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Biomedical subjects

B M Frier

Publications and source records attributed to B M Frier.

At least 37 records · Page 2Linked to original sources

Effects of acute hypoglycaemia on auditory information processing in adults with Type I diabetes.

AIMS/HYPOTHESIS: Acute hypoglycaemia in humans causes general impairment of cognitive function, but information about its effects on more specific cognitive processes is limited. METHODS: Basic aspects of auditory function were studied in 15 adults with uncomplicated Type I (insulin-dependent) diabetes mellitus. Two separate hyperinsulinaemic glucose clamp procedures were done on different study days, in a counterbalanced fashion, either maintaining euglycaemia (blood glucose 5.0 mmol x l(-1)) or inducing hypoglycaemia (blood glucose 2.6 mmol x l(-1)). During each study, the subjects performed a battery of auditory and cognitive function tasks. RESULTS: Hypoglycaemia caused deterioration in mental efficiency as assessed by Digit Symbol (p<0.001) and Trail Making B (p=0.004) tasks. Acute hypoglycaemia also caused deterioration in one of three measures of simple auditory processing (single-tone loudness, p=0.001) and in auditory temporal processing (p=0.007). The amplitude and latency of auditory N100, P200 and P300 event-related potentials were not affected, but the amplitude of the N240 potential was reduced during acute hypoglycaemia. CONCLUSION/INTERPRETATION: Our findings are consistent with other recognised disruptive effects of acute hypoglycaemia on sensory information processing in non-diabetic and diabetic adults, including adverse effects on auditory information processing in non-diabetic subjects. These derangements have implications for the everyday activities of people with Type I diabetes who are frequently exposed to acute hypoglycaemia.

Acute Disease↗

Basal-bolus insulin therapy in Type 1 diabetes: comparative study of pre-meal administration of a fixed mixture of insulin lispro (50%) and neutral protamine lispro (50%) with human soluble insulin.

AIMS: To ascertain whether pre-meal administration of 50% insulin lispro and 50% neutral protamine lispro (NPL), given as a fixed mixture (Humalog Mix50, human soluble (regular) insulin as a basal-bolus regimen in people with Type 1 diabetes. Both regimens included bedtime human isophane (NPH) insulin. METHODS: This was a multinational, multicentre, randomized, open-label, two-period crossover comparison of two insulin treatments for two 12-week periods in 109 patients with Type 1 diabetes. The protocol provided preliminary evaluations of dose requirements and recommendations for insulin dose adjustment when switching regimens on the basis of blood glucose (BG) values. Eight-point BG profiles, frequency of hypoglycaemia, HbA1c, insulin dose, time of injection, and frequency of snacking were assessed during each treatment. RESULTS: Total daily insulin dose was similar for both treatments, but the total pre-meal doses were higher (P < 0.001) and the bedtime dose of isophane was lower (P < 0.001) with Mix50. The pre-meal dose before breakfast and lunch, although statistically different (P = 0.006 and P < 0.001, respectively), was of similar magnitude, but the pre-evening meal dose was higher with Mix50 (P < 0.001). Median (interquartile range) time of insulin injection before meals was: Mix50 4.2 (25th percentile = 1.0; 75th percentile = 6.3) min, human soluble insulin 24.6 (25th percentile = 16.6; 75th percentile = 30.0) min. Pre-meal and bedtime BG concentrations did not differ between treatments. The BG 2 h after the evening meal was lower with Mix50 (8.40 +/- 2.95 mmol/l vs. 9.60 +/- 3.47 mmol/l) (P = 0.049). BG after breakfast and lunch, mean HbA1c, frequency of hypoglycaemia, frequency of snacks, and body weight were not different. CONCLUSION: The use of Mix50 in a basal-bolus regimen achieved similar control of pre-meal BG to human soluble insulin, and overall glycaemic control and hypoglycaemia risk were equivalent. This suggests that Mix50 can provide an adequate supply of insulin to control BG between meals while providing the convenience of injecting immediately before meals.

Adult↗

Acute hypoglycemia impairs the functioning of the central but not peripheral nervous system.

