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Exp Clin Endocrinol Diabetes 2013; 121(01): 54-57
DOI: 10.1055/s-0032-1321834
Article
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Genetic variants in GCKR, GIPR, ADCY5 and VPS13C and the risk of severe sulfonylurea-induced hypoglycaemia in patients with type 2 diabetes

J. D. Holstein
1   Medical Department, University of Leipzig, Leipzig, Germany
,
O. Patzer
2   First Department of Medicine, Lippe-Detmold Hospital, Detmold, Germany
,
A. Körner
3   University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany
,
M. Stumvoll
1   Medical Department, University of Leipzig, Leipzig, Germany
4   IFB Adiposity Diseases, University of Leipzig, Leipzig, Germany
,
P. Kovacs
1   Medical Department, University of Leipzig, Leipzig, Germany
,
A. Holstein
2   First Department of Medicine, Lippe-Detmold Hospital, Detmold, Germany
› Author Affiliations
Further Information

Publication History

received 01 June 2012
first decision 25 June 2012

accepted 04 July 2012

Publication Date:
06 September 2012 (online)

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Abstract

Objective:

Severe hypoglycaemia (SH) induced by sulfonylureas is a life-threatening condition. We hypothesized that recently identified polymorphisms associated with insulin secretion in GCKR, GIPR, ADCY5 and VPS13C genes affect the response to sulfonylureas in patients with type 2 diabetes (T2D) and so, result in reduced risk for SH.

Research design and methods:

We assessed the prevalence of GCKR, GIPR, ADCY5 and VPS13C polymorphisms in a case-control study including 111 patients with SH and 100 patients with T2D but without a history of SH. All patients were treated with the sulfonylurea drugs glimepiride, glibenclamide or gliquidon. SH was defined as a symptomatic event with blood glucose of <50 mg/dl requiring treatment with intravenous glucose.

Results:

In logistic regression analyses, a low HbA1c and a higher sulfonylurea dose appeared to be the only predictors of SH (P=0.001 and P=0.04, respectively). There was no significant difference in the genotype distribution between the control group and the cases with SH for any of the investigated polymorphisms (OR and 95% confidence intervals – 0.90 (0.59–1.38) for GCKR; 1.11 (0.67–1.85) for GIPR; 0.75 (0.48–1.17) for ADCY5; 1.43 (0.95–2.15) for VPS13C; all P-values >0.05). Also, there was no significant effect of the examined genetic variants on HbA1c levels (all P-values >0.05 adjusted for age, sex, BMI, diabetes duration, sulfonylurea dose).

Conclusions:

We found no detectable effect (with an OR >2.1) of the variants in GCKR, GIPR, ADCY5 and VPS13C on the response to sulfonylurea treatment, indicating that these variants are not significantly contributing to the risk of SH in patients with T2D.

Key words

sulfonylurea - severe hypoglycaemia - polymorphisms - type 2 diabetes
 

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