Severe autoimmune diabetes (SAID) – mechanisms and pathways
Leaders for work package 3: Luis Sarmiento-Pérez, Åke Lernmark, and Annelie Carlsson
Investigators at the LUDC-IRC have a long track record of conducting studies aimed at early prediction and prevention of type 1 diabetes (in our new sub classification also referred as SAID – severe autoimmune diabetes) and its complications in children. Efforts include the initiation and maintenance of well-characterised cohorts such as the BDD (Better Diabetes Diagnosis), the Diabetes Prediction in Skåne (DiPiS), and The Environmental Determinants of Diabetes in the Young (TEDDY).
This work package relies on genetic screening for type 1 diabetes in early childhood and follow-up of risk subjects by measurements of islet autoantibodies and testing of glucose tolerance and metabolic control in autoantibody positive subjects. This enables early diagnosis and follow-up of clinical type 1 diabetes to evaluate metabolic control and loss of C-peptide as well as early detection of complications. Screening follow-up design based on specific biomarkers also allows inclusion of subjects in prevention studies. By predicting and diagnosing the disease early on, we hope to prevent severe disease outcomes.
This work package also investigates how the immune system and viral infections interact to initiate and promote progression of type 1 diabetes. This knowledge can help us identify ways to protect pancreatic beta cells against viral infections and prevent the attack on the immune system.
Objectives
- To explore the influence of SAID heterogeneity on disease outcome.
- To identify targetable mechanisms and pathways underlying the initiation and progression of SAID.
- To identify predictive biomarkers for the development of other concomitant autoimmune disease.
Selected publications
- Title: Association of HLA-DQ Heterodimer Residues −18β and β57 With Progression From Islet Autoimmunity to Diabetes in the Diabetes Prevention Trial–Type 1
Reference: Diabetes Care, 45, 1610-1620 (2022) - Title: Possible Relationship between the HLA-DRA1 Intron Haplotype of Three Single-Nucleotide Polymorphisms in Intron 1 of the HLA-DRA1 Gene and Autoantibodies in Children at Increased Genetic Risk for Autoimmune Type 1 Diabetes
Reference: ImmunoHorizons, 6 (8), 614-629 (2022) - Title: Reduced expression of OXPHOS and DNA damage genes is linked to protection from microvascular complications in long-term type 1 diabetes: the PROLONG study
Reference: Scientific Reports, 11, 20735 (2021) - Title: Extracellular Vesicles Released by Enterovirus-Infected EndoC-βH1 Cells Mediate Non-Lytic Viral Spread
Reference: Microorganisms, 8 (11), 1753 (2020) - Title: Human enteroviral infection impairs autophagy in clonal INS(832/13) cells and human pancreatic islet cells
Reference: Diabetologia, 63, 2372-2384 (2020)
Contact
Luis Sarmiento-Pérez
Work Package Leader
Associate Researcher
+ 46 (0)70 306 76 26
luis [dot] sarmiento-perez [at] med [dot] lu [dot] se (luis[dot]sarmiento-perez[at]med[dot]lu[dot]se)
Åke Lernmark
Work Package Leader
Professor of experimental diabetes
+46 (0)70 772 27 50
+46 (0)40 39 19 01
ake [dot] lernmark [at] med [dot] lu [dot] se (ake[dot]lernmark[at]med[dot]lu[dot]se)
Annelie Carlsson
Work Package Leader
Specialist in pediatric endocrinology
Associate Professor of pediatric autoimmunity
+46 (0)76 826 71 70
+46 (0)46 17 82 28
annelie [dot] carlsson [at] med [dot] lu [dot] se