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Biomedical subjects

Brian M Frier

Publications and source records attributed to Brian M Frier.

At least 19 recordsLinked to original sources
PubMed2006

Effects of acute hypoglycemia on motivation and cognitive interference in people with type 1 diabetes.

AIMS: To examine the effect of acute hypoglycemia on motivation and cognitive interference in adult humans with type 1 diabetes. METHODS: A hyperinsulinemic glucose clamp was used to either maintain euglycemia (arterialized blood glucose 4.5 mmol/L) or induce hypoglycemia (2.6 mmol/L) in 16 adults with type 1 diabetes, each of whom were studied on 2 separate occasions in a counterbalanced order. During each study condition, the subjects completed parallel tests of cognitive function. The Dundee Stress State Questionnaire (DSSQ) was administered before and after the cognitive function tests. RESULTS: Hypoglycemia decreased task-relevant (P = 0.03) and increased task-irrelevant (P = 0.02) interference. Self-focus of attention was much higher after hypoglycemia than euglycemia (P = 0.02). Motivation declined to a similar extent during the euglycemia and hypoglycemia conditions (P = 0.07). Hypoglycemia produced a negative mood state with a significant fall in energy levels (P = 0.03) and a concomitant rise in anxiety level (P = 0.05). The subjective perception of concentration was unaffected during hypoglycemia (P = 0.14), and the scores for control and confidence did not fall (P = 0.19). CONCLUSIONS: In people with type 1 diabetes, hypoglycemia causes a state of heightened self-awareness and distraction during active mental activity. This is likely to leave fewer processing resources available to allow completion of cognitive tasks. Acute hypoglycemia induces a state of significant worry and anxiety that is likely to affect the social, personal, and work activities of people with diabetes.

Affect↗
PubMed2005

Hypoglycaemia and cognitive function.

Acute hypoglycaemia impairs cerebral function, and available data indicate that cognitive performance becomes impaired at a blood glucose level of 2.6-3.0 mmol/l in healthy subjects. Methodological problems limit comparisons between studies, but in general complex tasks are more sensitive to hypoglycaemia than simple tasks, and some cognitive abilities are completely abolished. The onset of hypoglycaemic cognitive dysfunction is immediate, but recovery may be considerably delayed. There is persuasive evidence of adaptation to hypoglycaemia, partly due to increased brain glucose uptake capacity, although other mechanisms may exist. Patients who are exposed to chronic or recurrent hypoglycaemia become remarkably tolerant to the state, but this is insufficient to prevent severe hypoglycaemia with neuroglycopenic decompensation, probably because symptomatic and counterregulatory responses adapt even more. During experimental hypoglycaemia, administration of non-glucose cerebral fuels preserves cognitive function. However, little progress has been made as yet towards protecting cognitive function during hypoglycaemia in clinical practice. The chronic effects of recurrent hypoglycaemia remain contentious. There are numerous case reports of hypoglycaemic brain damage and of cognitive deterioration attributed to repeated severe hypoglycaemia. The major prospective studies, including the Diabetes Control and Complications Trial, did not report cognitive declines in intensively treated patients, but had unrepresentative study populations and may have been too short to detect such effects. Structural and functional brain changes are not only associated with recurrent severe hypoglycaemia, but also with hyperglycaemia and early disease onset and may in part be due to hyperglycaemic microvascular disease. Children may be more prone to acute metabolic insults, and there is evidence of developmental disadvantage associated with hypoglycaemic episodes.

Acute Disease↗
PubMed2005

Frequency, severity, and morbidity of hypoglycemia occurring in the workplace in people with insulin-treated diabetes.

OBJECTIVE: Hypoglycemia was examined in regularly employed people with insulin-treated diabetes to ascertain the frequency and consequences of this problem in the workplace. RESEARCH DESIGN AND METHODS: A prospective 12-month survey of 243 employed people (age range 20-69 years) with insulin-treated diabetes was performed to record the frequency, severity, and morbidity of hypoglycemia occurring at work. Details of hypoglycemic episodes included time of day, place, activity, causation, blood glucose, treatment, and morbidity. Serial HbA(1c) measurements were recorded. RESULTS: A total of 1,955 mild (self-treated) episodes of hypoglycemia (8 per person per annum) and 238 severe (requiring external help) episodes (0.98 per person per annum) were recorded. Of the severe hypoglycemic episodes, 148 (62%) occurred at home, 35 (15%) occurred at work in 27 (11%) people (0.14 episodes per person per annum), and 54 (23%) occurred elsewhere; 52% of severe episodes occurred during sleep. Of the severe hypoglycemic episodes reported, adverse events were described in 54 (23%), with 29 losing consciousness (14%), 21 having a seizure (9%), 4 (2%) sustaining a head injury, 5 (2%) suffering another injury, 3 (1%) injuring someone else, and 2 (1%) damaging property. Severe hypoglycemia in the workplace was associated with six episodes of minor soft-tissue injuries. CONCLUSIONS: In this cohort, severe hypoglycemia in the workplace was uncommon and seldom caused disruption or serious morbidity. On the basis of the frequency and severity of hypoglycemia observed in the present study, restriction of employment opportunities for most people with insulin-treated diabetes may be difficult to justify.

