According to the Centers for Disease Control and Prevention (CDC), more than one third of adults in the United States are currently obese.1 Obesity is defined as having a body mass index (BMI) equal to or greater than 30.0. (BMI is determined by calculating a person’s weight in kilograms divided by the square of height in meters.) Some of the leading causes of preventable death are obesity-related conditions, including heart disease, stroke, type 2 diabetes and certain types of cancer. Long before the clinical status of obesity is reached, physiological changes within the body are occurring as the human body gains weight.
Determining the changes occurring inside the body in conjunction with weight gain is important for understanding the possible relationship between weight gain, diabetes, and obesity and Alzheimer’s disease. The body becomes more and more resistant to the blood-sugar lowering effects of insulin as it becomes more overweight. The body recognizes this shift and keeps making more insulin to counter the insulin resistance. Eventually this cycle of insulin resistance and insulin over-production may result in type 2 diabetes. This is significant, as people with diabetes are at a high risk of developing Alzheimer’s disease. The researchers in this study wanted to evaluate whether non-diabetic people with high levels of insulin were experiencing physiological changes in the brain that increased their risk for Alzheimer’s disease.
In participants with a normal concentration of sugar in their blood, higher insulin resistance corresponded to higher amyloid deposition in frontal and temporal areas of the brain (as assessed by Pittsburgh compound B detection).2
Researchers selected 186 late middle-aged adults from the Wisconsin Registry for Alzheimer’s Prevention (WRAP). These participants were part of an on-going study looking at genetic and biological factors that contribute to the development of dementia-related cognitive decline and neural dysfunction. They were classified as either having a positive or negative family history of Alzheimer’s disease, defined as having one or both parents with autopsy-confirmed or probable Alzheimer’s disease. All participants had normal cognitive function, no contraindication for PET or magnetic resonance imaging (MRI) and a subsequently normal MRI scan, no current diagnosis of major psychiatric disease or other major medical conditions (including heart attack or cancer), and no history of head trauma. Also, apolipoprotein genotyping was done and participants were categorized as “Non-APOE4” (no ε4 alleles) or “APOE4” (at least one ε4 allele).
Participants were instructed to fast (not eat or drink other than water) for 12 hours prior to blood collection. Their basal glucose and insulin values were measured in serum, which is the clear liquid that can be separated from clotted blood. The participants’ height and weight were measured to determine their BMI. Their hyperglycemia status was defined as either 1) having type 2 diabetes or being at risk for type 2 diabetes based on American Diabetes Association criteria or 2) taking medication to control type 2 diabetes. Finally, diastolic and systolic blood pressure measurements were taken and a total cholesterol value was measured in the blood.
The researchers used Pittsburgh compound B (PiB), which is a radioactive analog of thioflavin T, to be able to take images of beta-amyloid plaques in the brain using position emission tomography scans. In participants with a normal concentration of sugar in their blood, higher insulin resistance corresponded to higher PiB uptake in frontal and temporal areas. This reflects an increased amyloid deposition in their brain. However, the statistical analysis did not show a statistical effect among participants with hyperglycemia (high blood sugar). The researchers propose that this may be due to the limited range of hyperglycemia in their sample, noting there were relatively few participants with type 2 diabetes.
They reported that hyperglycemia may also impact amyloid burden independent of insulin resistance. Given that type 2 diabetes increases Alzheimer’s disease risk, the researchers recommend that larger studies of amyloid binding in patients with both treated and untreated diabetes will be needed to further examine these associations. They concluded that if insulin resistance influences amyloid aggregation, it may only begin to affect brain volume later in life or during early Alzheimer’s disease.
- Centers for Disease Control and Prevention. Overweight and Obesity. http://www.cdc.gov/obesity/data/adult.html
- Willette AA, Johnson SC, Birdsill AC, et al. Insulin resistance predicts brain amyloid deposition in late middle-aged adults. Alzheimers Dementia. 2015;11(5):504-510.