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Biomedical subjects

B F Clarke

Publications and source records attributed to B F Clarke.

At least 55 records · Page 3Linked to original sources
PubMed1987

Clinically apparent eating disorders in young diabetic women: associations with painful neuropathy and other complications.

Of 208 young women with insulin dependent diabetes, 15 (7%) had a clinically apparent eating disorder (anorexia nervosa or bulimia), a much higher prevalence than reported in non-diabetic women. Most, but not all, of these patients had a long history of poor glycaemic control. In contrast with previous suggestions, control did not deteriorate after the onset of the eating disorder. There was a high incidence and an early onset of diabetic complications. Eleven of the 15 patients had retinopathy, six with proliferative changes; six had nephropathy; and six neuropathy. Most strikingly, four patients with anorexia nervosa developed acute painful polyneuropathy. In each case pain started when the eating disorder developed, almost coinciding with the peak of weight reduction. Remission of pain occurred as weight was regained. The symptoms were accompanied by abnormalities in peripheral nerve electrophysiology and autonomic nerve function, some improvements in which accompanied weight recovery. It is suggested that nutritional factors may contribute to the high rate of early onset diabetic complications, particularly neuropathy.

Adolescent↗
PubMed1987

Impairment of monocyte "lectin-like" receptor activity in type 1 (insulin-dependent) diabetic patients.

In order to investigate whether the ability of peripheral blood monocytes to bind bacteria is impaired in diabetes, we studied carbohydrate-binding ("lectin-like") receptors and the receptor for the Fc portion of immunoglobulin on monocytes from 25 male Type 1 (insulin-dependent) diabetic patients and 10 age-matched healthy control subjects. Peripheral blood monocytes from the diabetic patients expressed lower levels of "lectin-like" receptors compared to the control subjects, whereas the expression of the receptor for the Fc portion of immunoglobulin was similar in both populations. There was no correlation between the degree of "lectin-like" binding activity and plasma glucose concentration or glycaemic control. Recognition of unopsonized bacteria by the "lectin-like" receptor is impaired in Type 1 diabetes; this may affect the efficient elimination of potential pathogens.

Adult↗
PubMed1987

Blood flow in the foot, polyneuropathy and foot ulceration in diabetes mellitus.

Comparable groups of diabetic patients asymptomatic of neuropathy (Group A), with chronic painful polyneuropathy (Group B) and painless polyneuropathy causing recurrent foot ulceration (Group C) were studied for differences in pedal blood flow, peripheral somatic and autonomic neuropathy and vascular calcification. Blood flow abnormalities detected by doppler waveform analysis, and consistent with reduced peripheral vascular resistance, were found in all three diabetic patient groups. The abnormalities were of similar severity in Group A and B but generally more marked in Group C. Tests of peripheral somatic nerve function became progressively more abnormal from Group A to Group C. Autonomic neuropathy was equally severe in Groups B and C, although mild abnormalities were recorded in diabetic patients asymptomatic of neuropathy. A similar pattern was seen for vascular calcification in the tarsal and metatarsal arteries: marked in both neuropathic groups (B and C) but mild in Group A. It was concluded that abnormal blood flow consistent with reduced peripheral vascular resistance is very common in the feet of diabetic patients whether or not they are symptomatic of neuropathy, and is most severe in those with chronic painless polyneuropathy and recurrent foot ulceration. No clear relationship was found between autonomic nerve dysfunction and the degree of abnormality of blood flow.

Adult↗
PubMed1987

Abnormal diurnal urinary sodium and water excretion in diabetic autonomic neuropathy.

1. Diurnal patterns of urine output and sodium and potassium excretion were studied in 10 diabetic patients with and 10 without autonomic neuropathy, and in 10 normal subjects. 2. The diurnal patterns of excretion in the diabetic patients with autonomic neuropathy differed significantly from the two other groups, as a smaller proportion of the 24 h output of urine, sodium and potassium was excreted during the day and a larger proportion was excreted at night. 3. Similar changes were noted in the diurnal patterns of urinary kallikrein excretion in diabetic patients with autonomic neuropathy, and urinary kallikrein output correlated significantly with urine volume but not with urinary sodium excretion. 4. The diurnal patterns of excretion of urinary prostaglandin E2 and 6-keto-PGF1 alpha were not significantly different in diabetic patients with autonomic neuropathy. 5. Nocturia was a common complaint in this group, and the number of nocturnal voidings correlated with night urine volume. There was no evidence of premature bladder emptying. 6. The changes observed in the day/night urine output and sodium excretion could not be explained by glycosuria, insulin regimens, impaired renal function or abnormal diurnal prostaglandin excretion; their possible relevance to the diurnal changes of urinary kallikrein excretion is discussed.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Increased bronchial reactivity to histamine in diabetic autonomic neuropathy.

