Background:
Advanced glycation end products (AGEs), thought to be a measure of cumulative glycemic exposure and glycemia-induced vascular damage, are increased both in renal disease and diabetes. As AGE formation increases the stiffness of the arterial wall and vascular matrix AGEs interfere with nitric oxide action, AGEs may be an important link between renal and coronary artery disease (CAD). Skin intrinsic fluorescence (SIF) is a noninvasive marker of AGEs. We sought to determine if SIF was associated with CAD in type 1 diabetes and whether this relationship was independent of renal function and renal disease.
Methods:
SIF was measured on the volar area of the forearm of 112 subjects from the Pittsburgh Epidemiology of Diabetes Complications study and 60 subjects from MedStar Health Research Institute when mean age and diabetes duration were 48 and 36years, respectively. CAD was defined as a history of myocardial infarction, bypass surgery/revascularization, percutaneous coronary intervention or stenosis >50%. Overt nephropathy (ON) was defined as albumin excretion rate > 200 µg/min, spot urine albumin/creatinine > 300 ug/mg, or history of dialysis/ renal transplant. Cumulative glycemic exposure (updated mean A1c) was determined by averaging HbA1c values collected over follow-up (mean of 18 years in EDC and 10.3 years in MedStar). SIF and serum creatinine were natural log transformed before analyses. Odds ratios (OR) are expressed as per standard deviation change in a given variable.
Results:
Of the 172 participants, 30 had CAD, with an equal number in each sex. SIF levels were higher in those with CAD (p<0.0001). Sex-specific analyses revealed a strong association between SIF and CAD in men in analyses controlled for age and updated mean HbA1c (HR=5.6, 95% CI=2.1-14.6), but a much weaker non-significant association in women (OR=1.4, 95% CI=0.61-3.3); however, formal analyses revealed no significant effect modification by sex (p=0.11) and thus the sexes were combined for the remainder of the analyses. In the combined analyses, controlling for age, sex, and updated mean A1c, each standard deviation change in SIF was associated with a 2.8 greater likelihood of CAD (95 % CI=1.6-5.1). Controlling for serum creatinine (OR=3.1, CI=1.7-5.6) or ON (OR=2.6, CI=1.4-4.8) rather than updated mean A1c did not change this relationship. Accounting for both updated mean A1c and serum creatinine in analyses that also included age and sex, each standard deviation change in SIF was associated with a 2.7-fold greater likelihood for CAD (CI=1.5-5.1) and remained significant when further controlled for ON (OR=2.0, CI=1.0-3.9, p=0.04)
Conclusion:
Skin intrinsic fluorescence is cross-sectionally associated with CAD, independent of renal function and updated mean A1c in subjects with type 1 diabetes.
Skin Intrinsic Fluorescence Is Associated With Coronary Artery Disease in Individuals With Long Duration of Type 1 Diabetes
