Nonalcoholic Steatohepatitis (NASH) and Atherosclerosis: Explaining Their Pathophysiology, Association and the Role of Incretin-Based Drugs

Galatou, Eleftheria; Mourelatou, Elena A.; Hatziantoniou, Sophia; Vizirianakis, Ioannis S.

doi:10.3390/antiox11061060

Cited by 7 publications

(3 citation statements)

References 177 publications

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“…Notably, it is reported that CVD accompanied by NAFLD exerts a more adverse metabolic burden than CVD alone [ 38 ]. In fact, the strong association between NAFLD and CVD is governed by numerous pathophysiological mechanisms, including oxidative stress, inflammation, lipid metabolism, and gut microbiota, etc.…”

Section: Discussionmentioning

confidence: 99%

Control of cardiometabolic risk factors and their association with carotid intima media thickness among patients with type 2 diabetes mellitus-single center experience in a developing country

WEERARATHNA,

LEKKAMWASAM,

KODIKARA

et al. 2024

Turkish Journal of Medical Sciences

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Background/aim Type 2 diabetes mellitus (T2DM) is closely associated with atherosclerotic cardiovascular diseases (ASCVD). The objective of this study was to describe the degree of ASCVD risk factor control and their association with carotid intima-media thickness (CIMT) in T2DM patients followed up at a diabetes clinic in Southern, Sri Lanka. Materials and methods A crosssectional study was conducted to examine the association between CIMT and nonalcoholic fatty liver disease (NAFLD)in 300 T2DM patients. Both CIMT and its associations with modifiable cardiometabolic risk factors were examined using ultrasonography. The recommended optimal targets for risk factors were defined as glycated hemoglobin (HbA 1C ) < 7 %, absence of NAFLD, albumin-to-creatinine ratio (ACR) < 30 mg, triglyceride (TG) < 150 mg/dL, low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL, high-density lipoprotein cholesterol (HDL-C) in men > 40 and in women > 50 mg/dL, systolic blood pressure (SBP) < 130 mmHg, and diastolic blood pressure (DBP) < 80 mmHg. Results SBP, DBP, LDL-C, TG, HDL-C, HbA 1C , and ACR were optimally controlled in 59.3%, 75.0%, 46.7%, 84.3%, 46.0%, 33.0%, and 18.7% of patients, respectively. Notably, nearly half of the study subjects did not have NAFLD. Only three patients (1%) had achieved all therapeutic targets. There were statistically significant differences in CIMT between optimally controlled TG and suboptimally controlled TG group (p = 0.027) and between the groups with and without NAFLD (p = 0.045) when adjusted for age and duration of diabetes. CIMT showed significant and positive associations with LDL-C (p = 0.024), TG (p = 0.026), and NAFLD (p = 0.005). Among these, the presence of NAFLD had the highest odds of having higher CIMT when compared to LDL-C and TG. Conclusion The majority of patients have not achieved the recommended targets for ASCVD risk factors and are at high risk of ASCVD. It is therefore necessary to identify the reasons for not achieving the treatment targets in order to reduce the ASCVD burden by controlling LDL-C, TG, and NAFLD.

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Section: Discussionmentioning

confidence: 99%

Control of cardiometabolic risk factors and their association with carotid intima media thickness among patients with type 2 diabetes mellitus-single center experience in a developing country

WEERARATHNA,

LEKKAMWASAM,

KODIKARA

et al. 2024

Turkish Journal of Medical Sciences

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“…We acknowledge that any mortality benefit from GLP1-RAs cannot be attributed entirely to glucose and weight control. Previous cardiovascular outcomes trials have underscored that GLP1-RA provides cardiovascular benefits by preventing atherosclerotic events and cardiomyopathy, which could be attributed to decreased M2 macrophage polarization and decreased monocyte-endothelium adhesion, as shown by preclinical studies [ 20 ]. In a similar vein, renal injury is a common complication of cirrhosis and T2DM that can eventually require patients to undergo hemodialysis [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Dual metformin and glucagon-like peptide-1 receptor agonist therapy reduces mortality and hepatic complications in cirrhotic patients with diabetes mellitus

