Type 2 diabetes: Stable A1C levels may be linked to lower dementia risk

• Older adults with diabetes are at a higher risk of developing Alzheimer’s disease and other forms of dementia.
• New research suggests that blood sugar stability, measured by HbA1c time in range (TIR), might provide better insights into this risk than traditional HbA1c levels.
• The study found that veterans with diabetes who maintained stable blood sugar levels within personalized targets had a lower risk of developing dementia.

A new study, published in the journal JAMA Network Open , indicates that maintaining more stable hemoglobin A1c (HbA1c) levels over time in ranges tailored to individuals is associated with a lower risk of developing Alzheimer’s disease and related dementias in older adults.

The researchers say this could help doctors identify people with diabetes who are at a higher risk of Alzheimer’s.

Dementia is a common issue for older adults with diabetes and research shows that people with diabetes are more likely to develop Alzheimer’s disease and other dementias than those without diabetes.

The reasons for this link are complicated, involving factors like consistently high HbA1c levels, low blood sugar, and fluctuations in blood sugar.

The A1C test, also known as the hemoglobin A1C or HbA1c test , is a blood test that measures a person’s average blood sugar levels over the past three months. It is used to diagnose and monitor diabetes.

Diabetes guidelines suggest tailoring blood sugar targets for older adults based on their life expectancy, other health conditions, and diabetes-related complications.

Healthcare professionals often aim to find a balance by setting less strict HbA1c targets to avoid low blood sugar while also keeping an upper limit to prevent high blood sugar and its complications.

However, a newer measure — HbA1c time in range (TIR) — which is what this study examined, looks at how stable blood sugar levels are over time within certain ranges.

This measure could provide better insights into how blood sugar levels relate to the development of dementia in people with diabetes.

Higher HbA1c TIR indicates better blood sugar stability, whereas lower HbA1c time in range reflects more instability in blood sugar levels. This measure might more accurately reflect the link between blood sugar control over time and the risk of developing dementia.

Examining the link between HbA1c time in range and dementia

For this study, researchers examined the association between HbA1c TIR and Alzheimer’s Disease and Related Dementias (ADRD) in a large group of older veterans with diabetes across the country.

The researchers calculated HbA1c time in range (TIR) as the percentage of days during the baseline period when HbA1c levels were within personalized target ranges based on clinical factors and life expectancy. Higher HbA1c TIR was considered better.

The study included 374,021 veterans with diabetes, with an average age of 73.2 years, and 99% were male. Over a follow-up period of up to 10 years, 11% (41,424) developed ADRD.

Corresponding author, Paul R. Conlin, MD , medical service chief for the VA Boston Healthcare System and professor of medicine at Harvard Medical School, explained the key findings to Medical News Today .

“We studied older adults with diabetes who had hemoglobin A1c levels measured over time,” Conlin explained.

“For each person, we determined a clinically appropriate range for their A1c levels. We then measured the percentage of time that A1c levels were in this target range over 3 years,” he said.

We found that patients who maintained a higher percentage time (at least 60% or greater) with A1c levels in their target range had lower risk of Alzheimer’s disease and related dementias. Dementia risks were particularly increased when A1c levels were mostly below the target range.
— Dr. Paul Conlin

Conlin added that “clinicians and patients should try to maintain A1c stability over time to reduce the risk of dementia.”

“For some patients, higher A1c levels may be appropriate. Having A1c levels consistently below clinically appropriate target ranges was associated with increased risk of dementia.”

Too early to say diabetes causes Alzheimer’s

Three experts who were not involved in the research also spoke to MNT .

Jason Krellman, PhD , an associate professor of neuropsychology in the Department of Neurology at Columbia University Irving Medical Center, told MNT that “this study found an association between maintaining hemoglobin A1c in the normal range for a given individual and a reduced risk of Alzheimer’s disease dementia in older adults.”

“This association held true even when participants’ age, race, use of medications, and brain and heart blood vessel health were taken in account.”

However, “because the study involved a review of medical information in the past, it could not establish a cause-and-effect relationship or explain how diabetes and Alzheimer’s disease are related,” Krellman explained.

“The study used almost 40,000 participants, but all were veterans and virtually all were men, so we don’t know whether the association exists in women and non-veterans. The study did not include data on how long participants had diabetes and included data from before newer, more effective diabetes medications were being prescribed, so we don’t know if the duration of diabetes or taking the most up to date diabetes medications would change the association between A1c stability and Alzheimer’s risk”
— Jason Krellman, PhD

Stable blood sugar may protect against cognitive decline

Krellman also said “the study supports the idea that living a heart-healthy lifestyle can protect our cognitive health and suggests that maintaining our A1c, a marker of the presence and severity of diabetes, in an acceptable range as determined by our doctor lowers the risk of cognitive decline and dementia due to Alzheimer’s disease.”

“Reducing risk of diabetes might in turn reduce risk of Alzheimer’s disease dementia. Therefore, eating a healthy diet and maintaining a healthy weight, exercising as tolerated, and taking medications as prescribed can stave off diabetes and in turn stave off dementia.  Also, if you have diabetes, this research suggests that avoiding episodes of very high or very low blood sugar can also reduce your risk of Alzheimer’s dementia.  So, even if you already have diabetes, keeping it under control might also have benefits for your brain health as well.”
— Jason Krellman, PhD

Future research on diabetes and Alzheimer’s

Scott Kaiser, MD , board certified geriatrician and director of geriatric cognitive health for the Pacific Neuroscience Institute in Santa Monica, CA, said this is a “very interesting and robust study that addresses important questions regarding managing diabetes in older adults and reducing the risk of Alzheimer’s disease and related dementias.”

“The study delivered several interesting insights that warrant further validation and raises a number of important questions to be investigated in future research.”

“While this study was not designed to prospectively demonstrate the impact of maintaining hemoglobin A1c stability over time—and the findings are limited to associations rather than proof of causation—the results suggest that working with patients to maintain hemoglobin A1c stability over time may be a helpful strategy in reducing the risk of Alzheimer’s disease and related dementia in older adults with diabetes.”
— Scott Kaiser, MD

Kaiser added that “the study reinforces the importance of personalizing treatment target ranges based on age, life expectancy, and comorbidities.”

“In other words, for managing diabetes in older adults, the goal shouldn’t be simply lowering blood sugar, but rather maintaining blood sugar in the right target range, tailored to any given individual as based upon well-established guidelines, and holding steady over time. Evidence supports this approach, for a number of reasons, and reducing the risk of Alzheimer’s disease and related dementia may, in fact, be another key benefit,” he concluded.