Summary: Yale researchers report people with type 2 diabetes and obesity have reduced levels of glucose in their brains. The finding may help explain why obese people and those with T2DM have increased risk of eating disorders and Alzheimer’s disease.
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 behavior — 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 glucose. 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 Janice Hwang, M.D.
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. Sherwin.
Funding: 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 Regeneron.
Source: Ziba Kashef – Yale
Publisher: Content organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is adapted from the Yale news release.
Original Research: Full open access research for “Blunted rise in brain glucose levels during hyperglycemia in adults with obesity and T2DM” by Janice J. Hwang, Lihong Jiang, Muhammad Hamza, Elizabeth Sanchez Rangel, Feng Dai, Renata Belfort-DeAguiar, Lisa Parikh, Brian B. Koo, Douglas L. Rothman, Graeme Mason, Robert S. Sherwin in JCI Insight. Published online October 19 2017 doi:10.1172/jci.insight.95913
[cbtabs][cbtab title=”MLA”]Yale “Lower Brain Glucose Levels in Brains of People With Obesity and Type 2 Diabetes.” NeuroscienceNews. NeuroscienceNews, 19 October 2017.
<https://neurosciencenews.com/brain-glucose-obesity-diabetes-7771/>.[/cbtab][cbtab title=”APA”]Yale (2017, October 19). Lower Brain Glucose Levels in Brains of People With Obesity and Type 2 Diabetes. NeuroscienceNews. Retrieved October 19, 2017 from https://neurosciencenews.com/brain-glucose-obesity-diabetes-7771/[/cbtab][cbtab title=”Chicago”]Yale “Lower Brain Glucose Levels in Brains of People With Obesity and Type 2 Diabetes.” https://neurosciencenews.com/brain-glucose-obesity-diabetes-7771/ (accessed October 19, 2017).[/cbtab][/cbtabs]
Blunted rise in brain glucose levels during hyperglycemia in adults with obesity and T2DM
n rodent models, obesity and hyperglycemia alter cerebral glucose metabolism and glucose transport into the brain, resulting in disordered cerebral function as well as inappropriate responses to homeostatic and hedonic inputs. Whether similar findings are seen in the human brain remains unclear. In this study, 25 participants (9 healthy participants; 10 obese nondiabetic participants; and 6 poorly controlled, insulin- and metformin-treated type 2 diabetes mellitus (T2DM) participants) underwent 1H magnetic resonance spectroscopy scanning in the occipital lobe to measure the change in intracerebral glucose levels during a 2-hour hyperglycemic clamp (glucose ~220 mg/dl). The change in intracerebral glucose was significantly different across groups after controlling for age and sex, despite similar plasma glucose levels at baseline and during hyperglycemia. Compared with lean participants, brain glucose increments were lower in participants with obesity and T2DM. Furthermore, the change in brain glucose correlated inversely with plasma free fatty acid (FFA) levels during hyperglycemia. These data suggest that obesity and poorly controlled T2DM progressively diminish brain glucose responses to hyperglycemia, which has important implications for understanding not only the altered feeding behavior, but also the adverse neurocognitive consequences associated with obesity and T2DM.
“Blunted rise in brain glucose levels during hyperglycemia in adults with obesity and T2DM” by Janice J. Hwang, Lihong Jiang, Muhammad Hamza, Elizabeth Sanchez Rangel, Feng Dai, Renata Belfort-DeAguiar, Lisa Parikh, Brian B. Koo, Douglas L. Rothman, Graeme Mason, Robert S. Sherwin in JCI Insight. Published online October 19 2017 doi:10.1172/jci.insight.95913