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Biomedical subjects

J C Pickup

Publications and source records attributed to J C Pickup.

At least 37 records · Page 2Linked to original sources
PubMed1995

Serum sialic acid concentration and coronary heart disease in NIDDM.

OBJECTIVE--To examine the association between serum sialic acid concentrations and coronary heart disease (CHD) in a cross-sectional study of non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS--NIDDM patients (n = 145) attending a diabetic clinic were studied. CHD status was assessed by questionnaire and electrocardiogram coding, and potential risk factor assessment included measurement of fasting serum lipid and lipoprotein concentrations, blood pressure, and urinary albumin excretion rate (AER). RESULTS--Male NIDDM patients with CHD had a higher serum sialic acid level than those without CHD: 2.56 (2.24, 2.72) mmol/l vs. 2.24 (2.18, 2.30) mmol/l, P = 0.01, mean (95% confidence interval). They were also older, had a longer duration of diabetes, had a higher AER, had higher total triglyceride, very-low-density lipoprotein triglyceride and cholesterol, and lipoprotein(a) concentrations, and had a lower apolipoprotein A1 concentration. In an age adjusted multiple lipoprotein(a), hypercholesterolemia, and hypertension were associated with CHD. In women, only hypertension treatment was associated with CHD. CONCLUSIONS--There is a strong univariate association between elevated serum sialic acid and CHD in men (but not women) with NIDDM.

Adult↗
PubMed1994

Serum sialic acid, a risk factor for cardiovascular disease, is increased in IDDM patients with microalbuminuria and clinical proteinuria.

OBJECTIVE: An elevated serum sialic acid concentration has recently been shown to be a potent cardiovascular risk factor in the general population. Because clinical proteinuria is associated with a high frequency of cardiovascular disease, and because microalbuminuria predicts the development of renal and cardiovascular disease in diabetes, we investigated whether serum sialic acid levels are increased in insulin-dependent diabetes mellitus (IDDM) patients with microalbuminuria or clinical proteinuria. RESEARCH DESIGN AND METHODS: We studied 23 patients with IDDM who had a normal urinary albumin excretion rate, 23 patients who had microalbuminuria, and 23 patients with clinical proteinuria. The patients were matched for age, sex, duration of diabetes, GHb levels, and body mass index (BMI). Fasting blood samples were taken for measurement of sialic acid, cholesterol, triglyceride, creatinine, and GHb. RESULTS: Serum sialic acid was significantly higher in the microalbuminuric patients compared with the normoalbuminuric group (mean +/- SD: 1.93 +/- 0.26 vs. 1.76 +/- 0.27 mM, P < 0.01). Moreover, serum sialic acid was also significantly higher in the group with clinical proteinuria compared with the microalbuminuric patients (2.34 +/- 0.24 vs. 1.93 +/- 0.26 mM, P < 0.001). Serum sialic acid was not related independently to age, BMI, diabetes duration, GHb, blood pressure, serum cholesterol, triglyceride, or creatinine concentration in any of the diabetic groups. CONCLUSIONS: These observations suggest that the serum sialic acid concentration is raised in IDDM patients with both microalbuminuria and clinical proteinuria and may play a role as a cardiovascular risk factor or disease marker in these conditions.

Adult↗
PubMed1994

Serum 1,5-anhydro-D-glucitol assay by high performance anion exchange chromatography.

Serum 1,5-anhydroglucitol (AG) concentrations may be an indicator of glycaemic control in diabetic patients. We have therefore developed an HPLC method for assay of serum AG. Serum samples were de-proteinised with trichloroacetic acid and neutralised with the addition of an anion exchange resin. Erythritol was added to serum as an internal standard. For HPLC, CarboPac MA1 ion exchange columns were used, eluting with 80 mmol/l sodium hydroxide solution. Peak detection was by pulsed amperometry using a gold electrode. The serum AG concentration in 37 non-insulin-dependent diabetic patients was significantly lower than in 28 normal subjects: mean and range 19(4-163) vs. 134(92-203) mumol/l, P < 0.001.

