Metabolomics and autoantibody development in individuals at high risk for type 1 diabetes

​The project seeks to identify risk metabolomic profiles for autoimmunity and type 1 diabetes. By further investigating the relationship of these metabolomic profiles with other established genetic and environmental risk factors for type 1 diabetes, we hope to contribute to the unraveling of this complex immunologic/metabolic disease and highlight potential new therapeutic targets.

​The incidence of type 1 diabetes (T1D) is rising in the western world, particularly among the youngest children. With increasing incidence and rising complication rates both the health care systems and the affected individuals and their families face a major economic and human burden. 

With new therapies to prevent or delay the onset of T1D emerging, there is an acute need for better risk and progression biomarkers. Traditional risk markers for T1D such as genotype at the HLA locus and the detection of islet autoantibodies lack sensitivity for the prediction and rate of disease progression, respectively.

Metabolomic profiling of cord blood has identified altered lipid profiles in at-risk newborns developing T1D in early childhood and we have shown that plasma metabolites can predict declining beta cell function in children with newly-diagnosed T1D.    

While effective preventive therapeutic strategies are yet to be realized for T1D, there is much effort toward this goal. Indeed, the successful completion of this project will provide a substantial boost to these efforts by providing the first temporal profile of lipid metabolism in early childhood and the association with T1D. 

Notwithstanding the need for improved therapeutic options, there is an immediate unmet need for improved prediction of disease risk in T1D. Ongoing clinical trials rely largely on risk prediction for the selection of participants (who are usually children). Thus, the better the prediction the smaller the trial needed to reach a significant endpoint. 

Early intervention is most likely to be effective in preserving beta cell function. Thus, as we move closer to effective therapies, the need for effective prognostics (prior to antibody development) increases. The successful completion of this project will identify and validate novel risk markers for T1D in early childhood. We anticipate that a panel of such markers has the potential to be translated into an inexpensive non-invasive fast assay applicable in the primary healthcare setting.

Aim

The overall aim of the project is to evaluate the ability of molecular species in blood to more accurately predict risk of autoimmunity, future T1D, and rate of T1D progression.

Collaborators

Peter J. Meikle, Baker IDI Heart and Diabetes Institute, Australia
Åke Lernmark, Lund University, Sweden
Henrik B. Mortensen, Copenhagen University Hospital Herlev, Denmark

Funding

The JDRF
Danish Diabetes Academy

Redaktør