Finnish scientists have reported a breakthrough in attempts to understand the development of type 1 diabetes.
They have discovered disturbances in lipid and amino acid metabolism in children that later developed type 1 diabetes, also known as juvenile diabetes.
The alterations preceded the autoimmune response by between months and years.
The study may prompt new approaches to predicting and preventing type 1 diabetes in the pre-autoimmune phase of the disease.
The results of the Finnish research team, which consists of scientists from VTT Technical Research Centre of Finland and the Universities of Turku, Oulu and Tampere, were published in the Journal of Experimental Medicine on 15 December 2008.
Type one diabetes is an autoimmune disease in which the immune system attacks the insulin-producing pancreatic beta cells.
The gradual loss of beta cells results in life-long dependence on exogenous insulin.
At the moment, the earliest identifiable process in the pathogenesis of type 1 diabetes has been the development of autoimmunity to pancreatic beta cells in the measurable form of islet autoantibodies.
Although the autoimmunity usually precedes the clinical disease by between months and years, its occurrence may be too late for therapeutic approaches aimed at preventing progression to overt diabetes.
The initiators of the autoimmune response have remained unknown and the mechanisms supporting progression towards beta cell failure have been poorly understood, making discovery of effective prevention a challenge.
The results of the SYSDIPP project, which was supported by the Tekes Finnwell Program, shed light on ways to combat the disease.
The SYSDIPP project has made use of metabolomics.
Metabolomics systematically studies the chemical fingerprints in cells, tissues and biofluids in a given physiological and environmental context.
The metabolic phenotype is sensitive to subtle factors such as age, lifestyle, nutrition and the microbe environment of the intestines.
Changes in the concentrations of metabolites may thus reflect both genetic and environmental factors influencing later susceptibility to chronic diseases.
In 1994, an ongoing birth cohort study (DIPP, the Type 1 Diabetes Prediction and Prevention study) was launched in Finland, supported by the Juvenile Diabetes Research Foundation International.
Over a period of 14 years, more than 130,000 newborn infants were screened for genetic risk and more than 8000 at-risk children were regularly followed.
The research team investigated metabolic profiles of DIPP children prospectively from birth and published the results in The Journal of Experimental Medicine on 15 December 2008.
The article reported the discovery of metabolic disturbances that precede the autoimmune response in children, which later progress to type 1 diabetes.
The investigators found that the individuals that developed diabetes had reduced serum levels of succinic acid and phosphatidylcholine at birth, reduced levels of triglycerides and antioxidant ether phospholipids throughout the follow-up and increased levels of proinflammatory lysophosphatidylcholines several months prior to autoimmunity to pancreatic beta cells.
The metabolic profile was partially normalised following the autoimmune response, suggesting autoimmunity may be a relatively late physiological response to the early metabolic disturbances.
The observed lipid changes were not attributable to HLA-associated genetic risk.
Metabolic profiling at early age may therefore aid in determining the risk of type 1 diabetes.
The findings imply that metabolic or immunomodulatory interventions during the pre-autoimmune period could be used to prevent type 1 diabetes.
The incidence of type 1 diabetes among children and adolescents has increased markedly in western countries during recent decades.
The incidence has reached record levels in Finland, where one child out of 120 develops type 1 diabetes before the age of 15.
The annual incidence is quickly increasing, with the number of new cases expected to double in the next 15 years.