Adult↗
PubMed2005

Influence of an early-onset age of type 1 diabetes on cerebral structure and cognitive function.

OBJECTIVE: Children who develop type 1 diabetes before age 7 years (early-onset diabetes; EOD) have comparatively poorer cognitive abilities. Whether this relates to psychosocial consequences of chronic illness or organic factors related to diabetes and its complications remains unresolved. We hypothesized that if differences in neuroradiological structure and cognitive ability coexisted in those who had EOD, then an organic component to their etiology was likely. RESEARCH DESIGN AND METHODS: A cohort of 71 young adults with long-duration type 1 diabetes diagnosed during childhood or adolescence participated in a cross-sectional evaluation of cognitive ability (neuropsychological test battery) and brain structure (magnetic resonance imaging). Diabetes onset age, preceding severe hypoglycemia exposure, retinopathy status, and diabetes duration were examined as potential correlates of cognitive and neuroradiological differences. No participants had previous neuropsychological pathology. RESULTS: In EOD participants (n = 26), current intellectual ability (Wechsler Adult Intelligence Scale-Revised performance IQ; P = 0.03) and information processing ability (Choice Reaction Time; P = 0.006) were comparatively poorer than was observed in those with later- onset diabetes (n = 45). Furthermore, lateral ventricular volumes were 37% greater (P = 0.002) and ventricular atrophy was more prevalent (61 vs. 20%; P = 0.01) in the EOD group than in those who had later-onset type 1 diabetes. CONCLUSIONS: An early childhood onset of type 1 diabetes was associated with mild central brain atrophy and significant differences in intellectual performance in adulthood, implying that neurodevelopment may be adversely affected by EOD. The differences observed in brain structure support an organic contribution to their etiology but do not exclude a coexistent contribution of psychosocial factors.

Adult↗
PubMed2004

The relationship between type 2 diabetes and cognitive dysfunction: longitudinal studies and their methodological limitations.

Type 2 diabetes and dementia in the elderly are major public health problems. Cross-sectional studies have suggested that these two conditions may be inter-related, but the nature of this association is uncertain. Causation can only be established through studies with a longitudinal design, taking into account the many potential confounding factors in any study of cognition. A literature search has identified 10 studies (nine population-based and one of case-controlled design) that included a definable diabetic population and assessments of cognitive function at baseline and at follow-up. These 10 studies utilised a combination of domain-specific cognitive assessments and a clinical diagnosis of dementia in the assessment of cognitive function. Diabetes was associated with either an accelerated cognitive decline or an increased incidence of dementia in eight of nine of the population-based studies. One study demonstrated a relationship between diabetes and vascular cognitive impairment, but not with other types of dementia. No association between type 2 diabetes and cognitive decline was demonstrated in the case-controlled study. These studies provide compelling evidence to support the view that people with type 2 diabetes are at increased risk of developing cognitive impairment in comparison with the general population.

Cognition Disorders↗
PubMed2004

Morbidity of hypoglycemia in type 1 diabetes.

Hypoglycemia is a common side effect of intensive insulin therapy in patients with type 1 diabetes. Mild hypoglycemia is any episode that can be self-treated, while a severe episode requires external help for recovery. Acute hypoglycemia produces autonomic and neuroglycopenic symptoms, including cognitive impairment and mood changes, while sympathoadrenal stimulation can provoke acute hemodynamic changes with alterations in regional vascular perfusion and a risk of cardiac dysrhythmias. Neurological manifestations include coma, convulsions and focal abnormalities. Long-term morbidities associated with hypoglycemia include impaired awareness of hypoglycemia, counterregulatory hormonal deficiencies, hypoglycemia-associated autonomic failure, and, in rare cases, permanent cognitive impairment. Hypoglycemia affects all aspects of life for the person with type 1 diabetes, including employment, social interactions, driving, sport and leisure activities, and sleep. Appreciation of the potential morbidities of hypoglycemia should encourage physicians to utilize therapeutic regimens that decrease the risk of severe hypoglycemia.

