Hypothalamic glucose transport in humans during experimentally induced hypoglycemia-associated autonomic failure

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Context: Upregulated brain glucose transport in response to recurrent hypoglycemia may contribute to the development of hypoglycemia-associated autonomic failure (HAAF) and impaired awareness of hypoglycemia. Whether recurrent hypoglycemia alters glucose transport in the hypothalamus is unknown. Objective: To test the hypothesis that hypothalamic glucose transport will increase in healthy volunteers preconditioned with recurrent hypoglycemia to induce HAAF. Setting: University medical center. Design and Participants: Thirteen healthy subjects underwent paired euglycemic and hypoglycemic preconditioning studies separated by at least 1 month. Following preconditioning, hypothalamic glucose transport was measured by magnetic resonance spectroscopy (MRS) in the afternoon on day 2 of each preconditioning protocol. Outcome Measure: The ratio of maximal transport rate to cerebral metabolic rate of glucose (Tmax/ CMRglc), obtained from MRS-measured glucose in the hypothalamus as a function of plasma glucose. Results: HAAF was successfully induced based on lower epinephrine, glucagon, and cortisol during the third vs first hypoglycemic preconditioning clamp (P # 0.01). Hypothalamic glucose transport was not different following recurrent euglycemia vs hypoglycemia (Tmax/CMRglc 1.62 6 0.09 after euglycemia preconditioning and 1.75 6 0.14 after hypoglycemia preconditioning; P was not significant). Hypothalamic glucose concentrations measured by MRS were not different following the two preconditioning protocols. Conclusions: Glucose transport kinetics in the hypothalamus of healthy humans with experimentally induced HAAF were not different from those measured without HAAF. Future studies of patients with diabetes and impaired awareness of hypoglycemia will be necessary to determine if the existence of the diabetes state is required for this adaptation to hypoglycemia to occur.

Original languageEnglish (US)
Pages (from-to)3571-3580
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Issue number9
StatePublished - Sep 1 2017

Bibliographical note

Funding Information:
This work was supported by National Institute of Neurologic Disorders and Stroke Grant R01 NS035192. The Center for Magnetic Resonance Research is supported by National Institute ofBiomedicalImagingandBioengineeringGrantP41EB015894, Institutional Center Cores for Advanced Neuroimaging Award P30 NS076408, and National Center for Research Resources Grants S10 RR023730 and S10 RR027290. A.M. was supported by Clinical and Translational Science Award 5KL2 TR000113. Research reported in this publication was also supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Awards UL1 TR000114, DK059637, and DK020593.

Publisher Copyright:
Copyright © 2017 Endocrine Society.


Dive into the research topics of 'Hypothalamic glucose transport in humans during experimentally induced hypoglycemia-associated autonomic failure'. Together they form a unique fingerprint.

Cite this