Evaluation of an electrochemical sensor for measuring blood ketones.

OBJECTIVE: To evaluate the performance of a hand-held ketone sensor that is able to measure blood beta-hydroxybutyrate (beta-HBA) concentrations within 30 s in patients with diabetic ketoacidosis (DKA) and patients who attend a weight management clinic. RESEARCH DESIGN AND METHODS: Two groups of patients were studied: 19 patients admitted with DKA and 156 patients attending a weight management clinic. Paired capillary and venous whole blood samples were measured using the ketone sensor and also using an enzymatic laboratory reference method. RESULTS: The ketone sensor accurately measured beta-HBA concentrations in patients with DKA (limits of agreement -0.9 to + 1.0 mmol/l) or starvation-induced ketonemia (limits of agreement -0.5 to +0.5 mmol/l). CONCLUSIONS: This ketone sensor accurately measures whole blood beta-HBA concentrations within 30 s.

Urinary excretion of albumin and retinol binding protein in systemic lupus erythematosus.

We have measured the urinary excretion of total protein, albumin and retinol binding protein (RBP) in random urine specimens obtained from 40 female patients with systemic lupus erythematosus (SLE). Thirty-three of these patients had no clinical evidence of any renal impairment (non-renal SLE); seven had overt renal disease (renal SLE). RBP:creatinine ratios were significantly higher in non-renal SLE patients compared with female controls (P = 0.002). There was no significant difference between urine total protein concentrations, albumin:creatinine or total protein:creatinine ratios in non-renal SLE patients when compared with controls, despite approximately 20% of these patients having elevated excretion of total protein or albumin. All seven renal SLE patients had elevated albumin:creatinine ratios but only four of them had an increased RBP:creatinine ratio. Of 29 non-renal SLE patients who had urinary total protein concentrations below 0.2 g/L, (i.e. approximating to a negative protein dipstick), 14 had increases in either albumin or RBP:creatinine ratios. Only two patients had increases in both. In the absence of clinical evidence of renal disease, increases in urinary albumin or RBP excretion could indicate subclinical nephropathy and measurements may have a role in the early diagnosis and subsequent monitoring of renal disease in SLE.

Transmission and ecology of trypanosomatid flagellates of water striders (Hemiptera: Gerridae).

An investigation of transmission and ecology of the monogenetic trypanosomatids, Blastocrithidia gerridis and Crithidia flexonema, in Gerris is described. Motile free-living flagellates of both species were found in the faeces of Gerris and in the water on which the bugs inhabited. Transmission of both trypanosomatid species occurred from naturally infected wild-caught bugs to flagellate-free laboratory-bred bugs via water. Crithidia flexonema was also transmitted to laboratory-bred bugs after being isolated in culture. Observations of experimentally infected bugs indicate that C. flexonema flagellates are imbibed and pass through the fore- and midgut to the hindgut where they become attached and multiply. There was no evidence to suggest transovarial transmission. In a 3-yr investigation into the prevalence of trypanosomatids in a natural population of adult Gerris odontogaster, it was found that the infection rate varied between 19% and 100%. There was no significant difference in infection rates between females and males. The infection rate peaked for each year in late spring or early summer. The significance of these results is discussed in relation to the ecology and behaviour of Gerris. The results indicate that the infections are maintained in hibernating bugs over winter.

Alternate site blood glucose testing: do patients prefer it?

AIMS: To examine patients' perspectives on ease of use and pain with the MediSense alternate site blood glucose testing device (Soft-Sense) compared with their current glucose testing method, and to evaluate the analytical performance of the MediSense device with the laboratory reference method. METHODS: Study participants were shown how to use the Soft-Sense glucose device and asked to perform two tests on their forearm. A capillary sample was collected from their finger and tested on the external port of the Soft-Sense meter and a laboratory method (YSI Glucose Analyser). Finally, one drop of blood was also directly tested from the finger onto the external port. Patients completed a questionnaire comparing ease of use and associated pain of their current testing method with the Soft-Sense meter. RESULTS: Patients preferred the Soft-Sense device to their own for ease of use and for less pain (93% found it easier to use and 96% less painful; P < 0.001). Glucose results correlated closely with the laboratory method (mean absolute percentage bias for the forearm 11.0%, finger 6.0%, and collected capillary sample 5.7%). Error grid analysis showed that all Soft-Sense results were clinically acceptable. CONCLUSIONS: Patients prefer the Soft-Sense alternate site testing device to their existing measuring method. The device accurately measures whole blood glucose.

