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Biomedical subjects

B M Frier

Publications and source records attributed to B M Frier.

At least 217 records · Page 12Linked to original sources
PubMed1981

Autonomic neural control mechanisms of substrate and hormonal responses to acute hypoglycaemia in man.

The contributions of adrenergic and cholinergic mechanisms to recovery from acute hypoglycaemia induced by insulin (0.15 units/kg i.v.) were examined in eleven normal subjects, six subjects with a pre-ganglionic sympathectomy (adrenergic denervation) and six sympathectomized subjects given atropine (combined adrenergic denervation and cholinergic blockade). Blood glucose recovery was impaired only in the sympathectomized subjects given atropine. The blood lactate response was reduced and the rise in free fatty acids was delayed in both groups of sympathectomized subjects, in whom the normal rises of plasma cyclic AMP and noradrenaline were absent. The plasma pancreatic glucagon response was appropriate to the prevailing blood glucose concentrations in all three groups. The cortisol response was impaired and the pattern of ACTH secretion was abnormal in sympathectomized subjects given atropine. Growth hormone levels were higher in both sympathectomized groups. Blood glucose homeostasis was impaired during combined adrenergic denervation and cholinergic blockade. Glucagon secretion was activated independently of vagal control. In the sympathectomized group given atropine, the rise in plasma cortisol was blunted despite a greater degree of hypoglycaemia. A blockade of central cholinergic receptors producing impaired activation of ACTH secretion at hypothalamic level may explain, at least in part, this delayed restoration of normoglycaemia.

Adrenergic Fibers↗
PubMed1981

Hormonal and substrate responses during recovery from hypoglycaemia in man during beta 1-selective and non-selective beta-adrenergic blockade.

Recovery from acute hypoglycaemia induced by the injection of insulin has been examined in six human subjects under control conditions, under non-selective beta blockade (propranolol) and under selective beta 1 blockade (metoprolol). The normal blood glucose recovery was biphasic with an initial rapid and a slower subsequent phase of recovery. The early recovery mechanism was unaffected by either form of beta blockade, but with propranolol the late phase of recovery was significantly prolonged. Rises in blood lactate and plasma free fatty acids following hypoglycaemia were markedly reduced by propranolol but to a much lesser degree with metoprolol. The counterregulatory hormonal responses of glucagon, cortisol and growth hormone were augmented appropriately for the prolonged hypoglycaemia associated with propranolol. Non-selective beta adrenergic blockade with propranolol is associated with an impairment of the late phase of blood glucose recovery from hypoglycaemia. The possible mechanisms of this impairment are discussed.

Acetoacetates↗
PubMed1981

Circulating C peptide: measurement and clinical application.

Pancreatic beta-cell function is usually assessed by the measurement of plasma insulin concentration in various clinical situations. However, the advent of an assay for the measurement of connecting-peptide (C-peptide) concentration in plasma has provided a further method for the assessment of the secretory capacity of the pancreatic beta cell in clinical disorders, particularly in the investigation of hypoglycaemia. The metabolism and immunoassay methodology of C-peptide are reviewed, and its application in clinical practice is outlined.

C-Peptide↗
PubMed1981

Syndrome of inappropriate ADH secretion concealed by hypokalaemia due to ectopic ACTH production.

A case is described of a patient with an oat cell carcinoma of the bronchus with moderately elevated levels of plasma corticotrophin (ACTH) and antidiuretic hormone (ADH). Ectopic secretion of ACTH induced severe hypokalaemia and concealed the effects of concomitant ADH secretion on renal function. Normal renal responsiveness was restored following correction of hypokalaemia. The hypokalaemia was associated with evidence of a marked increase in corticosteroid secretion but plasma ACTH concentrations did not show a proportionate elevation. Chromatographic studies on tumour extracts suggest that the presence of a large fraction of high molecular weight ACTH in plasma could explain this discrepancy.

Adrenocorticotropic Hormone↗
PubMed1981

Plasma insulin, C-peptide and glucagon concentrations in patients with insulin-independent diabetes treated with chlorpropamide.