Acute hypoglycemia impairs functions of the central nervous system, but few controlled studies have assessed the impact of hypoglycemia on the function of the peripheral nervous system. Sixteen non-diabetic humans underwent two separate hyperinsulinemic glucose clamp procedures on different study days, in a counter-balanced fashion. On one occasion, euglycemia was maintained (blood glucose, 5.0 mmol l(-1)), and on the other occasion, hypoglycemia (blood glucose, 2.6 mmol l(-1)) was induced. During each condition, subjects performed a combined psychometric, cognitive-experimental and psychophysical test battery, and measures were made (in the dominant median and common peroneal nerves) of the motor nerve conduction velocities and the amplitudes of the motor action potentials. Hypoglycemia caused impaired performance of general cognitive and information processing tasks (P<.05), but nerve conduction velocities and the amplitudes of motor action potentials were unaffected. Conduction velocities of the common peroneal nerve decreased from baseline within each experimental condition, perhaps due to hyperinsulinemia. Overall, these results demonstrate that multiple levels of information processing in the brain may alter while peripheral nerve function remains intact, and imply that peripheral neurons do not have the same obligate requirement for glucose as a metabolic fuel as neurons of the central nervous system.

Acute Disease↗

Child and parental mental ability and glycaemic control in children with Type 1 diabetes.

AIMS: Many psycho-social factors can affect the glycaemic control of children with Type 1 diabetes, but the influence of the intelligence of the child and their parents has not been reported. METHODS: Seventy-eight children and adolescents with Type 1 diabetes and their mothers performed standardized tests to assess psychometric intelligence. The children were aged (median (range)) 12.0 (5-17) years with duration of diabetes 5.0 (1.0-13.0) years and required an insulin dose of (mean +/- SD) 1.0 +/- 0.3 U/kg per day. The children completed the Wide Range Achievement Test 3 reading test (WRAT3) and Raven's Standard Progressive Matrices (RSPM). A mean annual HbA1c was calculated for each subject (8.6 +/- 1.4%). The mothers performed the National Adult Reading Test (NART) and provided details of the occupation of the main wage-earner in the family from which social class (SC) was derived. RESULTS: The HbA1c of the child correlated with their age (r = 0.26, P = 0.02), SC (Kendall's rank correlation, tau = 0.17, P = 0.03) and with the NART error score of their mother (r = 0.28, P = 0.01), but no correlation was observed with the child's WRAT3 or RSPM score. Stepwise regression revealed that age and NART error score were the strongest independent determinants of glycaemic control (total adjusted r2 = 0.117). CONCLUSIONS: Parental intelligence appears to have a significant influence on the glycaemic control of a child with Type 1 diabetes, accounting for 7.6% of the reliable variance in HbA1c.

Adolescent↗

Cognitive function and information processing in type 2 diabetes.

AIMS: To determine whether uncomplicated Type 2 diabetes is associated with impairment of cognitive function and information processing ability. METHODS: Thirty-eight participants with uncomplicated Type 2 diabetes and 38 non-diabetic controls were studied. The two groups were comparable for age and premorbid intellectual ability, and did not have other medical disorders likely to affect cognitive function. An extensive battery of tests was administered which assessed different levels and domains of cognitive functions including verbal and visual memory, executive function, general mental ability and efficiency of information processing. RESULTS: No significant differences were found between the diabetic and control groups on any measure of cognitive function or information processing. The performance on these tests was not associated with recent glycaemic control (assessed by HbA1c). Duration of diabetes, however, correlated significantly with poorer performance on several measures of verbal memory. CONCLUSIONS: The results of the present study suggest that some aspect of Type 2 diabetes (as indexed by the estimated duration of the disorder) does relate significantly to cognitive function within the group with diabetes. However, other diabetes-related factors, such as macrovascular disease, hypertension and depression, may contribute more to previously observed cognitive decrements in Type 2 diabetes.

Age of Onset↗

Symptoms of hypoglycaemia in people with diabetes.

