scholarly journals De Novo Hepatocellular Carcinoma in Hepatitis C-Related Cirrhosis: Are Advanced Glycation End Products a Key Driver?

2021 ◽  
Vol 11 ◽  
Author(s):  
Ahmed Abdel-Razik ◽  
Walaa Shabana ◽  
Ahmed Mohamed El Nakib ◽  
Mostafa Abdelsalam ◽  
Ahmed Abdelwahab ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Hepatitis C ◽  
Advanced Glycation End Products ◽  
Cox Regression ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Cox Regression Analysis ◽  
Glycation End Products ◽  
End Products

Background and PurposeThe advanced glycation end products (AGEs) have been implicated in different diseases’ pathogenesis, but their role in hepatocellular carcinoma (HCC) is still a matter of debate. This study aims to investigate the association of AGEs with HCC development in patients with hepatitis C-related cirrhosis.MethodsOnly 153 of the 181 non-diabetic patients with cirrhosis were consecutively involved in this pilot cohort prospective study, along with 34 healthy control participants. Demographic characteristics, biochemical parameters, clinical data, and AGEs levels in all subjects at the starting point and every year after that for two years were assessed. Multivariable Cox regression analysis was used to settle variables that could predict HCC development within this period.ResultsHCC developed in 13 (8.5%) patients. Univariate Cox regression analysis reported that body mass index (P=0.013), homeostatic model assessment-insulin resistance (P=0.006), alpha-fetoprotein (P <0.001), and AGEs levels (P <0.001) were related to HCC development. After adjusting multiple confounders, the multivariable Cox regression model has revealed that AFP and AGEs were the powerful parameters related to the HCC occurrence (all P<0.05). AGEs at a cutoff value of more than 79.6 ng/ml had 100% sensitivity, 96.4% specificity, and 0.999 area under the curve (all P<0.001), using the receiver operating characteristic curve, for prediction of HCC development.ConclusionThis work suggests that AGEs are associated with an increased incidence of HCC, particularly in cirrhosis, which is encouraging in decreasing the risk of HCC in these patients.

scholarly journals De Novo Hepatocellular Carcinoma in Hepatitis C-Related Cirrhosis: Are Advanced Glycation end Products a Key Driver?

2021 ◽  
Author(s):  
Ahmed Abdel-Razik ◽  
Walaa Shabana ◽  
Ahmed Mohamed El Nakib ◽  
Mostafa Abdelsalam ◽  
Ahmed Abdelwahab ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regression Analysis ◽  
Advanced Glycation End Products ◽  
Cox Regression ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Cox Regression Analysis ◽  
Starting Point ◽  
Glycation End Products ◽  
End Products

Abstract Background: The advanced glycation end products (AGEs) have been implicated in different diseases' pathogenesis, but their role in hepatocellular carcinoma (HCC) is still a matter of debate. This study aims to investigate the association of AGEs with HCC development in patients with cirrhosis. Methods: Only 153 of the 181 non-diabetic patients with cirrhosis were consecutively involved in this pilot cohort prospective study, along with 34 healthy control participants. Demographic characteristics, biochemical parameters, clinical data, and AGEs levels in all subjects at the starting point and every year after that for two years were assessed. Multivariable Cox regression analysis was used to settle variables that could predict HCC development within this period. Results: HCC developed in 13 (8.5%) patients. Univariate Cox regression analysis reported that age (P=0.043), treatment with direct-acting antivirals (DAAs) (P=0.021), and AGEs levels (P=0.04) were related to HCC development. After adjusting multiple confounders, the multivariable Cox regression model has revealed that treatment with DAAs and AGEs were the powerful parameters related to the HCC occurrence (all P<0.05). AGEs at a cutoff value of more than 79.6 ng/ml had 100% sensitivity, 96.4% specificity, and 0.999 area under the curve (all P<0.001), using the receiver operating characteristic curve, for prediction of HCC development. Conclusion: This work suggests that AGEs are associated with an increased incidence of HCC, particularly in cirrhosis, which is encouraging in decreasing the risk of HCC in these patients.

Advanced glycation end-products associate with podocytopathy in type II diabetic patients

2021 ◽  
Author(s):  
Rajkishor Nishad ◽  
Tahaseen V Syed ◽  
Manga Motrapu ◽  
Rajesh Kavvuri ◽  
Kiranmayi Kodali ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Function ◽  
Advanced Glycation End Products ◽  
Diabetic Patients ◽  
Type Ii ◽  
Advanced Glycation ◽  
Mesenchymal Transition ◽  
Glycation End Products ◽  
End Products ◽  
Carboxymethyl Lysine