The effect of chlorpropamide on blood glucose, plasma insulin, C-peptide and glucagon levels was studied in 21 patients with insulin-independent diabetes. A metabolic profile of these parameters was obtained throughout a normal day in seven newly-diagnosed diabetic patients (group A), before, and 3 to 8 weeks after treatment with chlorpropamide was established, and in 14 patients on longterm therapy with chlorpropamide (seven taking less than 250 mg. chlorpropamide--group B; seven taking 250-375 mg.--group C), before, and two weeks after withdrawal of the drug. In group A, correction of hyperglycaemia was not accompanied by a significant rise in the mean plasma insulin and C-peptide levels but a fall was observed in the mean plasma pancreatic glucagon concentrations. In groups B and C, withdrawal of chlorpropamide produced no significant change in plasma insulin, C-peptide or glucagon levels, although the mean blood glucose increased. This study supports an extrapancreatic effect of chlorpropamide to lower blood glucose after prolonged administration. In the short-term, it is possible that chlorpropamide may influence the secretion of pancreatic glucagon.

Adult↗
PubMed1980

Serum trypsin concentration and pancreatic trypsin secretion in insulin-dependent diabetes mellitus.

Fasting serum trypsin concentration and pancreatic trypsin output, stimulated by secretin and cholecystokinin-pancreozymin, were measured in 18 patients with insulin-dependent diabetes, to assess a possible correlation between these two indices of exocrine pancreatic function. Serum trypsin concentration was subnormal in 13, and pancreatic trypsin output was decreased in 14 patients, but there was no significant correlation between the two measurements. There was no correlation between serum trypsin and residual beta cell function measured by plasma C-peptide immunoreactivity (CPR). After an interval of four years serum trypsin measurements were repeated in 11 subjects. All individual trypsin levels were lower than the previous results, the difference being highly significant (t = 9.0; p < 0.001). Serum trypsin concentration therefore represents a qualitative index of reduced exocrine pancreatic function in diabetes, but has no value in quantitating the degree of deficiency.

Adolescent↗
PubMed1980

Driving and insulin-dependent diabetes.

A survey of 250 patients with insulin-dependent diabetes (IDD) holding a full motor vehicle driving licence revealed that 107 (42.8%) had not declared IDD on their application for a driving licence. 70 of these (28% of entire group) claimed that they were unaware of the statutory requirements. There was no difference in the declaration-rate between men and women. 159 patients (66%) declared IDD for their motor insurance. 86 patients (34.4%) had had severe or frequent hypoglycaemia in the preceding six months, during which they had been driving regularly. 34 patients (13.6%) admitted involvement in a driving accident since commencing treatment with insulin, and 13 of these patients were aware that hypoglycaemia had been an important causal factor. The prevalence of diabetic retinopathy and cataracts was considerable, but few patients (2.4%) had severe impairment of vision in both eyes.

Accident Prevention↗
PubMed1980

Attenuation of the pancreatic beta cell response to a meal following hypoglycaemia in man.

The plasma concentration of C-peptide, insulin (IRI) and glucose was measured in 9 healthy subjects during insulin-induced hypoglycaemia followed by a meal. Identical observations were made in the same subjects after an equivalent period of fasting without hypolycaemia (control study). Endogenous secretion of insulin was suppressed following administration of exogenous insulin and this persisted long after the blood glucose concentration had returned to normal. After the meal the mean blood glucose rose to a peak of 8.4 +/- 0.3 mmol/l (mean +/- SEM) at 60 min and was still raised at 7.5 +/- 0.3 mmol/l at 120 min, compared with a peak value of only 5.1 +/- 0.2 mmol/l at 30 min after the meal in the control study. Following hypoglycaemia the mean plasma IRI rose from 8.3 +/- 1.3 mU/l to a delayed peak of 81.6 +/- 12.7 mU/l at 60 min and was 123.5 +/- 14 mU/l at 120 min post-prandially, compared with a peak of 72.4 +/- 0.5 mU/l at 30 min after the meal in the control study. Acute hypoglycaemia may thus induce in abnormal pattern of insulin secretion in response to a meal, with impaired carbohydrate tolerance in normal subjects.

Adult↗
PubMed1980

Increase in coagulation factor VIII activity in man following acute hypoglycaemia: mediation via an adrenergic mechanism.

Coagulation factor VIII activity has been assayed in nine normal volunteers before and after acute hypoglycaemia. In all subjects there was a rise in activity with a mean increment of 96%. Control studies using saline failed to demonstrate any change. In four subjects with pre-ganglionic sympathetctomy no increase in activity was observed. In the normal subjects the increase was blocked by propranolol but not by metoprolol, indicating mediation via beta2 receptors.

Acute Disease↗
PubMed1980

Misleading plasma electrolytes in diabetic children with severe hyperlipidaemia.

