Driving and diabetes.
Explore the source record for details and available documents.
Automobile Driving↗
Biomedical subjects
B M Frier
Publications and source records attributed to B M Frier.
Human growth hormone and restoration of hypoglycaemia awareness.
Explore the source record for details and available documents.
Awareness↗
Intensified conventional insulin treatment and neuropsychological impairment.
Explore the source record for details and available documents.
Cognition Disorders↗
Pancreatic and pituitary hormonal responses to insulin-induced hypoglycaemia during muscarinic cholinergic blockade in man.
To investigate the role of muscarinic cholinergic mechanisms in mediating the pancreatic and pituitary hormonal responses to hypoglycaemia, six normal subjects were studied during acute insulin-induced hypoglycaemia under control conditions, and during blockade with intravenous atropine. During atropine blockade the response of pancreatic polypeptide was suppressed while the maximum response of plasma glucagon was significantly higher. The increment in plasma vasopressin was also increased significantly during cholinergic blockade. During blockade with atropine the responses of plasma prolactin was reduced, with a slight but significant reduction in the growth hormone response, and although a similar maximum response of plasma ACTH was achieved, this rise was delayed. These results implicate involvement of a cholinergic muscarinic inhibitory and stimulatory mechanisms in regulating the responses of pancreatic and pituitary hormones to hypoglycaemia.
Adrenocorticotropic Hormone↗
Changes in renal function during acute insulin-induced hypoglycaemia in patients with type 1 diabetes.
The effect of acute hypoglycaemia on renal function was examined in eight male patients with Type 1 diabetes who had normal urinary albumin excretion. Insulin was given as a bolus intravenous injection (0.125 U kg-1) and plasma glucose fell to a nadir of 1.6 (SE 0.2) mmol l-1, with all patients experiencing an acute autonomic reaction. Renal plasma flow fell from 674 (106) to 540 (198) ml min-1 during hypoglycaemia (p less than 0.01) and returned to 655 (181) ml min-1 (NS vs baseline). Glomerular filtration rate (GFR) declined from 143 (23) to 110 (36) ml min-1 during hypoglycaemia (p less than 0.02), rising to 150 (44) ml min-1 in the recovery period (NS vs baseline). The urinary flow rate and urinary albumin excretion rate both fell significantly in response to hypoglycaemia (10.6 (1.2) to 4.7 (1.1) ml min-1; p less than 0.002, and 46.2 (10.6) to 26.0 (10.5) micrograms min-1, respectively). Urinary dopamine excretion also declined, from 322 (37) to 211 (29) mumol min-1 (p less than 0.005) but sodium excretion was unchanged. Plasma adrenaline concentration (0.2 (0.03) to 1.7 (0.4) nmol l-1; p less than 0.01) and plasma renin activity (0.49 (0.13) to 1.08 (0.17) ng-Ang 1 l-1 h-1; p less than 0.01) increased during hypoglycaemia, but changes in plasma noradrenaline and angiotensin II levels did not attain significance. These acute changes in renal function, observed during hypoglycaemia in diabetic patients, may result from direct stimulation of the efferent sympathetic nerves to the kidney, complemented by the hormonal changes induced by hypoglycaemia.
Adult↗
Hospital in-patient statistics underestimate the morbidity associated with diabetes mellitus.
Hospital in-patient statistics are an important outcome measurement in the assessment of the morbidity associated with diabetes mellitus. A prospective study of 157 consecutive admissions over a 28-day period compared diagnoses obtained from the clinical records with the ICD9 coding of the same admissions recorded at the Information and Statistics Division of the Scottish Health Service. Sixty-one percent of all discharge summaries omitted the diagnosis of diabetes. Even when admission was principally related to diabetes complications, 47% of medical and 88% of surgical discharge summaries omitted diabetes as a diagnostic category. ICD9 coding underestimated the percentage of admissions accounted for by diabetic patients by 100% (2.8 vs 5.6%) and as a result underestimated bed occupancy by over 200% (4.3 vs 13.7%), and is thus failing to fulfil its potential as a demographic and epidemiological record of resource use by disease classification.
Adolescent↗
Oral disorders associated with diabetes mellitus.
