CHICAGO — Excessively high and extremely low levels of glycosylated hemoglobin were associated with an increased risk for dementia in elderly patients with type 2 diabetes, according to the findings of a cohort study involving more than 22,000 patients.
Dr. Rachel Whitmer surveyed a cohort of 22,852 patients older than age 55 from the Kaiser Permanente Northern California diabetes registry who had their HbA1c measured at least once between 1994 and 1996, and checked these same patients' records again between Jan. 1, 1997, and May 30, 2006, for a diagnosis of dementia, vascular dementia, or Alzheimer's disease. People who had a prior diagnosis of dementia at the initial survey were excluded from the study.
In presenting the data at the annual meeting of the American Academy of Neurology, Dr. Whitmer described the cohort, which was 48% female and 35% nonwhite, as a “very diverse sample.” The mean age at the time of the initial survey was 65 years.
A total of 2,488 participants (11%) were diagnosed with dementia during the follow-up period. Patients with dementia were more likely to be on insulin and have had a longer duration of diabetes than were those without dementia, said Dr. Whitmer, an investigator at the division of research, Kaiser Permanente Northern California.
The researchers used a reference glycosylated hemoglobin level of 7%, because this is the cutoff point that endocrinologists aim for to lower the risks of complications.
Surprisingly, “we really did not see an elevated risk of dementia until we got to values that were from 10% to 11.9% and really 12% or greater,” she said.
Diabetes patients with HbA1c values of 15% and above were 83% more likely to receive a diagnosis of dementia during the follow-up period than were their diabetic peers with glycosylated hemoglobin levels under 7%.
Diabetics with values of 12% or more had a 22% elevated risk of dementia.
However, the investigators also looked at people with extremely low levels of HbA1c—less than 5%–-and found that this group actually had the greatest risk of dementia. People with levels less than 5% were 2.2 times more likely to have dementia, compared with patients with levels between 5% and 7%.
All risk assessments were made after adjusting for age, education, race, sex, weight, treatment, diabetes duration, hypertension, hyperlipidemia, heart disease, and stroke.
“Most endocrinologists like to aim for [HbA1c] levels less than 8% or less than 7%,” said Dr. Whitmer. “It's been shown that this lowers the risk of stroke and hypertension.” However, physicians would do well to take into account these new cutoff points for dementia risk in their assessment of patients. “When we're looking at elderly people with diabetes, overcontrol can be just as much as a problem as not as much control,” Dr. Whitmer said.
One of the study's limitations is that HbA1c might have been underestimated for those patients whose dementia went undiagnosed. Furthermore, no brain imaging or cognitive tests were available to confirm the dementia diagnoses. Future studies are needed to confirm the findings.
It's unknown what the mechanism would be that links HbA1c and dementia, added Dr. Whitmer.
Dr. Whitmer reported no disclosures in relation to her presentation. One of her fellow researchers on this study disclosed relationships to Novartis Corp., Myriad Genetics Inc., and Posit Science.