Outcomes of monthly video consultations as an add-on to regular care for children with type 1 diabetes: A 6-month quasi-randomized clinical trial followed by an extension phase.

OBJECTIVE: To explore the outcomes of monthly video consultations for children with diabetes. METHODS: The Virtual Outpatient Diabetes Clinic for Children and Youth (VIDIKI) was a 6-month multicenter controlled clinical trial followed by an extension phase. The 240 participants (1-16 years), all using a CGM, were quasi-randomized by residence location to the intervention group (IG) or the waitlist-control group (WG). The IG started immediately after enrollment with monthly video consultations as an add-on to regular care, while the WG received regular care for 6 months before starting the intervention. The extension phase lasted between 12 months and 2 years, depending on the enrollment date. Linear regression was applied to model the primary outcome of HbA1c after 6 months and other metabolic and psychosocial outcomes. RESULTS: After covariate adjustments, the HbA1c at 6 months-corresponding to the controlled treatment phase-was 0.11% lower in the IG than that in the WG (95% CI -0.31 to 0.09, P = .277). For the total study sample, a significant HbA1c improvement was found after 12 months of video consultations, which increased further until month 15. The diabetes burden of the main caregivers was lower, and parental treatment satisfaction was significantly higher in the IG than that in the WG. CONCLUSIONS: The VIDIKI study found no significant HbA1c difference between IG and WG after 6 months in the controlled phase, but there was a decreased diabetes burden and increased treatment satisfaction for the parents. In the longitudinal perspective, a significant HbA1c improvement was found after 12 and 15 months.

Prevalence of vitamin D deficiency in pre-type 1 diabetes and its association with disease progression.

AIMS/HYPOTHESIS: Vitamin D deficiency is common in people with type 1 diabetes, but its role in disease progression is unclear. Our aim was to assess the prevalence of vitamin D deficiency in prediabetes (defined as the presence of multiple islet autoantibodies), and investigate whether or not progression to type 1 diabetes is faster in children with vitamin D deficiency and multiple islet autoantibodies. METHODS: Levels of 25-hydroxyvitamin D [25(OH)D] were measured in 108 children with multiple islet autoantibodies within 2 years of islet autoantibody seroconversion, in 406 children who remained islet autoantibody-negative and in 244 patients with newly diagnosed type 1 diabetes. Children with multiple islet autoantibodies were prospectively followed for a median of 5.8 years (interquartile range 3.4-8.6 years) to monitor progression to type 1 diabetes. RESULTS: In the cross-sectional analysis, 25(OH)D levels were lower and the prevalence of vitamin D deficiency (<50 nmol/l) was higher in children with prevalent multiple islet autoantibodies than in islet autoantibody-negative children (59.9 ± 3.0 vs 71.9 ± 1.5 nmol/l; p < 0.001; 39.8% vs 28.3%; p = 0.021). The differences in vitamin D levels between the groups were greatest in summer. The cumulative incidence of type 1 diabetes at 10 years after seroconversion was similar between children with vitamin D deficiency and those with sufficient vitamin D levels (51.8% [95% CI 29.3, 74.3] vs 55.4% [95% CI 35.5, 72.3], p = 0.8). CONCLUSIONS/INTERPRETATION: Vitamin D levels were lower in children with multiple islet autoantibodies and in children with type 1 diabetes than in autoantibody-negative children. However, vitamin D deficiency was not associated with faster progression to type 1 diabetes in children with multiple islet autoantibodies.

Concentration and activity of the soluble form of the interleukin-7 receptor α in type 1 diabetes identifies an interplay between hyperglycemia and immune function.

Soluble interleukin-7 (IL-7) receptor α (sCD127) is implicated in the pathogenesis of autoimmune diseases. We show that serum sCD127 concentrations are increased at the onset of type 1 diabetes (T1D; n = 390) as compared with concentrations in age-matched islet autoantibody-negative first-degree relatives of patients (n = 392; P = 0.00001). sCD127 concentration in patients was influenced by islet autoantibody status (P = 0.003) and genotype of the rs6897932 single nucleotide polymorphism within the IL-7RA gene (P = 0.006). Release of sCD127 in vitro was strongly upregulated by activation of T lymphocytes and affected by exposure to cytokines. sCD127 bound IL-7 and was antagonistic to IL-7 signaling and IL-7-mediated T-cell proliferation, suggesting a regulatory feedback mechanism on T-cell expansion. Remarkably, high glucose led to a glycated form of sCD127 that was ineffective as an IL-7 antagonist. The finding of glycated sCD127 in the circulation of patients at onset of T1D suggested that physiological regulation of IL-7-mediated T-cell survival and expansion by sCD127 may be compromised in T1D. The findings indicate that genetic, immunologic, and metabolic factors contribute to a dysregulation of the IL-7/IL-7 receptor pathway in T1D and identify a novel hyperglycemia-mediated interference of immune regulatory networks.

Does diabetes appear in distinct phenotypes in young people? Results of the diabetes mellitus incidence Cohort Registry (DiMelli).

INTRODUCTION: The diabetes mellitus Incidence Cohort Registry (DiMelli) aims to characterize diabetes phenotypes by immunologic, metabolic, and genetic markers. We classified patients into three groups according to islet autoantibody status and examined whether patients with multiple diabetes-associated autoantibodies, one autoantibody, or without autoantibodies differed with respect to clinical, metabolic, and genetic parameters, including an insulin sensitivity (IS) score based on waist, HbA1c, and triglycerides. We also assessed whether metabolic markers predicted the immune status. MATERIALS AND METHODS: As of June 2012, 630 patients in Bavaria, Germany, aged <20 years diagnosed with any type of diabetes within the preceding 6 months were registered in DiMelli. We compared the clinical and laboratory parameters between islet autoantibody status defined patient groups. Parameters showing the strongest associations were included in principal component analysis. Receiver operating characteristic curves were used to assess the ability of the IS Score to predict islet autoantibody status. RESULTS: Patients with multiple islet autoantibodies, one autoantibody, or without autoantibodies were significantly different in terms of BMI percentile, weight loss before diagnosis, fasting C-peptide (all, P<0.001), and IS Score (P=0.034). However, principal component analysis revealed no distinct patterns according to autoantibody status. At the optimal IS Score cut-off for predicting islet autoantibody positivity (single compared to none), the specificity was 52.0% and the sensitivity was 86.8%. With respect to prediction of multiple autoantibodies (compared to none), specificity and sensitivity were slightly lower and in combination inferior to those obtained using the BMI percentile and fasting C-peptide. DISCUSSION: The DiMelli study indicated that patients with and without islet autoantibodies differed with respect to metabolic and genetic markers but there was considerable overlap of phenotypes, and autoantibody status could not be predicted by these parameters. Thus, our results suggest that refined diabetes classification may require both immune and metabolic phenotyping.