Advanced glycation end-products are associated with diabetic neuropathy in young adults with type 1 diabetes.

Autor:	Al-Saoudi E; Department of Complication Research , Steno Diabetes Center Copenhagen, Herlev, Denmark., Christensen MMB; Department of Clinical Epidemiology, Steno Diabetes Center Copenhagen, Herlev, Denmark., Nawroth P; Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany.; Joint Heidelberg-Institute for Diabetes and Cancer (IDC) Translational Diabetes Programm, Helmholtz-Zentrum, Heidelberg, Germany., Fleming T; Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, Heidelberg, Germany.; German Center for Diabetes Research (DZD), Neuherberg, Germany., Hommel EE; Steno Diabetes Center Copenhagen, Herlev, Denmark., Jørgensen ME; Department of Clinical Epidemiology, Steno Diabetes Center Copenhagen, Herlev, Denmark.; Steno Diabetes Center Greenland, Nuuk, Greenland., Fleischer J; Steno Diabetes Center Aarhus, Aarhus, Denmark., Hansen CS; Department of Complication Research , Steno Diabetes Center Copenhagen, Herlev, Denmark.
Jazyk:	angličtina
Zdroj:	Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2022 Oct 11; Vol. 13, pp. 891442. Date of Electronic Publication: 2022 Oct 11 (Print Publication: 2022).
DOI:	10.3389/fendo.2022.891442
Abstrakt:	Aims/hypothesis: Advanced glycation end-products (AGEs) may contribute to the development of diabetic neuropathy. In young adults with type 1 diabetes, we aimed to investigate the association between AGEs and cardiovascular autonomic neuropathy (CAN) and distal symmetric polyneuropathy (DSPN). Methods: This cross-sectional study comprised 151 young adults. CAN was assessed by cardiovascular autonomic reflex tests; lying-to-standing test, deep breathing test (E/I), Valsalva manoeuvre, and heart rate variability indices; and the mean square of the sum of the squares of differences between consecutive R-R intervals and standard deviation of normal-to-normal intervals (SDNN), high- (HF) and low-frequency (LF) power, total frequency power, and the LF/HF ratio. DSPN was assessed by light touch, pain and vibration perception threshold (VPT), neuropathy questionnaires, and objective measures. AGEs were analysed in four groups using z-scores adjusted for relevant confounders and multiple testing: i) "glycolytic dysfunction", ii) "lipid peroxidation", iii) "oxidative stress", and iv) "glucotoxicity". Results: A higher z-score of "glycolytic dysfunction" was associated with higher VPT (4.14% (95% CI 1.31; 7.04), p = 0.004) and E/I (0.03% (95% CI 0.01; 0.05), p = 0.005), "lipid peroxidation" was associated with higher LF/HF ratio (37.72% (95% CI 1.12; 87.57), p = 0.044), and "glucotoxicity" was associated with lower SDNN (-4.20% (95% CI -8.1416; -0.0896), p = 0.047). No significance remained after adjustment for multiple testing. Conclusions/interpretations: In young adults with type 1 diabetes, increased levels of AGEs involving different metabolic pathways were associated with several measures of CAN and DSPN, suggesting that AGEs may play a diverse role in the pathogeneses of diabetic neuropathy. Competing Interests: JF holds stocks in Medicus Engineering. EH, MC and MJ hold shares in Novo Nordisk AS. MJ has received research grants from AMGEN, Astra Zeneca, Boehringer Ingelheim, Novo Nordisk, and Sanofi Aventis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Al-Saoudi, Christensen, Nawroth, Fleming, Hommel, Jørgensen, Fleischer and Hansen.)
Databáze:	MEDLINE
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