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PubMedDate not supplied

Development and evaluation of a wearable blood glucose monitor.

Complex operation, prolonged set-up time, reliability problems, high cost, and excessive size limits the use of currently available extracorporeal continuous blood glucose analyzers. A self-calibrating, wearable blood glucose monitor has been developed to overcome these impediments. The wearable blood glucose monitor is a 410 g forearm-mounted instrument with three miniature pumps for blood sampling, calibration, and insulin infusion, and a flow cell containing an enzyme-electrode sensor capable of determining plasma glucose levels accurately and precisely in undiluted whole blood. The unit is connected to a computer controller with graphics display. Venous blood is drawn from a 21 gauge single lumen cannula through the sensor flow cell. A rate determination of glucose is completed in 20 sec and the blood is returned to the arm vein. Heparinized saline wash solution follows. No blood loss or significant systemic heparinization occurs. Cycle time is set from 2 to 5 min. The method is linear to at least 300 mg/dl glucose, independent of hematocrit, and free of interferences from blood constituents at normal venous pO2 with a coefficient of variation of 1-3% between calibrations. The sensor has a service life of at least 3 weeks. This wearable blood glucose monitor, with its high performance sensor, reduced size, and ease of operation, shows promise for evaluating and treating diabetes.

Animals↗

PubMed2006

Anesthetic management of a parturient with carnitine palmitoyltransferase II deficiency.

PURPOSE: To report the anesthetic management of a patient with carnitine palmitoyltransferase II deficiency who presented for labour and delivery. CLINICAL FEATURES: A 30-yr-old primiparous woman with known carnitine palmitoyltransferase II deficiency and a past history of exercise induced muscle pain, weakness and myoglobinuria presented in active labour. Management consisted of an early epidural for labour and continuous dextrose infusion with frequent blood sugar monitoring. She had an uneventful spontaneous vaginal delivery. She experienced a single asymptomatic episode of hypoglycemia on the first postpartum day. Her serum creatine kinase was six times normal at 24 hr post-delivery and remained elevated for three days without evidence of rhabdomyolysis. The remainder of her postpartum course was uneventful. CONCLUSION: Labour and delivery is a potential precipitant of rhabdomyolysis in patients with carnitine palmitoyltransferase II deficiency. The normal postpartum creatine kinase elevation (two to four times baseline at 24 hr) must be taken into account when monitoring these patients. On the basis of the physiologic principles, institution of early epidural analgesia to blunt the stress response to labour and delivery, continuous dextrose infusion and frequent glucose monitoring during labour and postpartum are the mainstays of management.

Adult↗

PubMed1995

Kinetics of glucose delivery to subcutaneous tissue in rats measured with 0.3-mm amperometric microsensors.

The time between intravenous injection of a glucose bolus and the time the glucose concentration peaked in the subcutaneous tissue was measured in pentobarbital-anesthetized rats with implanted 290-microns-diameter amperometric sensors. Boluses of 100, 200, and 400 mg/kg body wt were injected. The glucose concentration in the jugular vein was monitored by frequent withdrawal and analysis of samples. The glucose concentration in the subcutaneous tissue was continuously monitored with the sensors. The times required for the subcutaneously implanted sensor to reach its maximum current, corrected for sensor response times, were 7.5 +/- 3.9, 9.8 +/- 5.5, and 10.0 +/- 4.4 min for the smallest to the largest dose, respectively. The shorter delay in response to the smallest dose was statistically significant (P < 0.03). The results were consistent with dilution of the bolus in the cardiovascular system and transport of glucose by both diffusion and facilitated transport via a saturable mediator. An understanding of the differences in the dynamics of venous vs. subcutaneous response to a glucose dose is important in developing algorithms for the control of blood glucose based on a subcutaneous measurement.

Animals↗

PubMedDate not supplied

Interpretation of glycosuria in the teenage diabetic patient.

