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Post Prandial Elevations Linked to Alzheimer’s Risk

Dementia risk may rise when glucose gets out of control, particularly after meals, according to a longitudinal study.

Yutaka Kiyohara, MD, PhD, of Kyushu University in Fukuoka, Japan, and colleagues found that, diabetes patients were 74% more likely to develop dementia of any type over 15 years of follow-up after adjustment for other confounding factors (P=0.004), and Alzheimer’s disease developed 2.05-fold more often with diabetes than with normal glucose tolerance after similar adjustment (P=0.01).

Richard Bergenstal, MD, of the International Diabetes Center at Park Nicollet in Minneapolis, commented that, “Perhaps more interesting, though, was the strong risk prediction of postload glucose levels during the oral glucose tolerance test, mimicking how meals are metabolized.”

Higher two-hour postload glucose levels correlated with greater risk of developing dementia (P<0.001 for trend for all-cause dementia and Alzheimer's disease, P=0.02 for trend for vascular dementia).

After adjustment for age, sex, hypertension, electrocardiogram abnormalities, body mass index, waist-to-hip ratio, total cholesterol, prior stroke, education, smoking, alcohol intake, and physical activity in the multivariate analysis:

  • Two-hour postload glucose levels of 7.8 to 11.0 mmol/L predicted 50% elevated risk of all-cause dementia and 87% elevated likelihood of Alzheimer’s disease (both P=0.02).
  • Two-hour postload glucose levels above 11.0 mmol/L predicted 2.47-fold higher risk of all-cause dementia and 3.42-fold elevated Alzheimer’s risk (both P<0.001) and 2.66-fold elevated vascular dementia risk (P=0.01).

Kiyohara’s group argued that, those findings suggest “that postprandial glucose regulation is critical to prevent future dementia.”

Bergenstal, a past president of the American Diabetes Association, cautioned that, “It’s not yet clear whether better control of mealtime insulin levels could impact risk for patients who have already developed diabetes.” “We need to understand it a lot better before we build this into our clinical practice.” “We don’t know yet from these studies how to intervene.”

Some prior epidemiologic studies have also implicated diabetes in dementia risk, though not consistently so, they noted.

“Our findings emphasize the need to consider diabetes as a potential risk factor for all-cause dementia, Alzheimer’s disease, and probably vascular dementia,” Kiyohara and colleagues agreed in the paper.

In the study, diabetes detected on an oral glucose tolerance test was associated with 2.07-fold higher age- and sex-adjusted risk of vascular dementia during follow-up compared with those with normal glucose tolerance (P=0.04). But the vascular dementia link lost statistical significance with further multivariable adjustment, though it still trended (HR 1.82, P=0.09).

This might have been due to small numbers of vascular dementia cases, or because diabetes impacts vascular dementia by mediating hypertension and other cardiovascular risk factors that were controlled for in the multivariate analysis, the researchers explained.

Hyperglycemia itself may have an impact on the brain through atherosclerosis, oxidative stress and accumulation of advanced protein glycation, and changes in insulin metabolism yielding distorted amyloid metabolism, they noted.

Their prospective Hisayama Study included 1,017 community-dwelling older adults without baseline dementia in Japan who had an oral glucose tolerance test at age 60 or older and were followed for dementia status for 15 years.

Unlike oral glucose tolerance test results, fasting plasma glucose levels at baseline didn’t correlate with dementia overall or by dementia subtype. Impaired glucose tolerance did show some trends and borderline significance in predicting dementia of any type and Alzheimer’s.

Adding those prediabetes cases together with overt diabetes also significantly predicted both in the multivariate-adjusted model. Diabetes and prediabetes together appeared to account for 14.6% of all-cause dementia, 20.1% of Alzheimer’s disease, and 17.0% of vascular dementia risk in the population studied.

The researchers cautioned that generalizability to other ethnic populations needs confirmation in further studies.

Other limitations included a single baseline measurement of diabetes status and inability to account for changes participants made in their risk factors during follow-up.

Practice Pearls:

  • Explain that in this study, diabetes was associated with elevated all-cause dementia risk.
  • Note that diabetes also was specifically associated with elevated Alzheimer’s disease

Ohara T, et al “Glucose tolerance status and risk of dementia in the community: The Hisayama Study” Neurology 2011; 77: 1126–1134.