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Age- and islet autoimmunity-associated differences in amino acid and lipid metabolites in children at risk for type 1 diabetes.

Pflueger M, Seppänen-Laakso T, Suortti T, Hyötyläinen T, Achenbach P, Bonifacio E, Orešič M, Ziegler AG - Diabetes (2011)

Bottom Line: Ultraperformance liquid chromatography and mass spectroscopy were used to measure metabolites and lipids quantitatively in the first autoantibody-positive and matched autoantibody-negative serum samples and in a second sample after 1 year of follow-up.Independent of age-related differences, autoantibody-positive children had higher levels of odd-chain triglycerides and polyunsaturated fatty acid-containing phospholipids than autoantibody-negative children and independent of age at first autoantibody appearance (P < 0.0001).Distinct metabolic profiles are associated with age and islet autoimmunity.

View Article: PubMed Central - PubMed

Affiliation: Forschergruppe Diabetes eV at Helmholtz Center Munich, Neuherberg, Germany.

ABSTRACT

Objective: Islet autoimmunity precedes type 1 diabetes and often initiates in childhood. Phenotypic variation in islet autoimmunity relative to the age of its development suggests heterogeneous mechanisms of autoimmune activation. To support this notion, we examined whether serum metabolite profiles differ between children with respect to islet autoantibody status and the age of islet autoantibody development.

Research design and methods: The study analyzed 29 metabolites of amino acid metabolism and 511 lipids assigned to 12 lipid clusters in children, with a type 1 diabetic parent, who first developed autoantibodies at age 2 years or younger (n = 13), at age 8 years or older (n = 22), or remained autoantibody-negative, and were matched for age, date of birth, and HLA genotypes (n = 35). Ultraperformance liquid chromatography and mass spectroscopy were used to measure metabolites and lipids quantitatively in the first autoantibody-positive and matched autoantibody-negative serum samples and in a second sample after 1 year of follow-up.

Results: Differences in the metabolite profiles were observed relative to age and islet autoantibody status. Independent of age-related differences, autoantibody-positive children had higher levels of odd-chain triglycerides and polyunsaturated fatty acid-containing phospholipids than autoantibody-negative children and independent of age at first autoantibody appearance (P < 0.0001). Consistent with our hypothesis, children who developed autoantibodies by age 2 years had twofold lower concentration of methionine compared with those who developed autoantibodies in late childhood or remained autoantibody-negative (P < 0.0001).

Conclusions: Distinct metabolic profiles are associated with age and islet autoimmunity. Pathways that use methionine are potentially relevant for developing islet autoantibodies in early infancy.

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Related in: MedlinePlus

Flowchart of study population for the metabolomic analysis. Heavy boxed categories (N = 70) were included in the analysis (material at −80°C was available). All 70 children were tested for metabolomics at seroconversion to islet autoantibodies (ABs) or at the respective age in AB− children as well as 1 year thereafter. T1D, type 1 diabetes.
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Figure 1: Flowchart of study population for the metabolomic analysis. Heavy boxed categories (N = 70) were included in the analysis (material at −80°C was available). All 70 children were tested for metabolomics at seroconversion to islet autoantibodies (ABs) or at the respective age in AB− children as well as 1 year thereafter. T1D, type 1 diabetes.

Mentions: To date (2010), 152 offspring developed persistent islet autoantibodies (i.e., antibodies that were confirmed positive in a second serum sample) (Fig. 1). Of these, 62 children developed islet autoantibodies early (age ≤2 years), 36 developed antibodies at age 5 years, and 54 developed antibodies late (age ≥8 years). The current study included 70 children (Fig. 1 and Table 1), consisting of 35 children with islet autoantibodies and 35 children without islet autoantibodies matched for age, date of birth, sex, and HLA genotype. Autoantibody-positive children were selected on the basis of 1) the availability of samples frozen at −80°C (a requisite for the metabolomic analysis), and 2) becoming autoantibody-positive early (age ≤2 years; n = 13) or late (age ≥8 years; n = 22) (Supplementary Table 1). Seven of the 35 autoantibody-positive and none of the 35 autoantibody-negative children progressed to type 1 diabetes at a median time from first islet autoantibody development of 3.0 years (interquartile range [IQR] 2.7–6.2). Of these, 42 children had a mother with type 1 diabetes, and 28 had a nondiabetic mother but a father with type 1 diabetes.


