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R J McCrimmon

Publications and source records attributed to R J McCrimmon.

13 recordsLinked to original sources
PubMed2002

AICAR and phlorizin reverse the hypoglycemia-specific defect in glucagon secretion in the diabetic BB rat.

Individuals with type 1 diabetes demonstrate a hypoglycemia-specific defect in glucagon secretion. To determine whether intraislet hyperinsulinemia plays a role in the genesis of this defect, glucagon-secretory responses to moderate hypoglycemia induced by either insulin or a novel combination of the noninsulin glucose-lowering agents 5-aminoimidazole-4-carboxamide (AICAR) and phlorizin were compared in diabetic BB rats (an animal model of type 1 diabetes) and nondiabetic BB rats. The phlorizin-AICAR combination was able to induce moderate and equivalent hypoglycemia in both diabetic and nondiabetic BB rats in the absence of marked hyperinsulinemia. Diabetic BB rats demonstrated impaired glucagon and epinephrine responses during insulin-induced hypoglycemia compared with nondiabetic rats. In contrast, both glucagon (9- to 10-fold increase) and epinephrine (5- to 6-fold increase) responses were markedly improved during phlorizin-AICAR hypoglycemia. Combining phlorizin, AICAR, and insulin attenuated the glucagon response to hypoglycemia by 70% in the diabetic BB rat. Phlorizin plus AICAR had no effect on counterregulatory hormones under euglycemic conditions. We conclude that alpha-cell glucagon secretion in response to hypoglycemia is not defective if intraislet hyperinsulinemia is prevented. This suggests that exogenous insulin plays a pivotal role in the etiology of this defect.

Aminoimidazole Carboxamide↗
PubMed1999

Appraisal of mood and personality during hypoglycaemia in human subjects.

This study used the biological model of experimental hypoglycaemia to examine the effect of a manipulation in mood-state on appraisal. Controlled hypoglycaemia was achieved using the hyperinsulinaemic glucose clamp technique. Mood, appraisal, and personality traits were assessed using well validated questionnaires. Our findings 1) reaffirm the existence of multiple arousal systems in the generation of moods, 2) show that the induction of a negative mood state does lead to more negative appraisals of a life situation, and 3) show that personality traits remain stable during the experience of negative emotions and cognitions. We conclude that hypoglycaemia, by inducing a state of tense tiredness in some individuals, may lead to more negative appraisals of a life situation but does not alter people's reporting of behavioural dispositions.

Adult↗
PubMed1999

Anger state during acute insulin-induced hypoglycaemia.

This study sought to examine the effects of insulin-induced hypoglycaemia on anger state, and to describe the associations between change in the anger state and measures of anger trait and anger expression (assessed using the State-Trait Anger Expression Inventory). A hyperinsulinaemic glucose clamp was used to achieve controlled euglycaemia (5.0 mmol/L) and hypoglycaemia (2.6 mmol/L) in 18 nondiabetic subjects and 30 people with insulin-dependent diabetes mellitus (IDDM). Subjects underwent both hypoglycaemic and euglycaemic conditions, separated by 2 weeks, in a counterbalanced order. During each study condition subjects were asked to complete a questionnaire on anger state. Results at euglycaemia and hypoglycaemia were compared, and differences between the conditions were correlated with measures of anger trait and anger expression. Hypoglycaemia caused both nondiabetic and IDDM subjects to report a significant increase in feelings of anger, despite being in a nonconfrontational setting. However, there were no clear associations between an individual's change in reported anger and measures of anger trait and anger expression. No association was found between the change in anger state and the intensity of an individual's symptomatic response to hypoglycaemia.

Adult↗
PubMed1998

Perceived symptoms of hypoglycaemia in elderly type 2 diabetic patients treated with insulin.

Elderly insulin-treated diabetic patients have a high risk of severe hypoglycaemia, yet their hypoglycaemic symptom profile has attracted little research. In this study, the frequency and intensity of symptoms of hypoglycaemia were recorded using a validated questionnaire in 132 insulin-treated diabetic patients, aged 70 years or more. Principal components analysis (PCA) was used to discover the factorial structure of the symptoms. Lightheadedness and unsteadiness were prominent symptoms in the elderly patients. PCA suggested three separate groups of symptoms: (1) those related specifically to impairment of co-ordination and articulation; (2) more general neuroglycopenic symptoms, and (3) autonomic symptoms. The frequency and classification of hypoglycaemic symptoms in this elderly population is different from those seen in younger diabetic patients treated with insulin. Neurological symptoms of hypoglycaemia were more commonly reported and may be misinterpreted as features of cerebrovascular disease. Health professionals and carers involved in the treatment and education of diabetic patients should be aware of the age-specific differences in hypoglycaemic symptoms.

