Glucose levels are reduced in the brains of individuals with
obesity and type 2 diabetes compared to lean individuals, according
to a new Yale study.
The finding might explain disordered eating behaviour - and even
a higher risk of Alzheimer's disease - among obese and diabetic
individuals, the researchers said.
The study was published Oct. 19 in JCI Insight.
Both obesity and type 2 diabetes are linked to decreased
metabolism in the brain.
This hypometabolism is also associated with Alzheimer's disease,
but researchers have not pinpointed why.
To examine the mechanism, the Yale team studied brain glucose
levels in three different groups of adults: individuals who are
lean and healthy, and those with either obesity or poorly
controlled type 2 diabetes.
After fasting overnight, the study participants received
intravenous infusions of glucose for two hours.
During the infusions, the researchers used a brain scanning
technique - magnetic resonance spectroscopy - to measure levels of
glucose in the brain.
While blood glucose levels among the participants were similar,
the researchers detected significant differences in brain
Among the obese and diabetic participants, "we found decreased
or blunted entry of glucose into the brain," said first author and
assistant professor of medicine Dr. Janice Hwang.
That blunting could be one mechanism that undermines the ability
of the brain to sense glucose, she noted.
The researchers also rated participants' hunger, satisfaction,
and fullness before and after the infusions. "The lean people who
had more glucose entry into the brain also felt more full, even
though they hadn't eaten overnight," she said.
Hwang explained further: "Glucose is the most primitive signal
to the brain that you've eaten. Could it be that obese individuals
are not getting sugar into the brain, and not sensing it; thus the
feedback loop to stop eating could also be blunted?"
The study points to the importance of sugar transport from the
blood into the brain as both a target for further research and
possible pharmacological intervention in people with obesity and
type 2 diabetes, the researchers noted.
Other study authors are Lihong Jiang, Muhammad Hamza, Elizabeth
Sanchez Rangel, Feng Dai, Renata Belfort-DeAguiar, Lisa Parikh,
Brian B. Koo, Douglas L. Rothman, Graeme Mason, and Robert S.
This study was supported in part by grants from the National
Institutes of Health, and the Yale Center for Clinical
Investigation, supported by the Clinical and Translational Science
Award, the Endocrine Fellows Foundation, and the American Diabetes
Association. Hwang reports research support from Pfizer and