Blunted Rise in Brain Glucose Levels during Hyperglycemia in Adults with Obesity and T2DM
Open accessAbstract
In 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 1 H 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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Glucose response in the brain is diminished in individuals with obesity and poorly controlled type 2 diabetes mellitus compared to individuals of normal weight, and this is related to low self-reported satiety and fullness.
“Glucose response in the brain has been found to be diminished in individuals with obesity and poorly controlled type 2 diabetes mellitus compared to individuals of normal weight, which has been found to be related to low self-reported scores of satiety and fullness [78].”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes.
Guilherme, A., Virbasius, J. V., Puri, V., & Czech, M. P. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2391 · Cited by 2,292 · see citing works
Flint, A., Raben, A., Blundell, J., & Astrup, A. (2000) · International Journal of Obesity · doi:10.1038/sj.ijo.0801083 · Cited by 2,238 · see citing works
Role of Fatty Acids in the Pathogenesis of Insulin Resistance and NIDDM
Boden, G. (1997) · Diabetes · doi:10.2337/diab.46.1.3 · Cited by 1,728 · see citing works
Cognitive decline and dementia in diabetes—systematic overview of prospective observational studies
Cukierman, T., Gerstein, H. C., & Williamson, J. D. (2005) · Diabetologia · doi:10.1007/s00125-005-0023-4 · Cited by 1,049 · see citing works
GLUT1 reductions exacerbate Alzheimer's disease vasculo-neuronal dysfunction and degeneration
Winkler, E. A., Nishida, Y., Sagare, A. P., Rege, S. V., Bell, R. D., Perlmutter, D., Sengillo, J. D., Hillman, S., Kong, P., Nelson, A. R., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.3966 · Cited by 689 · see citing works
Central Administration of Oleic Acid Inhibits Glucose Production and Food Intake
Obici, S., Feng, Z., Morgan, K., Stein, D., Karkanias, G., & Rossetti, L. (2002) · Diabetes · doi:10.2337/diabetes.51.2.271 · Cited by 654 · see citing works
Small, G. W. (1995) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1995.03520360056039 · Cited by 604 · see citing works
Hypothalamic sensing of circulating fatty acids is required for glucose homeostasis
Lam, T. K. T., Pocai, A., Gutierrez-Juarez, R., Obici, S., Bryan, J., Aguilar-Bryan, L., Schwartz, G. J., & Rossetti, L. (2005) · Nature Medicine · doi:10.1038/nm1201 · Cited by 432 · see citing works
Cognitive function, dementia and type 2 diabetes mellitus in the elderly
Strachan, M. W. J., Reynolds, R. M., Marioni, R. E., & Price, J. F. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2010.228 · Cited by 402 · see citing works
Inverse Association Between BMI and Prefrontal Metabolic Activity in Healthy Adults
Volkow, N. D., Wang, G., Telang, F., Fowler, J. S., Goldstein, R. Z., Alia‐Klein, N., Logan, J., Wong, C., Thanos, P. K., Ma, Y., et al. (2009) · Obesity · doi:10.1038/oby.2008.469 · Cited by 344 · see citing works
Myeloid-Cell-Derived VEGF Maintains Brain Glucose Uptake and Limits Cognitive Impairment in Obesity
Jaïs, A., Solas, M., Backes, H., Chaurasia, B., Kleinridders, A., Theurich, S., Mauer, J., Steculorum, S. M., Hampel, B., Goldau, J., et al. (2016) · Cell · doi:10.1016/j.cell.2016.03.033 · Cited by 253 · see citing works
Steady‐State Cerebral Glucose Concentrations and Transport in the Human Brain
Rolf Gruetter, A., Uǧurbil, K., & Seaquist, E. R. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70010397.x · Cited by 252 · see citing works
Direct measurement of brain glucose concentrations in humans by 13C NMR spectroscopy.