Awareness↗
PubMed2004

Food cravings during acute hypoglycaemia in adults with Type 1 diabetes.

BACKGROUND: Food craving is defined as an intense desire to eat a specific foodstuff. It may be distinguished from the sensation of hunger, which is relieved by nonspecific foodstuffs. No controlled studies have examined the effects of hypoglycaemia on food cravings. Thus, the aim of this study was to examine change in cravings for eight specified food types during euglycaemia and insulin-induced hypoglycaemia. METHODS: Thirteen adults with Type 1 diabetes attended two experimental sessions where acute hypoglycaemia was induced with either insulin aspart or human soluble insulin. Food cravings were assessed, using a questionnaire, at baseline and at the onset of the autonomic reaction to hypoglycaemia ("R"). RESULTS: The mean arterialised blood glucose concentration at baseline was 6.0+/-0.3 mmol l(-1) and at R was 1.9+/-0.4 mmol l(-1) (P<.01). Fifteen percent of subjects reported having a craving for food during euglycaemia. The prevalence increased to 65% during hypoglycaemia (P<.01). Cravings for seven of the eight food types increased during hypoglycaemia, but the greatest effect sizes (>1.0 standard deviations) were observed for three food types that had a high carbohydrate content. CONCLUSIONS: In people with Type 1 diabetes, acute hypoglycaemia produces a highly reliable generalised increase in cravings for food, particularly foodstuffs with a high content of carbohydrate. The mechanisms behind this response remain to be elicited.

Adult↗
PubMed2004

Serum thyrotropin is a better predictor of future thyroid dysfunction than thyroid autoantibody status in biochemically euthyroid patients with diabetes: implications for screening.

AIM: To ascertain the predictive values of thyroid autoantibodies and thyrotropin (TSH) levels for subsequent thyroid dysfunction in patients with diabetes. METHODS: Review of records of 467 patients who had attended diabetes clinics for a mean of 6.1 years. Baseline autoantibody and TSH results and thyroid status at annual review were determined. RESULTS: Thyroid disorders were known in 29 patients (6.2%), and newly identified in 32 (6.9%), at presentation. Of 406 patients with normal baseline thyroid status, 24 (5.9%) developed thyroid dysfunction during 6.1 years of mean follow-up. Higher baseline TSH concentration was associated with subsequent hypothyroidism; a threshold of 1.53 mU/L, approximately defining the top quartile, provided 75% sensitivity and specificity. Both TSH greater than 1.53 mU/L and positive autoantibody status predicted thyroid dysfunction, but only TSH was significant in multivariable analysis (odds ratio, 7.74, p < 0.001). No overt thyroid dysfunction developed in 293 patients with baseline TSH levels less than 1.53 mU/l. CONCLUSIONS: Baseline TSH level may be a better predictor of thyroid dysfunction than thyroid autoantibodies in people with diabetes. Patients with TSH levels below the top quartile have a risk of thyroid dysfunction similar to the general population. It may be appropriate to stop annual thyroid screening in this group, although confirmation is required.

Adolescent↗
PubMed2004

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

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/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. 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.

Acute Disease↗
PubMed2003

Insulin analogues and other developments in insulin therapy for diabetes.

Diabetes mellitus is a common chronic disorder, which is increasing in prevalence on a global scale. Insulin replacement therapy is required for all people with Type 1 diabetes and for many with Type 2 diabetes, to correct the metabolic abnormalities of these disorders. However, the pharmacokinetics and glucodynamics of available insulins have numerous limitations. Problems include delayed absorption from subcutaneous absorption sites (soluble [regular] insulin), and wide variability of absorption characteristics (insulin isophane suspension [NPH] and insulin lente) that is influenced by the adequacy of resuspension, and by a variable and insufficient duration of action, which usually requires intermediate-acting insulins to be administered twice-daily. All insulin preparations are associated with the common side effect of hypoglycaemia, and encourage weight gain.

Absorption↗
PubMed2003

Apolipoprotein-e influences aspects of intellectual ability in type 1 diabetes.

