Methylglyoxal and soluble RAGE in type 2 diabetes mellitus: Association with oxidative stress

Reyaz, Alisha; Alam, Md. Sayem; Chandra, Kailash; Kohli, Sunil; Agarwal, Sarita

doi:10.1007/s40200-020-00543-y

Cited by 17 publications

(8 citation statements)

References 27 publications

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“…This conclusion is based on our findings that mean plasma MG of COVID-19 patients admitted into the ICU that later died was 4.4-fold and 1.8-fold higher than that in uninfected non-DM controls and uninfected DM individuals, respectively. Similar levels of MG have been reported in plasma of uninfected controls 51 , Other have also reported similar fold increases in plasma MG in uninfected DM patients using other assay methods 52 – 54 . Mean plasma MG in COVID-19 patients on admission into ICU that survived, was 2.5-fold higher than that of uninfected non-DM controls, and not significantly different to that of uninfected DM patients.…”

Section: Discussionsupporting

confidence: 80%

Elevated plasma level of the glycolysis byproduct methylglyoxal on admission is an independent biomarker of mortality in ICU COVID-19 patients

Alomar

Alshakhs

Abohelaika

et al. 2022

Sci Rep

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Biomarkers to identify ICU COVID-19 patients at high risk for mortality are urgently needed for therapeutic care and management. Here we found plasma levels of the glycolysis byproduct methylglyoxal (MG) were 4.4-fold higher in ICU patients upon admission that later died (n = 33), and 1.7-fold higher in ICU patients that survived (n = 32),compared to uninfected controls (n = 30). The increased MG in patients that died correlated inversely with the levels of the MG-degrading enzyme glyoxalase-1 (r2 = − 0.50), and its co-factor glutathione (r2 = − 0.63), and positively with monocytes (r2 = 0.29). The inflammation markers, SSAO (r2 = 0.52), TNF-α (r2 = 0.41), IL-1β (r2 = 0.25), CRP (r2 = 0.26) also correlated positively with MG. Logistic regression analysis provides evidence of a significant relationship between the elevated MG upon admission into ICU and death (P < 0.0001), with 42% of the death variability explained. From these data we conclude that elevated plasma MG on admission is a novel independent biomarker that predicts mortality in ICU COVID-19 patients.

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Section: Discussionsupporting

confidence: 80%

Elevated plasma level of the glycolysis byproduct methylglyoxal on admission is an independent biomarker of mortality in ICU COVID-19 patients

Alomar

Alshakhs

Abohelaika

et al. 2022

Sci Rep

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“…In the first instance, Lys-C-dots could be effective for the detoxification of MGO, the key α-oxoaldehyde produced under hyperglycemia in the blood of type 2 diabetes patients. 52 In this case the scavenging of MGO, prevention of amino acid modification in proteins, and formation of advanced glycation end products (AGEs) 53 could be achieved directly in the blood after C-dot administration. However, in the case of DOPAL other factors should be considered.…”

Section: Resultsmentioning

confidence: 99%

Scavenging neurotoxic aldehydes using lysine carbon dots

et al. 2023

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“…Although several studies reported a significant increase in AGE levels in patients with type 2 diabetes [ 43 , 52 , 53 ], more conflicting evidence are available on sRAGE. Most cross-sectional studies focused on total sRAGE levels, with findings variable on type of diabetes, disease duration and presence of complications [ 54 – 57 ]. A smaller number of studies assessed more in-depth the sRAGE isoforms, with no conclusive results [ 29 , 53 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating levels of AGEs and soluble RAGE isoforms are associated with all-cause mortality and development of cardiovascular complications in type 2 diabetes: a retrospective cohort study

Sabbatinelli

Castiglione

Macrì

et al. 2022

Cardiovasc Diabetol

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Background Advanced glycation end-products (AGEs) and their interaction with the receptor for advanced glycation end-products (RAGE) play a pivotal role in the development and progression of type 2 diabetes. In this retrospective cohort study, we explored the association of circulating levels of soluble RAGE (sRAGE) isoforms, i.e., endogenous secretory esRAGE and cleaved cRAGE, AGEs and their respective ratios with 15-year all-cause mortality in type 2 diabetes. Methods Baseline AGEs and sRAGE isoforms concentration were measured by ELISA in 362 patients with type 2 diabetes and in 125 age- and gender-matched healthy control subjects (CTR). Independent predictors of mortality were determined using Cox proportional-hazards models and used to build and validate a nomogram for all-cause mortality prediction in type 2 diabetes. Results AGEs, total sRAGE, cRAGE and the AGEs/sRAGE and AGEs/esRAGE ratios were significantly increased in patients with type 2 diabetes compared to CTR (p < 0.001). In CTR subjects, but not in type 2 diabetes patients, a significant negative correlation between cRAGE and age was confirmed (p = 0.003), whereas the AGEs/sRAGE (p = 0.032) and AGEs/cRAGE (p = 0.006) ratios were positively associated with age. At an average follow-up of 15 years (4,982 person-years), 130 deaths were observed. The increase in the AGEs/cRAGE ratio was accompanied by a higher risk of all-cause mortality in patients with type 2 diabetes (HR per each SD increment = 1.30, 95% CI 1.15–1.47; p < 0.001). Moreover, sRAGE was associated with the development of major adverse cardiovascular events (MACE) in type 2 diabetes patients without previous MACE (OR for each SD increase: 1.48, 95% CI 1.11–1.89). A nomogram based on age, sex, HbA1c, systolic blood pressure, and the AGEs/cRAGE ratio was built to predict 5-, 10- and 15-year survival in type 2 diabetes. Patients were categorized into quartiles of the monogram scores and Kaplan-Meier survival curves confirmed the prognostic accuracy of the model (log-rank p = 6.5 × 10− 13). Conclusions The ratio between AGEs and the cRAGE isoform is predictive of 15-year survival in patients with type 2 diabetes. Our data support the assessment of circulating AGEs and soluble RAGE isoforms in patients with type 2 diabetes as predictors of MACE and all-cause mortality.

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Methylglyoxal and soluble RAGE in type 2 diabetes mellitus: Association with oxidative stress

Cited by 17 publications

References 27 publications

Elevated plasma level of the glycolysis byproduct methylglyoxal on admission is an independent biomarker of mortality in ICU COVID-19 patients

Elevated plasma level of the glycolysis byproduct methylglyoxal on admission is an independent biomarker of mortality in ICU COVID-19 patients

Scavenging neurotoxic aldehydes using lysine carbon dots

Circulating levels of AGEs and soluble RAGE isoforms are associated with all-cause mortality and development of cardiovascular complications in type 2 diabetes: a retrospective cohort study

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