, 2000). IL-6 is secreted by a variety of different cell types, including lymphoid and endothelial cells, fibroblasts, skeletal muscle, and adipose tissue. Circulating IL-6 levels correlative with obesity and insulin resistance and may predict the evolution of type 2 diabetes mellitus (Yudkin JS et al, 2000, Pradhan AD et al, 2001, Akira S et al, 1993, Mohamed-Ali V et al, 1997). Endothelial dysfunction is regarded as a causative factor in the development of atherosclerosis (Hansson GK, 2005). It is one of the earliest abnormalities that can be detected in people at risk for cardiovascular events, and it is linked to insulin resistance and type 2 diabetes (Steinberg HO and world-beater AD, 2002, Natali A et al, 2006). Cytokines have an important role in the endothelial accidental injury generate by inflammation. The vascular endothelium is involved in the inflammatory response to atherosclerosis (Hansson GK, 2005, Steinberg HO and Baron AD, 2002, Natali A et al, 2006, Widlansky ME et al, 2003), and changes in endothelium function could be the association between cardiovascular disease and inflammation.Obesity Related Insulin confrontation definition and PathogenesisInsulin resistance is a state in which a presumption tot up of insulin produces a subnormal biological response (Kahn CR, 1978). In particular, it is characterized by a decrease in the ability of insulin to stimulate the use of glucose by muscles and adipose tissue and to suppress hepatic glucose production and output (Matthaei et al, 2000). Furthermore, it accounts a resistance to insulin action on protein and lipid metabolism and on vascular endothelial function and genes expression (Bajaj M and Defronzo RA, 2003). Several defects in the insulin mark cascade down have been implicated in the pathogenesis of insulin resistance, Insulin resistance is believed to have both genetic and environmental factors implicated in its etiology (Matthaei et al, 2000 and Liu et al, 2004). The genetic fragment seems to be polygenic in nature, and several genes have been suggested as potential candidates (Matthaei et al, 2000). However, several other factors can influence insulin sensitivity, such as obesity, ethnicity, gender, perinatal factors, puberty, sedentary lifestyle and diet (Liu et al, 2004).The Role of spicyty Acids and AdipocytokinesObesity represents the major risk factor for the development of insulin resistance in children and adolescents (Caprio S, 2002), and insulin resistance/hyperinsulinemia is believed to be an important link between obesity and the associated metabolous abnormalities and cardiovascular risk (Weiss R and Kaufman FR, 2008). Approximately, 55% of the variance in insulin sensitivity in children can be explained by tota l adiposity, after adjusting for other confounders, such as age, gender, ethnicity and pubertal stage (Caprio S, 2002). Obese children have hyperinsulinemia and peripheral insulin resistance with an 40% commence insulin-stimulated glucose metabolism than non-obese children (Caprio S et al, 19996). Adipose tissue seems to play a key role in the pathogenesis of insulin resistance through several released metabolites, hormones and adipocytokines that can affect different steps in insulin action (Matsuzawa Y, 2005) (Fig. 1). Adipocytes produce non-esterified fatty acids, which inhibit carbohydrate metabolism via substrate competition and impaired intracellular insulin communicate (Matsuzawa Y, 2005, Griffin ME et al 1999 and Randle PJ, 1998). In children, as in adults, several adipocytokines have been related to adiposity indexes as well as to insulin resistance. Adiponectin is one of the most common cytokines produced by adipose tissue, with an important insulin sensitizing effect as sociated with anti-atherogenetic properties (Despres JP, 2006 and Gil-Campos M et al, 2004). Whereas obesity is generally associated with an increased release of metabolites by adipose tissue, levels of Adiponectin are in return related to adiposity (Matsuzawa Y, 2005). Therefore, reduced levels of this adipocytokine have been implicated in the pathogenesis of insulin resistance and metabolic syndrome (Matsuzawa Y, 2005). Decreased levels of Adiponectin have been detected across tertiles of insulin resistance in children and adolescents (Weiss R et al, 2004), where it is a good predictor of insulin sensitivity, severally of adiposity (Lee S et al, 2006). Adipose tissue also produces tumour necrosis factor-a, an inflammatory factor, which can alter insulin action at different levels in the intracellular pathway (Matsuzawa Y, 2005). Interleukin-6 (IL-6) is another inflammatory cytokine released by adipose tissue and its levels are increased in obesity (Matsuzawa Y, 2005). IL-6 stimul ates the hepatic production of C-reactive protein and this can explain the state of inflammation associated with obesity, and could mediate, at least partially, obesity-related insulin resistance (Matsuzawa Y, 2005). Data found mainly on animal studies also suggest that increased levels of resistin, another molecule produced by adipose tissue, could impair insulin sensitivity (Matsuzawa Y, 2005). The close relationship between Leptin levels and insulin resistance in children has also been suggested by the data (Chu