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Increased skin autofluorescence of advanced glycation end products (AGEs) in subjects with cardiovascular risk factors

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International Journal of Diabetes in Developing Countries Aims and scope Submit manuscript

Abstract

Background

As a clinical and non-invasive tool, the AGE Reader measures skin autofluorescence (SAF) to estimate the accumulation of advanced glycation end products (AGEs) in the skin. Accumulation of AGEs has been implicated in several inflammation-associated diseases, including diabetes and cardio-metabolic diseases. This study aimed to assess SAF in subjects with and without cardiovascular risk (CVR) factors and examine the association between SAF and various bio-clinical parameters.

Methods

In a cross-sectional study, we included 250 participants between 19 and 86 years of age divided into two groups: a healthy group (n = 88) and subjects with CVR factors (n = 162 in total, diabetes n = 48, hypertension n = 62, and both n = 52). We assessed skin AGE measures and biological and clinical data.

Results

SAF was significantly higher in subjects with CVR factors than in healthy participants (2.42 ± 0.38 vs 1.90 ± 0.29 respectively; p < 0.001). SAF was associated with age, gender, BMI, duration of diabetes, HbA1c, triglyceride, and obesity. Multivariate analysis showed that age and duration of diabetes were the independent determinants of SAF. The ROC analysis indicated that a SAF > 2.25 AU was the optimal cut-off point to predict the presence of diabetes and/or hypertension and dyslipidemia (p < 0.001).

Conclusion

This Tunisian population-based study shows an increased SAF level in subjects with diabetes and/or hypertension and dyslipidemia compared to healthy subjects. The AGE Reader device is a rapid and non-invasive tool in clinical practice to evaluate and screen CVR factors in Tunisia with a North African phototype.

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Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

AGEs:

advanced glycation end products

BMI:

body mass index

CVR:

cardiovascular risk

DBP:

diastolic blood pressure

DM:

diabetes mellitus

HbA1c:

glycated hemoglobin

HTA:

hypertension

SAF:

skin autofluorescence

SBP:

systolic blood pressure

References

  1. Ben Romdhane H, Ben Ali S, Aissi W, Traissac P, Aounallah-Skhiri H, Bougatef S, et al. Prevalence of diabetes in Northern African countries: the case of Tunisia. BMC Public Health. 2014;14:86.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Maoui A, Bouzid K, Ben Abdelaziz A, Ben abdelaziz A. Epidemiology of type 2 diabetes in the greater Maghreb. Example of Tunisia. Systematic review of the literature. La Tunisie Medicale. 2019;97:286–95.

    PubMed  Google Scholar 

  3. Romdhane HB, Ali SB, Skhiri H, Traissac P, Bougatef S, Maire B, et al. Hypertension among Tunisian adults: results of the TAHINA project. Hypertens Res. 2012;35:341–7.

    Article  PubMed  Google Scholar 

  4. Kechida M. Cardio-metabolic risk factors in Tunisia: state of the art. Intern Emerg Med. 2020;15:537–42.

    Article  PubMed  Google Scholar 

  5. Dal Canto E, Ceriello A, Rydén L, Ferrini M, Hansen TB, Schnell O, Standl E, Beulens JW. Diabetes as a cardiovascular risk factor: an overview of global trends of macro and micro vascular complications. Eur J Prev Cardiol. 2019;26:25–32.

    Article  PubMed  Google Scholar 

  6. Brownlee M. Lilly lecture 1993. Glycation and diabetes complications. Diabetes. 1994;43:836–41.

    Article  CAS  PubMed  Google Scholar 

  7. Baynes JW, Thorpe SR. Glycoxidation and lipoxidation in atherogenesis. Free Radic Biol Med. 2000;28:1708–16.

    Article  CAS  PubMed  Google Scholar 

  8. Van Waateringe RP, Fokkens B, Slagter SN, van der Klauw MM, van Vliet-Ostaptchouk JV, et al. Skin autofluorescence predicts incident type 2 diabetes, cardiovascular disease and mortality in general population. Diabetologia. 2019;62:269–80.

    Article  PubMed  Google Scholar 

  9. Van Waateringe RP, Slagter SN, van Beek AP, van der Klauw MM, van Vliet-Ostaptchouk JV, Graaff R, et al. Skin autofluorescence, a non-invasive biomarker for advanced glycation end products, is associated with the metabolic syndrome and its individual components. Diabetol Metab Syndr. 2017;9:42.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Huebschmann AG, Regensteiner JG, Vlassara H, Reusch JE. Diabetes and advanced glycoxidation end products. Diabetes Care. 2006;29:1420–32.

