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The role of proteomics in assessing beta-cell dysfunction and death in type 1 diabetes.

ABSTRACT: Introduction: Type 1 diabetes (T1D) is characterized by autoimmune-induced dysfunction and destruction of the pancreatic beta cells. Unfortunately, this process is poorly understood, and the current best treatment for type 1 diabetes is the administration of exogenous insulin. To better understand these mechanisms and to develop new therapies, there is an urgent need for biomarkers that can reliably predict disease stage. Areas covered: Mass spectrometry (MS)-based proteomics and complementary techniques play an important role in understanding the autoimmune response, inflammation and beta-cell death. MS is also a leading technology for the identification of biomarkers. This, and the technical difficulties and new technologies that provide opportunities to characterize small amounts of sample in great depth and to analyze large sample cohorts will be discussed in this review. Expert opinion: Understanding disease mechanisms and the discovery of disease-associated biomarkers are highly interconnected goals. Ideal biomarkers would be molecules specific to the different stages of the disease process that are released from beta cells to the bloodstream. However, such molecules are likely to be present in trace amounts in the blood due to the small number of pancreatic beta cells in the human body and the heterogeneity of the target organ and disease process.

SUBMITTER: Nakayasu ES

PROVIDER: S-EPMC6628911 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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The role of proteomics in assessing beta-cell dysfunction and death in type 1 diabetes.

Nakayasu Ernesto S ES Qian Wei-Jun WJ Evans-Molina Carmella C Mirmira Raghavendra G RG Eizirik Decio L DL Metz Thomas O TO

Expert review of proteomics 20190624 7

<b>Introduction</b>: Type 1 diabetes (T1D) is characterized by autoimmune-induced dysfunction and destruction of the pancreatic beta cells. Unfortunately, this process is poorly understood, and the current best treatment for type 1 diabetes is the administration of exogenous insulin. To better understand these mechanisms and to develop new therapies, there is an urgent need for biomarkers that can reliably predict disease stage. <b>Areas covered</b>: Mass spectrometry (MS)-based proteomics and c ...[more]

PMID: 31232620

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Project description:UnlabelledRole of the funding source: Funding from the NIH was used for support of the participating clinical centers and the coordinating center. The funding source did not participate in the collection or the analysis of the data.BackgroundThe β cell killing that characterizes type 1 diabetes (T1D) is thought to begin years before patients present clinically with metabolic decompensation; however, this primary pathologic process of the disease has not been measured.MethodsHere, we measured β cell death with an assay that detects β cell-derived unmethylated insulin (INS) DNA. Using this assay, we performed an observational study of 50 participants from 2 cohorts at risk for developing T1D from the TrialNet Pathway to Prevention study and of 4 subjects who received islet autotransplants.ResultsIn at-risk subjects, those who progressed to T1D had average levels of unmethylated INS DNA that were elevated modestly compared with those of healthy control subjects. In at-risk individuals that progressed to T1D, the observed increases in unmethylated INS DNA were associated with decreases in insulin secretion, indicating that the changes in unmethylated INS DNA are indicative of β cell killing. Subjects at high risk for T1D had levels of unmethylated INS DNA that were higher than those of healthy controls and higher than the levels of unmethylated INS DNA in the at-risk progressor and at-risk nonprogressor groups followed for 4 years. Evaluation of insulin secretory kinetics also distinguished high-risk subjects who progressed to overt disease from those who did not.ConclusionWe conclude that a blood test that measures unmethylated INS DNA serves as a marker of active β cell killing as the result of T1D-associated autoimmunity. Together, the data support the concept that β cell killing occurs sporadically during the years prior to diagnosis of T1D and is more intense in the peridiagnosis period.Trial registrationClinicaltrials.gov NCT00097292.FundingFunding was from the NIH, the Juvenile Diabetes Research Foundation, and the American Diabetes Association.

Dataset Information

The role of proteomics in assessing beta-cell dysfunction and death in type 1 diabetes.

Publications

The role of proteomics in assessing beta-cell dysfunction and death in type 1 diabetes.

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