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

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Abstract

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
Volume102
Issue number9
DOIs
StatePublished - Sep 1 2017

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Hypoglycemia
Glucose
Magnetic resonance spectroscopy
Hypothalamus
Medical problems
Hypoglycemic Agents
Magnetic Resonance Spectroscopy
Healthy Volunteers
Clamping devices
Glucagon
Epinephrine
Hydrocortisone
Brain
Plasmas
Kinetics
Outcome Assessment (Health Care)

Cite this

@article{5e56fac272f441a8aeaabab78e3d6c03,
title = "Hypothalamic glucose transport in humans during experimentally induced hypoglycemia-associated autonomic failure",
abstract = "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.",
author = "Seaquist, {Elizabeth R} and Amir Moheet and Anjali Kumar and Deelchand, {Dinesh K} and Melissa Terpstra and Kristine Kubisiak and Eberly, {Lynn E} and Pierre-Gilles Henry and Joers, {James M} and Gulin Oz",
year = "2017",
month = "9",
day = "1",
doi = "10.1210/jc.2017-00477",
language = "English (US)",
volume = "102",
pages = "3571--3580",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "9",

}

TY - JOUR

T1 - Hypothalamic glucose transport in humans during experimentally induced hypoglycemia-associated autonomic failure

AU - Seaquist, Elizabeth R

AU - Moheet, Amir

AU - Kumar, Anjali

AU - Deelchand, Dinesh K

AU - Terpstra, Melissa

AU - Kubisiak, Kristine

AU - Eberly, Lynn E

AU - Henry, Pierre-Gilles

AU - Joers, James M

AU - Oz, Gulin

PY - 2017/9/1

Y1 - 2017/9/1

N2 - 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.

AB - 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.

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U2 - 10.1210/jc.2017-00477

DO - 10.1210/jc.2017-00477

M3 - Article

VL - 102

SP - 3571

EP - 3580

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 9

ER -