The protean manifestations of diabetes include various associated oral disorders such as sialosis, xerostomia, impairment of taste, and localized infections of which oral candidosis is the most commonly observed. The association of specific oral diseases and diabetes is of importance both in the detection of undiagnosed diabetes and in the elucidation of the pathogenesis of various oro-facial diseases. The clinical features and possible causes of oral disorders recognized to be associated with diabetes are reviewed with emphasis on good oral hygiene in the diabetic patient.
Candidiasis↗
Suppression of plasma intact parathyroid hormone levels during insulin-induced hypoglycemia in humans.
The adrenergic control of intact PTH secretion was investigated by measuring its plasma concentration during insulin-induced hypoglycemia in normal human subjects under control conditions (n = 12) and after alpha (n = 5)- or beta (n = 6)-adrenoceptor blockade. Blood samples were taken at baseline, at the time of the acute hypoglycemic reaction, and at regular intervals for 60 min thereafter. Plasma concentrations of intact PTH, catecholamines, total calcium, magnesium, albumin, phosphate, and glucose were measured in all subjects, and plasma ionized calcium was also assayed in three subjects during acute hypoglycemia without pharmacological blockade. At the time of the acute hypoglycemic reaction, the plasma concentration of intact PTH in the control subjects fell to 60.8% of baseline values and was accompanied by a small but significant increase in plasma total calcium. Intact PTH concentrations remained suppressed after the plasma calcium concentration had returned to normal. The two groups of subjects who were exposed to adrenoceptor blockade exhibited a reduced fall in plasma intact PTH and showed no significant increase in plasma total calcium. Therefore, insulin-induced acute hypoglycemia was associated with a fall in plasma intact PTH. Adrenoceptor blockade reduced, but did not abolish, the response, suggesting that other factors are involved.
Adult↗
Vascular endothelial cell antibodies in diabetic patients. Association with diabetic retinopathy.
OBJECTIVE: To determine the incidence of antiendothelial cell antibodies in diabetic patients with and without retinopathy. RESEARCH DESIGN AND METHODS: The study consisted of 70 insulin-dependent diabetic (IDDM) subjects, 36 non-insulin-dependent diabetic (NIDDM) subjects, and 40 nondiabetic control subjects. Blood samples were obtained from diabetic patients and control subjects and patients with background and proliferative retinopathy were identified. RESULTS: Vascular endothelial cell (VEC) antibodies were examined in the sera of 36 NIDDM subjects, 70 IDDM subjects, and 40 nondiabetic control subjects by indirect immunofluorescence. VEC antibodies were present in 5 of 40 (12%) control subjects, 7 of 23 (30%) newly diagnosed IDDM patients, 6 of 17 (35%) IDDM patients without retinopathy, 12 of 18 (67%) IDDM patients with background retinopathy (P less than 0.05), and 9 of 12 (75%) IDDM patients with proliferative retinopathy (P less than 0.01). Three of 13 (23%) NIDDM patients with retinopathy and 6 of 23 (26%) without retinopathy were VEC antibody positive. No associations were observed between the presence of VEC antibodies and either the quality of glycemic control or the duration of diabetes. A significant association between VEC antibodies and large-vessel disease was found in IDDM patients with retinopathy (P less than 0.05). CONCLUSIONS: Antibodies directed against vascular endothelial cells may play a role in the development of microvascular, and possibly macrovascular, disease in diabetes.
Adult↗
Responses of peripheral blood cells to acute insulin-induced hypoglycaemia in humans: effect of alpha-adrenergic blockade.
Acute hypoglycaemia provokes rapid changes in peripheral blood cell counts. To examine possible adrenergic mechanisms modulating these changes, counts of peripheral blood cells including lymphocytes, granulocytes and red cells were measured in response to acute hypoglycaemia in a group of six normal subjects in control conditions (study 1), and during alpha-adrenergic blockade with phentolamine (study 2). In study 1 hypoglycaemia provoked a biphasic white cell response, with an early rise in lymphocyte count and a later rise in granulocyte count. The red cell count increased modestly following hypoglycaemia. During alpha-adrenergic blockade, the rise in total white cell count was diminished, with the rise in the lymphocyte count being greatly obtunded. The rise in the granulocyte count was unchanged. The increment of the red cell count during acute hypoglycaemia was abolished. These findings suggest that the increments of peripheral lymphocyte and red cell counts in response to acute insulin-induced hypoglycaemia are mediated via alpha-adrenoreceptors.
