Monocyte-mediated inflammation and cardiovascular risk factors in type 2 diabetes mellitus: A systematic review and meta-analysis of pre-clinical and clinical studies

Abstract

Background: Monocyte-mediated inflammation increases the risk of developing type 2 diabetes mellitus and cardiovascular disease. This is the first systematic review and meta-analysis of studies reporting on monocyte-mediated inflammation in type 2 diabetes mellitus. Methods: This systematic review and meta-analysis was registered in the international prospective register of a systematic review: CRD42019132902. The MEDLINE, EMBASE and Google scholar electronic databases were searched, and a random-effects model was used to generate pooled standardised mean differences between patients with type 2 diabetes mellitus and healthy controls. Results: The clinical studies (n ¼ 20) comprised of 1065 patients with type 2 diabetes mellitus and 1103 healthy controls. Notably, the levels of monocyte activation were higher in patients with type 2 diabetes mellitus compared to healthy controls (standardised mean difference ¼ 0.47, 95% confidence interval (0.10, 0.84), p ¼ 0.01) (v 2 ¼ 65.72, I 2 ¼ 83%, p < 0.00001). Patients with type 2 diabetes mellitus had an increased risk of cardiovascular disease compared to healthy controls (standardised mean difference ¼ 0.37, 95% confidence interval (0.13, 0.61), p ¼ 0.003) (v 2 ¼ 958.77, I 2 ¼ 95%, p < 0.00001). All included pre-clinical studies reported on the C57BL/6 mice strain, with a majority of the studies 57% of reporting on high fat diet-induced C57BL/6 mice model. The overall quality of the studies was good with a median score and range of 16 (13-19). Conclusion: Our meta-analysis suggests that there is increased monocyte activation in patients with type 2 diabetes mellitus.

A Review on the Antidiabetic Properties of Moringa oleifera Extracts: Focusing on Oxidative Stress and Inflammation as Main Therapeutic Targets

“…This is an essential result since tenacious hyperglycemia, seen in T1D, is already known to mediate iNOS induction, leading to the activation of protein kinase enzymes such as PKC/c-Jun N-terminal kinases (JNKs)/mitogen-activated protein kinase (MAPK) to propagate the detrimental effects of inflammation ( Giacco and Brownlee, 2010 ). Notably, activation of such pro-inflammatory mechanisms can directly cause excess generation of oxidation products that precede the onset of atherosclerosis and endothelial dysfunction, which are major risk factors for the development of cardiovascular diseases ( Rose et al, 2010 ; Mokgalaboni et al, 2020 ). Although there was limited information on its cardioprotective effects, much evidence suggests Moringa oleifera extracts can significantly decrease pro-inflammatory and apoptotic markers such as TNF-α, IL-1β, IL-6, NF-κβ, caspase 3, caspase 9, and tumor protein (p53) to alleviate the detrimental effects of hyperglycemia in preclinical models of T1D ( Muhammad et al, 2016 ; Omodanisi et al, 2017a ; Azevedo et al, 2018 ; Oguntibeju, 2019 ).…”

Recent Progress in the Diagnosis and Management of Type 2 Diabetes Mellitus in the Era of COVID-19 and Single Cell Multi-Omics Technologies

“…Factors released by the adipose tissue such as pro-inflammatory cytokines (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1b), non-esterified fatty acids, glycerol, and hormones may underly insulin resistance [ 115 ]. The disbalance of the immune system, the endothelial activation of monocytes, and macrophages in the adipose tissue may also release TNF-α and IL-6, thus exacerbating inflammation [ 116 , 117 ]. A meta-analysis of 20 clinical trials with 1065 T2DM patients versus 1103 healthy controls showed a correlation with monocyte activation and CVD risk in T2DM [ 116 ].…”

“…The disbalance of the immune system, the endothelial activation of monocytes, and macrophages in the adipose tissue may also release TNF-α and IL-6, thus exacerbating inflammation [ 116 , 117 ]. A meta-analysis of 20 clinical trials with 1065 T2DM patients versus 1103 healthy controls showed a correlation with monocyte activation and CVD risk in T2DM [ 116 ]. Obesity management with special diet, exercises resulting in at least 15% weight loss, and longer sleep may have great disease-modifying effect on T2DM [ 118 , 119 ].…”

Differential expression of glycoprotein IV on monocyte subsets following high-fat diet feeding and the impact of short-term low-dose aspirin treatment

“…Chronic inflammation and the persistent activation of peripheral monocytes and neutrophils are associated with the pathogenesis of type 2 diabetes mellitus (T2DM). Activated monocytes can further initiate atherosclerosis and increase the risk of complications in people living with T2DM [ [1] , [2] , [3] ]. For example, the monocyte chemoattractant protein 1 (MCP-1) plays a pivotal role in the recruitment of monocytes in response to atherogenic stimuli such as hyperglycaemia and dyslipidaemia [ 4 ].…”