NF et al, 2000). Serum levels of retinol-binding protein 4 (RBP4) correlate with insulin resistance in subjects with obesity as well as in those with impaired glucose tolerance (IGT) or type 2 diabetes mellitus, therefore suggesting that it could be useful in assessing insulin resistance and the associated risk for complications (Graham TE et al, 2006). Serum RBP4 is independently related to obesity as well as to components of the metabolic syndrome in normal weight and overweight children (Aeberli I et al, 2007). forage composition in obese children might be an additional factor promoting and/or worsening insulin resistance. Animal and human studies suggest that a high energy intake as well as a diet rich in fat and carbohydrates and low in quality could increase the risk of developing insulin resistance (Canete R et al, 2007).The Role of Fat dispersionAn altered partitioning of fat between subcutaneous and visceral or ectopic sites has been associated with insulin resistance (Weiss R and Kaufman FR, 2008). Visceral fat has a part correlation with insulin sensitivity than subcutaneous or total body fat (Caprio S et al, 1995), in both obese adults and children. Visceral fat has higher lipolytic activity compared with subcutaneous fat, therefore a greater meter of withdraw fatty acids and glycerol gain entry or carried out to the liver (Matthaei et al, 2000). Visceral fat in girls is directly correlate to the glucose-stimulated insulin levels and inversely correlated with insulin sensitivity and the rate of glucose uptake. No correlation was found between abdominal subcutaneous fat (Caprio S et al, 1995). Ectopic deposition of fat in the liver or muscle can also be responsible for(p) for insulin resistance in obese subjects, as the accretion of fat in these sites impairs insulin signaling, with a reduced glucose uptake in the muscle and a decrease insulin-mediated suppression of hepatic glucose production (Weiss R and Kaufman FR, 2008). Intramyocellular lipid (IMCL) accumulation has been shown as a factor related to decreased insulin sensitivity (Jacob S et al, 1999 and Thamer C et al, 2003). Obese insulin sensitive children and adolescents present lower levels of visceral fat and IMCL when compared with obese insulin resistant children (Weiss R et al, 2005). Accumulation of fat in the liver has also been associated with insulin resistance, independently of adiposity (Kelley DE et al, 2003). It has also been sugges ted that deposits of fat around blood vessels can produce several cytokines and therefore contribute to the development of insulin resistance, through a so-called vasocrine effect (Yudkin JS et al, 2005).Insulin Resistance and Associated ComplicationsInsulin resistance in obesity is stringently related to the development of hypertension (Marcovecchio ML et al, 2006 and Cruz ML et al, 2002), dyslipidemia (Howard BV and Howard WJ, 1994), impaired glucose tolerance (IGT) (Sinha R et al, 2002), hepatic steatosis (DAdamo E et al, 2008), as well as to the cabal of these factors, also known as metabolic syndrome (Eckel RH et al, 2005). Furthermore, insulin resistance is associated with systemic inflammation, endothelial dysfunction, early atherosclerosis and disordered fibrinolysis (Dan Dona P et al, 2002). It is terrible that these metabolic and cardiovascular complications are already found in obese children and adolescents (Dietz WH, 2004). The front man of these alterations in prep ubertal children is then particularly worrying, as insulin resistance and related complications might be further exacerbated by the influence of puberty, due to the physiological decrease in insulin sensitivity associated with normal pubertal development (Caprio S et al, 1989). Insulin resistance in childhood can track in adult life (Sinaiko AR et al, 2006). Insulin resistance at the age of 13 years predicts insulin resistance at age 19 years, independently of BMI, and is also associated with cardiovascular risk in adulthood (Sinaiko AR et al, 2006). The fundamental role of insulin resistance in human disease was already recognized in 1988 by Reaven (Reaven GM, 1988) who emphasized its role in the development of a separate of metabolic abnormalities, which he defined as syndrome X. Later studies strengthened the belief of insulin resistance as a key component of the metabolic syndrome, a practice bundling of impaired glucose tolerance (IGT), dyslipidemia, hypertension, hyperinsul inemia, associated with an increased risk of type 2 diabetes mellitus and cardiovascular disease (Eckel RH et al, 2005). Insulin resistance represents a serious and common complication of obesity during childhood and adolescence. A timely diagnosis and an appropriated prevention and treatment of obesity and insulin resistance are required in order to reduce theBiochemical and Hormonal Changes in Childhood ObesityBiochemical and Hormonal Changes in Childhood ObesityThe prevalence of chronic or non communicable disease is escalating much more rapidly in developing countries than in industrialized countries. According to World Health Organization (WHO) estimates, by the 2020, non communicable diseases will account for approximately three quarter of all deaths in the developing countries (WHO. Global