Impact of SLC22A1 variants rs622342 and rs72552763 on HbA1c and metformin plasmatic concentration levels in patients with type 2 diabetes mellitus
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SUBMITTER: Ortega-Ayala A
PROVIDER: S-EPMC11209864 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
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Project description:Type 2 diabetes mellitus (T2DM) constitutes a major portion of Jordan's disease burden, and incidence rates are rising at a rapid rate. Due to variability in the drug's response between ethnic groups, it is imperative that the pharmacogenetics of metformin be investigated in the Jordanian population. The objective of this study was to investigate the relationship between twenty-one single nucleotide polymorphisms (SNPs) in the SLC22A1, SLC22A2, and SLC22A3 genes and their effects on metformin pharmacogenetics in Jordanian patients diagnosed with type 2 diabetes mellitus. Blood samples were collected from 212 Jordanian diabetics who fulfilled the inclusion criteria, which were then used in SNP genotyping and determination of HbA1c levels. The rs12194182 SNP in the SLC22A3 gene was found to have a significant association (p < 0.05) with lower mean HbA1c levels, and this association more pronounced in patients with the CC genotype (i.e., p-value was significant before correcting for multiple testing). Moreover, the multinomial logistic regression analysis showed that SNP genotypes within the SLC22A1, SLC22A2, and SLC22A3 genes, body mass index (BMI) and age of diagnosis were significantly associated with glycemic control (p < 0.05). The results of this study can be used to predict response to metformin and other classes of T2DM drugs, making treatment more individualized and resulting in better clinical outcomes.
| S-EPMC6462993 | biostudies-literature
Project description:IntroductionAlu hypomethylation is a common epigenetic process that promotes genomic instability with aging phenotypes, which leads to type 2 diabetes mellitus (type 2 DM). Previously, our results showed significantly decreased Alu methylation levels in type 2 DM patients. In this study, we aimed to investigate the longitudinal changes in Alu methylation levels in these patients.ResultsWe observed significantly decreased Alu methylation levels in type 2 DM patients compared with normal (p = 0.0462). Moreover, our findings demonstrated changes in Alu hypomethylation over a follow-up period within the same individuals (p < 0.0001). A reduction in Alu methylation was found in patients with increasing HbA1c levels (p = 0.0013) and directly correlated with increased HbA1c levels in type 2 DM patients (r = -0.2273, p = 0.0387).ConclusionsAlu methylation in type 2 DM patients progressively decreases with increasing HbA1c levels. This observation suggests a potential association between Alu hypomethylation and the underlying molecular mechanisms of elevated blood glucose. Furthermore, monitoring Alu methylation levels may serve as a valuable biomarker for assessing the clinical outcomes of type 2 DM.
| S-EPMC10623537 | biostudies-literature
Project description:OBJECTIVES: To investigate whether younger patients with type 2 diabetes mellitus have higher glycated hemoglobin A1c (HbA1c) levels compared to older patients, and to determine the factors associated with higher HbA1c levels. METHODS: Data from 1,266 patients from all over Oman were used to obtain the mean HbA1c level, odds ratios (OR), and 95% confidence intervals (CI) from multiple logistic regression models with age groups, sex, duration of diabetes, diabetes treatment, body mass index, estimated glomerular filtration rate (eGFR), tobacco use, and healthcare index as predictors of good (HbA1c <7%) vs. poor (≥7%) glycemic control. RESULTS: Mean HbA1c levels were 8.9, 8.3, and 7.8 in the age groups 20-39, 40-59 and 60+ years, respectively. After controlling for all other covariates, the OR of good glycemic control increased with age, 40-59 years old (OR=1.7; 95% CI 1.1 to 2.6) and 60+ year (OR=2.5; 95% CI 1.6 to 4.0), female gender (OR=1.5; 95% CI 1.2 to 2.0) and in patients with eGFR ≥60 mL/min/1.73 m(2) (OR=1.9; 95% CI 1.1 to 3.3). Longer duration of diabetes (≥5 years) and treatment with oral agents or insulin were inversely related to good glycemic control. CONCLUSION: Younger Omani adults exhibit worse glycemic levels compared to older adults posing a formidable challenge to diabetes care teams.
