2. Academic Validation
  3. A variant of the glucose transporter gene SLC2A2 modifies the glycaemic response to metformin therapy in recently diagnosed type 2 diabetes

A variant of the glucose transporter gene SLC2A2 modifies the glycaemic response to metformin therapy in recently diagnosed type 2 diabetes

  • Diabetologia. 2019 Feb;62(2):286-291. doi: 10.1007/s00125-018-4759-z.
Wolfgang Rathmann 1 2,  Klaus Strassburger 3 4,  Brenda Bongaerts 3 4,  Oliver Kuss 3 4 5,  Karsten Müssig 4 6 7,  Volker Burkart 4 6,  Julia Szendroedi 4 6 7,  Jörg Kotzka 4 8,  Birgit Knebel 4 8,  Hadi Al-Hasani 4 8,  Michael Roden 4 6 7,  GDS Group
Affiliations

Affiliations

  • 1 Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Auf'm Hennekamp 65, D-40225, Düsseldorf, Germany. [email protected].
  • 2 German Center for Diabetes Research (DZD), München-Neuherberg, Germany. [email protected].
  • 3 Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Auf'm Hennekamp 65, D-40225, Düsseldorf, Germany.
  • 4 German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
  • 5 Institute of Medical Statistics, Heinrich Heine University, Medical Faculty, Düsseldorf, Germany.
  • 6 Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.
  • 7 Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
  • 8 Institute for Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.
PMID: 30413829 DOI: 10.1007/s00125-018-4759-z
Abstract

Aims/hypothesis: The aim of this study was to investigate the modifying effect of the glucose transporter (GLUT2) gene SLC2A2 (rs8192675) variant on the glycaemic response to metformin in individuals recently diagnosed with type 2 diabetes.

Methods: Individuals with type 2 diabetes (n = 508) from the prospective German Diabetes Study (age [mean ± SD] 53 ± 10 years; 65% male; BMI 32 ± 6 kg/m2, metformin use 57%) underwent detailed metabolic characterisation (hyperinsulinaemic-euglycaemic clamp, IVGTT) during the first year after diagnosis. Participants provided self-reported data from the time of diagnosis. The change in fasting glucose was assessed in relation to SLC2A2 genotype and glucose-lowering treatment using two-way ANCOVA with gene×treatment interactions adjusted for age, sex, BMI and diabetes duration.

Results: The C variant allele of rs8192675 was associated with a higher prevalence of diabetes symptoms at diabetes diagnosis. In the metformin monotherapy group only, patients with a C allele showed a larger adjusted blood glucose reduction during the first year after diabetes diagnosis than patients with the TT genotype (6.3 mmol/l vs 3.9 mmol/l; genotype difference 2.4 mmol/l, p = 0.02; p value for genotype interaction [metformin monotherapy vs non-pharmacological therapy] <0.01). The greater decline in fasting glucose (CC/CT vs TT) in metformin monotherapy persisted after further adjusting for glucose values at diagnosis (genotype difference 1.0 mmol/l, p = 0.01; genotype×treatment interaction p = 0.06).

Conclusions/interpretation: The variant rs8192675 in the SLC2A2 gene (C allele) is associated with an improved glucose response to metformin monotherapy during the first year after diagnosis in type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT01055093.

Keywords

Gene interaction; Metformin; Personalised medicine; Type 2 diabetes.

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