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Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide.

ABSTRACT: Previous studies showed associations between variants in TCF7L2 gene and the therapeutic response to sulfonylureas. All sulfonylureas stimulate insulin secretion by the closure of ATP-sensitive potassium (KATP) channel. The aim of the present study was to compare TCF7L2 genotype specific effect of gliclazide binding to KATP channel A-site (Group 1) with sulfonylureas binding to AB-site (Group 2). A total of 101 patients were treated with sulfonylureas for 6 months as an add-on therapy to the previous metformin treatment. TCF7L2 rs7903146 C/T genotype was identified by real-time PCR with subsequent melting curve analysis. Analyses using the dominant genetic model showed significantly higher effect of gliclazide in the CC genotype group in comparison with combined CT + TT genotype group (1.32 ± 0.15% versus 0.73 ± 0.11%, P (adj) = 0.005). No significant difference in ?HbA1c between the patients with CC genotype and the T-allele carriers was observed in Group 2. In the multivariate analysis, only the TCF7L2 genotype (P = 0.006) and the baseline HbA1c (P < 0.001) were significant predictors of ?HbA1c. After introducing an interaction term between the TCF7L2 genotype and the sulfonylurea type into multivariate model, the interaction became a significant predictor (P = 0.023) of ?HbA1c. The results indicate significantly higher difference in ?HbA1c among the TCF7L2 genotypes in patients treated with gliclazide than in patients treated with glimepiride, glibenclamide, or glipizide.

SUBMITTER: Javorsky M

PROVIDER: S-EPMC3590634 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide.

Javorský Martin M Babjaková Eva E Klimčáková Lucia L Schroner Zbynek Z Zidzik Jozef J Stolfová Mária M Salagovič Ján J Tkáč Ivan I

International journal of endocrinology 20130220

Previous studies showed associations between variants in TCF7L2 gene and the therapeutic response to sulfonylureas. All sulfonylureas stimulate insulin secretion by the closure of ATP-sensitive potassium (KATP) channel. The aim of the present study was to compare TCF7L2 genotype specific effect of gliclazide binding to KATP channel A-site (Group 1) with sulfonylureas binding to AB-site (Group 2). A total of 101 patients were treated with sulfonylureas for 6 months as an add-on therapy to the pre ...[more]

PMID: 23509454

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Project description:BackgroundDiabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. This study aims to assess the level of glycemic control and factors contributing to uncontrolled glycemia among diabetic patients at the Nekemte Referral Hospital, West Ethiopia.MethodsA cross sectional study was conducted on diabetic patients attending the diabetes clinic of Nekemte Referral Hospital. A total of 252 study participants were included in the study. Data were collected by interviewing patients during hospital visits and reviewing respective databases. The association between dependent and independent variables was assessed using bivariable and stepwise multivariable logistic regression. A variable with a p-value < 0.05 was considered as an independent predictor. A patient's written informed consent was obtained after explaining the purpose and procedures of the study.ResultsMean age of the participants was 41.7 ± 17.6 years. The majority of the participants (67.1%) had poor knowledge about diabetes. The glycemic rate control was 40.5%; while more than half of the participants (59.5%) had poor glycemic control. On multivariable logistic analysis poor glycemic control was more likely to occur among unemployed (p < 0.001), patients with no family/social support (p = 0.024), duration of diabetes >10 years (p = 0.005), poor knowledge about diabetes (p = 0.012), taking insulin (p = 0.004) and taking metformin plus glibenclamide (p < 0.001).ConclusionA finding of this study revealed that a glycemic control of study participants was poor. Thus greater effort is needed to improve glycemic control. Health care professionals should work on improving the adherence to anti-diabetic medications of diabetic patients and knowledge of diabetic patients on diabetes by providing education to the patients during follow up to improve glycemic control.

Project description:IntroductionType 2 diabetes mellitus (T2DM) and comorbid conditions require patients to take complex medication regimens. Greater regimen complexity has been associated with poorer T2DM management; however, the relationship between overall regimen complexity and glycemic control is unclear.ObjectivesOur objectives were: (1) to examine associations between regimen complexity (with the Medication Regimen Complexity Index [MRCI]) and glycemic control (A1C), and (2) to compare overall MRCI with other measures of regimen complexity (overall and diabetes-specific medication count) and diabetes-specific MRCI.MethodsThis was a secondary data analysis of cross-sectional data from a parent trial. Participants were patients with T2DM taking at least 3 chronic medications followed in safety net clinics in the Chicago area. The MRCI measures complexity based on dosing frequency, route of administration, and special instructions for prescribed medications. MRCI scores were created for overall regimens and diabetes-specific medications. Sociodemographics and outpatient visit utilization were included in models as covariates. Linear regression was used to examine the associations between variables of interest and hemoglobin A1C.ResultsParticipants (N = 432) had a mean age of 56.9 years, most were female (66.0%), and Hispanic or Latino (73.3%). Regimen complexity was high based on overall medications (mean = 6.6 medications, SD: 3.09) and MRCI (mean = 21.4, SD: 11.3). Higher diabetes-specific MRCI was associated with higher A1C in bivariate and multivariable models. In multivariable models, overall MRCI greater than 14, fewer outpatient health care visits, male gender, and absence of health insurance were independently associated with higher A1C. The variance in A1C explained by MRCI was higher compared to medication count for overall and diabetes-specific regimen complexity.ConclusionsMore complex regimens are associated with worse A1C and measuring complexity with MRCI may have advantages. Deprescribing, increasing insurance coverage, and promoting engagement in health care may improve A1C among underserved populations with complex regimens.