Acute Disease↗
Cumulative cognitive impairment following recurrent severe hypoglycaemia in adult patients with insulin-treated diabetes mellitus.
To examine the hypothesis that episodes of severe hypoglycaemia may cause cumulative cognitive impairment. 100 Type 1 (insulin-dependent) diabetic patients were examined. Their age range was 25-52 years, and the onset of diabetes had occurred after the age of 19 years. Patients with evidence of organic brain disease, including cerebrovascular disease, were excluded. A questionnaire was used to assess the number, frequency and severity of hypoglycaemic episodes experienced during treatment with insulin and the accuracy of this retrospective information was verified from general practice and hospital case-notes. A detailed neuropsychological assessment was undertaken, including tests of pre-morbid and present IQ (Wechsler-Revised), memory and information-processing speed. Significant correlations were observed between the frequency of severe hypoglycaemia and the magnitude of intellectual decline, Performance IQ, inspection time and reaction time (patients with the more frequent hypoglycaemia had poorer performance). Two sub-groups of patients were identified on the basis of their experience of severe hypoglycaemia, and were balanced for pre-morbid IQ, age and duration of diabetes. One sub-group (n = 23) had never experienced severe hypoglycaemia (Group A), whilst the other sub-group (n = 24) had suffered at least five episodes of severe hypoglycaemia (Group B). Group B had greater intellectual impairment than Group A, and Group B also had a significantly slower mean reaction time and higher reaction time variance when compared with Group A.
Adult↗
Salivary secretion of albumin in type 1 (insulin-dependent) diabetes.
The concentration of albumin in saliva is low in healthy humans. To determine whether alterations in capillary permeability in diabetes affects the salivary glands, the concentration of albumin in parotid saliva was measured in 26 Type 1 (insulin-dependent) diabetic patients, and compared to 32 non-diabetic control subjects. The diabetic patients were subdivided into 3 groups on the basis of the urinary excretion of albumin in timed overnight collections of urine: (1) normal albumin excretion (less than 30 micrograms/min) n = 13; (2) microalbuminuria (30-300 micrograms/min) n = 7, and (3) macroalbuminuria (greater than 300 micrograms/min) n = 6. Saliva was collected for one minute following stimulation with 1 ml 10% citric acid, and the concentration of albumin was measured by a sensitive ELISA method. No significant difference in salivary albumin concentration was found between the control group and any of the diabetic groups. Thus, although urinary albumin excretion was increased, suggesting altered capillary permeability, simultaneous leakage of albumin into saliva was not observed. Measurement of salivary albumin concentration does not, therefore, provide a marker of occult microvascular disease in diabetes.
Adult↗
Association between connective tissue changes and smoking habit in type 2 diabetes and in non-diabetic humans.
Two hundred type 2 (non-insulin-dependent) diabetic patients and 170 non-diabetic age- and sex-matched normotensive controls were examined for limited joint mobility (LJM) and Dupuytren's contracture (DC), and their smoking history was documented. The prevalences of LJM and DC were not significantly different in diabetic and control subjects (LJM: odds ratio 1.58, 95% CI 0.99 to 2.50; DC: odds ratio 1.34, CI 0.81 to 2.23). Cigarette smoking was positively associated with both LJM and DC in the diabetic patients (LJM: relative risk (R) = 1.96, 95% CI 1.10 to 3.49; DC: R = 2.88, CI 1.29 to 6.43) and in the control group (LJM: R = 2.22, CI 1.70 to 5.86; DC: R = 2.71, CI 1.23 to 5.89). Limited joint mobility and Dupuytren's contracture are both associated with cigarette smoking in type 2 diabetic patients and in age-matched non-diabetic subjects. This suggests that type 2 diabetes is only one of a number of factors which promote the development of these connective tissue changes.
Connective Tissue↗
Autonomic mechanisms underlying intraocular pressure changes during insulin-induced hypoglycaemia in normal human subjects: effects of pharmacological blockade.
