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Biomedical subjects

B M Frier

Publications and source records attributed to B M Frier.

At least 91 records · Page 5Linked to original sources

Changes in mood during acute hypoglycemia in healthy participants.

Acute hypoglycemia provides a reproducible method of investigating the effect of biological changes induced during hypoglycemia on mood states. Hypoglycemia was induced twice using a hyperinsulinemic glucose clamp in 24 nondiabetic human participants; a euglycemic placebo control study was also performed. Serial changes in mood were assessed using the UWIST Mood Adjective Checklist before, during, and after 60 min of controlled hypoglycemia (2.5 mmol/l). Hypoglycemia induced a significant reduction in hedonic tone (p = .001), a significant increase in tense arousal (p < .0005), and a significant decline in energetic arousal (p = .01) in comparison with the euglycemia control study. Profound changes in mood were observed in nondiabetic participants during acute hypoglycemia, and a state called tense tiredness persisted for at least 30 min after restoration of euglycemia.

Adult↗

Frequency, severity and symptomatology of hypoglycaemia: a comparative trial of human and porcine insulins in type 1 diabetic patients.

A randomized, double-blind, cross-over trial was performed to compare the frequency, severity, and symptomatology of hypoglycaemia during treatment with porcine and human insulins. Forty patients with Type 1 diabetes (20 newly diagnosed and 20 with diabetes of 5-20 years duration) were treated with human and porcine insulins for consecutive 3-month periods, in random order. Episodes of hypoglycaemia were recorded prospectively with self-reporting of the presence and intensity of symptoms using a standardized scoring technique. Serial measurements of glycated haemoglobin and review of home blood glucose tests confirmed that similar glycaemic control was achieved with each insulin species. On comparison of the treatment periods with human and porcine insulins, no differences were demonstrated in the total frequency of symptomatic hypoglycaemia (3.10 vs 3.06 episodes patient-1 3-months-1; p = 0.94), the frequency of severe hypoglycaemia (0.1 vs 0.2 episodes patient-1 3-months-1; p = 0.44), the occurrence of asymptomatic biochemical hypoglycaemia (0.75 vs 0.68 episodes patient-1 3-months-1; p = 0.81), and the capillary blood glucose concentration at the onset of hypoglycaemic symptoms (2.6 +/- 0.2 vs 2.4 +/- 0.3 mmol l-1; p = 0.40), with all results being expressed for human vs porcine treatment periods, respectively. The symptoms of hypoglycaemia did not differ during the treatment periods with each insulin species. In conclusion, treatment with human insulin had no effect upon the symptomatic response to hypoglycaemia, did not increase the total frequency of hypoglycaemia, and did not emerge as a significant risk factor for severe hypoglycaemia in these patients.

Adult↗

Frequency of thyroid dysfunction in diabetic patients: value of annual screening.

A randomly selected group of 1310 adult diabetic patients attending a diabetic outpatient clinic received annual screening for thyroid disease, by estimating serum free thyroxine and TSH concentrations. The overall prevalence of thyroid disease was found to be 13.4%, and was highest (31.4%) in Type 1 diabetic females, and lowest in Type 2 diabetic males (6.9%). As a direct result of screening, new thyroid disease was diagnosed in 6.8% (89 patients) of the population screened; the commonest diagnosis was subclinical hypothyroidism (4.8%), followed by hypothyroidism (0.9%), hyperthyroidism 0.5%), and subclinical hyperthyroidism (0.5%). Female patients with Type 1 diabetes had the highest annual risk of developing thyroid disease (12.3%), but all patient groups had a higher incidence of thyroid dysfunction, compared to that reported in the general population. This study suggests that thyroid function should be screened annually in diabetic patients to detect asymptomatic thyroid dysfunction which is increased in frequency in a diabetic population.

Adult↗

Symptoms of hypoglycemia in children with IDDM.

OBJECTIVE: To examine the symptoms of hypoglycemia in children with insulin-dependent diabetes, from the perspective both of the child and of the child's parents, and to compare the symptom reporting of the diabetic children with that of adult diabetic patients. RESEARCH DESIGN AND METHODS: Interviews were conducted with 100 parents and 43 of their children. The frequency and intensity of symptoms of hypoglycemia were documented using a structured interview and classified into groups using Principal Components Analysis (PCA). RESULTS: Diabetic children and their parents showed close agreement concerning the relative frequency and the intensity of symptoms reported. PCA of the symptom reports showed that diabetic children and their parents identified the same distinct subgroups of hypoglycemia-related symptoms: behavioral disturbance and autonomic-neuroglycopenic subgroups. CONCLUSIONS: Hypoglycemic symptoms in children with diabetes clearly differ from those experienced by insulin-treated adults and, in particular, include behavioral changes as primary features of a low blood glucose. These observations have important implications for parental education on hypoglycemia.

Adolescent↗

Regional cerebral blood flow in IDDM patients: effects of diabetes and of recurrent severe hypoglycaemia.

