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

Kathleen A. Page, Anne Williamson, Namyi Yu, Ewan C. McNay, James Dzuira, Rory J. McCrimmon, Robert S. Sherwin

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    Abstract

    OBJECTIVE-We examined whether ingestion of medium-chain triglycerides could improve cognition during hypoglycemia in subjects with intensively treated type 1 diabetes and assessed potential underlying mechanisms by testing the effect of beta-hydroxybutyrate and octanoate on rat hippocampal synaptic transmission during exposure to low glucose.

    RESEARCH DESIGN AND METHODS-A total of 11 intensively treated type 1 diabetic subjects participated in stepped hyperinsulinemic- (2 rnU . kg(-1) . min(-1)) euglycemic- (glucose similar to 5.5 mmol/1) hypoglycemic (glucose similar to 2.8 mmol/1) clamp studies. During two separate sessions, they randomly received either medium-chain triglycerides or placebo drinks and performed a battery of cognitive tests. In vitro rat hippocampal slice preparations were used to assess the ability of beta-hydroxybutyrate and octanoate to support neuronal activity when glucose levels are reduced.

    RESULTS-Hypoglycemia impaired cognitive performance in tests of verbal memory, digit symbol coding, digit span backwards, and map searching. Ingestion of medium-chain triglycerides reversed these effects. Medium-chain triglycerides also produced higher free fatty acids and beta-hydroxybutyrate levels compared with placebo. However, the increase in catecholamines and symptoms during hypoglycemia was not altered. In hippocampal slices beta-hydroxybutyrate 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-Medium-chain triglyceride ingestion improves cognition without adversely affecting adrenergic or symptomatic responses to hypoglycemia in intensively treated type 1 diabetic subjects. Medium-chain triglycerides offer the therapeutic advantage of preserving brain function under hypoglycemic conditions without causing deleterious hyperglycemia. Diabetes 58:1237-1244, 2009

    Original languageEnglish
    Pages (from-to)1237-1244
    Number of pages8
    JournalDiabetes
    Volume58
    Issue number5
    DOIs
    Publication statusPublished - May 2009

    Keywords

    • RAT HIPPOCAMPAL SLICES
    • HUMAN BRAIN
    • BETA-HYDROXYBUTYRATE
    • OXIDATIVE-METABOLISM
    • BODY-COMPOSITION
    • PRIMARY CULTURE
    • HEALTHY-MEN
    • GUINEA-PIG
    • OLEIC-ACID
    • SHORT-TERM

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