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Plasma 1-deoxysphingolipids are predictive biomarkers for type 2 diabetes mellitus


Othman, Alaa; Saely, Christoph H; Muendlein, Axel; Vonbank, Alexander; Drexel, Heinz; von Eckardstein, Arnold; Hornemann, Thorsten (2015). Plasma 1-deoxysphingolipids are predictive biomarkers for type 2 diabetes mellitus. BMJ Open Diabetes Research and Care, 3(1):e000073.

Abstract

OBJECTIVE: Serine palmitoyltransferase (SPT) catalyzes the condensation of serine and palmitoyl coenzyme A, the first step in the de novo sphingolipid synthesis. Apart from these canonical substrates, SPT can also metabolize alanine and other acyl coenzyme As. This forms a spectrum of atypical sphingoid bases which are altered in the context of the metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM). We investigated whether atypical sphingolipids can be used as prospective markers to predict the incidence of T2DM.
RESEARCH DESIGN AND METHODS: Using liquid chromatography/mass spectrometry, we analyzed the sphingoid base profile in a prospective cohort with 339 individuals. All individuals were followed up for a period of 8 years.
RESULTS: Confirming earlier results, we found 1-deoxysphingolipids (1-deoxySLs) to be significantly elevated in patients with MetS, impaired fasting glucose, and T2DM. Patients who developed T2DM during the follow-up period (n=32) showed significantly higher 1-deoxySL levels at baseline compared with those who did not develop T2DM until the end of the study (n=70). 1-Deoxysphingosine levels were independent predictors for T2DM even after adjusting for glycated hemoglobin (standardized adjusted OR=2.1, CI 95% (1.19 to 3.71); p=0.010), MetS (standardized adjusted OR=1.97, CI 95% (1.13 to 3.43); p=0.017), and other risk factors such as age, sex, BMI, and lipid-lowering drugs. Similar results were observed for the 1-deoxysphinganine levels.
CONCLUSIONS: Our results support a novel role for 1-deoxySL as predictive biomarkers for the development of T2DM in risk patients and warrants further larger prospective trials in lower risk cohorts.

Abstract

OBJECTIVE: Serine palmitoyltransferase (SPT) catalyzes the condensation of serine and palmitoyl coenzyme A, the first step in the de novo sphingolipid synthesis. Apart from these canonical substrates, SPT can also metabolize alanine and other acyl coenzyme As. This forms a spectrum of atypical sphingoid bases which are altered in the context of the metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM). We investigated whether atypical sphingolipids can be used as prospective markers to predict the incidence of T2DM.
RESEARCH DESIGN AND METHODS: Using liquid chromatography/mass spectrometry, we analyzed the sphingoid base profile in a prospective cohort with 339 individuals. All individuals were followed up for a period of 8 years.
RESULTS: Confirming earlier results, we found 1-deoxysphingolipids (1-deoxySLs) to be significantly elevated in patients with MetS, impaired fasting glucose, and T2DM. Patients who developed T2DM during the follow-up period (n=32) showed significantly higher 1-deoxySL levels at baseline compared with those who did not develop T2DM until the end of the study (n=70). 1-Deoxysphingosine levels were independent predictors for T2DM even after adjusting for glycated hemoglobin (standardized adjusted OR=2.1, CI 95% (1.19 to 3.71); p=0.010), MetS (standardized adjusted OR=1.97, CI 95% (1.13 to 3.43); p=0.017), and other risk factors such as age, sex, BMI, and lipid-lowering drugs. Similar results were observed for the 1-deoxysphinganine levels.
CONCLUSIONS: Our results support a novel role for 1-deoxySL as predictive biomarkers for the development of T2DM in risk patients and warrants further larger prospective trials in lower risk cohorts.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Clinical Chemistry
Dewey Decimal Classification:610 Medicine & health
540 Chemistry
Language:English
Date:2015
Deposited On:08 Jul 2015 09:27
Last Modified:14 Aug 2017 12:32
Publisher:BMJ Publishing Group
ISSN:2052-4897
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1136/bmjdrc-2014-000073
PubMed ID:25815206

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