Chronic hyperglycaemia and recurrent severe hypoglycaemia have both been implicated as causing cerebral damage in patients with diabetes. Although cognitive dysfunction and intellectual impairment have been demonstrated in patients with recurrent severe hypoglycaemia, structural correlates have not been described, and it is not known whether specific functional changes occur in the brains of affected patients. Regional cerebral blood flow was estimated by SPECT with 99mTechnetium Exametazime in 20 patients with IDDM. Ten patients had never experienced severe hypoglycaemia and 10 had a history of recurrent severe hypoglycaemia. Patient results were compared with 20 age- and sex-matched healthy volunteers. We observed differences between the two patient groups and the control group. Tracer uptake was greater in diabetic patients in the superior pre-frontal cortex. This effect was particularly pronounced in the group who had a history of previous severe hypoglycaemia. Patients with a history of recurrent hypoglycaemia also had a relative reduction in tracer uptake to the calcarine cortex. This suggests an alteration in the pattern of baseline regional cerebral blood flow in diabetic patients with frontal excess and relative posterior reduction in cerebral blood flow.

Adult↗

PASAT performance and the pattern of uptake of 99mTc-exametazime in brain estimated with single photon emission tomography.

The effect of the paced auditory serial addition test (PASAT) on the regional uptake of 99mTc-exametazime was determined by single photon emission computed tomography. Twenty insulin-treated diabetic outpatients were scanned at rest and during the performance of the PASAT task using split-dose injection of tracer. When resting and activation scans were compared there were significant decreases in tracer uptake in the right anterior cingulate and left posterior cingulate areas during PASAT activation. The findings are compared with previous studies which had implicated the anterior cingulate area in the mechanisms of attention in humans and other animals. The potentially confounding role of anxiety during attentional tasks is discussed.

Adult↗

Severe deterioration in cognitive function and personality in five patients with long-standing diabetes: a complication of diabetes or a consequence of treatment?

Changes in mood, personality, and social function were examined in a group of five Type 1 diabetic patients, aged 50 to 66 years, with duration of diabetes from 24 to 47 years. Information on medical history was obtained from their carers and hospital records. All patients had experienced multiple episodes of severe hypoglycaemia and had impaired awareness of hypoglycaemia. Cerebral dysfunction predated the development of minimal diabetic complications and had been apparent for between 1 and 17 years. The carers assessed the pre-morbid and present behaviour and personality of the patients using standard questionnaires. Significant deteriorations were demonstrated in cognitive (p = 0.04) and social functions (p = 0.04), compared with assessment of pre-morbid function. Patients had tended to become more neurotic (p = 0.08) and less extravert (p = 0.07). All of the patients and three of the carers recorded scores suggestive of psychiatric morbidity on the General Health Questionnaire. The patients had experienced loss of employment and the carers described a reduction in the patients' social interactions. Although the aetiology of their cerebral dysfunction can not be definitely ascertained this case series emphasizes the need for long-term prospective studies in patients with diabetes of long duration to assess the impact of the disorder on cognitive and social abilities particularly where there is evidence of cerebral dysfunction. The need for professional support for the carers of such patients should be recognized.

Affect↗

Psychological and demographic correlates of glycaemic control in adult patients with type 1 diabetes.

The relationship between an objective measure of glycaemic control (glycated haemoglobin (HbA1)) and personality variables was examined in two separate groups of adult Type 1 (insulin-dependent) diabetic patients. Study 1 included 121 patients, all of whom also had subjective self-reporting of treatment compliance assessed, while the first 57 patients had individual differences in intelligence, major dimensions of personality and forgetfulness documented. Study 2 examined 303 patients, all of whom had their major dimensions of personality assessed using a shortened and updated version of the original personality questionnaire. Demographic indices (age, onset-age, duration of diabetes) were assessed in both groups. No significant correlation was found between HbA1 and self-report compliance suggesting that self-reporting may be invalid as a measure of glycaemic control. In study 1 personality and intelligence variables did not correlate significantly with HbA1 values. Older patients with shorter duration of diabetes had significantly better glycaemic control (p < 0.05). A significant correlation was observed between HbA1 concentration and onset-age of diabetes (p < 0.001); the patients who had developed diabetes later in life were achieving better control of their blood glucose. In the larger number of subjects in study 2 no significant correlations were evident between HbA1 and personality variables. It is concluded that the predictors of glycaemic control indexed by HbA1 may be distinct from predictors of self-report compliance and that the latter have limited or no value in providing an assessment of quality of glycaemic control. There is no evidence of an effect of personality on glycaemic control as measured by HbA1.

Adolescent↗

Structural equation modeling of symptoms, awareness and fear of hypoglycemia, and personality in patients with insulin-treated diabetes.

