Changes in the lipidome in type 1 diabetes following low carbohydrate diet: Post-hoc analysis of a randomized crossover trial.

ABSTRACT

Aims: Lipid metabolism might be compromised in type 1 diabetes, and the understanding of lipid 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 links to early-stage dyslipidaemia. We hypothesized that (1) the lipidomic profiles after ingesting low or high carbohydrate diet for 12 weeks would be different; and (2) specific annotated lipid species could 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 57.6 ± 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 in fasting plasma samples obtained before and after each diet intervention. Longitudinal lipid levels were analysed using linear mixed-effects models. Results: In total, 289 lipid species were identified from 14 major lipid classes. Comparing the two diets, 11 lipid species belonging to sphingomyelins, phosphatidylcholines and LPC(O-160) were changed. All the 11 lipid species were significantly elevated during low carbohydrate diet. Two lipid species were most differentiated between diets, namely SM(d361) (ß ± SE 1.44 ± 0.28, FDR = 0.010) and PC(P-364)/PC(O-365) (ß ± SE 1.34 ± 0.25, FDR = 0.009) species. Polyunsaturated PC(354) was inversely associated with BMI and positively associated with HDL cholesterol (p < .001). Conclusion: Lipidome-wide outcome analysis of a randomized crossover 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 polyunsaturated phosphatidylcholine 354 was inversely associated with BMI and positively associated with HDL cholesterol (p < .001). Results from this study warrant for more investigation on the long-term effect of single lipid species in type 1 diabetes.