Severe abnormalities of plasma electrolyte concentrations were observed in 4 children who had massive hyperlipidaemia secondary to poorly-controlled, insulin-dependent diabetes mellitus. These electrolyte values were fallacious and invoked problems of clinical management, particularly with regard to fluid replacement. Each case is described and the interpretation of plasma elecytolyte values in hyperlipidaemia is discussed.

Adolescent↗
PubMed1979

Recovery mechanisms from acute hypoglycaemia in complete tetraplegia.

Acute hypoglycaemia has been achieved in tetraplegic subjects and in healthy controls using insulin. The recovery from hypoglycaemia has been followed by measuring appropriate substrate levels in blood. Abnormal responses of lactate and free fatty acid concentrations were observed; blood glucose recovery proceeded at a normal rate.

Adult↗
PubMed1979

Cholesterol metabolism in diabetes: the effect of insulin on the kinetics of plasma squalene.

The turnover of isotopically labeled squalene formed in plasma from [14C]mevalonate has been used to measure cholesterol synthesis in diabetics over a 7-h period. Five patients were studied while in poor diabetic control (mean daytime glycemia, 349 mg/dl) and at a later date once improved control was established by multiple daily insulin injections (mean glycemia, 175 mg/dl). This degree of diabetic control resulted in an increase in the fractional conversion of [14C]mevalonic acid to [14C]squalene from 55.2 +/- 1% to 67.5 +/- 4% (P less than 0.025). These data together with the area under the squalene specific activity curve yeild an estimated rate of cholesterol synthesis based on the likely assumption that mevalonate pool size did not decrease. Insulinization increased this calculated mean rate of cholesterol synthesis from 961 +/- 151 to 1206 +/- 223 mg/day (P less than 0.025). The use of squalene kinetics to evaluate changes in cholesterol synthesis deserves further study, particularly in metabolically unstable states such as diabetes in which conventional methods for measuring cholesterol synthesis are difficult to apply and to interpret.

Adult↗
PubMed1978

The effect of residual insulin secretion on exocrine pancreatic function in juvenile-onset diabetes mellitus.

Residual beta cell function was studied in 18 juvenile-onset diabetics by measuring serum C-peptide immunoreactivity (CPR) fasting, and after IV injection of glucagon (1 mg). This was compared with the exocrine pancreatic response to an IV infusion of secretin and cholecystokinin-pancreozymin. Outputs of pancreatic bicarbonate, amylase and trypsin were measured. Exocrine secretory pancreatic function was decreased in 14 patients. Fasting and maximal CPR showed that 9 patients had residual insulin secretion. For these 'CPR-secretors' there was a strong correlation between CPR and output of bicarbonate (r = 0.87, p less than 0.005) and amylase (r = 0.7, p less than 0.05), but not with trypsin. These results suggest the existence of an endocrine-exocrine relationship in the pancreas.

Adolescent↗
PubMed1978

Plasma squalene: lipoprotein distribution and kinetic analysis.

Plasma squalene concentration is increased in hypertriglyceridemia. In 24 normotriglyceridemic and 12 hypertriglyceridemic subjects, whole plasma squalene correlated strongly with plasma triglyceride (r = 0.973, P < 0.001) in the latter. In normal postabsorptive plasma, squalene was found in each lipoprotein fraction, 50.8% in very low density lipoprotein, 25.6% in low density lipoprotein, and 23.6% in high density lipoprotein. When plasma triglyceride was increased by dietary intake in humans or by experimental diabetes in rats, plasma squalene increased correspondingly. Conversion of [(14)C]mevalonic acid into [(14)C]squalene and kinetic analysis of [(14)C]squalene die-away curves were studied in 17 subjects. Hypertriglyceridemia significantly increased the estimated metabolically active plasma squalene pool. This together with an increase in radioactivity of squalene (dpm/ml plasma) in hypertriglyceridemia suggested that squalene production was increased. Squalene specific activity curves in lipoprotein fractions from four chylomicronemic subjects demonstrated that each fraction had newly synthesized squalene and that total plasma squalene kinetics represent the composite of several individual die-away curves. We conclude that squalene in whole plasma and in lipoprotein fractions varies directly with triglyceride content. Hypertriglyceridemia expands the plasma pool of metabolically active squalene, and each lipoprotein fraction contains squalene that is metabolically active in cholesterol synthesis.

Adult↗