More than 700 insulin-dependent diabetic patients of both sexes and all ages have attended an education and stabilization course. Twelve adult females and four adult males were subsequently issued the means to monitor their blood glucose in their homes. Two of the adult females were pregnant, while the other 14 patients had one or more of the following: renal failure, an abnormal renal threshold, diabetic retinopathy, or continued and unexplained instability. A number of children were also issued Ames reflectometers. Eleven out of 13 male patients between the ages of 12 and 18 yr had no special difficulties except for a poor correlation between minor degrees of glycosuria and blood glucose estimations. One youth had a renal threshold of 17 mmol/L, while a recently diagnosed youth had a varying renal threshold. Eleven out of 17 teenage female diabetic patients had no correlation between urinary and blood glucose estimations with an apparant varying renal threshold being common. Four of these patients had a reflectometer on loan for 6--8 wk, but in three there was continued instability. Two others, who had continued use of home monitoring of blood glucose, had normoglycemia upon review. One of these patients had what appeared to be a varying renal threshold while unstable but a normal threshold with diabetic stability. Regardless of the cause of the disparity between blood and uninary glucose estimations, it appears that the unstable teenage female diabetic patient cannot rely upon urinalysis as a guide to insulin dosage.

Adolescent↗

PubMed2000

Postprandial silent ischaemia following a fatty meal in patients with recently diagnosed coronary artery disease.

Silent myocardial ischaemia (SI) is recognised as an important prognostic factor in patients with coronary artery disease (CAD). Postprandial angina is related to severity of CAD. The effect of postprandial metabolic changes in the pathogenesis of SI is unclear. We studied the postprandial changes in glucose, insulin and triglyceride, and non-esterified fatty acids (NEFA) in relation to postprandial SI and exercise capacity, in patients with CAD. Forty elderly volunteers (63 +/- 1 years) mean age +/- s.e.m., with a history of angina were selected on the basis of a Rose questionnaire and a positive exercise stress test (modified Bruce protocol). The test meal contained 45% fat. The meal was consumed at 9.00 am and hourly blood samples were taken for glucose, insulin, triglyceride and NEFA. Continuous Holter monitoring for SI was conducted using a Spacelabs 2000 monitor. Twenty-five percent of the subjects had episodes of silent ischaemia. Postprandial glucose, insulin, triglyceride, and NEFA were not significantly different in the patients with SI (group 1, n = 10) compared with those without SI (group 2, n = 30). The mean exercise time was 6.1 +/- 0.8 min in group 1 compared with 6.8 +/- 0.5 minutes in group 2 (P = 0.48). The time to onset of ST depression during exercise test was also not significantly different in the two groups. The occurrence of postprandial SI cannot be related to changes in plasma levels of glucose, triglyceride, insulin, and NEFA. The explanation is not apparent from this study but may relate to a haemodynamic changes such as mesenteric steal. Journal of Human Hypertension (2000) 14, 391-394

Aged↗

PubMed1983

The honeybee syndrome: teratogenic effects of mannose during organogenesis in rat embryo culture.

The relevance of our present findings should not rest on the possible role of mannose as an important teratogen in man. Excessive exposure to mannose during pregnancy via dietary intake seems unlikely since mannose is absorbed poorly from the gastrointestinal tract and intestinal hydrolysis of mannosidic linkages may be minimal. Moreover, although some plasma mannose may be generated continuously from endogenous sources via the cleavage of mannose-6-phosphate by hepatic glucose-6-phosphatase or mannosidic linkages by other hydrolases, our ongoing surveys have not uncovered any specimens of plasma or amniotic fluid containing mannose in amounts which could compete effectively with prevailing levels of glucose. Although we are continuing to monitor clinical samples for unusual mannose levels, we believe that the major significance of our experiences with this hexose pertains to its applications as a physiological tool for evaluating the metabolic determinants of early organogenesis. Within the above context, our findings must be viewed in relation to the known features of energy metabolism in the embryo during the interval that we have studied (Fig. 9). The classic studies of Shepherd and colleagues, similar findings by others, and more recent experiments in our own laboratory have indicated that glycolysis constitutes the chief energy source for the post-implantation embryo prior to the establishment of the yolk sac circulation on day 10 1/2. Almost all of the assimilated glucose goes to lactic acid, mitochondrial electron transfer is poorly developed, and oxidative metabolism via the Krebs' cycle is minimal. Meaningful Krebs' cycle activity does not become operative until day 10 1/2 and full expression is not found until the establishment of the allantoic circulation on day 11 (Fig. 9). The present experiences with mannose provide the first documentation of how precariously development is balanced during that transitory 9 1/2-10 1/2 day phase of organogenesis when glycolysis predominates. We have shown that even minor perturbations of glycolytic flux during that interval can result in major dysmorphogenic sequelae. Thus, the proposition by Kalter and Warkany that "any meaningful attempt to reduce infant mortality further will have to address the still unresolved causes of congenital malformations" prompts our speculation that major congenital lesions may result from relatively minor disturbances in glycolysis occurring prior to oxidative maturation in the embryo unit. Such effects on glycolysis during this vulnerable phase of embryogenesis could provide a common basis for the teratogenic actions of many unrelated and as yet unidentified agents.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Drug-Induced↗