Strategy for non communicable disease prevention, 1997). In this regard, a potential emerging public health issue for the developing countries may be increasing incidence of childhood obesi ty with associated complications, which in turn is likely to create public health burden for poorer nations in the near future (Freedman et al, 2001). Lower to middle income nations face the double burden of having both malnourished and over nourished population, with most overweight and obese children being concentrated in urban areas. Rapid urbanization is associated with unhealthy lifestyle or New World Syndrome. In addition, in such communities, childhood obesity is still considered a sign of healthiness and high social class.There is no universal consensus on a cut off points for defining overweight and obesity in children and adolescents, usually, for clinical practice and epidemiological studies, child overweight and obesity are assessed by means of indicators based on weight and height measurements, such as weight for height measures or body mass index (weight (kg)/height (m2))(WHO. Report series no.847, 1995).The US Centers for Disease Control and Prevention (CDC) defines o bese as being at or above 95th percentile of body mass index for age (Kuczmarsk RJ et al, 2000).History of obesity is both interesting and gives details of its progression. Obesity is an age-old health condition. Through out the history of obesity, its reputation varies from appreciation and opposite among cultures and in time. Ancient Egyptians are said to consider obesity as disease. Perhaps the most famous and earliest evidence of obesity is the Venus figurines, Statuettes of an obese female torso that probably had a major role in rituals. Ancient China has also been aware of obesity and dangers that come with it. They always were a believer of prevention as a key to longevity. The Aztecs believed that obesity was supernatural, an affliction of the gods. Hippocrates, the father of medicines was aware of sudden deaths being more common among obese men than lean ones as stated in his writings. In certain cultures and areas where food is scarce and poverty is prevalent, is viewed as symbol of wealth and social status. To date, an African tribe purposely plumps up a bride to prepare her for child bearing. Before a wedding can be set, a slim bride is pampered to gain weight until she reaches the suitable weight.Through out the history of obesity, the publics view and status of obesity changed considerably in the 1900s. It was regarded as unfashionable by the French designer, Paul Poi ret who designed skin-revealing clothes for women. About the same time, the incidence of obesity began to increase and become wide spread. Later in 1940s, Metropolitan life insurance published a chart of ideal weight for various heights. They also advocated that weight gain parallel to age is unhealthy. The government and medical society become more hands-on with obesity by imitating campaign against it. This was preceded by a study of risk factors for cardiovascular disease revealing obesity in the high ranks. Since then various diets and exercise programs have emerged. In 1996, th e Body Mass Index (BMI) was published. This statistical calculation and index determined that a person is obese or not. At this time ,obesity incidence have soared, led by children and adolescent obesity, tripling in just a few short years, greater than any number in the history of obesity. This increase in the incidence of childhood obesity with associated cardiovascular risks, type 2 diabetes mellitus and stroke is supported by a considerable body of evidence.The prevalence of overweight and obesity in childhood and adolescents has been increasing throughout much of the developed and developing world for the past few decades. It has become increasingly clear that excess adiposity in childhood predisposes individual not only to increased risk of adiposity and its sequaele as adults (Freedman et al, 2001), but also to increased risk of multiple chronic diseases in childhood and adolescence (Rosen bloom et al, 1999). Though mechanism not clearly delineated, excess body weight and adi posity is associated with type 2 diabetes mellitus and its complications, cardiovascular disease risk factors, non alcoholic fatty liver disease and asthma in youth.Childhood Obesity 1930 1972Risk factors for coronary heart disease (CHD) such as hypertension, dyslipidemia, impaired glucose tolerance and vascular abnormalities were present in overweight children. CHD is likely to be increased in overweight children when they become adults as a result of established risk factors. This study investigated whether excess weight in childhood was associated with CHD in adulthood among a very large cohort of persons born in Denmark in 1930 through 1972. They underwent mandatory annual health examination at public or private schools in Copenhagen. Each child was examined by school doctors or nurses and was assigned a health card bearing childs name, date of birth, birth weight reported by parents. 