Dataset Information

Intensive Glucose Control Reduces the Risk Effect of TRIB3, SMARCD3, and ATF6 Genetic Variation on Diabetic Vascular Complications.

ABSTRACT: Type 2 diabetes mellitus is a complex disease. Our previous study revealed that TRIB3 genetic variations were strongly associated with diabetic vascular complications, although TRIB3 regulation pathways remain poorly understood. We used two extreme treatment groups from a 2 × 2 factorial randomized controlled trial to identify a positive association, which was further validated in patients receiving cross treatment to test the effect of genetic polymorphisms among the different treatment groups. A gene-centric score (GS)-weighted model including the three associated genetic variations TRIB3 rs2295490, ATF6 rs12086247, and SMARCD3 rs58125572 was used. The results of the GS model indicated a 46% reduction in the risk of primary vascular complications in patients bearing more than two risk alleles [hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.38-0.76, p < 0.001], following intensive glucose control treatment when compared with patients who received standard glucose control treatment. Furthermore, these patients benefited from active blood pressure-lowering treatment (HR 0.39, 95% CI 0.24-0.64, p < 0.001). However, no significant difference was observed between the two interventions in patients with fewer than two risk alleles (HR 1.09, 95% CI 0.86-1.39, p = 0.47). These results indicate that genetic variants in these three genes may be useful biomarkers for individualized drug therapy in diabetic patients.

SUBMITTER: He F

PROVIDER: S-EPMC6297143 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Intensive Glucose Control Reduces the Risk Effect of TRIB3, SMARCD3, and ATF6 Genetic Variation on Diabetic Vascular Complications.

He Fazhong F Shu Yan Y Wang Xingyu X Liu Xin X Liu Guojing G Chen Zhangren Z Wang Zhenmin Z Li Ling L Liu Rong R Zhou Honghao H Xu Heng H Zhang Wei W Zhou Gan G

Frontiers in pharmacology 20181211

Type 2 diabetes mellitus is a complex disease. Our previous study revealed that TRIB3 genetic variations were strongly associated with diabetic vascular complications, although TRIB3 regulation pathways remain poorly understood. We used two extreme treatment groups from a 2 × 2 factorial randomized controlled trial to identify a positive association, which was further validated in patients receiving cross treatment to test the effect of genetic polymorphisms among the different tre ...[more]

PMID: 30618737

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Project description:BackgroundComplication screening is recommended for patients with type 2 diabetes (T2D), but the optimal screening intensity and schedules are unknown. In this study, we evaluated whether intensive versus standard complication screening affects long-term cardiovascular outcomes.MethodsIn this observational study, we included 368 T2D patients referred for intensive screening provided as a 1-day session of clinical-instrumental evaluation of diabetic complications, followed by dedicated counseling. From a total of 4906 patients, we selected control T2D patients who underwent standard complication screening at different visits, by 2:1 propensity score matching. The primary endpoint was the 4p-MACE, defined as cardiovascular mortality, or non-fatal myocardial infarction, stroke, or heart failure. The Cox proportional regression analyses was used to compare outcome occurrence in the two groups, adjusted for residual confounders.Results357 patients from the intensive screening group (out of 368) were matched with 683 patients in the standard screening group. Clinical characteristics were well balanced between the two groups, except for a slightly higher prevalence of microangiopathy in the intensive group (56% vs 50%; standardized mean difference 0.11, p = 0.1). Median follow-up was 5.6 years. The adjusted incidence of 4p-MACE was significantly lower in the intensive versus standard screening group (HR 0.70; 95% CI 0.52-0.95; p = 0.02). All components of the primary endpoint had nominally lower rates in the intensive versus standard screening group, which was particularly significant for heart failure (HR 0.43; 95% CI 0.22-0.83; p = 0.01).ConclusionAmong T2D patients attending a specialist outpatient clinic, intensive complication screening is followed by better long-term cardiovascular outcomes. No significant effect was noted for cardiovascular and all-cause mortality and the benefit was mainly driven by a reduced rate of hospitalization for heart failure.

Dataset Information

Intensive Glucose Control Reduces the Risk Effect of TRIB3, SMARCD3, and ATF6 Genetic Variation on Diabetic Vascular Complications.

Publications

Intensive Glucose Control Reduces the Risk Effect of <i>TRIB3, SMARCD3</i>, and <i>ATF6</i> Genetic Variation on Diabetic Vascular Complications.

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