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Phenotypic and genetic characteristics of patients with type 2 diabetes with different responses to metformin therapy in Novosibirsk region

https://doi.org/10.14341/DM2004146-47

Abstract

Aim: The purpose of this study was to examine the phenotypic and genetic characteristics of patients with type 2 diabetes mellitus (T2DM) with different responses to treatment with metformin (MF) in the Novosibirsk region. 

Materials and methods: We examined 460 patients with T2DM in the Novosibirsk region. Patients were divided into groups according to their HbA1c level: patients who achieved the target HbA1c level during MF therapy (n = 209) and those who did not reach the target HbA1c level (n=251). Genotyping of ATM (rs11212617) was performed using polymerase chain reaction by TaqMan. 

Results: Patients who achieved the target HbA1c level during MF treatment (good response) were older (61. 1±9. 1 years vs. 57. 4±8. 4 years, p=0. 001), had later onset of diabetes (54. 6 ± 10. 1 years vs. 49. 2±8. 5 years, p = 0. 0001) and shorter duration of diabetes (6. 5±5. 9 years vs. 8. 2±6. 1 years, p=0. 03) compared with those who did not achieve the target HbA1c level. There was no statistically significant association between ATM rs11212617 and achieving the target HbA1c level among all patients [odds ratio (OR)=0. 94, 95% confidence interval = (0. 73–1. 23), p=0. 67] or those with MF monotherapy [OR=0. 90, (0. 65–1. 25), p=0. 54] or combination therapy [OR=1. 02, (0. 72–1. 43), p=0. 92]. There was an effect of age on response to MF therapy in all three groups (all patients: p=0. 001, MF monotherapy group: p=0. 04, combination therapy group: p=0. 0009). In the MF monotherapy group, low dose MF was associated with a good response (p=0. 03), and in the combination therapy group, males were more likely to have a good response (p=0. 003). Patients with genotype C/C or A/C for ATM (rs11212617) compared with those with genotype A/A were more likely to have high levels of triglycerides [2. 33 (1. 52–4. 2) mmol/l, 2. 09 (1. 35–3. 0) mmol/l and 1. 99 (1. 49–3. 21) mmol/l, respectively, p=0. 001], coronary heart disease (CHD) (13. 4%, 13. 4% and 9. 6%, respectively, p=0. 009) and myocardial infarction (7. 8%, 3. 2% and 4. 0%, respectively, p=0. 001). 

Conclusion: Patients with T2DM who had a good response to MF therapy were older, more likely to be male and had a later onset of T2DM. Genotype C/C for ATM rs11212617 was associated with high triglycerides, CHD and myocardial infarction. ATM rs11212617 was not associated with response to MF therapy in the Novosibirsk region. 

About the Authors

Irina A. Bondar
Novosibirsk State Medical University, Novosibirsk
Russian Federation
MD, PhD, Professor, Head of the Department of Endocrinology Medical University «Novosibirsk State Medical University"
Competing Interests: The authors declare no conflict (of duality) interests in writing this article


Olesya Y. Shabelnikova
Novosibirsk State Medical University, Novosibirsk; Novosibirsk State Regional Hospital, Novosibirsk
Russian Federation
MD, PhD, research assistant of the Department of Endocrinology «Novosibirsk State Medical University", Head of Regional Endocrinology Center "Novosibirsk Regional Hospital"
Competing Interests: The authors declare no conflict (of duality) interests in writing this article


Ekaterina A. Sokolova
Institute of Chemical Biology and Fundamental Medicine, Novosibirsk; Novosibirsk State University, Novosibirsk
Russian Federation

engineering laboratory "Pharmacogenomics" "Institute of Chemical Biology and Fundamental Medicine." "National Research Novosibirsk State University"


Competing Interests: The authors declare no conflict (of duality) interests in writing this article


Olga V. Pyankova
Novosibirsk State University, Novosibirsk
Russian Federation

Competing Interests: The authors declare no conflict (of duality) interests in writing this article


Maksim L. Filipenko
Institute of Chemical Biology and Fundamental Medicine, Novosibirsk; Novosibirsk State University, Novosibirsk
Russian Federation
PhD in Biology, Head of the laboratory "Pharmacogenomics" of "Institute of Chemical Biology and Fundamental Medicine"
Competing Interests: The authors declare no conflict (of duality) interests in writing this article


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For citations:


Bondar I.A., Shabelnikova O.Y., Sokolova E.A., Pyankova O.V., Filipenko M.L. Phenotypic and genetic characteristics of patients with type 2 diabetes with different responses to metformin therapy in Novosibirsk region. Diabetes mellitus. 2016;19(2):125-131. (In Russ.) https://doi.org/10.14341/DM2004146-47

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