Medium Chain Fatty Acids Improve Cognitive Function in Intensively Treated Type 1 Diabetic Patients and Support in vitro Synaptic Transmission During Acute Hypoglycemia

  1. Kathleen A. Page (kathleen.page{at}yale.edu)1,
  2. Anne Williamson2,
  3. Namyi Yu3,
  4. Ewan C. McNay4,
  5. James Dzuira5,
  6. Rory J. McCrimmon1 and
  7. Robert S. Sherwin1
  1. 1Section of Endocrinology, Yale School of Medicine, New Haven, Connecticut
  2. 2Department of Neurosurgery, Yale School of Medicine, New Haven, Connecticut
  3. 3Winthrop University Hospital, Long Island, New York
  4. 4Department of Psychology, State University of New York, University at Albany, Albany, New York
  5. 5Yale Center for Clinical Investigation, New Haven, Connecticut

    Abstract

    Objective: To examine whether ingestion of medium chain triglycerides (MCT) could improve cognition during hypoglycemia in subjects with intensively treated type 1 diabetes (TIDM) and assess potential underlying mechanisms by testing the effect of beta-hydroxybutyrate (BOHB) and octanoate on rat hippocampal synaptic transmission during exposure to low glucose.

    Research Design and Methods: Eleven intensively treated TIDM subjects participated in stepped hyperinsulinemic (2 mU• kg-1 • min-1) euglycemic (glucose ∼5.5 mmol/l) hypoglycemic (glucose ∼2.8 mmol/l) clamp studies. During two separate sessions they randomly received either MCT or placebo drinks and perfomed a battery of cognitive tests. In vitro rat hippocampal slice preparations were used to assess the ability of BOHB and octanoate to support neuronal activity when glucose levels are reduced.

    Results: Hypoglycemia impaired cognitive performance in tests of verbal memory (VM), digit symbol coding (DSC), digit span backwards, and map searching (MS). Ingestion of MCT reversed these effects. MCT also produced higher free fatty acids (FFA) and BOHB levels compared to placebo. However, the increase in catecholamines and symptoms during hypoglycemia was not altered. In hippocampal slices BOHB supported synaptic transmission under low glucose conditions, whereas octanoate could not. Nevertheless, octanoate improved the rate of recovery of synaptic function upon restoration of control glucose concentrations.

    Conclusions: MCT ingestion improves cognition without adversely affecting adrenergic or symptomatic responses to hypoglycemia in intensively treated TIDM subjects. MCT offer the therapeutic advantage of preserving brain function under hypoglycemic conditions without causing deleterious hyperglycemia.

    Footnotes

      • Received November 10, 2008.
      • Accepted February 4, 2009.

    This Article

    1. Diabetes
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