Abstract Background The prevalence of diabetes reaches epidemic proportions, affecting the incidence of diabetic nephropathy (DN) and associated end-stage kidney disease (ESKD). Diabetes is the leading cause of ESKD since 30–40% of diabetic patients develop DN. Albuminuria and eGFR have been considered a surrogate outcome of chronic kidney disease, and the search for a biomarker that predicts progression to diabetic kidney disease is intense.Methods We analyzed the association of serum advanced glycation end-products (AGEs) index (AGI) with impaired kidney function in uncontrolled diabetic patients (type II, n = 130) with albuminuria ranging from (150 to 450 mg/day). The kidney biopsy specimens were also examined for the association of AGEs, particularly carboxymethyl lysine (CML) with kidney function. Further, we also assessed the effect of carboxymethyl lysine on glomerular injury and podocytopathy in experimental animals.Results We observed a strong correlation between AGI and impaired kidney function in miroalbuminuric patients with hyperglycemia. A significant association between CML levels and impaired kidney function was noticed. Administration of CML in mice showed heavy proteinuria and glomerular abnormalities. Reduced podocyte number observed in mice administered with CML could be attributed to the epithelial-mesenchymal transition (EMT) of podocytes. Conclusion Serum AGEs could be independently related to the podocyte injury vis-a-vis the risk of DN progression to ESKD in patients with microalbuminuria. AGEs or CML could be considered a prognostic marker to assess microalbuminuria progression to ESKD in diabetic patients.

scholarly journals Detection of Noncarboxymethyllysine and Carboxymethyllysine Advanced Glycation End Products (AGE) in Serum of Diabetic Patients

1999 ◽  
Vol 5 (6) ◽  
pp. 393-405 ◽  
Author(s):  
Masayoshi Takeuchi ◽  
Zenji Makita ◽  
Katsuyuki Yanagisawa ◽  
Yukihiko Kameda ◽  
Takao Koike
Keyword(s):  
Advanced Glycation End Products ◽  
Diabetic Patients ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

scholarly journals Advanced Glycation End-Products Suppress Mitochondrial Function and Proliferative Capacity of Achilles Tendon-Derived Fibroblasts

2019 ◽  
Author(s):  
Shivam H. Patel ◽  
Feng Yue ◽  
Shannon K. Saw ◽  
Rachel Foguth ◽  
Jason R. Cannon ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Achilles Tendon ◽  
Advanced Glycation End Products ◽  
Mitochondrial Function ◽  
Diabetic Patients ◽  
Proliferative Capacity ◽  
Advanced Glycation ◽  
Tendon Degeneration ◽  
Glycation End Products ◽  
End Products

AbstractDebilitating cases of tendon pain and degeneration affect the majority of diabetic individuals. The high rate of tendon degeneration persists even when glucose levels are well controlled, suggesting that other mechanisms may drive tendon degeneration in diabetic patients. The purpose of this study was to investigate the impact of advanced glycation end-products on tendon fibroblasts to further our mechanistic understanding of the development and progression of diabetic tendinopathy. We proposed that advanced glycation end-products would induce limitations to mitochondrial function and proliferative capacity in tendon-derived fibroblasts, restricting their ability to maintain biosynthesis of tendon extracellular matrix. Using an in-vitro cell culture system, rat Achilles tendon fibroblasts were treated with glycolaldehyde-derived advanced glycation end-products (0, 50, 100, and 200μg/ml) for 48 hours in normal glucose (5.5mM) and high glucose (25mM) conditions. We demonstrate that tendon fibroblasts treated with advanced glycation end-products display reduced ATP production, electron transport efficiency, and proliferative capacity. These impairments were coupled with alterations in mitochondrial DNA content and expression of genes associated with extracellular matrix remodeling, mitochondrial energy metabolism, and apoptosis. Our findings suggest that advanced glycation end-products disrupt tendon fibroblast homeostasis and may be involved in the development and progression of diabetic tendinopathy.

scholarly journals Dietary Advanced Glycation End-Products and Colorectal Cancer Risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3132
Author(s):  
Elom K. Aglago ◽  
Ana-Lucia Mayén ◽  
Viktoria Knaze ◽  
Heinz Freisling ◽  
Veronika Fedirko ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Advanced Glycation End Products ◽  
Cox Regression ◽  
Anatomical Location ◽  
Inverse Association ◽  
Dietary Intakes ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Prospective Investigation

Dietary advanced glycation end-products (dAGEs) have been hypothesized to be associated with a higher risk of colorectal cancer (CRC) by promoting inflammation, metabolic dysfunction, and oxidative stress in the colonic epithelium. However, evidence from prospective cohort studies is scarce and inconclusive. We evaluated CRC risk associated with the intake of dAGEs in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intakes of three major dAGEs: Nε-carboxy-methyllysine (CML), Nε-carboxyethyllysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated in 450,111 participants (median follow-up = 13 years, with 6162 CRC cases) by matching to a detailed published European food composition database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of dAGEs with CRC were computed using multivariable-adjusted Cox regression models. Inverse CRC risk associations were observed for CML (HR comparing extreme quintiles: HRQ5vs.Q1 = 0.92, 95% CI = 0.85–1.00) and MG-H1 (HRQ5vs.Q1 = 0.92, 95% CI = 0.85–1.00), but not for CEL (HRQ5vs.Q1 = 0.97, 95% CI = 0.89–1.05). The associations did not differ by sex or anatomical location of the tumor. Contrary to the initial hypothesis, our findings suggest an inverse association between dAGEs and CRC risk. More research is required to verify these findings and better differentiate the role of dAGEs from that of endogenously produced AGEs and their precursor compounds in CRC development.

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