Context Participants at Stage 1 or 2 type 1 diabetes (T1D) qualify for prevention trials, but factors involved in screening for such trials are largely unknown. Objective To identify factors associated with screening for T1D prevention trials. Methods This study included TrialNet Pathway to Prevention participants who were eligible for a prevention trial: oral insulin (TN-07, TN-20), teplizumab (TN-10), abatacept (TN-18), and oral hydroxychloroquine (TN-22). Univariate and multivariate logistic regression models were used to examine participant, site, and study factors at the time of prevention trial accrual. Results Screening rates for trials were: 50% for TN-07 (584 screened/1172 eligible), 9% for TN-10 (106/1249), 24% for TN-18 (313/1285), 17% for TN-20 (113/667), and 28% for TN-22 (371/1336). Younger age and male sex were associated with higher screening rates for prevention trials overall and for oral therapies. Participants with an offspring with T1D showed lower rates of screening for all trials and oral drug trials compared to participants with other first-degree relatives as probands. Site factors, including larger monitoring volume and U.S. site versus international site, were associated with higher prevention trial screening rates. Conclusions Clear differences exist between participants who screen for prevention trials and those who do not screen, and between the research sites involved in prevention trial screening. Participant age, sex, and relationship to proband are significantly associated with prevention trial screening in addition to key site factors. Identifying these factors can facilitate strategic recruitment planning to support rapid and successful enrollment into prevention trials.

No abstract

Autoimmune loss of beta-cell function (measured by C-peptide) is the hallmark of type 1 diabetes (T1D) targeted by interventions that aim to prevent T1D or its progression after onset. We sought to determine whether T1D genetic risk score-2 (T1D-GRS2) and single nucleotide polymorphisms (SNPs) that have been previously associated with C-peptide preservation after T1D diagnosis (e.g., SNPs in CLEC16A, G6CP2, INS, JAZF1, PTPN22, SLC30A8 and TCF7L2) influence C-peptide levels before diagnosis. We studied islet autoantibody (Ab)-positive participants in the TrialNet Pathway to Prevention Study who had T1DExomeChip data and assessed the influence of these 12 SNPs and the T1D-GRS2 on area under the curve (AUC) C-peptide levels during oral glucose tolerance tests conducted between 0-9 months prior to the diagnosis of T1D. Participants (n=702) had a mean age of 13.5±10.3 years, 47% were female, mean BMI was 20.7±6.0 kg/m2, and mean HbA1c 5.4±0.4%. The T1D high-risk HLA-DR3-DQ2 haplotype was present in 47% and the high-risk HLA-DR4-DQ8 haplotype was present in 67% of participants. We performed univariate and multivariate analyses adjusting for BMI, age, sex, number of positive Ab, and the first 3 principal components of ancestry. A higher T1D-GRS2 was associated with lower C-peptide AUC 0-9 months prior to T1D diagnosis in univariate (β=-0.06, P<0.0001) and multivariate (β=-0.03, p=0.008) analyses. Participants with the JAZF1 rs864745 G allele had lower C-peptide AUC 0-9 months prior to T1D diagnosis in univariate (β=-0.10, p=0.003) and multivariate (β=-0.05, p=0.047) analysis. In conclusion, the JAZF1 rs864745 G allele (which has also been associated with type 2 diabetes risk) and higher T1D-GRS2 predict lower C-peptide AUC prior to the diagnosis of T1D. Studies on their effect on response to trials to prevent or delay T1D onset are warranted. Disclosure T. M. Triolo: None. S. S. Rich: None. A. Steck: None. M. J. Redondo: None. H. M. Parikh: None. M. Tosur: Advisory Panel; Provention Bio, Inc. L. A. Ferrat: Consultant; Johnson & Johnson. L. You: None. P. Gottlieb: Advisory Panel; ViaCyte, Inc., Board Member; ImmunoMolecular Therapeutics, Research Support; Imcyse, Hemsley Charitable Trust, Novartis, National Institute of Diabetes and Digestive and Kidney Diseases, Precigen, Inc., Dompé, Nova Pharmaceuticals, Provention Bio, Inc. R. A. Oram: Consultant; Janssen Research & Development, LLC, Research Support; Randox R & D. S. Onengut-gumuscu: None. J. Krischer: None. Funding National Institutes of Health (R01DK121843, R01DK124395)

Objective: Increased level of glycated hemoglobin (HbA1c) is associated with type 1 diabetes onset that in turn is preceded by one to several autoantibodies against the pancreatic islet beta cell autoantigens; insulin (IA), glutamic acid decarboxylase (GAD), islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8). The risk for type 1 diabetes diagnosis increases by autoantibody number. Biomarkers predicting the development of a second or a subsequent autoantibody and type 1 diabetes are needed to predict disease stages and improve secondary prevention trials. This study aimed to investigate whether HbA1c possibly predicts the progression from first to a subsequent autoantibody or type 1 diabetes in healthy children participating in the Environmental Determinants of Diabetes in the Young (TEDDY) study.Research Design and Methods: A joint model was designed to assess the association of longitudinal HbA1c levels with the development of first (insulin or GAD autoantibodies) to

Background: Vitamin D insufficiency contributes to muscle weakness and a higher risk of falls in older adults. Objectives: This study explored the impact of vitamin D supplementation on self-reported falls and physical function in older adults with low vitamin D levels and a recent fall history. Materials and Methods: Twenty-five older adults ≥ 70 years with two or more falls during the past year, low vitamin D blood levels (≥10 ng/ml and < 30 ng/mL), and slow gait speed (1.2 m/s) participated in a 6-month vitamin D supplementation (800 IU/day) study. A modified version of the Morse Fall Scale questionnaire was used to assess frequency of falls over one-year prior to study enrollment. Functional outcomes (short physical performance battery, handgrip strength, gait Timed Up and Go, and six-minute walk), and vitamin D levels were assessed at baseline and 6-month follow-up. Results: Based on diaries and pill counts, participants were generally adherent to the intervention (6 of 7 days per week). Supplementation with 800 IU/day of vitamin D for 6 months increased blood vitamin D levels from 23.25±4.8 ng/ml to 29.13±6.9 ng/ml (p<0.001). Self-reported number of falls decreased from an average of 3.76 ± 2.2 falls in one-year to 0.76 ± 1.4 falls (p <0.0001) over the 6-month intervention. No changes in functional outcome measures were observed. Conclusions: Vitamin D supplementation at the currently recommended dose of 800 IU/day increased blood vitamin D levels and reduced frequency of falls in older adults with low vitamin D levels and a recent fall history.