scholarly journals Diabetes and Colorectal Cancer Risk: A New Look at Molecular Mechanisms and Potential Role of Novel Antidiabetic Agents

2021 ◽  
Vol 22 (22) ◽  
pp. 12409
Author(s):  
Jelena Vekic ◽  
Aleksandra Zeljkovic ◽  
Aleksandra Stefanovic ◽  
Rosaria Vincenza Giglio ◽  
Marcello Ciaccio ◽  
...  

Epidemiological data have demonstrated a significant association between the presence of type 2 diabetes mellitus (T2DM) and the development of colorectal cancer (CRC). Chronic hyperglycemia, insulin resistance, oxidative stress, and inflammation, the processes inherent to T2DM, also play active roles in the onset and progression of CRC. Recently, small dense low-density lipoprotein (LDL) particles, a typical characteristic of diabetic dyslipidemia, emerged as another possible underlying link between T2DM and CRC. Growing evidence suggests that antidiabetic medications may have beneficial effects in CRC prevention. According to findings from a limited number of preclinical and clinical studies, glucagon-like peptide-1 receptor agonists (GLP-1RAs) could be a promising strategy in reducing the incidence of CRC in patients with diabetes. However, available findings are inconclusive, and further studies are required. In this review, novel evidence on molecular mechanisms linking T2DM with CRC development, progression, and survival will be discussed. In addition, the potential role of GLP-1RAs therapies in CRC prevention will also be evaluated.

2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.


Lupus ◽  
1998 ◽  
Vol 7 (2_suppl) ◽  
pp. 132-134 ◽  
Author(s):  
O Vaarala

In prospective studies, increased levels of cardiolipin-biding antibodies and autoantibodies to oxidized low-density lipoprotein (LDL) have been observed in patients with myocardial infarction (MI). These findings suggest that antiphospholipid antibodies may contribute to the development of MI. The ‘oxidative-modification hypothesis’ in the pathogenesis of atherosclerotic heart disease is based on the oxidation of LDL, its accumulation into arterial wall, and the development of chronic inflammation in the atheroma. Evidence of enhanced lipid peroxidation and its association with antiphospholipid antibodies has been recently reported in SLE patients. There is also epidemiological data showing a remarkably increased risk of MI in SLE. In this review, the role of different types of antiphospholipid antibodies in the development of atherosclerotic heart disease is evaluated with particular attention to their potential pathogenic mechanisms and the possibilities in the prevention of MI associated with antiphospholipid antibodies.


2019 ◽  
Vol 18 ◽  
Author(s):  
Sandra Maria Barbalho ◽  
Ricardo José Tofano ◽  
Marcela Bueno de Oliveira ◽  
Karina Rodrigues Quesada ◽  
Mariana Ricci Barion ◽  
...  

Abstract Background Dyslipidemias are associated with atherosclerosis and cardiovascular diseases. Recently, non-high-density lipoprotein cholesterol (non-HDL-c) has emerged as a new target for assessment and prediction of risk of cardiovascular disease (CVD) and is closely associated with atheroma plaque progression. Objectives To evaluate associations between HDL-c and non-HDL-c levels and anthropometric and biochemical parameters and with the Castelli risk indexes I and II. Methods 300 randomly selected people were subdivided into two groups: patients with normal values for non-HDL-c and patients with altered values for non-HDL-c. These parameters were analyzed for associations with glycemia, total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-c), Castelli Index I (CI-I), Castelli Index II (CI-II), waist circumference (WC), body mass index (BMI) and presence of metabolic syndrome (MS). Results Glycemia, TC, TG, LDL-c, CI-I, CI-II, WC and BMI were all significantly different between subjects with normal and altered values of HDL-c and non-HDL-c. TC and WC both exhibited significantly higher values among patients with abnormal non-HDL-c when compared to patients with abnormal HDL-c. A significant difference was observed in occurrence of MS among patients with altered values of HDL-c and non-HDL-c. Conclusions Our results show that both HDL-c and non-HDL-c are associated with insulin resistance, dyslipidemia, atherogenic indices, and obesity. There is therefore a need for randomized clinical intervention trials examining the potential role of non-HDL-c as a possible primary therapeutic target.


2020 ◽  
Vol 48 (6) ◽  
pp. 030006052093160
Author(s):  
Kazuhiko Hashimoto ◽  
Masao Akagi

Osteoarthritis (OA) is a chronic joint disorder that causes degeneration of cartilage, synovial inflammation, and formation of osteophytes. Aging, obesity, and sex are considered the main risk factors of OA. Recent studies have suggested that metabolic syndrome (MetS) disorders, such as hypertension, hyperlipidemia, diabetes mellitus, and obesity, may be involved in the pathogenesis and progression of OA. MetS disorders are common diseases that also result in atherosclerosis. Researchers believe that OA and atherosclerosis have underlying similar molecular mechanisms because the prevalence of both diseases increases with age. Oxidation of low-density lipoprotein (ox-LDL) is believed to play a role in the pathogenesis of atherosclerosis. Recent reports have shown that ox-LDL and low-density lipoprotein receptor 1 (LOX-1) are involved in the pathogenesis of OA. The purpose of this narrative review is to summarize the current understanding of the role of the LOX-1/ox-LDL system in the pathogenesis of OA and to reveal common underlying molecular pathways that are shared by MetS in OA and the LOX-1/ox-LDL system.


Author(s):  
Raushan Kumar ◽  
Syed Ibrahim Rizvi

Diets rich in fats and cholesterol are mainly responsible for the production of free radicals which contribute to the incidence of hyperlipidemia and hypercholesterolemia. Both of these are the major factors responsible for CVDs. Hyperlipidemia is characterized by elevated level of total cholesterol (TC), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL), and reduced level of high-density lipoprotein (HDL) in serum. The main role of diet is to provide ample amount of nutrients to meet the nutritional requirements of an individual. However, there are increasing scientific approaches helping the hypothesis that some food ingredients have beneficial effects over and above the provision of the basic nutrients. So in this chapter, the main focus is food categorized under nutraceutical and functional food and their various protective roles in the case of hyperlipidemia.


Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 784
Author(s):  
Salman Ul Islam ◽  
Muhammad Bilal Ahmed ◽  
Haseeb Ahsan ◽  
Young-Sup Lee

Abnormal lipid metabolism leads to the development of hyperlipidemia, a common cause of multiple chronic disorders, including cardiovascular disease (CVD), obesity, diabetes, and cerebrovascular disease. Low-density lipoprotein cholesterol (LDL-C) currently remains the primary target for treatment of hyperlipidemia. Despite the advancement of treatment and prevention of hyperlipidemia, medications used to manage hyperlipidemia are limited to allopathic drugs, which present certain limitations and adverse effects. Increasing evidence indicates that utilization of phytochemicals and plant-based whole foods is an alternative and promising strategy to prevent hyperlipidemia and CVD. The current review focuses on phytochemicals and their pharmacological mode of actions for the regulation of LDL-C and prevention of CVD. The important molecular mechanisms illustrated in detail in this review include elevation of reverse cholesterol transport, inhibition of intestinal cholesterol absorption, acceleration of cholesterol excretion in the liver, and reduction of cholesterol synthesis. Moreover, the beneficial effects of plant-based whole foods, such as fresh fruits, vegetables, dried nuts, flax seeds, whole grains, peas, beans, vegan diets, and dietary fibers in LDL-C reduction and cardiovascular health are summarized. This review concludes that phytochemicals and plant-based whole foods can reduce LDL-C levels and lower the risk for CVD.


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