Changes in the lipidome in type 1 diabetes following low carbohydrate diet: a randomized crossover trial
Authors: Al-Sari Naba , Schmidt Signe , Suvitaival Tommi , Kim Min , Trošt Kajetan , Ranjan Ajenthen G. , Christensen Merete B. , Overgaard Anne Julie , Pociot Flemming , Nørgaard Kirsten , Legido-Quigley Cristina 
Published: September 2020

AbstractAims/hypothesisLipid 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.MethodsTen 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 57.6±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 (< 100 g carbohydrates/day) or high 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.ResultsIn 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) (β±SE: 1.44±0.28, FDR = 0.010) and PC(P-36:4)/PC(O-36:5) (β±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/interpretationLipidome-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 registrationClinicaltrials.govNCT02888691Research in contextWhat is already known about this subject?Individuals with type 1 diabetes have an increased rate of cardiovascular disease for which dyslipidaemia is a major risk factor.Dysregulated lipid metabolism is recognized as an established risk factor in cardiovascular diseases.What is the key question?Which specific circulating lipid species are changed after 12 weeks of low- and –high carbohydrate diet and do they reflect dyslipidemia risk?What are the new findings?Plasma from individuals with type 1 diabetes showed a significant increase in phosphatidylcholine and sphingomyelin lipid species during low carbohydrate diet (n=11 lipid species).Poly-unsaturated phosphatidylcholine 35:4 was inversely associated with BMI and positively associated with HDL-cholesterol (p < 0.001).How might this impact on clinical practice in the foreseeable future?This study demonstrates that very-long-chain phosphatidylcholines and sphingomyelins elevates substantially with diet in individuals with type 1 diabetes following low carbohydrate diet. This points to a need for more specific dietary guidelines regarding fat intake to support individuals with type 1 diabetes. Lipidomics could be used to monitoring the lipid intake, thereby guiding the person to consume ‘good’ lipids that could prevent dyslipidemia.