نبذة مختصرة : Objectives We aimed to assess the potential time-varying associations between HbA 1c and mortality, as well as the terminal trajectory of HbA 1c in the elderly to reveal the underlying mechanisms. Design The design is a longitudinal study using data from the Health and Retirement Study. Setting and participants Data were from the Health and Retirement Study. A total of 10,408 participants aged ≥50 years with available HbA 1c measurements at baseline (2006/2008) were included. Methods Longitudinal HbA 1c measured at 2010/2012 and 2014/2016 were collected. HbA 1c values measured three times for their associations with all-cause mortality were assessed using Cox regression and restricted cubic splines. HbA 1c terminal trajectories over 10 years before death were analyzed using linear mixed-effect models with a backward time scale. Results Women constitute 59.6% of the participants with a mean age of 69 years, with 3,070 decedents during the follow-up (8.9 years). The mortality rate during follow-up was 29.5%. Increased mortality risk became insignificant for the highest quartile of HbA 1c compared to the third quartile (aHR 1.148, 1.302, and 1.069 for a follow-up of 8.9, 6.5, and 3.2 years, respectively) with a shorter follow-up, while it became higher for the lowest quartile of HbA 1c (aHR 0.986, 1.068, and 1.439 for a follow-up of 8.9, 6.5, and 3.2 years, respectively). Accordingly, for both decedents with and without diabetes, an initial increase in HbA 1c was followed by an accelerating terminal decline starting 5–6 years before death. Conclusions and implications The time-varying association between HbA 1c and mortality mapped to the terminal trajectory in HbA 1c . High and low HbA 1c may have different clinical relationships with mortality. The HbA 1c paradox may be partially explained by reverse causation, namely, early manifestation of death.
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