Associations of glycemic measures in the normal range with all-cause mortality in the absence of traditional risk factors

Abstract Context The investigation of the association between blood glucose within normal range and all-cause mortality among individuals without traditional risk factors is limited. Objective To determine the associations of 3 glycemic measures (fasting plasma glucose [FPG], hemoglobin A1c [HbA1c], and 2-h glucose) in the normal range with all-cause mortality among individuals without traditional risk factors. Design Retrospective cohort study. Setting US National Health and Nutrition Examination Survey in 1988-1994 and 1999-2018. Participants Non-pregnant adults who had a measurement of 2-h glucose, FPG, and HbA1c, and absence of traditional risk factors were included. Main Outcome Measures Cox proportional hazard models were performed to examine the associations of normal FPG (n=5793), normal HbA1c (n=8179), and normal 2-h glucose (n=3404) with all-cause mortality. Results The significant association was found between 2-h glucose within the normal range and all-cause mortality among those without traditional risk factors. Compared to participants with 2-h glucose <80 mg/dL, participants with a higher normal 2-h glucose level had a higher risk of all-cause mortality (110-139 mg/dL: HR, 1.80 [95% CI, 1.03-3.15]). In the subgroup analysis, significant associations were also found among people aged ≥60 years and men. No significant associations were found between normal FPG and HbA1c levels and all-cause mortality. Conclusions Among US adults without traditional risk factors, high normal 2-h glucose level was positively associated with all-cause mortality. This result highlights the potential importance of maintaining a lower normal level of 2-h glucose for preventing mortality in individuals who are conventionally considered to be cardiovascular healthy.