Lipidomic profiling of plasma free fatty acids in type-1 diabetes highlights specific changes in lipid metabolism

Abstract

Type-1 diabetes mellitus (T1DM) is associated with metabolic changes leading to alterations in glucose and lipid handling. While T1DM- associated effects on many major plasma lipids have been characterised, such effects on plasma free fatty acids (FFA) have not been fully examined. Using gas chromatography-mass spectrometry, we measured the plasma concentrations of FFA species in individuals with T1DM (n=44) and age/sex-matched healthy controls (n=44). Relationships between FFA species and various parameters were evaluated. Plasma concentrations of myristate (14:0), palmitoleate (16:1), palmitate (16:0), linoleate (18:2), oleate (18:1c9), cis-vaccenate (18:1c11), eicosapentaenoate (20:5), arachidonate (20:4) and docosahexanoate (22:6) were reduced in the T1DM group (p<0.0001 for all, except p=0.0020 for eicosapentaenoate and p=0.0068 for arachidonate); α-linolenate (18:3) and dihomo-γ- linolenate (20:3) concentrations were unchanged. Saturated/unsaturated FFA ratio, n-3/n-6 ratio, de novo lipogenesis index (palmitate (main lipogenesis product)/linoleate (only found in diet)) and elongase index (oleate/palmitoleate) were increased in the T1DM group (p=0.0166, p=0.0089, p<0.0001 and p=0.0008 respectively). The stearoyl-CoA desaturase 1 (SCD1) index 1 (palmitoleate/palmitate) and index 2 (oleate/stearate) were reduced in T1DM (p<0.0001 for all). The delta-(5)- desaturase (D5D) index (arachidonate/dihomo-γ-linolenate) was unchanged. Age and sex had no effect on plasma FFA concentrations in T1DM, while SCD1 index 1 was positively correlated (p=0.098) and elongase index negatively correlated with age (p=0.0363). HbA1c was negatively correlated with all plasma FFAs concentrations measured except α- linolenate and dihomo-γ-linolenate. Correlations were observed between plasma FFAs and cholesterol and HDL, but not LDL or diabetes duration. Collectively, these results aid our understanding of T1DM and its effects on lipid metabolism.