The identification of metabolic pathways and the core metabolites provide novel molecular targets for the prevention and treatment of diseases. Diabetes is often accompanied with multiple metabolic disorders including hyperglycemia and dyslipidemia. Analysis of the variances of plasma metabolites is critical for identifying potential therapeutic targets for diabetes. In the current study, non-diabetic subjects with normal glucose tolerance and diabetics (age 40–60 years; n = 42 per group) were selected and plasma samples were analyzed by GC–MS for various metabolites profiling followed by network analysis. Our study identified 24 differential metabolites that were mainly enriched in protein synthesis, lipid and amino acid metabolism. Furthermore, we applied the correlation network analysis on these differential metabolites in fatty acid and amino acid metabolism and identified glycerol, alanine and serine as the hub metabolites in diabetic group. In addition, we measured the activities of enzymes in gluconeogenesis and amino acid metabolism and found significant higher activities of fructose 1,6-bisphosphatase, pyruvate carboxylase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase in diabetic patients. In contrast, the enzyme activities of glycolysis pathway (e.g., hexokinase, phosphofructokinase and pyruvate kinase) and TCA cycle (e.g., isocitrate dehydrogenase, succinate dehydrogenase, fumarate hydratase and malate dehydrogenase) were reduced in diabetes. Together, our studies showed that the linoleic acid and amino acid metabolism were the most affected metabolic pathways and glycerol, alanine and serine could play critical role in diabetes. The integration of network analysis and metabolic data could provide novel molecular targets or biomarkers for diabetes.

代谢途径和核心代谢产物的鉴定为疾病的预防和治疗提供了新的分子靶标。糖尿病经常伴有多种代谢紊乱，包括高血糖症和血脂异常。血浆代谢物变化的分析对于确定糖尿病的潜在治疗靶点至关重要。在本研究中，葡萄糖耐量和糖尿病正常的非糖尿病受试者（年龄40-60岁；n 每组= 42），并通过GC-MS分析血浆样品的各种代谢物谱，然后进行网络分析。我们的研究确定了24种差异代谢产物，这些代谢产物主要富含蛋白质合成，脂质和氨基酸代谢。此外，我们对脂肪酸和氨基酸代谢中的这些差异代谢物进行了相关网络分析，并确定了甘油，丙氨酸和丝氨酸是糖尿病组的中枢代谢产物。此外，我们测量了糖异生和氨基酸代谢中酶的活性，发现糖尿病患者果糖1,6-双磷酸酶，丙酮酸羧化酶，乳酸脱氢酶，天冬氨酸转氨酶和丙氨酸转氨酶的活性明显更高。相反，糖酵解途径的酶活性（例如，己糖激酶，糖尿病患者的果糖磷酸激酶和丙酮酸激酶）和TCA周期（例如异柠檬酸脱氢酶，琥珀酸脱氢酶，富马酸水合酶和苹果酸脱氢酶）降低。总之，我们的研究表明，亚油酸和氨基酸代谢是受影响最大的代谢途径，甘油，丙氨酸和丝氨酸可能在糖尿病中起关键作用。网络分析和代谢数据的整合可以为糖尿病提供新的分子靶标或生物标志物。丙氨酸和丝氨酸可能在糖尿病中起关键作用。网络分析和代谢数据的整合可以为糖尿病提供新的分子靶标或生物标志物。丙氨酸和丝氨酸可能在糖尿病中起关键作用。网络分析和代谢数据的整合可以为糖尿病提供新的分子靶标或生物标志物。