1. Twelve male diabetic patients inhaled nebulized histamine in doubling concentrations from 0.03 mg/ml to 32 mg/ml until they reached the maximum concentration or until their forced expiratory volume in 1 s (FEV1.0) fell by at least 20%. Six had evidence of severe autonomic neuropathy (DAN), while the other six did not. 2. More of the DAN group decreased their FEV1.0 on histamine inhalation by at least 20% (P less than 0.02) and more of them decreased their maximal flow at 50% vital capacity by at least 20% than those in the group without DAN (P less than 0.05). 3. The fall in FEV1.0 and in maximal flow at 50% of vital capacity was greater (P less than 0.05) in the DAN group than in the group without DAN. 4. This suggests that diabetic patients with autonomic neuropathy have increased bronchial reactivity to histamine. This could either be due to differential damage of the respiratory autonomic nerves or, alternatively, to denervation hypersensitivity.

Autonomic Nervous System Diseases↗
PubMed1987

Effects of beta-adrenoceptor blockade on heart rate and physiological tremor in diabetics with autonomic neuropathy. A comparative study of epanolol, atenolol and pindolol.

Eight diabetics with autonomic neuropathy were given single oral doses of epanolol (200 mg), atenolol (50 mg), pindolol (5 mg) and placebo in a double-blind randomised order at weekly intervals. Supine resting heart rate, physiological tremor and blood glucose were measured before, 2 and 4 h after dosing, and ambulatory heart rate monitored for 24 h. Supine resting heart rate was significantly lowered by atenolol both at 2 and 4 h, and increased on pindolol at 4 h. Heart rate was unaffected by epanolol compared with placebo. Heart rate during the 'waking' period (14.00-23.00 h) was lower than placebo after epanolol and atenolol but unaffected by pindolol. During the 'sleeping' period (23.00 h-08.00 h) heart rate was significantly increased by pindolol, lowered with atenolol and unaffected on epanolol. Pindolol significantly increased physiological tremor at 4 h. No differences were seen between epanolol, atenolol and placebo. Plasma glucose was significantly increased by pindolol 2 h after dosing. These results suggest that pindolol probably produces its partial agonist activity at both beta 1- and beta 2-adrenoceptors, while the partial agonist activity of epanolol is beta 1-selective. Despite abnormal cardiovascular reflex tests in these diabetics, the heart rate responses obtained in this study after beta-adrenoceptor blockade were surprisingly normal, and suggest that the concept of 'cardiac denervation' in diabetes requires modification.

Adrenergic beta-Antagonists↗
PubMed1987

Transient atrial fibrillation precipitated by hypoglycaemia: two case reports.

We describe two insulin-dependent diabetic females who presented with severe hypoglycaemia associated with atrial fibrillation which reverted to sinus rhythm after intravenous dextrose. Atrial fibrillation has not previously been reported as a complication of hypoglycaemia in insulin-dependent diabetic patients.

Adult↗
PubMed1987

Six-month treatment with sorbinil in asymptomatic diabetic neuropathy. Failure to improve abnormal nerve function.

The effect of long-term treatment with the aldose reductase inhibitor sorbinil (125 mg daily for 6 mo) was examined in 22 diabetic patients with subclinical abnormalities of nerve function. This was a placebo-controlled, double-blind crossover trial in which each of the two treatment periods lasted 6 mo. Peripheral nerve function was assessed electrophysiologically and by quantitative sensory testing; autonomic function was assessed by measurement of five cardiovascular reflexes and of mean heart rate from a 24-h ECG recording. Measurement of erythrocyte sorbitol concentrations demonstrated very significant inhibition of aldose reductase activity with sorbinil treatment, but no concomitant improvement in either peripheral or autonomic nerve function was observed.

Adult↗
PubMed1987

Changes in some aspects of platelet function with improvement of glycaemic control over 6 months.

Numerous platelet abnormalities, particularly hyperaggregation, have been described in diabetic patients, and it has been suggested that these may contribute towards the pathogenesis of microvascular complications. In the present study, the changes that occur in ADP-induced aggregation, sensitivity to a stable prostacyclin analogue (Iloprost), aggregation-induced thromboxane B2 production and platelet cyclic AMP levels were investigated in 9 young insulin-dependent diabetics, in which the glycaemic control significantly improved in one group (n = 5; HbA1 from 11.9-9.0%) over a 6 month period. With improvement of glycaemic control there was no significant change in the concentration of ADP required to produce 50 percent of the maximum aggregation wave response. However, there was a significant increase in the responsiveness of platelets to Iloprost and increased platelet thromboxane B2 production. There was no significant difference between the basal platelet cAMP levels before or after exposure to Iloprost. This study suggests that with improved short-term glycaemic control, although there are changes in platelet function, there may be no alteration in the homeostatic balance.

