title: Inflammatory adipokines, high molecular weight adiponectin, and insulin resistance: a population-based survey in prepubertal schoolchildren.
abstract: BACKGROUND
  The aim of this study was to investigate sex differences and associations of high molecular weight (HMW) adiponectin, leptin and proinflammatory adipokines, individually or in combinations, with adiposity and insulin resistance (IR) measures in prepubertal childhood.
  
  
  METHODS
  We studied 305 prepubertal children (boys/girls: 144/161; Tanner stage 1; age: 5-13 yr), included in a cohort of 44,231 adolescents who participated in an extensive Italian school-based survey. According to Cole's criteria, 105 individuals were lean (L; boys/girls: 59/46), 60 overweight (OW; boys/girls: 32/28) and 140 obese (OB; boys/girls: 70/70). Measurements comprised total and HMW adiponectin, leptin, as well as a panel of proinflammatory adipokines/chemokines associated with diabetes risk.
  
  
  RESULTS
  Leptin-, and the leptin-to-HMW adiponectin ratio (L/HMW)-, increased progressively (p<0.0001) from L to OW to OB boys and girls. When compared with L peers, OW and OB girls exhibited lower (p<0.001) HMW adiponectin levels, while in boys the HMW multimers did not differ significantly across the BMI-stratified groups. OB girls displayed higher (p<0.05) IL-8, IL-18, monocyte chemoattractant protein-1 (MCP-1) and soluble intercellular adhesion molecule-1 levels (sICAM-1) than L girls, whereas increased macrophage migration inhibitory factor (MIF) concentrations in OB vs OW boys were seen. HMW adiponectin (negatively), leptin or inflammatory markers (positively) correlated with adiposity and IR measures. In multivariate models, leptin represented a strong and independent determinant of HOMA-IR (R(2) 0.378; p<0.01). Adjustment for age, BMI(z-score), lipids and inflammatory mediators abolished the association between leptin and HOMA-IR in boys, while in girls leptin remained still a significant predictor of IR (R(2) 0.513; p<0.01). Finally, in both sexes, the joint effect of the L/HMW did not improve the prediction of basal IR as compared with leptin levels alone, which were mainly explained by the BMI(z-score.)
  
  
  CONCLUSIONS
  In prepubertal children, leptin emerges as a sex-independent discrimination marker of adiposity degree and as a useful, sex-associated predictor of the systemic insulin resistance.
authors.affiliation: Section of Internal Medicine, Endocrine and Metabolic Sciences, Department of Internal Medicine, Perugia University, Perugia, Italy. gmurdolo@tiscalinet.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Murdolo
authors.forename: Bettina
authors.initials: B
authors.lastname: Nowotny
authors.forename: Federica
authors.initials: F
authors.lastname: Celi
authors.forename: Miranda
authors.initials: M
authors.lastname: Donati
authors.forename: Vittorio
authors.initials: V
authors.lastname: Bini
authors.forename: Francesco
authors.initials: F
authors.lastname: Papi
authors.forename: Gabi
authors.initials: G
authors.lastname: Gornitzka
authors.forename: Serena
authors.initials: S
authors.lastname: Castellani
authors.forename: Michael
authors.initials: M
authors.lastname: Roden
authors.forename: Adriano
authors.initials: A
authors.lastname: Falorni
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.forename: Alberto
authors.initials: A
authors.lastname: Falorni
mesh_terms: D054392:Adipokines / Q000097:blood*; D052242:Adiponectin / Q000097:blood / Q000737:chemistry; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006306:Health Surveys; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008970:Molecular Weight; D011153:Population; D011627:Puberty / Q000097:blood / Q000502:physiology; D012574:Schools
chemical_list: C499918:ADIPOQ protein, human; D054392:Adipokines; D052242:Adiponectin; D018836:Inflammation Mediators