PubMed2006

On-chip microdialysis system with flow-through sensing components.

Microdialysis probes have been used for diabetes treatment as continuous monitoring system coupled to a glucose sensor. An on-chip microdialysis system with in-line sensing electrodes is demonstrated. As a first step towards greater biosensor integration with this miniaturized microdialysis system, a stacked system with in-line sensing electrodes was developed. Impedance electrodes sputtered within the microchannels were used to determine fluid electrical resistance from a dialyzed phosphate buffered saline (PBS) solution, which characterizes solution conductivity as a function of PBS concentration. The permeability of the membrane to the salt ions was obtained as 0.246+/-0.028 microm/s (15 nm pores). Subsequently, experiments measuring PBS dialysis in the time-domain at 64.4% recovery were conducted. The PBS concentration of the reservoir was changed in both a step response and sinusoidally with an 800 s period. The subsequently measured impedance indicates that the system is able to continuously track concentration changes in the reservoir with a 210 s system response delay. Most of this delay is due to the dead volume within the tubing between the syringe pumps and the microsystem. In addition, the predicted response was modeled using linear systems theory and matches the experimental measurements (r=0.98). This system is expected to have the proper sensitivity to track physiologically relevant concentration changes of biomolecules such as glucose (which has a physiological maximum change rate of approximately 4 mg/dl min with a periodicity of 1h or greater) with minimal lag time and amplitude reduction.

Electrochemistry↗

PubMed1998

Evaluation of cell recycling in continuous fermentation of enzymatic hydrolysates of spruce with Saccharomyces cerevisiae and on-line monitoring of glucose and ethanol.

The maximum growth rate of Saccharomyces cerevisiae ATCC 96581, adapted to fermentation of spent sulphite liquor (SSL), was 7 times higher in SSL of hardwood than the maximum growth rate of bakers' yeast. ATCC 96581 was studied in the continuous fermentation of spruce hydrolysate without and with cell recycling. Ethanol productivity by ATCC 96581 in continuous fermentation of an enzymatic hydrolysate of spruce was increased 4.6 times by employing cell recycling. On-line analysis of CO2, glucose and ethanol (using a microdialysis probe) was used to investigate the effect of fermentation pH on cell growth and ethanol production, and to set the dilution rate. Cell growth in the spruce hydrolysates was strongly influenced by fermentation pH. The fermentation was operated in continuous mode for 210 h and a theoretical ethanol yield on fermentable sugars was obtained.

Acetic Acid↗

PubMed2004

Nutrient-specific effects in the coordination of cell growth with cell division in continuous cultures of Saccharomyces cerevisiae.

Cell cycle progression of Saccharomyces cerevisiae cells was monitored in continuous cultures limited for glucose or nitrogen. The G1 cell cycle phase, before initiation of DNA replication, did not exclusively expand when growth rate decreased. Especially during nitrogen limitation, non-G1 phases expanded almost as much as G1. In addition, cell size remained constant as a function of growth rate. These results contrast with current views that growth requirements are met before initiation of DNA replication, and suggest that distinct nutrient limitations differentially impinge on cell cycle progression.

Cell Cycle↗

PubMed1980

Intravenous infusions of nutrients and sleep in the rat: an ischymetric sleep regulation hypothesis.

