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Biomedical subjects

J C Pickup

Publications and source records attributed to J C Pickup.

At least 73 records · Page 4Linked to original sources
PubMed1985

Conference on insulin pump therapy in diabetes. Multicenter study of effect on microvascular disease. Origin and design of the Kroc Collaborative Study.

Although the benefits of metabolic intervention on the microvascular complications of diabetes mellitus remain unproven, it is generally assumed though not proven that prognosis in terms of blindness and renal failure will reflect the long-term glycemic response to therapy. Treatment goals however remain poorly defined. Costs and hazards of achieving near-normoglycemia in insulin-dependent diabetes mellitus (IDDM) are major. A multicenter trial was proposed to test the hypothesis that in IDDM two levels of mean glycemia, sufficiently separated to examine the control/complications relationship, could be maintained by the six collaborating centers, using randomized patient allocation to conventional insulin therapy (CIT) and continuous subcutaneous insulin infusion (CSII) as the alternative treatment modalities. Methods of maintaining and monitoring metabolic control and of assessing renal and retinal responses were to be applied, evaluated, and possibly improved. All clinics shared a common experimental protocol, which received ethical approval at each treatment center. Retinal assessment facilities were provided by the Fundus Photograph Reading Center at the University of Wisconsin in Madison, and at the Diabetic Retinopathy Department, Royal Postgraduate Medical School, Hammersmith, United Kingdom. The Central Biochemistry Laboratory was at the University of Newcastle, United Kingdom. Collaborators agreed on policy for recruitment, baseline assessment, and randomization of patients with IDDM, complicated by early microvascular disease. CIT took the form of the unchanged prestudy regimen; glycemic goals were set for CSII and their achievement based on inpatient and outpatient sampling of plasma glucose. Glycosylated hemoglobin was measured, retinal abnormalities recorded photographically, and urinary albumin excretion quantitated at baseline, 4, and 8 mo in all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗
PubMed1984

Glycaemic control in diabetic nephropathy.

To investigate the quality of glycaemic control that is achievable in diabetic patients with persistent proteinuria and asymptomatic but declining renal function three matched groups of patients were studied. The first comprised diabetics with proteinuria receiving continuous subcutaneous insulin infusion; the second, diabetics without proteinuria receiving continuous subcutaneous insulin infusion; and the third, diabetics with proteinuria receiving conventional insulin treatment. Glycaemic control in patients receiving continuous subcutaneous insulin infusion was shown to be appreciably worse during the daytime in diabetics with proteinuria than in diabetics without proteinuria, although greatly superior to that in diabetics with proteinuria receiving conventional insulin treatment. The loss of glycaemic control in patients with proteinuria receiving continuous subcutaneous insulin infusion probably occurred as a response to daytime hypoglycaemia and a consequent reduction in the proportion of the total insulin dose given prandially. Difficulty in controlling blood glucose concentrations may be a factor in the failure of intensified insulin regimens to influence the progression of diabetic renal disease.

Adult↗
PubMed1984

Prostaglandin E1 accelerates subcutaneous insulin absorption in insulin-dependent diabetic patients.

The powerful vasodilator, prostaglandin E1 (PGE1), was added to Actrapid insulin to try to accelerate the early phase of subcutaneous insulin absorption through increasing injection site blood flow. Actrapid insulin alone (6U) and insulin containing PGE1 (7.5 X 10(-6) M) were injected on different days into 13 fasting insulin-dependent diabetics. With the insulin/PGE1 mixture, increases in both free and total plasma insulin concentrations were greater at all times up to 120 minutes after injection than with insulin alone, with significant differences in the first 40 minutes. With insulin/PGE1 the area under the total plasma insulin curve increased significantly more rapidly between 80 and 120 minutes. Plasma glucose concentrations fell consistently more rapidly with insulin/PGE1 than with insulin alone although the differences were small (mean fall +/- S.E.M. at 120 minutes: 4.9 +/- 0.5 mmol/l vs 4.0 +/- 0.6; p = 0.02). Addition of local hyperaemic agents to short-acting insulin preparations could be therapeutically useful in hastening insulin entry to the circulation at mealtimes.

Adolescent↗
PubMed1984

Urinary insulin excretion rate: an index of free insulinaemia in insulin-dependent diabetics.

In 25 insulin-dependent diabetics, 14 managed by conventional insulin injection treatment (CIT) and 11 treated by continuous subcutaneous insulin infusion (CSII), there was a highly significant correlation between urinary insulin excretion rate (IER) per 1.73 m2 and mean serum free insulin concentration (r = 0.73, p less than 0.001), measured over a 24 h period. Urinary IER and mean daily serum free insulin levels were significantly higher in diabetics than in non-diabetics. CSII-treated patients had significantly lower mean 24 h plasma glucose levels than CIT-treated patients despite similar values of urinary IER and mean daily serum free insulin in the two groups. Urinary IER may be a useful indicator of average insulinaemia in large scale studies, avoiding the problems of multiple blood sampling and immunoassay in the presence of anti-insulin antibodies.

Adult↗
PubMed1984

Metabolic effects of physical exercise in insulin-dependent diabetics controlled by continuous subcutaneous insulin infusion or conventional injection therapy.