Age- and islet autoimmunity-associated differences in amino acid and lipid metabolites in children at risk for type 1 diabetes.

Pflueger M, Seppänen-Laakso T, Suortti T, Hyötyläinen T, Achenbach P, Bonifacio E, Orešič M, Ziegler AG - Diabetes (2011)

Flowchart of study population for the metabolomic analysis. Heavy boxed categories (N = 70) were included in the analysis (material at −80°C was available). All 70 children were tested for metabolomics at seroconversion to islet autoantibodies (ABs) or at the respective age in AB− children as well as 1 year thereafter. T1D, type 1 diabetes.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198092&req=5

Figure 1: Flowchart of study population for the metabolomic analysis. Heavy boxed categories (N = 70) were included in the analysis (material at −80°C was available). All 70 children were tested for metabolomics at seroconversion to islet autoantibodies (ABs) or at the respective age in AB− children as well as 1 year thereafter. T1D, type 1 diabetes.
Mentions: To date (2010), 152 offspring developed persistent islet autoantibodies (i.e., antibodies that were confirmed positive in a second serum sample) (Fig. 1). Of these, 62 children developed islet autoantibodies early (age ≤2 years), 36 developed antibodies at age 5 years, and 54 developed antibodies late (age ≥8 years). The current study included 70 children (Fig. 1 and Table 1), consisting of 35 children with islet autoantibodies and 35 children without islet autoantibodies matched for age, date of birth, sex, and HLA genotype. Autoantibody-positive children were selected on the basis of 1) the availability of samples frozen at −80°C (a requisite for the metabolomic analysis), and 2) becoming autoantibody-positive early (age ≤2 years; n = 13) or late (age ≥8 years; n = 22) (Supplementary Table 1). Seven of the 35 autoantibody-positive and none of the 35 autoantibody-negative children progressed to type 1 diabetes at a median time from first islet autoantibody development of 3.0 years (interquartile range [IQR] 2.7–6.2). Of these, 42 children had a mother with type 1 diabetes, and 28 had a nondiabetic mother but a father with type 1 diabetes.

Bottom Line: Ultraperformance liquid chromatography and mass spectroscopy were used to measure metabolites and lipids quantitatively in the first autoantibody-positive and matched autoantibody-negative serum samples and in a second sample after 1 year of follow-up.Independent of age-related differences, autoantibody-positive children had higher levels of odd-chain triglycerides and polyunsaturated fatty acid-containing phospholipids than autoantibody-negative children and independent of age at first autoantibody appearance (P < 0.0001).Distinct metabolic profiles are associated with age and islet autoimmunity.

View Article: PubMed Central - PubMed

Affiliation: Forschergruppe Diabetes eV at Helmholtz Center Munich, Neuherberg, Germany.

ABSTRACT

Objective: Islet autoimmunity precedes type 1 diabetes and often initiates in childhood. Phenotypic variation in islet autoimmunity relative to the age of its development suggests heterogeneous mechanisms of autoimmune activation. To support this notion, we examined whether serum metabolite profiles differ between children with respect to islet autoantibody status and the age of islet autoantibody development.

Research design and methods: The study analyzed 29 metabolites of amino acid metabolism and 511 lipids assigned to 12 lipid clusters in children, with a type 1 diabetic parent, who first developed autoantibodies at age 2 years or younger (n = 13), at age 8 years or older (n = 22), or remained autoantibody-negative, and were matched for age, date of birth, and HLA genotypes (n = 35). Ultraperformance liquid chromatography and mass spectroscopy were used to measure metabolites and lipids quantitatively in the first autoantibody-positive and matched autoantibody-negative serum samples and in a second sample after 1 year of follow-up.

Results: Differences in the metabolite profiles were observed relative to age and islet autoantibody status. Independent of age-related differences, autoantibody-positive children had higher levels of odd-chain triglycerides and polyunsaturated fatty acid-containing phospholipids than autoantibody-negative children and independent of age at first autoantibody appearance (P < 0.0001). Consistent with our hypothesis, children who developed autoantibodies by age 2 years had twofold lower concentration of methionine compared with those who developed autoantibodies in late childhood or remained autoantibody-negative (P < 0.0001).

Conclusions: Distinct metabolic profiles are associated with age and islet autoimmunity. Pathways that use methionine are potentially relevant for developing islet autoantibodies in early infancy.

Show MeSH
Related in: MedlinePlus