<p>Integrated Datasets of Proteomic and Metabolomic Biomarkers to Predict Its Impacts on Comorbidities of Type 2 Diabetes Mellitus</p>

Abstract

The objective of the current study is to accomplish a relative exploration of the biological roles of differentially dysregulated genes (DRGs) in type 2 diabetes mellitus (T2DM). The study aimed to determine the impact of these DRGs on the biological pathways and networks that are related to the associated disorders and complications in T2DM and to predict its role as prospective biomarkers. Methods: Datasets obtained from metabolomic and proteomic profiling were used for investigation of the differential expression of the genes. A subset of DRGs was integrated into IPA software to explore its biological pathways, related diseases, and their regulation in T2DM. Upon entry into the IPA, only 94 of the DRGs were recognizable, mapped, and matched within the database. Results: The study identified networks that explore the dysregulation of several functions; cell components such as degranulation of cells; molecular transport process and metabolism of cellular proteins; and inflammatory responses. Top disorders associated with DRGs in T2DM are related to organ injuries such as renal damage, connective tissue disorders, and acute inflammatory disorders. Upstream regulator analysis predicted the role of several transcription factors of interest, such as STAT3 and HIF alpha, as well as many kinases such as JAK kinases, which affects the gene expression of the dataset in T2DM. Interleukin 6 (IL6) is the top regulator of the DRGs, followed by leptin (LEP). Monitoring the dysregulation of the coupled expression of the following biomarkers (TNF, IL6, LEP, AGT, APOE, F2, SPP1, and INS) highlights that they could be used as potential prognostic biomarkers. Conclusion: The integration of data obtained by advanced metabolomic and proteomic technologies has made it probable to advantage in understanding the role of these biomarkers in the identification of significant biological processes, pathways, and regulators that are associated with T2DM and its comorbidities.

The Immunophenotyping Changes of Peripheral CD4+ T Lymphocytes and Inflammatory Markers of Class III Obesity Subjects After Laparoscopic Gastric Sleeve Surgery – A Follow-Up Study

“… 22 Several studies demonstrated that hsCRP seems to be the single biomarker of inflammation observed to consistently decreased after bariatric surgery. 23 , 24 Furthermore, the present study demonstrated a decrease of pro-inflammatory cytokines of TNF-alpha and IL-6, which is coherent with previous studies, 15 , 17 while other studies demonstrated no changes. 18 , 19 The inconsistent results of inflammatory cytokines profile between different studies could be due to the degree of insulin resistance at baseline, inflammatory markers’ expression, sample size, study design, technical assays, the timing of assessment of postoperative outcomes, and inherited factors of the study population, which could impact the heterogeneity among the studies.…”

“…The current data demonstrated that the anti-inflammatory markers, for instance, adiponectin and IL-10, were increased after LGS in the obese subjects, consistent with several studies that reported similar findings of these markers after bariatric surgery. 15 , 20 A previous study by Kalra et al 2017, demonstrated that plasma leptin level increases with the fat deposition in obese subjects, and a state of leptin resistance is observed in morbidly obese subjects due to the failure of signaling to the hypothalamic satiety center. 21 The present study demonstrated a significant reduction of leptin after 12 weeks of LGS, observed after bariatric surgery in other studies such as gastric plication, bypass, and gastric sleeve.…”

“…The assay was performed based upon the manufacturer’s protocol, as previously published by our lab. 15 …”

COVID-19 and diabetes mellitus: from pathophysiology to clinical management

“…Patients with COVID-19 also exhibit elevation of other inflammatory markers, such as D-dimer, ferritin and IL-6 (ref. 43 ), which might contribute to an increased risk of microvascular and macrovascular complications originating from low-grade vascular inflammation in patients with underlying diabetes mellitus 44 . In a nationwide study in France, microvascular and macrovascular complications of diabetes mellitus were significantly associated with increased risk of mortality in patients with COVID-19 (ref.…”

Effect of plasma glucose at admission on COVID-19 mortality: experience from a tertiary hospital

“…In the CORONADO study from France, chronic microvascular and macrovascular complications of diabetes were significantly associated with increased risk of mortality in patients with COVID-19 ( 48 ). Elevated inflammatory markers such as D-dimer, ferritin and IL6 may also contribute to an increased risk of chronic diabetic complications in patients with pre-existing DM ( 49 ). Presence and progression of diabetic complications were not systematically evaluated in our study.…”