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      Acute Hypoglycemia Impairs Executive Cognitive Function in Adults With and Without Type 1 Diabetes

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      , MRCP(UK) 1 , , PHD 2 , , MD 1
      Diabetes Care
      American Diabetes Association

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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).

          RESULTS

          Compared 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.

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          Most cited references29

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          Glucose clamp technique: a method for quantifying insulin secretion and resistance.

          Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique) are described. Hyperglycemic clamp technique. The plasma glucose concentration is acutely raised to 125 mg/dl above basal levels by a priming infusion of glucose. The desired hyperglycemic plateau is subsequently maintained by adjustment of a variable glucose infusion, based on the negative feedback principle. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism. Under these conditions of constant hyperglycemia, the plasma insulin response is biphasic with an early burst of insulin release during the first 6 min followed by a gradually progressive increase in plasma insulin concentration. Euglycemic insulin clamp technique. The plasma insulin concentration is acutely raised and maintained at approximately 100 muU/ml by a prime-continuous infusion of insulin. The plasma glucose concentration is held constant at basal levels by a variable glucose infusion using the negative feedback principle. Under these steady-state conditions of euglycemia, the glucose infusion rate equals glucose uptake by all the tissues in the body and is therefore a measure of tissue sensitivity to exogenous insulin.
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            Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia.

            To determine the frequency of hypoglycemia in patients with type I diabetes and impaired awareness of hypoglycemia by prospective assessment. A prospective study was undertaken for 12 months in 60 patients with type I diabetes: 29 had impaired awareness of hypoglycemia and 31 retained normal awareness of hypoglycemia. The two groups of patients were matched for age, age at onset of diabetes, duration of diabetes, and glycemic control. Episodes of severe hypoglycemia were recorded within 24 h of the event and verified where possible by witnesses. During the 12 months, 19 (66%) of the patients with impaired awareness had one or more episodes of severe hypoglycemia with an overall incidence of 2.8 episodes.patient-1.year-1. By comparison, 8 (26%) of the patients with normal awareness experienced severe hypoglycemia (P < 0.01) with an annual incidence of 0.5 episode.patient-1.year-1 (P < 0.001). Severe hypoglycemia occurred at different times of the day in the two groups: patients with impaired awareness experienced a greater proportion of episodes during the evening (P = 0.03), and patients with normal awareness experienced a greater proportion in the early morning (P = 0.05). An assessment of fear of hypoglycemia revealed that patients with impaired awareness of hypoglycemia worried more about hypoglycemia than did patients with normal awareness (P = 0.008), but did not modify their behavior accordingly. This prospective evaluation demonstrated that impaired awareness of hypoglycemia predisposes to a sixfold increase in the frequency of severe hypoglycemia, much of which occurred at home during waking hours.
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              Executive functions and their disorders.

              The term executive function defines complex cognitive processing requiring the co-ordination of several subprocesses to achieve a particular goal. Neuropsychological evidence suggests that executive processing is intimately connected with the intact function of the frontal cortices. Executive dysfunction has been associated with a range of disorders, and is generally attributed to structural or functional frontal pathology. Neuroimaging, with PET and fMRI, has confirmed the relationship; however, attempts to link specific aspects of executive functioning to discrete prefrontal foci have been inconclusive. Instead, the emerging view suggests that executive function is mediated by dynamic and flexible networks, that can be characterised using functional integration and effective connectivity analyses. This view is compatible with the clinical presentation of executive dysfunction associated with a range of pathologies, and also with evidence that recovery of executive function can occur after traumatic brain injury, perhaps due to functional reorganisation within executive networks.
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                Author and article information

                Journal
                Diabetes Care
                Diabetes Care
                diacare
                dcare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                October 2013
                14 September 2013
                : 36
                : 10
                : 3240-3246
                Affiliations
                [1] 1Department of Diabetes, Royal Infirmary of Edinburgh, Edinburgh, Scotland
                [2] 2Centre for Cognitive Ageing and Cognitive Epidemiology, Department of Psychology, University of Edinburgh, Edinburgh, Scotland.
                Author notes
                Corresponding author: Alex J. Graveling, alex.graveling@ 123456nhs.net .
                Article
                0194
                10.2337/dc13-0194
                3781527
                23780950
                3189d26e-894d-42d4-ad52-2a5874a32cc0
                © 2013 by the American Diabetes Association.

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

                History
                : 23 January 2013
                : 20 April 2013
                Page count
                Pages: 7
                Categories
                Original Research
                Pathophysiology/Complications

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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