Plasma Lipidomic n-6 Polyunsaturated Fatty Acids and Type 2 Diabetes Risk in the EPIC-Potsdam Prospective Cohort Study

Abstract

OBJECTIVE Evidence on plasma n-6 polyunsaturated fatty acids (PUFAs) and type 2 diabetes risk is inconsistent. We examined the associations of lipid class–specific PUFA concentrations with type 2 diabetes risk. RESEARCH DESIGN AND METHODS In the prospective European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (nested case-cohort study: subcohort 1,084 participants, 536 participants with type 2 diabetes, median follow-up 6.5 years), we measured plasma 18:2, 20:3, and 20:4 concentrations in 12 lipid (sub)classes, likely reflecting the plasma concentrations of linoleic acid (18:2n-6), dihomo-γ-linolenic acid (20:3n-6), and arachidonic acid (20:4n-6). The Δ-5 desaturase (D5D) activity was estimated as the 20:4/20:3 ratio. Associations with diabetes were estimated with Cox proportional hazards models. RESULTS Higher concentrations of 18:2 were inversely associated with type 2 diabetes risk, particularly in lysophosphatidylcholines (hazard ratio [HR] per 1 SD 0.53; 95% CI 0.23–1.26) and monoacylglycerols (HR 0.59; 0.38–0.92). Higher concentrations of 20:3 in phospholipid classes phosphatidylcholines (HR 1.63; 1.23–2.14), phosphatidylethanolamines (HR 1.87; 1.32–2.65), and phosphatidylinositol (HR 1.40; 1.05–1.87); free fatty acids (HR 1.44; 1.10–1.90); and cholesteryl esters (HR 1.47; 1.09–1.98) were linked to higher type 2 diabetes incidence, and these associations remained statistically significant after correction for multiple testing. Higher 20:4 concentrations were not associated with risk. The estimated D5D activity in phospholipids and cholesteryl esters was associated with lower type 2 diabetes risk. Single nucleotide polymorphisms in the D5D-encoding FADS genes explained relatively high proportions of variation of estimated D5D activity in those lipid classes. CONCLUSIONS Plasma n-6 PUFAs were associated differently with type 2 diabetes, depending on fatty acid and the lipid class.

Quantified Metabolomics and Lipidomics Profiles Reveal Serum Metabolic Alterations and Distinguished Metabolites of Seven Chronic Metabolic Diseases

“…There is increasing evidence suggesting the close connection between insulin resistance and the onset of chronic metabolic diseases, including visceral adiposity, hypertension, hyperglycemia, dyslipidemia, and hyperuricemia. − TGs are reacylated by diglyceride acyltransferase from their corresponding DG species, and excessive levels of TGs serve as an indicator of lipotoxicity . The majority of FAs showed shared patterns among hypertension, hyperglycemia, and fatty liver (Figure F), which is consistent with previous studies. − Most lipids including cholesterol esters (CEs), sphingomyelins (SMs), hexosylceramides (HexCers), dihexaglycosylceramides (Hex2Cers), phosphatidylcholines (PCs), and phosphatidylethanolamines (PEs) only exhibited a significant and strong association with hypercholesterolemia (Figure G–I, Table S6). Ceramides (Cers) and phosphatidylinositols (PIs) showed shared associations with hypercholesterolemia and the other chronic metabolic diseases (Figure H,I).…”

Development and validation of a plasmalogen score as an independent modifiable marker of metabolic health: population based observational studies and a placebo-controlled cross-over study

“… 17 In the context of T2DM, increased levels of PE have been consistently reported. 18 , 44 , 45 , 46 Conversely, decreased levels of PE(P) plasmalogen have been linked to increased risk, particularly in impaired glucose tolerance. 18 , 39 , 47 Furthermore, in conditions such as CAD and Alzheimer's disease (AD) reduced plasmalogen levels, alongside an increase in–or negligible alterations in- PE, have been reported.…”