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波兰2型糖尿病患者糖尿病视网膜病变的临床危险因素及维生素D受体基因多态性的作用

Clinical risk factors and the role of VDR gene polymorphisms in diabetic retinopathy in Polish type 2 diabetes patients.

作者信息

Cyganek K, Mirkiewicz-Sieradzka B, Malecki M T, Wolkow P, Skupien J, Bobrek J, Czogala M, Klupa T, Sieradzki J

机构信息

Department of Metabolic Diseases , Jagiellonian University Medical College, 15 Kopernika Street, 31-501, Krakow, Poland.

出版信息

Acta Diabetol. 2006 Dec;43(4):114-9. doi: 10.1007/s00592-006-0225-3.

Abstract

Evidence exists that some clinical, metabolic and genetic risk factors are associated with the development of diabetic retinopathy (DR). The aim of the study was: (1) to define the prevalence of DR in the examined group of 267 patients with type 2 diabetes mellitus (T2DM) from a Polish population; (2) to identify in cross-sectional analysis, the clinical features associated with DR in the study group; and (3) to search for the association of 4 markers of vitamin D receptor (VDR), a candidate gene for vascular complications in diabetes, with DR. The examined group consisted of 146 female and 121 male T2DM patients (mean age at examination: 61.3+/-9.4 years; age at T2DM diagnosis: 50.0+/-9.2; T2DM duration: 11.3+/-7.8 years; body mass index (BMI): 30.5+/-5.5 kg/m(2); HbA1c: 7.8+/-1.5%). In all patients, the clinical and metabolic profile was determined. Diagnosis of DR was determined by a trained ophthalmologist by ophthalmoscopy after pupillary dilatation. Colour photographic documentation was made. The examined T2DM patients were genotyped for FokI, ApaI, BsmI and TaqI frequent VDR polymorphisms based on the restriction fragment length polymorphism method. The statistical analysis was performed using univariate and multivariate logistic regression (SAS) and haplotype analysis (Haplostat). DR was detected in 85 (31.8%) patients with T2DM. The multivariate analysis revealed that significant predictors of this complication were: never-smoking status (odds ratio 2.2, 95% confidence interval 1.2-4), urea serum level (1.3, 1.1-1.5), HbA1c level (1.4, 1.1-1.8) and insulin treatment (2.7, 1.4-5.1). Other features such as age of T2DM diagnosis, T2DM duration prior to ophthalmic exam, obesity (BMI>30), serum creatinine level, albumin/creatinine ratio and arterial hypertension were univariate predictors of DR, however they lost significance as independent predictors in multivariate analysis. Similarly, the alleles, genotypes, haplotype and haplotype combination of VDR were not associated with the examined complication. However, there was a suggestion of a possible slight association between the fbaT haplotype and DR (p=0.11). In conclusion, our study showed that DR in T2DM patients remains a frequent complication in Polish T2DM patients. We were able to confirm the role of some clinical risk factors, surprisingly including not-smoking status, as was previously shown in the UK Prospective Diabetes Study (UKPDS). VDR gene polymorphisms did not constitute a risk factor for this size of study group.

摘要

有证据表明,一些临床、代谢和遗传风险因素与糖尿病视网膜病变(DR)的发生有关。本研究的目的是:(1)确定来自波兰人群的267例2型糖尿病(T2DM)患者检查组中DR的患病率;(2)在横断面分析中确定研究组中与DR相关的临床特征;(3)寻找维生素D受体(VDR)的4种标记物(糖尿病血管并发症的候选基因)与DR的关联。检查组由146例女性和121例男性T2DM患者组成(检查时的平均年龄:61.3±9.4岁;T2DM诊断时的年龄:50.0±9.2岁;T2DM病程:11.3±7.8年;体重指数(BMI):30.5±5.5kg/m²;糖化血红蛋白(HbA1c):7.8±1.5%)。对所有患者进行了临床和代谢特征测定。由训练有素的眼科医生在瞳孔散大后通过检眼镜检查确定DR诊断。进行了彩色照片记录。基于限制性片段长度多态性方法,对检查的T2DM患者进行FokI、ApaI、BsmI和TaqI常见VDR多态性的基因分型。使用单变量和多变量逻辑回归(SAS)以及单倍型分析(Haplostat)进行统计分析。在85例(31.8%)T2DM患者中检测到DR。多变量分析显示,该并发症的显著预测因素为:从不吸烟状态(优势比2.2,95%置信区间1.2 - 4)、血清尿素水平(1.3,1.1 - 1.5)、HbA1c水平(1.4,1.1 - 1.8)和胰岛素治疗(2.7,1.4 - 5.1)。其他特征,如T2DM诊断年龄、眼科检查前的T2DM病程、肥胖(BMI>30)、血清肌酐水平、白蛋白/肌酐比值和动脉高血压是DR的单变量预测因素,但在多变量分析中作为独立预测因素失去了显著性。同样,VDR的等位基因、基因型、单倍型和单倍型组合与所检查的并发症无关。然而,有迹象表明fbaT单倍型与DR之间可能存在轻微关联(p = 0.11)。总之,我们的研究表明,T2DM患者中的DR在波兰T2DM患者中仍然是一种常见并发症。我们能够证实一些临床风险因素的作用,令人惊讶的是包括不吸烟状态,正如英国前瞻性糖尿病研究(UKPDS)先前所示。对于这个规模的研究组,VDR基因多态性不构成风险因素。

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