Treatments that Improve Insulin Sensitivity May Delay or Ameliorate Alzheimer's Symptoms

Chicago, IL (June 26, 2007) - The biochemical pathways by which high levels of insulin in the blood (which occurs in people with pre-diabetes and type 2 diabetes) increase indicators in the brain characteristic of early Alzheimer's disease were presented today at the American Diabetes Association's 67th Annual Scientific Sessions.

"Insulin resistance and accompanying high levels of insulin in the blood increase the risk for late-life memory impairment and dementia, and our studies suggest specific mechanisms through which this risk may be elevated in people with impaired glucose tolerance and type 2 diabetes," said Suzanne Craft, PhD, Associate Director of Geriatric Research at the Veterans Affairs Puget Sound Health Care System and Professor of Psychiatry at the University of Washington School of Medicine, in a recent interview. "Further, our studies in people with pre-diabetes and type 2 showed that improving their insulin sensitivity also improved their memories."

Nearly 21 million Americans have diabetes, a group of serious diseases characterized by high blood glucose levels that result from defects in the body's ability to produce and/or use insulin. Diabetes can lead to severely debilitating or fatal complications, such as heart disease, blindness, kidney disease, and amputations. It is the fifth leading cause of death by disease in the U.S. Type 2 diabetes involves insulin resistance - the body's inability to properly use its own insulin. It used to occur mainly in adults who were overweight and ages 40 and older. Now, as more children and adolescents in the United States become overweight and inactive, type 2 diabetes is occurring more often in young people.

HYPERINSULINEMIA AND INSULIN RESISTANCE IN ALZHEIMER'S DISEASE

Dr. Craft presented her work in a symposium on The Link Between Alzheimer's and Diabetes. Recent studies suggest that diabetes and pre-diabetes are associated with about a 75% increased risk of developing Alzheimer's disease (AD). For 15 years, she has been studying the possibility that insulin resistance, and the hyperinsulinemia that accompanies it, contributes to the cause of AD.

She has previously shown that insulin plays a role in normal memory function and modulating levels of proteins that accumulate in the brains of people with AD. Further, she has demonstrated that hyperinsulinemia increases levels of inflammatory markers and neurotoxic peptides in the central nervous system. She theorized that these were two pathways through which conditions associated with insulin dysregulation, such as type 2 diabetes, may increase the risk of AD in older adults.

Today she presented new data from research that examined specific mechanisms through which this risk may be elevated in individuals with impaired glucose tolerance and type 2 diabetes. The research demonstrated that adults with insulin resistance show a pattern of reduced cerebral glucose metabolism characteristic of patients with early Alzheimer's disease.

Twenty-three newly diagnosed individuals with impaired glucose tolerance or type 2 diabetes, and 11 healthy older adults - all cognitively normal - underwent PET scanning of their brains, and their brain glucose metabolism was compared.

"Reduced glucose metabolism was observed in brain regions associated with early Alzheimer's disease in the insulin-resistant adults," said Dr. Craft. "The pattern was characteristic of that seen in people with Alzheimer's years before they show any clinical symptoms of dementia, and it is considered a pattern of vulnerability to dementia."

This pattern has never been reported before in people with diabetes, although it has been observed and well-established as existing in people at high risk for Alzheimer's due to genetic risk factors. The pattern has also been seen in studies of people tracked over long periods, and those with it are much more likely to develop AD.

TREATMENT TO IMPROVE MEMORY

"These results imply that reducing insulin resistance may benefit cognitive function," said Dr. Craft. "Theoretically, any intervention that improves insulin sensitivity, such as exercise or medication, may be predicted to have a beneficial effect on memory and potentially represents a strategy for reducing the risk of developing late-life dementia."

To test the theory, she conducted a double-blind, randomized clinical trial, treating non-demented, older adults with newly-diagnosed impaired glucose tolerance or type 2 diabetes, of whom 24 received an insulin sensitizer (pioglitazone), 23 received an insulin secretagogue (nateglinide), and 24 received a placebo. Cognitive function was assessed by memory testing at baseline and after four months of treatment. HOMA-IR, an index of insulin resistance based on fasting insulin and glucose levels, also was assessed at baseline and after four months.

"The pioglitazone-treated group showed improved memory with treatment, whereas for the nateglinide-treated group, only the 11 subjects whose insulin resistance improved showed memory improvement," said Dr. Craft. Pioglitazone is a known insulin sensitivity enhancer. That nateglinide sometimes enhances insulin sensitivity is a relatively new understanding, which was not known when the drug was originally chosen for this study.

The American Diabetes Association is the nation's leading voluntary health organization supporting diabetes research, information and advocacy. Founded in 1940, the Association has offices in every region of the country, providing services to hundreds of communities.

For more information, please call the American Diabetes Association at 1-800-DIABETES (1-800-342-2383) or visit www.diabetes.org. Information from both these sources is available in English and Spanish.

Symposium - Link Between Alzheimer's and Diabetes - Is There a Correlation?

Embargoed until: Tuesday, June 26th 8:00 am, CDT Contact: Diane Tuncer, (703) 299-5510 Elizabeth Magsig, (703) 549-1500, ext 2146 NEWS ROOM June 22 - 26, 2007: Room E270, McCormick Place Convention Center; (312) 949-3210; Fax (312) 949-3218

2007

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