Target lipidomics reveals associations between serum sphingolipids and insulin sensitivity by the glucose clamp

Background This study aimed to systematically investigate the associations between serum sphingolipids and insulin sensitivity as well as insulin secretion. This study also aimed to reveal potential predictors for insulin sensitivity or give perceptive insight into disease processes. Methods We conducted a lipidomics evaluation of molecularly distinct SPs in the serum of 86 consecutive Chinese adults with or without obesity and diabetes using electrospray ionization mass spectrometry coupled with liquid chromatography. The GIR30 was measured under steady conditions to assess insulin sensitivity by the gold standard hyperinsulinemic-euglycemic clamp. We created the ROC curves to detect the serum SMs diagnostic value and establish the diagnosis of insulin sensitivity. Results Differential correlation network analysis illustrated correlations amongst lipids, insulin sensitivity, insulin secretion and other clinical indexes. Total and subspecies of serum SMs and globotriaosylceramides (Gb3s) were positively related to GIR30, free FAs (FFA 16:1, FFA20:4), some long chain GM3 and complex ceramide GluCers showed strong negative correlations with GIR30. Notably, ROC curves showed that SM/Cer and SM d18:0/26:0 may be good serum lipid predictors of diagnostic indicators of insulin sensitivity close to conventional clinical indexes such as 1/HOMA-IR (all areas under the curve >0.80) based on GIR30 as standard diagnostic criteria. Conclusions These results provide novel associations between serum sphingolipid between insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp. We further identify two specific SPs that may represent prognostic biomarkers for insulin sensitivity. * SP : sphingolipid SM : sphingomyelin GM3 : sphingosine FAs : fatty acids GluCers : Glu-ceramides LacCers : Lac-ceramides GIR30 : glucose infusion rate over 30 minutes FPIR : first-phase insulin release IVGTT : intravenous glucose tolerance test ROC : receiver operating characteristic IR : insulin resistance LC-MS : liquid chromatography-mass spectrometry QUICKI : quantitative insulin sensitivity check index GDR : glucose disposal M : metabolizable glucose TC : total cholesterol TG : triglyceride LDL-c : LDL-cholesterol HDL-c : HDL-cholesterol ALT : alanine transaminase AST : aspartate transaminase Gb3 : globotriaosylceramides CerS : ceramide synthase SM/Cer : ratio of total serum SMs and Cers.