The symptoms of hypoglycaemia are fundamental to the early detection and treatment of this side-effect of insulin and oral hypoglycaemic therapy in people with diabetes. The physiology of normal responses to hypoglycaemia is described and the importance of symptoms of hypoglycaemia is discussed in relation to the treatment of diabetes. The symptoms of hypoglycaemia are described in detail. The classification of symptoms is considered and the usefulness of autonomic and neuroglycopenic symptoms for detecting hypoglycaemia is discussed. The many external and internal factors involved in the perception of symptoms are reviewed, and symptoms of hypoglycaemia experienced by people with Type 2 diabetes are addressed. Age-specific differences in the symptoms of hypoglycaemia have been identified, and are important for clinical and research practice, particularly with respect to the development of acquired hypoglycaemia syndromes in people with Type 1 diabetes that can result in impaired awareness of hypoglycaemia. In addition, the routine assessment of hypoglycaemia symptoms in the diabetic clinic is emphasized as an important part of the regular review of people with diabetes who are treated with insulin.

Aged↗

Acute hypoglycemia in humans causes attentional dysfunction while nonverbal intelligence is preserved.

OBJECTIVE: Experimentally induced hypoglycemia in humans causes progressive but reversible cognitive dysfunction, but it is not known to what extent neuropsychological tests index abilities of cognitive functioning that are important in everyday life. This study examines the effects of acute insulin-induced hypoglycemia on attention and intelligence in nondiabetic humans. RESEARCH DESIGN AND METHODS: A hyperinsulinemic glucose clamp was used to achieve controlled euglycemia (4.50 [0.22] mmol/l) and hypoglycemia (blood glucose 2.59 [0.19] mmol/l) in 20 healthy volunteers. Subjects were studied on two occasions in a counterbalanced order. During each study condition, subjects completed parallel tests of cognitive function. Cognitive function was assessed by the Test of Everyday Attention and Raven's Progressive Matrices. RESULTS: Hypoglycemia induced a significant deterioration in tests sensitive to both visual and auditory selective attention. During hypoglycemia, attentional flexibility deteriorated and speed of information processing was delayed. Sustained attention was preserved and intelligence scores did not deteriorate during hypoglycemia. CONCLUSIONS: During hypoglycemia, a significant deterioration occurs in attentional abilities, whereas fluid intelligence is preserved. On the basis of these results, it can be surmised that many complex attention tasks relevant to everyday life are impaired during moderate hypoglycemia.

Adult↗

Hypoglycaemia and cognitive function in diabetes.

The human brain is almost totally dependent on a continuous supply of glucose, deprivation of which rapidly causes malfunction. In the brain there are regional differences in the susceptibility to neuroglycopenia with the cerebral cortex being most sensitive while deeper structures are more resistant. A fall in blood glucose provokes a hierarchy of responses including secretion of counter-regulatory hormones and development of warning symptoms which alert the individual to treat the hypoglycaemia. Symptoms are generated when blood glucose falls to specific threshold concentrations, although these are dynamic and can be modified by various factors. Symptoms can be classified as autonomic and neuroglycopenic, with the latter being related to altered cognitive functioning. Acute hypoglycaemia produces electroencephalographic (EEG) changes as well as neurophysiological abnormalities including increased latency and/or reduced amplitude of sensory evoked potentials. At blood glucose below 3 mmol/l cognitive functioning becomes impaired but the degree of dysfunction differs in various domains and a battery of psychometric tests are required to assess impairment of cognitive function during hypoglycaemia. Complex, attention-demanding and speed-dependent responses are most impaired with accuracy often preserved at the expense of speed. Cognitive function does not recover fully until 40-90 min after blood glucose is restored to normal. Hypoglycaemia also provokes changes in mood, increases anxiety and may induce depression and fear of further hypoglycaemia, which can modify behaviour and influence quality of glycaemic control. Recurrent severe hypoglycaemia may have long-term sequelae in the form of cumulative cognitive impairment and impaired awareness of hypoglycaemia.

Acute Disease↗

The care of students with insulin-treated diabetes mellitus living in university accommodation: scope for improvement?