The metabolic and hormonal response to moderately severe exercise 2 h after breakfast was assessed in 8 insulin-dependent diabetics during conventional insulin injection therapy and after 3 weeks of continuous sc insulin infusion. Blood glucose fell from 12.1 to 4.4 mmol/l on injection therapy; this was accompanied by a significant rise (P less than 0.05) in free insulin to 57 mU/l. On infusion therapy plasma glucose fell and stabilised at 3.6 mmol/l from pre-exercise levels of 7.1 mmol/l, while free insulin level was unchanged at the end of the exercise period (31 mU/l). The fall in blood glucose on injection therapy was accompanied by an exaggerated growth hormone response to exercise that was normalised by 3 weeks of infusion therapy. Basal and post-prandial levels of intermediary metabolites, catecholamines and glucagon were comparable on the two insulin regimens. Responses during exercise were generally similar and no different from those of normal subjects, with the exception of plasma NEFA levels which became abnormally suppressed. Good metabolic control of diabetes is thus accompanied by nearly normal hormonal and metabolic response to moderately severe exercise.

Adult↗
PubMed1983

Subcutaneous aprotinin causes local hyperaemia. A possible mechanism by which aprotinin improves control in some diabetic patients.

Local changes in blood flow at the subcutaneous injection site of the proteinase inhibitor aprotinin and its diluent were measured by photoelectric plethysmography. Aprotinin, but not its diluent, caused local hyperaemia in five normal subjects and in five stable and five brittle insulin-dependent diabetic patients, local blood flow increasing by 80%-180%. The duration of the hyperaemic response was shorter in the brittle diabetic patients than in the other two groups, but there was wide individual variation. Aprotinin is known to enhance subcutaneous insulin absorption in normal subjects and in some brittle diabetic patients. The basis for this might be through increasing blood flow near the injection site rather than by inhibition of insulin breakdown.

Adult↗
PubMed1983

A new miniature, open-loop, extracorporeal insulin infusion pump.

This extracorporeal insulin infuser has been designed to be compact, simple to operate, and suitable either for clinical investigations of insulin-dependent diabetes mellitus or for long term treatment of the condition. A syringe driver of unconventional design is used, and the syringe will be available prefilled with insulin, specially formulated at standard strength for long term infusion. The device is electronically controlled to give variable rates of basal infusion, preset by switch and supplemented by bolus infusions demanded by pushbutton prior to meals. Sufficient insulin is carried in the syringe to meet the needs of most diabetics for at least a week without refilling, and the battery life is commensurately long. Signalling of the mealtime dose regime, and of alarm and failure conditions is by audible means. Insulin will most commonly be delivered subcutaneously, though other routes are possible.

Biomedical Engineering↗
PubMed1983

Practical experiences with insulin infusion pumps.

The future role of continuous subcutaneous insulin infusion as a routine treatment for insulin-dependent diabetics rests on clinical considerations such as patient reactions to the system, the possibilities and consequences of pump malfuntion and the effect of pump-induced strict metabolic control on diabetic complications. These issues are discussed in the light of recent evidence.

Consumer Behavior↗
PubMed1982

Safety of continuous subcutaneous insulin infusion: metabolic deterioration and glycaemic autoregulation after deliberate cessation of infusion.

To assess the rate of metabolic deterioration and potential risks of failure of continuous subcutaneous insulin infusion during basal insulin delivery, we deliberately stopped infusion in nine insulin dependent diabetics. Plasma glucose, blood 3-hydroxybutyrate and plasma free insulin were measured for 9 h whilst the patients remained supine and fasting. Mean plasma glucose remained unchanged at normal fasting levels for the first hour, then rose to plateau at about 10 mmol/l until the end of the experiment. The final plateau level of glucose varied from patient to patient; two C-peptide secreting diabetics plateaued at low glucose levels. In contrast, blood 3-hydroxybutyrate rose progressively, without plateauing. PLasma free insulin concentrations fell during the withdrawal period and there was a highly significant negative correlation between free insulin and 3-hydroxybutyrate. No patient was more than mildly unwell after 9 h of insulin deprivation. We conclude that under these experimental conditions there is glycaemic autoregulation and that ketones may sometimes be a more appropriate monitor of insulin deficiency or loss of diabetic control than is glucose. Accidental failure of continuous subcutaneous insulin infusion and interruption of basal delivery in resting and fasting diabetics will probably not cause dangerous metabolic or clinical deterioration.

3-Hydroxybutyric Acid↗
PubMed1982

Proteinuria in diabetes mellitus: role of spontaneous and experimental variation of glycemia.

The excretion rates of albumin, IgG and beta 2-microglobulin were studied in insulin-dependent diabetic patients with (Albustix positive) and without (Albustix negative) clinical proteinuria and in a group of nondiabetic controls. In patients negative for clinical proteinuria, the mean excretion rate of albumin and IgG was increased but that of beta 2-microglobulin was normal. HbA1, a measure of excess glycemia, was positively correlated with both albumin and IgG urinary excretion rates. Vigorous correction of glycemic control significantly reduced IgG excretion in nine patients. In patients positive for clinical proteinuria, albumin and IgG clearances were inversely correlated with GFR, the filtration of IgG increasing relatively more than that of albumin as GFR declined. A negative hyperbolic correlation was found between GFR and beta 2-micro-globulin excretion. In this group HbA1 was unrelated to excretion rates or clearances of albumin and IgG. In clinically proteinuric patients, long-term correction of hyperglycemia by continuous subcutaneous insulin infusion failed to check the increasing albumin and IgG filtration. The microproteinuria of diabetes is glomerular in origin, is influenced by prevailing glycemia, and is reversible by vigorous glycemic control. In the clinically proteinuric phase, by contrast, selectivity is progressively lost and, as GFR falls, proteinuria becomes of a mixed glomerular and tubular origin. There is no evident association with prevailing glycemia, and metabolic near-normalization dose not appear to affect progression over the period of observation considered. This study suggests that clinical proteinuria denotes the installation of a self-maintaining process, largely independent of the diabetic metabolic disturbance which gave rise to it. Prevention of clinical diabetic nephropathy by metabolic correction may be achievable only in the phase of early microproteinuria.

Adult↗
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

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↗