Glycemic reduction alters white blood cell counts and inflammatory gene expression in diabetes

Fang, Xiang; Dorcely, Brenda; Ding, Xiaoyu; Yin, Shi; Son, Ni-Huiping; Hu, Shilian; Goldberg, Ira J.

doi:10.1016/j.jdiacomp.2018.08.003

Cited by 11 publications

(6 citation statements)

References 49 publications

(52 reference statements)

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“…In this regard, chronic inflammation due mainly to the activation of the myeloid cell lineage (e.g., macrophages and neutrophils), is directly related to the induction of IR ( 4 , 122 ). Fang et al have shown that patients with T2DM have elevated numbers of circulating leukocytes that express high levels of inflammatory gene products but glycemic control can reverse the situation ( 123 ). De Souza Prestes et al have indicated that exposure of leukocytes to MGO changes their morphology by making them larger and more granular, increases their ability to produce ROS and decreases their expression of antioxidant genes ( 124 ).…”

Section: Effects Of T2dm On the Immune Systemmentioning

confidence: 99%

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

et al. 2020

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Metabolic abnormalities such as dyslipidemia, hyperinsulinemia, or insulin resistance and obesity play key roles in the induction and progression of type 2 diabetes mellitus (T2DM). The field of immunometabolism implies a bidirectional link between the immune system and metabolism, in which inflammation plays an essential role in the promotion of metabolic abnormalities (e.g., obesity and T2DM), and metabolic factors, in turn, regulate immune cell functions. Obesity as the main inducer of a systemic low-level inflammation is a main susceptibility factor for T2DM. Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. Hyperglycemia and the subsequent inflammation are the main causes of micro-and macroangiopathies in the circulatory system. They also promote the gut microbiota dysbiosis, increased intestinal permeability, and fatty liver disease. The impaired immune system together with metabolic imbalance also increases the susceptibility of patients to several pathogenic agents such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, the need for a proper immunization protocol among such patients is granted. The focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of T2DM patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases.

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Section: Effects Of T2dm On the Immune Systemmentioning

confidence: 99%

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

et al. 2020

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“…This threshold of 2.0 mM glucose is much lower than acceptable blood glucose levels, suggesting that there are other factors which maintain endothelial cell health in normoglycemia in vivo , i.e., up to 5.5mM/L. Indeed, there are damage limitation factors in the circulation which protect the endothelium, such as acute phase reactants ( 29 – 31 ) and circulating antiproteases ( 32 , 33 ), while the number and activation status of the circulating cells in the hyperglycemic milieu must also have an effect ( 24 , 34 ).…”

Section: What Triggers the Development Of Complications In Diabetes?mentioning

confidence: 99%

The Role of Inflammation in Diabetic Retinopathy

2020

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Inflammation is central to pathogenic processes in diabetes mellitus and the metabolic syndrome and particularly implicates innate immunity in the development of complications. Inflammation is a primary event in Type 1 diabetes where infectious (viral) and/or autoimmune processes initiate disease; in contrast, chronic inflammation is typical in Type 2 diabetes and is considered a sequel to increasing insulin resistance and disturbed glucose metabolism. Diabetic retinopathy (DR) is perceived as a vascular and neurodegenerative disease which occurs after some years of poorly controlled diabetes. However, many of the clinical features of DR are late events and reflect the nature of the retinal architecture and its cellular composition. Retinal microvascular disease is, in fact, an early event pathogenetically, induced by low grade, persistent leukocyte activation which causes repeated episodes of capillary occlusion and, progressive, attritional retinal ischemia. The later, overt clinical signs of DR are a consequence of the retinal ischemia. Metabolic dysregulation involving both lipid and glucose metabolism may lead to leukocyte activation. On a molecular level, we have shown that macrophage-restricted protein tyrosine phosphatase 1B (PTP1B) is a key regulator of inflammation in the metabolic syndrome involving insulin resistance and it is possible that PTP1B dysregulation may underlie retinal microvascular disease. We have also shown that adherent CCR5 + CD11b + monocyte macrophages appear to be selectively involved in retinal microvascular occlusion. In this review, we discuss the relationship between early leukocyte activation and the later features of DR, common pathogenetic processes between diabetic microvascular disease and other vascular retinopathies, the mechanisms whereby leukocyte activation is induced in hyperglycemia and dyslipidemia, the signaling mechanisms involved in diabetic microvascular disease, and possible interventions which may prevent these retinopathies. We also address a possible role for adaptive immunity in DR. Although significant improvements in treatment of DR have been made with intravitreal anti-VEGF therapy, a sizeable proportion of patients, particularly with sight-threatening macular edema, fail to respond. Alternative therapies targeting inflammatory processes may offer an advantage.

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“…Extracellular ROS production, pro-inflammatory cytokine release and NET formation are increased in diabetes, whereas neutrophil migration, apoptosis and intracellular ROS production are reduced, which ultimately impairs bacterial killing and inflammation ( 56 , 58 – 61 ). Phenotypic variations in neutrophil function are supported by transcriptomic data, showcasing a fundamentally altered profile in key pro-inflammatory genes in neutrophils in PWD ( 62 , 63 ).…”

Section: Introductionmentioning

confidence: 96%

A Bittersweet Response to Infection in Diabetes; Targeting Neutrophils to Modify Inflammation and Improve Host Immunity

et al. 2021

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Chronic and recurrent infections occur commonly in both type 1 and type 2 diabetes (T1D, T2D) and increase patient morbidity and mortality. Neutrophils are professional phagocytes of the innate immune system that are critical in pathogen handling. Neutrophil responses to infection are dysregulated in diabetes, predominantly mediated by persistent hyperglycaemia; the chief biochemical abnormality in T1D and T2D. Therapeutically enhancing host immunity in diabetes to improve infection resolution is an expanding area of research. Individuals with diabetes are also at an increased risk of severe coronavirus disease 2019 (COVID-19), highlighting the need for re-invigorated and urgent focus on this field. The aim of this review is to explore the breadth of previous literature investigating neutrophil function in both T1D and T2D, in order to understand the complex neutrophil phenotype present in this disease and also to focus on the development of new therapies to improve aberrant neutrophil function in diabetes. Existing literature illustrates a dual neutrophil dysfunction in diabetes. Key pathogen handling mechanisms of neutrophil recruitment, chemotaxis, phagocytosis and intracellular reactive oxygen species (ROS) production are decreased in diabetes, weakening the immune response to infection. However, pro-inflammatory neutrophil pathways, mainly neutrophil extracellular trap (NET) formation, extracellular ROS generation and pro-inflammatory cytokine generation, are significantly upregulated, causing damage to the host and perpetuating inflammation. Reducing these proinflammatory outputs therapeutically is emerging as a credible strategy to improve infection resolution in diabetes, and also more recently COVID-19. Future research needs to drive forward the exploration of novel treatments to improve infection resolution in T1D and T2D to improve patient morbidity and mortality.

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Glycemic reduction alters white blood cell counts and inflammatory gene expression in diabetes

Abstract: Significant glycemic reduction in subjects with poorly controlled diabetes led to reduced circulating WBC counts and inflammatory gene expression.

Cited by 11 publications

References 49 publications

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System

The Role of Inflammation in Diabetic Retinopathy

A Bittersweet Response to Infection in Diabetes; Targeting Neutrophils to Modify Inflammation and Improve Host Immunity

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