10,235 men and 4,318 women, for whom childhood BMI data were available, received a diagnosis o f CHD or died of CHD as adults. The risk of CHD event, a non fatal event, and a fatal event among adults was positively associated with BMI at 7-13 years of age for boys and 10 to 13 years of age as girls. The associations were linear for each age and risk increased across the entire BMI distribution.Childhood Obesity 1930 1972Risk factors for coronary heart disease (CHD) such as hypertension, dyslipidemia, impaired glucose tolerance and vascular abnormalities were present in overweight children. CHD is likely to be increased in overweight children when they become adults as a result of established risk factors. This study investigated whether excess weight in childhood was associated with CHD in adulthood among a very large cohort of persons born in Denmark in 1930 through 1972. They underwent mandatory annual health examination at public or private schools in Copenhagen. Each child was examined by school doctors or nurses and was assigned a health card bearing childs name, date o f birth, birth weight reported by parents. 10,235 men and 4,318 women, for whom childhood BMI data were available, received a diagnosis of CHD or died of CHD as adults. The risk of CHD event, a non fatal event, and a fatal event among adults was positively associated with BMI at 7-13 years of age for boys and 10 to 13 years of age as girls. The associations were linear for each age and risk increased across the entire BMI distribution.Childhood Obesity and Economic Growth 1930-1983Childhood obesity was related to the economic growth during the 50 years of economic growth in the industrialized world especially in Denmark. Annual measurements of height and weight were available for all children born between 1930 and 1983 attending primary schools in Copenhagen Municipality. 165,389 boys and 163,609 girls from the age of 7 through 13 years were included in this study. After computerization SBMI (kg/m2) were calculated and the prevalence of overweight and obesity according to internatio nal age and genderspecific criteria. Economics growth was indicated by the Gross National Product and the overall consumption per capita, adjusted for inflation. Prevalence of overweight and obesity among Danish children rose in phases, which were not paralleled by trends in economic growth. The microeconomics growth indicators seem inappropriate as proxies for the environmental exposures that have elicited the obesity epidemic.Childhood obesity and television viewingChildren spend a substantial portion of their lives watching television (TV). Investigators have hypothesized that TV viewing causes obesity by one or more than three mechanismsDisplacement of physical activity.Increased calorie consumption while watching or caused by the effects of advertising.Reduced resting metabolism.The relationship between TV viewing and obesity has been examined in a relatively large number of cross sectional epidemiological but few longitudinal studies. Many of them have found relatively weak, p ositive association or mixed results. Many experimental studies have found that reducing TV viewing may help to reduce the risk of obesity. One school based experimental study was designed specifically to test directly the casual relationship between TV viewing behaviors and body fatness. The results of this randomized controlled trial provide evidence that TV viewing is a cause of increased body fatness and that reducing the TV viewing is a promising strategy for preventing childhood obesity (Robinson 2001).The objective of another study (Utter J et al, 2006), was to explore how time spent watching television (TV) is associated with the dietary behavior of New Zealand children and young adolescents. Total number of participants was 3275 children aged 5-17 years. The findings suggest that longer duration of TV watching (thus more frequent exposure to advertising) influences the frequency of consumption of soft drinks, some sweets and snacks and some fast foods among children and you ng adolescents. Efforts to control the time spent watching TV may result in better dietary habits and weight control for children and adolescents.Childhood Obesity US- A decade of progress, 1990-1999Current data suggest that 20% of US children are overweight .An analysis of the secular trends suggest that 20% of US children are overweight, and a clear up ward trend in body weight in children of 0.2 Kg between 1973 and 1994. In addition, childhood obesity is more prevalent among minority sub groups such as African Americans. Obesity that begins early in life persists into adulthood and increases the risk of obesity related conditions later in life. There has been tremendous increase in the number of studies examining the etiology and health effects of obesity in children (Goran MI, 1990-1999).1980 (boys 0.2% girls 0.5%) and 1997 (boys 1.2%, girls 2.0%).Ten years trends of childhood obesity in Israel 1990-2000Cross sectional data was collected from 13284 second and fifth class school children between 1990-2000. Prevalence of obesity was determined using Israeli and US reference values. BMI values at 95th percentile increased overtime in all ages and sex categories.Between 1990 and 2000, 95th centile values were increased by 12.7%and 11.8% among second grade boys and girls respectively. Among fifth graders in 2000, 10.7% of boys and 