Plasma methylglyoxal levels are associated with amputations and mortality in severe limb ischemia patients with and without diabetes

Introduction Diabetes is a risk factor for severe limb ischemia (SLI), a condition associated with high mortality, morbidity and limb loss. The reactive glucose-derived dicarbonyl methylglyoxal (MGO) is a major precursor for advanced glycation endproducts (AGEs) and potential driver of cardiovascular disease. We investigated whether plasma MGO levels are associated with poor outcomes in SLI. Methods We measured plasma levels of MGO, free AGEs, and D-lactate, the detoxification endproduct of MGO, with ultra-performance liquid chromatography tandem mass spectrometry at baseline in 160 patients (64.8±13.3years, 67.5% male, 37.5% diabetes) with no-option SLI and recorded major adverse outcomes (n=86, containing death n=53 or amputations n=49 (First event counted)) over 5-year follow-up. Data were analyzed with linear or Cox regression, after Ln-transformation of the independent variables, adjusted for sex, age, trial arm, diabetes, eGFR, systolic blood pressure, cholesterol levels and BMI. Associations are reported per 1SD plasma marker. Results Higher plasma MGO levels were associated with more adverse outcomes (RR: 1.44; 95%CI: 1.11-1.86) and amputations separately (1.55; 1.13-2.21). We observed a similar, but weaker trend for mortality (1.28; 0.93-1.77). The MGO derived AGE Nε-(carboxyethyl)lysine was also associated with more adverse outcomes (1.46; 1.00-2.15) and amputations (1.71; 1.04-2.79). D-lactate was not associated with adverse incident outcomes. Higher plasma MGO levels were also associated with more inflammation and white blood cells and fewer progenitor cells. Conclusion Plasma MGO levels are associated with adverse outcomes in SLI. Future studies should investigate whether MGO-targeting therapies improve outcomes in SLI.

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Analysis of advanced glycation endproducts in selected food items by ultra-performance liquid chromatography tandem mass spectrometry: Presentation of a dietary AGE database

Food Chemistry ◽

10.1016/j.foodchem.2015.06.049 ◽

2016 ◽

Vol 190 ◽

pp. 1145-1150 ◽

Cited By ~ 88

Author(s):

Jean L.J.M. Scheijen ◽

Egbert Clevers ◽

Lian Engelen ◽

Pieter C. Dagnelie ◽

Fred Brouns ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Advanced Glycation Endproducts ◽

Ultra Performance Liquid Chromatography ◽

Tandem Mass ◽

Advanced Glycation ◽

Glycation Endproducts ◽

Food Items ◽

Chromatography Tandem Mass Spectrometry ◽

Liquid Chromatography Tandem Mass

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Prognostic Value of Right Ventricular 3D Speckle-Tracking Strain and Ejection Fraction in Patients With HFpEF

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.694365 ◽

2021 ◽

Vol 8 ◽

Author(s):

Yuanli Meng ◽

Shuangshuang Zhu ◽

Yuji Xie ◽

Yanting Zhang ◽

Mingzhu Qian ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Right Ventricular ◽

Speckle Tracking ◽

Cox Regression ◽

Predictive Performance ◽

Adverse Outcomes ◽

Cardiac Events ◽

End Point ◽

Poor Outcomes

Background: Right ventricular longitudinal strain of free wall (RV FWLS) assessed by two-dimensional speckle-tracking echocardiography (2D-STE) is recognized as an independent predictor of poor prognosis in patients with heart failure with preserved ejection fraction (HFpEF). However, the prognostic implications of three-dimensional STE (3D-STE) parameters in patients with HFpEF have not been well-established. The purpose of our study was to determine whether 3D-STE parameters were the more powerful predictors of poor outcomes in HFpEF patients compared with 2D-STE indices.Methods: Eighty-one consecutive patients with HFpEF were studied by 2D-STE and 3D-STE. RV volumes, ejection fraction (EF) and 3D-RVFWLS were measured by 3D-STE. 2D-RVFWLS was determined by 2D-STE. Patients were followed for the primary end point of heart failure (HF)-related hospitalization and death for HF.Results: After a median follow-up period of 17 months, 39 (48%) patients reached the end point of cardiovascular events. Compared with HFpEF patients without end-point events, those with end-point events had lower RVEF and 3D-RVFWLS (P < 0.05). Separate multivariate Cox regression analyses revealed that 3D-RVFWLS (HR 5.73; 95% CI 2.77–11.85; P < 0.001), RVEF (HR 3.47; 95% CI 1.47–8.21; P = 0.005), and 2D-RVFWLS (HR 3.17; 95% CI 1.54–6.53; P = 0.002) were independent predictors of adverse outcomes. The models with 3D-RVFWLS (AIC = 246, C-index = 0.75) and RVEF (AIC = 247, C-index = 0.76) had similar predictive performance for future clinical events as with 2D-RVFWLS (AIC = 248, C-index = 0.74).Conclusions: 3D-STE parameters are powerful predictors of poor outcomes, providing a similar predictive value as 2D-STE indices in patients with HFpEF. These findings support the potential of RV 3D-STE to identify HFpEF patients at higher risk for adverse cardiac events.

