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https://www.readbyqxmd.com/read/27704166/gad-vaccine-reduces-insulin-loss-in-recently-diagnosed-type-1-diabetes-findings-from-a-bayesian-meta-analysis
#1
Craig A Beam, Colleen MacCallum, Kevan C Herold, Diane K Wherrett, Jerry Palmer, Johnny Ludvigsson
AIMS/HYPOTHESIS: GAD is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD + alum vaccine in human participants have so far given conflicting results. METHODS: In this study, we sought to see whether a clearer answer to the question of whether GAD65 has an effect on C-peptide could be reached by combining individual-level data from the randomised controlled trials using Bayesian meta-analysis to estimate the probability of a positive biological effect (a reduction in C-peptide loss compared with placebo approximately 1 year after the GAD vaccine)...
October 4, 2016: Diabetologia
https://www.readbyqxmd.com/read/27579340/data-on-correlations-between-t-cell-subset-frequencies-and-length-of-partial-remission-in-type-1-diabetes
#2
Aditi Narsale, Rosita Moya, Hannah Kathryn Robertson, Joanna Davida Davies
Partial remission in patients newly diagnosed with type 1 diabetes is a period of good glucose control that can last from several weeks to over a year. The clinical significance of the remission period is that patients might be more responsive to immunotherapy if treated within this period. This article provides clinical data that indicates the level of glucose control and insulin-secreting β-cell function of each patient in the study at baseline (within 3 months of diagnosis), and at 3, 6, 9, 12, 18 and 24 months post-baseline...
September 2016: Data in Brief
https://www.readbyqxmd.com/read/27456836/do-electrochemiluminescence-assays-improve-prediction-of-time-to-type-1-diabetes-in-autoantibody-positive-trialnet-subjects
#3
Alexandra Fouts, Laura Pyle, Liping Yu, Dongmei Miao, Aaron Michels, Jeffrey Krischer, Jay Sosenko, Peter Gottlieb, Andrea K Steck
OBJECTIVE: To explore whether electrochemiluminescence (ECL) assays can help improve prediction of time to type 1 diabetes in the TrialNet autoantibody-positive population. RESEARCH DESIGN AND METHODS: TrialNet subjects who were positive for one or more autoantibodies (microinsulin autoantibody, GAD65 autoantibody [GADA], IA-2A, and ZnT8A) with available ECL-insulin autoantibody (IAA) and ECL-GADA data at their initial visit were analyzed; after a median follow-up of 24 months, 177 of these 1,287 subjects developed diabetes...
October 2016: Diabetes Care
https://www.readbyqxmd.com/read/27422577/fall-in-c-peptide-during-first-4-years-from-diagnosis-of-type-1-diabetes-variable-relation-to-age-hba1c-and-insulin-dose
#4
Wei Hao, Steven Gitelman, Linda A DiMeglio, David Boulware, Carla J Greenbaum
OBJECTIVE: We aimed to describe the natural history of residual insulin secretion in Type 1 Diabetes TrialNet participants over 4 years from diagnosis and relate this to previously reported alternative clinical measures reflecting β-cell secretory function. RESEARCH DESIGN AND METHODS: Data from 407 subjects from 5 TrialNet intervention studies were analyzed. All subjects had baseline stimulated C-peptide values of ≥0.2 nmol/L from mixed-meal tolerance tests (MMTTs)...
October 2016: Diabetes Care
https://www.readbyqxmd.com/read/27385327/elevations-in-the-fasting-serum-proinsulin-to-c-peptide-ratio-precede-the-onset-of-type-1-diabetes
#5
Emily K Sims, Zunaira Chaudhry, Renecia Watkins, Farooq Syed, Janice Blum, Fangqian Ouyang, Susan M Perkins, Raghavendra G Mirmira, Jay Sosenko, Linda A DiMeglio, Carmella Evans-Molina
OBJECTIVE: We tested whether an elevation in the serum proinsulin-to-C-peptide ratio (PI:C), a biomarker of β-cell endoplasmic reticulum (ER) dysfunction, was associated with progression to type 1 diabetes. RESEARCH DESIGN AND METHODS: Fasting total PI and C levels were measured in banked serum samples obtained from TrialNet Pathway to Prevention (PTP) participants, a cohort of autoantibody-positive relatives without diabetes of individuals with type 1 diabetes...