11.1% of girls exceeded the 1990 BMI reference values. The proportion of obese children increased over time using both Israeli and US reference values (Huerta Michael et al, 2008).Netherlands. Overweight, Obesity in 2003 V.1980-97.Data on 90,071 children, aged 4-16 years were routinely collected by 11 Community Heath Services during 2002-2004. International cut -off points for BMI to determine overweight and obesity. On average, 14.5% of boys and 17.5% of the girls were overweight (including obesity), which is a substantial increase since 1980 (boys 3.9% and girls 6.9%) and 1997 (boys 9.7% and girls 13%). Similarly 2.6% of the boys an d 3.3% 0f the girls aged 4-16 years were obese, which is much higher than in 1980 (boys 0.2% and girls 0.5%) and 1997 (boys 1.2% and girls 2.0%), (KatjaVan Den Husk, 2007).Obesity trends in US. 2003-2006Height and weight measurements were obtained from 8164 children and adolescents as apart of the 2003-2004 and 2005-2006 National Health and Nutrition Examination Survey (NHANES). Because no statistically significant differences in the prevalence of high BMI for age were found between the estimates for 2003-2004 and 2005-2006, data for four years were combined to provide more stable estimates for the most recent time period. Over all, in 2003-2006, 11.3% of children and adolescents aged 2 through years were at or above 97th percentile of the 2000 BMI- for- age growth charts, 16.3% were at or above 95th percentile. Prevalence estimates vary by age and by racial/ethnic group. Analysis of the trends in high BMI for age showed no statistically significant trend over the four time periods (1999-2000, 2001-2002, 2003-2004, and 2005-2006) for either boys or girls (Cynthia l.Ogden et al, 2008).11-March 2005. Public Release Date Consensus on Childhood Obesity, Recommends classification as diseaseA common statement on childhood obesity was published to day in the journal of Chemical Endocrinology and Metabolism (one of the journals of Endocrine Society). The consensus statement reflects the conclusions from an international summit held in Israel last year (2004) and includes a controversial recommendation to classify obesity as a disease. This decision was based upon the available research on the diagnosis, prevalence, causes (including endocrine disorders), risks, prevention and treatment of childhood obesity. Pediatric obesity is now recognized as a major health problem all over the world. Researcher have found that children who are obese have a higher risks adult obesity, which is strongly associated with many serious medical complications that impair quality of life a nd lead to additional increased risks. The statement also noted the prevalence of overweight/obesity among children 6-11 years (in the US) doubled between the years 1980-2000. By classifying obesity as legitimate disease, public funding and in user sreimbursement for obesity treatment becomes legalized (consensus on childhood obesity, 2005).Serious health risks will likely to begin to appear in obese children and adolescents as they grow older. These may include diabetes mellitus, metabolic syndrome, hyperandrogenism, heart disease, hypertension, respiratory factors, and sleep disorders. Obese children are also at greater risk of anxiety and depression. It also recommended a number of measures that can be implemented by parents schools, health providers and government and regulatory agencies to help to prevent the onset of childhood obesityEndocrine Regulation of Energy Metabolism Adipocytokines and ObesityThe mechanism underlying obesity was further explained by the discovery of a dipocytokines, the role of peripheral thyroid hormones (T4, T3), thyroid stimulating hormone and insulin the regulation of energy metabolism. The levels of some of the adipocytokines were shown to be related to visceral obesity, type 2 diabetes mellitus and coronary artery disease. Plasma levels of all the adipocytokines increase with the obesity except adiponectin (Yuji Matsuzawa et al, 2003).Recent studies point out to the adipose tissue as a highly active organ secreting a range of hormones, Leptin, Adiponectin, and Resistin. They are considered to take part in the regulation of energy metabolism. Leptin, Adiponectin and Resistin are produced by the adipose tissue. Leptin and Adiponectin are insulin sensitizing while Resistin increase the insulin resistance.LeptinThe notion that genetic abnormalities contribute to obesity gained important support with the identification of the Ob gene and its protein product in 1994 (Zhangy et al, 1996). The Ob gene termed Leptin from the Greek L eptos, meaning thin, is produced in adipose tissue and is thought to act as an afferent satiety signal in a feed back loop that affects the appetite and satiety centre in the hypothalamus of brain. The ultimate effect of this loop is to regulate body-fat mass. In human, as noted by Considine et al, 1996 caloric restriction reduces leptin concentrations and Ob mRNA levels in adipose tissue, and refeeding increases these levels. One fundamental mechanism of obesity is insensitivity to the action of Leptin, presumably in the hypothalamus. The Leptins primary physiological function is to provide a signal to suppress body fat