The Relationship Between Serum Amino Acids And Multiple Metabolic Factors Such As Blood Sugar, Blood Lipids, Insulin And Changes In Serum Amino Acid Levels After Glucose Load In Type2Diabetes

Objective:The development of metabolomics facilitate analysis of various different chemical moieties that together form the metabolic complement of an organism. Precise detections of small molecules (such as amino acids, fatty acids, etc.) provide new, effective and highly reproducible means for metabolic diseases, especially for prediction of diabetes and quantitative assessment of insulin resistance.This method has profound meaning to understand the pathogenesis of diabetes, make early diagnosis and choose a better therapy. Previous studies qualitativly screen predictors of type2diabetes using metabolomics approach.This study focused on amino acids (a large number of studies have confirmed a strong predictor of diabetes) in type2diabetes using targeted LC-MS/MS.In addition,we explore the relationship between Serum amino acids and multiple metabolic factors such as blood sugar, blood lipids, insulin. Changes in serum amino acid levels along with glucose and insulin in type2diabetes provide more information to deep reveal physiological response after glucose load.Methods:1. Fasting blood samples were obtained from116healthy volunteers who enrolled in Gaoyou type2diabetes prediction, prevention and intervention study as control group. Physical and biochemical examinations were performed on these objects. Serum amino acids were measured using targeted LC-MS/MS.2. Fasting blood samples were obtained from151type2diabetes who enrolled in the department of endocrinology and metabolism of Jiangsu Province Hospital between January2012to March2014. physical and biochemical examinations, and the severity of carotid artery and artery of lower extremity atherosclerosis assessment were performed on these objects.31of the participants underwent a2-hour75g oral glucose tolerance test (OGTT) after a12-hour overnight fast. Blood samples were obtained before and after OGTT. Serum amino acids were measured using targeted LC-MS/MS.Results:l.Type2diabetes had higher serum Val、Leu、Ile levels than control (P<0.05). Tyr and Phe levels was no significant difference between two groups, but Tyr levels in type2diabetes had an apparent tendency to increase compared to control.2. Ile、Tyr levels in the satisfied group were higher than those in the non-satisfied group (P<0.05). Val、Ile、Phe levels were no significant difference between two groups.3.In control group, Serum Val、Leu、He、Tyr、Phe levels were positively correlated with DBP, but weren’t associated with SBP.There were positively correlation between Val、Leu、Ile、Tyr and TG.VaL、Leu、Ile were significantly negative associated with HDL-C. Besides negative associations were between Val, Leu and30-BG. Furthermore,Ile was positively correlated with FINS、2h-INS、HOMA-IR、HOMA-β and negatively associated with Matsuda index. Tyr was positively correlated with FINS、30min-INS、2h-INS、HOMA-IR、HOMA-βand negatively associated with Matsuda index.Val、Phe were positively correlated with2h-INS and negatively associated with Matsuda index. The result of multiple stepwise regression analysis showed that serum Val levels was more closely with TG、DBP、Matsuda index. Leu、 Ile were more closely with TG、DBP.Additionally, Tyr、Phe were more closely corelated with Matsuda index、DBP.4.In type2diabetes group, Serum Val、Leu、Ile、Tyr、Phe levels were positively correlated with BMI, but weren’t connected with DBP、SBP.Val、Leu、Ile and TG were positively correlated; Val、Leu、Ile、Phe and HDL-C were negatively correlated. There were negatively correlation between Ile、Tyr and HbAlc. Besides negative associations were between Ile、Phe and30-BG. Furthermore, Ile、Tyr were negatively correlated with2h-BG. Val、Leu、Ile、Tyr、Phe were significantly positive associated with FINS、30min-INS.2h-INS、HOMA-β and were significantly negative associated with Matsuda index. The result of multiple stepwise regression analysis showed that serum Val、Leu levels was more closely with BMI、HDL-C. While, Ile、tyr and Phe were more closely with BMI.5. Type2diabetes without AS group had higher serum Leu than type2diabetes with AS group(P<0.05). Val and Phe levels were no significant difference between two groups, but type2diabetes without AS group had an apparent tendency to increase compared to type2diabetes with AS group.6. Serum amino acid levels weren’t associated with R-IMT, L-IMT and M-IMT in whole group and satisfied group. However, branched chain amino acids were significantly negative related to R-IMT, L-IMT and M-IMT in the non-satisfied group.7. Amino acid levels were significantly decreased after75g glucose load.Conclusions:1、Between control and diabetes huge differences of serum amino acids concentrations are occurring. Type2diabetes had higher serum Val、Leu、He levels than control. Serum amino acid levels are closely related to multiple metabolic factors such as blood sugar, blood lipids, insulin, insulin resistance and Islet function in both groups. In combination with traditional evaluation indexes of insulin resistance and islet function, serum amino acids will provide more information for assessment of insulin resistance and islet function. Testing serum amino acids routinely will not only have a great clinical significance but also bring certain economic benefits2、Ile、Tyr levels in the satisfied group were higher than those in the non-satisfied group.Additionally, Branched-chain amino acids are negatively associated with R-IMT、L-IMT and M-IMT in the non-satisfied group.These results indicate serum amino acid levels can be used as biomarkers of monitoring glycemic control and can predict the risk of cardiovascular disease in patients with type2diabetes under the condition of unsatisfied blood glucose control. 3、The glucose load triggers a series of metabolic changes helping us further understanding of the pathogenesis of diabetes. Serum amino acid levels are significantly decreased after75g glucose load, suggesting that protein degradation decreased after the glucose load.