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[寻找糖尿病中铁代谢受损的其他标志物]

[Searching for additional markers of impaired iron metabolism in diabetes mellitus].

作者信息

Musina Nadezhda N, Saprina Tatiana V, Prokhorenko Tatiana S, Zima Anastasia P

机构信息

Siberian State Medical University.

Siberian State Medical University; Tomsk Regional Blood Center.

出版信息

Probl Endokrinol (Mosk). 2020 Aug 30;66(2):61-70. doi: 10.14341/probl12277.

Abstract

BACKGROUND

It is known that metabolic disorders in diabetes mellitus have a regulating effect on ferrokinetics, and therefore diabetes mellitus is often accompanied by various disorders of iron metabolism, both anemia and secondary iron overload. The main problem is timely and accurate differential diagnosis between anemia of chronic diseases and iron deficiency anemia. It is necessary to establish reliable laboratory markers of anemia of chronic diseases in order to solve this problem, as well as to understand what metabolic disorders can lead to the occurrence and aggravate the course of this type of anemia.

AIMS

To study the frequency of occurrence of violations of ferrokinetics in patients with diabetes mellitus, as well as to establish clinical and biochemical correlations that are significant in the differential diagnosis of various disorders of iron metabolism: iron deficiency anemia, anemia of chronic diseases and dysmetabolic iron overload syndrome in diabetes mellitus.

MATERIALS AND METHODS

The research design a single-stage observational single-center research. The research was conducted on the basis of the endocrinological clinic of the Federal State Budgetary Educational Institution of Higher Education Siberian State Medical University in Tomsk. The research included 76 patients with type 1 and type 2 diabetes mellitus. We conducted an assessment of all patients as follows: anthropometric data assessment; glycated hemoglobin study; creatinine level study with the calculation of glomerular filtration rate (GFR) using the CKD-EPI formula. We also evaluated the number of erythrocytes, reticulocytes, the hemoglobin concentration, haematocrit level and biochemical parameters of iron metabolism: serum iron and ferritin concentrations; the concentration of hepsidin and non-specific markers of inflammation: erythrocyte sedimentation rate (ESR) and highly sensitive C-reactive protein (CRP).

RESULTS

20 people (26.3%) of the 76 patients included in the study, had type 1 diabetes mellitus and 56 people (73.3%) had type 2 diabetes mellitus. The parameters of ferrokinetics did not significantly differ in patients with type 1 and type 2 diabetes mellitus, while in the group of patients with 20 patients (26.3%) from the 76 ones included into the research had type 1 diabetes mellitus and 56 (73.3%) from them had type 2 diabetes mellitus. The parameters of ferrokinetics did not significantly differ in patients with type 1 and type 2 diabetes mellitus, while in the group of patients with type 2 diabetes mellitus, the levels of CRP (p=0.034) and blood leukocytes (p=0.020) were significantly higher than in patients with type 1 diabetes mellitus. Both in the main group of patients with impaired carbohydrate metabolism, and in patients with type 2 diabetes mellitus, anemia of chronic diseases prevailed in the structure of the anemia syndrome. After dividing the main group of patients into groups by type of anemia syndrome: absence of anemia, anemia of chronic diseases and iron deficiency anemia, a comparative analysis of the average values of markers of inflammation and the level of hepsidin in these groups was performed. It was found that in patients with anemia of chronic diseases, the level of hepsidin is significantly higher than in patients without anemic syndrome (p=0.033). Paired correlation analysis showed a positive correlation of ESR with microalbuminuria (r=0.515; P<0.0001), creatinine level (r=0.467; P<0.0001) and negative — with GFR (r= -0.436; P<0.0001) and iron in serum (r=-0.276; p=0.017). As the result of ROC analysis the most informative in the diagnosis of anemia of chronic disease were: ferritin — sensitivity 78%, specificity 52% with a diagnostic threshold of 75.5 ng/ml (area under the curve 0,695; p=0.006); ESR — sensitivity 67%, specificity 64% with a diagnostic threshold of 15.5 mm/HR (area under the curve of 0.750 in; p=0.040) and the CRP — sensitivity 67%, specificity 64% with a diagnostic threshold of 5.2 ng/ml (area under the curve 0,646; р<0.0001).

CONCLUSION

Thus, the studied markers of inflammation — ESR and CRP, as well as hepsidin in combination with the classic diagnostic parameter — ferritin, demonstrated high value in the diagnosis of anemia of chronic diseases and can be included in the modified algorithm for differential diagnosis of anemia syndrome in patients with diabetes mellitus.

摘要

背景

众所周知,糖尿病中的代谢紊乱对铁动力学有调节作用,因此糖尿病常伴有各种铁代谢紊乱,包括贫血和继发性铁过载。主要问题是及时准确地区分慢性病贫血和缺铁性贫血。为了解决这个问题,有必要建立可靠的慢性病贫血实验室标志物,同时了解哪些代谢紊乱会导致这种贫血的发生并加重其病程。

目的

研究糖尿病患者铁动力学异常的发生率,以及建立在鉴别诊断各种铁代谢紊乱(缺铁性贫血、慢性病贫血和糖尿病代谢紊乱性铁过载综合征)中有重要意义的临床和生化相关性。

材料和方法

本研究设计为单阶段观察性单中心研究。研究在托木斯克的西伯利亚国立医科大学联邦国家预算高等教育机构内分泌诊所进行。研究纳入76例1型和2型糖尿病患者。我们对所有患者进行了如下评估:人体测量数据评估;糖化血红蛋白研究;肌酐水平研究,并使用CKD-EPI公式计算肾小球滤过率(GFR)。我们还评估了红细胞、网织红细胞数量、血红蛋白浓度、血细胞比容水平以及铁代谢的生化参数:血清铁和铁蛋白浓度;铁调素浓度以及炎症非特异性标志物:红细胞沉降率(ESR)和高敏C反应蛋白(CRP)。

结果

纳入研究的76例患者中,20人(26.3%)患有1型糖尿病,56人(73.3%)患有2型糖尿病。1型和2型糖尿病患者的铁动力学参数无显著差异,而在2型糖尿病患者组中,CRP水平(p = 0.034)和血白细胞水平(p = 0.020)显著高于1型糖尿病患者。在碳水化合物代谢受损的主要患者组以及2型糖尿病患者中,慢性病贫血在贫血综合征结构中占主导。将主要患者组按贫血综合征类型分为:无贫血、慢性病贫血和缺铁性贫血组后,对这些组中炎症标志物平均值和铁调素水平进行了比较分析。发现慢性病贫血患者的铁调素水平显著高于无贫血综合征患者(p = 0.033)。配对相关分析显示ESR与微量白蛋白尿呈正相关(r = 0.515;P < 0.0001)、与肌酐水平呈正相关(r = 0.467;P < 0.0001),与GFR呈负相关(r = -0.436;P < 0.0001)以及与血清铁呈负相关(r = -0.276;p = 0.017)。ROC分析结果显示,在诊断慢性病贫血中最具信息量的指标为:铁蛋白——敏感性78%,特异性52%,诊断阈值为75.5 ng/ml(曲线下面积0.695;p = 0.006);ESR——敏感性67%,特异性64%,诊断阈值为15.5 mm/HR(曲线下面积0.750;p = 0.040);CRP——敏感性67%,特异性64%,诊断阈值为5.2 ng/ml(曲线下面积0.646;p < 0.0001)。

结论

因此,所研究的炎症标志物——ESR和CRP,以及铁调素与经典诊断参数——铁蛋白相结合,在诊断慢性病贫血中显示出高价值,可纳入糖尿病患者贫血综合征鉴别诊断的改良算法中。

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