Aged↗
PubMed1998

Hypoglycaemic symptoms reported by children with type 1 diabetes mellitus and by their parents.

To compare the hypoglycaemic symptoms reported by children with Type 1 diabetes and signs observed by and symptoms reported to their parents, 101 pairs, consisting of a child with diabetes and one of their parents, were asked to report the frequency with which they experienced, or witnessed, each of 31 symptoms during hypoglycaemia. The hypoglycaemic symptoms reported by the children and the reported symptoms and signs observed by their parents were classified, using multivariate statistical analyses, and compared. Close agreement was observed between the children and their respective parents' scores for frequencies of most symptoms/signs, as demonstrated by Spearman's rank correlations (median tau s = 0.25, p < 0.02). Principal Components Analysis of the symptoms/signs observed by the parents showed three factors: autonomic, neuroglycopenic, and behavioural disturbance. Analysis of the symptoms experienced by the children also identified three factors: behavioural disturbance, malaise and a third factor consisting of a combination of autonomic and neuroglycopenic symptoms. The parents could differentiate three separate groups of reported hypoglycaemic symptoms and signs (autonomic, neuroglycopenic, and behavioural disturbance) in their children. The children reported a similar group of behavioural symptoms but did not discriminate between autonomic and neuroglycopenic symptoms. These findings have important implications for the education of parents and children with Type 1 diabetes regarding the symptoms and signs of hypoglycaemia.

Adolescent↗
PubMed1998

Effect of acute hypoglycemia on visual information processing in adults with type 1 diabetes mellitus.

Acute hypoglycemia in people with type 1 (insulin-dependent) diabetes mellitus causes general impairment in cognitive performance. The effects on more specific cognitive processes are less well defined. Acute hypoglycemia has been shown to impair visual information processing in nondiabetic human subjects and has now been examined in 16 adult subjects with type 1 diabetes. All subjects had normal visual acuity and no diabetic retinopathy, and their median (range) age was 24 (18-47) years with a median (range) duration of type 1 diabetes of 8 (2-18) years and a mean (SD) HbA1c of 8.5 (1.3)%. A hyperinsulinemic glucose clamp technique was used to maintain arterialized blood glucose at 5.0 mmol l(-1), and on separate test days, either euglycemia was continued or hypoglycemia (2.6 mmol l(-1)) was induced. During each condition subjects performed tests of visual processing and cognitive function. Hypoglycemia caused a significant disruption in general cognitive ability as assessed by digit symbol (p < 0.001) and trail-making B (p < 0.05) tasks. Conventional measures of visual acuity were unaffected by hypoglycemia, but visual information processing deteriorated significantly as indexed by inspection time (p < 0.005) and visual change detection (p < 0.01). Contrast sensitivity tended to deteriorate during hypoglycemia (p = 0.06). In conclusion, hypoglycemia impairs important aspects of early visual information processing and contrast sensitivity in adults with type 1 diabetes. Further research is needed to evaluate the functional relevance of such changes for everyday tasks that require the intake of visual information at speed and under conditions of low contrast.

Adolescent↗
PubMed1997

Symptomatic and physiological responses to hypoglycaemia induced by human soluble insulin and the analogue Lispro human insulin.

The aim of this study was to compare the glycaemic threshold for onset of the clinically detectable sympatho-adrenal (autonomic) reaction (defined as 'R') to hypoglycaemia induced by Lispro human insulin, with that induced by human soluble insulin (HS). The hypoglycaemia symptom profile, counterregulatory hormonal responses, and cognitive performance at R were also compared. Sixteen patients with IDDM, aged 32.5 (20-45) (median (range)) years and duration of IDDM 3.0 (0.5-4.5) years participated in a randomized, double-blind study during which intravenous infusions of either Lispro or HS insulin (2.0 mU kg(-1) min(-1)) were used on separate occasions to lower the blood glucose to the level at which R was induced. For both HS and Lispro, significant increments in systolic blood pressure (p<0.05), heart rate (p<0.05), and in autonomic (p<0.05) and neuroglycopenic symptom scores (p<0.05) occurred at R, and a significant deterioration was observed in cognitive performance (p<0.05). In response to hypoglycaemia, a significant increase from baseline occurred in plasma concentrations of all of the counterregulatory hormones (p<0.01) and the magnitude of response and temporal pattern did not differ, nor were any significant differences apparent between HS and Lispro insulins for any of the variables studied. The autonomic reaction occurred at a blood glucose (mean +/- SD) of 2.0 (+/- 0.6) mmol(-1) for Lispro and 1.9 (+/- 0.6) mmol(-1) for HS, which did not differ significantly. Thus, at the autonomic reaction to hypoglycaemia no significant differences were evident in the glycaemic threshold, symptom profile, physiological responses, and counterregulatory hormonal responses between Lispro and human soluble insulin in IDDM patients.

