A new US study suggests that episodes of hypoglycemia (low blood sugar) raise the risk of dementia in elderly patients with type 2 diabetes, with those who have at least 3 diagnosed episodes having nearly double the risk of those who have had no diagnosed episodes. The researchers suggest that tight glycemic control may be inadvisable for older patients with type 2 diabetes if their treatment causes hypoglycemia.

The study was the work of researchers from the Division of Research, Section of Etiology and Prevention, Kaiser Permanente, Oakland, California, and the Departments of Psychiatry, Neurology and Epidemiology at the University of California, San Francisco and is published in the 15 April online issue of the Journal of the American Medical Association, JAMA.

The authors wrote that although acute hypoglycemia has been linked with cognitive impairment in children with type 1 diabetes, scientists have not yet established whether it might be a risk factor for dementia in older people who have type 2 diabetes.

For the longitudinal cohort study, which lasted from 1980 to 2007, they followed 16,667 patients of mean age 65 years who had type 2 diabetes. The patients were members of a healthcare delivery system in California, and the researchers were primarily interested in investigating hypoglycemic episodes that required hospitalization.

Using hospital records from 1980 to 2002, the researchers collected and reviewed data on hypoglycemic events and pulled out those that related to elderly patients with no prior diagnosis of dementia, mild cognitive impairment or general memory complaints, as of the start of 2003 and followed them, looking for any diagnoses of dementia, until early 2007.

The researchers assessed dementia risk using statistical models and adjusted for potential confounders such as age, sex, race/ethnicity, BMI, how long they had been diabetic, and other disease-related factors.

The results showed that:

  • 1,465 patients (8.8 per cent of the cohort) had at least one episode of diagnosed hypoglycemia.
  • 1,822 patients (11 per cent of the cohort) were diagnosed with dementia during follow up.
  • Of the patients who had at least one episode of hypoglycemia, 250 (17 per cent) of them were also diagnosed with dementia.
  • Compared with patients with no hypoglycemia, those who did have it had a higher risk of dementia that went up in tandem with the number of diagnosed episodes, whereby three or more episodes of hypoglycemia was linked to nearly double the risk of dementia..
  • The hazard ratio (HR) for 1 episode was 1.26 (95 per cent confidence interval [CI] ranged from 1.10 to 1.49); for 2 episodes it was 1.80 (95% CI 1.37-2.36); and for 3 or more it was 1.94 (95% CI 1.42-2.64).
  • Compared with patients with no history of hypoglycemia, those with such a history had a risk of dementia that went up by 2.39 per cent per year (95% CI, 1.72-3.01%).
  • The figures didn’t change when the researchers added the following information to the model: how often the patients used the medical services, how long they had been members of the health plan, or how long it had been since their initial diabetes diagnosis.
  • The results were similar when they looked only at emergency department admissions for hypoglycemia (as opposed to hospitalization records).

The researchers concluded that:

“Among older patients with type 2 diabetes, a history of severe hypoglycemic episodes was associated with a greater risk of dementia. Whether minor hypoglycemic episodes increase risk of dementia is unknown.”

Principal investigator Dr Rachel A Whitmer, a research scientist with Kaiser Permanente told the press that:

“We know that the brain becomes more vulnerable with age, and we need a better understanding of how glycemic control can affect brain health over the long term.”

“This study adds to the evidence base that perhaps we should rethink the notion of very tight glycemic control for our elderly patients with diabetes mellitus.”

In the study, Whitmer and colleagues wondered if cognitive impairment from early dementia could somehow be increasing the chance of having a hypoglycemic episode, but they found that even having one or more hypoglycemic episodes in midlife (mean age 52) still presented a 32 per cent higher risk of dementia later.

Co-author Dr Joe Selby, who is the director of the Kaiser Permanente Division of Research, explained:

“Our findings suggest that pursuit of ‘tight’ glycemic control (ie to hemoglobin A1c levels less than 7 percent) may be inadvisable in older patients with type 2 diabetes if required treatment is causing hypoglycemia.”

“Hypoglycemic Episodes and Risk of Dementia in Older Patients With Type 2 Diabetes Mellitus.”
Rachel A. Whitmer; Andrew J. Karter; Kristine Yaffe; Charles P. Quesenberry, Jr; Joseph V. Selby.
JAMA. 2009;301(15):1565- 1572.
Vol. 301 No. 15, April 15, 2009.

Sources: Journal Abstract, Kaiser Permanente via PR Newswire.

Written by: Catharine Paddock, PhD