Project description:Importance:Numerous factors are associated with the ability of patients with type 2 diabetes to achieve optimal glycemic control. However, many of these factors are not modifiable by quality improvement interventions. In contrast, the structure of how diabetes care is delivered, such as whether patients visit an endocrinologist or how prescriptions are filled, is potentially modifiable, yet its associations with glycemic control have not been rigorously evaluated. Objective:To investigate the association of diabetes care delivery with glycemic control in patients with type 2 diabetes using insulin. Design, Setting, and Participants:This retrospective cohort study used baseline claims and laboratory insurer data within a large pragmatic trial to identify individuals with type 2 diabetes using insulin with data for at least 1 hemoglobin A1c (HbA1c) test result from before trial randomization (July 1, 2014, to October 5, 2016) and for key nonmodifiable patient factors as well as diabetes care delivery and behavioral factors measured before the HbA1c test. Analyses were conducted from February 4, 2017, to November 13, 2018. Main Outcomes and Measures:Multivariable modified Poisson regression was used to evaluate the independent associations of nonmodifiable patient factors and potentially modifiable diabetes care delivery and patient behavioral factors with achieving adequate diabetes control (ie, HbA1c level <8%). The extent of measured variation explained in glycemic control by these factors was also explored using pseudo R2 and C statistics. Results:Of 1423 patients included, 565 (39.7%) were women, and the mean (SD) age was 56.4 (9.0) years. In total, 690 (48.5%) had HbA1c levels less than 8%. Age (relative risk [RR] per 1-unit increase, 1.01; 95% CI, 1.00-1.02), persistent use of basal insulin (RR, 1.20; 95% CI, 1.00-1.43), more frequent filling of glucose self-testing supplies (RR, 1.01; 95% CI, 1.01-1.02), visiting an endocrinologist (RR, 1.41; 95% CI, 1.19-1.67), and receipt of insulin prescriptions by mail order (RR, 1.23; 95% CI, 1.03-1.48) were all independently associated with adequate control. Measured potentially modifiable diabetes care factors explained more variation in adequate glycemic control than measured nonmodifiable patient factors (C statistic, 0.661 vs 0.598; pseudo R2 = 0.11 vs 0.04). Conclusions and Relevance:These findings suggest that for patients with type 2 diabetes using insulin, the way in which care is delivered may be more strongly associated with achieving adequate control of HbA1c levels than patient factors that cannot be altered are. Given the potential for intervention, these care delivery factors could be the focus of efforts to improve diabetes outcomes.

Project description:Objective The aim of the study was to investigate the potential interaction between TCF7L2 rs7903146 genotype, which is implicated for type-2 diabetes mellitus genetic susceptibility, HbA1c levels, and the periodontal status of dental patients.Materials and methodsHbA1c levels, clinical periodontal parameters (probing depth, clinical attachment level, bleeding on probing, and plaque index), and several parameters (such as body mass index [BMI], smoking habits, education level, and age) were recorded in 150 patients who fulfilled the criteria for screening for prediabetes/diabetes of the Centers for Disease Control and Prevention. DNA was extracted and the TCF7L2 single nucleotide polymorphism (SNP) rs7903146 was genotyped in all participants.Results Thirty-one patients out of 150 tested were found with unknown hyperglycemia (20.7%). Regarding sex, education, parent with diabetes, normal BMI, smoking, age ≥45 years and prior testing for diabetes, no differences were observed between patients displaying HbA1c < 5.7 and ≥ 5.7% (Pearson's Chi-square test, p > 0.05). Regarding periodontal parameters and differences between subgroups (HbA1c levels ≥ 5.7 and HbA1c levels < 5.7), statistically significant differences were observed for probing depth (3.20 ± 0.94 vs. 2.81 ± 0.78 mm), clinical attachment level (3.54 ± 1.20 vs. 3.18 ± 1.06 mm) and bleeding on probing (0.62 ± 0.25 vs. 0.50 ± 0.24%) with hyperglycemic patients exhibiting worse periodontal conditions (Mann-Whitney test p < 0.05). The allelic and genotype frequencies for the transcription factor 7-like 2 (TCF7L2) gene, SNPs 7903146 did not exhibit a significant difference between the HbA1c > 5.7 and HbA1c < 5.7 groups and the periodontitis and nonperiodontitis subgroups respectively (Fisher's exact test >0.05). Statistical Analysis Patient characteristics and their association with prediabetes were tested by Pearson's Chi-square test (asymptotic, two sided). Differences of periodontal parameters between subgroups were tested with the Mann-Whitney U-test. The associations of allele and genotype frequencies in the patient and control groups were analyzed using the Fisher's exact test of independence.The significance level was set at the 0.05 for all tests.Conclusion A statistically significant association between TCF7L2 rs7903146 genotype and periodontal condition or HbA1c levels was not observed in contrast to statistically significant differences of clinical parameters of periodontitis in patients with hyperglycemia.

Dataset Information

Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide.

Publications

Association between TCF7L2 Genotype and Glycemic Control in Diabetic Patients Treated with Gliclazide.

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