School of Public Health, National University of Singapore, 16 Medical Drive MD3, Singapore 117597.
J Clin Endocrinol Metab. 2013 Jun;98(6):E1060-5. doi: 10.1210/jc.2012-4132. Epub 2013 Apr 30.
Metabolic profiling of small molecules offers a snapshot of physiological processes. To identify metabolic signatures associated with type 2 diabetes and impaired fasting glucose (IFG) beyond differences in glucose, we used mass spectrometry-based metabolic profiling.
Individuals attending an institutional health screen were enrolled. IFG (n = 24) was defined as fasting glucose (FG) of 6.1 to 6.9 mmol/L and 2-hour post glucose load <11.1 mmol/L or glycosylated hemoglobin <6.5%, type 2 diabetes (n = 27), FG ≥7.0 mmol/L, or 2-hour post glucose load ≥11.1 mmol/L, or glycosylated hemoglobin ≥6.5%, and healthy controls (n = 60), FG <6.1 mmol/L. Fasting serum metabolomes were profiled and compared using gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry.
Compared to healthy controls, those with IFG and type 2 diabetes had significantly raised fructose, α-hydroxybutyrate, alanine, proline, phenylalanine, glutamine, branched-chain amino acids (leucine, isoleucine, and valine), low carbon number lipids (myristic, palmitic, and stearic acid), and significantly reduced pyroglutamic acid, glycerophospohlipids, and sphingomyelins, even after adjusting for age, gender, and body mass index.
Using 2 highly sensitive metabolomic techniques, we report distinct serum profile change of a wide range of metabolites from healthy persons to type 2 diabetes mellitus. Apart from glucose, IFG and diabetes mellitus are characterized by abnormalities in amino acid, fatty acids, glycerophospholipids, and sphingomyelin metabolism. These early broad-spectrum metabolic changes emphasize the complex abnormalities present in a disease defined mainly by elevated blood glucose levels.
小分子的代谢组学分析提供了生理过程的快照。为了鉴定与 2 型糖尿病和空腹血糖受损（IFG）相关的代谢特征，我们采用基于质谱的代谢组学分析方法。
我们招募了参加机构健康筛查的个体。IFG（n=24）定义为空腹血糖（FG）为 6.1 至 6.9mmol/L，2 小时后血糖负荷<11.1mmol/L 或糖化血红蛋白<6.5%，2 型糖尿病（n=27）定义为 FG≥7.0mmol/L，或 2 小时后血糖负荷≥11.1mmol/L，或糖化血红蛋白≥6.5%，健康对照组（n=60）定义为 FG<6.1mmol/L。使用气相色谱/质谱和液相色谱/质谱对空腹血清代谢组进行分析和比较。
与健康对照组相比，IFG 和 2 型糖尿病患者的果糖、α-羟丁酸、丙氨酸、脯氨酸、苯丙氨酸、谷氨酰胺、支链氨基酸（亮氨酸、异亮氨酸和缬氨酸）、低碳数脂质（肉豆蔻酸、棕榈酸和硬脂酸）显著升高，而 pyroglutamic 酸、甘油磷酸脂和神经鞘磷脂显著降低，即使在调整年龄、性别和体重指数后也是如此。
我们使用 2 种高灵敏度的代谢组学技术，报告了从健康个体到 2 型糖尿病患者的广泛代谢物血清谱的明显变化。除了葡萄糖之外，IFG 和糖尿病还表现为氨基酸、脂肪酸、甘油磷脂和神经鞘磷脂代谢异常。这些早期的广谱代谢变化强调了主要由血糖升高定义的疾病中存在的复杂异常。