Adenosine Diphosphate↗
PubMed1987

The use of captopril and captopril plus frusemide as antihypertensive agents in non-insulin dependent diabetes.

After all previous antihypertensive treatment had been stopped, blood pressure and glucose tolerance were measured in 16 hypertensive non-insulin treated diabetics before and again six weeks after treatment with captopril, an angiotensin-converting enzyme inhibitor. Supine blood pressure fell from 184 +/- 4.1/103 +/- 2.6 to 165 +/- 5.2/88 +/- 2.1 mmHg (P less than 0.001) and erect from 179 +/- 5.2/102 +/- 3.2 to 158 +/- 5.6/87 +/- 2.6 mmHg (P less than 0.005). The area under the oral glucose tolerance curve fell from 2313.6 +/- 154 to 2192.8 +/- 146 mmol/min/l (P less than 0.02). There was no change in plasma insulin, total glycosylated haemoglobin or fructosamine. Four patients who failed to show lowering of supine diastolic pressure below 95 mmHg were additionally given oral frusemide with further improvement in blood pressure and no alteration in carbohydrate intolerance. It was concluded that captopril alone is usually an effective antihypertensive agent in non-insulin dependent diabetes with the addition of frusemide benefiting resistant cases. Glucose intolerance did not worsen with either captopril alone or captopril plus frusemide.

Blood Glucose↗
PubMed1987

Noradrenaline response to edrophonium (Tensilon) and its relation to other autonomic tests in diabetic subjects.

Noradrenaline responses following 10 mg intravenous edrophonium were assessed in 32 insulin-treated diabetic men, allocated to 4 groups according to their responses to 5 cardiovascular autonomic tests. The group with the most severe autonomic involvement had no rise in plasma noradrenaline, in contrast to the other 3 groups, whereas the heart rate fell in all 4 groups. There were significant correlations between individual noradrenaline responses, cardiovascular reflex tests, 24 hour heart rate variation and pupil cycle time, depending on whether predominantly parasympathetic or sympathetic pathways or both were involved. These results indicate that the noradrenaline response to edrophonium cannot be used as a test of early sympathetic dysfunction in diabetics; and that autonomic nervous system involvement occurs simultaneously in different body systems.

Autonomic Nervous System Diseases↗
PubMed1986

Increased platelet thromboxane receptor sensitivity in diabetic patients with proliferative retinopathy.

Platelet aggregation to collagen in 12 Type 1 (insulin-dependent) diabetic patients with background retinopathy and 12 Type 1 diabetic patients with proliferative retinopathy was compared with an age- and sex-matched control group. An analogue of prostaglandin H2, 11,9 epoxymethano-prostaglandin H2, which directly stimulates thromboxane receptors, and EP 092, which is a competitive thromboxane A2 receptor antagonist, were used to investigate changes at platelet thromboxane receptor level in these groups. The concentration of collagen (EC50) required to give 50% of maximum aggregation did not differ between the two diabetic groups and the control group. However, platelets from the proliferative retinopathy group were significantly more sensitive to the thromboxane mimetic (11,9 epoxymethano-prostaglandin H2) (p less than 0.005) than the background retinopathy and control groups. This change may be a factor in the development of proliferative retinopathy.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1986

Progression of subclinical polyneuropathy in young patients with type 1 (insulin-dependent) diabetes: associations with glycaemic control and microangiopathy (microvascular complications).

The progression of subclinical polyneuropathy over 2.5 years has been studied in a representative group of 75 young patients with Type 1 (insulin-dependent) diabetes (initial age 16-19 years). The relationships between changes in nerve function, glycaemic control and concurrently developing microvascular complications (retinopathy, microproteinuria) were investigated. Deterioration of motor, sensory and autonomic nerve function, retinopathy and microproteinuria was related to poor glycaemic control. In addition, there was an association between developing neural and microvascular complications which was not diminished when their common relationship to hyperglycaemia was taken into account. These findings suggest that, although poor glycaemic control is an essential permissive factor in the early development of diabetic polyneuropathy, other influences, shared with microvascular complications, must also be important.

Adolescent↗
PubMed1986

Correlation of cardiovascular and neuroendocrine tests of autonomic function in diabetes.