| S-EPMC3515045 | biostudies-other
Project description:BackgroundMetformin is the most widely used oral antidiabetic agent and can reduce insulin resistance (IR) effectively. Organic cation transporter 1 (encoded by SLC22A1) is responsible for the transport of metformin, and ataxia-telangiectasia-mutated (ATM) is a gene relating to the DNA repair and cell cycle control. The aim of this study was to evaluate if the genetic variants in SLC22A1 rs622342 and ATM rs11212617 could be effective predictors of islet function improvement in patients with type 2 diabetes mellitus (T2DM) on metformin treatment.MethodsThis cross-sectional study included 111 patients with T2DM treated with metformin. Genotyping was performed by the dideoxy chain-termination method. The homeostatic indexes of IR (HOMA-IR) and beta-cell function (HOMA-BCF) were determined according to the homeostasis model assessment.ResultsFasting plasma glucose (FPG) levels, HbA1c levels, and HOMA-IR were significantly higher in patients with the rs622342 AA genotype than in those with C allele (P < 0.05). However, these significant differences were not observed between rs11212617 genotype groups. Further data analysis revealed that the association between the rs622342 polymorphism and HOMA-IR was gender related, and so was rs11212617 polymorphism and HOMA-BCF. HOMA-IR was significantly higher in males with rs622342 AA genotype than in those with C allele (P=0.021), and HOMA-BCF value was significantly higher in females carrying rs11212617 CC genotype than in those with A allele (P=0.038). The common logarithm (Lg10) of HOMA-BCF was positively correlated with the reciprocal of HbA1c (r = 0.629, P < 0.001) and negatively associated with Lg10 FPG (r = -0.708, P < 0.001).ConclusionsThe variant of rs622342 could be a predictor of insulin sensitivity in patients with T2DM treated with metformin. The association between the rs622342 polymorphism and HOMA-IR and the association between the rs11212617 polymorphism and HOMA-BCF were both gender related.
| S-EPMC7231067 | biostudies-literature
Project description:AimsTo investigate the effect of serotonin transporter (5-HTT) polymorphisms on change in HbA1c levels six months after metformin initiation in type 2 diabetes patients.Materials and methodsParticipants of PROVALID (PROspective cohort study in patients with type 2 diabetes mellitus for VALidation of biomarkers) within the GIANTT (Groningen Initiative to ANalyse Type 2 Diabetes Treatment) cohort who initiated metformin were genotyped for combined 5-HTTLPR/rs25531 (L∗L∗, L∗S∗, and S∗S∗) and 5-HTT VNTR (STin 2.12, 12/-, and 10/-) polymorphisms, respectively. Multiple linear regression was applied to determine the change in HbA1c level from baseline date to six months across 5-HTTLPR/VNTR genotype groups, adjusted for baseline HbA1c, age, gender, triglyceride level, low-density lipoprotein level, and serum creatinine.Results157 participants were included, of which 56.2% were male. The average age was 59.3 ± 9.23 years, and the mean baseline HbA1c was 7.49% ± 1.21%. 5-HTTLPR was characterized in 46 patients as L∗L∗, 70 patients as L∗S∗, and 41 patients as S∗S∗ genotypes. No significant association was found between 5-HTTLPR and 5-HTT VNTR genotypes and change in HbA1c after adjustments.Conclusions5-HTT polymorphisms did not affect HbA1c levels six months after the start of metformin. Further long-term studies in large samples would be relevant to determine which polymorphisms can explain the variation in response to metformin treatment.
