Skin autofluorescence predicts new cardiovascular disease and mortality in people with type 2 diabetes

Abstract

Background: Skin autofluorescence (SAF) is a non-invasive marker of tissue accumulation of advanced glycation endproducts (AGE). Recently, we demonstrated in the general population that elevated SAF levels predict the development of type 2 diabetes (T2D), cardiovascular disease (CVD) and mortality. We evaluated whether elevated SAF may predict the development of CVD and mortality in individuals with T2D.

Methods: We included 2349 people with T2D, available baseline SAF measurements (measured with the AGE reader) and follow-up data from the Lifelines Cohort Study. Of them, 2071 had no clinical CVD at baseline. 60% were already diagnosed with diabetes (median duration 5, IQR 2-9 years), while 40% were detected during the baseline examination by elevated fasting blood glucose ≥7.0 mmol/l) and/or HbA1c ≥6.5% (48 mmol/mol).

Results: Mean (±SD) age was 57 ± 12 yrs., BMI 30.2 ± 5.4 kg/m². 11% of participants with known T2D were treated with diet, the others used oral glucose-lowering medication, with or without insulin; 6% was using insulin alone. Participants with known T2D had higher SAF than those with newly-detected T2D (SAF Z-score 0.56 ± 0.99 vs 0.34 ± 0.89 AU, p < 0.001), which reflects a longer duration of hyperglycaemia in the former group. Participants with existing CVD and T2D had the highest SAF Z-score: 0.78 ± 1.25 AU. During a median follow-up of 3.7 yrs., 195 (7.6%) developed an atherosclerotic CVD event, while 137 (5.4%) died. SAF was strongly associated with the combined outcome of a new CVD event or mortality (OR 2.59, 95% CI 2.10-3.20, p < 0.001), as well as incidence of CVD (OR 2.05, 95% CI 1.61-2.61, p < 0.001) and death (OR 2.98, 2.25-3.94, p < 0.001) as a single outcome. In multivariable analysis for the combined endpoint, SAF retained its significance when sex, systolic blood pressure, HbA1c, total cholesterol, eGFR, as well as antihypertensive and statin medication were included. In a similar multivariable model, SAF was independently associated with mortality as a single outcome, but not with incident CVD.

Conclusions: Measuring SAF can assist in prediction of incident cardiovascular disease and mortality in individuals with T2D. SAF showed a stronger association with future CVD events and mortality than cholesterol or blood pressure levels.

Keywords: Ageing; Cardiovascular disease; Diabetes; Mortality; Prediction; Skin autofluorescence.

Fig. 1

Z-score of skin autofluorescence in relationship to presence of type 2 diabetes and cardiovascular disease. Data are presented as mean ± SEM. For comparison, age-corrected SAF scores are compared with Lifelines participants without diabetes (‘No T2D’). * denotes p < 0.001 versus people with New T2D; $ p = 0.009 vs New T2D; # p < 0.001 vs Known T2D. All are p < 0.001 vs No T2D