Hyperglycemia with high hemoglobin A1c (HbA1c) levels is associated with significant health risks. However, the relationship between HbA1c levels and the physical functioning status in later life remains uncertain and so is the possible underlying mechanism. Dr. I-Chien Wu and his team from the Institute of Population Health Sciences conducted a prospective cohort study of 2,565 initially well-functioning community-dwelling older adult aged 55 years and older from the Healthy Aging Longitudinal Study in Taiwan to determine the relationship between these two.
Each participant received baseline measurements of HbA1c levels and repeated assessments of physical functioning over a mean follow-up period of 5.3 years. Dr. Wu and the team found that HbA1c levels showed a U-shaped relationship with changes in the odds ratio for physical functioning impairment and SPPB score (p for quadratic term < .001). Compared with participants with an HbA1c of 5.5% to <6.0%, those with an HbA1c of <5.5% or ≥7.0% had a higher annual increase in the odds ratio for physical functioning impairment (odds ratio [95% confidence interval] per year, 1.25 [1.04–1.50] and 1.21 [1.04–1.41]) and a higher annualized decrease in SPPB score (coefficient [95% confidence interval], −0.05 [−0.10 to 0.00] and −0.04 [−0.08 to 0.00]).
Does this non-linear relationship have a biological basis? The team discovered that, compared with those with mid-range HbA1c levels, individuals with the highest and lowest HbA1c levels tended to have higher serum levels of certain inflammatory mediators-soluble interleukin-6 receptor (sIL-6r) and tumor necrosis factor receptor 1 (TNFR1) (figure). Notably, the nonlinear relationships between HbA1c levels and physical functioning change were only found in participants with high soluble interleukin-6 receptor levels (>48,124 pg/mL; p for interaction < .05).
In summary, Dr. Wu and the team found that high and low HbA1c levels are associated with faster physical functioning decline. This nonmonotonic relationship observed in humans is likely to have a biological basis. These findings have been published in The Journals of Gerontology: Series A. 2018 Jun 21 (article in press).
Citation: Wu, IC; Hsu, CC; Chen, CY; Chuang, SC; Cheng, CW; Hsieh, WS; Wu, MS; Liu, YT; Liu, YH; Tsai, TL; Lin, CC; Hsiung, CA. Paradoxical relationship between glycated hemoglobin and longitudinal change in physical functioning in older adults: A prospective cohort study. The Journals of Gerontology: Series A. 2018 Jun 21.