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 ~ =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.