The influence of body mass index and age on C-peptide at the diagnosis of type 1 diabetes in children who participated in the diabetes prevention trial-type 1

BACKGROUND/OBJECTIVE: The extent of influence of BMI and age on C-peptide at the diagnosis of type 1 diabetes (T1D) is unknown. We thus studied the impact of body mass index Z-scores (BMIZ) and age on C-peptide measures at and soon after the diagnosis of T1D. METHODS: Data from Diabetes Prevention Trial-Type 1 (DPT-1) participants <18.0 years at diagnosis was analyzed. Analyses examined associations of C-peptide measures with BMIZ and age in 2 cohorts: oral glucose tolerance tests (OGTTs) at diagnosis (n = 99) and mixed meal tolerance tests (MMTTs) <6 months after diagnosis (n = 80). Multivariable linear regression was utilized. RESULTS: Fasting and area under the curve (AUC) C-peptide from OGTTs (n = 99) at diagnosis and MMTTs (n = 80) after diagnosis were positively associated with BMIZ and age (P < .001 for all). Associations persisted when BMIZ and age were included as independent variables in regression models (P < .001 for all). BMIZ and age explained 31%-47% of the variance of C-peptide measures. In an example, 2 individuals with identical AUC C-peptide values had an approximate 5-fold difference in values after adjustments for BMIZ and age. The association between fasting glucose and C-peptide decreased markedly when fasting C-peptide values were adjusted (r = 0.30, P < .01 to r = 0.07, n.s.). CONCLUSIONS: C-peptide measures are strongly and independently related to BMIZ and age at and soon after the diagnosis of T1D. Adjustments for BMIZ and age cause substantial changes in C-peptide values, and impact the association between glycemia and C-peptide. Such adjustments can improve assessments of β-cell impairment at diagnosis

Use of Dried Capillary Blood Sampling for Islet Autoantibody Screening in Relatives:A Feasibility Study

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. Both samples were tested for glutamic acid decarboxylase, islet antigen 2, and zinc transporter 8 autoantibodies, and venous samples were additionally tested for insulin autoantibodies and islet cell antibodies. We defined multiple autoantibody positive as two or more autoantibodies in venous serum and DBS screen positive if one or more autoantibodies were detected. Participant questionnaires compared the sample collection methods. Results: Of 44 relatives who were multiple autoantibody positive in venous samples, 42 (95.5%) were DBS screen positive, and DBS accurately detected 145 of 147 autoantibody-negative relatives (98.6%). Capillary blood sampling was perceived as more painful than venous blood draw, but 60% of participants would prefer initial screening using home fingerstick with clinic visits only required if autoantibodies were found. Conclusions: Capillary blood sampling could facilitate screening for type 1 diabetes prevention studies.</p

Participant and parent experiences in the oral insulin study of the Diabetes Prevention Trial for Type 1 Diabetes

OBJECTIVE: To assess the experiences of participants and parents of children in the oral insulin study of the Diabetes Prevention Trial –Type 1. METHOD: Before trial results were publicized, surveys were completed by 124 participants and 219 parents of children in the oral trial. RESULTS: Although most of those surveyed were positive about the trial, survey results suggest that participant perspective (adult, child, parent, and gender), study procedures, and beliefs about placebo vs. active drug assignment have important implications for planning future clinical trials. Parents and children reported greater distress, worry, and difficulty making the decision to join the trial compared with adult participants. Mothers and female participants were particularly interested in additional psychosocial support during the study. Random assignment was viewed negatively by both parents and children, and close observation for diabetes onset was viewed as the most favorable aspect of the study. Adherence to study procedures declined over time and behaviors outside the study protocol to prevent/delay diabetes onset were common, particularly among those who believed the participant was taking a placebo. Children and respondents who believed that the participant was taking the active drug expressed confidence in oral insulin’s ability to delay or prevent type 1 diabetes. CONCLUSIONS: Although most participants were positive about the trial and many expressed optimism about the intervention’s potential for success, future trials need to address negative reactions to random assignment, the unique concerns of children and their parents, declining adherence, and behaviors – external to the trial – designed to delay or prevent diabetes

Type 1 Diabetes TrialNet:a multifaceted approach to bringing disease-modifying therapy toclinical use in type 1 diabetes

What will it take to bring disease-modifying therapy to clinical use in type 1 diabetes? Coordinated efforts of investigators involved in discovery, translational, and clinical research operating in partnership with funders and industry and in sync with regulatory agencies are needed. This Perspective describes one such effort, Type 1 Diabetes TrialNet, a National Institutes of Health–funded and JDRF-supported international clinical trials network that emerged from the Diabetes Prevention Trial–Type 1 (DPT-1). Through longitudinal natural history studies, as well as trials before and after clinical onset of disease combined with mechanistic and ancillary investigations to enhance scientific understanding and translation to clinical use, TrialNet is working to bring disease-modifying therapies to individuals with type 1 diabetes. Moreover, TrialNet uses its expertise and experience in clinical studies to increase efficiencies in the conduct of trials and to reduce the burden of participation on individuals and families. Herein, we highlight key contributions made by TrialNet toward a revised understanding of the natural history of disease and approaches to alter disease course and outline the consortium’s plans for the future.</jats:p

Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial--Type 1

This randomized, double-masked, placebo-controlled clinical trial tested whether oral insulin administration could delay or prevent type 1 diabetes in nondiabetic relatives at risk for diabetes. We screened 103,391 first- and second-degree relatives of patients with type 1 diabetes and analyzed 97,273 samples for islet cell antibodies. A total of 3,483 were antibody positive; 2,523 underwent genetic, immunological, and metabolic staging to quantify risk of developing diabetes; 388 had a 5-year risk projection of 26-50%; and 372 (median age 10.25 years) were randomly assigned to oral insulin (7.5 mg/day) or placebo. Oral glucose tolerance tests were performed every 6 months. The median follow-up was 4.3 years, and the primary end point was diagnosis of diabetes. Diabetes was diagnosed in 44 oral insulin and 53 placebo subjects. Annualized rate of diabetes was similar in both groups: 6.4% with oral insulin and 8.2% with placebo (hazard ratio 0.764, P = 0.189). In a hypothesis-generating analysis of a subgroup with insulin autoantibody (IAA) levels confirmed (on two occasions) > or =80 nU/ml (n = 263), there was the suggestion of benefit: annualized diabetes rate 6.2% with oral insulin and 10.4% with placebo (0.566, P = 0.015). It is possible to identify individuals at high risk for type 1 diabetes and to enroll them in a large, multisite, randomized, controlled clinical trial. However, oral insulin did not delay or prevent type 1 diabetes. Further studies are needed to explore the potential role of oral insulin in delaying diabetes in relatives similar to those in the subgroup with higher IAA levels