期刊
PLOS ONE
卷 8, 期 9, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0074341
关键词
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资金
- Dairy Health and Nutrition Consortium, Australia
- National Health and Medical Research Council of Australia
- OIS Program of the Victorian Government, Australia
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, USA [1R01DK088972-01]
- National Health and Medical Research Council (NHMRC) [233200]
- Australian Government Department of Health and Ageing
- Dairy Health and Nutrition Consortium
- Abbott Australasia Pty Ltd
- Alphapharm Pty Ltd
- AstraZeneca
- Bristol-Myers Squibb
- City Health Centre-Diabetes Service-Canberra
- Department of Health and Community Services - Northern Territory
- Department of Health and Human Services - Tasmania
- Department of Health - New South Wales
- Department of Health - Western Australia
- Department of Health - South Australia
- Department of Human Services - Victoria
- Diabetes Australia
- Diabetes Australia Northern Territory
- Eli Lilly Australia
- Estate of the Late Edward Wilson
- GlaxoSmithKline
- Jack Brockhoff Foundation
- Janssen-Cilag
- Kidney Health Australia
- Marian FH Flack Trust
- Menzies Research Institute
- Merck Sharp Dohme
- Novartis Pharmaceuticals
- Novo Nordisk Pharmaceuticals
- Pfizer Pty Ltd
- Pratt Foundation
- Queensland Health
- Roche Diagnostics Australia
- Royal Prince Alfred Hospital, Sydney
- Sanofi Aventis
- sanofi-synthelabo
- National Institutes of Health [P01 HL045522, R01 DK082610, R01 DK079169, R01 HL091035]
- National Center for Research Resources of the National Institutes of Health [C06 RR013556, C06 RR017515]
The relationship between lipid metabolism with prediabetes (impaired fasting glucose and impaired glucose tolerance) and type 2 diabetes mellitus is poorly defined. We hypothesized that a lipidomic analysis of plasma lipids might improve the understanding of this relationship. We performed lipidomic analysis measuring 259 individual lipid species, including sphingolipids, phospholipids, glycerolipids and cholesterol esters, on fasting plasma from 117 type 2 diabetes, 64 prediabetes and 170 normal glucose tolerant participants in the Australian Diabetes, Obesity and Lifestyle Study (AusDiab) then validated our findings on 1076 individuals from the San Antonio Family Heart Study (SAFHS). Logistic regression analysis of identified associations with type 2 diabetes (135 lipids) and prediabetes (134 lipids), after adjusting for multiple covariates. In addition to the expected associations with diacylglycerol, triacylglycerol and cholesterol esters, type 2 diabetes and prediabetes were positively associated with ceramide, and its precursor dihydroceramide, along with phosphatidylethanolamine, phosphatidylglycerol and phosphatidylinositol. Significant negative associations were observed with the ether-linked phospholipids alkylphosphatidylcholine and alkenylphosphatidylcholine. Most of the significant associations in the AusDiab cohort (90%) were subsequently validated in the SAFHS cohort. The aberration of the plasma lipidome associated with type 2 diabetes is clearly present in prediabetes, prior to the onset of type 2 diabetes. Lipid classes and species associated with type 2 diabetes provide support for a number of existing paradigms of dyslipidemia and suggest new avenues of investigation.
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