Human Serum Metabonomic Analysis Reveals Progression Axes for Glucose Intolerance and Insulin Resistance Statuses

摘要

Understanding the metabolic basis of glucose intolerances and insulin resistance is essential to facilitateearly diagnosis, satisfactory therapies and personalized treatments of type 2 diabetes (T2DM). Here,we analyzed the serum metabolic variations from 231 human participants with normal glucose tolerance(NGT, n = 80, M/F = 34/46, mean age 53 ± 10 years), impaired glucose regulation (IGR, n = 77, M/F =33/44, mean age 51 ± 10 years) and T2DM (n = 74, M/F = 32/42, mean age 51 ± 9 years) to establishthe relationship between the serum metabolite compositions and the development of diabetes. Byusing the proton nuclear magnetic resonance spectroscopy in conjunction with the multivariate dataanalysis, we found that the development of both glucose intolerances and insulin resistances are closelycorrelated with the progressive changes of human serum metabonome. Compared with NGT subjects,the IGR and T2DM participants showed clear dysfunctions of choline metabolism, glucose metabolism,lipid and amino acid metabolisms, and disruptions of TCA cycle. The insulin resistance statuses wereclosely associated with the serum metabonomic changes in terms of glucose, fatty acid and protein/amino acid metabolisms. We also found greater metabonomic heterogeneity among the populationswith T2DM and high insulin resistance status. These findings provide useful information to bridge thegaps in our understandings to the metabolic alterations associated with the progression of glucoseintolerances and insulin resistance status.