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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

Metabolite concentrations are relatively consistent over time. The concentrations of methionine (left panels) and LC8 (right panels) in the first sample at seroconversion and respectively matched samples from autoantibody-negative (AB−) children are plotted against the concentrations in a second sample obtained 1 year later. Correlations are shown for children age ≤2 years (upper panels) and ≥8 years (lower panels). Islet autoantibody-positive (AB+) children (●) and AB− children (○) are indicated.
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Figure 4: Metabolite concentrations are relatively consistent over time. The concentrations of methionine (left panels) and LC8 (right panels) in the first sample at seroconversion and respectively matched samples from autoantibody-negative (AB−) children are plotted against the concentrations in a second sample obtained 1 year later. Correlations are shown for children age ≤2 years (upper panels) and ≥8 years (lower panels). Islet autoantibody-positive (AB+) children (●) and AB− children (○) are indicated.

Mentions: Differences in methionine with respect to islet autoantibody positivity and age of seroconversion at the seroconversion time point were also consistent in the follow-up samples (Fig. 4), with a significant contribution to methionine concentration by autoantibody positivity (P = 4 × 10−6) and the interaction of autoantibody positivity and age at seroconversion (P = 4 × 10−6).FIG. 4.


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)

Metabolite concentrations are relatively consistent over time. The concentrations of methionine (left panels) and LC8 (right panels) in the first sample at seroconversion and respectively matched samples from autoantibody-negative (AB−) children are plotted against the concentrations in a second sample obtained 1 year later. Correlations are shown for children age ≤2 years (upper panels) and ≥8 years (lower panels). Islet autoantibody-positive (AB+) children (●) and AB− children (○) are indicated.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 4: Metabolite concentrations are relatively consistent over time. The concentrations of methionine (left panels) and LC8 (right panels) in the first sample at seroconversion and respectively matched samples from autoantibody-negative (AB−) children are plotted against the concentrations in a second sample obtained 1 year later. Correlations are shown for children age ≤2 years (upper panels) and ≥8 years (lower panels). Islet autoantibody-positive (AB+) children (●) and AB− children (○) are indicated.
Mentions: Differences in methionine with respect to islet autoantibody positivity and age of seroconversion at the seroconversion time point were also consistent in the follow-up samples (Fig. 4), with a significant contribution to methionine concentration by autoantibody positivity (P = 4 × 10−6) and the interaction of autoantibody positivity and age at seroconversion (P = 4 × 10−6).FIG. 4.

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