维吾尔族青少年发病的成人型糖尿病家系成员血清代谢组学研究

Serum metabonomic study of two Uyghur families with maturity-onset diabetes of the young

目的 研究2个维吾尔族青少年发病的成人型糖尿病（MODY）家系成员血清代谢产物变化的特点。方法收集到2个新疆喀什地区维吾尔族四代健在的MODY家系，成员共52名，分析其成员一般资料及血糖、血脂、血压等指标，运用核磁共振氢谱（1HNMR）对各成员血清代谢产物进行检测，对采集图谱进行数据预处理后，采用主成分分析法（PCA）进行数据解读。根据血糖、血压、体重指数（BMI）高低各分两组对代谢产物进行比较。通过Pearson相关系数显著性差异检测及二维谱技术确定各组间血清中的差异性代谢成分。结果家系成员中糖尿病组与非糖尿病组血液代谢产物比较，异亮氨酸、酪氨酸含量降低，仅．葡萄糖、β-葡萄糖含量增加，且差异均有统计学意义（均P〈0．05）。家系成员中高血压组与正常血压组血液代谢产物比较，柠檬酸、肌醇、1-甲基组氨酸及酪氨酸含量均显著降低（均P〈0．05）。正常BMI组与高BMI组血液代谢产物比较无显著差异。结论MODY家系成员中糖尿病和高血压患者体内三羧酸循环代谢紊乱，反映糖尿病患者体内肝糖原分解和肌糖原酵解下降，而高血压患者体内脂肪代谢受阻。

Objective To study the characteristics of serum metabolites in two Uyghur families with maturityonset diabetes of the young（MODY）. Methods Two MODY families were composed of four generations of Uyghur with 52 members collected from Kashgar region, Xinjiang Uyghur Autonomous Region. The general information, blood glucose and lipid levels, and blood pressure were analyzed. Using 1H nuclear magnetic resonance （ 1 HNMR ） spectroscopy, serum metabolites were measured for each subject. After having conducted data pretreatment on the spectrogram, orthogonal partial least squares diseriminant analysis （OPLS-DA） was used to interpret data. The subjects were divided into two groups according to blood glucose（ diabetes and non-diabetes） , blood pressure, body mass index （ BMI ） for comparing differences in the metabolites. The differences of serum metabolic components between two groups were determined using pearson correlation coefficients with significant difference detection and two-dimensional spectrum technology. Results Isoleucine and tyrosine levels in diabetes group were decreased significantly, while a-glucose and 13-glucose levels were increased significantly compared with non-diabetes group （ all P〈0.05 ）. Citrate, phaseomannite, 1 -methyl histidine, and tyrosine levels in hypertension group were all decreased significantly compared with normal blood pressure group（ all P〈0.05 ）. No significant metabonomic differences were observed between normal BMI group and high BMI group. Conclusions Metabonomic changes in diabetic patients from MODY families indicate that diabetic patients suffer from disordered tricarboxylic acid cycle （ TCA cycle ） metabolism, with reduced glycolysis of glycogen in liver and muscle. There exist the metabolic disorder in TCA cycle and obstruction of fat metabolism in patients with hypertension from the MODY families.