Heterozygous PAX6 mutations may lead to hyper‐proinsulinaemia and glucose intolerance: A case–control study in families with congenital aniridia.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Additional Information
    • Subject Terms:
    • Abstract:
      Aim: PAX6 is a transcription factor involved in embryonic development of many organs, including the eyes and the pancreas. Mutations of PAX6 gene is the main cause of a rare disease, congenital aniridia (CA). This case–control study aims to investigate the effects of PAX6 mutations on glucose metabolism and insulin secretion in families with CA. Methods: In all, 21 families with CA were screened by Sanger sequencing. Patients with PAX6 mutations and CA (cases) and age‐matched healthy family members (controls) were enrolled. Oral glucose tolerance test (OGTT) was performed to detect diabetes or impaired glucose tolerance (IGT). Insulin and proinsulin secretion were evaluated. Results: Among 21 CA families, heterozygous PAX6 mutations were detected in five families. Among cases (n = 10) from the five families, two were diagnosed with newly identified diabetes and another two were diagnosed with IGT. Among controls (n = 12), two had IGT. The levels of haemoglobin A1c were 36 ± 4 mmol/mol (5.57 ± 0.46%) and 32 ± 5 mmol/L (5.21 ± 0.54%) in the cases and the controls, respectively (p = 0.049). More importantly, levels of proinsulin in the cases were significantly higher than that of the controls, despite similar levels of total insulin. The areas under the curve of proinsulin in the cases (6425 ± 4390) were significantly higher than that of the controls (3709 ± 1769) (p = 0.032). Conclusion: PAX6 may participate in the production of proinsulin to insulin and heterozygous PAX6 mutations may be associated with glucose metabolism in CA patients. [ABSTRACT FROM AUTHOR]
    • Abstract:
      Copyright of Diabetic Medicine is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)