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

doi:10.2337/db08-1557

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

Research output: Contribution to journal › Article › peer-review

127 Citations (Scopus)

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 language	English
Pages (from-to)	1237-1244
Number of pages	8
Journal	Diabetes
Volume	58
Issue number	5
DOIs	https://doi.org/10.2337/db08-1557
Publication status	Published - May 2009

Keywords

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.2337/db08-1557

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@article{7518500f78e34e8e9a7ee6851a785b21,

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

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",

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

author = "Page, {Kathleen A.} and Anne Williamson and Namyi Yu and McNay, {Ewan C.} and James Dzuira and McCrimmon, {Rory J.} and Sherwin, {Robert S.}",

year = "2009",

month = may,

doi = "10.2337/db08-1557",

language = "English",

volume = "58",

pages = "1237--1244",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association Inc.",

number = "5",

}

TY - JOUR

T1 - Medium-Chain Fatty Acids Improve Cognitive Function in Intensively Treated Type 1 Diabetic Patients and Support In Vitro Synaptic Transmission During Acute Hypoglycemia

AU - Page, Kathleen A.

AU - Williamson, Anne

AU - Yu, Namyi

AU - McNay, Ewan C.

AU - Dzuira, James

AU - McCrimmon, Rory J.

AU - Sherwin, Robert S.

PY - 2009/5

Y1 - 2009/5

N2 - 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

AB - 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

KW - RAT HIPPOCAMPAL SLICES

KW - HUMAN BRAIN

KW - BETA-HYDROXYBUTYRATE

KW - OXIDATIVE-METABOLISM

KW - BODY-COMPOSITION

KW - PRIMARY CULTURE

KW - HEALTHY-MEN

KW - GUINEA-PIG

KW - OLEIC-ACID

KW - SHORT-TERM

U2 - 10.2337/db08-1557

DO - 10.2337/db08-1557

M3 - Article

C2 - 19223595

SN - 0012-1797

VL - 58

SP - 1237

EP - 1244

JO - Diabetes

JF - Diabetes

IS - 5

ER -

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

Abstract

Keywords

UN SDGs

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