In order to conserve limited resources and increase participation, some screening programmes are transitioning from a multiple-time-point OGTT to the standard clinical model in which sampling is performed only at baseline and 120 min. However, these additional time points greatly increase the costs and complicate the logistics of the OGTT. OGTTs performed in a number of research studies have collected glucose values at the 30, 60 and 90 min time points to further define risk characteristics. To differentiate between type 1 diabetes stages 1, 2 and 3, autoantibody-positive individuals undergo OGTTs, in which glucose is measured at baseline and 120 min after the glucose load. While this staging system is important for helping the medical and lay communities understand the progression of a largely silent autoimmune disease, staging is also used to determine eligibility for prevention trials. Stage 3 satisfies current diagnostic criteria for diabetes mellitus and is usually accompanied by symptoms of hyperglycaemia. Stage 1 is defined by normal glucose tolerance and HbA 1c, and stage 2 by impaired glucose tolerance and HbA 1c from 39 to 46 mmol/mol (5.7% to 6.4%), inclusive. Three disease stages based on oral glucose tolerance and HbA 1c have been defined. Type 1 diabetes is now diagnosed when two or more islet autoantibodies are detected. The presence of two or more autoantibodies confers a very high lifetime risk of disease progression to insulin dependence and has prompted the reclassification of type 1 diabetes as an autoimmune beta cell disorder defined primarily by immune rather than metabolic markers. Type 1 diabetes screening programmes underway in Europe, North America, Australia and New Zealand test for autoantibodies against insulin (IAA), GAD (GADA), insulinoma antigen-2 (IA-2A) and zinc transporter-8 (ZnT8A). Interest in autoantibody screening for type 1 diabetes risk has increased following the demonstration that early diagnosis prevents ketoacidosis and provides opportunities to delay disease progression with immune therapies. The operational simplicity of M 120, its validity across different at-risk populations and the requirement for 120 min sampling to stage type 1 diabetes suggest M 120 could be readily applied to decrease the cost and complexity of risk stratification. Prediction models based on a single OGTT blood draw accurately predict disease progression from stage 1 or 2 to stage 3 type 1 diabetes. In Fr1da, the M 120 AUC of 0.742 was significantly greater than the M 60 AUC of 0.615. In TEDDY, where only 120 min blood sampling had been performed, the M 120 AUC was 0.865.
#Survival curve data input graphpad prism 8 define survivor trial
These were not significantly different from the AUC of 0.760 for the gold standard Diabetes Prevention Trial Risk Score, which requires five OGTT blood samples. In TrialNet, the AUC for receiver operating characteristic curves for models named M 60, M 90 and M 120, based on sampling at 60, 90 and 120 min, was 0.760, 0.761 and 0.745, respectively. ResultsĬox proportional hazards models combining plasma glucose, C-peptide, sex, age, BMI, HbA 1c and insulinoma antigen-2 autoantibody status predicted disease progression in all populations. Models to predict disease progression using a single OGTT time point (0, 30, 60, 90 or 120 min) were developed using TrialNet data collected from relatives with type 1 diabetes and validated in independent populations at high genetic risk of type 1 diabetes (TrialNet, Diabetes Prevention Trial–Type 1, The Environmental Determinants of Diabetes in the Young ) and in a general population of Bavarian children who participated in Fr1da. Our aim was to develop and validate a simpler tool based on a single blood draw. Current tools for predicting risk require multiple blood samples taken during an OGTT. Accurate prediction of disease progression in individuals with pre-symptomatic type 1 diabetes has potential to prevent ketoacidosis and accelerate development of disease-modifying therapies.
0 kommentar(er)
