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Biomedical subjects

B F Clarke

Publications and source records attributed to B F Clarke.

At least 109 records · Page 6Linked to original sources

Reduced airway vagal tone in diabetic patients with autonomic neuropathy.

1. Forced expiratory flow rates and specific airways conductance were measured before and after the inhalation of the atropine-like drug ipratropium bromide in 11 diabetic patients with autonomic neuropathy and a control group of 11 diabetic patients without autonomic neuropathy. Respiratory muscle function was assessed by recording maximal inspiratory and expiratory mouth pressures. 2. There was no difference between the two groups of diabetic patients in airway calibre before ipratropium bromide or in maximal mouth pressures. 3. Bronchodilatation after ipratropium bromide was greater in the control group than in the autonomic neuropathy group of patients. 4. It is concluded that, despite the lack of clinical evidence of respiratory involvement, patients with diabetic autonomic neuropathy have reduced airway vagal tone.

Adolescent↗

Hypercholesterolemia in diabetics with clinically unrecognised primary thyroid failure.

Forty-nine diabetics with primary thyroid failure, as indicated by an elevated TSH concentration (TSH 38.0 +/- 5.4 mU/L, T4 63.0 +/- 4.0 nmol/L), without overt clinical evidence of hypothyroidism, had a higher (p less than 0.025) mean plasma cholesterol concentration (6.8 +/- 0.2 nmol/L vs 6.0 +/- 0.2 nmol/L) than 49 euthyroid diabetics (TSH 3.16 +/- 0.2 mU/L, T4 99.1 +/- 2.81 nmol/L) of equivalent age, sex, weight, diabetic treatment and duration of diabetes. No significant difference in triglyceride concentration was observed between the two groups of diabetics. Thyroxine replacement therapy in 18 diabetics with subnormal T4 concentrations was associated with a reduction (p less 0.01) in mean plasma cholesterol concentration to 5.8 +/- 0.3 nmol/L, but no significant change in triglyceride concentration. Clinically unrecognised thyroid failure may contribute to the high mortality from ischaemic heart disease observed in diabetics by virtue of accompanying, reversible hypercholesterolemia.

Cholesterol↗

Relationship of glycosylated haemoglobin to C-peptide secretory status and antibody binding of insulin in insulin-dependent diabetes.

Diabetic control, assessed by measuring the concentration in venous blood of total glycosylated haemoglobin (HbA1), endogenous insulin secretion, as estimated by the C-peptide response (delta C-P) to intravenous glucagon, and serum beef insulin antibody binding were measured in 50 juvenile onset insulin dependent diabetics (IDDM) receiving a single daily injection of soluble and protamine zinc insulin. The delta C-P correlated inversely with duration of diabetes (tau = -0.27, p less than 0.01) and daily insulin requirement (tau = -0.22, p less than 0.05) in the 50 IDDM studied of whom 28 exhibited a measurable delta C-P. In C-peptide nonresponders, but not in the C-peptide responders, and inverse regression (t = 2.19, p less than 0.05) was observed between beef insulin antibody and HbA1. In the 25 IDDM having the lowest insulin antibody binding, and inverse correlation (tau = 0.36, p less than 0.02) was observed between delta CP and HbA1, which was not found (tau = 0.05) in the remaining 25 IDDM who had the highest insulin antibody binding. These findings suggest that, in the absence of endogenous insulin secretion, diabetic control in IDDM receiving a single daily injection of conventional beef insulin is better in patients with high beef insulin antibody binding. Conversely, in patients with low beef insulin antibody binding, diabetic control appears to be better in those with persisting endogenous insulin secretion.

Adolescent↗

The prevalence of diabetic impotence.

In a survey of 541 diabetic males, aged 20-59 years, 190 (35%) had erectile impotence. Using linear logistic regression models for analysis the five most significant associations with impotence were age (p < 0.001), treatment with either insulin or oral hypoglycaemic agents (p < 0.001), retinopathy (p < 0.001), symptomatic peripheral neuropathy (p < 0.001) and symptomatic autonomic neuropathy (p < 0.005). The greatest correlations were found in patients with severe microangiopathy, as demonstrated by proliferative retinopathy and symptomatic autonomic neuropathy. In addition the duration of diabetes and the presence of ischaemic heart disease, nephropathy and poor diabetic control may also be associated with diabetic impotence. It is concluded that diabetic impotence is still a common problem and may have a multifactorial aetiology.

Adult↗

Plasma beta-thromboglobulin in diabetes mellitus.

