Effect of lactate administration on cerebral blood flow during hypoglycemia in people with type 1 diabetes
Van Meijel, Lian A.; Van Asten, Jack J.A.; Grandjean, Joanes; Heerschap, Arend; Tack, Cornelis J.; Van Der Graaf, Marinette; Wiegers, Evita C.; De Galan, Bastiaan E.
(2022) BMJ Open Diabetes Research and Care, volume 10, issue 2
(Article)
Abstract
Introduction Impaired awareness of hypoglycemia, clinically reflected by the inability to timely detect hypoglycemia, affects approximately 25% of the people with type 1 diabetes. Both altered brain lactate handling and increased cerebral blood flow (CBF) during hypoglycemia appear to be involved in the pathogenesis of impaired awareness of hypoglycemia. Here
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we examine the effect of lactate on CBF during hypoglycemia. Research design and methods Nine people with type 1 diabetes and normal awareness of hypoglycemia underwent two hyperinsulinemic euglycemic-hypoglycemic (3.0 mmol/L) glucose clamps in a 3T MR system, once with sodium lactate infusion and once with sodium chloride infusion. Global and regional changes in CBF were determined using pseudocontinuous arterial spin labeling. Results Lactate (3.3±0.6 vs 0.9±0.2 mmol/L during lactate infusion vs placebo infusion, respectively) suppressed the counter-regulatory hormone responses to hypoglycemia. Global CBF increased considerably in response to intravenous lactate infusion but did not further increase during hypoglycemia. Lactate also blunted the hypoglycemia-induced regional redistribution of CBF towards the thalamus. Conclusions Elevated lactate levels enhance global CBF and blunt the thalamic CBF response during hypoglycemia in patients with type 1 diabetes, mimicking observations of impaired awareness of hypoglycemia. These findings suggest that alteration of CBF associated with lactate may play a role in some aspects of the development of impaired awareness of hypoglycemia. Trial registration number NCT03730909.
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Keywords: awareness, clinical study, diabetes mellitus, type 1, hypoglycemia, Hypoglycemia/chemically induced, Cerebrovascular Circulation/physiology, Humans, Glucose Clamp Technique, Lactic Acid/adverse effects, Diabetes Mellitus, Type 1/complications, Endocrinology, Diabetes and Metabolism, Clinical Study, Research Support, Non-U.S. Gov't, Journal Article
ISSN: 2052-4897
Publisher: BMJ Publishing Group
Note: Funding Information: Funding The research was financially supported by the European Foundation for the Study of Diabetes. Publisher Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
(Peer reviewed)