Elsevier

Metabolism

Volume 78, January 2018, Pages 1-12
Metabolism

Clinical Science
Lipidome as a predictive tool in progression to type 2 diabetes in Finnish men

https://doi.org/10.1016/j.metabol.2017.08.014Get rights and content
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Abstract

Background

There is a need for early markers to track and predict the development of type 2 diabetes mellitus (T2DM) from the state of normal glucose tolerance through prediabetes. In this study we tested whether the plasma molecular lipidome has biomarker potential to predicting the onset of T2DM.

Methods

We applied global lipidomic profiling on plasma samples from well-phenotyped men (107 cases, 216 controls) participating in the longitudinal METSIM study at baseline and at five-year follow-up. To validate the lipid markers, an additional study with a representative sample of adult male population (n = 631) was also conducted. A total of 277 plasma lipids were analyzed using the lipidomics platform based on ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry. Lipids with the highest predictive power for the development of T2DM were computationally selected, validated and compared to standard risk models without lipids.

Results

A persistent lipid signature with higher levels of triacylglycerols and diacyl-phospholipids as well as lower levels of alkylacyl phosphatidylcholines was observed in progressors to T2DM. Lysophosphatidylcholine acyl C18:2 (LysoPC(18:2)), phosphatidylcholines PC(32:1), PC(34:2e) and PC(36:1), and triacylglycerol TG(17:1/18:1/18:2) were selected to the full model that included metabolic risk factors and FINDRISC variables. When further adjusting for BMI and age, these lipids had respective odds ratios of 0.32, 2.4, 0.50, 2.2 and 0.31 (all p < 0.05) for progression to T2DM. The independently-validated predictive power improved in all pairwise comparisons between the lipid model and the respective standard risk model without the lipids (integrated discrimination improvement IDI > 0; p < 0.05). Notably, the lipid models remained predictive of the development of T2DM in the fasting plasma glucose-matched subset of the validation study.

Conclusion

This study indicates that a lipid signature characteristic of T2DM is present years before the diagnosis and improves prediction of progression to T2DM. Molecular lipid biomarkers were shown to have predictive power also in a high-risk group, where standard risk factors are not helpful at distinguishing progressors from non-progressors.

Abbreviations

2HPG
2-hour plasma glucose
ALT
alanine aminotransferase
AUC
area under curve
Cer
ceramide
ChoE
cholesterol ester
FPG
fasting plasma glucose
FINDRISC
Finnish diabetes risk score
hs-CRP
high-sensitivity C-reactive protein
IDI
integrated discrimination improvement
IFG
impaired fasting glucose
IGT
impaired glucose tolerance
LysoPC
lysophosphatidylcholine
LysoPE
lysophosphatidylethanolamine
NAFLD
non-alcoholic fatty liver disease
NGT
normal glucose tolerance
OGTT
oral glucose tolerance test
PC
diacyl phosphatidylcholine
PCe
alkylacyl phosphatidylcholine
PE
phosphatidylethanolamine
PEe
alkylacyl phosphatidylethanolamine
PL
glycerophospholipid
ROC
receiver operating characteristic
SM
sphingomyelin
TG
triacylglycerol
UPLC-QTOFMS
ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry

Keywords

Lipidomics
Mass-spectrometry
METSIM study
Plasma profiling
Type 2 diabetes mellitus

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Shared senior authorship.