September 2016: Diabetes Care
https://www.readbyqxmd.com/read/27302256/profile-type-1-diabetes-trialnet
#6
Rita Rubin
No abstract text is available yet for this article.
June 4, 2016: Lancet
https://www.readbyqxmd.com/read/27208341/prognostic-classification-factors-associated-with-development-of-multiple-autoantibodies-dysglycemia-and-type-1-diabetes-a-recursive-partitioning-analysis
#7
Ping Xu, Jeffrey P Krischer
OBJECTIVE: To define prognostic classification factors associated with the progression from single to multiple autoantibodies, multiple autoantibodies to dysglycemia, and dysglycemia to type 1 diabetes onset in relatives of individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS: Three distinct cohorts of subjects from the Type 1 Diabetes TrialNet Pathway to Prevention Study were investigated separately. A recursive partitioning analysis (RPA) was used to determine the risk classes...
June 2016: Diabetes Care
https://www.readbyqxmd.com/read/27114212/a-pilot-study-showing-associations-between-frequency-of-cd4-memory-cell-subsets-at-diagnosis-and-duration-of-partial-remission-in-type-1-diabetes
#8
Rosita Moya, Hannah Kathryn Robertson, Dawson Payne, Aditi Narsale, Jim Koziol, Joanna Davida Davies
In some patients with type 1 diabetes the dose of insulin required to achieve euglycemia is substantially reduced soon after diagnosis. This partial remission is associated with β-cell function and good glucose control. The purpose of this study was to assess whether frequencies of CD4(+) T cell subsets in children newly diagnosed with type 1 diabetes are associated with length of partial remission. We found that the frequency of CD4(+) memory cells, activated Treg cells and CD25(+) cells that express a high density of the IL-7 receptor, CD127 (CD127(hi)) are strongly associated with length of partial remission...
May 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/26995649/the-relationship-between-bmi-and-insulin-resistance-and-progression-from-single-to-multiple-autoantibody-positivity-and-type-1-diabetes-among-trialnet-pathway-to-prevention-participants
#9
Farah A Meah, Linda A DiMeglio, Carla J Greenbaum, Janice S Blum, Jay M Sosenko, Alberto Pugliese, Susan Geyer, Ping Xu, Carmella Evans-Molina
AIMS/HYPOTHESIS: The incidence of type 1 diabetes is increasing at a rate of 3-5% per year. Genetics cannot fully account for this trend, suggesting an influence of environmental factors. The accelerator hypothesis proposes an effect of metabolic factors on type 1 diabetes risk. To test this in the TrialNet Pathway to Prevention (PTP) cohort, we analysed the influence of BMI, weight status and insulin resistance on progression from single to multiple islet autoantibodies (Aab) and progression from normoglycaemia to diabetes...
June 2016: Diabetologia
https://www.readbyqxmd.com/read/26991969/ecl-iaa-and-ecl-gada-can-identify-high-risk-single-autoantibody-positive-relatives-in-the-trialnet-pathway-to-prevention-study
#10
Andrea K Steck, Alexandra Fouts, Dongmei Miao, Zhiyuan Zhao, Fran Dong, Jay Sosenko, Peter Gottlieb, Marian J Rewers, Liping Yu
BACKGROUND: Relatives with single positive islet autoantibodies have a much lower risk of progression to diabetes than those with multiple autoantibodies. MATERIALS AND METHODS: TrialNet subjects positive for single autoantibody to insulin (mIAA) (n = 50) or single autoantibody to glutamic acid decarboxylase (GADA) (n = 50) were analyzed using new electrochemiluminescence (ECL) assays (ECL-IAA and ECL-GADA, respectively) at their initial visit and longitudinally over time...
July 2016: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/26991448/a-model-based-approach-to-sample-size-estimation-in-recent-onset-type-1-diabetes
#11
Brian N Bundy, Jeffrey P Krischer
BACKGROUND: The area under the curve C-peptide following a 2-h mixed meal tolerance test from 498 individuals enrolled on five prior TrialNet studies of recent onset type 1 diabetes from baseline to 12 months after enrolment were modelled to produce estimates of its rate of loss and variance. RESULTS: Age at diagnosis and baseline C-peptide were found to be significant predictors, and adjusting for these in an ANCOVA resulted in estimates with lower variance. CONCLUSIONS: Using these results as planning parameters for new studies results in a nearly 50% reduction in the target sample size...
