Higher Glucose Levels Linked to Increased Risk of Dementia

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Higher glucose levels have been linked to increased risk of dementia in older, nondiabetic people, investigators have reported.

According to Paul Crane and his colleagues at the University of Washington in Seattle, nondiabetic patients who developed dementia had a mean blood glucose level of 115 mg/dL in the preceding 5 years compared with 100 mg/dL in similar patients who did not have dementia. The higher levels were associated with almost a 20% increase in the hazard for dementia. This is a significant finding in that it links an increase in a person’s blood sugar over an extended amount of years to one’s chances of one day having dementia.

There already has been an established connection between diabetes and dementia. Now, it has been shown that diabetic patients who subsequently developed dementia also had significantly higher average glucose levels as compared with diabetic patients who did not develop dementia. That was the conclusion that Crane and his colleagues drew and they published their research in the New England Journal of Medicine.

According to Crane and his fellow researchers:

We found that higher glucose levels were associated with an increased risk of dementia in populations without and with diabetes.

“These data suggest that higher levels of glucose may have deleterious effects on the aging brain. Our findings underscore the potential consequences of temporal trends in obesity and diabetes and suggest the need for interventions that reduce glucose levels.”

The findings are consistent with much of the literature on dementia, but conflict with those of another recent study, which showed an association between dementia and hypoglycemia.

Diabetes is a recognized risk factor for dementia. Obesity is the leading risk factor for diabetes. However, the relationship among obesity, diabetes, and dementia has remained unclear. While all three are linked, studies of the association have yielded mixed results.

Crane and colleagues sought to make the associations clearer, and they took the approach of retrospectively evaluating longitudinal clinical data on a large prospective cohort.

They included in the study 2,581 dementia-free individuals who were randomly selected from the Group Health Cooperative. Also, all participants in the study were 65 or older at enrollment from 1994 through 1996.

An additional 811 participants enrolled from 2000 through 2002. At 2-year intervals, the participants were asked to return for dementia evaluation. 2,067 of the participants had at least one follow-up visit.

Prior to enrollment in the study, the 2,067 patients had been members of Group Health for at least 5 years. They also had at least five measurements of blood glucose or glycated hemoglobin (HbA1c) over 2 or more years before joining the study.

At the scheduled follow-up visits, dementia was assessed by means of the Cognitive Abilities Screening Instrument. It has scores ranging from 0 to 100 with higher scores reflecting better cognitive function. Diagnoses of dementia or Alzheimer’s disease in the participants of the study were based on research criteria.

The final analysis by Crane and the other researchers encompassed 35,264 glucose measurements and 10,208 measurements of HbA1c obtained from 839 men and 1,228 women who had a baseline mean age of 76. The participants included 232 patients with diabetes.

524 participants during a median follow-up of 6.8 years developed dementia. Of these 524, 74 had been diagnosed as having diabetes and 450 did not.

In the study, patients without diabetes who developed dementia had significantly higher average glucose levels in the 5 years before diagnosis of dementia (P=0.01). The difference translated into a “hazard ratio” of 1.18 (95% CI 1.04-1.33).

Glucose levels among the patients with diabetes averaged 190 mg/dL in those who developed dementia versus 160 mg/dL in those who did not. The difference represented a 40% increase in the hazard for dementia.

Some limitations in the study included a reliance on available clinical laboratory measurements obtained at irregular intervals for estimates of glucose levels.

Suzanne DeLaMonte, MD, of Brown University in Providence, R.I., who was not involved in the study, stated:

This concept has been demonstrated in humans and experimental animals. The connection was made at least 8 years ago and finally has reached the mainstream. I’m very happy about this because it opens doors for the development of new [treatments] or retooling of old treatments for neurodegeneration.

“There are emerging data showing that brain ‘abnormalities’ dysregulate food intake which of course could lead to ‘irresponsible’ eating [which would lead to] hyperglycemia. However, for the most part, I think insulin resistance can overlap in brain and other organs. The hyperglycemia [not yet diabetes] reflects insulin resistance and should be used as a very easy screen for trouble looming, not just risk for diabetes.”

Dallas Anderson, a scientist at the National Institute on Aging, which paid for the study, said: “This is part of a larger picture” and he adds evidence that exercising and controlling blood pressure, blood sugar and cholesterol are a viable way to delay or prevent dementia.

Researchers suggest that keeping glucose at a healthy level might be one way to try to prevent Alzheimer’s disease.

While more research is necessary, Crane and his fellow researchers, by re-evaluating various data over the past five years, have discovered a link between higher glucose levels and an increased risk of dementia.

Written by: Douglas Cobb

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