期刊
DIABETOLOGIA
卷 58, 期 7, 页码 1430-1435出版社
SPRINGER
DOI: 10.1007/s00125-015-3593-9
关键词
Dosing; Glibenclamide; Glyburide; HbA(1c); K-ATP channel; KCNJ11; Monogenic diabetes; Neonatal diabetes; Pharmacotherapy; Sulfonylurea
资金
- University of Chicago Diabetes Research and Training Center (DRTC)
- SWG's K Award - National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [DK020595, K23 DK094866]
- ADA [1-11-CT-41]
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://monogenicdiabetes.uchicago.edu/registry). We assessed the influence of age at initiation of SU therapy on treatment outcomes. Results HbA(1c) 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.
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