Increased expression of serum IL-18 and IL-18R in newly diagnosed type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a heterogeneous metabolic disorder in which genetic, sedentary lifestyle, obesity, and environmental factors come together to produce insulin resistance in target tissues, leading to hyperglycemia. Evidence reveals that inflammation may play an essential role in the pathogenesis of T2DM. Interleukin-18 (IL-18), a proinflammatory cytokine, plays a crucial role in the acute and chronic inflammatory process. The association of IL-18 levels with IL-18R expression in T2DM has not been investigated so far. The aim of this study was to compare the peripheral changes in serum IL-18 levels and its receptor (IL18R) expression in newly diagnosed T2DM and healthy controls. METHODS: A total of 35 newly diagnosed type 2 diabetic cases and 35 non-diabetic controls were enrolled after obtaining informed consent. Venous whole blood was taken under aseptic conditions. Biochemical parameters were estimated in an auto-analyzer. Serum IL-18 levels were calculated using ELISA, whereas IL-18R expression was determined via RT-PCR. GAPDH was used as an internal control. RESULTS: When compared to non-diabetic controls, the serum IL-18 levels were significantly higher in T2DM patients (P=0.010) along with a significant upregulation of IL18R (P=0.0018). Serum IL-18 levels in T2DM and non-diabetic controls were 669.5 (445) and 498.3 (404.9) pg/mL respectively, and IL-18R showed a fold change of 10.33. CONCLUSIONS: Both serum IL-18 and its receptor IL-18R is significantly higher in newly diagnosed T2DM patients.

Altered expression of specific antioxidant (SOD1 and SOD2) and DNA repair (XRCC1 and OGG1) genes in patients with newly diagnosed type-2 diabetes mellitus.

BACKGROUND: Uncontrolled increase in Reactive Oxygen Species (ROS) leads to the release of free radicals. Additionally, when antioxidants go below a certain level, major molecules of our system such as DNA, proteins, and many other macromolecules get damaged, leading to cancer, heart diseases, and metabolic syndromes like diabetes. Therefore, we in our study focused on newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients and tried to evaluate the expression of antioxidant enzyme encoding genes; Superoxide Dismutase 1(SOD1) and Superoxide Dismutase 2 (SOD2) and DNA repair genes; X-ray repair cross-complementing 1(XRCC1) and 8-oxoguanine DNA glycosylase 1 (OGG1) in them. METHODS: Expression analysis was performed by RT-PCR on 60 subjects (30 T2DM cases and 30 non-diabetic controls). The level of the SOD enzyme was also estimated in a serum sample by the colorimetric method. Biochemical parameters such as fasting plasma glucose (FBG), glycated haemoglobin (HbA1c), high sensitivity C-reactive protein (hsCRP), and lipid profile were estimated in an auto analyzer. Receiver operating characteristic (ROC) curve analysis was done, the area under the curve for mRNA expression and enzyme level was calculated to determine their potential as markers in newly diagnosed T2DM. RESULTS: Down-regulation of both SOD1 (0.43 fold, p=0.02) and SOD2(0.41 fold, p=0.13) and up-regulation of both XRCC1(1.15 fold, p>0.05) and OGG1(1.49 fold, p>0.05) was observed in patients with T2DM. We also observed a significant decrease (p=0.02) in SOD enzyme levels in diabetic cases than in controls (599.8 ± 178.9 and 691.3 ±127.3). CONCLUSIONS: We report that antioxidant repair genes are downregulated and DNA repair genes are upregulated in newly diagnosed T2DM patients. SOD levels and SOD1 gene expression can serve as informative biomarkers for identifying T2DM patients.

Role of interleukin-2 and interleukin-18 in newly diagnosed type 2 diabetes mellitus.

OBJECTIVES: The study aimed to compare the levels of anti-inflammatory interleukin-2 (IL-2) and proinflammatory interleukin-18 (IL-18) among newly diagnosed type 2 diabetes mellitus (T2DM) and nondiabetic volunteers, to predict their roles as markers in the diagnosis of newly diagnosed T2DM. METHODS: In the study, 60 subjects were enrolled (30 T2DM cases and 30 non-diabetic controls). Biochemical parameters such as fasting plasma glucose (FBS), glycated haemoglobin (HbA1c), high sensitivity C-reactive protein (hs-CRP) and lipid profile were estimated in auto-analyser. Serum IL-2 and IL-18 levels were assessed by enzyme-linked immune sorbent assay (ELISA). RESULTS: Significant differences were observed in the levels of interleukins among study groups. The median (95% confidence interval) of IL-2 in cases and controls were 8.55 (6.07-47.23) and 45.87 (12.81-145.4) (p=0.02). The median (95% CI) of IL-18 on the other hand in cases and controls were 691.6 (580.3-872.6) and 511.1 (452.6-557.5) (p=0.0014). CONCLUSIONS: Our study is the first to correlate IL-2 and IL-18 in newly diagnosed T2DM patients. Findings from this study highlight the anti-inflammatory role of IL-2 and proinflammatory role of IL-18 in T2DM. ROC analysis helped predict their role as markers in T2DM diagnosis.

Inflammation, Immunity and Immunogenetics in COVID-19: A Narrative Review.

The novel Coronavirus Disease 2019 (COVID-19), that began in Wuhan Province, China was labelled as an International Public Health Emergency on January 30, 2020 and later was declared a pandemic by the World Health Organisation (WHO) on March 11, 2020. The causative agent, SARS-CoV-2 was the third coronavirus responsible for causing major disease outbreaks in human population after Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) caused by SARS-CoV and MERS-CoV respectively. The patients of COVID-19 present with a clinical feature resembling mild form of viral pneumonia which in certain cases progress to a severe form characterised by adult respiratory distress syndrome (ARDS) and/or multiorgan failure leading to death. The transition from mild to severe form of COVID-19 is affected by a lot of factors like age, co-morbidities etc. In the absence of an absolute cure, it is essential to explore the molecular pathogenesis of the disease to identify people at risk of developing severity so that alternative treatment modalities may be planned. The aim of this review is to provide an update on the general characteristics of SARS-CoV-2 and highlight the inflammatory changes and immune dysregulation that may help in identification of molecular predictors of disease severity.