Nucleic acid biomarkers of β cell stress and death in type 1 diabetes

Syed, Farooq; Evans‐Molina, Carmella

doi:10.1097/med.0000000000000261

Cited by 8 publications

(5 citation statements)

References 52 publications

(46 reference statements)

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“…Reliable biomarkers capable of dissecting T1D-associated heterogeneity, guiding immunomodulatory interventions, and identifying individuals at the highest risk of disease remains an unmet clinical need. The advent of sequencing technologies has made it possible to obtain an overview of multiple classes of RNAs within biological samples, spurring interest in the potential for protein coding and noncoding RNAs to serve as noninvasive biomarkers of T1D (reviewed in [24] and [25]). Circulating RNAs, such as miRNAs, facilitate cell-to-cell communication and exert important biological functions via uptake of miRNAs by recipient cells, where they can act to modulate recipient cell gene regulatory function.…”

Section: Discussionmentioning

confidence: 99%

Profiling of RNAs from Human Islet-Derived Exosomes in a Model of Type 1 Diabetes

Krishnan

Syed

Kang

et al. 2019

IJMS

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Type 1 diabetes (T1D) is characterized by the immune-mediated destruction of insulin-producing islet β cells. Biomarkers capable of identifying T1D risk and dissecting disease-related heterogeneity represent an unmet clinical need. Toward the goal of informing T1D biomarker strategies, we profiled coding and noncoding RNAs in human islet-derived exosomes and identified RNAs that were differentially expressed under proinflammatory cytokine stress conditions. Human pancreatic islets were obtained from cadaveric donors and treated with/without IL-1β and IFN-γ. Total RNA and small RNA sequencing were performed from islet-derived exosomes to identify mRNAs, long noncoding RNAs, and small noncoding RNAs. RNAs with a fold change ≥1.3 and a p-value <0.05 were considered as differentially expressed. mRNAs and miRNAs represented the most abundant long and small RNA species, respectively. Each of the RNA species showed altered expression patterns with cytokine treatment, and differentially expressed RNAs were predicted to be involved in insulin secretion, calcium signaling, necrosis, and apoptosis. Taken together, our data identify RNAs that are dysregulated under cytokine stress in human islet-derived exosomes, providing a comprehensive catalog of protein coding and noncoding RNAs that may serve as potential circulating biomarkers in T1D.

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Section: Discussionmentioning

confidence: 99%

Profiling of RNAs from Human Islet-Derived Exosomes in a Model of Type 1 Diabetes

Krishnan

Syed

Kang

et al. 2019

IJMS

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“…Recently, circulating unmethylated insulin DNA has aroused great interest as a biomarker target for early detection of β-cell death in T1D. [102,103] This is based on the fact that certain cytosine-guanine (CpG) sites in the insulin gene are specifically unmethylated in pancreatic β-cells and methylated in most other tissues. During progression of T1D, fragments of the characteristic unmethylated insulin DNA due to β-cell death are leaked into the bloodstream and become detectable.…”

Section: Predictive Biomarkers For T1d Developmentmentioning

confidence: 99%

Serum biomarkers for diagnosis and prediction of type 1 diabetes

Lee

Swensen

Qian

2018

Translational Research

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Type 1 diabetes (T1D) culminates in the autoimmune destruction of the pancreatic βcells, leading to insufficient production of insulin and development of hyperglycemia. Serum biomarkers including a combination of glucose, glycated molecules, C-peptide, and autoantibodies have been well established for the diagnosis of T1D. However, these molecules often mark a late stage of the disease when ∼90% of the pancreatic insulin-producing β-cells have already been lost. With the prevalence of T1D increasing worldwide and because of the physical and psychological burden induced by this disease, there is a great need for prognostic biomarkers to predict T1D development or progression. This would allow us to identify individuals at high risk for early prevention and intervention. Therefore, considerable efforts have been dedicated to the understanding of disease etiology and the discovery of novel biomarkers in the last few decades. The advent of high-throughput and sensitive "-omics" technologies for the study of proteins, nucleic acids, and metabolites have allowed large scale profiling of protein expression and gene changes in T1D patients relative to disease-free controls. In this review, we briefly discuss the classical diagnostic biomarkers of T1D but mainly focus on the novel biomarkers that are identified as markers of β-cell destruction and screened with the use of state-of-the-art "-omics" technologies.

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“…Prevention studies mentioned above used autoantibodies as biomarkers for T1D. Other potential biomarkers of T1D development include: genetic predisposition (13, 58, 107-109), unmethylated preproinsulin (110, 111), proinsulin-to-C-peptide ratios (112, 113), and microRNA species (114). In addition, β-cell derived neo-antigens offer another potential biomarker of T1D, but also a target for T1D prevention (115, 116).…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Combination Immunotherapy for Type 1 Diabetes

Bone

Evans‐Molina

2017

Curr Diab Rep

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Purpose of Review Type 1 Diabetes (T1D) is an autoimmune disease marked by β-cell destruction. Immunotherapies for T1D have been investigated since the 1980s and have focused on restoration of tolerance, T-cell or B-cell inhibition, regulatory T-cell (Treg) induction, suppression of innate immunity and inflammation, immune system reset, and islet transplantation. The purpose of this review is to provide an overview and lessons learned from single immunotherapy trials, describe recent and ongoing combination immunotherapy trials, and provide perspectives on strategies for future combination clinical interventions aimed at preserving insulin secretion in T1D. Recent Findings Combination immunotherapies have had mixed results in improving short-term glycemic control and insulin secretion in recent-onset T1D. Summary A handful of studies have successfully reached their primary end-point of improved insulin secretion in recent-onset T1D. However, long-term improvements glycemic control and the restoration of insulin independence remain elusive. Future interventions should focus on strategies that combine immunomodulation with efforts to alleviate β-cell stress and address the formation of antigens that activate autoimmunity.

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Nucleic acid biomarkers of β cell stress and death in type 1 diabetes

Cited by 8 publications

References 52 publications

Profiling of RNAs from Human Islet-Derived Exosomes in a Model of Type 1 Diabetes

Profiling of RNAs from Human Islet-Derived Exosomes in a Model of Type 1 Diabetes

Serum biomarkers for diagnosis and prediction of type 1 diabetes

Combination Immunotherapy for Type 1 Diabetes

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