In the JournalsPerspective

Brain glucose levels diminished in obesity, type 2 diabetes during hyperglycemia

Janice Hwang
Janice J. Hwang

Adults with obesity or poorly controlled type 2 diabetes have decreased intracerebral glucose levels that can lead to adverse neurocognitive consequences, according to findings published in JCI Insight.

Janice J. Hwang, MD, assistant professor of medicine in the section of endocrinology, department of internal medicine at Yale School of Medicine, and colleagues evaluated nine healthy adults, 10 adults with obesity and six adults with poorly controlled, insulin- and metformin-treated type 2 diabetes who underwent magnetic resonance spectroscopy to scan the occipital lobe to measure the change in intracerebral glucose levels during a 2-hour hyperglycemic clamp. Researchers sought to determine how obesity and poorly controlled type 2 diabetes modify changes in brain glucose levels during acute hyperglycemia.

Differences were observed for changes in intracerebral glucose levels among the groups (P = .0001) despite similar plasma glucose levels. Brain glucose concentrations were reduced in participants with obesity and type 2 diabetes compared with the healthy participants when plasma and brain glucose levels reached a steady state (healthy, 1.46 mmol/mol vs. obese, 1.06 mmol/mol vs. type 2 diabetes, 0.71 mmol/mol). A further reduction was found in participants with type 2 diabetes compared with participants with obesity (P = .04).

Significant differences were observed between the groups for insulin and free fatty acids levels. A predictable rise in plasma insulin levels was observed in healthy participants and participants with obesity, but the rise in insulin levels was higher in the participants with obesity during hyperglycemia. No significant changes in insulin levels in response to hyperglycemia were observed among participants with type 2 diabetes. Mean change in brain glucose levels between 60 and 120 minutes was inversely correlated with free fatty acids levels during hyperglycemia (P = .04).

Before and after the hyperglycemic clamp and magnetic resonance spectroscopy, researchers scored hunger, satisfaction and fullness ratings. No differences were observed among the three groups for hunger, satisfaction or fullness at baseline or immediately after the scan. However, during the hyperglycemic clamp, average brain glucose levels were positively correlated with feelings of fullness (P = .02) and satiety (P = .04), but not hunger.

“Obesity and poorly controlled type 2 diabetes may lead to decreased ability of glucose to get into the brain,” Hwang told Endocrine Today. “However, the mechanisms for why this occurs remain unclear. More studies will be needed to identify the underlying mechanisms behind our observation.” – by Amber Cox

For more information:

Janice J. Hwang, MD, can be reached at Janice.hwang@yale.edu.

Disclosures: Hwang reports she receives research support from Pfizer and Regeneron. Please see the study for all other authors’ relevant financial disclosures.

Janice Hwang
Janice J. Hwang

Adults with obesity or poorly controlled type 2 diabetes have decreased intracerebral glucose levels that can lead to adverse neurocognitive consequences, according to findings published in JCI Insight.

Janice J. Hwang, MD, assistant professor of medicine in the section of endocrinology, department of internal medicine at Yale School of Medicine, and colleagues evaluated nine healthy adults, 10 adults with obesity and six adults with poorly controlled, insulin- and metformin-treated type 2 diabetes who underwent magnetic resonance spectroscopy to scan the occipital lobe to measure the change in intracerebral glucose levels during a 2-hour hyperglycemic clamp. Researchers sought to determine how obesity and poorly controlled type 2 diabetes modify changes in brain glucose levels during acute hyperglycemia.

Differences were observed for changes in intracerebral glucose levels among the groups (P = .0001) despite similar plasma glucose levels. Brain glucose concentrations were reduced in participants with obesity and type 2 diabetes compared with the healthy participants when plasma and brain glucose levels reached a steady state (healthy, 1.46 mmol/mol vs. obese, 1.06 mmol/mol vs. type 2 diabetes, 0.71 mmol/mol). A further reduction was found in participants with type 2 diabetes compared with participants with obesity (P = .04).

Significant differences were observed between the groups for insulin and free fatty acids levels. A predictable rise in plasma insulin levels was observed in healthy participants and participants with obesity, but the rise in insulin levels was higher in the participants with obesity during hyperglycemia. No significant changes in insulin levels in response to hyperglycemia were observed among participants with type 2 diabetes. Mean change in brain glucose levels between 60 and 120 minutes was inversely correlated with free fatty acids levels during hyperglycemia (P = .04).

Before and after the hyperglycemic clamp and magnetic resonance spectroscopy, researchers scored hunger, satisfaction and fullness ratings. No differences were observed among the three groups for hunger, satisfaction or fullness at baseline or immediately after the scan. However, during the hyperglycemic clamp, average brain glucose levels were positively correlated with feelings of fullness (P = .02) and satiety (P = .04), but not hunger.

“Obesity and poorly controlled type 2 diabetes may lead to decreased ability of glucose to get into the brain,” Hwang told Endocrine Today. “However, the mechanisms for why this occurs remain unclear. More studies will be needed to identify the underlying mechanisms behind our observation.” – by Amber Cox

For more information:

Janice J. Hwang, MD, can be reached at Janice.hwang@yale.edu.

Disclosures: Hwang reports she receives research support from Pfizer and Regeneron. Please see the study for all other authors’ relevant financial disclosures.

    Perspective

    Shuchi Jaggi

    The type 2 diabetes and obesity epidemic have immensely affected Americans and are common issues encountered by endocrinologists on a daily basis. This study provides insight on the disease correlation of serum glucose elevation with intracerebral glucose variations that subsequently may affect eating habits and weight control for many of our patients. The superior aspect of the study is the use of human subjects and research protocol providing objective information on the effect of serum hyperglycemia via the use of a euglycemic clamp on intracerebral (occipital cortex) blood glucose. The small number of subjects and the low objectivity of pre- and post-experiment questionnaires are limitations of the research study. However, the correlation of blunted glucose elevations with increased hunger and decreased satiety provide an intuitive answer to the difficulty of many patients with obesity and type 2 diabetes to have controlled eating habits. In a type 1 diabetes patient, this same blunted response during an episode of hypoglycemia is detrimental and overall causes a long-term decreased awareness of hypoglycemia. The study currently is in the early phases and will require a higher subject number with increased information on glucose transporter 1 expression along with an objective measurement of caloric intake to be truly applicable to clinical practice.

    Shuchi Jaggi, DO

    Department of Medicine
    Northwell Health Physician Partners
    Manhasset, NY

    Disclosure: Jaggi reports no relevant financial disclosures.