OBJECTIVEThe aim of this study was to evaluate HbA1c as an alternative criterion for impaired glucose tolerance (IGT) or type 1 diabetes (T1D) in high-risk subjects <21 years of age.RESEARCH DESIGN AND METHODSSubjects <21 years of age who participated in the prospective DPT-1, TEDDY, TRIGR, and Type 1 Diabetes TrialNet Natural History (TrialNet) studies and had an HbA1c within 90 days of an OGTT with a 2-h plasma glucose (2-hPG) measure were included. An OGTT of 140–199 mg/dL defined IGT, and an OGTT with 2-hPG ≥200 mg/dL or fasting plasma glucose ≥126 mg/dL defined diabetes. HbA1c ≥5.7% defined IGT, and HbA1c ≥ 6.5% defined diabetes. Receiver-operating characteristic curve analysis was used to assess diagnostic accuracy of HbA1c compared with OGTT.RESULTSThere were 587 subjects from DPT-1, 884 from TrialNet, 91 from TEDDY, and 420 from TRIGR. As an indicator for IGT, HbA1c sensitivity was very low across the studies (8–42%), and specificity was variable (64–95%). With HbA1c ≥6.5% threshold used for T1D diagnosis, the sensitivity was very low and specificity was high (sensitivity and specificity: DPT-1 24 and 98%, TrialNet 28 and 99%, TEDDY 34 and 98%, and TRIGR 33 and 99%, respectively). The positive predictive value of HbA1c ≥6.5% for the development of T1D was variable (50–94%) across the four studies.CONCLUSIONSHbA1c ≥6.5% is a specific but not sensitive early indicator for T1D in high-risk subjects <21 years of age diagnosed by OGTT or asymptomatic hyperglycemia. Redefining the HbA1c threshold is recommended if used as an alternative criterion in diagnosing T1D.

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Background The Trial to Reduce Insulin Dependent Diabetes Mellitus in the Genetically at Risk (TRIGR) is the first multicenter international type 1 diabetes (T1D) prevention trial to be undertaken. A unique feature of TRIGR has been recruitment of eligible pregnant women and enrollment of newborns for long-term follow-up assessments. Purpose Our purpose is to summarize the recruitment and retention strategies used to conduct TRIGR from the perspective of the study coordinators. Methods TRIGR was designed to test whether weaning to formula containing hydrolyzed vs. intact cow’s milk protein would be efficacious in decreasing risk for development of T1D-associated autoantibodies and T1D among infants identified to be at increased risk for T1D based on their human leukocyte antigen (HLA) profile and family history. Multiple strategies tailored to local issues were required to enroll and follow the target number of infants. Results The study was conducted in the United States, Canada, Australia and 12 countries in Europe. Of the 5,606 mothers registered world-wide, 5,000 of their infants were randomized. Of these, 2,159 were HLA eligible and enrolled in the 8-month intervention and 10-year follow-up phases of the study. The TRIGR study met the accrual goal after 4.7 years of recruitment, 2.7 years longer than projected initially. Challenges included difficulty in finding fathers with T1D, a higher than expected rate of premature delivery amongst T1D mothers, and implementation of new privacy regulations mid-trial. The majority of participants were recruited from primary care antenatal clinics located near the study centers and from a general hospital or pediatric center that was affiliated with a TRIGR Study center. Internet and magazine advertisements were found to be useful for recruitment of families. Alternative follow-up strategies are offered to families who wish to reduce or discontinue participation. Limitations Our experience is limited to a single international multicenter trial. Conclusions TRIGR coordinators played key roles in the recruitment and intervention periods and continue to be instrumental in retaining families and children during the 10-year follow-up period for each child.

Objective To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial. Design Longitudinal study. Setting Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months. Subjects Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia. Results Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80% of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71% v. 44% at 6 months of age). Less than 2% of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements. Conclusions Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.