Plasma Lipid Profiling Shows Similar Associations with Prediabetes and Type 2 Diabetes

PLOS ONE, Dec 2019

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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Plasma Lipid Profiling Shows Similar Associations with Prediabetes and Type 2 Diabetes

et al. (2013) Plasma Lipid Profiling Shows Similar Associations with Prediabetes and Type 2 Diabetes. PLoS ONE 8(9): e74341. doi:10.1371/journal.pone.0074341 Plasma Lipid Profiling Shows Similar Associations with Prediabetes and Type 2 Diabetes Peter J. Meikle 0 1 Gerard Wong 0 1 Christopher K. Barlow 0 1 Jacquelyn M. Weir 0 1 Melissa A. Greeve 0 1 Gemma L. MacIntosh 0 1 Laura Almasy 0 1 Anthony G. Comuzzie 0 1 Michael C. Mahaney 0 1 Adam Kowalczyk 0 1 Izhac Haviv 0 1 Narelle Grantham 0 1 Dianna J. Magliano 0 1 Jeremy B. M. Jowett 0 1 Paul Zimmet 0 1 Joanne E. Curran 0 1 John Blangero 0 1 Jonathan Shaw 0 1 Clarissa Menezes Maya-Monteiro, Fundacao Oswaldo Cruz, Brazil 0 of America, 3 National ICT Australia (NICTA), University of Melbourne , Melbourne, Victoria , Australia 1 1 Baker IDI Heart and Diabetes Institute , Melbourne, Victoria , Australia , 2 Department of Genetics, Texas Biomedical Research Institute , San Antonio, Texas , United States 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. - Funding: This work was supported by funding from the Dairy Health and Nutrition Consortium, Australia, The National Health and Medical Research Council of Australia, the OIS Program of the Victorian Government, Australia and by Award Number 1R01DK088972-01 from the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, USA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the aforementioned funding bodies. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The AusDiab study co-coordinated by the Baker IDI Heart and Diabetes Institute, gratefully acknowledges the generous support given by: The National Health and Medical Research Council (NHMRC grant 233200), Australian Government Department of Health and Ageing, the 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 and sanofi-synthelabo. Also, for their invaluable contribution to the set-up and field activities of AusDiab, we are enormously grateful to A Allman, B Atkins, S Bennett, S Chadban, M de Courten, M Dalton, D Dunstan, T Dwyer, D Jolley, D McCarty, A Meehan, S Murray, P Phillips, C Reid, A Stewart, R Tapp, H Taylor, and F Wilson (Baker IDI Heart and Diabetes Institute). Data collection for the SAFHS was supported by grant P01 HL045522 from the National Institutes of Health (to JB). Additional work w (...truncated)


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Peter J. Meikle, Gerard Wong, Christopher K. Barlow, Jacquelyn M. Weir, Melissa A. Greeve, Gemma L. MacIntosh, Laura Almasy, Anthony G. Comuzzie, Michael C. Mahaney, Adam Kowalczyk, Izhac Haviv, Narelle Grantham, Dianna J. Magliano, Jeremy B. M. Jowett, Paul Zimmet, Joanne E. Curran, John Blangero, Jonathan Shaw. Plasma Lipid Profiling Shows Similar Associations with Prediabetes and Type 2 Diabetes, PLOS ONE, 2013, 9, DOI: 10.1371/journal.pone.0074341