Hamano Kumiko, Nakadaira Ikue, Suzuki Jun, Gonai Megumi
Department of Diabetes and Endocrinology, Kanto Rosai Hospital, Kawasaki, Japan.
Vasc Health Risk Manag. 2014 Oct 3;10:585-9. doi: 10.2147/VHRM.S67753. eCollection 2014.
AIM/INTRODUCTION: Circulating levels of N-terminal fragment of probrain natriuretic peptide (NT-proBNP) are established as a risk factor for cardiovascular disease and mortality in patients with diabetes, as well as in the general population. We sought to examine the possibility of NT-proBNP as a biomarker of microvascular complications in patients with type 2 diabetes.
In total, 277 outpatients with type 2 diabetes were consecutively enrolled as a hospital cohort. Two hundred and seventeen of these patients (132 males; mean age, 63.4 years) were designated as cases with any of the diabetic complications (retinopathy, neuropathy, nephropathy, ischemic heart disease, strokes, peripheral artery disease), and 60 (42 males; mean age, 54.1 years) were set as controls without clinical evidence of diabetic complications. Diabetic complications were evaluated by medical record and routine laboratory examinations. NT-proBNP was measured and investigated with regard to the associations with diabetic complications.
Mean NT-proBNP levels were significantly higher in patients with any of the diabetic complications (59 versus 33 pg/mL; P<0.0001). In logistic regression analysis, NT-proBNP levels >79 pg/mL, which was the highest tertile, were independently associated with a 5.04 fold increased risk of all complications (P<0.0051) compared to the lowest tertile (NT-proBNP levels <31 pg/mL). Odd ratios of cardiovascular disease and nephropathy, neuropathy, and retinopathy were 9.33, 6.23, 6.6 and 13.78 respectively, in patients with NT-proBNP values in the highest tertile (>79 pg/mL), independently of age, sex, duration of diabetes or other risk factors, such as body mass index or hemoglobin A1c. In addition, NT-proBNP levels were associated with surrogate markers of atherosclerosis, such as brachial-ankle pulse wave velocity (r=0.449, P<0.0001) and left ventricular hypertrophy (r=0.212, P<0.001).
In this hospital-based cohort of type 2 diabetes, the NT-proBNP levels were associated with systemic atherosclerosis and comorbid diabetic microvascular as well as macrovascular complications. It is useful to stratify high-risk diabetic patients by measuring NT-proBNP and to start comprehensive care for preventing the progression of diabetic complications. It is necessary to elucidate the underlying mechanism for the progression of diabetic complications represented by an elevation of NT-proBNP and to demonstrate the ability of NT-proBNP as a predictive global biomarker for diabetic complications in Japanese type 2 diabetic patients.
目的/引言：脑钠肽前体N端片段（NT-proBNP）的循环水平已被确认为糖尿病患者以及普通人群心血管疾病和死亡的危险因素。我们试图研究NT-proBNP作为2型糖尿病患者微血管并发症生物标志物的可能性。
总共连续纳入277例2型糖尿病门诊患者作为医院队列。其中217例患者（132例男性；平均年龄63.4岁）被指定为患有任何糖尿病并发症（视网膜病变、神经病变、肾病、缺血性心脏病、中风、外周动脉疾病）的病例，60例（42例男性；平均年龄54.1岁）被设为无糖尿病并发症临床证据的对照组。通过病历和常规实验室检查评估糖尿病并发症。测量NT-proBNP并研究其与糖尿病并发症的关联。
患有任何糖尿病并发症的患者NT-proBNP平均水平显著更高（59对33 pg/mL；P<0.0001）。在逻辑回归分析中，NT-proBNP水平>79 pg/mL（最高三分位数）与所有并发症风险增加5.04倍独立相关（P<0.0051），相比最低三分位数（NT-proBNP水平<31 pg/mL）。NT-proBNP值处于最高三分位数（>79 pg/mL）的患者，心血管疾病、肾病、神经病变和视网膜病变的比值比分别为9.33、6.23、6.6和13.78，独立于年龄、性别、糖尿病病程或其他危险因素，如体重指数或糖化血红蛋白。此外，NT-proBNP水平与动脉粥样硬化的替代标志物相关，如臂踝脉搏波速度（r=0.449，P<0.0001）和左心室肥厚（r=0.212，P<0.001）。
在这个基于医院的2型糖尿病队列中，NT-proBNP水平与全身动脉粥样硬化、合并的糖尿病微血管以及大血管并发症相关。通过测量NT-proBNP对高危糖尿病患者进行分层并开始全面护理以预防糖尿病并发症进展是有用的。有必要阐明以NT-proBNP升高为代表的糖尿病并发症进展的潜在机制，并证明NT-proBNP作为日本2型糖尿病患者糖尿病并发症预测性整体生物标志物的能力。
