scholarly journals Zinc transporter 8 autoantibody testing requires age-related cut-offs

2021 ◽  
Vol 9 (1) ◽  
pp. e002296
Author(s):  
Sian Louise Grace ◽  
Angela Cooper ◽  
Angus G Jones ◽  
Timothy James McDonald
Keyword(s):  
Limit Of Detection ◽  
Autoimmune Diabetes ◽  
Zinc Transporter ◽  
Islet Autoantibody ◽  
Zinc Transporter 8 ◽  
False Positive Test ◽  
Age Related ◽  
Test Specificity ◽  
Design And Methods ◽  
The Impact

IntroductionZinc transporter 8 autoantibodies (ZnT8A) are biomarkers of beta cell autoimmunity in type 1 diabetes that have become more widely available to clinicians in recent years. Robust control population-defined thresholds are essential to ensure high clinical specificity in islet autoantibody testing. We aimed to determine the optimal cut-offs for ZnT8A testing.Research design and methods97.5th and 99th centile cut-offs were determined using residual clinical sera from 1559 controls aged between 0 and 83 years with no history of diabetes and a hemoglobin A1c level of less than 6.0% (<42 mmol/mol). ZnT8A were measured by ELISA (RSR, Cardiff, UK) on a Dynex DS2 ELISA robot (Dynex, Preston, UK). We assessed the impact of age-related cut-offs in comparison with the manufacturer’s recommended threshold in a mixed cohort of young-onset (<age 30) diabetes (UNITED study (Using pharmacogeNetics to Improve Treatment in Early-onset Diabetes), n=145).ResultsUsing the manufacturer’s limit of detection, 6 WHO U/mL, 16.2% of people in the control cohort had detectable levels of ZnT8A and those who had detectable ZnT8A were much more likely to be younger (p<0.0001). The 97.5th and 99th centile thresholds were substantially higher in younger participants: 18 and 127 WHO U/mL (tested under 30 years) in comparison with 9 and 21 WHO U/mL (tested 30 years and over). In the UNITED cohort some of those found to be ZnT8A-positive by the manufacturer’s threshold but negative using the appropriate 99% centile cut-off (127 WHO U/mL) displayed characteristics suggestive of type 2 diabetes.ConclusionsAge-related thresholds are needed for ZnT8A testing. In those aged <30 years, use of manufacturers’ recommended cut-offs may result in low test specificity and potentially high rates of false positive test results in patients who do not have autoimmune diabetes.

scholarly journals An Age-Related Exponential Decline in the Risk of Multiple Islet Autoantibody Seroconversion During Childhood

2021 ◽  
Author(s):  
Ezio Bonifacio ◽  
Andreas Weiß ◽  
Christiane Winkler ◽  
Markus Hippich ◽  
Marian J. Rewers ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Confidence Interval ◽  
Islet Autoantibodies ◽  
Islet Autoimmunity ◽  
Islet Autoantibody ◽  
Age Related ◽  
At Risk Children ◽  
Exponential Decline ◽  
Design And Methods

<b>Objective</b>. Islet autoimmunity develops prior to clinical type 1 diabetes and includes multiple and single autoantibody phenotypes. The objective was to determine age-related risks of islet autoantibodies that reflect etiology and improve screening for pre-symptomatic type 1 diabetes. <p><b>Research Design and Methods</b>. The Environmental Determinants of Diabetes in the Young study prospectively followed 8,556 genetically at-risk children at 3–6-month intervals from birth for the development of islet autoantibodies and type 1 diabetes. The age-related change in the risk of developing islet autoantibodies was determined using landmark and regression models. </p> <p><b>Results</b>. The 5-year risk of developing multiple islet autoantibodies was 4.3% (95% confidence interval, 3.8–4.7) at 7.5 months of age and declined to 1.1% (95% confidence interval, 0.8–1.3) at a landmark age of 6.25 years (<i>P</i><0.0001). Risk decline was slight or absent in single insulin- and GAD-autoantibody phenotypes. The influence of sex, <i>HLA</i> and other susceptibility genes on risk subsided with increasing age and was abrogated by age six years. Highest sensitivity and positive predictive value of multiple islet autoantibody phenotypes for type 1 diabetes was achieved by autoantibody screening at 2 years and again at 5–7 years of age. </p> <p><b>Conclusions</b>. The risk of developing islet autoimmunity declines exponentially with age and the influence of major genetic factors on this risk is limited to the first few years of life. </p>

scholarly journals A UNIQUE CASE OF ATEZOLIZUMAB-INDUCED AUTOIMMUNE DIABETES

2020 ◽  
Vol 6 (1) ◽  
pp. e30-e32
Author(s):  
Mimi Wong ◽  
Nirjhar Nandi ◽  
Ashim Sinha
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Autoimmune Diabetes ◽  
Case Reports ◽  
Zinc Transporter ◽  
Prior History ◽  
Unique Case ◽  
Cell Lung Carcinoma ◽  
Zinc Transporter 8 ◽  
First Case