by decreasing food intake or increasing energy expenditure. Serum leptin concentrations change more during weight loss than during weight gain (Rosenbaum M et al, 1997).AdiponectinAdiponectin or Adipo Q, an adipocyte specific secreted protein with roles in glucose and lipid homeostasis (Insulin stimulates the secretion of adiponectin). Circulating adiponectin concen trations are high 500-30,000 g/l (5-30mg/ml) accounting for 0.01% of total plasma proteins (Berget et al, 2002).Adiponectin was discovered in the mid 1990s by four different groups of researchers (Hu E et al, 1996). Adiponectin has various biological functions including insulin sensitizing (Hotta K et al, 2000), antiatherogenic (Yamauchi T et al, 2003), anti-inflammatory (Ouchi N et al, 2003), antiangiogenic and anti tumor functions (Brakenhielm E et al, 2004). Adiponectin acts through Adiponectin receptors, Adipo R1 and Adipo R2. Adipo R1 is mostly expressed in skeletal muscles and Adipo R2 is abundant in liver. These receptors are also expressed by the pancreatic cells (Kharroubi et al, 2003), macrophages and atherosclerotic lesions (Chinetti et al, 2004) as well as in brain (Yamauchi et al, 2003). Circulating Adiponectin levels display diurnal variation with a nocturnal decline and maximum levels in the late morning (Gavrila et al, 2003). Adiponectin is also found in breast milk , which in turn is implicated in childhood obesity prevention (Savino et al, 2008).Among the various adipocytokines, adiponectin, which is an abundant circulating protein (247 amino acids) synthesized purely in adipose tissue, appears to play a very important role in carbohydrates, lipid metabolism and vascular biology. Adiponectin appears to be a major modulator of insulin action and its levels are reduced in type 2 diabetes mellitus, which could contribute to peripheral insulin resistance in this condition. It has significant insulin sensitizing as well as anti inflammatory properties that include suppression of macrophage phagocytosis and TNF-a secretion and blockage of monocytes adhesion to endothelial cells in vitro. Although further investigations are required, Adiponectin administration, as well as regulation of the pathway controlling its production, represents a promising target for managing obesity, hyperlipidemia, insulin resistance, type 2 diabetes mellitus, and vascular inflammation (Manju Chandran et al, 2003).ResistinHuman resistin is 108 amino acids prepeptide and is cleaved before its secretion from the Adipose tissue. Resistin circulates in the blood as dimeric protein consisting of 92 amino acids polypeptides that are linked by a disulfide bridge. Holcomb et al, 2000 first described the gene family and its tissue specific distribution. Originally described as lung specific, is also produced by the adipose tissue and peripheral blood monocytes. It is also present in dividing epithelia of the intestine. Resistin increase blood glucose and insulin concentration in the mice and impairs hypoglycemic response to insulin infusion. In addition, anti resistin antibodies decrease blood glucose and insulin sensitivity in obese mice (Ukkalo O, 2002). The physiological role of resistin in human remains controversial. There more resistin protein in obese than lean individuals, with a significant positive correlation between resistin and BMI. BMI is a sign ificant predictor of insulin resistance, but resistin adjusted for BMI is not. These data demonstrate that resistin protein is present in human adipose tissue and blood and that there is significantly more resistin in serum of obese individuals. Serum resistin is not a significant predictor of insulin resistance in human (Youn et al, 2003, Rear R and Donnelly R, 2004).Tumor Necrosis Factor-aIt will be unreasonable not to mention the Tumor Necrosis Factor a and its role in vascular inflammation related to atherosclerosis especially in obesity.It is a cytokine involved in systemic inflammation and is a member of a group of cytokines that stimulate the acute phase reaction. The primary role of TNF is in the regulation of immune cells. TNF is able to induce apoptotic cell death, to induce inflammation and to inhibit tumourgenesis and viral replication. Dysregulation and, in particular, over production of TNF have been implicated in a variety of human diseases, as well as cancer (Locksle y et al, 2001).The theory of antitumoural response of the immune system in vivo was recognized by the physician William B in 1968. Dr A Granger reported a cytotoxic factor produced by lymphocytes and named it Lymphotoxin (Kalli WB and Granger GA, 1968). Dr L Loyal old, in 1975 reported another cytotoxic factor produced by macrophages and named it Tumor Necrosis Factor (TNF) (Cars well et al, 1975).Interleukin 6 (IL-6)Chronic inflammation is linked to endothelial dysfunction, atherosclerosis, and insulin resistance (Fernandez-Real JM and Ricart W, 2003 and Fernandez-Real JM, Ricart W, 2005). Plasma concentrations of proinflammatory cytokines, such as interleukin (IL) 18, IL-6, and tumor necrosis factor (TNF)-a, and of several other inflammatory markers are increased in patients with ischemic heart disease (Fernandez-Real JM and Ricart W, 2003, Ridker PM et al, 2002, Engstrom G et al, 