Jingya Ye1, Xuan Ye1, Wanzi Jiang1, Chenyan Lu1, Xiaomei Geng1, Chenxi Zhao1, Yizhe Ma1, Panpan Yang1, Sin Man Lam2, Guanghou Shui2, Tao Yang1, John Zhong Li3, Yingyun Gong4, Zhenzhen Fu5, Hongwen Zhou6. 1. Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), Nanjing, Jiangsu, China. 2. Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China. 3. Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China. 4. Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), Nanjing, Jiangsu, China. Electronic address: gongyingyun@126.com. 5. Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), Nanjing, Jiangsu, China. Electronic address: zhenzhen1127@foxmail.com. 6. Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), Nanjing, Jiangsu, China. Electronic address: drhongwenzhou@njmu.edu.cn.
Abstract
AIMS: Sphingolipids(SPs) and their substrates and constituents, fatty acids (FAs), are implicated in the pathogenesis of various metabolic diseases associated. This study aimed to systematically investigate the associations between serum sphingolipids and insulin sensitivity as well as insulin secretion. METHODS: We conducted a lipidomics evaluation of molecularly distinct SPs in the serum of 86 consecutive Chinese adults using LC/MS. The glucose infusion rate over 30 min (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. RESULTS: Total and subspecies of serum SMs and globotriaosyl ceramides (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 (areas under the curve > 0.80) based on GIR30 as standard diagnostic criteria, and (SM/Cer)/(BMI*LDLc) areas under the curve = 0.93) is the best. CONCLUSIONS: These results provide novel associations between serum sphingolipid between insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp and identify two specific SPs that may represent prognostic biomarkers for insulin sensitivity.
AIMS: Sphingolipids(SPs) and their substrates and constituents, fatty acids (FAs), are implicated in the pathogenesis of various metabolic diseases associated. This study aimed to systematically investigate the associations between serum sphingolipids and insulin sensitivity as well as insulin secretion. METHODS: We conducted a lipidomics evaluation of molecularly distinct SPs in the serum of 86 consecutive Chinese adults using LC/MS. The glucose infusion rate over 30 min (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. RESULTS: Total and subspecies of serum SMs and globotriaosyl ceramides (Gb3s) were positively related to GIR30, free FAs (FFA 16:1, FFA20:4), some long chain GM3 and complex ceramideGluCers 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 (areas under the curve > 0.80) based on GIR30 as standard diagnostic criteria, and (SM/Cer)/(BMI*LDLc) areas under the curve = 0.93) is the best. CONCLUSIONS: These results provide novel associations between serum sphingolipid between insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp and identify two specific SPs that may represent prognostic biomarkers for insulin sensitivity.