Blood Glucose↗
PubMed1993

Serum sialic acid and acute phase proteins in type 1 and type 2 diabetes mellitus.

Serum sialic acid is a risk factor for cardiovascular disease in the general population. Serum total sialic acid concentrations were therefore measured in 20 type 1 diabetic patients and in 20 age- and sex-matched non-diabetic subjects. Serum sialic acid were not significantly different in the type 1 diabetic patients and the normal subjects (2.00 +/- 0.37 vs. 1.98 +/- 0.67 mmol/l), but was significantly correlated with serum total cholesterol (r = 0.55, P < 0.02) and serum triglyceride concentration (r = 0.63, P < 0.01) in the type 1 diabetic patients. There was no relationship of sialic acid levels to age, duration of diabetes, smoking, body mass index, systolic or diastolic blood pressure, plasma glucose, serum fructosamine, or daily insulin dosage. Six of the type 1 diabetic patients with retinopathy had higher total serum sialic acid concentrations than those patients without retinopathy (2.38 +/- 0.33 vs. 1.85 +/- 0.26 mmol/l, P < 0.01). A further study of 16 type 1 and 16 type 2 diabetic patients matched for serum fructosamine and blood glucose concentrations and without tissue complications showed that the serum total sialic acid concentration was significantly higher in the type 2 diabetic patients compared with the type 1 patients (2.32 +/- 0.41 vs. 1.84 +/- 0.24 mmol/l, P < 0.001). Although the serum concentrations of the non-sialylated acute phase protein, C-reactive protein, was higher in type 2 than type 1 diabetes, sialylated acute phase protein levels did not explain differences in serum total sialic acid in diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute-Phase Proteins↗
PubMed1993

Responses and calibration of amperometric glucose sensors implanted in the subcutaneous tissue of man.

Glucose sensors based on immobilized glucose oxidase and hydrogen peroxide detection at a platinum base electrode were constructed and studied before, during and after implantation into the subcutaneous tissue of 11 non-diabetic subjects. A 75-g oral glucose load was given to elevate the blood glucose concentration. Seven of 14 sensors responded to the oral glucose administration with an increase in current and the output of the remainder was unchanged by the glucose load. Apparent subcutaneous glucose levels calculated from the pre-implantation calibration were a mean 58% of the plasma glucose values at baseline. A two-point in vivo calibration using paired current and glucose readings at baseline and at the maximum glucose and current after glucose ingestion showed a significantly reduced sensitivity in vivo compared with pre-implantation values (mean +/- SEM 52 +/- 21.5 vs 369 +/- 127 pA/mmol-1 per litre, P = 0.003). Recalibration of the subcutaneous glucose concentrations using the in vivo calibration sensitivity and extrapolated background current (I0) gave values similar to those in plasma. The sensitivity of five sensors recalibrated in vitro after explantation was also reduced compared with pre-implantation levels and not significantly different from the in vivo characteristics. Responding and non-responding sensors did not differ with respect to preimplantation I0, sensitivity or response time. However, provisional examination of some explanted sensors by scanning electron microscopy showed coating by cellular and other amorphous material in the non-functioning electrodes. We conclude that the sensitivity of glucose sensors of this design is markedly reduced, sometimes to zero, on implantation in the subcutaneous tissue of humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Elevated serum sialic acid concentration in NIDDM and its relationship to blood pressure and retinopathy.

