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      Cognitive Function Is Disrupted by Both Hypo- and Hyperglycemia in School-AgedChildren With Type 1 Diabetes: A Field Study

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          Abstract

          OBJECTIVE

          We developed a field procedure using personal digital assistant (PDA) technology to test the hypothesis that naturally occurring episodes of hypo- and hyperglycemia are associated with deterioration in cognitive function in children with type 1 diabetes.

          RESEARCH DESIGN AND METHODS

          A total of 61 children aged 6–11 years with type 1 diabetes received a PDA programmed with two brief cognitive tests (mental math and choice reaction time), which they completed just before home glucose readings. The computer recorded time to complete each test and number of correct responses. Children completed several trials per day over 4–6 weeks for a total of 70 trials. Performance variables were compared across glucose ranges. Individual impairment scores (IISs) were also computed for each child by calculating the SD between performance during euglycemia and that during glucose extremes.

          RESULTS

          Time to complete both mental math and reaction time was significantly longer during hypoglycemia. During hyperglycemia, time to complete math was significantly longer and reaction time was marginally significant ( P = 0.053). There were no differences on task accuracy. Decline in mental math performance was equivalent at glucose levels <3.0 and >22.2 mmol/l. IISs varied greatly across children, with no age or sex differences.

          CONCLUSIONS

          A decrease in mental efficiency occurs with naturally occurring hypo- and hyperglycemic glucose fluctuations in children with type 1 diabetes, and this effect can be detected with a field procedure using PDA technology. With blood glucose levels >22.2 mmol/l, cognitive deterioration equals that associated with significant hypoglycemia.

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          Rating scales to assess depression in school-aged children.

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            Acute hyperglycemia alters mood state and impairs cognitive performance in people with type 2 diabetes.

            To examine the effects of acute hyperglycemia on cognitive function and mood in people with type 2 diabetes. Twenty subjects with type 2 diabetes, median age 61.5 years (range 53.1-72.0), known duration of diabetes 5.9 years (range 2.8-11.2), BMI 29.8 kg/m2 (range 22.0-34.6), and HbA1c 7.5% (range 6.7-8.4) were studied. Treatment modalities varied from antidiabetic medications to insulin. A hyperinsulinemic glucose clamp was used to maintain arterialized blood glucose at either 4.5 (euglycemia) or 16.5 mmol/l (hyperglycemia) on two occasions in a randomized and counterbalanced fashion. Tests of information processing, immediate and delayed memory, working memory, and attention were administered, along with a mood questionnaire, during each experimental condition. Speed of information processing, working memory, and some aspects of attention were impaired during acute hyperglycemia. Subjects were significantly more dysphoric during hyperglycemia, with reduced energetic arousal and increased sadness and anxiety. During acute hyperglycemia, cognitive function was impaired and mood state deteriorated in a group of people with type 2 diabetes. These findings are of practical importance because intermittent or chronic hyperglycemia is common in people with type 2 diabetes and may interfere with many daily activities through adverse effects on cognitive function and mood. Copyright 2004 American Diabetes Association
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              Tandem-pore K+ channels mediate inhibition of orexin neurons by glucose.

              Glucose-inhibited neurons orchestrate behavior and metabolism according to body energy levels, but how glucose inhibits these cells is unknown. We studied glucose inhibition of orexin/hypocretin neurons, which promote wakefulness (their loss causes narcolepsy) and also regulate metabolism and reward. Here we demonstrate that their inhibition by glucose is mediated by ion channels not previously implicated in central or peripheral glucose sensing: tandem-pore K(+) (K(2P)) channels. Importantly, we show that this electrical mechanism is sufficiently sensitive to encode variations in glucose levels reflecting those occurring physiologically between normal meals. Moreover, we provide evidence that glucose acts at an extracellular site on orexin neurons, and this information is transmitted to the channels by an intracellular intermediary that is not ATP, Ca(2+), or glucose itself. These results reveal an unexpected energy-sensing pathway in neurons that regulate states of consciousness and energy balance.
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                Author and article information

                Journal
                Diabetes Care
                diacare
                dcare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                June 2009
                26 March 2009
                : 32
                : 6
                : 1001-1006
                Affiliations
                [1] 1Behavioral Medicine Center, Department of Psychiatry and Neurobehavioral Sciences, University of Virginia Health Sciences Center, Charlottesville, Virgina;
                [2] 2Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts;
                [3] 3Patton State Hospital, Patton, California;
                [4] 4Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville, Virginia.
                Author notes
                Corresponding author: Linda Gonder-Frederick, lag3g@ 123456virginia.edu .
                Article
                1722
                10.2337/dc08-1722
                2681021
                19324943
                cd9f4447-a52a-49a1-95fe-53546dfe39c5
                © 2009 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
                : 18 September 2008
                : 7 March 2009
                Funding
                Funded by: National Institutes of Health
                Award ID: R01 060039
                Categories
                Original Research
                Clinical Care/Education/Nutrition/Psychosocial Research

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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