title: Abnormalities in glucose tolerance are common in children with fanconi anemia and associated with impaired insulin secretion.
abstract: BACKGROUND
  To determine prevalence of abnormal glucose metabolism in Fanconi Anemia (FA).
  
  
  METHODS
  Thirty-nine children with FA underwent 2-hr oral glucose tolerance test (OGTT). Reference lean adolescents (REF) were older than FA patients (mean +/- SD: FA 8.6 +/- 3.9 years, REF 19.8 +/- 0.3 years, P < 0.001), but comparable in BMI Z-scores (FA 1.25 +/- 0.58, REF -0.02 +/- 0.24; P = 0.24). Patients had normal glucose tolerance (NGT) or abnormal glucose metabolism (AGM) by American Diabetes Association Criteria. Insulinogenic index estimated beta-cell function. Insulin resistance estimation used homeostatic model assessment (HOMA-IR). Insulin secretion estimation relative to insulin sensitivity used disposition index (DI).
  
  
  RESULTS
  Among FA patients, 46% had AGM. Compared to REF, there were significant differences in glycemic responses (area under curve: FA-NGT 344 +/- 42, FA-AGM 596 +/- 35, REF 208 +/- 25 mM, P < 0.0001) and insulinogenic index (FA-NGT 105 +/- 29, FA-AGM 44 +/- 8, and REF 173 +/- 41 pM/mM, P < 0.05). Insulin sensitivity did not differ among NGT, AGM, and REF (HOMA-IR: FA-NGT 1.9 +/- 0.4, FA-AGM 2.2 +/- 0.5, REF 1.3 +/- 0.2, P = NS). However, DI was significantly lower in both FA groups than REF [NGT 63.6 +/- 16.5 vs. AGM 26.4 +/- 3.5 (P < 0.048); REF 132.6 +/- 24.5 (NGT and AGM vs. REF, both P < 0.0002)].
  
  
  CONCLUSIONS
  Abnormalities in glucose metabolism are frequent in young FA patients without prior diagnosis of diabetes, and are associated with marked defects in insulin secretion.
authors.affiliation: Division of Endocrinology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, MLC 7012, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA. deborah.elder@cchmc.org
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Elder
authors.forename: David A
authors.initials: DA
authors.lastname: D'Alessio
authors.forename: Ori
authors.initials: O
authors.lastname: Eyal
authors.forename: Robin
authors.initials: R
authors.lastname: Mueller
authors.forename: Franklin O
authors.initials: FO
authors.lastname: Smith
authors.forename: Alvina R
authors.initials: AR
authors.lastname: Kansra
authors.forename: Susan R
authors.initials: SR
authors.lastname: Rose
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005199:Fanconi Anemia / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007223:Infant; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D008297:Male
chemical_list: D007328:Insulin; D005947:Glucose