Rolf Gruetter, A., Novotny, E. J., Boulware, S. D., Rothman, D. L., Mason, G. F., Shulman, G. I., Shulman, R. G., & Tamborlane, W. V. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.3.1109 · Cited by 243 · see citing works
Self-citationBoyle, P. J., Kempers, S. F., O’Connor, A. M., & Nagy, R. J. (1995) · New England Journal of Medicine · doi:10.1056/nejm199512283332602 · Cited by 221 · see citing works
Circulating glucose levels modulate neural control of desire for high-calorie foods in humans
Page, K. A., Seo, D., Belfort-DeAguiar, R., Lacadie, C., Dzuira, J., Naik, S., Amarnath, S., Constable, R. T., Sherwin, R. S., & Sinha, R. (2011) · Journal of Clinical Investigation · doi:10.1172/jci57873 · Cited by 212 · see citing works
Self-citationRestoration of hypothalamic lipid sensing normalizes energy and glucose homeostasis in overfed rats
Pocai, A. (2006) · Journal of Clinical Investigation · doi:10.1172/jci26640 · Cited by 211 · see citing works
Increased Brain Fatty Acid Uptake in Metabolic Syndrome
Karmi, A., Iozzo, P., Viljanen, A. P. M., Hirvonen, J., Fielding, B. A., Virtanen, K. A., Oikonen, V., Kemppainen, J., Viljanen, T., Guiducci, L., et al. (2010) · Diabetes · doi:10.2337/db09-0138 · Cited by 204 · see citing works
Seaquist, E. R., Damberg, G., Tkáč, I., & Rolf Gruetter, A. (2001) · Diabetes · doi:10.2337/diabetes.50.10.2203 · Cited by 185 · see citing works
Downregulation of Blood-Brain Barrier Glucose Transporter in Experimental Diabetes
Pardridge, W. M., Triguero, D., & Farrell, C. R. (1990) · Diabetes · doi:10.2337/diab.39.9.1040 · Cited by 184 · see citing works
No effect of insulin on glucose blood-brain barrier transport and cerebral metabolism in humans.
Hasselbalch, S. G., Knudsen, G. M., Videbæk, C. S., Pinborg, L. H., Schmidt, J. F., Holm, S., & Paulson, O. B. (1999) · Diabetes · doi:10.2337/diabetes.48.10.1915 · Cited by 172 · see citing works
Erythrocyte/HEPG2-type glucose transporter is concentrated in cells of blood-tissue barriers
Takata, K., Kasahara, T., Kasahara, M., et al. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(05)81022-8 · Cited by 166 · see citing works
Insulin increases glucose transfer across the blood-brain barrier in man.
Hertz, M. M., Paulson, O. B., Barry, D. I., Christiansen, J. S., & Svendsen, P. A. (1981) · Journal of Clinical Investigation · doi:10.1172/jci110073 · Cited by 115 · see citing works
Differentiation of Glucose Transport in Human Brain Gray and White Matter
de Graaf, R. A., Pan, J. W., Telang, F., Lee, J. H., Brown, P. B., Novotny, E. J., Hetherington, H. P., & Rothman, D. L. (2001) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200105000-00002 · Cited by 110 · see citing works
Self-citation1 H NMR Studies of Glucose Transport in the Human Brain
Rolf Gruetter, A., Novotny, E. J., Boulware, S. D., Rothman, D. L., & Shulman, R. G. (1996) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199605000-00009 · Cited by 98 · see citing works
Self-citationBrain glucose concentrations in patients with type 1 diabetes and hypoglycemia unawareness
Criego, A. B., Tkáč, I., Kumar, A. F., Thomas, W. T. B., Rolf Gruetter, A., & Seaquist, E. R. (2004) · Journal of Neuroscience Research · doi:10.1002/jnr.20296 · Cited by 96 · see citing works
Duelli, R., Maurer, M. H., Staudt, R., Heiland, S., Dümbgen, L., & Kuschinsky, W. (2000) · Brain Research · doi:10.1016/s0006-8993(00)01942-9 · Cited by 91 · see citing works
INSULIN AND THE WAY THE BRAIN HANDLES GLUCOSE1
Daniel, P. M., Love, E. R., & PRATT, O. E. (1975) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1975.tb04352.x · Cited by 66 · see citing works
Down-regulation of blood-brain glucose transport in the hyperglycemic nonobese diabetic mouse
Cornford, E. M., Hyman, S., Cornford, M. E., & Clare-Salzler, M. J. (1995) · Neurochemical Research · doi:10.1007/bf00969700 · Cited by 62 · see citing works
Response of metabolites with coupled spins to the STEAM sequence
Thompson, R. B., & Allen, P. S. (2001) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1128 · Cited by 61 · see citing works
Detection and assignment of the glucose signal in 1h nmr difference spectra of the human brain