The epsilon4 allele of the apolipoprotein-E (APOE) gene is associated with poor outcome following various cerebral insults. The relationship between APOE genotype and cognitive function in patients with type 1 diabetes is unknown. In a cross-sectional study of 96 people with type 1 diabetes, subjects were APOE genotyped, previous exposure to severe hypoglycemia was estimated by questionnaire, and cognition was assessed by neuropsychological testing. Cognitive abilities were compared using multivariate general linear modeling (multiple analysis of covariance, MANCOVA) in those with (n = 21) and without (n = 75) the APOE epsilon4 allele. APOE epsilon4 selectively influenced cognitive ability in a sex-specific manner (F = 2.3, P = 0.044, Eta(2) = 0.15); women with APOE epsilon4 performed less well on tests of current, nonverbal intellectual ability (Wechsler Adult Intelligence Scale-Revised performance test score, P = 0.001, Eta(2) 0.26) and frontal lobe and executive function (Borkowski verbal fluency, P = 0.016, Eta(2) = 0.15). Previous exposure to severe hypoglycemia did not interact with APOE epsilon4 to produce cognitive disadvantage. The APOE epsilon4 genotype is associated with specific cognitive disadvantage in young women with type 1 diabetes. APOE epsilon4 is unlikely to mediate susceptibility to hypoglycemia-induced cognitive disadvantage.

Adult↗
PubMed2003

Cognitive ability and brain structure in type 1 diabetes: relation to microangiopathy and preceding severe hypoglycemia.

Type 1 diabetes is associated with chronic hyperglycemia and exposure to intermittent severe hypoglycemia. The long-term cerebral effects of these consequences of diabetes are ill defined. In this study, the history of preceding severe hypoglycemia and the presence of background retinopathy were examined in relation to cognitive ability (neuropsychological test battery) and brain structure (magnetic resonance imaging) in a cross-sectional evaluation of 74 young people with type 1 diabetes. Participants differed by their severe hypoglycemia exposure and degree of diabetic retinopathy and none had previous neuropsychological pathology. Severe hypoglycemia did not influence cognitive ability or brain structure. Background diabetic retinopathy was associated with small focal white-matter hyperintensities in the basal ganglia (33.3 vs. 4.7%, after correction for age, P = 0.005) and significant cognitive disadvantage, affecting fluid intelligence (P = 0.008, Eta(2) = 0.14), information processing (P = 0.001, Eta(2) = 0.22), and attention and concentration ability (P = 0.03, Eta(2) = 0.09). In conclusion, recurrent exposure to severe hypoglycemia alone in young people with type 1 diabetes had no detrimental impact on brain structure or function over the duration of diabetes examined. Chronic hyperglycemia (inferred by the presence of background diabetic retinopathy) may affect brain structure and function.

Adult↗
PubMed2003

Short-term, delayed, and working memory are impaired during hypoglycemia in individuals with type 1 diabetes.

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.

Acute Disease↗
PubMed2003

Frequency of severe hypoglycemia requiring emergency treatment in type 1 and type 2 diabetes: a population-based study of health service resource use.

OBJECTIVE: To determine the incidence, predisposing factors, and costs of emergency treatment of severe hypoglycemia in people with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Over a 12-month period, routinely collected datasets were analyzed in a population of 367,051 people, including 8,655 people with diabetes, to measure the incidence of severe hypoglycemia that required emergency assistance from Ninewells Hospital and Medical School (NHS) personnel including those in primary care, ambulance services, hospital accident and emergency departments, and inpatient care. Associated costs with these episodes were calculated. RESULTS: A total of 244 episodes of severe hypoglycemia were recorded in 160 patients, comprising 69 (7.1%) people with type 1 diabetes, 66 (7.3%) with type 2 diabetes treated with insulin, and 23 (0.8%) with type 2 diabetes treated with sulfonylurea tablets. Incidence rates were 11.5 and 11.8 events per 100 patient-years for type 1 and type 2 patients treated with insulin, respectively. Age, duration, and socioeconomic status were identified as risk factors for severe hypoglycemia. One in three cases were treated solely by the ambulance service with no other contact from health care professionals. The total estimated cost of emergency treatment of severe hypoglycemia was </= pound 92,078 in one year. CONCLUSIONS: Hypoglycemia requiring emergency assistance from health service personnel is as common in people with type 2 diabetes treated with insulin as in people with type 1 diabetes. It is associated with considerable NHS resource use that has a significant economic and personal cost.

Adult↗