Adult↗
PubMed1997

Auditory information processing during acute insulin-induced hypoglycaemia in non-diabetic human subjects.

Acute insulin-induced hypoglycaemia impairs performance on tests of general mental ability in humans. It is recognized that different brain functions vary in their sensitivity to neuroglycopenia, but little is known about the effects of neuroglycopenia on specific brain processes. The effect of controlled hypoglycaemia on two aspects of auditory information processing (auditory temporal processing and simple auditory processing) was examined in a homogeneous group of 20 healthy non-diabetic human subjects. Auditory temporal processing (temporal order discrimination) and simple auditory processing (pitch discrimination, single-tone duration and single-tone loudness discrimination) tests were part of the Test of Basic Auditory Capabilities (TBAC). Two tests of general cognitive performance (Digit Symbol Substitution and Trail Making B) were included to provide a measure of general brain functioning during hypoglycaemia. Hypoglycaemia lead to a significant deterioration in auditory temporal processing (P < 0.01), and a deterioration in one of three tasks of simple auditory processing (discrimination of single-tone loudness, P < 0.05). Significant disruptions also occurred in both tests of general brain functioning. These results are congruent with other studies in human subjects, showing a disruptive effect of hypoglycaemia on visual information processing when examined under conditions of limited perceptual time, and they provide further evidence of the importance of sensory processing speed in basic perceptual and cognitive functions. The disruptive effect of moderate insulin-induced hypoglycaemia on auditory perception may have implications for insulin-treated diabetic humans exposed to this metabolic stress, because of the importance of hearing in everyday life.

Acoustic Stimulation↗
PubMed1996

Visual information processing during controlled hypoglycaemia in humans.

A general impairment of cognitive performance occurs during acute insulin-induced hypoglycaemia, but little objective evidence is available for disruption of more specific cognitive processes. The effect of controlled hypoglycaemia on the early stages of visual information processing and contrast sensitivity was examined in a homogeneous group of 20 nondiabetic human subjects. Hypoglycaemia caused a significant disruption in general cognitive performance as assessed by a digit symbol task (P < 0.001) and the trail making B task (P < 0.05). Hypoglycaemia also produced a highly significant deterioration in performance on all of the visual information processing tasks, namely inspection time (IT) (P = 0.01), visual change detection (VCD) (P < 0.005) and visual movement detection (VMD) (P < 0.005). A significant deterioration in contrast sensitivity was observed during hypoglycaemia (P < 0.005). In contrast, no significant effect of hypoglycaemia was demonstrated on standard clinical measures of visual acuity or stereoscopic vision. Thus, although hypoglycaemia caused no detectable deterioration in visual acuity as measured by Snellen-type tests, a marked deterioration occurred in the speed of visual information processing and in contrast sensitivity. As many decisions are made under conditions of limited perceptual time and low visual contrast (e.g. when driving), the disruptive effect of moderate insulin-induced hypoglycaemia on visual perception will have important practical implications in diabetic humans exposed to this metabolic stress. The present results are congruent with other evidence which shows that the early stages of visual information processing are susceptible to deterioration by general cerebral insults.

Adult↗
PubMed1995

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↗
PubMed1995

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↗
PubMedDate not supplied

Hypoglycaemia, the most feared complication of insulin therapy.

Insulin-induced hypoglycaemia, the most frequent side-effect of insulin-therapy, is a potential source of considerable morbidity and has a recognised mortality. Acute hypoglycaemia produces an intense physiological stress with profound sympathoadrenal stimulation and widespread activation of hormonal counterregulatory systems, leading to secondary haemodynamic and haemorheological changes. The clinical effects of acute and recurrent severe hypoglycaemia are associated with significant morbidity including reversible, and permanent, abnormalities of cardiovascular, neurological and cognitive function, in addition to trauma and road traffic accidents. Comprehension of the morbidity of hypoglycaemia is important when designing insulin regimens and determining therapeutic goals for individual patients if the frequency and adverse effects of this dangerous side-effect of insulin therapy are to be limited.

Diabetes Mellitus, Type 1↗