Role of Inflammatory Markers in Development of Type 2 Diabetes Mellitus (original) (raw)
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The impact of low alcohol consumption on the liver and inflammatory cytokines in diabetic rats
Advances in Clinical and Experimental Medicine, 2018
Background. Diabetes mellitus (DM) and alcohol consumption is still one of the important research models that simulate variable clinical conditions and metabolic diseases, such as alcoholic liver diseases. Objectives. The aim of this study was to evaluate the long-term cumulative effects of low alcohol consumption on the liver tissue, biochemical assays and some inflammatory cytokines in experimentally-induced DM rats. Material and methods. Ethanol was administered in the drinking water (3% v/v) for 30 days to adult male Sprague-Dawley rats, with or without DM induced by streptozocin injection. Histological and biochemical parameters as well as some inflammatory cytokines-interleukin (IL)-4, IL-6, IL-10, and tumor necrosis factor alpha (TNF-α)-were measured. Results. A significant increase in blood glucose level in the combination group was accompanied by a significant decrease in plasma insulin (p < 0.001 vs controls). Hepatic histopathology of the combination group revealed steatosis and fibrosis in addition to a significant increase in the gamma-glutamyltransferase (γ-GT) and alkaline phosphatase (ALP) levels (p < 0.05 and p < 0.001, respectively). A non-high-density lipoprotein (HDL) lipid profile (total cholesterol (TC), triglycerides (TG) and low-density lipoprotein (LDL)) revealed a significant increase in comparison to controls (p < 0.05), while HDL showed no significant change. The IL-4 and IL-6 levels were significantly higher (p < 0.05), while IL-10 and TNF-α revealed non-significant changes. Conclusions. Depletion of the hyperglycemic response in the case of low alcohol consumption in DM rats was associated with elevated plasma cytokines, especially IL-6 and IL-4, which could be a part of a host defense mechanism to repair the hepatic and pancreatic damage through this inflammatory process. The severe liver damage under insult of low alcohol consumption and DM could serve as inhibitory factors in gluconeogenesis and glycogenolysis, with little or no impact on insulin levels.
Type 2 Diabetes Mechanisms, Role of Cytokines and Their Variations in Disease Development
2018
Type 2 diabetes is a chronic and complex disease characterized by impaired pancreatic beta cell function and insulin resistance. Several genetic and environmental factors are playing role in the Type 2 diabetes development. Recent studies pointed out a relationship between the inflammation generation and development of the disease. The inflammation induced-activation of the monocytes enhances the insulin resistance and decreases the insulin secretion due to the impairment of the pancreatic beta cells and also oxidative stress occurring after the disorder of the lipid metabolism affects the disease development. Following the oxidative stress formation, the levels of the reactive oxygen species (ROS) increase and insulin resistance develops consequently. Cytokines are the keystones in regulation of the homeostatic mechanisms such as inflammation and tissue repair. Thus, variations in their levels and structures are the reasons for the occurrence of various diseases. The single nucleot...
Inflammatory Process in Type 2 Diabetes: The Role of Cytokines
Annals of the New York Academy of Sciences, 2006
Population-based studies have shown strong relationship between inflammatory markers and metabolic disturbances, obesity, and atherosclerosis, whereas inflammation has been considered as a &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;common soil&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; between these clinical entities and type 2 diabetes (T2D). The accumulation of macrophages in adipose tissue (AT), the common origin of macrophages and adipocytes, the prevalent presence of peripheral mononuclear cells, and apoptotic beta cells by themselves seem to be the sources of inflammation present in T2D, since they generate the mediators of the inflammatory processes, namely cytokines. The main cytokines involved in the pathogenesis of T2D are interleukin-1beta (IL-1beta), with an action similar to the one present in type 1 diabetes, tumor necrosis factor-alpha (TNF-alpha), and IL-6, considered as the main regulators of inflammation, leptin, more recently introduced, and several others, such as monocyte chemoattractant protein-1, resistin, adiponectin, with either deleterious or beneficial effects in diabetic pathogenesis. The characterization of these molecules targeted diabetes treatment beyond the classical interventions with lifestyle changes and pharmaceutical agents, and toward the determination of specific molecular pathways that lead to low grade chronic inflammatory state mainly due to an immune system&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s unbalance.
