TY - JOUR

T1 - Changes in the lipidome in type 1 diabetes following low carbohydrate diet

T2 - Post-hoc analysis of a randomized crossover trial

AU - Al-Sari, Naba

AU - Schmidt, Signe

AU - Suvitaival, Tommi

AU - Kim, Min

AU - Trošt, Kajetan

AU - Ranjan, Ajenthen G.

AU - Christensen, Merete B.

AU - Overgaard, Anne J.

AU - Pociot, Flemming

AU - Nørgaard, Kirsten

AU - Legido-Quigley, Cristina

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - cardiovascular disease

KW - dyslipidaemia

KW - lipidomics

KW - low carbohydrate diet

KW - randomized trial

KW - type 1 diabetes

U2 - 10.1002/edm2.213

DO - 10.1002/edm2.213

M3 - Journal article

C2 - 33855215

AN - SCOPUS:85099025530

VL - 4

JO - Endocrinology, Diabetes and Metabolism

JF - Endocrinology, Diabetes and Metabolism

SN - 2398-9238

IS - 2

M1 - e00213

ER -