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Robust Detection of Advanced Glycation Endproducts in Milk Powder Using Ultrahigh Performance Liquid Chromatography Tandem Mass Spectrometry (UHPLC-MS/MS)

Food Analytical Methods ◽

10.1007/s12161-021-01986-6 ◽

2021 ◽

Author(s):

Chunhai Li ◽

Ling Zhang ◽

Weifang Gao ◽

Chenghui Lai ◽

Hao Dong

Keyword(s):

Mass Spectrometry ◽

Advanced Glycation Endproducts ◽

Milk Powder ◽

Tandem Mass ◽

Advanced Glycation ◽

Robust Detection ◽

Glycation Endproducts ◽

Chromatography Tandem Mass Spectrometry ◽

Liquid Chromatography Tandem Mass ◽

Ultrahigh Performance Liquid Chromatography

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High dietary glycemic load is associated with higher concentrations of urinary advanced glycation endproducts: the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) Study

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqz119 ◽

2019 ◽

Vol 110 (2) ◽

pp. 358-366 ◽

Cited By ~ 4

Author(s):

Kim Maasen ◽

Marleen M J van Greevenbroek ◽

Jean L J M Scheijen ◽

Carla J H van der Kallen ◽

Coen D A Stehouwer ◽

...

Keyword(s):

Multiple Testing ◽

Advanced Glycation Endproducts ◽

Glycemic Load ◽

Plasma Concentrations ◽

Ultra Performance Liquid Chromatography ◽

Dietary Factors ◽

Oral Glucose ◽

Advanced Glycation ◽

Cross Sectional ◽

Glycation Endproducts

ABSTRACT Background Advanced glycation endproducts (AGEs) and their precursors (dicarbonyls) are associated with the progression of diseases such as diabetes and cardiovascular disease. Plasma concentrations of dicarbonyls methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG) are increased after an oral glucose load indicating that consumption of diets high in carbohydrates may induce the endogenous formation of dicarbonyls and AGEs. Objective To examine the associations of dietary glycemic index (GI) and glycemic load (GL) with concentrations of dicarbonyls and AGEs in plasma and urine. Methods Cross-sectional analyses were performed in a human observational cohort [Cohort on Diabetes and Atherosclerosis Maastricht (CODAM), n = 494, 59 ± 7 y, 25% type 2 diabetes]. GI and GL were derived from FFQs. Dicarbonyls and AGEs were measured in the fasting state by ultra-performance liquid chromatography-tandem MS. MGO, GO, and 3-DG and protein-bound Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL), and pentosidine were measured in plasma. Free forms of CML, CEL, and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were measured in both plasma and urine. Multiple linear regression was performed with dicarbonyls and AGEs as dependent variables, and dietary GI or GL as main independent variables (all standardized). Models were adjusted for health and lifestyle factors, dietary factors, and reciprocally for GI and GL. As this was an explorative study, we did not adjust for multiple testing. Results GI was not associated with any of the dicarbonyls or AGEs. GL was positively associated with free urinary MG-H1 (β = 0.34; 95% CI: 0.12, 0.55). Furthermore, GL was positively associated with free plasma MG-H1 and free urinary CML (β = 0.23; 95% CI: 0.02, 0.43; and β = 0.28; 95% CI: 0.06, 0.50), but these associations were not independent of dietary AGE intake. Conclusions A habitual diet higher in GL is associated with higher concentrations of free urinary MG-H1. This urinary AGE is most likely a reflection of AGE accumulation and degradation in tissues, where they may be involved in tissue dysfunction.

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