Huynh¹

2023

aog

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Background Type 2 diabetes (T2DM) can accelerate the progression of cirrhosis. The potential for oral diabetes medications to counteract the mortality and morbidity of chronic liver diseases is unclear. Methods We compared the effectiveness of dual metformin and glucagon-like peptide-1 receptor agonists (GLP1-RA) vs. metformin treatment alone in reducing mortality and hepatic complications in cirrhotic patients with T2DM. We evaluated propensity score-matched cohorts of T2DM and cirrhosis patients treated with metformin or dual metformin and GLP1-RA therapy. Data were obtained from the TriNetX Research Network. Our outcomes were all-cause mortality, composite risk of hepatic decompensation, and hepatocellular carcinoma (HCC). Results Compared to patients on metformin alone, dual metformin and GLP1-RA therapy users had a lower risk for both death (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.42-0.89; P=0.011) and hepatic decompensation (HR 0.65, 95%CI 0.46-0.93; P=0.02) over 5 years. Patients on dual therapy had a lower risk for HCC (HR 0.44, 95%CI 0.26-0.74; P=0.001) compared to mono-metformin therapy patients. Conclusion In our multicenter retrospective study, dual therapy was associated with better mortality and morbidity in cirrhosis patients with T2DM compared to those on metformin alone.

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“…Hepatic lipid accumulation causes insulin resistance and chronic inflamma increasing the risk of fibrosis, cirrhosis, and HCC. Besides liver lipid metabolism, the o possibilities contributing to the pathogenesis of NAFLD include adipose tissue dysf tion/inflammation, dysbiosis of gut microbiota, and gut barrier function regulating se intrahepatic metabolic and inflammatory pathways (Figure 2) [28,29]. It is interesting to note that obesity is strongly associated with NAFLD but not an independent factor.…”

Section: Pathogenesis Of Nafldmentioning

confidence: 99%

The Pivotal Role of the Membrane-Bound O-Acyltransferase Domain Containing 7 in Non-Alcoholic Fatty Liver Disease

Chandrasekaran,

Weiskirchen

2023

Livers

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Non-alcoholic fatty liver disease (NAFLD) is a common and prevalent disorder affecting 25 percent of the adults in the United States and 32 percent of adults globally. It is one of the common causes of chronic liver disease characterized by steatosis, which can lead to inflammation, fibrosis, and cirrhosis. NAFLD is strongly associated with obesity and insulin resistance. Multiple genetic variants have been consistently found to be associated with NAFLD; one of them is found in the TMC4-MBOAT7 loci. One variant (rs641738 C>T) within MBOAT7 encoding lysophosphatidyl inositol acyltransferase increases the risk for NAFLD development and triggers hepatic inflammation by regulating arachidonic acid levels. This review provides an overview of the MBOAT7 gene, pathogenesis of NAFLD, understanding the regulation of MBOAT7 and mechanistic link between MBOAT7 and NAFLD. It further summarizes pathophysiologically relevant in vivo and in vitro studies on MBOAT7 and challenges in treating complex NAFLD with recent progress made in the treatment of NAFLD. As such, this review provides useful information on MBOAT7 and NAFLD interrelation, which has the potential of deciphering novel therapeutic targets rather than well-known genetic variants such as PNPLA3 and TM6SF2.

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Nonalcoholic Steatohepatitis (NASH) and Atherosclerosis: Explaining Their Pathophysiology, Association and the Role of Incretin-Based Drugs

Cited by 7 publications

References 177 publications

Control of cardiometabolic risk factors and their association with carotid intima media thickness among patients with type 2 diabetes mellitus-single center experience in a developing country

Control of cardiometabolic risk factors and their association with carotid intima media thickness among patients with type 2 diabetes mellitus-single center experience in a developing country

Dual metformin and glucagon-like peptide-1 receptor agonist therapy reduces mortality and hepatic complications in cirrhotic patients with diabetes mellitus

The Pivotal Role of the Membrane-Bound O-Acyltransferase Domain Containing 7 in Non-Alcoholic Fatty Liver Disease

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