Unrestrained food-deprived rats received their daily caloric needs through continuous or discontinuous intravenous infusions of specific nutritive substances over a period of 3 consecutive days each, and the effect on sleep monitored by electroencephalogram was examined. Continuous glucose or lipid infusions did not affect the daily sleep quotas. Amino-acid infusion brought about a significant increase in paradoxical sleep (PS), whereas slow-wave sleep (SWS) remained unchanged. Rats that received the highly nutritive composite solution showed significant increase in both SWS and PS. The same increase in SWS and PS was observed when exogenous insulin was coinfused with continuous infusion of glucose or when glucose infusions were discontinuous. These findings suggest that sleep might be related to both the nature and the degree of utilization of the circulating metabolites. A model for the action on sleep of nutrients at the systemic level was proposed; only when substances are metabolized is there a direct effect on sleep mechanisms.

Amino Acids↗

PubMed2002

Performance evaluation of the Precision PCx point-of-care blood glucose analyzer using discriminant ratio methodology.

Point-of-care glucose testing needs to be integrated into a laboratory information system to provide continuous care. Selecting a particular glucose monitoring system is based on both analytical performance and on user's preference. We evaluated accuracy, performance and regulatory compliance of the Precision PCx glucose analyzer (Abbott), with automatic download into a central station, for remote quality control (QC) management and automatic upgrading. We used the discriminant ratio (DR) methodology, which determines the DR of a test (e.g. the ratio between the underlying SD and the within-subject SD), and compares it to that of another test allegedly measuring the same parameter. Accuracy was evaluated by Clarke's error grid method. Seven hundred and ninety four blood samples were taken from 22 diabetic patients, combined with two capillary blood samples: one for analysis by reference method and the second for PCx analysis. Linear regression analysis revealed, over a 2.1 to 26.9 mmol/l glucose concentration range, a correlation coefficient of 0.963, an intercept of 0.7 mmol/l and a slope of 0.851. Mean difference between meter-generated results and the reference method was -7.1+/-10.8%. Between-run imprecision for PCx using Abbott's controls at low and mid-low concentrations was 5.4 and 3.8%, respectively. Clarke's error grid did not show any clinical impact related to difference between methods. DRs were of similar magnitude using both methods. Nursing staff found PCx easy for everyday use. Our data show that PCx results agree with those obtained with the reference method, as shown by lack of significant difference in DRs, and by excellent correlation.

Blood Glucose↗

PubMed2003

Technological advances in the treatment of diabetes mellitus: better bioengineering begets benefits in glucose measurement, the artificial pancreas, and insulin delivery.

The management of type 1 diabetes is being advanced by innovations in glucose measurement, development of an artificial pancreas, and in alternate routes of insulin delivery. Emerging technologies will allow insulin to be delivered more effectively. In the future, patients with type 1 diabetes will receive insulin in optimal quantities (because of more information about blood glucose values) at optimal times (because of better integration of blood glucose values with appropriate insulin dosages) by way of optimal routes into the body (because of needle-free routes of administration) in order to achieve optimal blood glucose control. Emerging technologies for improved care of patients with type 1 diabetes include: 1. new methods for monitoring glucose, including noninvasive, minimally invasive, continuous, and alternate site measurement technologies; 2. new methods for integrating glucose values and insulin dosages, known as the artificial pancreas; and 3. new routes of insulin administration, including inhaled, oral, buccal, nasal, and transdermal drug delivery systems. These new technologies will facilitate proper treatment of type 1 diabetes and improve the lives of affected patients.

Biomedical Engineering↗

PubMed1982

[Use of the endocrine artificial pancreas (GCIIS; Biostator) in heart surgery].

It is well known that deep hypothermia used in open-heart surgery is usually associated with a marked reduction in carbohydrate tolerance, especially dangerous in the diabetic patient, since it might result in severe metabolic complications, namely ketosis and hyperosmolar coma. In order to prevent the occurrence of such complications we treated an insulin-dependent diabetic patient undergoing cardiovascular surgery, with a feed-back insulin infusion operated by an artificial pancreas (GCIIS, Biostator). The Biostator was then used to perform a continuous (minute by minute) blood glucose monitoring in 2 more patients, a type II (non insulin-dependent) diabetic and a non diabetic. Blood samples were drawn sequentially in order to determine plasma free insulin concentration. The glycemic profile observed in the insulin-dependent diabetic under artificial pancreas treatment was similar to that in the non-diabetic. Plasma free insulin levels dropped near to zero during by-pass cooling, returning toward basal level during the rewarming phase. Such results are then discussed by the Authors and given a pathogenetic interpretation.

