Metabolic perturbations of post-load hyperglycemia vs. fasting hyperglycemia

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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.

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This work was funded by the National Natural Science Foundation of China (81300666), Natural Science Foundation of Shanghai (17ZR1421300), the Shanghai Municipal Education Commission—Gaofeng Clinical Medicine Grant Support (20161430), and the innovation foundation of translational medicine of Shanghai Jiao Tong University School of Medicine and Shanghai SJTUSM Biobank (15ZH4006). We would like to thank all of the involved clinicians, nurses, and technicians at each of the participating centers for dedicating their time and skill to the completion of this study.

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J.-y.L., J.-h.P. and J.Z. contributed to study design, data analysis, and writing the paper. Y.-n.Z. contributed to data analysis. W.Z., X.-x.H. and L.-w.Y. contributed to conduction of study and data collection. X.-j.M. contributed to study design, data analysis, and interpretation of data. Y.-q.B. and W.-p.J. contributed to interpretation of data and revision of the manuscript.

Correspondence to Xiao-jing Ma or Jian Zhou.

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  • Type 2 diabetes
  • insulin resistance
  • insulin secretion
  • metabolomics