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

Diabetes. 2009 May;58(5):1237-44. doi: 10.2337/db08-1557. Epub 2009 Feb 17.

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 mU x kg(-1) x min(-1)) euglycemic- (glucose approximately 5.5 mmol/l) hypoglycemic (glucose approximately 2.8 mmol/l) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Hydroxybutyric Acid / therapeutic use*
  • Acute Disease
  • Cognition / drug effects
  • Cognition / physiology*
  • Cognition Disorders / drug therapy
  • Cognition Disorders / etiology*
  • Cognition Disorders / psychology
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / psychology*
  • Fatty Acids, Nonesterified / pharmacology
  • Fatty Acids, Nonesterified / therapeutic use*
  • Glucose Clamp Technique
  • Humans
  • Hypoglycemia / drug therapy
  • Hypoglycemia / psychology*
  • Memory / drug effects
  • Memory / physiology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Triglycerides / therapeutic use

Substances

  • Fatty Acids, Nonesterified
  • Triglycerides
  • 3-Hydroxybutyric Acid