TY - JOUR
T1 - Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetes
AU - Dujic, Tanja
AU - Bego, Tamer
AU - Malenica, Maja
AU - Velija-Asimi, Zelija
AU - Ahlqvist, Emma
AU - Groop, Leif
AU - Pearson, Ewan R.
AU - Causevic, Adlija
AU - Semiz, Sabina
N1 - Funding Information:
The authors acknowledge medical doctors from the Health Centre of Sarajevo Canton and paramedical staff from the Clinic for Endocrinology and Diabetes, University Clinical Centre of Sarajevo, who assisted in the study. The study was supported by grants received from the Council of Ministers/Ministry of Civil Affairs of Bosnia and Herzegovina and the Federal Ministry for Education and Science of Bosnia and Herzegovina awarded to S.S., by a European Foundation for the Study of Diabetes Albert Renold Travel Fellowship to T.D., and by grants to E.A. from Diabetes Wellness Sweden (25-420 PG) and the Swedish Research Council (Dnr. 2017-02688). T.D. holds a Wellcome Trust Seed Award in Science (209943/Z/17/Z). E.R.P. holds a Wellcome Trust New Investigator Award (102820/Z/13/Z).
Funding Information:
The study was supported by grants received from the Council of Ministers/Ministry of Civil Affairs of Bosnia and Herzegovina and the Federal Ministry for Education and Science of Bosnia and Herzegovina awarded to S.S., by a European Foundation for the Study of Diabetes Albert Renold Travel Fellowship to T.D., and by grants to E.A. from Diabetes Wellness Sweden (25–420 PG) and the Swedish Research Council (Dnr. 2017–02688). T.D. holds a Wellcome Trust Seed Award in Science (209943/Z/17/Z). E.R.P. holds a Wellcome Trust New Investigator Award (102820/Z/13/Z).
Publisher Copyright:
© 2019, Association of Basic Medical Sciences of FBIH. All rights reserved.
PY - 2019
Y1 - 2019
N2 - The response to metformin, the most commonly used drug for the treatment of type 2 diabetes (T2D), is highly variable. The common variant rs7903146 C>T within the transcription factor 7-like 2 gene (TCF7L2) is the strongest genetic risk factor associated with T2D to date. In this study, we explored the effects of the TCF7L2 rs7903146 genotype on metformin response in T2D. The study included 86 newly diagnosed patients with T2D, incident users of metformin. Levels of fasting glucose, insulin, HbA1c, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and anthropometric parameters were measured prior to metformin therapy, and 6 and 12 months after the treatment. Genotyping of the TCF7L2 rs7903146 was performed by the Sequenom MassARRAY® iPLEX® platform. At baseline, the diabetes risk allele (T) showed an association with lower triglyceride levels (p = 0.037). After 12 months of metformin treatment, the T allele was associated with 25.9% lower fasting insulin levels (95% CI 10.9-38.3%, p = 0.002) and 29.1% lower HOMA-IR index (95% CI 10.1-44.1%, p = 0.005), after adjustment for baseline values. Moreover, the T allele was associated with 6.7% lower fasting glucose levels (95% CI 1.1-12.0%, p = 0.021), adjusted for baseline glucose and baseline HOMA-%B levels, after 6 months of metformin treatment. This effect was more pronounced in the TT carriers who had 16.8% lower fasting glucose levels (95% CI 7.0-25.6%, p = 0.002) compared to the patients with CC genotype. Our results suggest that the TCF7L2 rs7903146 variant affects markers of insulin resistance and glycemic response to metformin in newly diagnosed patients with T2D within the first year of metformin treatment.
AB - The response to metformin, the most commonly used drug for the treatment of type 2 diabetes (T2D), is highly variable. The common variant rs7903146 C>T within the transcription factor 7-like 2 gene (TCF7L2) is the strongest genetic risk factor associated with T2D to date. In this study, we explored the effects of the TCF7L2 rs7903146 genotype on metformin response in T2D. The study included 86 newly diagnosed patients with T2D, incident users of metformin. Levels of fasting glucose, insulin, HbA1c, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and anthropometric parameters were measured prior to metformin therapy, and 6 and 12 months after the treatment. Genotyping of the TCF7L2 rs7903146 was performed by the Sequenom MassARRAY® iPLEX® platform. At baseline, the diabetes risk allele (T) showed an association with lower triglyceride levels (p = 0.037). After 12 months of metformin treatment, the T allele was associated with 25.9% lower fasting insulin levels (95% CI 10.9-38.3%, p = 0.002) and 29.1% lower HOMA-IR index (95% CI 10.1-44.1%, p = 0.005), after adjustment for baseline values. Moreover, the T allele was associated with 6.7% lower fasting glucose levels (95% CI 1.1-12.0%, p = 0.021), adjusted for baseline glucose and baseline HOMA-%B levels, after 6 months of metformin treatment. This effect was more pronounced in the TT carriers who had 16.8% lower fasting glucose levels (95% CI 7.0-25.6%, p = 0.002) compared to the patients with CC genotype. Our results suggest that the TCF7L2 rs7903146 variant affects markers of insulin resistance and glycemic response to metformin in newly diagnosed patients with T2D within the first year of metformin treatment.
KW - Metformin
KW - Pharmacogenetics
KW - TCF7L2
KW - Transcription factor 7-like 2 gene
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85074743887&partnerID=8YFLogxK
U2 - 10.17305/bjbms.2019.4181
DO - 10.17305/bjbms.2019.4181
M3 - Article
C2 - 31070566
AN - SCOPUS:85074743887
SN - 1512-8601
VL - 19
SP - 368
EP - 374
JO - Bosnian Journal of Basic Medical Sciences
JF - Bosnian Journal of Basic Medical Sciences
IS - 4
ER -