We provided a weighted risk model with selected SNPs that could be considered for recruitment of infants into studies of early type 1 diabetes natural history or appropriately safe prevention.

Very little is known about the role of the innate immune system in the course of human type 1 diabetes. Here we investigated neutrophil numbers along with other leukocyte populations in patients at diagnosis of type 1 diabetes and during prediabetes. Complete and differential blood counts were analyzed from 107 adult patients with newly diagnosed type 1 diabetes, 21 children with persistent islet autoantibodies and a family history of type 1 diabetes, and 1 238 age and gender matched control subjects, all individuals without any signs of acute infection.Adult patients with newly diagnosed type 1 diabetes had significantly lower total WBC (p<1×10⁻⁶), neutrophil (p<1×10⁻⁶), basophil (p<1×10⁻⁶), monocyte (p=4×10⁻⁶) and lymphocyte (p<1×10⁻⁶) counts compared to control subjects. Erythrocyte, eosinophil and platelet counts did not differ between groups. Similarly, children with persistent islet autoantibodies had decreased WBC (p=0.001), neutrophils (p=0.003), and lymphocytes (p=0.006) in comparison to control children. Our findings demonstrate a perturbation of leukocyte homeostasis at and prior to onset of type 1 diabetes suggesting a general involvement of the innate immune system in the pathogenesis of type 1 diabetes.

Aims/hypothesis Autoantibodies that precede type 1 diabetes frequently develop in early childhood and target distinct beta cell proteins. The aim of this study was to determine the heterogeneity of islet autoantibody development and fate. Methods The ages of development of insulin autoantibodies (IAA) and GAD autoantibodies (GADA), followed by multiple islet autoantibodies and progression to diabetes were examined in 2,441 children participating in two German birth cohorts. Results In 218 children who developed islet autoantibodies, the first islet autoantibody-positive sample was characterised by single IAA in 80 (37%), multiple islet autoantibodies in 68 (31%) and single GADA in 63 (29%) children. Of the children who were single antibody positive at seroconversion, 35 (44%) IAA-positive and 15 (24%) GADA-positive children developed multiple islet autoantibodies. Single persistent antibodies had heterogeneous affinities; GADA were also heterogeneous in their binding to N-terminally truncated GAD65 and in an ELISA. Progression to diabetes occurred in >50% of children within 10 years in all groups that developed multiple islet autoantibodies and in 44% of children with persistent single high-affinity IAA or persistent single GADA that were positive in both a radiobinding assay and ELISA. The earliest autoantibody development was seen in children with single IAA that progressed to multiple islet autoantibodies or in those with persistent high-affinity single IAA, with a sharp peak in incidence observed at age 9 months. The peak incidence occurred at age 2 years for children who underwent seroconversion directly to multiple islet autoantibodies and at 5 years for children who first seroconverted to GADA and subsequently developed other autoantibodies. Seroconversion to low-affinity IAA or persistent single GADA occurred at a low incidence after the age of 9 months. Conclusions/interpretation Children of different ages have differing susceptibilities to autoimmunisation against specific beta cell autoantigens.

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An autologous cord blood infusion does not change the natural course of metabolic and immune parameters after disease onset. However, the content of CD34+ cells in the stored blood sample might offer potential for improvement of future cell therapies.

Background and Objective Type 1 diabetes is an important risk factor for the development of cardiovascular disease. Pulse wave velocity (PWV) and carotid intima‐media thickness (cIMT) measurements are well recognized as independent predictors for future cardiovascular disease. The aim of the present study was to systematically review the literature and conduct a meta‐analysis assessing measures of subclinical arterial damage in children and adolescents with type 1 diabetes in comparison to healthy controls. Methods PubMed and Cochrane Library were searched to identify studies comparing cIMT and carotid‐femoral PWV levels between children with type 1 diabetes and healthy controls. Meta‐analysis was performed to compare the difference of overall mean cIMT and carotid‐femoral PWV levels between the two groups. New Castle Ottawa quality assessment scale for case‐control studies was used to assess study quality. Results Twenty‐three studies were finally included in the meta‐analysis (20 studies for cIMT and 4 studies for carotid‐femoral PWV). Youth with type 1 diabetes had significantly higher cIMT levels than controls (mean difference [d] = 0.03, 95% confidence interval [CI] = 0.02‐0.04), as well as higher carotid‐femoral PWV levels (d = 0.26, 95% CI = 0.18‐0.34). Heterogeneity was present only in the cIMT analysis (I2 > 90%). Conclusions Youth with type 1 diabetes showed signs of subclinical arterial damage, as suggested by higher levels of cIMT and carotid‐femoral PWV compared to healthy controls at childhood and adolescence. Preventive and therapeutic interventions early in course of disease may be further studied to decrease morbidity in this high‐risk young patient group. PROSPERO registration number: 2018 CRD42018094354.

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.