Type 1 Diabetes (T1D)
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, 50/100,000 children (1 child in 170 develops T1D before the age of 15 years), and is increasing. T1D is caused by loss of insulin-secreting capacity of the β cells and, finally, by selective death of these cells in the islets of Langerhans in the pancreas. T1D is an autoimmune disease characterized by a relatively long 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 β cell specific autoantibodies. Clinical T1D occurs when 80-90% of the β cells have been destroyed. At this point 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 biobank of the Type 1 Diabetes Prediction and Prevention Project in Finland (DIPP), which during the past 15 years has collected sequential sera samples from a genetic risk group of children.
In collaboration with the VTT Technical Research Centre of Finland robust methodology for transcriptomics and proteomics measurements and data analysis have been set up and applied. Within this research consortium it was observed that dysregulation of lipid and amino acid metabolism preceded islet autoimmunity in children who later progress to type 1 diabetes (Oresic M. et al. J Exp Med. 2008 Dec 22;205(13):2975-84.). In transcriptomic analyses of serum samples from DIPP subjects (cases and controls), we have observed significant expression changes in genes associated with pathways in the development of T1D. Similarly, at the proteomic level, distinct serum protein abundance changes were observed in association with T1D development.
Team members
Riitta Lahesmaa, M.D., Ph.D., Professor
Group Leader
riitta.lahesmaa (at) btk.fi
Robert Moulder, Ph.D.
Senior Scientist
robert.moulder (at) btk.fi
Laura Elo-Uhlgren, Ph.D.
Postdoctoral Fellow
laura.elo (at) btk.fi
Henna Järvenpää, M.Sc.
Graduate Student
henna.jarvenpaa (at) btk.fi
Minna Kyläniemi, M.Sc.
Graduate Student
minna.kylaniemi (at) btk.fi
Päivi Junni, technician
paivi.junni (at) btk.fi
Collaborators
We collaborate with the Type 1 Diabetes Prediction and Prevention Project
in Finland (DIPP).
Our key collaborators within these projects include:
Olli Simell, M.D., Ph.D., Professor
University of Turku, Finland
Dr. Matej Oresic, Ph.D., Professor
VTT Biotechnology, Espoo, Finland
David Goodlett, Ph.D., Professor
University of Washington, Seattle, USA
Heikki Hyöty, M.D., Ph.D., Professor
University of Tampere, Finland
Jorma Ilonen, M.D., Ph.D., Professor
University of Kuopio, Finland
Mikael Knip, M.D., Ph.D., Professor
University of Helsinki, Finland
Olli Nevalainen, Ph.D., Professor
University of Turku, Finland
Funding
JDRF
The Academy of Finland
The National Technology Agency of Finland
EU FP7 Diabimmune