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Diabetologia
Published in: Diabetologia 7/2015

01-07-2015 | Article

Age at the time of sulfonylurea initiation influences treatment outcomes in KCNJ11-related neonatal diabetes

Authors: Brian W. Thurber, David Carmody, Elizabeth C. Tadie, Ashley N. Pastore, Jazzmyne T. Dickens, Kristen E. Wroblewski, Rochelle N. Naylor, Louis H. Philipson, Siri Atma W. Greeley, the United States Neonatal Diabetes Working Group

Published in: Diabetologia | Issue 7/2015

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Abstract

Aims/hypothesis

Individuals with heterozygous activating mutations of the KCNJ11 gene encoding a subunit of the ATP-sensitive potassium channel (KATP) can usually be treated with oral sulfonylurea (SU) pills in lieu of insulin injections. The aim of this study was to test our hypothesis that younger age at the time of initiation of SU therapy is correlated with lower required doses of SU therapy, shorter transition time and decreased likelihood of requiring additional diabetes medications.

Methods

We performed a retrospective cohort study using data on 58 individuals with neonatal diabetes due to KCNJ11 mutations identified through the University of Chicago Monogenic Diabetes Registry (http://​monogenicdiabete​s.​uchicago.​edu/​registry). We assessed the influence of age at initiation of SU therapy on treatment outcomes.

Results

HbA1c fell from an average of 8.5% (69 mmol/mol) before transition to 6.2% (44 mmol/mol) after SU therapy (p < 0.001). Age of initiation of SU correlated with the dose (mg kg−1 day−1) of SU required at follow-up (r = 0.80, p < 0.001). Similar associations were observed across mutation subtypes. Ten participants required additional glucose-lowering medications and all had initiated SU at age 13 years or older. No serious adverse events were reported.

Conclusions/interpretation

Earlier age at initiation of SU treatment is associated with improved response to SU therapy. Declining sensitivity to SU may be due to loss of beta cell mass over time in those treated with insulin. Our data support the need for early genetic diagnosis and appropriate personalised treatment in all cases of neonatal diabetes.
Appendix
Available only for authorised users
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Metadata
Title
Age at the time of sulfonylurea initiation influences treatment outcomes in KCNJ11-related neonatal diabetes
Authors
Brian W. Thurber
David Carmody
Elizabeth C. Tadie
Ashley N. Pastore
Jazzmyne T. Dickens
Kristen E. Wroblewski
Rochelle N. Naylor
Louis H. Philipson
Siri Atma W. Greeley
the United States Neonatal Diabetes Working Group
Publication date
01-07-2015
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 7/2015
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-015-3593-9

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