Inflammatory cytokines in insulin-treated patients with type 2 diabetes
Nutrition, Metabolism and Cardiovascular Diseases, 2008
An association between type 2 diabetes mellitus and inflammation has been described in several studies. The aim of this study was to search for the presence of low-grade inflammation in a special group of insulin-treated patients with type 2 diabetes, and to investigate a possible correlation between inflammation and obesity, glucose homeostasis and insulin requirement (IU insulin/kg body weight, BW). We studied 85 subjects with type 2 diabetes that were receiving insulin treatment (group A) and 32 receiving sulfonylurea treatment (group B), and 57 subjects without diabetes (group C). Interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), and the soluble TNF-alpha receptors sTNFR-60 and sTNFR-80 were measured in serum samples taken from all patients. The mean serum cytokine levels in group A vs. group B were: IL-6, 8.54+/-11 vs. 2.71+/-1.9 pg/ml (p=0.000); TNF-alpha, 14.33+/-24 vs. 5.12+/-15 pg/ml (p=0.016); sTNFR60, 3.9+/-2.8 vs. 2.36+/-1.4 ng/ml (p=0.000); and sTNFR80, 11.9+/-7 vs. 9.4+/-6 ng/ml (p=0.080). The mean serum cytokine levels in group A vs. group C were: IL-6, 8.54+/-11 vs. 4.74+/-7 pg/ml (p=0.017); TNF-alpha, 14.33+/-24 vs. 5.94+/-3.4 pg/ml (p=0.003); sTNFR60, 3.9+/-2.8 vs. 2.54+/-1.4 ng/ml (p=0.000); and sTNFR80, 11.9+/-7 vs. 10.85+/-8 ng/ml (p=0.470). A positive association between waist circumference and IL-6 (r=0.165, p=0.030) and sTNFR-60 (r=0.276, p=0.000) was detected. A significant correlation coefficient was observed between haemoglobin A1c (HbA1c) and both IL-6 (r=0.278, p=0.000) and sTNFR-60 (r=0.293, p=0.000), when the groups were studied as one. No correlation between inflammation and units of insulin/kg BW was found. In conclusion, low-grade chronic inflammation, as estimated by the relative levels of inflammatory cytokines, was present in patients with type 2 diabetes that were receiving insulin treatment, with significantly higher cytokine levels recorded compared to sulfonylurea-treated patients. In addition, an association between inflammation and both obesity and glucose homeostasis was detected.
Heliyon
There has been growing evidence that inflammatory markers play a role in the development as well as severity of Type 2 diabetes mellitus (T2DM). This study has been designed to decipher the involvement of C-Reactive Protein (CRP), Tumor Necrosis Factor (TNFα), Interleukin-6 (IL-6) and Interleukin-10 (IL-10) in the etiopathogenesis of T2DM. Basic procedures: A total of 480 T2DM cases and 540 healthy controls were recruited for the study. Blood samples were collected from each study subject to measure the serum levels of CRP, TNFα, IL-6 and IL-10. Main findings: We found that serum levels of CRP in mg/dl (4.2 AE 0.9), TNFα in pg/ml (34.5 AE 8.8), IL-6 in pg/ml (19.2 AE 7.2) in T2DM patients were significantly high as compared to control participants (CRP; 1.4 AE 0.6, TNFα; 12.7 AE 3.4, IL-6; 3.1 AE 1.4; P < 0.0001). The serum levels of IL-10 in pg/ml were lower in T2DM cases compared to controls (4.35 AE 1.2 vs. 9.6 AE 1.2). In addition, we observed a significant association of CRP levels with insulin resistance, obesity and dyslipidemia. Increased TNFα levels were strongly associated with female gender, Poor glycemic control and strong family history of diabetes. Poor glycemic control was significantly associated with elevated IL-6 levels. Moreover, significantly reduced IL-10 levels were found in T2DM patients with sedentary lifestyle; low educational and rural background. Conclusions: This study showed a strong relationship between TNFα, IL-6, CRP, IL-10 and T2DM patients of Kashmiri ethnicity, treated at SMHS Hospital. Thus, supporting other studies and showing that cytokines may be good markers for T2DM development.
