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Biomedical subjects

H Keen

Publications and source records attributed to H Keen.

At least 163 records · Page 9Linked to original sources
PubMed1982

Urinary excretion of albumin in normal man: the effect of water loading.

The urinary excretion of albumin and beta 2-microglobulin in response to two different types of oral water load was studied in 18 healthy subjects. Both acute water loading (1 litre of tap water given over 10 min) and chronic water loading (250 ml of water given every 20 min for the 4-h duration of the test) produced a short-lived but significant increase in the urinary excretion of albumin, but not in beta 2-microglobulin. Albumin excretion returned promptly to basal values in spite of high and sustained urine flow. The decrease in haematocrit, plasma osmolality, plasma sodium concentration and pulse rate and the increase in creatinine clearance suggest that the elevation in albumin excretion might be the result of a transient volume expansion associated with an increase in glomerular filtration rate and in filtration of albumin. However, a washout of proteins from the tubular lumen with preferential reabsorption of small molecular weight proteins (i.e. beta 2-microglobulin) during high tubular flow cannot be excluded. Studies investigating changes in urinary albumin excretion should be performed after baseline conditions of stable urinary excretion of albumin have been established.

Adolescent↗
PubMed1982

Relation of habitual diet to fasting plasma insulin concentration and the insulin response to oral glucose.

Blood glucose and plasma insulin levels during a 50 g oral glucose tolerance test were measured in a population sample of 220 people (109 men; 111 women), who also earlier recorded their diet over a 2-d period. In the men, but not the women, there was a statistically significant inverse relationship between total daily energy intake and both fasting and post-load plasma insulin concentrations. This correlation, which was independent of the degree of adiposity, may be a confounding factor in epidemiological studies relating plasma insulin levels to subsequent coronary heart disease.

Blood Glucose↗
PubMed1981

Patient reactions to long-term outpatient treatment with continuous subcutaneous insulin infusion.

Fourteen of the first 15 insulin-dependent diabetics to be treated in our unit by three weeks or more of outpatient continuous subcutaneous insulin infusion with a portable syringe pump completed a questionnaire about their reactions to the system. Motivation was more important to a favourable response than occupation or intelligence. Most patients thought that diabetic control was better with the pump than conventional injection treatment and several felt subjectively better. Features such as the greater flexibility of diet and insulin delivery rates during continuous subcutaneous infusion were appreciated. The most consistent adverse criticism was about the size of the device used, nearly all patients thinking that smaller and lighter infusion systems should be developed. Psychological reactions to the infusion and difficulties with interpersonal relationships were identified; these must be clearly appreciated and discussed with patients and family before and during treatment. Nine of the 14 patients said they would undertake continuous subcutaneous infusion for one year and a further two said they would do so if the infuser was smaller. These results provide guidance on future technological development of continuous subcutaneous insulin infusion and indicate that the major constraint to long-term trials of the present system is the size of the pump.

Activities of Daily Living↗
PubMed1981

Management of severely brittle diabetes by continuous subcutaneous and intramuscular insulin infusions: evidence for a defect in subcutaneous insulin absorption.

Severely brittle diabetes is defined as a rare subtype of insulin-dependent diabetes with wide, fast, unpredictable, and inexplicable swings in blood glucose concentration, often culminating in ketoacidosis or hypoglycaemic coma. To assess the role of inappropriate type, amount, or timing of insulin treatment and the route of administration as a cause of severe brittleness six patients with continuous subcutaneous insulin infusion, which provides a high degree of optimisation of dosage with exogenous insulin in stable diabetics. The glycaemic control achieved during continuous subcutaneous insulin infusion was compared with that during continuous intramuscular insulin infusion. Six patients with non-brittle diabetes were also treated by continuous subcutaneous insulin infusion. These patients achieved the expected improvement in glycaemic control (mean +/- SD plasma glucose concentration 5.1 +/- 2.3 mmol/l (92 +/- 41 mg/100 ml)), but not the patients with brittle diabetes remained uncontrolled with continuous subcutaneous infusion (13.6 +/- 5.8 mmol/1 (245 +/- 105 mg/100 ml) compared with 10.3 +/- 4.1 mmol/l (186 +/- 74 mg/100 ml) during treatment with optimised conventional subcutaneous injections). During continuous intramuscular infusion, however, glycaemic control in five of the patients with brittle diabetes was significantly improved (7.7 +/- 2.6 mmol/l (139 +/- 47 mg/100 ml). The remaining patient with brittle diabetes, previously safely controlled only with continuous intravenous insulin, did not respond to continuous intramuscular infusion. It is concluded that in five of the six patients with brittle diabetes studied here impaired or irregular absorption of insulin from the subcutaneous site played a more important part in their hyperlability than inappropriate injection strategies. This absorption defect was presumably bypassed by the intramuscular route.

Absorption↗
PubMed1981

Beta 2-microglobulinaemia: a sensitive index of diminishing renal function in diabetics.

A sensitive single measure of diminishing renal function is of importance in attempts to modify the progression of diabetic nephropathy. In 12 insulin-dependent diabetics with proteinuria plasma concentrations of beta 2-microglobulin were found to correlate more closely than plasma creatinine concentrations or creatinine clearance with glomerular function as measured by clearance of 52Cr-EDTA. The plasma beta 2-microglobulin concentration was raised in all patients with diminished glomerular filtration rate (below 80 ml/min/1.73 m2). By contrast, in two of these patients plasma creatinine concentration was normal. Plasma beta 2-microglobulin concentrations were stable throughout the day and not affected by food intake, unlike plasma creatinine concentrations, which rose in the afternoon and evening and after a meat meal. Plasma beta 2-microglobulin concentrations were the same in venous and capillary blood, the capillary blood being readily self-collected. Concentrations of beta 2-microglobulin were stable for up to 24 hours when whole blood was stored at 4 degrees C; adding aprotinin inhibited loss of beta 2-microglobulin for up to seven days. The results of this study suggest, therefore, that measuring beta 2-microglobulin concentrations is a simple and accurate method of detecting minor degrees of renal impairment and monitoring the effects of treatment.

