Vanderbilt Epidemiology Center, Vanderbilt University , Nashville, Tennessee, USA.
Diabetes Technol Ther. 2010 May;12(5):339-45. doi: 10.1089/dia.2009.0152.
Coronary artery calcification (CAC) is more severe and occurs at an earlier age in type 1 diabetes. Risk factors for this subclinical marker of atherosclerotic burden, like coronary artery disease (CAD) itself, are not fully identified. One postulated mechanism for the increased CAC observed in type 1 diabetes is the accumulation of advanced glycation end products (AGEs). As certain collagen AGEs fluoresce, skin intrinsic fluorescence (SIF) can act as a novel marker of levels of collagen AGEs. We thus sought to determine the relationship between skin intrinsic fluorescence and CAC in type 1 diabetes.
One hundred five participants in the Pittsburgh Epidemiology of Diabetes Complications study of childhood-onset (age <17 years) type 1 diabetes who had previously undergone electron beam tomography scanning for CAC (80 of whom had follow-up data) had SIF measurements taken using the SCOUT DM (VeraLight, Inc., Albuquerque, NM). Mean age and diabetes' duration were 49 and 40 years, respectively, at the time of SIF measurement.
Seventy-one percent of the study participants had some measurable CAC that was univariately (but not after age adjustment) cross-sectionally associated with SIF (odds ratio = 2.51, 1.37-4.59). However, for CAC severity using natural logarithmically transformed scores, SIF was both univariately (P < 0.0001) and multivariably (P = 0.03) associated with CAC. This relationship was independent of age, a history of CAD, renal function, or renal damage. Receiver operator characteristic analyses revealed that the discriminative ability of SIF to detect CAC went from an area under the curve of 71% for the presence of any CAC to 85% for those with a CAC score >400.
The relationship between SIF and CAC appears stronger with more severe calcification. Given the strong relationship of CAC with CAD this finding has important implications and suggests that SIF maybe a useful marker of CAC/CAD risk and potentially a therapeutic target.
1 型糖尿病患者的冠状动脉钙化(CAC)更为严重,且发病年龄更早。这种亚临床动脉粥样硬化负担标志物的风险因素,如冠心病(CAD)本身,尚未完全确定。1 型糖尿病中观察到 CAC 增加的一个假设机制是晚期糖基化终产物(AGEs)的积累。由于某些胶原 AGE 具有荧光性,因此皮肤固有荧光(SIF)可以作为胶原 AGE 水平的新型标志物。因此,我们试图确定 1 型糖尿病患者的皮肤固有荧光与 CAC 之间的关系。
先前曾对 105 名儿童期(年龄 <17 岁)1 型糖尿病患者进行过电子束计算机断层扫描(EBT)扫描以评估 CAC(其中 80 名患者有随访数据)的匹兹堡糖尿病并发症流行病学研究(Pittsburgh Epidemiology of Diabetes Complications study)参与者进行了 SIF 测量,使用的是 SCOUT DM(VeraLight,Inc.,新墨西哥州阿尔伯克基)。在进行 SIF 测量时,参与者的平均年龄和糖尿病病程分别为 49 岁和 40 年。
研究参与者中有 71%的人有可测量的 CAC,SIF 与 CAC 呈正相关(比值比=2.51,1.37-4.59),但这种相关性未经年龄校正。然而,对于使用自然对数转换评分的 CAC 严重程度,SIF 不仅与 CAC 呈正相关(P <0.0001),而且与 CAC 呈多变量相关(P = 0.03)。这种关系独立于年龄、CAD 病史、肾功能或肾脏损伤。受试者工作特征分析显示,SIF 检测 CAC 的区分能力从存在任何 CAC 的曲线下面积(AUC)的 71%提高到 CAC 评分>400 的 AUC 为 85%。
SIF 与 CAC 之间的关系似乎与更严重的钙化程度更密切。鉴于 CAC 与 CAD 之间的紧密关系,这一发现具有重要意义,并表明 SIF 可能是 CAC/CAD 风险的有用标志物,并且可能是一种有治疗作用的靶点。