2004, Ridker PM et al, 1997, Pradham AD et al, 2002). Circulating cytokines also are elevated in ty pe 2 diabetes, obesity, and insulin resistance syndrome and play a central role in the pathogenesis of these disorders (Fernandez-Real JM and Ricart W, 2003). IL-6 is a mediator of the inflammatory response, and it is linked to dyslipidemia, type 2 diabetes, and risk of myocardial infarction (Fernandez-Real JM and Ricart W, 2003, Ridker PM et al, 2000, Esteve E et al, 2005, Yudkin JS et al, 2000). IL-6 is secreted by a variety of different cell types, including lymphoid and endothelial cells, fibroblasts, skeletal muscle, and adipose tissue. Circulating IL-6 levels correlate with obesity and insulin resistance and may predict the development of type 2 diabetes mellitus (Yudkin JS et al, 2000, Pradhan AD et al, 2001, Akira S et al, 1993, Mohamed-Ali V et al, 1997). Endothelial dysfunction is regarded as a causal factor in the development of atherosclerosis (Hansson GK, 2005). It is one of the earliest abnormalities that can be detected in people at risk for cardiovascular events, and it is linked to insulin resistance and type 2 diabetes (Steinberg HO and Baron AD, 2002, Natali A et al, 2006). Cytokines have an important role in the endothelial injury induced by inflammation. The vascular endothelium is involved in the inflammatory response to atherosclerosis (Hansson GK, 2005, Steinberg HO and Baron AD, 2002, Natali A et al, 2006, Widlansky ME et al, 2003), and changes in endothelium function could underlie the association between cardiovascular disease and inflammation.Obesity Related Insulin Resistance Definition and PathogenesisInsulin resistance is a state in which a given amount of insulin produces a subnormal biological response (Kahn CR, 1978). In particular, it is characterized by a decrease in the ability of insulin to stimulate the use of glucose by muscles and adipose tissue and to suppress hepatic glucose production and output (Matthaei et al, 2000). Furthermore, it accounts a resistance to insulin action on protein and lipid metabolism and on vasc ular endothelial function and genes expression (Bajaj M and Defronzo RA, 2003). Several defects in the insulin signaling cascade have been implicated in the pathogenesis of insulin resistance, Insulin resistance is believed to have both genetic and environmental factors implicated in its etiology (Matthaei et al, 2000 and Liu et al, 2004). The genetic component seems to be polygenic in nature, and several genes have been suggested as potential candidates (Matthaei et al, 2000). However, several other factors can influence insulin sensitivity, such as obesity, ethnicity, gender, perinatal factors, puberty, sedentary lifestyle and diet (Liu et al, 2004).The Role of Fatty Acids and AdipocytokinesObesity represents the major risk factor for the development of insulin resistance in children and adolescents (Caprio S, 2002), and insulin resistance/hyperinsulinemia is believed to be an important link between obesity and the associated metabolic abnormalities and cardiovascular risk (Weiss R and Kaufman FR, 2008). Approximately, 55% of the variance in insulin sensitivity in children can be explained by total adiposity, after adjusting for other confounders, such as age, gender, ethnicity and pubertal stage (Caprio S, 2002). Obese children have hyperinsulinemia and peripheral insulin resistance with an 40% lower insulin-stimulated glucose metabolism than non-obese children (Caprio S et al, 19996). Adipose tissue seems to play a key role in the pathogenesis of insulin resistance through several released metabolites, hormones and adipocytokines that can affect different steps in insulin action (Matsuzawa Y, 2005) (Fig. 1). Adipocytes produce non-esterified fatty acids, which inhibit carbohydrate metabolism via substrate competition and impaired intracellular insulin signaling (Matsuzawa Y, 2005, Griffin ME et al 1999 and Randle PJ, 1998). In children, as in adults, several adipocytokines have been related to adiposity indexes as well as to insulin resistance. Adiponectin is one of the most common cytokines produced by adipose tissue, with an important insulin sensitizing effect associated with anti-atherogenetic properties (Despres JP, 2006 and Gil-Campos M et al, 2004). Whereas obesity is generally associated with an increased release of metabolites by adipose tissue, levels of Adiponectin are inversely related to adiposity (Matsuzawa Y, 2005). Therefore, reduced levels of this adipocytokine have been implicated in the pathogenesis of insulin resistance and metabolic syndrome (Matsuzawa Y, 2005). Decreased levels of Adiponectin have been detected across tertiles of insulin resistance in children and adolescents (Weiss R et al, 2004), where it is a good predictor of insulin sensitivity, independently of adiposity (Lee S et al, 2006). Adipose tissue also produces tumour necrosis factor-a, an inflammatory factor, which can alter insulin action at different levels in the intracellular pathway (Matsuzawa Y, 2005). Interleukin-6 (IL-6) is another inflam matory cytokine released by adipose tissue and its levels are increased in obesity (Matsuzawa Y, 2005). IL-6 stimulates the hepatic production of C-reactive protein and this