Severe hypoglycemia linked to increased risk for dementia

Increased risk was independent of glycemic control.

Issue: May 2009

Patients with type 2 diabetes and a history of severe hypoglycemic episodes appear to be at higher risk for dementia, according to new study findings.

“Trying to get a handle on glycemic control and how it might affect the brain in older patients is a key issue,” Rachel A. Whitmer, PhD, investigator at the Division of Research at Kaiser Permanente Northern California, said during a press briefing held by the Journal of the American Medical Association in Washington, D.C.

The longitudinal study included 16,667 patients (mean age, 65 years) in the Kaiser Permanente of Northern California Diabetes Registry. The researchers examined data on hypoglycemic episodes and diagnosis of dementia from 1980 to 2007.

During 27 years of follow-up, 11% of patients were diagnosed with dementia, and 8.8% had one or more severe hypoglycemic episodes: 68.5% had one, 18% had two and 13.5% had three or more.

“Hypoglycemic episodes that were severe enough to require hospitalization or emergency room visits were associated with greater risk for dementia, particularly for patients with multiple episodes,” Whitmer said.

After adjustment for age, BMI, ethnicity, education, gender and duration of diabetes, the risk for dementia was greater among patients with history of two (115%) or three (160%) severe hypoglycemic episodes compared with one episode (29%).

When stroke, hyperlipidemia and other comorbidities were considered, patients with one episode had a 29% increased risk for dementia compared with 86% with two episodes and 110% with three episodes, according to Whitmer.

Multiple severe hypoglycemic episodes were associated with a graded increase of risk for dementia when glycemic control and diabetes treatment were considered: one episode, 26%; two episodes, 80%; and three or more episodes, 94%.

However, the risk for dementia associated with minor hypoglycemic episodes is unknown, according to the researchers.

These data were published simultaneously in JAMA. – by Christen Haigh

This study was an association — not causation — study, and the hypothesis that hypoglycemia causes cognitive decline is supported but not proven. While hypoglycemia is associated with dementia, a key aspect of this study is that, 'compared with patients without hypoglycemia, those with hypoglycemia were also most likely to be older, African American, treated with insulin, and to have hypertension, stroke and end-stage renal disease.' All of these variables cannot be taken care of in one study. This is not a placebo-controlled study, but we do not have a better study currently nor can we think of a good design for one. Yet, we should take the findings at face value and remember that unless proven differently, hypoglycemia is harmful for older patients in regard to cognitive function. A priority should be finding a proven treatment available for the elderly that does not cause hypoglycemia. Sitagliptin (Januvia, Merck) is the only drug to date that has been tested in the elderly, and has been shown to have no more hypoglycemia than placebo. So, we should always consider first a drug that is effective in lowering glucose without causing hypoglycemia. The elderly are under-represented in drug studies, and when they are studied, their risk for harmful dementia should be one of the outcomes. Until more studies are done in the elderly, the lesson of this paper is to avoid hypoglycemia in order to preserve cognitive function.

– Nir Barzilai, MD

Director, Institute for Aging Research
Albert Einstein College of Medicine, Bronx, NY

For more information:

Whitmer R. JAMA. 2009;301:1565-1572.

Whitmer R. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes. Presented at: JAMA News Briefing; April 14, 2009; Washington D.C.