Concern has been expressed about the welfare of young adults with Type 1 diabetes mellitus who leave home to attend university or college for tertiary education. This has been highlighted by the local experience in Edinburgh of two male students with Type 1 diabetes, both of whom died from metabolic complications of diabetes during their first term at universities distant from their homes. One student died following the development of cerebral oedema secondary to diabetic ketoacidosis, which was probably precipitated by prolonged coma after an episode of severe hypoglycaemia. Another student, who was found 'dead in bed', had a history of previous severe hypoglycaemia. At a Fatal Accident Inquiry in Edinburgh, held following the death of the first student, recommendations were made to improve the care and personal safety of students with diabetes living in university accommodation. Despite the report being circulated to all Scottish universities, the second student died within three years of the inquiry. Further efforts to protect the welfare of students with Type 1 diabetes who are attending centres for tertiary education away from their home environment may require the more active participation by diabetes healthcare professionals.

Adolescent↗

Evaluation of an on-call diabetes service in a large teaching hospital.

AIMS: To assess prospectively the activity and effectiveness of a diabetes specialist on-call service. METHODS: All requests for specialist advice received by the doctor on-call for diabetes in a large teaching hospital were recorded and analysed over a period of 3 weeks. RESULTS: The total number of calls was 135 (mean 45 per week) of which 48.1% were outside normal working hours. Requests for advice from surgical and medical ward staff accounted for 43% of calls, the remainder were from staff in the maternity ward (12.6%), staff in other hospitals in the city (3.7%), general practitioners (13.3%) and patients (27.4%). The time spent by the on-call doctor for diabetes responding to calls was a mean of 8.6 h per week. The number of acute admissions prevented by this service was estimated to be 11 (3.6 per week). CONCLUSIONS: Open access to specialist advice provided by a doctor with expertise in diabetes is an effective adjunct to the delivery of diabetes care in the setting of a large teaching hospital.

Adult↗

Prevalence of pernicious anaemia in patients with Type 1 diabetes mellitus and autoimmune thyroid disease.

AIMS: To determine the prevalence of pernicious anaemia in patients with Type 1 diabetes mellitus and autoimmune thyroid disease. METHODS: A randomly selected asymptomatic group of 63 patients with Type 1 diabetes who also had autoimmune thyroid disease was studied. Blood samples were taken and assayed for serum B12. Those subjects with serum B12 concentrations below the reference range had a further blood sample taken for determination of intrinsic factor antibody. RESULTS: One patient had been diagnosed previously to have pernicious anaemia. Three patients had low serum B12 concentration and positive intrinsic factor antibody, confirming the diagnosis of pernicious anaemia. The prevalence of pernicious anaemia in this population with Type 1 diabetes and concomitant autoimmune thyroid disease was 6.3%. In female patients the prevalence of pernicious anaemia was 8.5%. CONCLUSIONS: Patients who have both Type 1 diabetes mellitus and autoimmune thyroid disease are at risk of developing pernicious anaemia.

Aged↗

Addison's disease in type 1 diabetes presenting with recurrent hypoglycaemia.

Primary adrenal insufficiency (Addison's disease) often develops insidiously. Although a rare disorder, it is more common in type 1 diabetes mellitus. A 19 year old male with type 1 diabetes and autoimmune hypothyroidism experienced recurrent severe hypoglycaemia over several months, despite a reduction in insulin dose, culminating in an adrenal crisis. Recurrent severe hypoglycaemia resolved after identification and treatment of the adrenocortical insufficiency. In type 1 diabetes, undiagnosed Addison's disease can influence glycaemic control and induce severe hypoglycaemia.

Addison Disease↗

Renal resistance to vasopressin in poorly controlled type 1 diabetes mellitus.

To investigate the hypothesis that diabetes induces nephrogenic diabetes insipidus, we studied the urine-concentrating ability in response to vasopressin (AVP) in 12 patients with insulin-dependent diabetes mellitus (IDDM) and 12 nondiabetic controls. Subjects were euglycemic-clamped, and after oral water loading, AVP was infused intravenously for 150 min. AVP induced a greater (P<0.001) rise in urine osmolality in controls (67.6+/-10.7 to 720+/-31.1 mosmol/kg, P<0.001) than in IDDM patients (64.3+/-21.6 to 516.7+/-89.3 mosmol/kg, P<0.001). Urinary aquaporin-2 concentrations after AVP infusion were higher in controls (611.8+/-105.6 fmol/mg creatinine) than in IDDM (462.0+/-94.9 fmol/mg creatinine, P = 0. 003). Maximum urine osmolality in IDDM was inversely related to chronic blood glucose control, as indicated by Hb A(Ic) (r = -0.87, P = 0.002). To test the hypothesis that improved glycemic control could reverse resistance to AVP, 10 IDDM subjects with poor glycemic control (Hb A(Ic) >9%) were studied before (B) and after (A) intensified glycemic control. Maximum urine osmolality in response to AVP increased with improved glycemic control (B, 443.8+/-49.0; A, 640.0+/-137.2 mosmol/kg, P<0.001), and urinary aquaporin-2 concentrations after AVP increased from 112.7 +/-69 to 375+/-280 fmol/mg creatinine (P = 0.006), with improved glycemic control. Poorly controlled IDDM is associated with reversible renal resistance to AVP.