| S-EPMC10824573 | biostudies-literature
Project description:BackgroundThe rapid increase in prevalence of diabetes mellitus over the last decades warrants more attention to the effects of environmental and occupational exposures on glucose metabolism. Our study aimed to assess the association between the plasma levels of various congeners of polychlorinated biphenyls (PCBs) and the serum concentration of glycated haemoglobin (HbA1c).MethodsOur study population consisted of 140 Iranian adults from seven different occupational groups and a group of non-occupationally exposed female participants. The plasma concentration of PCBs were determined at the laboratory of occupational toxicology at RWTH Aachen University, Germany. We considered an HbA1c concentration of 5.7% and more as indicating a disturbed glucose metabolism. Logistic regression was used to assess the association between quartiles of concentrations of PCB congeners and serum HbA1c.ResultsParticipants with an increased HbA1c value had higher plasma levels of PCB 138, 153, 180 and the PCB sum, although this association was statistically not significant. There was no significant difference between the levels of PCB 138, 153, 180, the sum of these congeners, and PCB 118 in their quartiles when comparing with HbA1c concentrations.ConclusionsFor our cohort, we could not demonstrate a significant association between PCB and HbA1c concentrations indicating a disturbance of glucose metabolism.
| S-EPMC5984357 | biostudies-literature
Project description:(1) Background: Magnesium deficiency is usually associated with type 2 diabetes mellitus (T2DM). Individuals living with T2DM with hypomagnesemia show a more rapid disease progression and have an increased risk for diabetes complications. (2) Methods: This is a cross-sectional and descriptive study in the National Institute of Nutrition and Food Technology of Tunis in Tunisia, including all adult outpatients (≥18 years old) with a diagnosis of T2DM from 1 September 2018 to 31 August 2019. The aim of this study was to evaluate the prevalence of plasmatic magnesium deficiency in a Tunisian population of T2DM and to study the relationship between magnesium status and intake, glycemic control and long-term diabetes-related complications. (3) Results: Among the 101 T2DM outpatients, 13 (12.9%) presented with a plasmatic magnesium deficiency. The mean age was 56 ± 7.9 years with a female predominance (62%, n = 63). The mean of the plasmatic magnesium level was 0.79 ± 0.11 mmol/L (0.5-1.1), and the mean of 24 h urinary magnesium excretion was 87.8 ± 53.8 mg/24 h [4.8-486.2]. HbA1c was significantly higher in the plasmatic magnesium deficiency group than the normal magnesium status group (10% ± 1.3 vs. 8.3% ± 1.9; p = 0.04), with a significant difference in participants with a poor glycemic control (HbA1c > 7%) (100%, n = 13/13 vs. 53%, n = 47/88; p = 0.001). A weak negative relationship was also found between plasmatic magnesium and HbA1c (r = -0.2, p = 0.03). Peripheral artery disease was more commonly described in individuals with low plasmatic magnesium levels than in individuals with normal levels (39%, n = 5 vs. 0%, n = 0; p < 0.001). The mean plasmatic magnesium level in participants without diabetic nephropathy and also peripheral artery disease was significantly higher compared to individuals with each long-term diabetes-related complication (0.8 mmol/L ± 0.1 vs. 0.71 mmol/L ± 0.07; p = 0.006) and (0.8 mmol/L ± 0.1 vs. 0.6 mmol/L ± 0.08; p < 0.001), respectively. (4) Conclusions: Hypomagnesemia was identified in individuals with T2DM, causing poor glycemic control and contributing to the development and progression of diabetes-related microvascular and macrovascular complications.
