Lower-than-normal glycemic levels to achieve optimal reduction of diabetes risk among individuals with prediabetes: A prospective cohort study.

AIMS/HYPOTHESIS: To determine whether lower than currently accepted glycemic levels could lead to optimal risk reduction of incident diabetes among individuals with prediabetes.

METHODS: We enrolled 9903 individuals with prediabetes and 16,902 individuals with normoglycemia from a prospective cohort participating health check-ups between 2006 and 2017. While classifying fasting glucose into <5.0, 5.0-5.5, and 5.6-6.9 mmol/L and postprandial glucose into <6.7, 6.7-7.7, and 7.8-11.0 mmol/L, we grouped fasting/postprandial glucose into five categories (<5.0/<6.7, <5.0/6.7-7.7, 5.0-5.5/<6.7, 5.0-5.5/6.7-7.7 mmol/L, 5.6-6.9/7.8-11.0 mmol/L). The primary outcome was incident diabetes.

RESULTS: In individuals with prediabetes, the presence of a baseline fasting glucose <5.0 mmol/L or a postprandial glucose <6.7 mmol/L led to a greater risk reduction of incident diabetes with hazard ratios of 0.34 (95% confidence interval, 0.27-0.42) and 0.47 (0.41-0.54), respectively, relative to a fasting glucose 5.6-6.9 mmol/L and a postprandial glucose 7.8-11.0 mmol/L. For individuals with prediabetes having fasting/postprandial glucose <5.0/<6.7 mmol/L, the incidence of 6.4 (4.7-8.8) per 1000 person-years corresponded to that of 5.8 (4.2-8.0) per 1000 person-years for individuals with normoglycemia having 5.0-5.5/6.7-7.7 mmol/L.

CONCLUSIONS/INTERPRETATION: Given that lower-than-normal glycemic levels were plausible for optimal risk reduction of diabetes, stringent glycemic management could be beneficial for diabetes prevention among individuals with prediabetes.