Skin fluorescence correlates strongly with coronary artery calcification severity in type 1 diabetes

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

FIG. 1.

Median (log 10) CAC by tertiles of SIF. Color images available online at www.liebertonline.com/dia.

FIG. 2.

Receiver operator characteristic curves for the detection of CAC in those with a total volume CAC score >0, >200, and >400. The SIF score was swept from 0.018 to 0.052 arbitrary units to generate each of the ROC curves, and the equal error rates (EERs) and associated SIF thresholds were as follows: for CAC volume score >0, EER = 0.31 at SIF = 0.029; for CAC volume score >200, EER = 0.24 at SIF = 0.033; and for CAC volume score >400, EER = 0.26 at SIF = 0.034. AUC, area under the curve. Color images available online at www.liebertonline.com/dia.