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Biomedical subjects

B M Frier

Publications and source records attributed to B M Frier.

At least 127 records · Page 7Linked to original sources
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

Effects of adrenergic blockade on serum potassium changes in response to acute insulin-induced hypoglycemia in nondiabetic humans.

OBJECTIVE: To determine the possible role of adrenergic mechanisms in mediating the fall in serum potassium concentration after intravenous injection of insulin. RESEARCH DESIGN AND METHODS: Eighteen nondiabetic male volunteers, divided into three groups of six subjects, comprised the study. Hypoglycemia was induced by a bolus of short-acting insulin (0.15 U/kg body wt). Six subjects were studied in control conditions, six during alpha-adrenergic blockade with phentolamine, and six during beta-adrenergic blockade with propranolol. RESULTS: In the control group, there was an immediate fall in serum potassium from 4.0 +/- 0.1 to 3.6 +/- 0.1 mM at baseline + 15 min. After the onset of acute hypoglycemia, potassium decreased further in the control group, reaching a lowest concentration of 3.3 +/- 0.1 mM. In the propranolol group, the late decrease in potassium was inhibited, and there were no further changes in serum potassium. During alpha-blockade, there was an exaggerated fall to 2.6 +/- 0.1 mM at 30 min after the onset of hypoglycemia. CONCLUSIONS: The later fall in serum potassium, which occurs after the onset of hypoglycemia, is probably mediated by stimulation of beta-adrenoreceptors, whereas coincidental stimulation of alpha-adrenoreceptors opposes this fall in potassium and may prevent the development of severe hypokalemia in response to acute hypoglycemia.

Adrenergic Fibers↗
PubMed1990

Airway responses to deep inspiration in diabetic autonomic neuropathy.

The role of vagal mechanisms in the reversal of pharmacologically-induced bronchoconstriction by deep inspiration is unclear. We examined the effect of lung inflation on methacholine-induced bronchoconstriction in six patients with severe diabetic autonomic neuropathy compared with five patients with diabetes mellitus and normal tests of autonomic function. The effect of deep inspiration on bronchomotor tone was expressed as the ratio of maximal flow rates at 70% of expiratory vital capacity (V30) calculated from complete (V30(c)) and partial (V30(p)) flow-volume curves (V30(c)/V30(p)). In patients with autonomic neuropathy the mean (range) of this ratio was 1.31 (1.19-1.47) and was not significantly different from the control patients with a mean ratio of 1.69 (1.28-2.13). These results suggest that the reversal of methacholine-induced bronchoconstriction by a deep inspiration is not mediated via vagal nerves.

Adult↗
PubMed1990

Splenic responses to acute insulin-induced hypoglycaemia in humans.

1. The effects of acute hypoglycaemia on the spleen were examined in normal humans using radioisotopic techniques, complemented by ultrasonic examination of the spleen. Hypoglycaemia had a modest effect on splenic area, measured by ultrasonography, which declined to 62 +/- 6% (mean +/- SEM) of the basal value after the onset of the acute hypoglycaemic reaction. 2. Hypoglycaemia had a pronounced effect on the splenic radioactivity, which decreased significantly to a mean of 10 +/- 7% of basal radioactivity at 15 min after the onset of hypoglycaemia. The splenic image completely disappeared at some time after hypoglycaemia in all subjects. 3. The reduction of splenic radioactivity was abolished during non-selective alpha-adrenergic blockade with phentolamine, but was unaffected by beta-adrenergic blockade with propranolol, or cholinergic blockade with atropine, which suggests that the response of vessels perfusing the spleen is mediated by alpha-adrenoceptors.

Adult↗
PubMed1990

The effect of alpha-adrenergic blockade on responses of peripheral blood cells to acute insulin-induced hypoglycaemia in humans.

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 erythrocytes 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 leucocyte response, with an early rise in lymphocyte count and a later rise in granulocyte count. The erythrocyte count increased modestly following hypoglycaemia. During alpha-adrenergic blockage, the rise in total leucocyte count was diminished, with the rise in the lymphocyte count being greatly obtunded. These findings suggest that the increments of peripheral lymphocyte and erythrocyte counts in response to acute insulin-induced hypoglycaemia are mediated via alpha-adrenoreceptors.

