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

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 -