Abnormalities in glucose tolerance are common in children with fanconi anemia and associated with impaired insulin secretion.
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.
Elder
Deborah A
DA
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
D'Alessio
David A
DA
Eyal
Ori
O
Mueller
Robin
R
Smith
Franklin O
FO
Kansra
Alvina R
AR
Rose
Susan R
SR
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
D007328:Insulin; D005947:Glucose