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). Procedure. 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 β-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)]. Conclusion. Abnormalities in glucose metabolism are frequent in young FA patients without prior diagnosis of diabetes, and are associated with marked defects in insulin secretion.