Type 1 Diabetes

Project Description

Molecular mechanisms and early diagnosis of Type 1 Diabetes (T1D)

Type 1 diabetes (T1D) is the most common metabolic-endocrine disorder in children in western countries. The annual incidence of T1D in Finland is at a global record high, 60/100,000 children (1 child in 170 develops T1D before the age of 15 years). T1D is caused by loss of insulin-secreting capacity of the ? cells and, finally, by selective death of these cells in the islets of Langerhans in the pancreas. T1D is an –immune-mediated disease characterized by a symptom-free period that precedes the flair-up of clinical signs of the disease In almost all children, progression to clinical T1D is associated with the presence of ? cell specific autoantibodies, but the timing and rate of disease development is highly individual. After clinical diagnosis,T1D patient is dependent on a daily insulin substitution for the rest of his/her life and there is a high risk of developing acute and long-term complications.

Objectives

Our objective is to discover molecular markers that indicate the risk and development of diabetes-associated autoimmunity and progression towards overt clinical Type 1 diabetes (T1D). With the integration of transcriptomics, proteomics and metabolomics data, correlated with those of HLA-gene alleles, autoantibodies, and markers of enterovirus infections (antibodies, enterovirus RNA), together with any demographic and metabolic features common between the children studied, we aim to identify putative associations between a particular biomolecular profile and these key parameters. Potentially these could be used in the development of early diagnostics that would enable early therapy and possibly preventive treatments.

Analyses are made from sequential samples of subjects during the development of T1D, together with the equivalent material from their matched healthy controls. The samples are selected from the unique of the Type 1 Diabetes Prediction and Prevention Project in Finland (DIPP), which since over 20 years has collected different types of sequential samples from a genetic risk group of children.

Team Members

Riitta Lahesmaa, M.D., Ph.D., Professor
Group Leader

Henna Kallionpää, Ph.D.
Postdoctoral Fellow

Niina Lietzen, Ph.D.
Postdoctoral Fellow

Robert Moulder, Ph.D.
Senior Scientist

Santosh Bhosale, M.Sc.
Graduate Student

Karoliina Hirvonen, M.Sc.
Graduate student

Essi Laajala, M.Sc. (Tech)
Graduate student (on leave)

Elina Komsi

Undergraduate student
Sarita Heinonen, technician

Päivi Junni, technician

Collaborators

We collaborate with the Type 1 Diabetes Prediction and Prevention Project
in Finland (DIPP) and DIABIMMUNE, PEVNET and INNODIA Projects.

Our key collaborators within these projects include: 

Knip Mikael, M.D., Ph.D., Professor
University of Helsinki, Finland

Lähdesmäki Harri, D.Sc. (Tech), Professor
Aalto University, Espoo, Finland

Toppari Jorma, M.D., Ph.D., Professor
University of Turku, Finland

DIPP study PIs:
Hyöty Heikki, M.D., Ph.D., Professor
University of Tampere, Finland

Ilonen Jorma, M.D., Ph.D., Professor
University of Turku, Finland

Riitta Veijola, M.D., Ph.D.
University of Oulu, Finland

Funding

JDRF
The Academy of Finland
INNODIA

Publications

Moulder R, Lahesmaa R. (2016) Early signs of disease in type 1 diabetes. Pediatr Diabetes. 17 Suppl 22:43-8.

Heinonen MT, Moulder R, Lahesmaa R. (2015) New Insights and Biomarkers for Type 1 Diabetes: Review for Scandinavian Journal of Immunology. Scand J Immunol. 82(3):244-53. Review.

Moulder R, Bhosale SD, Erkkilä T, Laajala E, Salmi J, Nguyen EV, Kallionpää H, Mykkänen J, Vähä-Mäkilä M, Hyöty H, Veijola R, Ilonen J, Simell T, Toppari J, Knip M, Goodlett DR, Lähdesmäki H, Simell O, Lahesmaa R. (2015) Serum proteomes distinguish children developing type 1 diabetes in a cohort with HLA-conferred susceptibility. Diabetes. 64(6):2265-78.

Kallionpää H, Laajala E, Öling V, Härkönen T, Tillmann V, Dorshakova NV, Ilonen J, Lähdesmäki H, Knip M, Lahesmaa R; DIABIMMUNE Study Group. (2014) Standard of hygiene and immune adaptation in newborn infants. Clin Immunol. 155(1):136-47.

Kallionpää H, Elo LL, Laajala E, Mykkänen J, Ricaño-Ponce I, Vaarma M, Laajala TD, Hyöty H, Ilonen J, Veijola R, Simell T, Wijmenga C, Knip M, Lähdesmäki H, Simell O, Lahesmaa R. (2014) Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility. Diabetes. 63(7):2402-14.

Elo LL, Mykkänen J, Nikula T, Järvenpää H, Simell S, Aittokallio T, Hyöty H, Ilonen J, Veijola R, Simell T, Knip M, Simell O, Lahesmaa R. (2010) Early suppression of immune response pathways characterizes children with prediabetes in genome-wide gene expression profiling. J Autoimmun. 35(1):70-6.