Glycemia and Healthy Aging: A Paradox Revealed by a Human Study of Aging

January 19, 2019

Healthy aging is the “process of developing and maintaining the functional ability that enables well-being in older age.” A recent work done by Dr. I-Chien Wu’s team and his collaborators revealed the surprisingly complex nature of the process. These new findings are recently published in the Journals of Gerontology: MEDICAL SCIENCES, an official journal of the Gerontological Society of America.

Most, if not all, older people want to be independent. Few health issues elicit more fear than losing the ability to carry out the routines of daily life (e.g., dressing, washing, toileting, taking care of oneself). Being independent requires maintaining physical function. Indeed, maintaining physical function is a core defining concept of healthy aging. Unfortunately, physical function often declines with age, leading to physical function impairment in later life. Older adults with impaired physical function are not only more likely to become dependent but also at high risk of multiple adverse medical outcomes.

Understanding the mechanisms of physical function decline during aging and identifying high-risk individuals would enable timely prevention and therapy. In response to the aging population and in recognition of the urgent need to increase our understanding of the healthy aging process, National Health Research Institutes launched the Healthy Aging Longitudinal Study in Taiwan (HALST), an ongoing prospective cohort study of more than five thousand individuals aged 55 and older since 2009. In this human study of aging, each individual received comprehensive health status assessments and biological measurements at multiple time points throughout the follow-up period.

Exacerbated by the aging of multiple systems, hyperglycemia becomes increasingly prevalent as people age. The research team conducted a prospective cohort study to determine whether higher glycemia levels, indicated by higher HbA1c levels, are associated with faster physical function decline. A total of 2565 HALST participants entered this study. Each participant received a measurement of blood HbA1c levels at baseline and comprehensive assessment of physical function at multiple time points during a mean follow-up period of 5 years.

Compared with participants with an HbA1c of 5.5% to <6.0%, those with higher HbA1c tended to experience a faster decline in physical function during the follow-up period. “In clinical use, a HbA1c of 6.5% or greater may lead to a diagnosis of diabetes, whereas a HbA1c below this value but above or equal to 5.7% indicates an increased risk for diabetes. Our results did suggest that higher glycemia levels are associated with a faster decline in physical function,” said Dr. Wu.

However, to their surprise, the researchers found that participants with an HbA1c of less than 5.5% also experienced a faster decline in physical function than those with an HbA1c of 5.5% to <6.0%. “Most of these individuals had a lower HbA1c value that falls within the normal range. Even after taking into account other factors that may affect HbA1c levels, we still obtained the same results,” said Dr. Wu. “If this is correct, the question is raised of the possible biological basis of this association.”

Inflammation is a hallmark of aging. Serum levels of multiple key inflammatory markers were measured in each HALST participant. Interestingly, the research team observed high serum soluble interleukin-6 receptor (sIL-6r) and tumor necrosis factor receptor 1 (TNFR1) levels in some of these participants with a low HbA1c. Notably, they found that participants with a low HbA1c were far more likely to experience a decline in physical function if they also had a high sIL-6r level. “A distinct pathogenic mechanism is likely at play in these individuals,” said Dr. Wu.

In summary, Dr. Wu and the team found that high and low HbA1c levels are associated with faster physical functioning decline. Studies along this line will further clarify the states of ill health that low-normal HbA1c levels may signal and are of high priority. “This observed nonmonotonic relationship, together with emerging evidence, may indicate a universal U-shaped curve phenomenon with glycemia measures,” said Dr. Wu. “Our findings could open up a new direction in healthy aging research.”

For the full text of our publication in the Journals of Gerontology: MEDICAL SCIENCES, please visit:    

Media contact:

I-Chien Wu, MD, PhD, Institute of Population Health Sciences, National Health Research Institutes, TEL: +886-37-246-166 ext.37303, E-mail:

Nathalie Huang, Secretariat, National Health Research Institutes, TEL: +886-37-246-166 ext.32113, E-mail:

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