Plasma beta-thromboglobulin was measured, using the Edinburgh radioimmunoassay technique and anticoagulant mixture (containing prostaglandin E1) in 61 normal subjects, 67 diabetics with and 54 diabetics without microangiopathic complications. Plasma beta-thromboglobulin was significantly higher in the diabetic patients (p < 0.01) but there was no significant difference between the two diabetic groups. Twenty-six normal subjects, 27 diabetics with and 39 diabetics without complications were studied further by measuring beta-thromboglobulin in four different ways using two different radioimmunoassay techniques and two anticoagulant mixtures (with and without prostaglandin E1). The Edinburgh assay gave a value 1.97 times that obtained with the Amersham assay, and the Edinburgh anticoagulant a value 0.78 times that with the Amersham anticoagulant. Beta-thromboglobulin concentration in the meniscus layer was approximately twice that in the middle layer. The lower beta-thromboglobulin values obtained with the Edinburgh anticoagulant may result from a different sampling technique or from prevention of in vitro beta-thromboglobulin release, after venepuncture, by prostaglandin E1. Abnormal platelet behaviour in diabetes was confirmed although its role in the pathogenesis of microangiopathic complications remains unclear.

Adult↗

Autonomic mechanisms in the initial heart rate response to standing.

Autonomic mechanisms underlying the initial heart rate response to standing were analyzed in nine normal subjects. The normal pattern of response was altered by atropine to a small and gradual R-R interval shortening over 30 beats, with no rebound R-R interval lengthening. With additional propranolol, R-R interval shortening was even less and confined to the first 15-20 beats, whereas propranolol alone did not affect the normal response pattern, showing that this is under vagal control with increased cardiac sympathetic activity occurring only if the vagus is blocked. The response was reproducible in 23 normal subjects. Heart rate variation during quiet standing was almost completely abolished by atropine, but unaffected by propranolol, confirming that it is also under vagal control. In four normal subjects no rebound R-R interval lengthening occurred during either "fast" or "slow" tilt, whereas it was present during both "slow" and "fast" standing. The rebound R-R interval lengthening is determined by the muscular activity involved in standing up, rather than by the speed of the maneuver.

Adult↗

Prevalence of subclinical thyroid failure in insulin-dependent diabetes.

A study was made of the distribution of primary thyroid failure, indicated by a raised serum TSH concentration, in 605 (294 males and 311 females) insulin-dependent (type I) diabetics, aged 21-84 yr, not previously suspected of having thyroid disease. The prevalence of a raised serum TSH concentration in females of all ages (17%) was significantly greater (P less than 0.0005) than that in males (6.1%) and increased with increasing age at onset of diabetes (P less than 0.05) and age at time of study (P less than 0.001) in females but not in males. There was no significant difference in the duration of diabetes when comparing patients with normal and raised serum TSH concentrations. The prevalence of a raised TSH concentration in late-onset insulin-dependent diabetics was no greater in patients requiring insulin within 3 months of diagnosis of diabetes than in those exhibiting secondary sulfonylurea failure, who required insulin more than 3 months after diagnosis. In type I diabetes, the prevalence of subclinical primary thyroid failure is considerably greater than has previously been suspected, with female late-onset insulin-dependent diabetics being at the greatest risk.

Adult↗

Assessment of cardiovascular effects in diabetic autonomic neuropathy and prognostic implications.

Cardiovascular effects of diabetic autonomic neuropathy include postural hypotension, resting tachycardia, and, possibly, painless myocardial infarction. Involvement of cardiovascular reflexes in diabetes can be assessed using simple noninvasive tests: the Valsalva maneuver, beat-to-beat heart rate variation, the heart rate response to standing, postural fall in blood pressure, and the sustained handgrip test. Tests of parasympathetic function appear to be abnormal more frequently and earlier in cardiac autonomic involvement, whereas sympathetic damage usually occurs later and is associated with clinical symptoms. When test results are abnormal, in association with symptoms suggestive of autonomic neuropathy, the prognosis is grave. Some sudden deaths that occur may be due to abnormal autonomic reflexes.

Autonomic Nervous System↗

Gastric emptying in diabetic autonomic neuropathy.

