Acute Hyperglycemia Alters Mood State and Impairs, Can it Cause Altered Mental Status?

The aim is to examine the effects of acute hyperglycemia on cognitive function and mood in people with type 2 diabetes.

Twenty subjects with type 2 diabetes have a median age of 61.5 years and a known duration of diabetes of 5.9 years.Antidiabetic medications were used in the treatment.In a randomized and counterbalanced fashion, a hyperinsulinemic glucose clamp was used to maintain blood sugar at either 4.5 or 16.5mmol/l on two occasions.During each experimental condition, tests of information processing, immediate and delayed memory, working memory and attention were administered along with a mood questionnaire.

During acute hyperglycemia, speed of information processing, working memory, and some aspects of attention were impaired.The subjects were more sad and anxious during hyperglycemia.

A group of people with type 2 diabetes had impaired cognitive function during acute hyperglycemia.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 can cause rapid fluctuations in blood sugar.Hyperglycemia is a frequent consequence of the relative or absolute deficiency that is inherent to diabetes, and it's a common side effect of treatment with insulin and some antidiabetic medications.Changes in blood sugar concentration can affect cerebral function because the brain is dependent on a continuous supply of glucose.Acute hypoglycemia can have adverse effects on cognitive function and mood.Less is known about the effects of hyperglycemia on cerebral function.According to anecdotal descriptions by patients with diabetes, when bloodglucose is high, there are changes in mood, such as increased irritability and feelings of diminished well-being.

There are conflicting data on the effects of acute hyperglycemia on cognitive function.Impaired language skills and reduced IQ have been shown in two studies.There was no effect of acute hyperglycemia on cognitive function or mood.The study was done by Gschwend et al.Only two tests were used to assess cognitive function.They were joined by Weinger et al.The study cohort had chronically poor metabolic control, which may have allowed cerebral adaptation to occur.The study was done by Sindrup et al.There was a correlation between short-term hyperglycemia and increased sensory nerve conduction and decreased motor latency in nondiabetic subjects.

People with type 1 diabetes have been the focus of earlier studies.People with type 2 diabetes are more likely to develop cognitive impairment.The central nervous system undergoes structural and functional changes as part of the normal aging process.People with type 2 diabetes may be at risk of cognitive impairment.The study looked at the effects of acute hyperglycemia on a group of people with type 2 diabetes.

Twenty adults with type 2 diabetes were recruited from the diabetes outpatient clinic at the Royal Infirmary of Edinburgh.The median age was 61.5 years and the known duration of diabetes was 5.8 years.In the month before the study, HbA1c was measured by high- performance liquid chromatography (Variant II Hemoglobin Testing System; BioRad Diagnostics Group, Hercules, CA) with a local nondiabetic reference range of 4.3–6.5%.Nine of the subjects were taking a combination of antidiabetic drugs and three of them had to take once-daily isophane to treat their diabetes.None of the participants had a history of chronic disease, previous head injury, seizure, or alcohol or drug abuse.If they had evidence of microvascular disease, they were excluded from the screening.Direct ophthalmoscopy, peripheral neuropathy, and established microalbuminuria were used to determine the presence of retinopathy.The local medical research ethics committee approved the study.The subjects consented to the study in writing.

Two laboratory sessions were separated by at least 2 weeks.A modified hyperinsulinemic glucose clamp was used to maintain blood sugar.The bloodglucose concentration was initially stable at 4.5mmol/l for 30 min in each study condition.The bloodglucose concentration was maintained at 4.5mmol/l throughout the study in the euglycemia condition.Over a period of 20 minutes, the bloodglucose was raised to 16.2mmol/l in the hyperglycemia condition.The bloodglucose concentration was maintained for 10 minutes before the cognitive testing began and was kept at the target level for 80 minutes while the tests were administered.The two sessions were performed in a randomized and counterbalanced fashion because the subjects were not told which arm of the study was being done.

The tests of information processing, memory, and attention were administered.

Trail Making B.This test has a motor component and was run on a handheld computer.

The time test is reaction time.Psychomotor speed and information processing are tested.The coefficients of variation were also calculated for the Simple and Four-Choice Reaction Times.

The memory and learning tests that were used in this study were chosen because they have previously been shown to be sensitive to metabolic disturbances.

There are verbal memory tests.The Auditory Verbal Learning Test is immediate and delayed.This is a test of learning and memory capacity.Longer-term retention is measured by the delayed component.Immediate and delayed Logical Memory Test.Immediate and delayed recall are measures of the Logical Memory test.

There are visual memory tests.Immediate and delayed visual reproduction.The test measures immediate and delayed recall.There is a visual retention test.This is a visual recall test.

There are working memory tests.There are forwards and backwards.In this test, a series of lists of numbers are presented to the subject, and the lists increase in length.There is a letter and a number.A series of numbers and letters are presented.

In order to measure attention, the Test of Everyday Attention battery was used.

In the present study, parallel versions of the tests were used to minimize the learning effect between the two study conditions.The tests were carried out in order.

The University of Wales Institute of Science and Technology used a checklist to document changes in mood experienced by the subjects.There are three main mood states, which are energetic arousal, tense a stimulation, and hedonic tone.

