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-hour glucose) in the normal range with all-cause mortality among individuals without traditional risk factors. Methods Retrospective cohort study of US National Health and Nutrition Examination Survey in 1988-1994 and 1999-2018. Nonpregnant adults who had a measurement of 2-hour glucose, FPG, and HbA1c, and absence of traditional risk factors were included. Cox proportional hazard models were performed to examine the associations of normal FPG (n = 5793), normal HbA1c (n = 8179), and normal 2-hour glucose (n = 3404) with all-cause mortality. Results A significant association was found between 2-hour glucose within the normal range and all-cause mortality among those without traditional risk factors. Compared with participants with 2-hour glucose 80 mg/dL, participants with a higher normal 2-hour 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. Conclusion Among US adults without traditional risk factors, high normal 2-hour glucose level was positively associated with all-cause mortality. This result highlights the potential importance of maintaining a lower normal level of 2-hour glucose for preventing mortality in individuals who are conventionally considered to be cardiovascular healthy.