Medium-Chain Fatty Acids Improve Cognitive Function in Intensively Treated Type 1 Diabetic Patients and Support In Vitro Synaptic Transmission During Acute Hypoglycemia
Article Figures & Tables
Figures
- FIG. 1.
Variable rate glucose infusion and primed continuous infusion of insulin (2 mU · kg−1 · min−1). Hyperinsulinemic clamps were used to maintain euglycemic conditions for 90 min followed by a 90-min hypoglycemic phase. Cognitive tests were administered during steady-state euglycemia and hypoglycemia. The study drink (medium-chain triglycerides or placebo) was given at time = 75, 100, and 125 min. Upward arrows indicate time of drink administration.
- FIG. 2.
A–D: PG (A), plasma insulin (B), plasma FFA (C), and plasma β-hydroxybutyrate (D) profiles during the euglycemic-hypoglycemic clamp studies with medium-chain triglycerides or placebo ingestion. ■, medium-chain triglycerides; ○, placebo. Down arrows indicate drink administration.
- FIG. 3.
Medium-chain triglyceride ingestion preserved cognitive performance under hypoglycemic conditions in tests of verbal memory. A: Immediate verbal memory. B: Delayed verbal memory. C: Verbal memory recognition. Figures show change in test scores (euglycemia-hypoglycemia) after medium-chain triglycerides (■) or placebo (○). *P < 0.01 medium-chain triglycerides vs. placebo.
- FIG. 4.
A: Symptoms of hypoglycemia were significantly greater during hypoglycemia compared with euglycemia. *P < 0.05. There was no difference in symptoms of hypoglycemia after medium-chain triglyceride ingestion when compared with placebo ingestion. B and C: Plasma epinephrine (B) and plasma norepinephrine (C) profiles during euglycemic-hypoglycemic clamp studies with medium-chain triglycerides or placebo ingestion. ■, medium-chain triglycerides; ○, placebo.
- FIG. 5.
β-Hydroxybutyrate (BOHB) supports synaptic activity during a stimulus train. Data were taken from the 1st, 10th, and final stimulus during the last of a series of three 10-Hz, 10-s trains delivered under three conditions: control (10 mmol/l glucose), 2 mmol/l glucose, and 2 mmol/l glucose with 8 mmol/l β-hydroxybutyrate. Note that there was a profound decrease in the percent change in the amplitude of the evoked response in 2 mmol/l glucose that was reversed in the presence of 2 mmol/l glucose + 8 mmol/l β-hydroxybutyrate. Also note that β-hydroxybutyrate was able to sustain synaptic activity during the train to a greater degree than 10 mmol/l glucose, as shown by the effect on the 10th stimulus. Data are from a total of 21 slices: β-hydroxybutyrate was applied to 10 of these.
- FIG. 6.
Octanoate does not support synaptic transmission under hypoglycemic conditions. Graph shows the effect of bath application of 2 mmol/l glucose with or without equimolar substitution of either β-hydroxybutyrate or octanoate. Note that β-hydroxybutyrate was able to substitute for glucose under basal conditions, whereas octanoate had no effect. Data are shown 10 min after the last of three stimulus trains, n = 10 β-hydroxybutyrate, n = 6 octanoate.
Tables
- TABLE 1
Cognitive test scores during euglycemia and hypoglycemia with medium-chain triglycerides or placebo ingestion
Cognitive test Medium-chain triglycerides euglycemia (∼5.5 mmol · l−1 · l−1) Medium-chain triglycerides hypoglycemia (∼2.8 mmol · l−1 · l−1) Placebo euglycemia (∼5.5 mmol · l−1 · l−1) Placebo hypoglycemia (∼2.8 mmol · l−1 · l−1) Immediate verbal memory 15.85 ± 0.66 14.97 ± 1.13* 17.36 ± 1.03 13.28 ± 1.04† Delayed verbal memory 14.82 ± 1.25 14.80 ± 1.31* 15.33 ± 1.40 11.58 ± 0.71† Verbal memory recognition 13.19 ± 0.53 13.29 ± 0.50* 14.27 ± 0.23 12.14 ± 0.19† Digit span backwards 0.60 ± 0.05 0.58 ± 0.05 0.64 ± 0.05 0.54 ± 0.05† Letter/number sequencing 12.04 ± 0.81 10.97 ± 0.76 11.07 ± 0.85 9.92 ± 0.71 Digit symbol coding 72.50 ± 5.27 74.99 ± 4.56* 74.04 ± 4.59 68.56 ± 3.54† Map search (1 min) 53.11 ± 4.16 48.42 ± 3.19 50.35 ± 3.27 42.94 ± 2.31† Map search (2 min) 73.30 ± 1.70 75.11 ± 1.51* 75.04 ± 1.92 74.67 ± 1.51 Telephone search 2.86 ± 0.17 3.06 ± 0.20 3.14 ± 0.26 3.46 ± 0.34 -
Data are least square means ± SE.
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*P < 0.05 change from euglycemia to hypoglycemia after medium-chain triglycerides vs. placebo;
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†P < 0.05 between euglycemia and hypoglycemia.
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