Each test's results were analyzed on their own.A general linear model (repeated-measures ANOVA) was used to model a condition and a fixed effect.The models were repeated with the following variables added: sex as a fixed effect, age, HbA1c, and three mood states.When the results were reported, the order effect was retained.Significant is a P value of 0.05.The P values reported in the tables for the core model were generated from analyses without sex and the covariates.The P value is reported in the tables for the additional fixed effect of sex and the covariates.The effect size was calculated.A score of 0.25–0.5 indicates a moderate effect size.2 based power is given for univariate repeated-measures ANOVA.was set at 0.05.The correlation was set at zero so that it would offer a conservative power estimate.The power to detect an effect size of 0.25 is 85%.All analyses were done using the same software.

During each study condition, a stable blood sugar level was achieved.During the euglycemia condition, the mean arterialized bloodglucose concentration was 4.5 0.2mmol/l and during the hyperglycemic condition it was 16.7%.There were no significant order effects for any of the outcome variables.The effects of acute hyperglycemia on cognitive function remained significant after controlling for sex, age, and HbA1c.

Table 1 summarizes the results of these tests.Performance was impaired in the Trail Making B, Digit Symbol, and Four-Choice Reaction Time tests.The performance in the Simple Reaction Time test was unaffected.The Simple and Four-Choice Reaction Time tests had the same coefficients of variation.

Table 2 summarizes the results of the memory function tests.There was no effect on tests of immediate or delayed memory.During acute hyperglycemia, performance in two tests of working memory was impaired.

During hyperglycemia, the mean number of map symbols was significantly less.During hyperglycemia, the number of symbols circled in 2 min was lower, but the difference did not achieve statistical significance.In the telephone search task, there was no difference in the number of symbols found.The time taken to complete the task was much faster during euglycemia.

The elevator test was affected by hyperglycemia.The performance in the elevator was not affected by the distraction test.

There was no difference in the raw score between the two study conditions.A longer time was required to complete each switch of the visual elevator task.

There was no significant difference in the number of symbols that were located during either study condition when searching for a telephone directory while counting.The difference in time taken to complete the task was not significant.The time-per-target score, which is the ratio of the number of symbols circled divided by the time taken for the task, was higher during acute hyperglycemia.

The results of the questionnaire are shown.1.Hedonic Tone and Energetic Arousal scores were lower during hyperglycemia.

The study showed that people with type 2 diabetes have impaired speed of information processing, working memory, and some aspects of attention.It had a negative effect on mood states.

According to the results of the present study, performance was impaired during acute hyperglycemia in tests that required a quick response, suggesting that accuracy was preserved at the expense of speed.When compared with euglycemia, fewer symbols were identified after 1 min in the Map Search.The ceiling effect is reached after 2 min in the overall 2-min score.In the Telephone Search test, there was no difference in the total number of symbols found, but the time taken to complete the tests was longer during hyperglycemia.The time taken to complete each switch was significantly greater during hyperglycemia than it was in the visual elevator task.

Information processing speed and working memory were adversely affected by hyperglycemia in people with type 2 diabetes.During hyperglycemia, performance in three of the four processing speed tests was impaired.The only two tests that were affected were of working memory and not of immediate and delayed memory.This suggestion is supported by the "attention" results, which showed a reduction in speed of information processing (rather than accuracy), and this was particularly apparent in tests of attention that made demands on working memory.

In addition to the specific cognitive demands of the tasks affected by hyperglycemia, impairment of performance in these tests may reflect their relative complexity.Davis et al.Children with type 1 diabetes have impaired cognitive function, but this is limited to complex tests of cognitive ability.In the present study, performance in relatively simple tests of information processing, memory, and attention were unaffected by hyperglycemia.A decrement in performance was observed in tasks that were more difficult, such as the Four-Choice Reaction Time test.

Mood was affected by hyperglycemia.The changes in mood were caused by increased feelings of anxiety, fatigue, and depression, as well as decreases in happiness and hedonic tone.The impairment in cognitive function occurred regardless of the changes in mood state.

Acute hyperglycemia has an adverse effect on cognitive function and mood according to the results of the present study.The tests of cognitive function had modest Eta2 values, with the exception of the Four-Choice Reaction Time test.80% of the study's power was used to detect the effect size.We weren't able to detect small effect sizes.They may not be of great practical significance at that level.The number of subjects included in the study is large.This was done because of the large number of cognitive outcomes, which were found to be sensitive to the effects of hypoglycemia, as well as giving more confidence in the results.It will be useful to use a larger sample to try and replicate these findings, as they carry the possibility of type I errors.The main domain of cognitive function was included in the study of the cognitive effects of hyperglycemia.Within 90 min of the restoration of euglycemia, the effects of acute hypoglycemia on cognitive function have been observed to return to normal.The effect of hyperglycemia on cognitive function or mood is not known and will require further investigation.

There is some evidence that shows adverse effects on cerebral function from hyperglycemia.Acute hyperglycemia has been shown to increase cerebral damage from a stroke.There is growing evidence to suggest that chronic hyperglycemia is involved in the development of cognitive impairment associated with diabetes.

The results of two recent studies show that the findings of the present study are in line with anecdotal reports from people with type 2 diabetes.Cox et al.There have been studies that show changes in mood and cognitive function in people with type 1 and type 2 diabetes.Exposure to moderate and intermittent hyperglycemia is common in people with type 2 diabetes.Processing speed and working memory are important aspects of cognitive function.The effects of hyperglycemia on cognitive function and mood states may affect many activities of daily living.

The graph shows the scores of the mood checklist during euglycemia.

20 adults with type 2 diabetes were tested for information processing during euglycemia.

A.J.S.Research funding was provided by Eli Lilly.I.J.D.The Royal Society-Wolfson Research Merit Award was given to him.

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