Blood Glucose↗

PubMed1999

New developments in the treatment of type 1 diabetes mellitus.

Treatment of type 1 diabetes mellitus has made tremendous advances within the last decades. With concern to insulin delivery there are two promising new approaches. One is the intrapulmonary insulin delivery which has become feasible by the development of new inhalation devices which provide a sufficient degree of intrapulmonary drug retention. Also oral insulin delivery seems feasible when surface active substances are used to cross the mucosal membrane in the gut. Clinical research has also focussed on coatings for the insulin molecules to solve the problem raised by the proteolytic activity of the digestive system. A very new agent produced by a fungus called Pseudomassaria has been demonstrated to reverse the clinical signs of diabetes mellitus in mice. The compound diffuses through the cell membrane, binds to the inner part of the insulin receptor and activates the insulin typical biological effects. Nowadays a variety of insulin analogs are designed and tested for their clinical use. By shifting the isoelectric point towards to a slightly acidic pH, HOE 901 precipitates at physiologic pH resulting in a constant and peakless insulin delivery. NN 304 is a 14-carbon aliphatic fatty acid acylated analog that binds to serum albumin resulting in a flatter time-action profile than NPH insulin. Also rapid acting insulin analogs are or will be launched in the near future aiming to ensure an improved postprandial glucose regulation. Glucagon-like peptide-1 (GLP-1) improves metabolic control by a variety of effects, e.g. the enhancement of insulin secretion and inhibition of glucagon secretion. Moreover, GLP-1 reduces food and water intake controlled by the brain, and inhibits gastric emptying. A disadvantage of GLP-1 is its very short half-life. Novel derivatives with the beneficial effects of GLP-1 but a better resistance against degradation have been designed. In addition substances have been developed inhibiting GLP-1 degradation or augmenting GLP-1 release from its abundant endogenous pool. Finally, there is a variety of interesting approaches aiming to improve or ease blood glucose self-monitoring. One is the development of subcutaneous catheters for continuous blood glucose control. In another system reverse iontophoresis is used for sampling interstitial fluid which reflects capillary blood glucose levels. Instead of using an electric current, a brandnew system creates micropores in the skin by a laser ablation system. Through these micropores a specific device performs a mild suction to obtain intersitial fluid. Further systems which measure blood glucose by near infrared spectroscopy are still investigated in order to improve their technical function and to reduce their weight. This article intends to give an overview over the new developments in the treatment and management of type-1-diabetes mellitus.

Animals↗

PubMed2005

Biosensors for real-time in vivo measurements.

The current status of sensors capable of continuous measurement of analytes in biological media is reviewed. This review containing 173 references deals with devices whose use in single cells, tissue slices, animal models and humans has been demonstrated. In addition to sensors specific for glucose, lactate, glutamate, pyruvate, choline and acetylcholine, insights obtained from monitoring nitric oxide, Na(+), K(+), Ca(2+), and dopamine are presented. Performance criteria for sensor performance are described as is the subject of biosensor calibration. Biocompatibility issues are dealt with in some detail as is the status of continuous blood glucose monitoring in humans.

Biosensing Techniques↗

PubMedDate not supplied

Heat flux measurements for the fast monitoring of dynamic responses to glucose additions by yeasts that were subjected to different feeding regimes in continuous culture.

