Etiology, prediction and prevention of childhood type 1 diabetes
PI and head of research group: Helena Elding Larsson, MD, PhD, Associate Professor
The aim of our research is to identify genetic and immunological risk factors and predictive factors for type 1 diabetes, and ultimately to prevent the disease through primary or secondary prevention.
The research is based upon our large prospective population-based studies Diabetes Prediction in Skåne (DiPiS) and The Environmental Determinants of Diabetes in the young (TEDDY), screening for autoantibodies in relatives within TrialNet and a number of clinical trials aiming to prevent or delay the disease (Figure 1).
Children with genetic risk are followed to identify risk factors and triggers of the autoimmune process destroying the beta-cells. During the progressive autoimmune process we have a window of opportunity to prevent clinically overt disease. In our clinical trials with immune tolerance with Alum-GAD (Diabetes Prevention – Immune Tolerance 1 and 2) we are for the first time ever testing if the drug may act preventive in children with islet autoimmunity but not yet diabetes. Within TrialNet, immune tolerance with oral insulin is tested in children with autoimmunity trying to prevent disease. In TEFA we are testing it glutenfree diet may increase insulin-secretion in subjects with islet autoimmunity. Additionally, CTLA-4 inhibitors and GLP-1 inhibitors will be tested for prevention.
In children that have developed type 1 diabetes we are involved in trials to save remaining beta-cells, as well as studies to investigate complications such as early recognition of neuropaty.
Thyroid autoimmune disease is more common in children with type 1 diabetes. We are investigating genetic and immunologic background and co-occurrence with type 1 diabetes autoantibodies both in children with diabetes and within our prospective cohorts. Additionally we are investigating environmental risk factors for the disease.
Both type 1 diabetes and autoimmune thyroiditis are common diseases that are important to find and treat early. In our prospective cohorts of children with risk for type 1 diabetes, we have shown that the children followed are diagnosed early with less symptom and serious disease. To prevent or delay type 1 diabetes in children with autoimmunity would be of uttermost importance.
Growth and risk for islet autoimmunity and progression to type 1 diabetes in early childhood: The Environmental Determinants of Diabetes in the Young Study.
Larsson HE, Vehik K, Haller MJ, Liu X, Akolkar B, Hagopian W, Krischer J, Lernmark Å, She JX, Simell O, Toppari J, Ziegler AG, Rewers M; TEDDY study.
Diabetes. 2016 Mar 18.
Baseline heterogeneity in glucose metabolism marks the risk for type 1 diabetes and complicates secondary prevention. Elding Larsson H, Larsson C, Lernmark Å; DiAPREV-IT study group. Acta Diabetol. 2015 Jun;52(3):473-81.
Cord blood insulinoma-associated protein 2 autoantibodies are associated with increased risk of type 1 diabetes in the population-based Diabetes Prediction in Skåne study. Lundgren M, Lynch K, Larsson C, Elding Larsson H; Diabetes Prediction in Skåne study group. Diabetologia. 2015 Jan;58(1):75-8.
Immune therapy in type 1 diabetes mellitus. Lernmark A, Larsson HE.
Nat Rev Endocrinol. 2013 Feb;9(2):92-103.
Reduced prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in young children participating in longitudinal follow-up.Elding Larsson H, Vehik K, Bell R, Dabelea D, Dolan L, Pihoker C, Knip M, Veijola R, Lindblad B, Samuelsson U, Holl R, Haller MJ; TEDDY Study Group; SEARCH Study Group; Swediabkids Study Group; DPV Study Group; Finnish Diabetes Registry Study Group.
Diabetes Care. 2011 Nov;34(11):2347-52.
Thyroid autoimmunity in relation to islet autoantibodies and HLA-DQ genotype in newly diagnosed type 1 diabetes in children and adolescents. Jonsdottir B, Andersson C, Carlsson A, Delli A, Forsander G, Ludvigsson J, Marcus C, Samuelsson U, Ortqvist E, Lernmark A, Ivarsson SA, Larsson HE; Better Diabetes Diagnosis (BDD) study group. Diabetologia. 2013 Aug;56(8):1735-42.