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

Section of Endocrinology, Yale School of Medicine, New Haven, Connecticut, USA.
Diabetes (Impact Factor: 8.1). 03/2009; 58(5):1237-44. DOI: 10.2337/db08-1557
Source: PubMed

ABSTRACT 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.
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.
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.
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.

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Available from: Rory J Mccrimmon, Sep 27, 2015
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    • "Research with diabetics has shown that MCT consumption can preserve executive function even during states of hypoglycemia (extremely low levels of blood glucose) (Page et al., 2009). As mentioned earlier, we chose to measure the depletion of persistence on an unsolvable puzzle task. "
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    ABSTRACT: It has been hypothesized that self-control is constrained by a limited energy resource that can be depleted through exertion. Once depleted, this resource can be replenished by the consumption or even the taste of glucose. For example, the need to inhibit reduces subsequent persistence at problem solving by humans and dogs, an effect that is not observed when a glucose drink (but not placebo) is administered following initial inhibition. The mechanism for replenishment by glucose is currently unknown. Energy transfer is not necessary, though insulin secretion may be involved. This possibility was investigated in the current study by having dogs exert self-control (sit–stay) and subsequently giving them (1) glucose that causes the release of insulin, (2) fructose that does not result in the release of insulin nor does it affect glucose levels (but is a carbohydrate), or (3) a calorie-free drink. Persistence measures indicated that both glucose and fructose replenished canine persistence, whereas the calorie-free drink did not. These results indicate that insulin release is probably not necessary for the replenishment that is presumed to be responsible for the increase in persistence. This article is part of a Special Issue entitled: Canine Behavior.
    Behavioural Processes 09/2014; 110. DOI:10.1016/j.beproc.2014.09.030 · 1.57 Impact Factor
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    • "During hypoglycemia, alternative substrates may be used as energy sources, although in general, they ameliorate but do not reverse the effects of neuroglycopenia (33). Administration of some of these alternative fuels (e.g., amino acids, lactate) has been shown to reduce the decrement in cognitive performance observed during hypoglycemia (34,35). In these studies, insufficient information was given to determine whether there had been a significant improvement in the quality of the answers given. "
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    ABSTRACT: OBJECTIVE Acute hypoglycemia impairs cognitive function in several domains. Executive cognitive function governs organization of thoughts, prioritization of tasks, and time management. This study examined the effect of acute hypoglycemia on executive function in adults with and without diabetes.RESEARCH DESIGN AND METHODS Thirty-two adults with and without type 1 diabetes with no vascular complications or impaired awareness of hypoglycemia were studied. Two hyperinsulinemic glucose clamps were performed at least 2 weeks apart in a single-blind, counterbalanced order, maintaining blood glucose at 4.5 mmol/L (euglycemia) or 2.5 mmol/L (hypoglycemia). Executive functions were assessed with a validated test suite (Delis-Kaplan Executive Function). A general linear model (repeated-measures ANOVA) was used. Glycemic condition (euglycemia or hypoglycemia) was the within-participant factor. Between-participant factors were order of session (euglycemia-hypoglycemia or hypoglycemia-euglycemia), test battery used, and diabetes status (with or without diabetes).RESULTSCompared with euglycemia, executive functions (with one exception) were significantly impaired during hypoglycemia; lower test scores were recorded with more time required for completion. Large Cohen d values (>0.8) suggest that hypoglycemia induces decrements in aspects of executive function with large effect sizes. In some tests, the performance of participants with diabetes was more impaired than those without diabetes.CONCLUSIONS Executive cognitive function, which is necessary to carry out many everyday activities, is impaired during hypoglycemia in adults with and without type 1 diabetes. This important aspect of cognition has not received previous systematic study with respect to hypoglycemia. The effect size is large in terms of both accuracy and speed.
    Diabetes care 06/2013; 36(10). DOI:10.2337/dc13-0194 · 8.42 Impact Factor
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    • "Whether ketone brain metabolism is also decreasing in healthy aging or in AD is not yet known, but Cunnane's team developed a ketone radiotracer ( 11 Cacetoacetate ) especially to be able to study brain ketone metabolism in the elderly; studies are ongoing. Based on the fact that ketones are energetic molecules and used by the brain as an alternative to glucose, some studies have demonstrated the ability of ketones to improve some cognitive dysfunction in diabetic hypoglycemia (Page et al., 2009) and even in case AD (Henderson et al., 2009). Although brain ketone metabolism is less known in the elderly population, fundamental and clinical studies suggests that they could represents an interesting therapeutic potential for cognitive decline (reviewed in Veech et al., 2001) "
    Pharmacology, 03/2012; , ISBN: 978-953-51-0222-9
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