Human insulin and awareness of acute hypoglycaemic symptoms in insulin-dependent diabetes.

Some insulin-dependent diabetic patients who have clear symptoms of hypoglycaemia during animal insulin treatment have reported loss of these symptoms when human insulin preparations are introduced. A survey of Mersey Region, UK, identified eleven patients whose awareness of hypoglycaemia was lost after introduction of human insulin but returned with animal insulin treatment; seven took part in the study. Acute hypoglycaemia was induced in these patients on two occasions by intravenous infusion of porcine or human soluble insulin (2.5 mU.kg-1, min-1) in random order. There was no significant difference between porcine and soluble insulin in the plasma glucose profile; mean (SEM) plasma glucose fell from 7.1 (0.4) mmol/l to a nadir of 1.5 (0.1) mmol/l with porcine insulin and from 7.1 (0.5) mmol/l to 1.6 (0.2) mmol/l with human insulin. An acute autonomic reaction occurred in all seven patients, at a similar plasma glucose concentration (1.9 [0.1] mmol/l with porcine insulin; 2.0 [0.2] mmol/l with human insulin). There were no significant differences in the frequency of symptoms or signs of hypoglycaemia between the two insulin species, nor any consistent differences in plasma glucagon, cortisol, growth hormone, adrenaline, or noradrenaline responses to hypoglycaemia. Symptomatic and hormonal responses to acute hypoglycaemia induced by porcine and human soluble insulins therefore seem to be almost indistinguishable, even in patients carefully selected for their apparent loss of hypoglycaemia awareness with human insulin.

Gender and the clinical usefulness of the albumin: creatinine ratio.

One hundred and eighty-seven diabetic and 105 control subjects collected timed overnight urine samples to measure the inter-individual variation in creatinine excretion rate and its determinants, and to test the relationship between albumin excretion rate (AER) and two 'surrogate measures', the albumin concentration and albumin:creatinine ratio. Creatinine excretion was 55% higher in men than women (geometric mean 8.9 mumol min-1 (95% confidence limits 4.7-17.0) compared with 5.7 (3.0-10.9); p < 0.001). Gender accounted for 31% of the variation in creatinine excretion and body mass index 1.4%; neither age nor the diabetic state had a significant effect. The relationships between AER and the two surrogate measures differed between diabetic subjects and controls such that relationships constructed from non-diabetic data would not hold true for diabetes. Likewise, the relationship between AER and albumin:creatinine ratio differed between men and women such that a ratio of 4.0 mg mmol-1 corresponded to a predicted AER of 35 micrograms min-1 in men and 23 micrograms min-1 in women. The albumin:creatinine ratio outperformed albumin concentration in terms of sensitivity and specificity and its performance was better in women than men. We conclude that the albumin:creatinine ratio is a better surrogate for AER than albumin concentration. If 'action levels' are to be defined for screening programmes, they should be derived from diabetic and not non-diabetic data and should be different in men and women. We propose a direct rather than screening role for the albumin:creatinine ratio in the management of diabetic nephropathy.

Accurate and precise blood glucose measurement in the hypoglycaemic range.

The aim of the study was to evaluate the performance of an electrochemical blood glucose sensor, the satellite G, in the low-normal and hypoglycaemic range. Eighty-five venous blood samples with glucose concentrations below 4.0 mmol I-1 from six patients with Type 1 diabetes undergoing induced hypoglycaemia were measured in duplicate on the sensor and a reference method, the Yellow Springs whole blood glucose analyser. The sensor values correlated well with the reference method (r = 0.9, p < 0.001) with a mean absolute percentage bias of 10.7%. The 95% confidence limits of agreement between methods were +0.7 and -0.6 mmol I-1 with a mean difference of 0.004 mmol I-1. More than 80% of the sensor measurements were within 20%, and 60% were within 10% of the reference method. Measured over all samples, the sensor had a coefficient of variation of 7.2% for paired measurements. The coefficients of variation of 20 measurements on each of two samples with glucose concentrations of 1.3 and 2.6 mmol I-1 were 9.1% and 5.8%, respectively. We conclude that the satellite G measures blood glucose accurately and precisely in the low range.

