title: Family history of type 2 diabetes is associated with decreased insulin sensitivity and an impaired balance between insulin sensitivity and insulin secretion in white youth.
abstract: OBJECTIVE
  Family history of type 2 diabetes is a major risk factor for type 2 diabetes in youth, which is increasing. This investigation aimed to evaluate the impact of family history of type 2 diabetes on insulin secretion relative to insulin sensitivity in healthy children. beta-Cell compensation for insulin sensitivity was calculated as the product of insulin sensitivity x first-phase insulin secretion, termed glucose disposition index (GDI).
  
  
  METHODS
  A total of 28 healthy white children (12 boys and 16 girls; 12.1 +/- 0.5 years of age) with a positive family history of type 2 diabetes and 26 healthy white children (13 boys and 13 girls; 11.5 +/- 0.4 years of age) with a negative family history of type 2 diabetes underwent a 3-h 40 mU.m(-2).min(-1) hyperinsulinemic-euglycemic clamp to assess insulin sensitivity and clearance and a 2-h hyperglycemic clamp to assess insulin secretion. Body composition and visceral adiposity were evaluated with dual-energy X-ray absorptiometry and computed tomography at the L4-L5 intervertebral space.
  
  
  RESULTS
  Insulin sensitivity was lower in children with a family history of type 2 diabetes versus children without a family history (8.8 +/- 0.9 vs. 12.2 +/- 1.1 micromol.kg(-1).min(-1) per pmol/l, P = 0.02). Similarly, insulin clearance was lower. First- and second-phase insulin levels were not different between groups with and without a positive family history. The GDI was lower in youth with versus youth without a positive family history (4.1 +/- 0.3 vs. 5.2 +/- 0.5 mmol.kg(-1).min(-1), P = 0.039). IGF binding protein-1 (IGFBP-1) was 60% lower in youth with versus youth without the positive family history.
  
  
  CONCLUSIONS
  These results demonstrate that family history of type 2 diabetes in white children is associated with decreased insulin sensitivity and clearance, decreased IGFBP-1, and an impaired relationship between insulin action and beta-cell compensation. Detection of these alterations in hormonal and metabolic parameters in children with a positive family history suggests that at least some of the determinants of GDI are genetic/heritable.
authors.affiliation: Division of Pediatric Endocrinology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA. silva.arslanian@chp.edu
authors.forename: Silva A
authors.initials: SA
authors.lastname: Arslanian
authors.forename: Fida
authors.initials: F
authors.lastname: Bacha
authors.forename: Rola
authors.initials: R
authors.lastname: Saad
authors.forename: Neslihan
authors.initials: N
authors.lastname: Gungor
mesh_terms: D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005190:Family; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D008297:Male; D012016:Reference Values; D014481:United States; D044465:White People
chemical_list: D007328:Insulin