Context: Insulin resistance (IR) remained a global health challenge. Lipidomics offers a unique opportunity to identify biomarkers; a key step towards understanding mechanisms of IR associated with abnormal lipid metabolism.

Objective: To determine whether plasma lipid species are associated with indices of insulin resistance and to evaluate the plasma lipidome response to an OGTT.

Design and Setting: Community based cross-sectional

Participants and sample: Plasma samples (collected at 0 and 120 min during an OGTT) from non-obese, young adults aged between 18-34 years (n = 246) were analysed using liquid chromatography tandem mass spectrometry.

Main outcome measures: Using linear models (controlling for age, sex, BMI, total cholesterol, HDL-cholesterol and triglycerides), the associations between indices of insulin resistance and individual lipid species or changes in lipid levels during an OGTT were tested.

Results: Some (213) and (199) lipid species associate with HOMA-IR and insulin AUC respectively. Alkylphosphatidylcholine (10), alkenylphosphatidylcholine (23) and alkylphosphatidylethanolamine (6) species were associated with insulin AUC in men only. Species of phosphatidylcholine (7) and sphingomyelin (5) were associated in women only. In response to an oral glucose tolerance test, a perturbation in the plasma lipidome, particularly in acylcarnitine species was observed; and the changes in many lipid species were associated with insulin AUC.

Conclusions: The plasma lipidome and changes in lipid levels during an OGTT were associated with indices of insulin resistance. These findings underlie the involvement of molecular lipid species in the pathogenesis of insulin resistance and possibly crosstalk between insulin resistance and sex-specific regulation of lipid metabolism.