| 1. |
- Dujic, Tanja, et al.
(författare)
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Effects of TCF7L2 rs7903146 variant on metformin response in patients with type 2 diabetes
- 2019
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Ingår i: Bosnian Journal of Basic Medical Sciences. - : Association of Basic Medical Sciences of FBIH. - 1512-8601 .- 1840-4812. ; 19:4, s. 368-374
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Mahmutovic, Lejla, et al.
(författare)
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Association of IRS1 genetic variants with glucose control and insulin resistance in type 2 diabetic patients from Bosnia and Herzegovina
- 2019
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Ingår i: Drug Metabolism and Personalized Therapy. - : Walter de Gruyter GmbH. - 2363-8907 .- 2363-8915. ; 34:1
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies reported conflicting results regarding association of insulin receptor substrate 1 (IRS1) gene variation with type 2 diabetes (T2D) and insulin resistance (IR) in different ethnic groups. We examined the association of rs7578326, rs2943641, and rs4675095 in the IRS1 gene with T2D and related traits in a population from Bosnia and Herzegovina, which is one of the European countries with the highest T2D prevalence of 12.5%. Our study included 390 T2D patients and 252 control subjects. Biochemical parameters, including fasting glucose (FG), fasting insulin (FI), homeostasis model assessment insulin resistance index (HOMA-IR), and HbA 1c were measured in all participants. Genotyping analysis was performed by Mass Array Sequenom iPlex platform. Our results demonstrated that rs7578326 and rs4675095 variants were associated with increased FG levels. The rs7578326 was also associated with higher FI, HOMA-IR (B = 0.08, 95% CI [0.01, 0.15], p add = 0.025; B = 0.079, 95% CI [0.006, 0.150], p add = 0.033, respectively) in T2D, and with HbA 1c (B = 0.034, 95% CI [0.003, 0.065], p dom = 0.035) in non-drug-treated T2D. In contrast, rs2943641 C allele was associated with lower FG levels in control subjects (B = -0.17, 95% CI [-0.03, -0.002], p add = 0.030) and HbA 1c (B = 0.03, 95% CI [0.002, 0.06], p dom = 0.040) in non-drug-treated T2D. We report the association between common variants in IRS1 gene with insulin resistance, glucose, and HbA 1c levels in Bosnia and Herzegovina's population.
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