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Jeffrey P Krischer, Desmond A Schatz, Brian Bundy, Jay S Skyler, Carla J Greenbaum
Importance: Type 1 diabetes requires major lifestyle changes and carries increased morbidity and mortality. Prevention or delay of diabetes would have major clinical effect. Objective: To determine whether oral insulin delays onset of type 1 diabetes in autoantibody-positive relatives of patients with type 1 diabetes. Design, Setting, and Participants: Between March 2, 2007, and December 21, 2015, relatives with at least 2 autoantibodies, including insulin autoantibodies and normal glucose tolerance, were enrolled in Canada, the United States, Australia, New Zealand, the United Kingdom, Italy, Sweden, Finland, and Germany...
November 21, 2017: JAMA: the Journal of the American Medical Association
Christine T Ferrara, Susan Geyer, Carmella Evans-Molina, Ingrid Libman, Dorothy Becker, John M Wentworth, Antoinette Moran, Stephen Gitelman, Maria J Redondo
Background: Given the global rise in both type 1 diabetes incidence and obesity, the role of BMI on type 1 diabetes pathophysiology has gained great interest. Sustained excess BMI in pediatric participants of the TrialNet Pathway to Prevention cohort (PTP) increased risk of progression to type 1 diabetes, but the effects of age and obesity in adults remain largely unknown. Objective: To determine the effect of age and sustained obesity on the risk of type 1 diabetes in adult participants in the TrialNet PTP cohort, i...
October 6, 2017: Journal of Clinical Endocrinology and Metabolism
Maria J Redondo, Susan Geyer, Andrea K Steck, Jay Sosenko, Mark Anderson, Peter Antinozzi, Aaron Michels, John Wentworth, Ping Xu, Alberto Pugliese
OBJECTIVE: The phenotypic diversity of type 1 diabetes suggests heterogeneous etiopathogenesis. We investigated the relationship of type 2 diabetes-associated transcription factor 7 like 2 (TCF7L2) single nucleotide polymorphisms (SNP) with immunologic and metabolic characteristics at type 1 diabetes diagnosis. RESEARCH DESIGN AND METHODS: We studied TrialNet participants with newly diagnosed autoimmune type 1 diabetes with available TCF7L2 rs4506565 and rs7901695 SNP data (n = 810; median age 13...
October 12, 2017: Diabetes Care
Heba M Ismail, Ping Xu, Ingrid M Libman, Dorothy J Becker, Jennifer B Marks, Jay S Skyler, Jerry P Palmer, Jay M Sosenko
AIMS/HYPOTHESIS: We aimed to examine: (1) whether specific glucose-response curve shapes during OGTTs are predictive of type 1 diabetes development; and (2) the extent to which the glucose-response curve is influenced by insulin secretion. METHODS: Autoantibody-positive relatives of people with type 1 diabetes whose baseline OGTT met the definition of a monophasic or biphasic glucose-response curve were followed for the development of type 1 diabetes (n = 2627)...
September 27, 2017: Diabetologia
Manuela Battaglia, Mark S Anderson, Jane H Buckner, Susan M Geyer, Peter A Gottlieb, Thomas W H Kay, Åke Lernmark, Sarah Muller, Alberto Pugliese, Bart O Roep, Carla J Greenbaum, Mark Peakman
No abstract text is available yet for this article.
September 26, 2017: Diabetologia
Brandon M Nathan, David Boulware, Susan Geyer, Mark A Atkinson, Peter Colman, Robin Goland, William Russell, John M Wentworth, Darrell M Wilson, Carmella Evans-Molina, Diane Wherrett, Jay S Skyler, Antoinette Moran, Jay M Sosenko
OBJECTIVE: We assessed dysglycemia and a T1D Diagnostic Index60 (Index60) ≥1.00 (on the basis of fasting C-peptide, 60-min glucose, and 60-min C-peptide levels) as prediagnostic end points for type 1 diabetes among Type 1 Diabetes TrialNet Pathway to Prevention Study participants. RESEARCH DESIGN AND METHODS: Two cohorts were analyzed: 1) baseline normoglycemic oral glucose tolerance tests (OGTTs) with an incident dysglycemic OGTT and 2) baseline Index60 <1...
November 2017: Diabetes Care
Manuela Battaglia, Mark S Anderson, Jane H Buckner, Susan M Geyer, Peter A Gottlieb, Thomas W H Kay, Åke Lernmark, Sarah Muller, Alberto Pugliese, Bart O Roep, Carla J Greenbaum, Mark Peakman
Type 1 diabetes is an autoimmune disease arising from the destruction of pancreatic insulin-producing beta cells. The disease represents a continuum, progressing sequentially at variable rates through identifiable stages prior to the onset of symptoms, through diagnosis and into the critical periods that follow, culminating in a variable depth of beta cell depletion. The ability to identify the very earliest of these presymptomatic stages has provided a setting in which prevention strategies can be trialled, as well as furnishing an unprecedented opportunity to study disease evolution, including intrinsic and extrinsic initiators and drivers...
