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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

Methionine concentrations preseroconversion. A: Comparison of methionine concentration in the preseroconversion samples from early autoantibody-positive (AB+) children and their matched control subjects. B: Methionine concentrations in sequential samples from preseroconversion to postseroconversion in the early AB+ children (n = 13, left panel) and their matched control subjects (n = 13, right panel). AB−, autoantibody-negative.
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Figure 5: Methionine concentrations preseroconversion. A: Comparison of methionine concentration in the preseroconversion samples from early autoantibody-positive (AB+) children and their matched control subjects. B: Methionine concentrations in sequential samples from preseroconversion to postseroconversion in the early AB+ children (n = 13, left panel) and their matched control subjects (n = 13, right panel). AB−, autoantibody-negative.

Mentions: Samples collected before seroconversion and stored at −80°C were available from children who developed islet autoantibodies at age 2 years or younger and the matched autoantibody-negative control children. At a median age of 1.0 year (IQR 0.6–1.3), no significant differences between the two groups were observed for the concentrations of amino acid metabolites (data not shown), including methionine (Fig. 5A). Methionine concentrations decreased at seroconversion in the early autoantibody-positive children (P = 0.002), whereas they increased over the same period in the children who remained islet autoantibody-negative (P = 0.0007) (Fig. 5B). Glutamine, which the Diabetes Prediction and Prevention Project (DIPP) showed was decreased preseroconversion (10), increased in concentration from the preseroconversion sample to the seroconversion sample (P = 0.007), but this was also observed for the autoantibody-negative control children (P = 0.007).


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)

Methionine concentrations preseroconversion. A: Comparison of methionine concentration in the preseroconversion samples from early autoantibody-positive (AB+) children and their matched control subjects. B: Methionine concentrations in sequential samples from preseroconversion to postseroconversion in the early AB+ children (n = 13, left panel) and their matched control subjects (n = 13, right panel). AB−, autoantibody-negative.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 5: Methionine concentrations preseroconversion. A: Comparison of methionine concentration in the preseroconversion samples from early autoantibody-positive (AB+) children and their matched control subjects. B: Methionine concentrations in sequential samples from preseroconversion to postseroconversion in the early AB+ children (n = 13, left panel) and their matched control subjects (n = 13, right panel). AB−, autoantibody-negative.
Mentions: Samples collected before seroconversion and stored at −80°C were available from children who developed islet autoantibodies at age 2 years or younger and the matched autoantibody-negative control children. At a median age of 1.0 year (IQR 0.6–1.3), no significant differences between the two groups were observed for the concentrations of amino acid metabolites (data not shown), including methionine (Fig. 5A). Methionine concentrations decreased at seroconversion in the early autoantibody-positive children (P = 0.002), whereas they increased over the same period in the children who remained islet autoantibody-negative (P = 0.0007) (Fig. 5B). Glutamine, which the Diabetes Prediction and Prevention Project (DIPP) showed was decreased preseroconversion (10), increased in concentration from the preseroconversion sample to the seroconversion sample (P = 0.007), but this was also observed for the autoantibody-negative control children (P = 0.007).

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