General population screening for T1D
Killing two birds with one stone: should diabetes screening be combined?
Abstract
Background and Aims / Part 1
The presence of ≥2 diabetes-related autoantibodies predicts the development of clinical disease within 15-20 years after the seroconversion in both, first-degree relatives and children from general population. Although the seroconversion can happen at any time of age, there is a clear peak of its incidence around 18 to 24 months of age. Thus, more than 80 percent of children who will develop type 1 diabetes (T1D) before the age of 14 years will get multiple diabetes-related autoimmunity already before the age of 5. That period could be optimal to screen for multiple diabetes autoimmunity, in order to detect T1D early and prevent the development of DKA at its clinical onset by providing appropriate education and standardized clinical follow-up. This strategy has been successfully followed by screening studies as the Fr1da in Bavaria, Germany, which screens for early T1D in 2-5 years old children from the general population. An alternative approach is used in the TrialNet, which focuses on relatives of people with T1D and those who are not family members and are known to have 1 or more islet antibodies.
Methods / Part 2
A third novel approach is a combination screening strategy offered to young children, although this screening strategy is presently not established beyond the neonatal screening programs. The Fr1dolin-Trial is a feasibility study for a population-based screening offered to 2-6 years old children from Lower Saxony and Hamburg, Germany. The Fr1dolin-Trial includes a screening for the early detection of T1D and Familial Hypercholesterolemia.
Results / Part 3
Fr1dolin started in November 2016 and has included meanwhile >12,000 children. Results, experiences and challenges with performing a combined screening program in young children from the general population will be discussed.
Conclusions / Part 4
Current developments regarding prevention strategies forT1D favor the establishment of diabetes screening programs, not only as study initiatives, but also as a part of the routine care.
Efficacy of low dose antithymocyte globulin in new-onset type 1 diabetes: Implication for prevention
Abstract
Background and Aims / Part 1
Several immunotherapies (including rituximab, abatacept, teplizumab, alefacept, high-dose anti-thymocyte globulin (ATG), and low-dose ATG±G-CSF) have demonstrated transient endogenous insulin preservation in recent-onset type 1 diabetes. Study sought to determine two year outcome of new onset type 1 patients treated with ATG±G-CSF compared to placebo. Futher anaylases were undertaken to determine most efficaceous therapy.
Methods / Part 2
1. Double blind plecebo controlled study 2. C-peptide 2 hour area under curve means modeled using ANCOVA
Results / Part 3
Low -dose anti-thymocyte globulin (ATG, 2.5mg/kg) has been shown to preserve β cell function for now at least 2 years following the onset of type 1 diabetes (T1D) as well as improving HbA1c. Immunological studies suggest a depletion in conventional CD4 T cells whilst preserving regulatory T cells. Preliminary studies suggest that of the `successful’ studies performed to date, low-dose ATG demonstrates the greatest C-peptide preservation.
Conclusions / Part 4
Future studies are being planned to determine whether low-dose ATG might prevent or delay the onset of type 1 diabetes.