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Aims: Previous studies showed that serum 1,5-anhydroglucitol (1,5-AG) levels are significantly reduced in patients with diabetes mellitus (DM). However, it remains unclear how 1,5-AG levels acutely change in response to a glucose load. This study explored acute changes in 1,5-AG levels after a glucose load and the related influencing factors in individuals with differing degrees of glucose tolerance. Methods: A total of 681 participants (353 without DM and 328 with DM) without a prior history of DM were enrolled. All participants underwent an oral glucose tolerance test. Fasting and postload (30, 60, 120, and 180 min) levels of plasma glucose, serum 1,5-AG, and insulin were measured. Results: In all participant groups, serum 1,5-AG levels were slightly elevated after a glucose load and reached peak values at 120 min after loading (all P < 0.05). Regression analysis showed that body weight was negatively associated with the difference between peak and baseline 1,5-AG levels (Δ1,5-AG, standardized β = −0.119, P < 0.01). A strong and positive association between 1,5-AG and Δ1,5-AG was also found independent of other confounding factors (standardized β = 0.376, P < 0.01). The ratio of the Δ1,5-AG to the 1,5-AG was higher in DM patients (7.3% [3.4-11.5%]) than in those without DM (6.2% [3.6-9.2%]). Conclusions: In contrast to the established decline in 1,5-AG levels with long-term hyperglycemia, the present study showed that serum 1,5-AG levels slightly increased by 6-7% after a glucose load. Further studies in different 1,5-AG transport models are needed to investigate the relevant metabolic pathways. [ABSTRACT FROM AUTHOR]