title: Increased maternal Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) associated with older age at diagnosis of Type 1 diabetes in offspring.
abstract: OBJECTIVE
  Obesity and insulin resistance have been linked to rising incidence and earlier onset of Type 1 diabetes. Inherited differences in insulin action might also influence the evolution of Type 1 diabetes.Our aim was to determine whether parental BMI and insulin resistance influences age of onset of Type 1 diabetes in their offspring.
  
  
  METHODS
  BMI standard deviation score and age at diagnosis of Type 1 diabetes was examined in 227 children, and in 206 of these was compared with local matched control subjects. Non-diabetic parents of a subgroup of 80 children with Type 1 diabetes were recruited. Parental BMI was compared with local adult control subjects. The relationship between parental BMI, waist-hip ratio, homeostasis model assessment of insulin resistance (HOMA-IR), leptin and adiponectin levels and age at diagnosis of Type 1 diabetes in offspring was examined.
  
  
  RESULTS
  We found no relationship between age at diagnosis of Type 1 diabetes in children and BMI standard deviation score (P = 0.5). Children with Type 1 diabetes and their parents were heavier than matched control subjects (mean BMI standard deviation score sd in children = 0.66 1.06 vs. 0.32 1.16 in control subjects, P = 0.002; mean parental BMI sd 27.7 0.4 vs. 25.5 0.4 kg ⁄m2 in control subjects; P < 0.0001). Maternal HOMA-IR accounted for 20% of variation in age at diagnosis (P < 0.001) with increasing maternal insulin resistance associated with later age at diagnosis of Type 1 diabetes.
  
  
  CONCLUSIONS
  Childrenwith Type 1 diabetes and their parents have an increased BMI at diagnosis.Maternal insulin resistance is associated with later onset of Type 1 diabetes in children.
authors.affiliation: Department of Medicine, Newcastle upon Tyne Hospitals Foundation Trust, Newcastle University, Newcastle upon Tyne, UK. Nicola.leech@nuth.nhs.uk
authors.forename: N J
authors.initials: NJ
authors.lastname: Leech
authors.forename: J
authors.initials: J
authors.lastname: O'Sullivan
authors.forename: P
authors.initials: P
authors.lastname: Avery
authors.forename: C
authors.initials: C
authors.lastname: Howey
authors.forename: K
authors.initials: K
authors.lastname: Burling
authors.forename: S
authors.initials: S
authors.lastname: Iyer
authors.forename: L
authors.initials: L
authors.lastname: Pascoe
authors.forename: M
authors.initials: M
authors.lastname: Walker
authors.forename: T
authors.initials: T
authors.lastname: Cheetham
mesh_terms: D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D015992:Body Mass Index; D002648:Child; D016241:Child of Impaired Parents; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009035:Mothers; D009765:Obesity / Q000150:complications / Q000235:genetics*