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

Abstract

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, HbA_1c 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 HbA_1c 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 HbA_1c and consequently in lower risk for SH.

Key words

sulfonylurea-induced hypoglycemia - type 2 diabetes - KCNJ11

References

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