'Hospital hyperglycaemia'; perception or reality?

Patients' perceptions that clinic fasting blood glucose measurements in Type 2 diabetes are artefactually high were investigated. Eighteen men and 14 women in the Salford cohort of the United Kingdom Prospective Diabetes Study (UKPDS) with a median age of 51 (range 37-69) years measured their fasting blood glucose concentration at home with visually read sticks or meters; they then collected capillary blood into fluoride tubes both at home and in clinic after a median lapse of 77 (range 25-173) min. The clinic samples were measured immediately and after a time lapse equivalent to the time taken to reach clinic to control for continued glycolysis in the home sample. Mean fasting blood glucose was 5.9 +/- 1.9 mmol 1(-1) by the patients' own measurement and 6.0 +/- 1.8 mmol 1(-1) on the home collected sample compared with 6.2 +/- 2.0 mmol 1(-1) and 6.1 +/- 2.0 mmol 1(-1) on the hospital immediate and time-lapsed measurements, respectively (p > 0.05 for all comparisons between home and hospital measurements); although there were no systematic differences, occasional measurements differed more than 2 mmol 1(-1). These data support the use of the fasting blood glucose level as a stable, patient-independent measure of glycaemic control in Type 2 diabetes.

Evaluation of a second-generation electrochemical blood glucose monitoring system.

One hundred and ninety-five diabetic patients attending hospital clinics gave blood samples to test the accuracy and precision of a second generation glucose sensor (satellite G, MediSense Inc., Abingdon, UK) with particular emphasis on its performance with venous blood. Sensor results correlated closely with a standard laboratory method; analysis of residuals showed no deviation from zero slope. Mean percentage difference was low (< +/- 6.0%) and the 95% limits of agreement were < +/- 30% with both capillary and venous blood. Error Grid Analysis showed that none of the measurements would have led to serious management errors. Precision of the system was good with coefficients of variation (CV) between 2.8% and 7.1% for glucose concentrations ranging from 3.0 to 24.0 mmol l-1. The mean CV for duplicate measurements was 5.4% with capillary and 4.4% with venous blood. We conclude that the electrochemical glucose method gives accurate and precise measurements of venous and capillary blood glucose.

Evaluation of a bedside blood ketone sensor: the effects of acidosis, hyperglycaemia and acetoacetate on sensor performance.

AIMS: To assess the performance of a handheld bedside ketone sensor in the face of likely metabolic disturbances in diabetic ketoacidosis, namely: pH, glucose and acetoacetate. METHODS: The effects of pH (7.44-6.83), glucose (5-50 mmol/l) and acetoacetate (0-5 mmol/l) were examined in venous blood to investigate the accuracy of betahydroxybutyrate measurement (0-5 mmol/l) by a handheld ketone sensor. Sensor results were compared with a reference method. Linear regression models were fitted to the difference between the methods with the concentration of metabolite as the explanatory factor. RESULTS: Decreasing pH and increasing glucose had no effect on the accuracy of the handheld ketone sensor; the gradients of the fitted lines were -0.14 and -0.003, respectively. The 95% confidence intervals were -0.7-0.4 and -0.01-0.004, respectively (P = 0.59 and 0.4, respectively). In the acetoacetate study, a positive relationship between the sensor and reference method results was found, the gradient was 0.09. The 95% confidence interval was 0.05-0.14 (P < or = 0.001), indicating that high concentrations of acetoacetate interfere with the sensor performance. CONCLUSIONS: Acidosis and hyperglycaemia have minimal effects on the sensor performance. However, high concentrations of acetoacetate result in some overestimation of betahydroxybutyrate. This bedside ketone sensor provides useful data over a broad range of conditions likely to be encountered during moderate to severe diabetic ketoacidosis.