Adolescent↗

Recovery of cognitive function and mood after severe hypoglycemia in adults with insulin-treated diabetes.

OBJECTIVE: Acute hypoglycemia in humans impairs cognitive functions and alters mood states. The time required for cognitive functions and moods to return to normal after an acute episode of severe hypoglycemia is unknown. RESEARCH DESIGN AND METHODS: Cognitive functions and moods were studied prospectively in 20 subjects with insulin-treated diabetes who had recently experienced a spontaneous episode of severe hypoglycemia ("hypo" subjects) and 20 matched control subjects with insulin-treated diabetes who had not experienced severe hypoglycemia during the preceding year. The hypo subjects had a history of a greater number of episodes of severe hypoglycemia (P = 0.000). Cognitive function tests and mood scales were administered at 1.5, 9, and 30 days after the severe hypoglycemia and at similar intervals for the control subjects. RESULTS: For most of the cognitive tests, no evidence of a "hangover" effect of the acute hypoglycemia on cognitive function was observed (P > 0.05). A trend was noted for levels of hedonic tone (P = 0.082) and energetic arousal (P = 0.053) to improve with time in the hypo subjects but not in the control subjects. However, the hypo subjects had chronically elevated levels of depression (P = 0.011) and anxiety (P = 0.049) and persistently performed more poorly in several cognitive tests, such as the Digit Symbol Test (P = 0.009) and the Stroop Task (P = 0.007). CONCLUSIONS: These results suggest that, in general, recovery from any acute cognitive decrement after severe hypoglycemia was complete by 1.5 days. The cognitive decrements and altered mood states noted in the hypo subjects may be persistent and may be a consequence of previous exposure to recurrent episodes of severe hypoglycemia.

Adult↗

Do diabetes guidelines influence the content of referral letters by general practitioners to a diabetes specialist clinic?

OBJECTIVE: To ascertain whether local guidelines for diabetes management influence the content of GP referral letters to a diabetes specialist clinic. DESIGN: Retrospective survey of hospital outpatient clinic casenotes and GP referral letters of patients with Type 2 diabetes. METHODS: An examination was made of 200 GP referral letters submitted before (Set 1), and 200 GP referral letters submitted after (Set 2), local guidelines on the management of adult diabetes had been issued to GPs in Lothian. The frequency with which micro- and macrovascular complications of diabetes were documented in the GP referral letters was compared with the frequency ascertained at the first attendance to the specialist clinic. MAIN RESULTS: Following the distribution of diabetes guidelines, no significant change was noted in the frequency with which specific conditions were documented in GP referral letters (Set 1 vs Set 2): hypertension (72% vs 79%); cerebrovascular disease (89% vs 80%); ischaemic heart disease (74% vs 79%); peripheral vascular disease (42% vs 64%); cataract (35% vs 44%); retinopathy (18% vs 40%) and peripheral neuropathy (17% vs 12%). At the diabetic clinic many unreported diabetic complications were found in patients who had been referred after varying periods of treatment in primary care. However, the guidelines did appear to have encouraged the active treatment of hyperglycaemia by GPs before referral of newly-diagnosed diabetic patients. CONCLUSIONS: Diabetes guidelines per se appeared to have very little effect on increasing the information provided in GP referral letters on relevant medical problems and did not appear to have influenced screening for complications in patients with Type 2 diabetes by GPs before specialist referral. Methods other than the issue of written guidelines are required to achieve optimal assessment of diabetic patients in the community.

Correspondence as Topic↗