| S-EPMC8628662 | biostudies-literature
Project description:ObjectiveThis study aimed to evaluate whether the M420del variants of SLC22A1 (rs72552763) is associated with metformin treatment response in Ethiopian patients with type 2 diabetes mellitus (T2DM).Patients and methodsA prospective observational cohort study was conducted on 86 patients with T2DM who had been receiving metformin monotherapy for <1 year. Patients showing ≥0.5% reduction in HbA1c levels from baseline within 3 months and remained low for at least another 3 months were defined as responders while those patients with <0.5% reduction in HbA1c levels and/or those whom started a new class of glucose-lowering drug(s) because of unsatisfactory reduction were defined as non-responders. In addition, good glycemic control was observed when HbA1c ≤7.0%, and the above values were regarded as poor. Genotyping of rs72552763 SNP was performed using TaqMan® Drug Metabolism Enzyme Genotyping Assay and its association with metformin response and glycemic control were assessed by measuring the change in HbA1c and fasting blood glucose levels using Chi-square, logistic regression and Mann-Whitney U-test. Statistical significance was set at p <0.05.ResultsThe minor allele frequency of the rs72552763 SNP of SLC22A1 was 9.3%. Metformin response was significantly higher in deletion_GAT (del_G) genotypes as compared to the wild-type GAT_GAT (G_G) genotypes. Furthermore, a significantly lower median treatment HbA1 level was found in del_G genotypes as compared to G_G genotypes. However, the association of rs72552763 with metformin response was not replicated at the allele level. In contrast, the minor del_allele was significantly associated with good glycemic control compared to the G_allele, though not replicated at del_G genotypes level.ConclusionThis study demonstrated that metformin response was significantly higher in study participants with a heterozygous carrier of M420del variants of SLC22A1 as compared to the wild-type G_G genotypes after 3 months of treatment.
| S-EPMC10460611 | biostudies-literature
Project description:Metabolic syndrome and its pathological sequel, type 2 diabetes are considered as important global health problems. Metformin is the most common drug prescribed for patients with this disorder. Consequently, understanding the genetic pathways involved in pharmacokinetics and pharmacodynamics of this drug can have a considerable effect on the personalized treatment of type 2 diabetes. In this study, we evaluated the association between rs11212617 polymorphism of ATM gene and rs628031 of SLC22A1 gene with response to treatment in newly diagnosed type 2 diabetes patients. We genotyped rs11212617 and rs628031 polymorphism by PCR based restriction fragment length polymorphism (RFLP) and assessed the role of this polymorphisms on response to treatment in 140 patients who have been recently diagnosed with type 2 diabetes and were under monotherapy with metformin for 6 months. Response to metformin was defined by HbA1c and fasting blood sugar (FBS) values. Based on such evaluations, patients were divided into two groups: responders (n= 63) and non-responders (n= 77). No significant association was found between these polymorphisms and response to treatment (OR= 0.86, [95% CI 0.52-1.41], P= 0.32) for rs11212617 and (OR= 0.45, [95% CI 0.64-1.76], P= 0.45) for rs 628031. The reported gene variants in ATM and SLC22A1 are not significantly associated with metformin treatment response in type 2 diabetic patients in an Iranian population.
| S-EPMC4916778 | biostudies-literature
Project description:Improving diabetes self-management (DSM) is facing real-world challenges among people with type 2 diabetes mellitus (T2DM) who have a low education level in resource-limited areas. This study aimed to investigate whether diabetes knowledge could predict glycemic levels in people with T2DM in rural China. This analytical cross-sectional study recruited 321 people with T2DM from eight villages by purposive sampling at baseline. After 10 months, 206 patients completed the follow-up survey and HbA1c tests, with a response rate of 64.17% (206/321). Multiple regression analysis was employed to explore the correlation between diabetes knowledge and HbA1c levels. The patient's diabetes knowledge was significantly negatively correlated with HbA1c levels before and after controlling for covariates in both hierarchical multiple regression and multiple logistic regression (p < 0.01). In addition, other influencing factors, including sex, age, marital status, employment status, income, and HbA1c levels at baseline, were also identified. Diabetes knowledge could predict HbA1c levels significantly among patients with low education levels in rural China. Therefore, interventions on improving diabetes knowledge need to be strengthened for patients in rural China so that they can improve their health outcomes and reduce the disease burden.
| S-EPMC10600128 | biostudies-literature