Objective: Immunotherapy is a novel treatment that can cause autoimmune diabetes in rare cases. More cases occur following use of the inhibitor to the protein programmed cell death-1 rather than the inhibitor to programmed cell death-ligand 1. Methods: We report a unique case of autoimmune diabetes following atezolizumab use. Results: A 55-year-old, Aboriginal Australian female with no prior history of diabetes was commenced on atezolizumab for recurrent squamous cell lung carcinoma. Two months following its commencement, there was the onset of fatigue, polyuria, polydipsia, and new hyperglycemia. Subsequently she was found to have a borderline-low C peptide level of 0.6 nmol/L (reference range is 0.5 to 1.0 nmol/L), and positive zinc transporter-8 antibodies. Following the diagnosis of autoimmune diabetes, 5 units of glargine insulin was commenced which maintained euglycemia and resolved her symptoms of hyperglycemia. Conclusion: There are few case reports of atezolizumab-induced autoimmune diabetes. We present the first case associated with zinc transporter-8 antibodies, and a unique case of autoimmune diabetes in a patient of Aboriginal Australian background.

scholarly journals An Age-Related Exponential Decline in the Risk of Multiple Islet Autoantibody Seroconversion During Childhood

2021 ◽  
Author(s):  
Ezio Bonifacio ◽  
Andreas Weiß ◽  
Christiane Winkler ◽  
Markus Hippich ◽  
Marian J. Rewers ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Confidence Interval ◽  
Islet Autoantibodies ◽  
Islet Autoimmunity ◽  
Islet Autoantibody ◽  
Age Related ◽  
At Risk Children ◽  
Exponential Decline ◽  
Design And Methods

<b>Objective</b>. Islet autoimmunity develops prior to clinical type 1 diabetes and includes multiple and single autoantibody phenotypes. The objective was to determine age-related risks of islet autoantibodies that reflect etiology and improve screening for pre-symptomatic type 1 diabetes. <p><b>Research Design and Methods</b>. The Environmental Determinants of Diabetes in the Young study prospectively followed 8,556 genetically at-risk children at 3–6-month intervals from birth for the development of islet autoantibodies and type 1 diabetes. The age-related change in the risk of developing islet autoantibodies was determined using landmark and regression models. </p> <p><b>Results</b>. The 5-year risk of developing multiple islet autoantibodies was 4.3% (95% confidence interval, 3.8–4.7) at 7.5 months of age and declined to 1.1% (95% confidence interval, 0.8–1.3) at a landmark age of 6.25 years (<i>P</i><0.0001). Risk decline was slight or absent in single insulin- and GAD-autoantibody phenotypes. The influence of sex, <i>HLA</i> and other susceptibility genes on risk subsided with increasing age and was abrogated by age six years. Highest sensitivity and positive predictive value of multiple islet autoantibody phenotypes for type 1 diabetes was achieved by autoantibody screening at 2 years and again at 5–7 years of age. </p> <p><b>Conclusions</b>. The risk of developing islet autoimmunity declines exponentially with age and the influence of major genetic factors on this risk is limited to the first few years of life. </p>

scholarly journals Autoantibodies against zinc transporter 8 are related to age and metabolic state in patients with newly diagnosed autoimmune diabetes

2018 ◽  
Vol 55 (3) ◽  
pp. 287-294 ◽  
Author(s):  
Elżbieta Niechciał ◽  
Anita Rogowicz-Frontczak ◽  
Stanisław Piłaciński ◽  
Marta Fichna ◽  
Bogda Skowrońska ◽  
...  
Keyword(s):  
Autoimmune Diabetes ◽  
Zinc Transporter ◽  
Newly Diagnosed ◽  
Metabolic State ◽  
Zinc Transporter 8

The Role of Vascular Aging in Atherosclerotic Plaque Development and Vulnerability

2019 ◽  
Vol 25 (29) ◽  
pp. 3098-3111 ◽  
Author(s):  
Luca Liberale ◽  
Giovanni G. Camici
Keyword(s):  
Atherosclerotic Plaque ◽  
Molecular Mechanisms ◽  
Driving Forces ◽  
Plaque Burden ◽  
Vascular Aging ◽  
Age Related ◽  
Plaque Development ◽  
Increased Risk ◽  
The Impact ◽  
Over Time

Background: The ongoing demographical shift is leading to an unprecedented aging of the population. As a consequence, the prevalence of age-related diseases, such as atherosclerosis and its thrombotic complications is set to increase in the near future. Endothelial dysfunction and vascular stiffening characterize arterial aging and set the stage for the development of cardiovascular diseases. Atherosclerotic plaques evolve over time, the extent to which these changes might affect their stability and predispose to sudden complications remains to be determined. Recent advances in imaging technology will allow for longitudinal prospective studies following the progression of plaque burden aimed at better characterizing changes over time associated with plaque stability or rupture. Oxidative stress and inflammation, firmly established driving forces of age-related CV dysfunction, also play an important role in atherosclerotic plaque destabilization and rupture. Several genes involved in lifespan determination are known regulator of redox cellular balance and pre-clinical evidence underlines their pathophysiological roles in age-related cardiovascular dysfunction and atherosclerosis. Objective: The aim of this narrative review is to examine the impact of aging on arterial function and atherosclerotic plaque development. Furthermore, we report how molecular mechanisms of vascular aging might regulate age-related plaque modifications and how this may help to identify novel therapeutic targets to attenuate the increased risk of CV disease in elderly people.

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