OBJECTIVE -To examine the effects of acute hyperglycemia on cognitive function and mood in people with type 2 diabetes.RESEARCH DESIGN AND METHODS -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/m 2 (range 22.0 -34.6), and HbA 1c 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.RESULTS -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.CONCLUSIONS -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. Diabetes Care 27:2335-2340, 2004D iabetes is associated with rapid fluctuations in blood glucose. Hyperglycemia is a frequent consequence of the relative or absolute insulin deficiency that is intrinsic to diabetes, and hypoglycemia is a common side effect of treatment with insulin and some antidiabetic medications (1). Because the brain is dependent on a continuous supply of glucose as its principal source of energy, changes in blood glucose concentration rapidly affect cerebral function. The adverse effects of acute hypoglycemia on cognitive function and on mood are recognized (2,3). However, less is known about the effects of acute hyperglycemia on cerebral function. Anecdotal descriptions by patients with diabetes suggest that when blood glucose is elevated, changes in mood (such as increased irritability and feelings of diminished wellbeing) occur and rapid thinking is more difficult.Published data on the effects of acute hyperglycemia on cognitive function are contradictory. Two studies (4,5) have demonstrated impaired language skills and reduced IQ during hyperglycemia compared with euglycemia. Other studies have shown no effect of acute hyperglycemia on cognitive function (6 -8) or mood (9). However, in the study by Gschwend et al. (6), only two tests were used to assess cognitive function, and in the studies by Draelos et al. (8) and Weinger et al. (9) the study cohorts had chronically poor metabolic control, which may have allowed cerebral adaptation to occur in response to prevailing high blood glucose concentrations. A further study by Sindrup et al. (10) showed that short-term...

OBJECTIVE -To examine the effects of acute insulin-induced hypoglycemia on short-term, delayed, and working memory in individuals with type 1 diabetes. RESEARCH DESIGN AND METHODS-A hyperinsulinemic glucose clamp was used to maintain arterialized blood glucose level at either 4.5 mmol/l (euglycemia) or 2.5 mmol/l (hypoglycemia) on two separate occasions in 16 adults with type 1 diabetes. The participants completed tests of immediate and delayed verbal memory, immediate and delayed visual memory, and working memory during each experimental condition. Two other mental tests, the Trail Making B Test and the Digit Symbol Test, were also administered.RESULTS -Performance in tests of immediate verbal and immediate visual memory was significantly impaired during hypoglycemia. The effect of hypoglycemia on working memory and delayed memory was more profound. Performance in the nonmemory tests, the Trail Making B Test, and the Digit Symbol Test also deteriorated during hypoglycemia.CONCLUSIONS -All of the memory systems examined in the present study were affected significantly by acute hypoglycemia, particularly working memory and delayed memory. Mild (self-treated) hypoglycemia is common in individuals with insulin-treated diabetes; therefore, these observed effects of hypoglycemia on memory are of potential clinical importance because they could interfere with many everyday activities.

Compared with age- and sex-matched nondiabetic controls, people who had type 1 diabetes for a long duration had increased stiffness of vessel walls. The opposing responses in peripheral and central systolic pressures during hypoglycemia may be related to the reduction in AIx, which causes diminished amplification of the systolic pressure wave. Changes in AIx are probably mediated by a direct action of insulin on arterial endothelium, or changes in heart rate. These functional changes may contribute to the increased cardiovascular morbidity that is associated with type 1 diabetes of long duration.

The effects of acute insulin-induced hypoglycemia on short-term, delayed, and working memory were examined in healthy adults. A hyperinsulinemic glucose clamp was used to maintain arterialized blood glucose at either 4.5 (euglycemia) or 2.5 (hypoglycemia) mmol/L on 2 separate occasions in 16 healthy volunteers. Tests of immediate and delayed verbal memory, immediate and delayed visual memory, and working memory were administered during each experimental condition. All memory systems were impaired during acute hypoglycemia, with working memory and delayed memory being particularly susceptible. These findings are informative concerning the metabolic basis of adequate memory function and are of practical importance to people with insulin-treated diabetes, in whom hypoglycemia is common.

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