    Article  CAS  PubMed  Google Scholar 

  11. Busch M, Franke S, Rüster C, Wolf G. Advanced glycation end-products and the kidney. Eur J Clin Invest. 2010;40:742–55.

    Article  CAS  PubMed  Google Scholar 

  12. de Vos LC, Mulder DJ, Smit AJ, Dullaart RP, Kleefstra N, Lijfering WM, Kamphuisen PW, Zeebregts CJ, Lefrandt JD. Skin autofluorescence is associated with 5-year mortality and cardiovascular events in patients with peripheral artery disease. Arterioscler Thromb Vasc Biol. 2014;34:933–8.

    Article  PubMed  Google Scholar 

  13. Kouidrat Y, Zaitouni A, Amad A, Diouf M, Desailloud R, Loas G, Lalau JD. Skin autofluorescence (a marker for advanced glycation end products) and erectile dysfunction in diabetes. J Diabetes Complications. 2017;31:108–13.

    Article  PubMed  Google Scholar 

  14. Schmitt A, Schmitt J, Mȕnch G, Gasic-Milencovic J. Characterization of advanced glycation end products for biochemical studies: side chain modifications and fluorescence characteristics. Anal Biochem. 2005;338:201–15.

    Article  CAS  PubMed  Google Scholar 

  15. Weiss MF, Erhard P, Kader-Attia FA, Wu YC, Deoreo PB, Araki A, Glomb MA, Monnier VM. Mechanisms for the formation of glycoxidation products in end-stage renal disease. Kidney Int. 2000;57:2571–85.

    Article  CAS  PubMed  Google Scholar 

  16. Kerkeni M, Saïdi A, Bouzidi H, Ben Yahya S, Hammami M. Elevated serum levels of AGEs, sRAGE, and pentosidine in Tunisian patients with severity of diabetic retinopathy. Microvasc Res. 2012;84:378–83.

    Article  CAS  PubMed  Google Scholar 

  17. Kerkeni M, Saïdi A, Bouzidi H, Ben Yahya S, Hammami M. Pentosidine as a biomarker for microvascular complications in type 2 diabetic patients. Diab Vasc Dis Res. 2013;10:239–45.

    Article  CAS  PubMed  Google Scholar 

  18. Kerkeni M, Weiss IS, Jaisson S, Dandana A, Addad F, Gillery P, Hammami M. Increased serum concentrations of pentosidine are related to presence and severity of coronary artery disease. Thromb Res. 2014;134:633–8.

    Article  CAS  PubMed  Google Scholar 

  19. Fokkens BT, Smit AJ. Skin fluorescence as a clinical tool for non-invasive assessment of advanced glycation and long-term complications of diabetes. Glycoconj J. 2016;33:527–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Fokkens BT, van Waateringe RP, Mulder DJ, Wolffenbuttel BHR, Smit AJ. Skin autofluorescence improves the Finnish Diabetes Score in the detection of diabetes in a large population based cohort: The LifeLines Cohort Study. Diabetes Metab. 2018;44:424–30.

    Article  CAS  PubMed  Google Scholar 

  21. Boersma HE, van Waateringe RP, van der Klauw MM, Graaff R, Paterson AD, Smit AJ, Wolffenbuttel BHR. Skin autofluorescence predicts new cardiovascular disease and mortality in people with type 2 diabetes. BMC Endocr Disord. 2021;21(1):14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Koetsier M, Lutgers HL, de Jonge C, Links TP, Smit AJ, Graaff R. Reference values of skin autofluorescence. Diabetes Technol Ther. 2010;12:399–403.

    Article  CAS  PubMed  Google Scholar 

  23. Mook-Kanamori MJ, El-Din Selim MM, Takiddin AH, AI-Homsi H, AI-Mahmoud KAS, AI-Obaidli A, et al. Ethnic and gender differences in advanced glycation end products measured by skin auto-fluorescence. Dermato-Endocrinology. 2013;5:325–30.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ahmad MS, Kimhofer T, Ahmad S, AIAma MN, Mosli HH, Hindawi SI, Mook-Kanamori DO, et al. Ethnicity and skin autofluorescence based risk engines for cardiovascular disease and diabetes mellitus. PLoS ONE. 2017;12(9):e0185175.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Van Waateringe RP, Mook-Kanamori MJ, Slagter SN, van der Klauw MM, van Vliet-Ostaptchouk JV, Graaff R, et al. The association between various smoking behaviors, cotinine biomarkers and skin autofluorescence. PLoS ONE. 2017;12(6):e0179330.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Botros N, Sluik D, van Waateringe RP, de Vries JH, Geelen A, Feskens EJ. Advanced glycation end products (AGEs) and associations with cardio-metabolic, lifestyle and dietary factors in a general population: the NQplus study. Diabetes Metab Res Rev. 2017;17:259.