can explain the state of inflammation associated with obesity, and could mediate, at least partially, obesity-related insulin resistance (Matsuzawa Y, 2005). Data based mainly on animal studies also suggest that increased levels of resistin, another molecule produced by adipose tissue, could impair insulin sensitivity (Matsuzawa Y, 2005). The close relationship between Leptin levels and insulin resistance in children has also been suggested by the data (Chu NF et al, 2000). Serum levels of retinol-binding protein 4 (RBP4) correlate with insulin resistance in subjects with obesity as well as in those with impaired glucose tolerance (IGT) or type 2 diabetes mellitus, therefore suggesting that it could be useful in assessing insulin resistance and the associated risk for complications (Graham TE et al, 2006). Serum RBP4 is independently related to obesity as well as to components of the metabolic syndrome in normal weight and overweight children (Aeberli I et al, 2007). Diet composition in obese children might be an additional factor promoting and/or worsening insulin resistance. Animal and human studies suggest that a high energy intake as well as a diet rich in fat and carbohydrates and low in fiber could increase the risk of developing insulin resistance (Canete R et al, 2007).The Role of Fat DistributionAn altered partitioning of fat between subcutaneous and visceral or ectopic sites has been associated with insulin resistance (Weiss R and Kaufman FR, 2008). Visceral fat has a better correlation with insulin sensitivity than subcutaneous or total body fat (Caprio S et al, 1995), in both obese adults and children. Visceral fat has higher lipolytic activity compared with subcutaneous fat, therefore a greater amount of free fatty acids and glycerol gain entry or carried out to the liver (Mat thaei et al, 2000). Visceral fat in girls is directly correlated to the glucose-stimulated insulin levels and inversely correlated with insulin sensitivity and the rate of glucose uptake. No correlation was found between abdominal subcutaneous fat (Caprio S et al, 1995). Ectopic deposition of fat in the liver or muscle can also be responsible for insulin resistance in obese subjects, as the accumulation of fat in these sites impairs insulin signaling, with a reduced glucose uptake in the muscle and a decreased insulin-mediated suppression of hepatic glucose production (Weiss R and Kaufman FR, 2008). Intramyocellular lipid (IMCL) accumulation has been shown as a factor related to decreased insulin sensitivity (Jacob S et al, 1999 and Thamer C et al, 2003). Obese insulin sensitive children and adolescents present lower levels of visceral fat and IMCL when compared with obese insulin resistant children (Weiss R et al, 2005). Accumulation of fat in the liver has also been associated wi th insulin resistance, independently of adiposity (Kelley DE et al, 2003). It has also been suggested that deposits of fat around blood vessels can produce several cytokines and therefore contribute to the development of insulin resistance, through a so-called vasocrine effect (Yudkin JS et al, 2005).Insulin Resistance and Associated ComplicationsInsulin resistance in obesity is strictly related to the development of hypertension (Marcovecchio ML et al, 2006 and Cruz ML et al, 2002), dyslipidemia (Howard BV and Howard WJ, 1994), impaired glucose tolerance (IGT) (Sinha R et al, 2002), hepatic steatosis (DAdamo E et al, 2008), as well as to the combination of these factors, also known as metabolic syndrome (Eckel RH et al, 2005). Furthermore, insulin resistance is associated with systemic inflammation, endothelial dysfunction, early atherosclerosis and disordered fibrinolysis (Dan Dona P et al, 2002). It is alarming that these metabolic and cardiovascular complications are already fou nd in obese children and adolescents (Dietz WH, 2004). The presence of these alterations in prepubertal children is then particularly worrying, as insulin resistance and related complications might be further exacerbated by the influence of puberty, due to the physiological decrease in insulin sensitivity associated with normal pubertal development (Caprio S et al, 1989). Insulin resistance in childhood can track in adult life (Sinaiko AR et al, 2006). Insulin resistance at the age of 13 years predicts insulin resistance at age 19 years, independently of BMI, and is also associated with cardiovascular risk in adulthood (Sinaiko AR et al, 2006). The fundamental role of insulin resistance in human disease was already recognized in 1988 by Reaven (Reaven GM, 1988) who emphasized its role in the development of a grouping of metabolic abnormalities, which he defined as syndrome X. Later studies strengthened the concept of insulin resistance as a key component of the metabolic syndrome, a cluster of impaired glucose tolerance (IGT), dyslipidemia, hypertension, hyperinsulinemia, associated with an increased risk of type 2 diabetes mellitus and cardiovascular disease (Eckel RH et al, 2005). Insulin resistance represents a serious and common complication of obesity during childhood and adolescence. A timely diagnosis and an appropriated prevention and treatment of obesity and insulin resistance are required in order to reduce the