Six normal subjects and 16 insulin-dependent diabetics with varying degrees of autonomic damage each had blood sampled for norepinephrine and pancreatic polypeptide for fifteen minutes after a mixed meal and intravenous (IV) edrophonium (Tensilon). The normal subjects showed a brisk but short-lived rise in norepinephrine after edrophonium (average maximum increase 70% between 2 and 6 minutes), as did most diabetics. However, diabetics with cardiovascular reflex evidence of sympathetic damage showed no rise in norepinephrine. Pancreatic polypeptide concentrations increased up to 400% above baseline after a mixed meal in both the normal and the diabetic group with normal cardiovascular reflexes. There was no significant rise in pancreatic polypeptide either in the diabetics with parasympathetic damage alone or in those with additional sympathetic damage. These results provide further evidence for the diffuse nature of the damage in diabetic autonomic neuropathy.

Adult↗
PubMed1986

Autonomic neuropathy: its diagnosis and prognosis.

Autonomic neuropathy is now well established as a relatively common and significant complication of diabetes mellitus. Its importance has been clarified in recent years during which the extent of autonomic control over all areas of body function has been defined. Using simple cardiovascular reflex tests, autonomic abnormalities can be demonstrated without any corresponding symptoms. The often stated concept of 'patchy' involvement in diabetic autonomic neuropathy should now be rejected as too should the view that autonomic neuropathy is either 'present' or 'absent' based on a single test result. When generalized and predominantly metabolic disturbances, as in diabetes, give rise to impaired nerve function, autonomic as well as somatic components of the nerve are affected. Where damage is severe this leads to the characteristic florid picture of symptomatic autonomic neuropathy with its particularly poor prognosis. For the physician in a busy clinic, much of the theoretical and experimental basis for autonomic neuropathy may not appear of direct relevance. However, he has now to be aware of the clinical implications of autonomic damage in the diabetic. This may have particular relevance in the care of the diabetic foot (see Chapter 10), the recognition of many of the vague symptoms associated with autonomic damage, the treatment of disabling features such as postural dizziness and nocturnal diarrhoea, and an awareness of the poor prognosis associated with symptomatic autonomic neuropathy. He will also need to be alert to the dangers of general anaesthesia in such patients, and the possibility of sudden unexpected deaths. Diabetic autonomic neuropathy causes widespread abnormalities, some of which are clinically apparent, some of which can be detected by sensitive tests, and others which have yet to be discovered. Inclusion of the neuropeptides and other hormones within the compass of autonomic control has opened up a whole new area of investigative interest, with many complex interrelationships which still need to be unravelled. This should lead to better understanding of the pathophysiological processes that cause damage to diabetic nerves. With so much research effort directed towards better glycaemic control and aldose reductase inhibitors (see Chapter 8), it may eventually be possible to reverse or prevent this potentially disabling and lethal complication of diabetes.

Autonomic Nervous System Diseases↗
PubMed1986

Reversal of insulin resistance in type 1 diabetes following initiation of insulin treatment.

The biological action and pharmacokinetics of insulin were assessed in nine type 1 (insulin-dependent) diabetic patients before and after 3 months conventional insulin treatment, and in seven age and weight-matched non-diabetic controls, by means of the euglycaemic insulin clamp technique. The mean (+/- S.E.) metabolic clearance rate of insulin, when infused at 1 mU/kg/min, was similar in untreated and treated diabetic patients and in controls (22.7 +/- 2.0, 19.3 +/- 3.8, and 22.9 +/- 3.3 ml/kg/min) but, when infused at 6 mU/kg/min, was greater (p less than 0.01 and less than 0.01) in untreated patients (18.0 +/- 2.5 ml/kg/min) than in treated patients (11.5 +/- 1.4 ml/kg/min) and controls (12.7 +/- 1.3 ml/kg/min). Insulin-mediated glucose disposal was reduced (p less than 0.01 and less than 0.01) at insulin infusion rates 1 and 6 mU/kg/min in untreated patients (18.5 +/- 1.9 and 33.8 +/- 4.5 mumol/kg/min) when compared with controls (35.8 +/- 3.4 and 62.0 +/- 4.7 mumol/kg/min) and was improved (p less than 0.01 and less than 0.01) following insulin treatment (36.1 +/- 4.6 and 64.8 +/- 4.2 mumol/kg/min). Daily insulin requirement fell by 33% following 3 months insulin treatment with improvement in mean HbA1 from 16.3 +/- 0.7 to 8.2 +/- 0.4%, but without significant increase in endogenous insulin secretion. The 'honeymoon phenomenon', which has traditionally been attributed exclusively to resurrection of endogenous insulin release, may also be related to normalization of insulin action following institution of insulin treatment.

3-Hydroxybutyric Acid↗