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

Endocrinol Diabetes Metab. 2021 Jan 4;4(2):e00213. doi: 10.1002/edm2.213. eCollection 2021 Apr.

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-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. Polyunsaturated PC(35:4) 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 35:4 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.

Trial registration: ClinicalTrials.gov NCT02888691.

Keywords: cardiovascular disease; dyslipidaemia; lipidomics; low carbohydrate diet; randomized trial; type 1 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Mass Index
  • Cholesterol, HDL / metabolism
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diet, Carbohydrate-Restricted*
  • Dyslipidemias / etiology
  • Dyslipidemias / metabolism
  • Female
  • Humans
  • Lipid Metabolism*
  • Lipidomics / methods
  • Male
  • Middle Aged
  • Phosphatidylcholines / metabolism
  • Sphingomyelins / metabolism
  • Time Factors

Substances

  • Cholesterol, HDL
  • Phosphatidylcholines
  • Sphingomyelins
  • polyene phosphatidylcholine

Associated data

  • ClinicalTrials.gov/NCT02888691