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Biomedical subjects

J C Pickup

Publications and source records attributed to J C Pickup.

At least 55 records · Page 3Linked to original sources
PubMed1988

Salivary insulin in normal and type I diabetic subjects.

We studied the relationship of salivary insulin to serum insulin concentrations in normal subjects and type I (insulin-dependent) diabetic patients to test the hypothesis that salivary insulin might be a simple measure of insulinemia in diabetes. In 8 nondiabetic subjects, salivary insulin levels increased after an oral glucose load but with a delay in peak concentrations of approximately 45 min in comparison with serum insulin levels. There was a significant correlation (r = .810, P less than .01) between mean serum insulin and the salivary insulin 30 min later. In 12 type I diabetic patients, day profiles of saliva and serum insulin were obtained during usual insulin treatment, diet, and physical activity. In serum, the mean (+/- SE) percentage of bound insulin was 58.8 +/- 5.2%, and in saliva it was 45 +/- 3.5%. The mean ratio of salivary to serum free insulin throughout the day was 1:1.6. Although there was a significant correlation (r = .913, P less than .001) between mean serum free insulin for all patients and the corresponding mean free salivary insulin, several individual profiles showed marked discrepancies between the timing and magnitude of insulin changes in the two compartments. We would not, therefore, recommend salivary insulin concentrations as a reliable index of insulinemia in individuals with type I diabetes.

Adult↗
PubMed1988

The natural history of brittle diabetes.

The natural history of brittle diabetes is unknown. We have followed up 13 patients with disabling brittle diabetes unresponsive to continuous subcutaneous insulin infusion (CSII) for 3-6 yr. All were young, C-peptide deficient females. One patient has died (of hypoglycaemia). In the others, disruption of life has generally lessened, but only one patient is currently considered metabolically stable. Insulin treatment regimens have included long-term intravenous insulin infusions and intraperitoneal insulin, but all but four have now reverted to subcutaneous injections. Eleven patients intermittently required greater than 200 U/day of insulin and two have needed greater than 1,000 U/day. Insulin dosages have fallen significantly during follow-up (from 6.8 +/- 3.1 to 1.4 +/- 0.3 U/kg/day). Diabetic complications, initially present in only 2 cases (1 cataract, 1 proliferative retinopathy), have now developed in 5 others (2 background retinopathy, 1 proliferative retinopathy, 1 mixed peripheral neuropathy and 1 intermittent proteinuria). Psychosocial disturbance and non-compliance were common. We conclude that brittleness generally seems to improve, which probably explains the scarcity of older brittle patients. However, these patients are at considerable risk from diabetes, its complications and its treatment.

Adolescent↗
PubMed1988

Progress towards in vivo glucose sensing with a ferrocene-mediated amperometric enzyme electrode.

A range of miniature, amperometric enzyme electrodes have been constructed using the principle of mediated transfer of electrons. Ferrocene, or one of its derivatives, can be used in conjunction with immobilised glucose oxidase to produce sensors which are linear to at least 20 mmol/l glucose, have fast response times, are relatively oxygen insensitive and are suitable for implantation studies. In preliminary experiments in non-diabetic pigs, electrode responses followed blood responses, although mean tissue levels were about one fifth of those in blood. The ferrocene technology thus appears to be suitable for adaptation to the construction of implantable glucose electrodes for use in diabetic man.

Animals↗
PubMed1987

Massive insulin resistance apparently due to rapid clearance of circulating insulin.

A 23-year-old insulin-dependent diabetic woman demonstrated increasing resistance to insulin administered by all routes, eventually requiring up to 20,000 units per day intravenously. Therapeutic trials of human and chemically modified insulin and of aprotinin were unsuccessful. Inappropriately low plasma free insulin levels (less than 60 mU/liter) during administration of extremely high insulin dosages (300 to 10,000 units per day) suggested that resistance was caused by rapid clearance of circulating insulin. There were several short periods of normal insulin sensitivity with hyperinsulinemia (more than 300 mU/liter) persisting long after intravenous insulin withdrawal, suggesting reentry to the circulation of intact, previously sequestered insulin. For four years, she has been treated with ambulatory continuous intravenous insulin infusion, which has been complicated by septicemia and central venous thrombosis. Her condition remains poorly controlled with documented intravenous insulin requirements of 2 to 20 units/hour.

Adult↗
PubMed1986

Subcutaneous implantation of a ferrocene-mediated glucose sensor in pigs.

Miniature, amperometric glucose sensors were constructed using entrapped 1,1'-dimethylferrocene to mediate electron transfer between immobilised glucose oxidase and a carbon base electrode. Electrodes were calibrated in buffered glucose solutions and then implanted in the subcutaneous tissue of anaesthetised, non-diabetic pigs. Subcutaneous tissue glucose concentrations, as measured by the sensor, were about 20% of blood glucose values, measured by a conventional glucose oxidase assay. After an intravenous 0.07 mol bolus glucose injection, electrode responses increased with almost no time lag, but the subsequent rates of rise and fall of electrode-measured tissue glucose concentrations were slower than that of the blood values. After an intravenous 0.2 U/Kg bolus short-acting insulin injection the electrode response was also rapid, but decreased at a slower rate than the blood glucose concentrations. We conclude that this is a feasible technology for future development as an implantable glucose sensor for use in diabetic man.

Animals↗
PubMed1986

Potentially-implantable, ferrocene-mediated glucose sensor.