1. A fall in intraocular pressure is induced by acute hypoglycaemia in humans. The role of the autonomic nervous system in mediating this response was investigated in 24 normal volunteers in whom hypoglycaemia was induced with intravenous soluble insulin, under four experimental conditions: (1) control (n = 6), (2) non-selective alpha-adrenoceptor blockade (phentolamine) (n = 6), (3) non-selective beta-adrenoceptor blockade (propranolol) (n = 6) and (4) cholinergic blockade (atropine) (n = 6). Intraocular pressure was measured by using an applanation tonometer. In 12 subjects intraocular pressure was measured during each type of pharmacological blockade of similar duration without induction of hypoglycaemia, to assess the effects of individual antagonists. 2. In the control study intraocular pressure fell during hypoglycaemia from 15 +/- 1.0 to 10 +/- 1.3 mmHg (P less than 0.01) 10 min after the autonomic reaction. beta-Adrenoceptor blockade caused a reduction in intraocular pressure from 15 +/- 1.1 to 9 +/- 1.0 mmHg (P less than 0.001) before the administration of insulin, and when hypoglycaemia was induced intraocular pressure decreased further to 7 +/- 1.0 mmHg (P less than 0.05, compared with immediately before insulin). A decrease in intraocular pressure of similar magnitude was observed with propranolol alone (16 +/- 1.0 to 10 +/- 1.0 mmHg, P less than 0.05). 3. Cholinergic blockade had no immediate effect on intraocular pressure, and the reduction in intraocular pressure during hypoglycaemia was of similar magnitude to that observed during the control study.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Hypoglycaemia unawareness in type 1 diabetes: a lower plasma glucose is required to stimulate sympatho-adrenal activation.
To investigate the relationship between awareness of symptoms and the autonomic reaction of hypoglycaemia, acute hypoglycaemia was induced with intravenous insulin (2.5 mU kg-1 min-1) in diabetic and non-diabetic subjects, all of whom had normal cardiovascular autonomic function tests. Three groups were studied: (1) nine patients with Type 1 diabetes with loss of awareness of hypoglycaemia; (2) eight patients who had normal awareness of hypoglycemia, matched for duration of diabetes and blood glucose control; (3) eleven non-diabetic volunteers. The onset of the acute autonomic reaction was identified objectively by the sudden and rapid responses of heart rate and sweating. Cognitive function and hypoglycaemia symptom scores were estimated serially. Acute autonomic activation was observed to occur in all subjects in response to hypoglycaemia. In the 'unaware' diabetic patients, onset of the reaction occurred at a significantly lower plasma glucose (1.0 +/- 0.1 mmol l-1) than in the 'aware' diabetic patients (1.6 +/- 0.2 mmol l-1) (p less than 0.05) or in the non-diabetic control group (1.4 +/- 0.1 mmol l-1) (p less than 0.05). Obvious neuroglycopenia was observed only in the 'unaware' diabetic group and developed when plasma glucose had declined to approximately 1.4 +/- 0.1 mmol l-1, and thus preceded the reaction (p less than 0.02 vs the autonomic threshold). The maximal rise in plasma adrenaline was of similar magnitude in all three groups but a lower plasma glucose was required to stimulate this hormonal response in the 'unaware' patients, in whom the plasma adrenaline concentration was lower at the time of the reaction. Thus, the plasma glucose at which activation of the autonomic reaction was observed was lower in the diabetic patients with unawareness of hypoglycaemia.
Adrenal Glands↗
Renal responses to angiotensin II infusion in early type 1 (insulin-dependent) diabetes.
The renal response to infusion of sub-pressor doses of angiotension II was examined in nine euglycaemic Type 1 (insulin-dependent) diabetic patients with diabetes of short duration and nine non-diabetic control subjects. Plasma concentrations of angiotensin II and of free insulin were similar in both groups at baseline and during angiotensin II infusion. Glomerular filtration rate (Inutest clearance) fell to a similar extent during angiotensin II infusion in both groups (diabetic 116(SE 5) to 102(5) ml min-1 1.73-m-2; control 113(6) to 100(5) ml min-1 1.73-m-2). There was a large dose-dependent fall in effective renal plasma flow (p-aminohippurate clearance) during angiotensin II infusion which was of similar magnitude in both groups (diabetic; 694(46) to 521(21) ml min-1 1.73-m-2; control 665(41) to 498(30) ml min-1 1.73-m-2). The absolute and the fractional rates of urinary excretion of sodium were both lower in the diabetic group throughout the study, but there was a comparable antinatriuretic response to angiotensin II. Thus, the renal haemodynamic response to angiotensin II infusion is normal in early well-controlled Type 1 diabetes. Differences were found in the renal handling of sodium, which could not be related to altered renal tubular responses to angiotensin II or to peripheral hyperinsulinaemia.