    Google Scholar 

  27. Brownlee M. Advanced protein glyocsylation in diabetes and aging. Annu Rev Med. 1995;46:223–34.

    Article  CAS  PubMed  Google Scholar 

  28. Chakraborty S, Mandal J, Yang T, Cheng X, Yeo JY, McCarthy CG, Wenceslau CF, Koch LG, Hill JW, Vijay-Kumar M, Joe B. Metabolites and hypertension: insights into hypertension as a metabolic disorder. Hypertension. 2020;75:1386–96.

    Article  CAS  PubMed  Google Scholar 

  29. Aronson D. Cross-linking of glycated collagen in the pathogenesis of arterial and myocardial stiffening of aging and diabetes. J Hypertens. 2003;21:3–12.

    Article  CAS  PubMed  Google Scholar 

  30. Noordzij MJ, Mulder DJ, Oomen PHN, Brouwer T, Jager J, Castro Cabezas M, Lefrandt JD, Smit AJ. Skin autofluorescence and risk of micro- and macrovascular complications in patients with diabetes mellitus a multi-center study. Diabt Med. 2012;29:1556–61.

    Article  CAS  Google Scholar 

  31. Lutgers HL, Graaff R, Links TP, Ubink-Veltmaat LJ, Bilo HJ, Gans RO, et al. Skin autofluorescence as a non-invasive marker of vascular damage in patients with type 2 diabetes. Diabetes care. 2006;29:2654–9.

    Article  PubMed  Google Scholar 

  32. den Engelsen C, van den Donk M, Gorter KJ, Salomé PL, Rutten GE. Advanced glycation end products measured by skin autofluorescence in a population with central obesity. Dermato Endocrinol. 2012;4:33–8.

    Article  Google Scholar 

  33. Noordzij MJ, Lefrandt JD, Graaff R, Smit AJ. Skin autofluorescence and glycemic variability. Diabetes Technol Ther. 2010;12:581–5.

    Article  CAS  PubMed  Google Scholar 

  34. Kellow NJ, Coughlan MT, Reid CM. Association between habitual dietary and lifestyle behaviours and skin autofluorescence (SAF), a marker of tissue accumulation of advanced glycation endproducts (AGEs), in healthy adults. Eur J Nutr. 2018;57:2209–16.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank all the people who participated in this study

Author information

Authors and Affiliations

  1. Laboratory of Research on Biologically Compatible Compounds, Faculty of Dental Medicine, University of Monastir, Monastir, Tunisia

    Rim Sakly, Salwa Abid & Mohsen Kerkeni

  2. Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

    Bruce H. R. Wolffenbuttel

  3. Endocrinology and Internal Medicine Department, Fattouma Bourguiba University Hospital, Monastir, Tunisia

    Ines Khochtali

  4. Emergency Department, Fattouma Bourguiba University Hospital, Research Laboratory LR12SP18, University of Monastir, Monastir, Tunisia

    Wahid Bouida, Hamdi Boubaker & Semir Nouira

  5. Higher Institute of Biotechnology, Avenue Taher Haddad BP 74, 5000, Monastir, Tunisia

    Mohsen Kerkeni

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  1. Rim Sakly
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Contributions

MK, BHRW, SA, and SN conceived the idea and edited and finalized the manuscript. RS and MK performed the study design, skin autofluorescence measurement, data analysis, data interpretation, and writing. IK, WB, and HB helped in the recruitment of patients and clinical fulfillment. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mohsen Kerkeni.

Ethics declarations

The study protocol follows the ethical guidelines of the declaration of Helsinki and has been approved by the ethics committees at the Hospital of Fattouma Bourguiba at Monastir-Tunisia. All participants signed the informed consent in writing before inclusion in the study.

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Not applicable

Competing interests

The authors declare no competing interests.

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Sakly, R., Wolffenbuttel, B.H.R., Khochtali, I. et al. Increased skin autofluorescence of advanced glycation end products (AGEs) in subjects with cardiovascular risk factors. Int J Diabetes Dev Ctries 43, 613–620 (2023). https://doi.org/10.1007/s13410-022-01121-z

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  • DOI: https://doi.org/10.1007/s13410-022-01121-z

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