Skin collagen fluorophore LW-1 versus skin fluorescence as markers for the long-term progression of subclinical macrovascular disease in type 1 diabetes.
Skin collagen fluorophore LW-1 versus skin fluorescence as markers for the long-term progression of subclinical macrovascular disease in type 1 diabetes.
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DOI：
10.1186/s12933-016-0343-3
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发表时间：
2016-02-11
影响因子：
9.3
通讯作者：
Monnier VM
中科院分区：
文献类型：
--
作者：
Sell DR;Sun W;Gao X;Strauch C;Lachin JM;Cleary PA;Genuth S;DCCT/EDIC Research Group;Monnier VM
皮肤胶原长波长荧光（LWF）被广泛用作晚期糖基化终产物积累的替代标记物。在这里，我们确定了来自DCCT的216名参与者在EDIC期间LWF与血糖、皮肤荧光和并发症进展的关系。LW-1和胶原连接的荧光（CLF）通过具有荧光检测的高效液相色谱（HPLC）（LW-1）或从DCCT结束时获得的皮肤活检中提取的不溶性皮肤胶原中的胶原酶抑制剂（CLF）的总荧光来测量（1993）。在EDIC第16年，通过SCOUT DS仪器在前臂掌侧皮肤上非侵入性地测量皮肤固有荧光（SIF）。LW-1水平随着年龄和糖尿病病程的增加而显著增加（P < 0.0001），在初级（P < 0.0001）和次级（P < 0.037）DCCT队列中，与常规血糖治疗相比，强化治疗显著降低。水平与13-16年视网膜病变进展风险（>3个持续性微动脉瘤，P = 0.0004）和白蛋白排泄率（P = 0.0038）相关，后者尽管调整了HbA 1c。对未来亚临床大血管疾病风险的所有三种荧光指标的比较分析显示，在调整年龄、糖尿病病程和HbA 1c后，以下显著（P < 0.05）相关性：冠状动脉钙与SIF和CLF;内膜中层厚度与SIF和LW-1;左心室质量与LW-1和CLF。LW-1是一种新的风险标志物，与1型糖尿病微血管疾病、内膜中层厚度和左心室质量的未来进展密切相关。在clinicaltrials.gov上注册NCT 00360815和NCT 00360893本文的在线版本（doi：10.1186/s12933-016-0343-3）包含补充材料，可供授权用户使用。
Skin collagen Long Wavelength Fluorescence (LWF) is widely used as a surrogate marker for accumulation of advanced glycation end-products. Here we determined the relationship of LWF with glycemia, skin fluorescence, and the progression of complications during EDIC in 216 participants from the DCCT. LW-1 and collagen-linked fluorescence (CLF) were measured by either High Performance Liquid Chromatography (HPLC) with fluorescence detection (LW-1) or total fluorescence of collagenase digests (CLF) in insoluble skin collagen extracted from skin biopsies obtained at the end of the DCCT (1993). Skin intrinsic fluorescence (SIF) was noninvasively measured on volar forearm skin at EDIC year 16 by the SCOUT DS instrument. LW-1 levels significantly increased with age and diabetes duration (P < 0.0001) and significantly decreased by intensive vs. conventional glycemic therapy in both the primary (P < 0.0001) and secondary (P < 0.037) DCCT cohorts. Levels were associated with 13–16 year progression risk of retinopathy (>3 sustained microaneurysms, P = 0.0004) and albumin excretion rate (P = 0.0038), the latter despite adjustment for HbA1c. Comparative analysis for all three fluorescent measures for future risk of subclinical macrovascular disease revealed the following significant (P < 0.05) associations after adjusting for age, diabetes duration and HbA1c: coronary artery calcium with SIF and CLF; intima-media thickness with SIF and LW-1; and left ventricular mass with LW-1 and CLF. LW-1 is a novel risk marker that is robustly and independently associated with the future progression of microvascular disease, intima-media thickness and left ventricular mass in type 1 diabetes. Trial registration NCT00360815 and NCT00360893 at clinicaltrials.gov The online version of this article (doi:10.1186/s12933-016-0343-3) contains supplementary material, which is available to authorized users.