Horm Metab Res 2009; 41(5): 387-390
DOI: 10.1055/s-0029-1192019
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

The E23K Variant of KCNJ11 and the Risk for Severe Sulfonylurea-induced Hypoglycemia in Patients with Type 2 Diabetes

A. Holstein 1 , M. Hahn 1 , M. Stumvoll 2 , P. Kovacs 3
  • 1First Department of Medicine, Clinic Lippe-Detmold, Detmold, Germany
  • 2Medical Department III, University of Leipzig, Leipzig, Germany
  • 3Interdisciplinary Centre for Clinical Research, University of Leipzig, Germany
Further Information

Publication History

received 13.10.2008

accepted 07.01.2009

Publication Date:
12 February 2009 (online)


Severe sulfonylurea-induced hypoglycemia (SH) is a life-threatening and frequently misdiagnosed condition leading to a mortality of up to 10%. Pharmacogenetic factors could be of critical importance for the risk of SH. We investigated the effects of the E23K variant of KCNJ11 (potassium inwardly-rectifying channel, subfamily J, member 11) on risk for SH in patients with type 2 diabetes (T2D). In a case-control study, the frequency of the E23K KCNJ11 polymorphism of 43 diabetic patients with SH admitted to the emergency department was compared with a matched control group of 54 patients with T2D, but without a history of SH. All patients have been treated with the sulfonylureas glimepiride or glibenclamide. SH was defined as a symptomatic event requiring treatment with intravenous glucose and was confirmed by a blood glucose measurement of <50 mg/dl. The K variant was significantly more frequent in the control group (46%) than in cases with SH (31%) (p=0.04). However, in multivariate logistic regression analyses, age, HbA1c and sulfonylurea dose appeared to be the strongest predictors of SH. Nevertheless, in generalized linear model analyses, the E23K variant was significantly associated with increased HbA1c levels (adjusted p=0.04) independent of age, sex, body mass index, diabetes duration and sulfonylurea dose. Our data suggest that patients with T2D carrying the K variant of the E23K polymorphism in KCNJ11 have reduced response to sulfonylurea therapy, which results in increased HbA1c and consequently in lower risk for SH.



P. Kovacs, PhD 

Interdisciplinary Centre for Clinical Research

University of Leipzig

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