Genetic variants of the insulin receptor substrate-1 are influencing the therapeutic efficacy of oral antidiabetics
| Autor: | Elena R. Lebedeva, Kai Pitterle, Julia Kirchheiner, Axel Fischer, Sumit Parmar, Ivar Roots, Bruna Stringari Altissimo, Angela Seeringer, Lisa Zondler |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class Endocrinology Diabetes and Metabolism medicine.medical_treatment Type 2 diabetes Pharmacology Endocrinology Internal medicine Internal Medicine Medicine Humans Hypoglycemic Agents Acarbose Aged Glycated Hemoglobin Polymorphism Genetic biology business.industry Insulin medicine.disease Sulfonylurea IRS1 Metformin Insulin receptor Diabetes Mellitus Type 2 biology.protein Insulin Receptor Substrate Proteins Female business Pharmacogenetics medicine.drug |
| Zdroj: | Diabetes, obesitymetabolism. 12(12) |
| ISSN: | 1463-1326 |
| Popis: | Aim: The therapeutic efficacy of oral hypoglycaemic drugs varies between individuals, and pharmacogenetic factors contribute to this variability. The Gly972Arg polymorphism in the insulin receptor substrate-1 (IRS-1) has been shown to play a role in insulin signal transduction and therapeutic failure to sulphonylurea drugs. Methods: We studied the association between the IRS-1 polymorphism and the haemoglobin A1c (HbA1c) level in diabetic patients treated with insulinotropic versus non-insulinotropic hypoglycaemic drugs as a marker for the efficacy of an antidiabetic treatment. Genotyping of the IRS-1 Arg972 variant was performed in type 2 diabetes patients treated with either sulphonylurea drugs, glinides or insulin or with metformin, acarbose or glitazones using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Significantly higher HbA1c levels were observed in carriers of the Arg972 variant after treatment with insulinotropic drugs compared to wild-type carriers (8.3 vs. 7.6%, p = 0.005, independent t-test). Furthermore, patients with secondary failure to insulinotropic hypoglycaemic drugs switching finally to insulin showed even higher HbA1c levels in carriers of Arg972 compared to wild-type (8.7 vs. 7.6%, p = 0.005, independent t-test). Conclusions: Thus, we were able to replicate the earlier findings of an association between the IRS-1 Arg972 variant and secondary failure to sulphonylurea drugs, and further observed a general association between HbA1c and this polymorphism in type 2 diabetes patients treated with insulinotropic hypoglycaemic drugs but not with metformin. |
| Databáze: | OpenAIRE |
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