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α-Hydroxybutyric acid is a selective metabolite biomarker of impaired glucose tolerance

Cobb, Jeff; Eckhart, Andrea; Motsinger-Reif, Alison; Carr, Bernadette; Groop, Leif LU and Ferrannini, Ele (2016) In Diabetes Care 39(6). p.988-995
Abstract

OBJECTIVE Plasma metabolites that distinguish isolated impaired glucose tolerance (iIGT) from isolated impaired fasting glucose (iIFG) may be useful biomarkers to predict IGT, a high-risk state for the development of type 2 diabetes. RESEARCH DESIGN AND METHODS Targeted metabolomics with 23 metabolites previously associated with dysglycemia was performed with fasting plasma samples from subjects without diabetes at time 0 of an oral glucose tolerance test (OGTT) in two observational cohorts: RISC (Relationship Between Insulin Sensitivity and Cardiovascular Disease) and DMVhi (Diabetes Mellitus and Vascular Health Initiative). Odds ratios (ORs) for a one-SD change in the metabolite level were calculated using multiple logistic regression... (More)

OBJECTIVE Plasma metabolites that distinguish isolated impaired glucose tolerance (iIGT) from isolated impaired fasting glucose (iIFG) may be useful biomarkers to predict IGT, a high-risk state for the development of type 2 diabetes. RESEARCH DESIGN AND METHODS Targeted metabolomics with 23 metabolites previously associated with dysglycemia was performed with fasting plasma samples from subjects without diabetes at time 0 of an oral glucose tolerance test (OGTT) in two observational cohorts: RISC (Relationship Between Insulin Sensitivity and Cardiovascular Disease) and DMVhi (Diabetes Mellitus and Vascular Health Initiative). Odds ratios (ORs) for a one-SD change in the metabolite level were calculated using multiple logistic regression models controlling for age, sex, and BMI to test for associations with iIGT or iIFG versus normal. Selective biomarkers of iIGT were further validated in the Botnia study. RESULTS α-Hydroxybutyric acid (α-HB) was most strongly associated with iIGT in RISC (OR 2.54 [95% CI 1.86-3.48], P value 5E-9) and DMVhi (2.75 [1.81-4.19], 4E-5) while having no significant association with iIFG. In Botnia, a-HB was selectively associated with iIGT (2.03 [1.65-2.49], 3E-11) and had no significant association with iIFG. Linoleoyl-glycerophosphocholine (L-GPC) and oleic acid were also found to be selective biomarkers of iIGT. In multivariate IGT prediction models, addition of α-HB, L-GPC, and oleic acid to age, sex, BMI, and fasting glucose significantly improved area under the curve in all three cohorts. CONCLUSIONS α-HB, L-GPC, and oleic acid were shown to be selective biomarkers of iIGT, independent of age, sex, BMI, and fasting glucose, in 4,053 subjects without diabetes from three European cohorts. These biomarkers can be used in predictive models to identify subjects with IGT without performing an OGTT.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
α-Hydroxybutyric acid , metabolite biomarker , impaired glucose tolerance
in
Diabetes Care
volume
39
issue
6
pages
8 pages
publisher
American Diabetes Association
external identifiers
  • scopus:84971280944
  • wos:000376980500025
ISSN
0149-5992
DOI
10.2337/dc15-2752
language
English
LU publication?
yes
id
ec600342-122f-49f7-99df-336fb4509db3
date added to LUP
2016-06-16 13:24:41
date last changed
2017-08-20 04:59:41
@article{ec600342-122f-49f7-99df-336fb4509db3,
  abstract     = {<p>OBJECTIVE Plasma metabolites that distinguish isolated impaired glucose tolerance (iIGT) from isolated impaired fasting glucose (iIFG) may be useful biomarkers to predict IGT, a high-risk state for the development of type 2 diabetes. RESEARCH DESIGN AND METHODS Targeted metabolomics with 23 metabolites previously associated with dysglycemia was performed with fasting plasma samples from subjects without diabetes at time 0 of an oral glucose tolerance test (OGTT) in two observational cohorts: RISC (Relationship Between Insulin Sensitivity and Cardiovascular Disease) and DMVhi (Diabetes Mellitus and Vascular Health Initiative). Odds ratios (ORs) for a one-SD change in the metabolite level were calculated using multiple logistic regression models controlling for age, sex, and BMI to test for associations with iIGT or iIFG versus normal. Selective biomarkers of iIGT were further validated in the Botnia study. RESULTS α-Hydroxybutyric acid (α-HB) was most strongly associated with iIGT in RISC (OR 2.54 [95% CI 1.86-3.48], P value 5E-9) and DMVhi (2.75 [1.81-4.19], 4E-5) while having no significant association with iIFG. In Botnia, a-HB was selectively associated with iIGT (2.03 [1.65-2.49], 3E-11) and had no significant association with iIFG. Linoleoyl-glycerophosphocholine (L-GPC) and oleic acid were also found to be selective biomarkers of iIGT. In multivariate IGT prediction models, addition of α-HB, L-GPC, and oleic acid to age, sex, BMI, and fasting glucose significantly improved area under the curve in all three cohorts. CONCLUSIONS α-HB, L-GPC, and oleic acid were shown to be selective biomarkers of iIGT, independent of age, sex, BMI, and fasting glucose, in 4,053 subjects without diabetes from three European cohorts. These biomarkers can be used in predictive models to identify subjects with IGT without performing an OGTT.</p>},
  author       = {Cobb, Jeff and Eckhart, Andrea and Motsinger-Reif, Alison and Carr, Bernadette and Groop, Leif and Ferrannini, Ele},
  issn         = {0149-5992},
  keyword      = {α-Hydroxybutyric acid ,metabolite biomarker ,impaired glucose tolerance},
  language     = {eng},
  month        = {06},
  number       = {6},
  pages        = {988--995},
  publisher    = {American Diabetes Association},
  series       = {Diabetes Care},
  title        = {α-Hydroxybutyric acid is a selective metabolite biomarker of impaired glucose tolerance},
  url          = {http://dx.doi.org/10.2337/dc15-2752},
  volume       = {39},
  year         = {2016},
}