November 2016: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/26822082/hla-drb1-15-01-dqa1-01-02-dqb1-06-02-haplotype-protects-autoantibody-positive-relatives-from-type-1-diabetes-throughout-the-stages-of-disease-progression
#12
Alberto Pugliese, David Boulware, Liping Yu, Sunanda Babu, Andrea K Steck, Dorothy Becker, Henry Rodriguez, Linda DiMeglio, Carmella Evans-Molina, Leonard C Harrison, Desmond Schatz, Jerry P Palmer, Carla Greenbaum, George S Eisenbarth, Jay M Sosenko
The HLA-DRB1*15:01-DQA1*01:02-DQB1*06:02 haplotype is linked to protection from the development of type 1 diabetes (T1D). However, it is not known at which stages in the natural history of T1D development this haplotype affords protection. We examined a cohort of 3,358 autoantibody-positive relatives of T1D patients in the Pathway to Prevention (PTP) Study of the Type 1 Diabetes TrialNet. The PTP study examines risk factors for T1D and disease progression in relatives. HLA typing revealed that 155 relatives carried this protective haplotype...
April 2016: Diabetes
https://www.readbyqxmd.com/read/26692253/interleukin-1-antagonism-moderates-the-inflammatory-state-associated-with-type-1-diabetes-during-clinical-trials-conducted-at-disease-onset
#13
Susanne M Cabrera, Xujing Wang, Yi-Guang Chen, Shuang Jia, Mary L Kaldunski, Carla J Greenbaum, Thomas Mandrup-Poulsen, Martin J Hessner
It was hypothesized that IL-1 antagonism would preserve β-cell function in new onset Type 1 diabetes (T1D). However, the Anti-Interleukin-1 in Diabetes Action (AIDA) and TrialNet Canakinumab (TN-14) trials failed to show efficacy of IL-1 receptor antagonist (IL-1Ra) or canakinumab, as measured by stimulated C-peptide response. Additional measures are needed to define immune state changes associated with therapeutic responses. Here, we studied these trial participants with plasma-induced transcriptional analysis...
April 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/26676824/the-implications-of-autoantibodies-to-a-single-islet-antigen-in-relatives-with-normal-glucose-tolerance-development-of-other-autoantibodies-and-progression-to-type-1-diabetes
#14
Polly J Bingley, David C Boulware, Jeffrey P Krischer
AIMS/HYPOTHESIS: Autoantibodies directed at single islet autoantigens are associated with lower overall risk of type 1 diabetes than multiple autoantibodies, but individuals with one autoantibody may progress to higher risk categories. We examined the characteristics of this progression in relatives followed prospectively in the TrialNet Pathway to Prevention. METHODS: The study population comprised 983 relatives who were single autoantibody positive with normal baseline glucose tolerance (median age 16...
March 2016: Diabetologia
https://www.readbyqxmd.com/read/26404927/defining-pathways-for-development-of-disease-modifying-therapies-in-children-with-type-1-diabetes-a-consensus-report
#15
REVIEW
Diane K Wherrett, Jane L Chiang, Alan M Delamater, Linda A DiMeglio, Stephen E Gitelman, Peter A Gottlieb, Kevan C Herold, Daniel J Lovell, Trevor J Orchard, Christopher M Ryan, Desmond A Schatz, David S Wendler, Carla J Greenbaum
Emerging data suggest that type 1 diabetes is a more aggressive disease in children than in adults, with important differences in pathophysiology and clinical course. Therefore, the efficacy of disease-modifying therapies may be different in the two populations. Understanding the developmental and regulatory pathways for type 1 diabetes-modifying therapies in children will enable industry, academia, funders, advocacy groups, and regulators to translate new science to clinical care. This consensus report characterizes the fundamental differences in type 1 diabetes between children and adults and proposes a thoughtful approach to better understand the development and regulatory pathways for type 1 diabetes therapies...
