Advanced Glycation End Products as a Predictor of Diabetes Mellitus in Chronic Hepatitis C-Related Cirrhosis

Abdel‐Razik, Ahmed; Mousa, Nasser; Zakaria, Sahar; Abdelsalam, Mostafa; Eissa, Mohamed; El-Ghany, Mohammed Abd; Hasan, Ahmad S.; Elhelaly, Rania; Elzehery, Rasha; El‐Wakeel, Niveen; Eldars, Waleed

doi:10.3389/fmed.2020.588519

Cited by 2 publications

(2 citation statements)

References 47 publications

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“…This resultant hyperinsulinemia can lead to resistance to insulin through insulin receptor downregulation [ 16 ]. Other described mechanisms of liver cirrhosis effect on glucose homeostasis include increased advanced glycations products, increased formation of hypoxia-inducible factors, and reduced pancreatic beta-cell function, which will lead to decreased insulin secretion [ 17 - 19 ]. All of these mechanisms will lead to increased insulin resistance in cirrhotic patients and thus may contribute to worse outcomes of patients who develop DKA.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Cirrhosis on Outcomes of Patients Admitted With Diabetic Ketoacidosis: A Nationwide Study

Mansour¹,

Obeidat²,

Darweesh³

et al. 2022

Cureus

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Introduction Diabetic ketoacidosis (DKA) is the most common acute hyperglycemic emergency in people with diabetes mellitus (DM). Cirrhosis is a consequence of chronic inflammation that is followed by hepatic fibrosis. It has been noted that cirrhosis is associated with an increased risk of developing type II DM due to altered glucose homeostasis. The prognostic value of DM in cirrhotic patients has been studied before and was found to be associated with lower survival. However, the risk of mortality and adverse events in cirrhotic patients admitted with DKA needs further evaluation. The aim of this study is to compare outcomes in patients with cirrhosis admitted to the hospital with DKA compared to non-cirrhotic patients. Methods The data for this study were extracted from the National Inpatient Sample (NIS) 2016-2019. The NIS was queried for all patients who had a discharge diagnosis of DKA. Patients with cirrhosis were identified and subclassified into compensated and decompensated cirrhosis using the International Classification of Diseases 10th revision, Clinical Modification (ICD-10-CM) codes. Patients without cirrhosis were the control group. ICD-10-CM codes that have been validated for cirrhosis were utilized. The primary outcome was in-hospital mortality. Secondary outcomes were hospital charges, length of stay (LOS), and in-hospital complications, including shock, mechanical ventilation, and acute kidney injury (AKI) requiring dialysis. Results We included 1,098,875 hospitalizations with a discharge diagnosis of DKA. Overall, 9,190 patients had compensated cirrhosis and 4,355 had decompensated cirrhosis. Cirrhotic patients had overall worse outcomes compared to non-cirrhotics. Decompensated cirrhotics had the highest mortality (11.26%; 95% confidence interval [CI]: 9.36% to 13.49%) compared to compensated cirrhotics (3.54%; 95% CI: 2.79% to 4.48%) and non-cirrhotics (2.15%; 95% CI: 1.89% to 2.43%). Similarly, decompensated cirrhotics also had the highest LOS, total charges, and in-hospital complications among the groups. On multivariate analysis, decompensated cirrhosis, rather than compensated cirrhosis, was an independent predictor of higher mortality (adjusted odds ratio [AOR]: 2.30; 95% CI: 1.81 to 2.92), LOS (regression coefficient: +1.82 days; 95% CI: +1.19 to +2.44 days), hospital charges (regression coefficient: +$28,497; 95% CI: +$18,107 to +$38,887), shock (AOR: 2.31; 95% CI: 1.68 to 3.18), mechanical ventilation (AOR: 1.91; 95% CI: 1.58 to 2.29), and AKI requiring dialysis (AOR: 2.31; 95% CI: 1.68 to 3.18). Conclusion This study showed that patients with decompensated liver cirrhosis who were admitted with DKA had the worst in-hospital outcomes. Additionally, only decompensated cirrhosis was an independent predictor of worse outcomes. Decompensated cirrhotics who develop DKA should be approached with more caution with a probable lower threshold for intensive care unit admission for a higher level management.

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Section: Discussionmentioning

confidence: 99%

The Impact of Cirrhosis on Outcomes of Patients Admitted With Diabetic Ketoacidosis: A Nationwide Study

Mansour¹,

Obeidat²,

Darweesh³

et al. 2022

Cureus

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“…Advanced glycation end products (AGEs), a heterogeneous cluster of irreversible reactive end products created by oxidation of lipids and proteins, and non-enzymatic glycation, have been embroiled in the pathogenesis of numerous disorders (Marta et al, 2004;Zhou et al, 2004;Hyogo et al, 2007;Piarulli et al, 2013;Abdel-Razik et al, 2020a) because they stimulate the oxidative stress generation and consequently induce inflammation (Yamagishi et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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

Ahmed

Shabana

Nakib

et al. 2021

Front. Cell. Infect. Microbiol.

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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.

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Advanced Glycation End Products as a Predictor of Diabetes Mellitus in Chronic Hepatitis C-Related Cirrhosis

Cited by 2 publications

References 47 publications

The Impact of Cirrhosis on Outcomes of Patients Admitted With Diabetic Ketoacidosis: A Nationwide Study

The Impact of Cirrhosis on Outcomes of Patients Admitted With Diabetic Ketoacidosis: A Nationwide Study

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

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