Terminal trajectory of HbA 1c for 10 years supports the HbA 1c paradox: a longitudinal study using Health and Retirement Study data

• Published in: Frontiers in endocrinology (Lausanne) Vol. 15; p. 1383516
• Main Authors: Zhang, Zeyi, Yang, Longshan, Cao, Heng
• Format: Journal Article
• Language: English
• Published: Switzerland 2024
• Subjects: Aged; Female; Follow-Up Studies; Glycated Hemoglobin - analysis; Glycated Hemoglobin - metabolism; Humans; Longitudinal Studies; Male; Middle Aged; Mortality - trends; Retirement; Risk Factors; mortality; time-varying; glycated hemoglobin (HbA1c); terminal decline; trajectory
• ISSN: 1664-2392; 1664-2392

We aimed to assess the potential time-varying associations between HbA and mortality, as well as the terminal trajectory of HbA in the elderly to reveal the underlying mechanisms. The design is a longitudinal study using data from the Health and Retirement Study. Data were from the Health and Retirement Study. A total of 10,408 participants aged ≥50 years with available HbA measurements at baseline (2006/2008) were included. Longitudinal HbA measured at 2010/2012 and 2014/2016 were collected. HbA values measured three times for their associations with all-cause mortality were assessed using Cox regression and restricted cubic splines. HbA terminal trajectories over 10 years before death were analyzed using linear mixed-effect models with a backward time scale. 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 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 (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 was followed by an accelerating terminal decline starting 5-6 years before death. The time-varying association between HbA and mortality mapped to the terminal trajectory in HbA . High and low HbA may have different clinical relationships with mortality. The HbA paradox may be partially explained by reverse causation, namely, early manifestation of death.