Adult↗
PubMed1981

The influence of glucose-induced hyperinsulinaemia on renal glomerular function and circulating catecholamines in normal man.

The circulatory, renal, and hormonal responses to physiological elevation of plasma insulin induced with oral glucose have been studied in seven healthy subjects. glomerular filtration rate, urinary excretion rates of albumin and Beta2-microglobulin, haematocrit, pulse rate, blood pressure and plasma catecholamine concentrations have been measured. Physiological hyperinsulinaemia following glucose ingestion was associated with an increase in noradrenaline levels and brief tachycardia. No effect was noted on haematocrit, creatinine clearance, urinary albumin excretion, plasma adrenaline concentrations and arterial blood pressure. Urinary Beta2-microglobulin excretion rates fell shortly after the elevation of plasma insulin, probably indicating enhanced tubular reabsorption. Thus, glucose-induced physiological hyperinsulinaemia does not reduce glomerular filtration rate nor does it increase transglomerular passage of albumin, effects seen after the intravenous bolus injection of 6-8 U of insulin in diabetics.

Adult↗
PubMed1981

Continuous subcutaneous insulin infusion: comparison of plasma insulin profiles after infusion or bolus injection of the mealtime dose.

To help optimize meal-time blood glucose control in diabetic patients by continuous subcutaneous insulin infusion we have studied plasma insulin profiles in six normal subjects, suppressing endogenous insulin secretion with somatostatin. Insulin was administered subcutaneously either as a bolus or by high-rate infusion. Mean infusion profiles were similar on the two occasions, with peak levels at 75 and 90 min respectively, and a linear decline to 34% and 36% of peak concentrations at 5 h. Bolus injection resulted in a faster rise in insulin concentration, more consistent with physiological requirements. It is concluded that bolus delivery would be similar in effect while mechanically simpler to achieve than infusion, when part of a dual rate subcutaneous infusion system. The dose should be given 30 min before meals, if peak insulin concentrations are to be coincident with those found physiologically. Insulin concentrations remain high in the post-absorptive phase.

Adult↗
PubMed1981

Reversal of diabetic retinopathy by continuous subcutaneous insulin infusion: a case report.

We report the case history of a 20-year-old diabetic girl with long-standing poorly controlled disease who presented with severe retinopathic features and who was treated with continuous subcutaneous insulin infusion (CSII). When first seen she had macular oedema and a visual acuity of 6/18 in her only eye, together with multiple blot haemorrhages and intraretinal microvascular abnormalities. Marked reversal of the retinal lesions occurred within 65 days of initiating SCII and after only 36 days of constant normoglycaemia. Subsequent good blood glucose control on conventional subcutaneous insulin injections has been achieved, and the retinopathy remains quiescent with a visual acuity of 6/5. We suggest that CSII may be a potentially useful method of arresting and reversing early diabetic retinopathy.

Adult↗
PubMed1981

Correction of exercise-induced microalbuminuria in insulin-dependent diabetics after 3 weeks of subcutaneous insulin infusion.

The effect of metabolic near-normalization, induced by continuous subcutaneous insulin infusion, on the exaggerated microalbuminuria of exercise was studied in eight insulin-dependent diabetic men selected for normal resting albuminuria. Patients were studied in randomized order during the ordinary glycemic control of conventional insulin treatment (CIT) and after 3 wk of "super-control" with continuous subcutaneous insulin infusion (CSII). Seven age-matched healthy men were used as controls. In the diabetics the albuminuric response to fixed-load bicycle exercise (600 kpm/min for 20 min) during CIT greatly exceeded that of the normal controls (P less than 0.01). After 3 wk of optimal plasma glucose control, urinary albumin excretion rates in response to the same exercise load were significantly reduced (P less than 0.02) in the diabetics and became statistically indistinguishable from that of the normal controls. The urinary excretion rate of beta 2-microglobulin, an index of tubular function, was not increased significantly by exercise either during CIT or CSII. The plasma glucose fall after exercise was greater (P greater than 0.001) on CIT (8.5 +/- 0.9 mmol/L) than on CSII (4.0 +/- 0.6 mmol/L). The pulse rate acceleration in response to exercise was significantly reduced after 3 wk of CSII (P less than 0.05). The exercise-induced systolic blood pressure rise was similar in controls and diabetics on both therapeutic regimens. Thus, a period of metabolic near-normalization in the diabetic corrects the abnormal transglomerular passage of albumin induced by moderately strenuous muscular exercise and reduces the exercise tachycardia. Improved control with CSII appears to reduce greatly the risk of exercise-induced hypoglycemia, despite much tighter glycemic control.

Adult↗
PubMed1981

Hyperglycemia and arterial disease.

Clinical and autopsy evidence support the increased risk of atherosclerotic disease in diabetes mellitus (DM). However, mechanisms other than arterial occlusion may also contribute to clinical syndromes often assumed to be atherosclerotic in origin. There is considerable geographical variability in the frequency of arterial disease in the diabetic. Glucose intolerance short of unequivocal DM is found in some (though not all) populations to carry increased atherosclerotic risk. Morbidity and mortality data suggest that women are particularly vulnerable (as with DM). The Whitehall prospective study of cardiovascular mortality shows that risk does not rise smoothly with increasing degrees of glucose intolerance but that it doubles sharply at the 95th percentile of the 2-h post-glucose blood sugar distribution.

Adult↗