We describe the construction and in vitro testing of a new potentially-implantable amperometric glucose sensor which is based on mediated electron transfer between immobilized glucose oxidase and a graphite base electrode. Under potentiostatic control, entrapped 1,1'-dimethylferrocene acts as an alternative electron acceptor to oxygen and provides a sensing strategy which is relatively unaffected by possible fluctuations in in vivo oxygen tension. Simple 1 mm wide electrodes with a polyurethane membrane gave linear current responses to at least 20 mmol/l glucose with a mean response time of 68 s. An acceptable proportion (17%) of electrodes had low or zero drift over 17 h at 37 degrees C. With plasma samples from diabetic and non-diabetic subjects, glucose concentrations measured by the sensor were significantly correlated with values obtained by a reference laboratory glucose analyser but were proportionally lower. Extension of this study to in vivo testing and further miniaturization of electrodes is justified.

Blood Glucose↗
PubMed1985

Continuous subcutaneous insulin infusion does not induce a significant acute phase response of serum amyloid A protein.

In a study of 23 matched pairs of Type 1 (insulin-dependent) diabetic patients receiving continuous subcutaneous insulin infusion or conventional insulin injection therapy respectively, there were no significant differences in serum levels of the acute phase proteins, serum amyloid A and C-reactive protein. These results do not support the suggestion that continuous subcutaneous insulin infusion stimulates serum amyloid A production or that it carries a risk of inducing reactive systemic amyloidosis.

Adolescent↗
PubMed1985

Frequency of diabetic ketoacidosis and hypoglycemic coma during treatment with continuous subcutaneous insulin infusion. Audit of medical care.

The frequency of diabetic ketoacidosis and hypoglycemic coma in a large series of patients with insulin-dependent diabetes treated by long-term continuous subcutaneous insulin infusion was compared with the frequency of these events in a matched group of patients treated by conventional insulin injections at the same hospital over the same period of time. Ketoacidosis and hypoglycemic coma occurred no more frequently in continuous subcutaneous insulin infusion-treated patients. Therefore, intensified insulin therapy achieved by continuous subcutaneous insulin infusion does not appear to be associated with a greater risk of ketoacidosis or hypoglycemic coma than does conventional insulin therapy.

Adult↗
PubMed1985

Diabetes mellitus: biosensors for research and management.

The condition of diabetes mellitus is described with particular reference to the parameters that it would be desirable to monitor in order to improve management and understanding of the disease. Previous attention has largely focused on analysis of glucose, but many other intermediates of carbohydrate, fat and protein metabolism are deranged in diabetes and may be alternative measures of control. The need for laboratory analysers, self-monitoring, closed-loop devices and alarms are detailed and the problems associated with implantable sensors discussed. Progress in the development of biosensors is reviewed using glucose sensors as the main example. Electrochemical, optoelectronic and calorimetric approaches to sensing are considered and it is concluded that configurations based either on hydrogen peroxide detection or on mediated electron transfer are most likely to provide a raid route to in vivo monitoring. The extension of biosensor technology to tackle other important substrates is discussed, the principal hurdle to success being seen as the lack of long-term stability of the biological component.

Blood Glucose↗
PubMed1985

Sample preparation and radioimmunoassay for circulating free and antibody-bound insulin concentrations in insulin-treated diabetics: a re-evaluation of methods.

Methods for blood sample preparation and radioimmunoassay of free and antibody-bound serum or plasma insulin concentrations, using polyethylene glycol (PEG) solution to precipitate bound insulin, have been evaluated and compared. Method A was rapid mixing of whole blood with PEG, followed by separation of bound insulin by centrifugation into Ficoll; method B was rapid PEG addition to whole blood, followed by centrifugation alone; method C was conventional PEG addition to thawed plasma or serum, followed by centrifugation to remove bound insulin. Method A was found to have acceptable performance and reproducibility; serum free insulin levels were not significantly different from those measured by the simpler method B. In samples from insulin-dependent diabetics, serum free insulin was significantly higher and bound insulin significantly lower in method A compared to the conventional method C. However, in samples from non-diabetics there was no significant difference between methods A and C. Spurious results were obtained by addition of PEG and assay of plasma and serum samples after either freezing and thawing or incubation at 37 degrees C for 2h, compared to PEG addition and assay of fresh plasma or serum samples. We conclude that conventional, delayed addition of PEG to plasma or serum may result in redistribution of free and bound insulin and that values more representative of in vivo blood insulin levels are obtained by rapid PEG addition methods.

Diabetes Mellitus↗
PubMed1985

Conference on insulin pump therapy in diabetes. Multicenter study of effect on microvascular disease. The pump life. Patient responses and clinical and technological problems.

As part of a randomized, prospective trial in subjects with insulin-dependent diabetes assigned to either continuous subcutaneous insulin infusion (CSII) or to their unchanged conventional insulin treatment (CIT) for 8 mo, patients completed questionnaires dealing with general responses and clinical and technological problems. Although there was no significant difference between treatment groups with respect to the number of patients experiencing severe hypoglycemia (i.e., requiring intravenous glucose or intramuscular glucagon injection), there were nine episodes in six patients during CSII compared with one episode during CIT. Diabetic ketoacidosis occurred significantly more often in the CSII group (nine episodes in eight patients) than in the CIT group (no episodes). A number of CSII-related failures occurred, including omission of premeal bolus, needle dislodgement, pump accidentally turned off, and leakage at the infusion site. At 8 mo, 85% of CSII-treated patients wished to continue indefinitely on the pump, and almost all would continue with self-monitoring of blood glucose even if they stopped CSII.

Canada↗