Prediabetes Phenotypes and All-Cause or Cardiovascular Mortality: Evidence from a Population-Based Study

Objectives: Fasting plasma glucose (FPG), glycated hemoglobin A_1C (HbA_1C), and 2-hour post-load plasma glucose (2h PG) are all currently used to define prediabetes. We aimed to determine whether a higher number of prediabetes defects corresponds to an increased all-cause and cardiovascular disease (CVD) mortality.

Methods: Individuals with prediabetes and available information on FPG, HbA_1C, 2h PG, and mortality data were derived from the 2005 - 2016 National Health and Nutrition Examination Survey. Kaplan-Meier survival curves, Cox proportional hazards regression analysis, and stratified analysis were used to compare all-cause and CVD mortality among participants with one, two, and all three defects.

Results: Among the 4511 individuals included, 76.31%, 30.89%, and 41.65% met the FPG-, 2h PG-, and HbA_1C-defined criteria for prediabetes, respectively. There were 2609 (60.78%), 1420 (29.60%), and 482 (9.62%) adults meeting one, two, and all three criteria for prediabetes, respectively. During a median follow-up of 100 months, a total of 534 (180 CVD-related) deaths occurred. The multivariable-adjusted hazard ratios and 95% confidence intervals in those meeting two and three criteria were 1.341 (1.042-1.727) and 1.369 (1.027-1.824), respectively, for all-cause mortality (P for trend = 0.006), and 1.836 (1.228-2.744) and 2.037 (1.092-3.801), respectively, for CVD mortality (P for trend = 0.002), with those meeting only one criterion as the reference. In subgroup analysis, the association between the number of diagnostic criteria for prediabetes and CVD mortality was observed only in men.

Conclusions: A higher number of diagnostic criteria for prediabetes was associated with increased all-cause and CVD mortality.