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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

Islet autoimmunity–associated differences. Concentrations of metabolites of the amino acid metabolism (left panels) and lipid metabolism (right panels) are plotted for islet autoantibody-positive (AB+) children (n = 35) and autoantibody-negative (AB−) children (n = 35). Only metabolites where significant differences were observed (P < 0.05) are shown. Medians are indicated.
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Figure 2: Islet autoimmunity–associated differences. Concentrations of metabolites of the amino acid metabolism (left panels) and lipid metabolism (right panels) are plotted for islet autoantibody-positive (AB+) children (n = 35) and autoantibody-negative (AB−) children (n = 35). Only metabolites where significant differences were observed (P < 0.05) are shown. Medians are indicated.

Mentions: Characteristic metabolite patterns were observed in relation to the appearance of islet autoantibodies. Children who were islet autoantibody-positive had significantly lower median concentrations of methionine (27.9 vs. 33.7 μmol/L, P = 0.005) and hydroxyproline (24.9 vs. 28.5 μmol/L, P = 0.04) compared with children who were islet autoantibody-negative and had higher median concentrations of lipids in the functionally diverse LC1 (0.3 vs. −0.1, P = 0.01) and LC8 (0.5 vs. −0.5, P = 2 × 10−10) (Fig. 2), both of which are dominated by polyunsaturated fatty acid-containing PCs and specific TGs. All measured PCs in LC8 were significantly higher in islet autoantibody-positive children (Supplementary Table 3).


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)

Islet autoimmunity–associated differences. Concentrations of metabolites of the amino acid metabolism (left panels) and lipid metabolism (right panels) are plotted for islet autoantibody-positive (AB+) children (n = 35) and autoantibody-negative (AB−) children (n = 35). Only metabolites where significant differences were observed (P < 0.05) are shown. Medians are indicated.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 2: Islet autoimmunity–associated differences. Concentrations of metabolites of the amino acid metabolism (left panels) and lipid metabolism (right panels) are plotted for islet autoantibody-positive (AB+) children (n = 35) and autoantibody-negative (AB−) children (n = 35). Only metabolites where significant differences were observed (P < 0.05) are shown. Medians are indicated.
Mentions: Characteristic metabolite patterns were observed in relation to the appearance of islet autoantibodies. Children who were islet autoantibody-positive had significantly lower median concentrations of methionine (27.9 vs. 33.7 μmol/L, P = 0.005) and hydroxyproline (24.9 vs. 28.5 μmol/L, P = 0.04) compared with children who were islet autoantibody-negative and had higher median concentrations of lipids in the functionally diverse LC1 (0.3 vs. −0.1, P = 0.01) and LC8 (0.5 vs. −0.5, P = 2 × 10−10) (Fig. 2), both of which are dominated by polyunsaturated fatty acid-containing PCs and specific TGs. All measured PCs in LC8 were significantly higher in islet autoantibody-positive children (Supplementary Table 3).

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