Changes in the lipidome in type 1 diabetes following low carbohydrate diet: a randomized crossover trial

Aims/hypothesis: Lipid metabolism might be compromised in type 1 diabetes and the understanding of their physiology is critically important. This study aimed to compare the change in plasma lipid concentrations during carbohydrate dietary changes in individuals with type 1 diabetes and identify predictive biomarkers and early-stage pathophysiology for dyslipidaemia. We hypothesized that: (1) the lipidomics profiles before and after ingesting low or high carbohydrate diet for 12 weeks would be different; and (2) specific annotated lipid species would have significant associations with metabolic outcomes. Methods: Ten adults with type 1 diabetes (mean+/-SD: age 43.6+/-13.8 years, diabetes duration 24.5+/-13.4 years, BMI 24.9+/-2.1 kg/m2, HbA1c 57.67+/-2.6 mmol/mol) using insulin pumps participated in a randomized 2-period crossover study with a 12-week intervention period of low carbohydrate diet ( 250 g carbohydrates/day) respectively, separated by a 12-week washout period. A large-scale non-targeted lipidomics was performed with mass spectrometry for fasting plasma samples obtained before and after each diet intervention. Logitudinal lipid levels were analysed using linear mixed-effects models. Results: In total, 289 lipid species were identified from 14 major lipid classes (triacylglycerides, phosphatidylcholines, phosphatidylethanolamines, hexosyl-ceramide, sphingomyelins, lyso-phosphatidylcholines, ceramides, lactosyl-ceramide, lyso-phoshatidylethanolamine, free fatty acids, phosphatidylinositols, phosphatidylglycerols, phosphatidylserines and sulfatides). Comparing the two diets, 11 lipid species belonging to sphingomyelins, phosphatidylcholines and LPC(O-16:0) were changed. All the 11 lipid species were significantly elevated during low carbohydrate diet. Two lipid species were most differentiated between diets, namely SM(d36:1) (B+/-SE: 1.44+/-0.28, FDR = 0.010) and PC(P-36:4)/PC(O-36:5) (B+/-SE: 1.34+/-0.25, FDR = 0.009) species. Poly-unsaturated PC(35:4) was inversely associated with BMI and positively associated with HDL-cholesterol (p < 0.001). Conclusion/interpretation: Lipidome-wide outcome analysis of a randomized cross-over trial of individuals with type 1 diabetes following a low carbohydrate diet showed an increase in sphingomyelins and phosphatidylcholines which are thought to reduce dyslipidaemia. The poly-unsaturated phosphatidylcholine 35:4 was inversely associated with BMI and positively associated with HDL-cholesterol (p < 0.001). Results from this study warrant for more investigation on the long-term effect of PC(35:4) lipid-species in lipid homeostasis in type 1 diabetes. Trial registration Clinicaltrials.gov NCT02888691 Keywords Biomarker ∙ Cardiovascular disease ∙ Dyslipidaemia ∙ Lipidomics ∙ Low carbohydrate diet ∙ Randomized trial ∙ Type 1 diabetes.