New potential avenues for early disease detection and prevention
A study led by Matej Oresic from VTT Technical Research Centre of Finland
suggests that autoimmune diabetes is preceded by diminished gut microbial
diversity of the Clostridium leptum subgroup, elevated plasma leptin and
enhanced glucose-stimulated insulin secretion.
In collaboration with the DIPP - Finnish Type 1 Diabetes and Prediction study,
VTT researches have previously found that specific metabolic disturbances
precede early β-cell autoimmunity markers in children who subsequently
progress to type 1 diabetes. However, the question remained what are the
environmental causes and tissue-specific mechanisms leading to these
Matej Orešič from VTT Technical Research Centre
of Finland and collaborators Eriika Savontaus from the University of Turku,
Samuel Kaski from Aalto University and Mikael Knip from the University of
Helsinki set out to address this question, and the results were published on
October 27, 2011 in PLoS Computational Biology Journal.
team carried out a study using non-obese diabetic (NOD) mice that
recapitulated the protocol used in the DIPP clinical study, followed up by
independent studies in which NOD mice were studied in relation to the risk of
diabetes progression. Researchers found that young female NOD mice that later
progress to autoimmune diabetes exhibit the same metabolic pattern as
prediabetic children. These metabolic changes are accompanied by enhanced
glucose-stimulated insulin secretion, upregulation of insulinotropic amino
acids in islets, elevated plasma leptin and adiponectin, and diminished gut
microbial diversity of the Clostridium leptum subgroup.
elucidation of early metabolic pathways associated with progression to Type 1
diabetes points to novel avenues for early disease prevention. The ongoing
efforts of VTT researchers are focused on the potential of specific bacteria
from the C. leptum subgroup to help prevent Type 1 diabetes.
study was supported by the Finnish Funding Agency for Technology and
Innovation Tekes, the Seventh Framework Program of the European Community, and
Juvenile Diabetes Research Foundation.
factors and molecular mechanisms leading to Type 1 diabetes are poorly
understood and of great public health interest. The incidence of inflammatory
and autoimmune diseases is rising faster than for any other major disease, and
these diseases are affecting a wide spectrum of the population. The number of
new cases of Type 1 diabetes in European children less than 5 years of age is
expected to double between 2005 and 2020.
Sysi-Aho, A. Ermolov, P. V. Gopalacharyulu, A. Tripathi, T. Seppänen-Laakso,
J. Maukonen, I. Mattila, S. T. Ruohonen, L. Vähätalo, L. Yetukuri, T.
Härkönen, E. Lindfors, J. Nikkilä, J. Ilonen, O. Simell, M. Saarela, M. Knip,
S. Kaski, E. Savontaus, M. Orešič, Metabolic
regulation in progression to autoimmune diabetes, PLoS Comp. Biol. 7 (10),
Orešič (photo by Antonin Halas)