Higher Blood Glucose Levels Linked to Increased Dementia Risk

A new study finds that higher blood glucose levels are associated with a greater risk of dementia, even among individuals without diabetes.

“Our findings suggest that there may be dementia risk associated with glucose levels far below those associated with diabetes,” said study author Paul K. Crane, MD, MPH, associate professor of medicine, University of Washington School of Medicine, adjunct associate professor of health services, University of Washington School of Public Health, and affiliate investigator at Group Health Research Institute, Seattle.

Crane and colleagues analyzed blood glucose and glycated hemoglobin measurements from 2067 participants from the Adult Changes in Thought (ACT) study who did not have dementia; 232 individuals had diabetes and 1835 individuals did not.

Dementia developed in 524 participants (450 nondiabetics and 74 diabetics) during a median follow-up of nearly 7 years. Researchers found that higher average glucose levels within the preceding 5 years were related to an increased risk of dementia among individuals with and without diabetes. In individuals without diabetes, for example, the risk of dementia was 18% higher for those with an average glucose level of 115 mg/dL than for those with an average glucose level of 100 mg/dL; in persons with diabetes, the risk of dementia was 40% higher for those with an average glucose level of 190 mg/dL than for those with an average glucose level of 160 mg/dL.

The authors also discovered that the dementia risk was particularly associated with recent glucose exposure when they included both recent and distant exposures in the model at the same time, a finding that Crane found interesting. “To us, this highlighted the importance of using glucose as a time-varying exposure,” he said. “If we had averaged up lifetime exposure levels, we would have blunted our power, since we would be combining more distant and more recent levels.” The results of this study may also provide some clues as to mechanism and may even suggest some reversibility, he added.

This study is unique and differs from previous studies on the association of glucose levels and risk of dementia in that researchers “were able to use clinically obtained glucose and HbA1c measures to generate a smoothed estimate of average glucose levels over the preceding five years,” said Crane. He added that, although several other studies have measured glucose either once at baseline or only a few times throughout the study, they were able to evaluate glucose exposures as a “time-varying phenomenon.”

“We also used a spline model for risk, which is a flexible approach that doesn’t require us to categorize people into a few groups (eg, “impaired fasting glucose,” “impaired glucose tolerance”),” he said. This allowed the authors to determine the functional form of risk associated with different average glucose levels, and to find “a monotonically increasing relationship among people who didn’t have diabetes.”

Dr. Crane suspects that future research “will evaluate gradations of glucose exposures among people who do not have diabetes.”

This study was supported by a grant (U01 AG 06781 to Dr. Larson) from the National Institutes of Health. A full report can be found in The New England Journal of Medicine.

–Meredith Edwards White

Reference:

Crane PK, Walker R, Hubbard RA, et al. Glucose levels and risk of dementia. N Engl J Med. 2013;369(6):540-548.