Proteomic analysis to identify candidate biomarkers associated with type 1 diabetes

Oliveira, Valzimeire do Nascimento de; Lima-Neto, Abelardo Barbosa Moreira; Tilburg, Maurício Fraga van; Monteiro-Moreira, Ana Cristina de Oliveira; Lobo, Marina Duarte Pinto; Rondina, Davide; Fernandes, Virgínia Oliveira; Montenegro, Ana Paula Dias Rangel; Júnior, Renan Magalhães Montenegro; Guedes, Maria Izabel Florindo

doi:10.2147/dmso.s162008

Cited by 21 publications

(10 citation statements)

References 70 publications

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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: 97%

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

confidence: 97%

The Role of Inflammation in Diabetic Retinopathy

2020

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“…Moreover, proteomics studies have also shown significant changes in plasma protein levels in patients with T1D. For example, alpha-1-microglobulin, alpha-2-macroglobulin, beta-2-glycoprotein I, Ig alpha-2 chain C region, apolipoprotein A-II, and prothrombin are elevated [ 44 , 45 ]. Combined proteomics and ATAC-seq transcriptomics analyses in β cells treated with IFNα also showed activated genes and metabolic pathways consistent with T1D [ 46 , 47 ].…”

Section: Introductionmentioning

confidence: 99%

Parallel Multi-Omics in High-Risk Subjects for the Identification of Integrated Biomarker Signatures of Type 1 Diabetes

et al. 2021

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Background: Biomarkers are crucial for detecting early type-1 diabetes (T1D) and preventing significant β-cell loss before the onset of clinical symptoms. Here, we present proof-of-concept studies to demonstrate the potential for identifying integrated biomarker signature(s) of T1D using parallel multi-omics. Methods: Blood from human subjects at high risk for T1D (and healthy controls; n = 4 + 4) was subjected to parallel unlabeled proteomics, metabolomics, lipidomics, and transcriptomics. The integrated dataset was analyzed using Ingenuity Pathway Analysis (IPA) software for disturbances in the at-risk subjects compared to controls. Results: The final quadra-omics dataset contained 2292 proteins, 328 miRNAs, 75 metabolites, and 41 lipids that were detected in all samples without exception. Disease/function enrichment analyses consistently indicated increased activation, proliferation, and migration of CD4 T-lymphocytes and macrophages. Integrated molecular network predictions highlighted central involvement and activation of NF-κB, TGF-β, VEGF, arachidonic acid, and arginase, and inhibition of miRNA Let-7a-5p. IPA-predicted candidate biomarkers were used to construct a putative integrated signature containing several miRNAs and metabolite/lipid features in the at-risk subjects. Conclusions: Preliminary parallel quadra-omics provided a comprehensive picture of disturbances in high-risk T1D subjects and highlighted the potential for identifying associated integrated biomarker signatures. With further development and validation in larger cohorts, parallel multi-omics could ultimately facilitate the classification of T1D progressors from non-progressors.

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“…In the group of diabetes type II, A2MG levels are within the normal range. After division of diabetics according to the presence of diabetic complications, A2MG levels in patients with diabetic complications were significantly higher than in the group of diabetics without complications [32,33]. The increase in plasma A2MG levels in diabetes may be a correlative measure to encounter the potential proteolytic challenge associated with diabetic microangiopathy, even very early in the course of the disease.…”

Section: Discussionmentioning

confidence: 99%

Urinary Peptides Associated Closely with Gestational Diabetes Mellitus

Tian

et al. 2020

Disease Markers

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Gestational diabetes mellitus (GDM) is a common disease of pregnant women, which has a higher incidence in recent years. The purpose of this study is to explore urinary biomarkers that could predict and monitor gestational diabetes mellitus (GDM). Urine samples from 30 normal pregnant women and 78 GDM patients were collected and purified by weak cationic exchange magnetic beads (MB-WCX), then analyzed by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The urinary peptide signatures of the two groups were compared by BioExplorer software. The potential ability of the differently expressed peptides to distinguish GDM patients from normal pregnant women was evaluated by receiver operating characteristic (ROC) analysis. At last, the differently expressed peptides were identified by liquid chromatography tandem mass spectrometry (LC-MS). There were four differently expressed peptides (m/z 1000.5, 1117.5, 1142.9, and 2022.9) between two groups, which were identified as fragments of urinary albumin, α2-macroglobulin, human hemopexin, and α1-microglobulin, respectively. The diagnostic efficacy of m/z 1142.9 was better than the other peptides. The area under the curve (AUC) of the m/z 1142.9 was 0.690 (95% CI: 0.583-0.796). The discovery of urinary polypeptides provides the possibility for the early prediction of GDM and the monitoring of glucose metabolism in GDM patients by a noninvasive method.

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Proteomic analysis to identify candidate biomarkers associated with type 1 diabetes

Cited by 21 publications

References 70 publications

The Role of Inflammation in Diabetic Retinopathy

The Role of Inflammation in Diabetic Retinopathy

Parallel Multi-Omics in High-Risk Subjects for the Identification of Integrated Biomarker Signatures of Type 1 Diabetes

Urinary Peptides Associated Closely with Gestational Diabetes Mellitus

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