Type 1 Diabetes: Fr1da study shows milder diabetes at manifestation through early detection
Diagnosis of type 1 diabetes (T1D) can come with serious complications for families: too often, the autoimmune disease is only detected after severe symptoms develop. In Germany, more than 20 percent of all children and adolescents diagnosed with T1D have diabetic ketoacidosis (DKA). This acute complication can be life-threatening and is associated with an increased risk for secondary long-term health problems and impaired cognitive function. Among participants of the Fr1da study, only 2.5 percent of children who were diagnosed with early-stage T1D in the screening, presented with DKA at the clinical onset of T1D. The new findings from the Fr1da study group highlight the advantages of population-based screening for early-stage T1D.
Diagnosing autoimmune Type 1 Diabetes before symptoms appear improves clinical presentation at the onset of the metabolic disease
The underlying cause of T1D is an autoimmune reaction against the insulin-producing beta-cells in the pancreas, leading to impaired glucose metabolism. In most cases, T1D is not recognized until typical symptoms appear. However, the underlying autoimmune process already starts months to years before the first symptoms develop. Thus, three stages of T1D are defined: In Stage 1, several different T1D-associated autoantibodies are detectable in the blood. In Stage 2, glucose metabolism is dysregulated in addition to the presence of autoantibodies. Stage 3 marks the clinical onset of T1D with advanced insulin deficiency and elevated blood sugar levels leading to the typical symptoms. To detect children at an early pre-symptomatic stage, researchers from the Helmholtz Munich Institute for Diabetes Research have established the Fr1da study. Since 2015, over 180 000 children were screened for T1D-associated autoantibodies within the population-based study.
In their recent publication, the researcher analyzed data from 128 children at clinical T1D manifestation (stage 3) who had previously been diagnosed with early-stage T1D in the Fr1da screening. They report significant clinical benefits in children with a prior pre-symptomatic stage (stage 1 or 2) diagnosis compared to data from 736 children diagnosed with stage 3 T1D without prior screening in the DiMelli study. “Children with a diagnosis at early stage showed significantly lower HbA1c levels, lower fasting glucose, and higher fasting C-peptide levels at clinical manifestation, “says Prof. Dr. Sandra Hummel, first author of the study. While lower HbA1c levels indicate improved long-term blood glucose regulation, C-peptide levels are a marker of the residual function of the insulin-producing beta-cells. Both parameters are associated with a reduced risk for secondary complications of T1D. “Most striking is the rate of DKA among the study participants: Only 2.5 percent of the children diagnosed with early-stage T1D in the Fr1da-screening presented with DKA at the time of clinical manifestation,“ highlights Hummel.
The new findings confirm what had previously been observed in individuals at familial or genetic risk of T1D. “If T1D is already diagnosed in a pre-symptomatic stage within a population-based screening, severe complications at clinical presentation can be prevented and the children have a reduced risk for secondary diseases later in life,“ says Prof. Dr. Peter Achenbach, last author of the study. The researchers point out their findings’ relevance for considerations of screening children for pre-symptomatic T1D at a population-based level.
The Fr1da study is available in Bavaria, Saxony, Lower-Saxony, and Hamburg for children between 2 to 10 years of age. In addition, children from other German federal states with a family history of T1D can participate. More information on www.fr1da.de.
About the researchers
Prof. Dr. Sandra Hummel is Lead Scientist of the research area “Lifestyle, obesity, and epigenetic programming in type 1 diabetes and gestational diabetes” at the Institute of Diabetes Research. Prof. Dr. Peter Achenbach is Deputy Director of the Institute of Diabetes Research and Lead Scientist of the Study Center for Childhood Diabetes
Hummel et al. (2023): Children diagnosed with presymptomatic type 1 diabetes through public health screening have milder diabetes at clinical manifestation. Diabetologia. DOI: 10.1007/s00125-023-05953-0