Adult↗
Effect of alpha-adrenergic blockade on pituitary hormonal responses to insulin-induced hypoglycemia in humans.
Arginine vasopressin, oxytocin and ACTH are released from the pituitary gland in response to acute hypoglycemia. To investigate the role of alpha-adrenergic mechanisms in mediating this response, 6 non-diabetic subjects were studied during hypoglycemia induced by 0.15 IU/kg i.v. insulin under control conditions, and during non-selective alpha-adrenergic blockade with phentolamine. In the control study plasma arginine vasopressin rose from 1.6 +/- 0.8 pmol/l (mean +/- SEM) basally to a maximum of 2.5 +/- 0.8 pmol/l following hypoglycemia (p less than 0.05). An exaggerated response was found during phentolamine blockade, with a maximum plasma vasopressin of 11.5 +/- 0.4 pmol/l (by analysis of variance, p less than 0.05). The plasma oxytocin response to hypoglycemia was similarly increased during phentolamine compared to control. Plasma growth hormone rose to 94 +/- 19 mU/l, and during blockade with phentolamine the response was significantly reduced reaching a peak of 34 +/- 7 mU/l (by analysis of variance, p less than 0.05). ACTH and prolactin both increased in response to hypoglycemia, but the increases were not affected by phentolamine. An alpha-adrenergic mechanism appears to inhibit the release of arginine vasopressin and oxytocin in response to hypoglycemia, but does not appear to affect the secretion of ACTH.
Adrenergic alpha-Antagonists↗
Symptoms of acute insulin-induced hypoglycemia in humans with and without IDDM. Factor-analysis approach.
OBJECTIVE: This study allocated the symptoms identified during acute hypoglycemia objectively to the autonomic or neuroglycopenic groups of symptoms by the use of factor analysis. RESEARCH DESIGN AND METHODS: Twenty-five nondiabetic subjects, 14 newly diagnosed insulin-dependent diabetic patients, and 16 insulin-dependent diabetic patients with diabetes greater than 4 yr duration were studied. Acute hypoglycemia was induced with insulin (2.5 mU.kg-1 body wt.min-1 i.v.), and symptoms of hypoglycemia were recorded with a seven-point scale at regular time points throughout the studies. Factor analysis of the symptom scores at the time of the acute autonomic reaction with principal component analysis followed by Varimax rotation was used to separate those symptoms that might belong to neuroglycopenic and autonomic groups. RESULTS: Hypoglycemia was induced to a mean +/- SE plasma glucose nadir of 1.3 +/- 0.1 mM in nondiabetic subjects, to 2.0 +/- 0.3 mM in newly diagnosed diabetic patients, and 1.4 +/- 0.2 mM in patients with diabetes of greater than 4 yr duration. The most frequently reported autonomic symptoms were sweating, trembling, and warmness, and the most frequently reported neuroglycopenic symptoms were inability to concentrate, weakness, and drowsiness. Neuroglycopenic symptoms were reported more commonly at the onset of hypoglycemia, which was identified by the development of symptoms. Factor analysis grouped trembling, anxiety, sweating, warmness, and nausea together, and this grouping was labeled an autonomic factor. A second factor was identified that included dizziness, confusion, tiredness, difficulty in speaking, shivering, drowsiness, and inability to concentrate, which was labeled a neuroglycopenic factor. CONCLUSIONS: This study demonstrated the high frequency with which neuroglycopenic symptoms occur at the onset of hypoglycemia and the symptoms that could be used by an individual patient as a warning of the development of acute hypoglycemia, although the rapid reduction of plasma glucose is faster than experienced by the ambulant diabetic patient. Factor analysis assisted with the allocation of symptoms to either the autonomic or neuroglycopenic groupings, but the allocation of some symptoms remained undefined, and care must be taken when assessing symptoms such as hunger, weakness, blurred vision, and drowsiness when comparing the frequency of autonomic versus neuroglycopenic symptoms. To reduce the confusion resulting from the use of different symptom questionnaires in studies of hypoglycemia, a sample questionnaire is presented, the development of which was assisted by our analysis.
Adult↗