OBJECTIVE: In view of the possible link between serum sialic acid and cardiovascular disease in the general population, we investigated whether serum total and lipid-associated sialic concentrations are elevated in NIDDM patients compared with normal subjects. We also investigated how sialic acid levels relate to glycemic control, blood pressure, microalbuminuria, retinopathy, and serum lipid levels. RESEARCH DESIGN AND METHODS: We selected 20 NIDDM patients at random and matched them for age and sex with 20 normal subjects. The patients also had a similar BMI as the control subjects. A first morning blood sample was taken for sialic acid, glucose, fructosamine, and lipid analysis, as was a first morning urine sample for assessment of microalbuminuria. Retinopathy was assessed by fundoscopy. RESULTS: Both total and lipid-associated sialic acid levels were elevated in the NIDDM patients compared with control subjects (mean +/- SD, total: 0.74 +/- 0.11 vs. 0.60 +/- 0.22 g/L, P < 0.02; lipid-associated: 0.18 +/- 0.04 vs 0.12 +/- 0.04 g/L, P < 0.001). Total serum sialic acid was correlated with systolic blood pressure (r = 0.58, P < 0.01) and diastolic blood pressure (r = 0.58, P < 0.02). There was no significant relationship of total sialic acid with age, duration of diabetes, BMI, microalbuminuria, serum triglyceride, blood glucose, or serum fructosamine. A relationship of lipid-associated sialic acid levels and systolic blood pressure did not reach significance (P = 0.09). In 9 patients with background retinopathy with or without maculopathy, the total serum sialic acid concentration was higher than in those without retinopathy (0.81 +/- 0.09 vs. 0.69 +/- 0.10 g/L, P < 0.008). Lipid-associated sialic acid levels were similar in those with and without retinopathy. (The conversion factor for standard units to SI units is 1 gL = 3.2 mM.) CONCLUSIONS: Total serum sialic acid levels were significantly elevated in a relatively small group of NIDDM patients and were correlated with hypertension and retinopathy. A larger study of circulating sialic acid concentrations as a risk factor for the development or marker of diabetic angiopathy is therefore justified.

Albuminuria↗
PubMed1993

Serum sialic acid enzymatic assay based on microtitre plates: application for measuring capillary serum sialic acid concentrations.

We have adapted a commercially-available kit for the enzymatic determination of sialic acid so that the reaction can be carried out in microtitre wells and the coloured end product quantitated on an ELISA plate reader. The small volume of serum used allows sialic acid to be measured in capillary blood samples. The assay was based on release of sialic acid from glycoconjugates by neuraminidase, cleavage of sialic acid by N-acetyl neuraminic acid aldolase to pyruvate, and then oxidation of pyruvate to hydrogen peroxide by pyruvate oxidase. Hydrogen peroxide was determined by the red product formed in the presence of peroxidase, 4-aminoantipyrine and N-ethyl-N-2-hydroxyethyl-3-toluidine. The assay was linear to at least 10 mmol/l and unaffected by haemolysis, and by the addition of glucose, 3-hydroxybutyrate, bilirubin and pyruvate. Capillary serum sialic acid concentrations were not significantly different from simultaneously measured venous serum sialic acid levels. Self-collected capillary blood samples were obtained from healthy subjects over 6 h during the day. No variations in serum sialic acid concentrations were found in response to a meal. We conclude that this micro-adaptation of a specific sialic acid assay will be suitable for epidemiological surveys of serum sialic acid collected by patients and normal subjects.

Biomarkers↗
PubMed1991

'Brittle' diabetes.

Explore the source record for details and available documents.

Diabetes Mellitus, Type 1↗
PubMed1991

In vitro testing of a simply constructed, highly stable glucose sensor suitable for implantation in diabetic patients.

We have constructed and tested in vitro a potentially implantable, needle-type amperometric enzyme electrode which is suitable for continuous monitoring of glucose concentrations in diabetic patients. The major requirements of stability during operation and ease of manufacture have been met with a sensor design which involves a simple dip-coating procedure for applying to a platinum base electrode an inner membrane of glucose oxidase immobilised in polyhydroxyethyl methacrylate (pHEMA), and an outer membrane composed of a pHEMA/polyurethane mixture. Sensors were operated at 700 mV for detection of hydrogen peroxide. Calibration curves for the sensor were linear to at least 20 mM glucose and were unaffected by a reduction in PO2 from 20 to 5 kPa. During continuous operation in 5 mM buffered glucose solutions in vitro, sensors suffered no significant loss of response over periods of up to 60 h. Such electrodes are, therefore, useful for development as in vivo glucose sensors.

Biosensing Techniques↗
PubMed1989

In vivo molecular sensing in diabetes mellitus: an implantable glucose sensor with direct electron transfer.

