Severe hypoglycemic events are a significant risk factor for developing
dementia in older patients with type 2 diabetes, according to an
epidemiological study from Kaiser Permanente published in the April 15
Journal of the American Medical Association.
For patients with type 2 diabetes, having had at least one episode of
hypoglycemia severe enough for hospitalization or an emergency department
visit was associated with a 50 percent increase in the risk of being diagnosed
with dementia in the next few years.
The risk of dementia appeared to rise with the number of severe
hypoglycemic events documented in the past. Using patients with no
hypoglycemic events as reference, the risk of dementia was 25 percent higher
for patients who had had one hypoglycemic episode, 80 percent higher for those
with two episodes, and 94 percent for those with three or more episodes. All
the risk ratios were statistically significant after adjusting for age and
other potential confounding factors.
Rachel Whitmer, Ph.D., an investigator at the Division of Research at
Kaiser Permanente Northern California (KPNC), and colleagues collected medical
data on 16,667 type 2 diabetic patients in the KPNC Diabetes Registry who were
aged 55 or older in January 2003 and had not been diagnosed with dementia,
mild cognitive impairment, or general memory complaints at the time. The risk
of getting dementia was analyzed for potential correlation with records of
hypoglycemia-related hospitalizations and emergency department visits from
1980 and 2002. Approximately 1 in 10 of the diabetic patients was later
diagnosed for dementia of any type, including Alzheimer's disease and vascular
dementia, in the follow-up years from 2003 through January 2007.
The increased risk of developing dementia was also significantly predicted
by emergency department admissions related to hypoglycemia. Patients who had
had two or more emergency department admissions before 2003 had more than
double the risk of being diagnosed with dementia after 2003.
There has been evidence to suggest a link between diabetes and the
development of dementia, but scientists are only beginning to explore the
mechanisms of the connections between neurological disorders and metabolic
abnormalities, including but not limited to diabetes, dyslipidemia, and
obesity. The authors of the JAMA study speculated that, because
severe hypoglycemia episodes can impair nutrient delivery to the brain and
increase the amount of neurotoxic glutamate, some patients experiencing
hypoglycemia might have subclinical but permanent neurological damage that
subsequently exacerbated the risk of developing dementia.
A neuropathology study on brain tissue and autopsies published in the March
Archives of Neurology suggested that dementia patients with and
without diabetes may have two patterns of cerebral injury that lead to
dementia. Joshua Sonnen, M.D., and colleagues at the University of Washington
and Oregon Health and Sciences University found that the cerebral cortex of
dementia patients without diabetes had more amyloid-beta peptide deposits and
higher levels of F2-iso-prostanes, which are a molecular marker for
neural injury caused by free radicals. In contrast, the brains of patients with
diabetes and dementia showed more microvascular infarcts and elevated levels
of interleukin-6, a chemical related to inflammation.
An abstract of "Hypoglycemic Episodes and Risk of Dementia in
Older Patients With Type 2 Diabetes Mellitus" is posted at<jama.ama-assn.org/cgi/content/abstract/301/15/1565>.▪