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

Abstract

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.

Efficacy of nutritional interventions to lower circulating ceramides in young adults: FRUVEDomic pilot study

“…In support of our findings, Meikle et al. (2013) did not observe a relationship between circulating C16:0 ceramide and type 2 diabetes. The ability of C16:0 ceramide to antagonize insulin action may be reliant upon the intracellular tissue concentration of this sphingolipid which was not characterized in our investigation.…”

“…2013), and circulating C24:0 ceramide is inversely related to insulin‐stimulated glucose disposal in humans (Meikle et al. 2013). High dietary intake of saturated palmitic acid can increase C24:0 ceramide accrual (Larsen and Tennagels 2014).…”

“…Recent evidence suggests that nonglycosylated ceramides are stronger circulating biomarkers for diabetes or prediabetes in adults as compared with GlcCer or LacCer (Meikle et al. 2013). Nevertheless, both nonglycosylated ceramides and GlcCer have been implicated in the pathogenesis of insulin resistance at the cellular level (Chavez et al.…”

“…2013; Meikle et al. 2013), however the potential for dietary recommendations to lower ceramide levels in humans has been underexplored.…”

Specific roles of phosphatidylglycerols in hosts and microbes

“…PG levels rise in obesityassociated fatty liver disease (1), type-II diabetes (2), breast cancer (3) and perhaps other still to be defined conditions. In the present paper, we will concentrate on specific features of PGs to review our present knowledge on specific roles and properties of this unique phospholipid class (figure 1).…”