IDF21-0047 Association between the advanced glycation end-products and the vascular complications in T1D – The DIABAGE study

Background: Type 1 Diabetes (T1D) is associated with an increased risk of vascular complications. Among the pathobiological mechanisms involved, the accumulation of advanced glycation end-products (AGEs) due to non-enzymatic glycation seems to play a key role by promoting inflammation and endothelial dysfunction. Aim: We aimed to investigate the association between the Advanced Glycation End products (AGEs) and vascular complications in Type1 Diabetes. Method: We conducted a cross-sectional study on 196 adults with T1D. AGEs were measured in blood serum (i.e., carboxymethyllysine (CML), methylglyoxal-hydroimidazolone-1 (MGH1), and pentosidine) and by measurement of Skin Autofluorescence (SAF). Associations between AGEs levels and vascular complications were analyzed using a binary logistic regression. Correlations between AGEs and pulse wave velocity (PWV) were also assessed by linear regressions. Significant differences were set for p-values less than 0.05. Results: We found positive associations between different AGEs and vascular complications. SAF was associated with both Microangiopathy (Retinopathy: OR=1.92, p=0.011; Neuropathy: OR=2.02, p=0.04; Nephropathy: OR=1.63, p=0.10; Any microangiopathy: OR=2.83, p<0.0001) and Macroangiopathy (Coronaropathy: OR=3.11, p=0.009; Arteriopathy: OR=1.84, p=0.08; Stroke: OR=2.24, p=0.06; Any macroangiopathy: OR=2.78, p=0.003). For circulating AGEs, only pentosidine was significantly associated with coronaropathy (OR=1.61, p=0.01) and any macroangiopathy (OR=1.52, p=0.005). Furthermore, a significant linear correlation was found between PWV and SAF (r=0.43, p<0.001), pentosidine (r=0.28, p<0.001), and MGH1 (r=0.16, p=0.031). Discussion: SAF appears to be a useful marker for investigating both micro-and macro-vascular complications in T1D. Among the circulating AGES, only pentosidine was associated with macroangiopathy. Furthermore, the correlations between PWV and AGEs may suggest their role in early arterial wall changes. Further studies could help assess the role of each type of AGE and identify sub-populations of T1D at higher risk of vascular complications. Definition of specific thresholds could be useful for routine practice to prevent vascular events in T1D.