Department of Endocrinology and Metabolism, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Shanghai Key Laboratory of Diabetes, The Metabolic Diseases Biobank, Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Acta Pharmacol Sin. 2019 Feb;40(2):216-221. doi: 10.1038/s41401-018-0018-6. Epub 2018 May 17.
There is evidence that post-load/post-meal hyperglycemia is a stronger risk factor for cardiovascular disease than fasting hyperglycemia. The underlying mechanism remains to be elucidated. The current study aimed to compare the metabolic profiles of post-load hyperglycemia and fasting hyperglycemia. All subjects received an oral glucose tolerance test (OGTT) and were stratified into fasting hyperglycemia (FH) or post-load hyperglycemia (PH). Forty-six (FH, n = 23; PH, n = 23) and 40 patients (FH, n = 20; PH, n = 20) were recruited as the exploratory and the validation set, respectively, and underwent metabolic profiling. Eighty-seven subjects including normal controls (NC: n = 36; FH: n = 22; PH: n = 29) were additionally enrolled and assayed with enzyme-linked immunosorbent assay (ELISA). In the exploratory set, 10 metabolites were selected as differential metabolites of PH (vs. FH). Of them, mannose and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) were confirmed in the validation set to be significantly higher in FH than in PH. In the 87 subjects measured with ELISA, FH had numerically higher mannose (466.0 ± 179.3 vs. 390.1 ± 140.2 pg/ml) and AICAR (523.5 ± 164.8 vs. 512.1 ± 186.0 pg/ml) than did PH. In the pooled dataset comprising 173 subjects, mannose was independently associated with FPG (β = 0.151, P = 0.035) and HOMA-IR (β = 0.160, P = 0.026), respectively. The associations of AICAR with biochemical parameters did not reach statistical significance. FH and PH exhibited distinct metabolic profiles. The perturbation of mannose may be involved in the pathophysiologic disturbances in diabetes.
有证据表明，餐后/餐后脑血糖升高是心血管疾病的一个比空腹高血糖更强的危险因素。其潜在机制仍有待阐明。本研究旨在比较餐后高血糖和空腹高血糖的代谢特征。所有受试者均接受口服葡萄糖耐量试验（OGTT），并按空腹高血糖（FH）或餐后高血糖（PH）进行分层。分别纳入 46 例（FH，n=23；PH，n=23）和 40 例患者（FH，n=20；PH，n=20）作为探索性和验证性队列，并进行代谢组学分析。另外还纳入了 87 例受试者，包括正常对照组（NC：n=36；FH：n=22；PH：n=29），并进行酶联免疫吸附测定（ELISA）检测。在探索性队列中，选择了 10 种代谢物作为 PH（与 FH 相比）的差异代谢物。其中，甘露糖和 5-氨基咪唑-4-甲酰胺核糖核苷酸（AICAR）在验证性队列中被证实明显高于 FH。在 87 例用 ELISA 检测的受试者中，FH 的甘露糖（466.0±179.3 比 390.1±140.2 pg/ml）和 AICAR（523.5±164.8 比 512.1±186.0 pg/ml）数值更高。在包括 173 例受试者的综合数据集，甘露糖与 FPG（β=0.151，P=0.035）和 HOMA-IR（β=0.160，P=0.026）均独立相关。AICAR 与生化参数的相关性没有达到统计学意义。FH 和 PH 表现出明显不同的代谢特征。甘露糖的紊乱可能与糖尿病的病理生理紊乱有关。