November 2017: Diabetologia
Srinath Sanda
OBJECTIVE: Determine if autoantibody titer magnitude and variability predict glucose abnormalities in subjects at risk for type 1 diabetes. RESEARCH DESIGNS AND METHODS: Demographic information, longitudinal autoantibody titers, and oral glucose tolerance test (OGTT) data were obtained from the TrialNet Pathway to Prevention study. Subjects (first and second degree relatives of individuals with type 1 diabetes) with at least 2 diabetes autoantibodies were selected for analysis...
July 14, 2017: Pediatric Diabetes
Emanuele Bosi, David C Boulware, Dorothy J Becker, Jane H Buckner, Susan Geyer, Peter A Gottlieb, Courtney Henderson, Amanda Kinderman, Jay M Sosenko, Andrea K Steck, Polly J Bingley
Context: Islet autoantibodies are markers of type 1 diabetes, and an increase in number of autoantibodies detected during the preclinical phase predicts progression to overt disease. Objective: To refine the effect of age in relation to islet antibody type on progression from single to multiple autoantibodies in relatives of people with type 1 diabetes. Research Design and Methods: We examined 994 relatives with normal glucose tolerance who were positive for a single autoantibody, followed prospectively in the TrialNet Pathway to Prevention...
August 1, 2017: Journal of Clinical Endocrinology and Metabolism
Andrea K Steck, Ping Xu, Susan Geyer, Maria J Redondo, Peter Antinozzi, John M Wentworth, Jay Sosenko, Suna Onengut-Gumuscu, Wei-Min Chen, Stephen S Rich, Alberto Pugliese
Context: Genome-wide association studies identified >50 type 1 diabetes (T1D) associated non-human leukocyte antigens (non-HLA) loci. Objective: The purpose of this study was to assess the contribution of non-HLA single nucleotide polymorphisms (SNPs) to risk of disease progression. Design and Setting: The TrialNet Pathway to Prevention Study follows relatives of T1D patients for development of autoantibodies (Abs) and T1D. Participants: Using the Immunochip, we analyzed 53 diabetes-associated, non-HLA SNPs in 1016 Ab-positive, at-risk non-Hispanic white relatives...
August 1, 2017: Journal of Clinical Endocrinology and Metabolism
Isaac V Snowhite, Gloria Allende, Jay Sosenko, Ricardo L Pastori, Shari Messinger Cayetano, Alberto Pugliese
AIMS/HYPOTHESIS: MicroRNAs (miRNAs) are key regulators of gene expression and novel biomarkers for many diseases. We investigated the hypothesis that serum levels of some miRNAs would be associated with islet autoimmunity and/or progression to type 1 diabetes. METHODS: We measured levels of 93 miRNAs most commonly detected in serum. This retrospective cohort study included 150 autoantibody-positive and 150 autoantibody-negative family-matched siblings enrolled in the TrialNet Pathway to Prevention Study...
August 2017: Diabetologia
Y Liu, L E Rafkin, D Matheson, C Henderson, D Boulware, R E J Besser, C Ferrara, L Yu, A K Steck, P J Bingley
AIMS: To evaluate the feasibility of using self-collected capillary blood samples for islet autoantibody testing to identify risk in relatives of people with Type 1 diabetes. METHODS: Participants were recruited via the observational TrialNet Pathway to Prevention study, which screens and monitors relatives of people with Type 1 diabetes for islet autoantibodies. Relatives were sent kits for capillary blood collection, with written instructions, an online instructional video link and a questionnaire...
February 22, 2017: Diabetic Medicine: a Journal of the British Diabetic Association
Christine Therese Ferrara, Susan Michelle Geyer, Yuk-Fun Liu, Carmella Evans-Molina, Ingrid M Libman, Rachel Besser, Dorothy J Becker, Henry Rodriguez, Antoinette Moran, Stephen E Gitelman, Maria J Redondo
OBJECTIVE: We aimed to determine the effect of elevated BMI over time on the progression to type 1 diabetes in youth. RESEARCH DESIGN AND METHODS: We studied 1,117 children in the TrialNet Pathway to Prevention cohort (autoantibody-positive relatives of patients with type 1 diabetes). Longitudinally accumulated BMI above the 85th age- and sex-adjusted percentile generated a cumulative excess BMI (ceBMI) index. Recursive partitioning and multivariate analyses yielded sex- and age-specific ceBMI thresholds for greatest type 1 diabetes risk...
May 2017: Diabetes Care
Jay M Sosenko, Liping Yu, Jay S Skyler, Jeffrey P Krischer, Peter A Gottlieb, David Boulware, Dongmei Miao, Jerry P Palmer, Andrea K Steck
BACKGROUND: Electrochemiluminescence (ECL) assays have shown promise for enhancing the prediction of type 1 diabetes (T1D) with autoantibodies. We thus studied relatives of T1D patients to determine whether ECL assays can be used to refine risk assessments for T1D among individuals either positive for single GADA or single mIAA autoantibodies. SUBJECTS AND METHODS: TrialNet Pathway to Prevention (PTP) study participants with either GADA or mIAA single autoantibodies were tested for ECL positivity during their participation in the TrialNet PTP study...
March 2017: Diabetes Technology & Therapeutics
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)...
January 2017: Diabetologia
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
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
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
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
Rita Rubin
No abstract text is available yet for this article.
June 4, 2016: Lancet
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