Rolf Gruetter, A., Rothman, D. L., Novotny, E. J., Shulman, G. I., Prichard, J. W., & Shulman, R. G. (1992) · Magnetic Resonance in Medicine · doi:10.1002/mrm.1910270118 · Cited by 53 · see citing works
Self-citationSeaquist, E. R., Tkáč, I., Damberg, G., Thomas, W. T. B., & Rolf Gruetter, A. (2005) · Metabolism · doi:10.1016/j.metabol.2005.02.018 · Cited by 52 · see citing works
Myeloid-Cell-Derived VEGF Maintains Brain Glucose Uptake and Limits Cognitive Impairment in Obesity
Jaïs, A., Solas, M., Backes, H., Chaurasia, B., Kleinridders, A., Theurich, S., Mauer, J., Steculorum, S. M., Hampel, B., Goldau, J., et al. (2016) · Cell · doi:10.1016/j.cell.2016.08.010 · Cited by 47 · see citing works
Evidence for a Relationship between Body Mass and Energy Metabolism in the Human Brain
Schmoller, A., Hass, T., Strugovshchikova, O., Melchert, U. H., Scholand-Engler, H. G., Peters, A., Schweiger, U., Hohagen, F., & Oltmanns, K. M. (2010) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2010.48 · Cited by 40 · see citing works
Patients with type 1 diabetes exhibit altered cerebral metabolism during hypoglycemia
van de Ven, K. C. C., Tack, C. J., Heerschap, A., van der Graaf, M., & de Galan, B. E. (2013) · Journal of Clinical Investigation · doi:10.1172/jci62742 · Cited by 39 · see citing works
Blunted Brain Energy Consumption Relates to Insula Atrophy and Impaired Glucose Tolerance in Obesity
Jauch‐Chara, K., Binkofski, F., Loebig, M., Reetz, K., Jahn, G., Melchert, U. H., Schweiger, U., & Oltmanns, K. M. (2015) · Diabetes · doi:10.2337/db14-0421 · Cited by 36 · see citing works
Heikkilä, O., Lundbom, N. M. I., Timonen, M. H., et al. (2010) · Metabolic Brain Disease · doi:10.1007/s11011-010-9199-5 · Cited by 22 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Hansen, T. T., Astrup, A., & Sjödin, A. (2021) · Nutrients · doi:10.3390/nu13093193 · Cited by 77 · see citing works
“Glucose response in the brain has been found to be diminished in individuals with obesity and poorly controlled type 2 diabetes mellitus compared to individuals of normal weight, which has been found to be related to low self-reported scores of satiety and fullness [78].”
BackgroundRebelos, E., Rinne, J. O., Nuutila, P., & Ekblad, L. L. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10071532 · Cited by 66 · see citing works
Personalized dietary management of overweight and obesity based on measures of insulin and glucose
Hjorth, M. F., Zohar, Y., Hill, J. O., & Astrup, A. (2018) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-082117-051606 · Cited by 60 · see citing works
Astrup, A., & Hjorth, M. F. (2018) · European Journal of Clinical Nutrition · doi:10.1038/s41430-018-0227-6 · Cited by 18 · see citing works
- Authors
- Hwang, J. J., Jiang, L., Hamza, M., Sanchez Rangel, E., Dai, F., Belfort-DeAguiar, R., Parikh, L., Koo, B. B., Rothman, D. L., Mason, G., & Sherwin, R. S.
- Affiliations
- Section of Endocrinology, Department of Internal Medicine, and
- Yale University (US)
- ORCID
- Venue
- JCI Insight
- Published
- 2017-10-19
- Volume
- 2
- Issue
- 20
- ISSN
- 2379-3708 (ISSN-L)
- PMC
- PMC5846903
- OpenAlex
- W2766411218
- Cited by
- 106
- References
- 36
- Citations by year
- 2026: 8 · 2025: 14 · 2024: 13 · 2023: 16 · 2022: 14 · 2021: 12 · 2020: 10 · 2019: 9 · 2018: 10
- FWCI
- 4.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- JCI Insight (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIDDK (KL2TR000140, K23DK109284, R01DK020495, P30DK045735)
- NIAA (R01AA021984)
- NINDS (R01NS087568)
- NIH (SIG 11S10OD010613, UL1 RR024139)
- Endocrine Fellows Foundation (Young Investigator Award)
- American Diabetes Association (Innovative Clinical, Translational Science Award)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- brain glucose metabolism, hyperglycemia, obesity, type 2 diabetes, hyperglycemic clamp, plasma free fatty acids, insulin resistance, metformin, feeding behavior
- MeSH terms
- Adult, Blood Glucose, Brain, Diabetes Mellitus, Type 2, Fatty Acids, Female, Glucose, Humans, Hyperglycemia, Insulin, Magnetic Resonance Imaging, Male, Middle Aged, Obesity, Young Adult
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