Heat measurements have been successfully as an analytical tool for the study of the dynamics of energy metabolism of Saccharomyces cerevisiae and Candida utilis grown in continuous culture under fluctuating substrate supply. A low average dilution rate (D = 0.05 h-1) was maintained either by adding the medium as continuously (dropwise) as possible or (blockwise) by adding the medium at high speed during a short period (D = 0.5 h-1 for 40 s) and not at all during the following period (D = 0.00 h-1 for 360 s). The resulting biological activity was monitored on-line with conventional (O2 and CO2) off-gas analyses, DOT measurements, and heat flux measurements. In C. utilis cultures, the biomass-specific maximum oxygen consumption rate (qO2,max), the biomass yield (Ys,x), and the dynamic responses to a glucose pulse and to a change in feeding regime were not significantly affected by different preceding feeding regimes. In contrast, S. cerevisiae grown in continuous culture with blockwise feed showed a 50% increase in qO2,max and a 25% drop in Ys,x compared to the culture grown with dropwise feed. The dynamic response to a glucose pulse (0.6 g L-1) was slower for the continuous (dropwise) than for the blockwise grown S. cerevisiae. With a second testing method for the dynamic response of the yeasts, the feeding regime was changed. The blockwise fed S. cerevisiae proved to be better "trained" to cope with sudden changes in glucose supply and, therefore, was more "shockproof" toward a change in feeding regime. This clearly points to major differences in the intracellular metabolic flux control between the yeasts. These findings are of relevance for industrial baker's yeast production, where reactor mixing times of one to several minutes are not uncommon. The observed, heat production, together with the dissolved oxygen concentration, appeared to give the fastest response to actual changes in the culture. It is suggested that heat measurements can be a very useful tool to monitor and control the growth of S. cerevisiae in laboratory and industrial fermenter operations.

Biomass↗

PubMed1998

Splanchnic retention of intraduodenal and intrajejunal glucose in healthy adults.

Estimates of the spanchnic retention and appearance in the systemic circulation of orally administered glucose vary among laboratories even after recently identified sources of error have been accounted for [Livesey, G., P. D. G. Wilson, J. R. Dainty, J. C. Brown, R. M. Faulks, M. A. Roe, T. A. Newman, J. Eagles, F. A. Mellon, and R. Greenwood. Am. J. Physiol. 275 (Endocrinol. Metab. 38): E717-E728, 1998]. We questioned whether, in healthy humans, D-glucose delivered intraluminally to the midjejunum appeared systemically as extensively as that delivered intraduodenally. Subjects were infused over a period of 90 min with 50 g of glucose in 1 liter of isotonic saline (incorporating 0.5 g D-[13C6]glucose) per 70 kg of body weight. Infusions were via enteral tubes terminating approximately 15 and 100 cm postpylorus. The systemic appearance of glucose was monitored by means of a primed-continuous intravenous infusion of D-[6,6-2H2]glucose. Whereas 98 +/- 2% (n = 7) of the duodenally infused glucose appeared in the systemic circulation, only 35 +/- 9% (n = 7) of midjejunally infused glucose did so, implying that 65 +/- 9% was retained in the splanchnic bed. Either glucose was less efficiently absorbed at the midintestinal site or hepatic glucose sequestration was increased 10-fold, or both. The proximal intestine plays a key role in the delivery of glucose to the systemic circulation, and the distal intestine potentially delivers more glucose to the liver.

Adult↗

PubMed1992

The effect of maternal intravenous glucose administration on fetal activity.

OBJECTIVE: The study was designed to objectively evaluate the effect of maternal intravenous glucose infusion on fetal activity. STUDY DESIGN: Twenty-one volunteers at 30.7 +/- 3.0 weeks' gestation were objectively evaluated for fetal activity with a Doppler monitor before and during an intravenous glucose test. Baseline fetal activity monitoring began 10 minutes before a fasting blood glucose level was obtained. A standard 1-hour intravenous glucose tolerance test was then performed, and fetal activity monitoring was continued for the duration of the test. Twenty-one women at 29.8 +/- 3.0 weeks' gestation volunteered to serve as controls and were continuously monitored for fetal activity. The control patients did not receive intravenous glucose. RESULTS: Linear regression analysis revealed an increase in fetal activity in both groups; however, the increase in the glucose infusion group was significantly greater than in the control group. CONCLUSIONS: Maternal glucose infusion causes short-term stimulation of fetal activity; however, some other factor in the monitoring process also stimulates fetal activity.

Blood Glucose↗