Adult↗
PubMed1990

The natural history and associations of microalbuminuria in type 2 diabetes during the first year after diagnosis.

The prevalence of microalbuminuria was assessed in 149 consecutive, newly-diagnosed and untreated patients with Type 2 diabetes, 129 of whom were followed up for 1 year, with at least three urine specimens being obtained during this period. At initial presentation, 39 (26%) patients had a urinary albumin to creatinine ratio (ACR) of greater than 2.5 mg mmol-1 and compared with patients who had a normal ACR, they were older (64 (11) (SD) vs 58 (11) yr, p less than 0.002), with higher random blood glucose (14.4 (4.5) vs 12.3 (4.4) mmol l-1, p less than 0.02) and glycosylated haemoglobin (13.0 (3.1) vs 11.3 (2.7)%, p less than 0.01) concentrations. An elevated ACR was also associated with a higher systolic blood pressure (149 (22) vs 140 (22), p less than 0.05) and the presence of macrovascular disease, particularly peripheral vascular disease (p less than 0.001), with this association persisting after adjustment for the effect of age. Ten patients reverted to normal albumin excretion on improving blood glucose control, this group having a significantly higher glycosylated haemoglobin concentration at initial presentation than the group with a persistently elevated ACR (14.4 (2.5) vs 12.0 (3.0)%, p less than 0.05). The 21 (16%) patients with a persistently elevated ACR from diagnosis of Type 2 diabetes were older than those with normal albumin excretion throughout (64 (7) vs 58 (10) yr, p less than 0.02) and it is probable that these patients have abnormal albumin excretion secondary to established renal pathology.

Albuminuria↗
PubMed1990

Leucocyte mobilization and release of neutrophil elastase following acute insulin-induced hypoglycaemia in normal humans.

Insulin-induced hypoglycaemia in humans is associated with the rapid mobilization of leucocytes in peripheral blood. The aim of the present study was to determine whether neutrophil activation, manifested in plasma by neutrophil elastase concentration, occurs in response to insulin-induced hypoglycaemia. Acute hypoglycaemia (mean blood glucose 1.3 +/- 0.2 mmol l-1; mean +/- SD) was induced with intravenous insulin in 15 normal human subjects, and provoked an increase in the neutrophil count from 3.4 (range 1.9-6.5) to 10.7 (9.4-16.3) X 10(9) l-1 (p less than 0.001), and in the total leucocyte counts from 5.7 (4.1-8.1) to 12.8 (11.3-18.6) X 10(9) l-1 (p less than 0.001), with associated elevations in plasma neutrophil elastase concentration from 21 (12-34) to 29 (14-70) micrograms l-1 (p less than 0.05), and in total neutrophil elastase concentration from 5.90 (3.13-8.20) to 25.20 (23.00-52.00) mg l-1 (p less than 0.001). As neutrophil elastase is implicated in the development of vascular disease, this rise in response to hypoglycaemia may be of pathological importance in insulin-treated diabetic patients.

Adult↗
PubMed1990

Secretion of epidermal growth factor in parotid saliva in diabetic patients: role of autonomic innervation.

Parotid saliva was collected over a 12-min period from 24 insulin dependent diabetic patients with varying degrees of autonomic neuropathy and 12 age and sex matched non-diabetic controls. Epidermal growth factor (EGF) concentrations in saliva were measured by radio-immunoassay. The EGF concentrations in diabetics with no autonomic neuropathy or with combined autonomic neuropathy were equivalent but secretion of EGF was significantly elevated at the 6- and 12-min periods of collection in diabetic patients with early or established autonomic neuropathy. It is postulated that when parasympathetic autonomic neuropathy is present a relative "over-activity" of the sympathetic innervation promotes release of salivary EGF. This sympathetic predominance may maintain salivary EGF concentration despite the elevated salivary flow and volume which is associated with parasympathetic autonomic neuropathy.

Autoimmune Diseases↗