OBJECTIVE: To assess the possible influence of personality on self-reported awareness, symptoms, and fear of hypoglycemia and also to identify the relationship among these self-reported measures using formal structural equation modeling. RESEARCH DESIGN AND METHODS: A structured questionnaire, which included questions about sociodemographic details, awareness of the onset of hypoglycemia, and a list of symptoms of hypoglycemia, was completed by 305 consecutive insulin-treated diabetic patients attending the diabetic clinic at the Royal Infirmary of Edinburgh. They also completed the Hypoglycemia Fear Survey (HFS), and personality was assessed using the short form of the shortened Eysenck Personality Questionnaire-Revised (EPQ-R). Formal structural equation modeling was performed using the following variables: awareness, autonomic symptoms, neuroglycopenic symptoms, severe hypoglycemic episodes in the last year, worry and behavior (from the HFS), and extroversion and neuroticism (from the short EPQ-R). This allowed a model to be constructed that expressed the putative causal associations among the variables that could be tested statistically. RESULTS: Of the 302 patients who had experienced hypoglycemia, 111 (37%) reported reduced awareness, and these patients scored higher on the worry subscale of the HFS (reduced awareness: 41 +/- 12 vs. normal awareness: 34 +/- 12, P < 0.001). The patients with reduced awareness scored higher for neuroticism than did the patients with normal awareness (reduced awareness: 6.1 +/- 3.4 vs. normal awareness: 4.9 +/- 3.3, P < 0.01) and scored lower for extroversion (reduced awareness: 5.8 +/- 3.7 vs. normal awareness: 7.1 +/- 3.7, P < 0.01). In the structural equation modeling exercise, neuroticism was a significant putative determinant of many of the other variables. CONCLUSIONS: Personality was the major determinant of the variance that could be accounted for in this study and influenced self-reported symptoms, awareness, and fear of hypoglycemia. Personality factors may, therefore, influence self-reports from patients, particularly when soft measures, such as symptoms, are assessed and even when using validated clinical questionnaires. This finding stresses the importance of using additional evidence, such as reports from relatives, to substantiate reports from patients of loss of hypoglycemia awareness.

Adolescent↗

Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia.

OBJECTIVE: To determine the frequency of hypoglycemia in patients with type I diabetes and impaired awareness of hypoglycemia by prospective assessment. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗

Renal tubular responses to low-dose infusion of angiotensin II in type 1 diabetes mellitus; relation to chronic glycaemic control.

Renal responses to low-dose infusion of angiotensin II (ANGII, 1.25 and 2.5 ng.kg-1 min-1) were examined in 15 patients with type 1 diabetes and in 10 control subjects after pretreatment with lithium carbonate (750 mg, 20 mmol). Mean arterial pressure rose during ANGII infusion in both groups. The renal haemodynamic response to angiotensin II was not abnormal in the diabetic patients. Absolute proximal reabsorption of sodium was increased at baseline in the diabetic group, and fell during ANGII. Fractional lithium excretion was reduced in the diabetic patients at baseline (P < 0.05), and the fall in fractional lithium excretion during ANGII was less than in the control group (P = 0.012). In the diabetic group correlations existed between glycated haemoglobin and baseline glomerular filtration rate (P < 0.05), baseline fractional lithium excretion (P = 0.03), and the fall in fractional lithium excretion during angiotensin II infusion (P = 0.013). There was no correlation between glycated haemoglobin and absolute lithium clearance. Some indices of sodium reabsorption by the proximal renal tubule in diabetic patients correlate with prevailing chronic glycaemic control, largely reflecting changes in glomerular filtration rate. Reduced fractional proximal tubular responsiveness to exogenous angiotensin II is consistent with a role for endogenous angiotensin II as one mediator of increased tubular reabsorption of sodium in type 1 diabetes, but the data does not exclude alternative mechanisms.

Adult↗

Partitioning the symptoms of hypoglycaemia using multi-sample confirmatory factor analysis.

The allocation of hypoglycaemic symptoms to autonomic or neuroglycopenic groups tends to occur on an a priori basis. In view of the practical need for clear symptom markers of hypoglycaemia more scientific approaches must be pursued. Substantial evidence is presented from two large scale studies we performed which support a three factor model of hypoglycaemic symptomatology, based on the statistical associations discovered among symptoms reported by diabetic patients. Study 1 involved 295 insulin-treated out-patients and found that 11 key hypoglycaemic symptoms segregated into three clear factors: autonomic (sweating, palpitation, shaking and hunger) neuroglycopenic (confusion, drowsiness, odd behaviour, speech difficulty and incoordination), and malaise (nausea and headache). The three factors were validated on a separate group of 303 insulin-treated diabetic out-patients. Confirmatory factor analyses showed that the three factor model was the optimal model for explaining symptom covariance in each group. A multi-sample confirmatory factor analysis tested the rigorous assumptions that the relative loadings of symptoms on factors across groups were equal, and that the residual variance for each symptom was identical across groups. These assumptions were successful, indicating that the three factor model was replicated in detail across these two large samples. It is suggested that the results indicate valid groupings of symptoms that may be used in future research and in clinical practice.

Adolescent↗