Dataset Information

Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes.

ABSTRACT: The risk determinants of type 1 diabetes, initiators of autoimmune response, mechanisms regulating progress toward beta cell failure, and factors determining time of presentation of clinical diabetes are poorly understood. We investigated changes in the serum metabolome prospectively in children who later progressed to type 1 diabetes. Serum metabolite profiles were compared between sample series drawn from 56 children who progressed to type 1 diabetes and 73 controls who remained nondiabetic and permanently autoantibody negative. Individuals who developed diabetes had reduced serum levels of succinic acid and phosphatidylcholine (PC) at birth, reduced levels of triglycerides and antioxidant ether phospholipids throughout the follow up, and increased levels of proinflammatory lysoPCs several months before seroconversion to autoantibody positivity. The lipid changes were not attributable to HLA-associated genetic risk. The appearance of insulin and glutamic acid decarboxylase autoantibodies was preceded by diminished ketoleucine and elevated glutamic acid. The metabolic profile was partially normalized after the seroconversion. Autoimmunity may thus be a relatively late response to the early metabolic disturbances. Recognition of these preautoimmune alterations may aid in studies of disease pathogenesis and may open a time window for novel type 1 diabetes prevention strategies.

SUBMITTER: Oresic M

PROVIDER: S-EPMC2605239 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes.

Oresic Matej M Simell Satu S Sysi-Aho Marko M Näntö-Salonen Kirsti K Seppänen-Laakso Tuulikki T Parikka Vilhelmiina V Katajamaa Mikko M Hekkala Anne A Mattila Ismo I Keskinen Päivi P Yetukuri Laxman L Reinikainen Arja A Lähde Jyrki J Suortti Tapani T Hakalax Jari J Simell Tuula T Hyöty Heikki H Veijola Riitta R Ilonen Jorma J Lahesmaa Riitta R Knip Mikael M Simell Olli O

The Journal of experimental medicine 20081215 13

The risk determinants of type 1 diabetes, initiators of autoimmune response, mechanisms regulating progress toward beta cell failure, and factors determining time of presentation of clinical diabetes are poorly understood. We investigated changes in the serum metabolome prospectively in children who later progressed to type 1 diabetes. Serum metabolite profiles were compared between sample series drawn from 56 children who progressed to type 1 diabetes and 73 controls who remained nondiabetic an ...[more]

PMID: 19075291

Similar Datasets

Project description:AIMS/HYPOTHESIS:We sought to assess the frequency, determinants and prognosis for future diabetes in individuals with islet autoimmunity and whether these factors differ depending on the age of onset of islet autoimmunity. METHODS:A prospective cohort (n = 2547) of children from the general population who had a high-risk HLA genotype and children who had a first-degree relative with type 1 diabetes were followed for up to 21 years. Those with the persistent presence of one or more islet autoantibodies were categorised as early-onset (<8 years of age, n = 143, median 3.3 years) or late-onset (?8 years of age, n = 64, median 11.1 years), and were followed for a median of 7.4 and 4.7 years, respectively. Progression to diabetes was evaluated by Kaplan-Meier analysis with logrank test. Factors associated with progression to diabetes were analysed using the parametric accelerated failure time model. RESULTS:Children with late-onset islet autoimmunity were more likely to be Hispanic or African-American than non-Hispanic white (p = 0.004), and less likely to be siblings of individuals with type 1 diabetes (p = 0.04). The frequencies of the HLA-DR3/4 genotype and non-HLA gene variants associated with type 1 diabetes did not differ between the two groups. However, age and HLA-DR3/4 were important predictors of rate of progression to both the presence of additional autoantibodies and type 1 diabetes. Late-onset islet autoimmunity was more likely to present with a single islet autoantibody (p = 0.01) and revert to an antibody-negative state (p = 0.01). Progression to diabetes was significantly slower in children with late-onset islet autoimmunity (p < 0.001). CONCLUSIONS/INTERPRETATION:A late onset of islet autoimmunity is more common in African-American and Hispanic individuals. About half of those with late-onset islet autoimmunity progress to show multiple islet autoantibodies and develop diabetes in adolescence or early adulthood. Further investigation of environmental determinants of late-onset autoimmunity may lead to an understanding of and ability to prevent adolescent and adult-onset type 1 diabetes.

Dataset Information

Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes.

Publications

Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets