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Strategies for individual phenotyping of linoleic and arachidonic acid metabolism using an oral glucose tolerance test.

ABSTRACT: The ability to restore homeostasis upon environmental challenges has been proposed as a measure for health. Metabolic profiling of plasma samples during the challenge response phase should offer a profound view on the flexibility of a phenotype to cope with daily stressors. Current data modeling approaches, however, struggle to extract biological descriptors from time-resolved metabolite profiles that are able to discriminate between different phenotypes. Thus, for the case of oxylipin responses in plasma upon an oral glucose tolerance test we developed a modeling approach that incorporates a priori biological pathway knowledge. The degradation pathways of arachidonic and linoleic acids were modeled using a regression model based on a pseudo-steady-state approximated model, resulting in a parameter A that summarizes the relative enzymatic activity in these pathways. Analysis of the phenotypic parameters As suggests that different phenotypes can be discriminated according to preferred relative activity of the arachidonic and linoleic pathway. Correlation analysis shows that there is little or no competition between the arachidonic and linoleic acid pathways, although they share the same enzymes.

SUBMITTER: Saccenti E

PROVIDER: S-EPMC4364740 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Strategies for individual phenotyping of linoleic and arachidonic acid metabolism using an oral glucose tolerance test.

Saccenti Edoardo E van Duynhoven John J Jacobs Doris M DM Smilde Age K AK Hoefsloot Huub C J HC

PloS one 20150318 3

The ability to restore homeostasis upon environmental challenges has been proposed as a measure for health. Metabolic profiling of plasma samples during the challenge response phase should offer a profound view on the flexibility of a phenotype to cope with daily stressors. Current data modeling approaches, however, struggle to extract biological descriptors from time-resolved metabolite profiles that are able to discriminate between different phenotypes. Thus, for the case of oxylipin responses ...[more]

PMID: 25786212

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Project description:BackgroundDiabetes is an increasingly important risk factor for ischemic stroke and worsens stroke prognosis. Yet a large proportion of stroke patients who are eventually diabetic are undiagnosed. Therefore, it is important to have sensitive assessment of unrecognized hyperglycaemia in stroke patients.DesignSecondary outcome analysis of a randomized controlled trial focussing on parameters of glucose metabolism and detection of diabetes and prediabetes in patients with acute ischemic stroke (AIS).MethodsA total of 130 consecutively admitted patients with AIS without previously known type 2 diabetes mellitus (T2DM) were screened for diabetes or prediabetes as part of secondary outcome analysis of a randomized controlled trial that tested lifestyle intervention to prevent post-stroke cognitive decline. Patients had the oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) measurements in the second week after stroke onset and after 1 year. The detection rates of diabetes and prediabetes based on the OGTT or HbA1c values were compared.ResultsBy any of the applied tests at the second week after stroke onset 62 of 130 patients (48%) had prediabetes or T2DM. Seventy-five patients had results from both tests available, the OGTT and HbA1c; according to the OGTT 40 (53.3%) patients had normal glucose metabolism, 33 (44%) had prediabetes, two (2.7%) T2DM. In 50 (66.7%) patients the HbA1c results were normal, 24 (32%) in the prediabetic and one (1.3%) in the diabetic range. The detection rate for disorders of glucose metabolism was 10% higher (absolute difference; relative difference 29%) with the OGTT compared with HbA1c. After 1 year the detection rate for prediabetes or T2DM was 7% higher with the OGTT (26% relative difference). The study intervention led to a more favourable evolution of glycemic status after 1 year.ConclusionThe OGTT is a more sensitive screening tool than HbA1c for the detection of previously unrecognized glycemic disorders in patients with acute stroke with an at least a 25% relative difference in detection rate. Therefore, an OGTT should be performed in all patients with stroke with no history of diabetes. Trial registration http://clinicaltrials.gov . Unique identifier: NCT01109836.

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Strategies for individual phenotyping of linoleic and arachidonic acid metabolism using an oral glucose tolerance test.

Publications

Strategies for individual phenotyping of linoleic and arachidonic acid metabolism using an oral glucose tolerance test.

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