title: Age before stage: insulin resistance rises before the onset of puberty: a 9-year longitudinal study (EarlyBird 26).
abstract: OBJECTIVE
  Insulin resistance (IR) is associated with diabetes. IR is higher during puberty in both sexes, with some studies showing the increase to be independent of changes in adiposity. Few longitudinal studies have reported on children, and it remains unclear when the rise in IR that is often attributed to puberty really begins. We sought to establish from longitudinal data its relationship to pubertal onset, and interactions with age, sex, adiposity, and IGF-1.
  
  
  METHODS
  The EarlyBird Diabetes study is a longitudinal prospective cohort study of healthy children aged 5-14 years. Homeostasis model assessment (HOMA-IR), skinfolds (SSF), adiposity (percent fat, measured by dual-energy X-ray absorptiometry), serum leptin, and IGF-1 were measured annually in 235 children (134 boys). Pubertal onset was adduced from Tanner stage (TS) and from the age at which luteinizing hormone (LH) first became serially detectable (≥0.2 international units/L).
  
  
  RESULTS
  IR rose progressively from age 7 years, 3-4 years before TS2 was reached or LH became detectable. Rising adiposity and IGF-1 together explained 34% of the variance in IR in boys and 35% in girls (both P < 0.001) over the 3 years preceding pubertal onset. The contribution of IGF-1 to IR was greater in boys, despite their comparatively lower IGF-1 levels.
  
  
  CONCLUSIONS
  IR starts to rise in mid-childhood, some years before puberty. Its emergence relates more to the age of the child than to pubertal onset. More than 60% of the variation in IR prior to puberty was unexplained. The demography of childhood diabetes is changing, and prepubertal IR may be important.
authors.affiliation: University Medicine, Peninsula Medical School, Plymouth, UK. alison.jeffery@pms.ac.uk
authors.forename: Alison N
authors.initials: AN
authors.lastname: Jeffery
authors.forename: Brad S
authors.initials: BS
authors.lastname: Metcalf
authors.forename: Joanne
authors.initials: J
authors.lastname: Hosking
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Streeter
authors.forename: Linda D
authors.initials: LD
authors.lastname: Voss
authors.forename: Terence J
authors.initials: TJ
authors.lastname: Wilkin
mesh_terms: D015502:Absorptiometry, Photon; D050154:Adiposity / Q000502:physiology; D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D020738:Leptin / Q000097:blood; D008137:Longitudinal Studies; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D011446:Prospective Studies; D011627:Puberty / Q000097:blood* / Q000502:physiology*
chemical_list: D020738:Leptin; D007334:Insulin-Like Growth Factor I; D007986:Luteinizing Hormone