Gastric emptying was studied in 12 diabetic patients, six with and six without objective evidence of autonomic neuropathy and in 20 nondiabetic controls, using a double isotope scintiscanning technique which differentiated between solid and liquid emptying. Three patients with autonomic neuropathy exhibited gastric stasis, although this was detected by conventional radiology in only one. Neither the patients with stasis nor those without exhibited abnormally rapid early gastric emptying. In patients without stasis, the normal differentiation between solid and liquid emptying was impaired, suggesting an abnormality of antral peristalsis not attributable to vagal denervation. Both intravenous and oral metoclopramide produced symptomatic improvement in two patients with gastric stasis and restored their gastric emptying to normal.

Adult↗

The significance of pancreatic islet cell antibody and abnormal glucose tolerance during pregnancy.

Five out of 50 pregnant subjects with impaired glucose tolerance (a 2 hr venous plasma glucose concentration over 6.6 mmol/1) had cytoplasmic islet cell antibody (ICAb cyto) in their sera. Three of these 5 developed unequivocal insulin-dependent diabetes in the first year following pregnancy, while none of the others did so. When taken in conjunction with the presence of islet cell antibody, the severity of impairment of glucose tolerance during pregnancy (but not obesity) was an additional indicator of the likelihood of developing insulin-dependent diabetes during the first postpartum year.

Antibodies↗

The natural history of diabetic autonomic neuropathy.

Seventy-three diabetics (62 males and 11 females) who complained of symptoms suggestive of autonomic neuropathy were followed prospectively for up to five years. Thirty patients presented with impotence alone, while the other 43 presented with one or more of the following: postural hypotension, intermittent diarrhoea, hypoglycaemic unawareness, sweating abnormalities and gastric fullness. Most subjects with impotence alone had normal autonomic function tests (responses to the Valsalva manoeuvre and sustained handgrip) whereas the majority with other symptoms had abnormal tests. Twenty-six subjects (20 males and six females) died during the follow-up period. Of the 33 with initially normal autonomic function tests, five (15 per cent) died, whereas of the 40 with initially abnormal tests, 21 (53 per cent) died. Diabetics with symptoms of autonomic neuropathy and abnormal autonomic function tests, had a calculated mortality rate after two-and-a-half years of 44 per cent and after five years of 56 per cent. Half the deaths in those with abnormal tests were from renal failure, and the remainder were either sudden and unexpected, or from other causes which may have been associated with the autonomic neuropathy. Autonomic function testing repeated during the follow-up period showed that some normal tests later became abnormal, but once tests were abnormal, they usually remained abnormal. A number of subjects with impotence alone developed other features of autonomic neuropathy and abnormal tests during the follow up period. Symptoms of autonomic neuropathy, particularly postural hypotension, gastric symptoms and hypoglycaemic unawareness, together with abnormal autonomic function tests, carry a very poor prognosis. Diarrhoea and importence, on their own, cannot be relied on as symptoms of autonomic neuropathy. Autonomic function testing using simple cardiovascular reflexes give a good guide to the prognosis of diabetic autonomic neuropathy.

Adult↗

Obstetric history of diabetics: its relevance to the aetiology of diabetes.

The birth weights of infants born to patients with insulin-dependent diabetes (IDD) and insulin-independent diabetes (IID) before the disease was diagnosed were compared. An appreciable excess of infants above the 90th centile for weight was found, the proportions being 27% of infants born to mothers with IDD and 30% of those born to mothers with IID. These findings suggest that many patients with both types of diabetes have a prolonged period of metabolic abnormality before overt symptoms of diabetes arise and that the apparent acute onset of the disease in patients who are insulin dependent is illusory.

Adult↗

Glycosylated haemoglobin concentrations in newly diagnosed diabetics before and during treatment.

Concentrations of total glycosylated haemoglobins (Hb A1) were measured in 40 diabetics at diagnosis and at monthly intervals after treatment with chlorpropamide, insulin, or diet alone was begun. The mean Hb A1 concentration at presentation in 16 patients treated with chlorpropamide was significantly higher than that in 12 patients treated with insulin, and the duration of glycaemic symptoms was much longer in the chlorpropamide-treated group. In contrast, the mean plasma glucose concentration was similar in both groups. The mean concentrations of Hb A1 and plasma glucose at diagnosis in the 12 patients treated by diet alone were lower than those in the other two groups, and most of these patients were free of symptoms. Treatment quickly relieved symptoms and lowered plasma glucose in all patients. The Hb A1 concentration fell significantly with treatment such that after two months there was no significant difference between the three groups, although results remained above the normal range. These findings support the theory that the Hb A1 concentration reflects the blood glucose control over the previous one to two months and suggest that the duration of hyperglycaemia may be important in determining the Hb A1 concentration as well as the absolute blood glucose concentration.

Adult↗