Lipidomic analysis has provided candidate lipid biomarkers for early diagnosis of type 2 diabetes and cardiovascular disease. While it is known that hyperlipidaemia (particularly hypertriglyceridaemia) is associated with gestational diabetes (GDM), few studies have investigated the association between specific lipid species and GDM. This study aimed to investigate whether changes in serum lipid species are associated with GDM.
Serum samples at fasting, 1-hour and 2-hour post-glucose load, of 175 pregnant women (mean age 29.6±4.7 years) were collected at 26-28 weeks’ gestation during oral glucose tolerance tests. 17 women in this cohort developed GDM according to the ADIPS 1998 criteria. Lipidomic analysis of 305 individual lipid species was performed on fasting serum samples, using liquid chromatography electrospray ionisation-tandem mass spectrometry and MultiQuant 2.1.1. Insulin was measured by ELISA. Mixed effects models and Spearman’s rank correlations were used to analyse the data. Two controls for each GDM patient were selected from the cohort, matched for age, ethnicity, vitamin D supplementation dose and pre-pregnancy BMI for comparison with the GDM.
Across the whole cohort, there were significant positive associations between fasting insulin and most triacylglycerols, diacyglycerols, and phosphatidylethanolamines (FDR adjusted p<0.05). Insulin also correlated with certain ceramides, sphingomyelins, and cholesterol esters. There were negative associations between insulin and di- and tri-hexosylceramides, lysoalkylphosphatidylcholines, and GM3 gangliosides. Associations were not found between lipid species and fasting glucose or HbA1c.
When compared to the matched controls, women with GDM had significantly lower circulating phosphatidylcholines (PC(34:0); PC(35:2); PC(36:0); PC 36:4 (a)), alkylphosphatidylcholines (PC(O-34:2); PC(O-38:4)), ceramides (Cer(d18:1/16:0)), di- and tri-hexosylceramides (Hex2Cer(d18:1/16:0); Hex2Cer(d18:1/18:0); Hex2Cer(d18:1/20:0); Hex2Cer(d18:1/22:0); Hex2Cer(d18:1/24:0); Hex3Cer(d18:1/18:0)), alkylphosphatidylethanolamines (PE(P-18:1/18:2); PE(P-18:1/22:4)), and sphingomyelins (SM(36:3); SM(38:2)) (p<0.01).
Results from this study demonstrate that in pregnant women, fasting insulin is associated with certain lipid species, especially triacylglycerols, diacyglycerols, and phosphatidylethanolamines and that GDM patients show dysregulation of lipid metabolism.