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. 2022 Aug;13(8):1531-1546.
doi: 10.1007/s13300-022-01285-1. Epub 2022 Jul 2.

Association Between the Tissue and Circulating Advanced Glycation End-Products and the Micro- and Macrovascular Complications in Type 1 Diabetes: The DIABAGE Study

Alpha M Diallo  1   2 , Stéphane Jaisson  3 , Romain Barriquand  4 , Céline Lukas  4 , Sara Barraud  4   5 , Bénédicte Decoudier  4 , Maud Francois  4 , Sang Ly  4 , Rachid Mahmoudi  6   7 , Carl Arndt  8 , Pierre Nazeyrollas  6   9 , Philippe Gillery  3 , Brigitte Delemer  4   5
Affiliations

Association Between the Tissue and Circulating Advanced Glycation End-Products and the Micro- and Macrovascular Complications in Type 1 Diabetes: The DIABAGE Study

Alpha M Diallo et al. Diabetes Ther. 2022 Aug.

Abstract

Introduction: Type 1 diabetes is associated with an increased risk of vascular complications. We aimed to investigate the association between serum and tissue advanced glycation end-products (AGEs) and micro- and macrovascular complications in type 1 diabetes (T1D).

Methods: We conducted a cross-sectional study on 196 adults with T1D (mean age 44.53 ± 16, mean duration of diabetes 22 ± 12 years, mean HbA1c 8 ± 1.2%). 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 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; any microangiopathy: OR = 2.83, p < 0.0001) and macroangiopathy (coronaropathy: OR = 3.11, p = 0.009; any macroangiopathy: OR = 2.78, p = 0.003). For circulating AGEs, pentosidine was significantly associated with coronaropathy (OR = 1.61, p = 0.01) and any macroangiopathy (OR = 1.52, p = 0.005) while MGH1 was associated with nephropathy (OR 1.72, p = 0.03). 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), but not for CML (r = 0.03, p = 0.598).

Conclusions: Skin autofluorescence appears to be a useful marker for investigating both micro- and macrovascular complications in T1D. In this study, pentosidine was associated with macroangiopathy and MGH1 with nephropathy among the circulating AGEs. Furthermore, the correlations between PWV and AGEs may suggest their value in early prediction of vascular complications in T1D.

Keywords: Advanced glycation end-products; Carboxymethyllysine; Macroangiopathy; Methylglyoxal; Microangiopathy; Pentosidine; Skin autofluorescence; Type 1 diabetes; Vascular complications.

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Figures

Fig. 1
Fig. 1
Comparison of tissue (evaluated by SAF) and circulating (i.e., CML, pentosidine, MGH1) AGEs between patients with macroangiopathy and those without macroangiopathy. Data are presented in box plots comparing patients with macroangiopathy and those without macroangiopathy. Skin autofluorescence (SAF), which reflects the tissue content of advanced glycation end-products, is represented in box plot A and circulating AGE are represented in box plots B for pentosidine, C for carboxymethylation, and D for methylglyoxal, respectively
Fig. 2
Fig. 2
Linear correlation between the pulse wave velocity and tissue (evaluated by SAF) and circulating AGEs (i.e., pentosidine, CML, and MGH1)
Fig. 3
Fig. 3
Comparison of tissue (evaluated by SAF) and circulating (i.e., CML, pentosidine, MGH1) AGEs between patients with microangiopathy and those without microangiopathy. Data are presented in box plots comparing patients with microangiopathy and those without microangiopathy. Skin autofluorescence (SAF), which reflects the tissue content of advanced glycation end-products, is represented in box plot A and circulating AGE are represented in box plots B for pentosidine, C for carboxymethyllisine, and D for methylglyoxal, respectively
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