Connelly, P.J. , Smith, N., Chadwick, R., Exley, A.R., Shneerson, J.M. and Pearson, E.R. (2016) Recessive mutations in the cancer gene Ataxia Telangiectasia Mutated (ATM), at a locus previously associated with metformin response, cause dysglycaemia and insulin resistance. Diabetic Medicine, 33(3), pp. 371-375. (doi: 10.1111/dme.13037) (PMID:26606753) (PMCID:PMC4832393)
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Abstract
Aim: To investigate glucose and insulin metabolism in participants with ataxia telangiectasia in the absence of a diagnosis of diabetes. Methods: A standard oral glucose tolerance test was performed in participants with ataxia telangiectasia (n = 10) and in a control cohort (n = 10). Serial glucose and insulin measurements were taken to permit cohort comparisons of glucose‐insulin homeostasis and indices of insulin secretion and sensitivity. Results: During the oral glucose tolerance test, the 2‐h glucose (6.75 vs 4.93 mmol/l; P = 0.029), insulin concentrations (285.6 vs 148.5 pmol/l; P = 0.043), incremental area under the curve for glucose (314 vs 161 mmol/l/min; P = 0.036) and incremental area under the curve for insulin (37,720 vs 18,080 pmol/l/min; P = 0.03) were higher in participants with ataxia telangiectasia than in the controls. There were no significant differences between groups in fasting glucose, insulin concentrations or insulinogenic index measurement (0.94 vs 0.95; P = 0.95). The Matsuda index, reflecting whole‐body insulin sensitivity, was lower in participants with ataxia telangiectasia (5.96 vs 11.03; P = 0.019) than in control subjects. Conclusions: Mutations in Ataxia Telangiectasia Mutated (ATM) that cause ataxia telangiectasia are associated with elevated glycaemia and low insulin sensitivity in participants without diabetes. This indicates a role of ATM in glucose and insulin metabolic pathways
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Connelly, Dr Paul |
Authors: | Connelly, P.J., Smith, N., Chadwick, R., Exley, A.R., Shneerson, J.M., and Pearson, E.R. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | Diabetic Medicine |
Publisher: | Wiley |
ISSN: | 0742-3071 |
ISSN (Online): | 1464-5491 |
Published Online: | 25 November 2015 |
Copyright Holders: | Copyright © 2016 The Authors |
First Published: | First published in Diabetic Medicine 33(3): 371-375 |
Publisher Policy: | Reproduced under a Creative Commons License |
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