Miniature, amperometric glucose sensors were constructed for implantation in the subcutaneous tissue of normal and insulin-dependent diabetic subjects. To minimise dependence on fluctuating tissue oxygen tension, we employed the technology of mediated electron transfer, with 1,1'-dimethylferrocene acting as the redox shuttle between immobilized glucose oxidase and a platinum base electrode. In 6 normal subjects, the subcutaneous sensor responses mirrored the simultaneously-measured changes in blood glucose concentration after a 75 g oral glucose load and after intravenous injection of 0.15 U/kg short-acting insulin, though increases and decreases in the sensor output were slower than the glycaemic changes. The mean peak delay in sensor response after the oral glucose was 40 min (range 0-45 min) and the delay in the hypoglycaemic nadir was 4 min (range 0-15 min). In 5 insulin-dependent diabetic subjects, spontaneous and induced hypoglycaemia was detectable by the implanted sensor. In addition, marked and frequent oscillations in the sensor current occurred in several normal and diabetic individuals as the blood glucose fell below about 1.9 mmol/l. These oscillations were present in a diabetic subject who had lost adrenergic warning symptoms to hypoglycaemia. Continuous metabolic monitoring in diabetes, particularly the detection of hypoglycaemia, may be possible with implanted sensors based on this technology.

Adult↗
PubMed1989

Potentially-implantable, amperometric glucose sensors with mediated electron transfer: improving the operating stability.

The major problems with existing amperometric enzyme electrodes for glucose sensing are oxygen sensitivity and output drift. The recently described miniature glucose sensors using immobilised ferrocene (dicyclopentadienyl iron) to mediate electron transfer from glucose oxidase to a base electrode are oxygen-independent but are often unstable. In this study, we test the hypothesis that the stability of ferrocene-based sensors can be markedly improved by better retention of the enzyme at the electrode. Sensors with graphite foil as the base electrode, dimethylferrocene as the mediator and carbodiimide/glutaraldehyde for enzyme immobilisation lost most of their activity when calibration curves were compared before and after 18 h operation in vitro at 37 degrees C (mean current decrease at 20 mmol/litre glucose was 91%). This sensor type with a covering cellulose membrane also lost activity (mean current decrease of 40% after 18 h). Electrodes in which the base sensor was platinum and the enzyme was covalently attached to agarose lost no activity when operated either at 700 mV without mediator (as a hydrogen peroxide detector) or at 160 mV with mediator. We conclude that both ferrocene-mediated and hydrogen peroxide-detecting amperometric glucose sensors with a high density of covalently-linked enzyme have an operating stability in vitro which may render them suitable for clinical use as, for example, an overnight hypoglycaemia alarm.

Biosensing Techniques↗
PubMed1989

Patterns of hyperinsulinaemia in type 1 diabetic patients with and without nephropathy.

The prevalence and patterns of insulinaemia in five groups of patients with Type 1 diabetes have been reinvestigated using a free insulin assay which minimizes in vitro redistribution of the free and antibody-bound insulin components. In 18 diabetic patients managed by conventional insulin injection treatment and 19 patients treated by continuous subcutaneous insulin infusion (CSII), the mean 24-h serum free insulin level exceeded a non-diabetic reference range in 78% (injections) and 68% (CSII). Twenty-four-hour profiles showed that hyperinsulinaemia occurred in the basal state before meals and at night, but not immediately post-prandially. The serum free insulin concentration at 0800 h, 1200 h, and 1600 h was significantly (p less than 0.001) correlated with mean 24-h free insulin in injection-treated and CSII patients, and samples at one of these time-points may thus provide a simple, single measure of integrated insulinaemia for population studies. There was no significant difference in 24-h mean free insulin levels in 7 patients randomly crossed-over between injection treatment and CSII, but the profiles had a more physiological pattern during CSII, with a mean post-prandial serum free insulin level which was significantly higher on CSII than injections (mean +/- SE = 37.2 +/- 3.1 vs 26.9 +/- 2.5 mU l-1, p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