Research Article Analysis of Inflammatory Mediators in Type 2 Diabetes Patients
2013
Copyright © 2013 Ahmed Al-Shukaili et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Themain aim of this study is to assess the inflammatory markers in type 2 diabetes mellitus (T2DM) by measuring some cytokines concentrations and lymphocytes subset and correlate them with other laboratory investigations. Fifty-seven patients with type-2 diabetes and 30 healthy volunteers were enrolled in this study. Data for the C-reactive protein (CRP), haemoglobin, HbA1c, and autoantibody levels were obtained from the patients files. The cytokine concentrations were measured in patient’s serum using commercially available ELISA assays. Lymphocytes subsets were measured by flow cytometric methods. The levels of IL-1
Analysis of Inflammatory Mediators in Type 2 Diabetes Patients
International Journal of Endocrinology, 2013
The main aim of this study is to assess the inflammatory markers in type 2 diabetes mellitus (T2DM) by measuring some cytokines concentrations and lymphocytes subset and correlate them with other laboratory investigations. Fifty-seven patients with type-2 diabetes and 30 healthy volunteers were enrolled in this study. Data for the C-reactive protein (CRP), haemoglobin, HbA1c, and autoantibody levels were obtained from the patients files. The cytokine concentrations were measured in patient’s serum using commercially available ELISA assays. Lymphocytes subsets were measured by flow cytometric methods. The levels of IL-1β, IL-6, IL-15, and TNF-αwere found to be decreased in T2DM patients, whereas the levels of IL-10, IFN-γ, and caspase-1 were increased, compared to normal controls. T2DM patients with hypertension show significantly decreased levels of IL-1βand caspase-1 compared to patients without hypertension. No significant differences in lymphocytes subset between cases and normal...
Changes in Cytokine Levels During Acute Hyperinsulinemia in Offspring of Type 2 Diabetic Subjects
Atherosclerosis, 2010
Offspring of type 2 diabetic patients type 2 diabetes cytokines hyperinsulinemia a b s t r a c t Objective: To investigate the changes in the levels of cytokines and adhesion molecules in response to acute hyperinsulinemia in the offspring of type 2 diabetic subjects. Methods: Forty healthy offspring of type 2 diabetic subjects and 19 control offspring of healthy parents were included in the study. Twenty offspring had normal glucose tolerance (NGT) and twenty offspring impaired glucose tolerance (IGT). Insulin sensitivity was determined by the hyperinsulinemic euglycemic clamp and insulin secretion with the intravenous glucose tolerance test. The levels of cytokines and adhesion molecules were measured before and at the end of the clamp. Results: Acute hyperinsulinemia induced by the euglycemic hyperinsulinemic clamp reduced the levels of TNF-␣, IL-8, IL-10 and IL-18 in healthy controls but not in the offspring of type 2 diabetic subjects having NGT or IGT. In response to insulin, levels of hs-CRP decreased and levels of IL-6 increased significantly in all study groups. The levels of adhesion molecules (ICAM-1, VCAM-1, E-Selectin) remained unchanged in response to hyperinsulinemia. Conclusions: The suppression of cytokine levels (particularly proinflammatory cytokines) during acute hyperinsulinemia observed in healthy controls was not present in offspring of type 2 diabetic patients. This emphasizes the crucial role of low-grade inflammation in insulin resistance in subjects with high risk of developing diabetes.