Medium-chain fatty acids improve cognitive function in intensively treated type 1 diabetic patients and support in vitro synaptic transmission during acute hypoglycemia.
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.


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.
Page
Kathleen A
KA
Section of Endocrinology, Yale School of Medicine, New Haven, Connecticut, USA. kathleen.page@yale.edu
Williamson
Anne
A
Yu
Namyi
N
McNay
Ewan C
EC
Dzuira
James
J
McCrimmon
Rory J
RJ
Sherwin
Robert S
RS
D020155:3-Hydroxybutyric Acid / Q000627:therapeutic use*; D000208:Acute Disease; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology* / Q000523:psychology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000523:psychology*; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology / Q000627:therapeutic use*; D015309:Glucose Clamp Technique; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy / Q000523:psychology*; D008568:Memory / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014280:Triglycerides / Q000627:therapeutic use
D005230:Fatty Acids, Nonesterified; D014280:Triglycerides; D020155:3-Hydroxybutyric Acid