October 2015: Diabetes Care
https://www.readbyqxmd.com/read/26375197/use-of-dried-capillary-blood-sampling-for-islet-autoantibody-screening-in-relatives-a-feasibility-study
#16
MULTICENTER STUDY
Polly J Bingley, Lisa E Rafkin, Della Matheson, Andrea K Steck, Liping Yu, Courtney Henderson, Craig A Beam, David C Boulware
BACKGROUND: Islet autoantibody testing provides the basis for assessment of risk of progression to type 1 diabetes. We set out to determine the feasibility and acceptability of dried capillary blood spot-based screening to identify islet autoantibody-positive relatives potentially eligible for inclusion in prevention trials. MATERIALS AND METHODS: Dried blood spot (DBS) and venous samples were collected from 229 relatives participating in the TrialNet Pathway to Prevention Study...
December 2015: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/26336066/screening-and-monitoring-for-infectious-complications-when-immunosuppressive-agents-are-studied-in-the-treatment-of-autoimmune-disorders
#17
Brett J Loechelt, Michael Green, Peter A Gottlieb, Emily Blumberg, Adriana Weinberg, Scott Quinlan, Lindsey R Baden
Significant progress has been made in the development, investigation, and clinical application of immunosuppressive agents to treat a variety of autoimmune disorders. The expansion of clinical applications of these new agents requires the performance of large multicenter clinical trials. These large clinical trials are particularly important as one considers these agents for the treatment of type 1 diabetes, which although autoimmune in its pathogenesis, is not classically treated as an autoimmune disorder...
September 2015: Journal of the Pediatric Infectious Diseases Society
https://www.readbyqxmd.com/read/26077017/the-development-validation-and-utility-of-the-diabetes-prevention-trial-type-1-risk-score-dptrs
#18
REVIEW
Jay M Sosenko, Jay S Skyler, Jerry P Palmer
This report details the development, validation, and utility of the Diabetes Prevention Trial-Type 1 (DPT-1) Risk Score (DPTRS) for type 1 diabetes (T1D). Proportional hazards regression was used to develop the DPTRS model which includes the glucose and C-peptide sums from oral glucose tolerance tests at 30, 60, 90, and 120 min, the log fasting C-peptide, age, and the log BMI. The DPTRS was externally validated in the TrialNet Natural History Study cohort (TNNHS). In a study of the application of the DPTRS, the findings showed that it could be used to identify normoglycemic individuals who were at a similar risk for T1D as those with dysglycemia...
August 2015: Current Diabetes Reports
https://www.readbyqxmd.com/read/25941648/understanding-type-1-diabetes-through-genetics-advances-and-prospects
#19
Nikhil Tandon
The largest contribution of type 1 diabetes mellitus (T1DM) from a single locus comes from several genes located in the major histocompatibility complex on chromosome 6p21. Because DQB1 is the best single genetic marker for T1DM, it is the gene most often used to identify individuals with a high risk of developing disease. As per the data collected from the All India Institute of Medical Sciences, among the human leukocyte antigen (HLA)-DRB1 genes, HLA-DR3 showed strongest association with the disease; however, unlike Caucasians and other populations, DR4 was not significantly increased in these patients...
April 2015: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/25773405/cgm-measured-glucose-values-have-a-strong-correlation-with-c-peptide-hba1c-and-idaac-but-do-poorly-in-predicting-c-peptide-levels-in-the-two-years-following-onset-of-diabetes
#20
RANDOMIZED CONTROLLED TRIAL
Bruce Buckingham, Peiyao Cheng, Roy W Beck, Craig Kollman, Katrina J Ruedy, Stuart A Weinzimer, Robert Slover, Andrew A Bremer, John Fuqua, William Tamborlane
AIMS/HYPOTHESIS: The aim of this work was to assess the association between continuous glucose monitoring (CGM) data, HbA1c, insulin-dose-adjusted HbA1c (IDAA1c) and C-peptide responses during the first 2 years following diagnosis of type 1 diabetes. METHODS: A secondary analysis was conducted of data collected from a randomised trial assessing the effect of intensive management initiated within 1 week of diagnosis of type 1 diabetes, in which mixed-meal tolerance tests were performed at baseline and at eight additional time points through 24 months...
June 2015: Diabetologia
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