Advances in Glucose Monitoring

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DEFINITIONSGlucose is frequently measured in the blood and urine of veterinary patients. Blood glucose monitors are used to quickly provide accurate measurements of blood glucose levels; they are commonly used in the hospital to monitor severely ill patients and at home for patients with diabetes mellitus. In the hospital, interpretation of how well blood glucose measurement reflects control of diabetes is notoriously difficult because of both the high level of stress experienced by animals in the hospital environment and the handling and restraint required for blood sampling.

Blood GlucoseRecent advances in blood glucose monitoring techniques have been designed to minimize stress and to allow owners to perform serial blood glucose monitoring at home. These less-invasive techniques should more accurately reflect blood glucose levels by decreasing the stress experienced by the animal.

Related Article: The Role of the Glucose Curve

Urine GlucoseUrine glucose is commonly measured as part of routine urinalysis in healthy pets, for screening patients for diabetes mellitus, and for monitoring glycemic control in patients being treated for diabetes mellitus. Urine glucose test strips are easy to use and interpret and require only a small amount of urine, so they can be used by owners at home. Urine dipsticks often combine glucose indicators with ketone indicators to detect glucosuria and ketonuria in diabetics.

PATHOPHYSIOLOGYAccurate measurement of blood glucose is important for monitoring diabetes control because treatment decisions, such as altering the type or amount of insulin administered, may be based on these measurements. The technique used to measure blood glucose must minimize stress on the animal because increased levels of catecholamines released during stress cause a rapid increase in blood glucose levels that can exceed 300 mg/dl. Advances in glucose monitoring include measurement of glucose levels in body fluids other than blood, as glucose in circulation is distributed quickly through most body compartments due to capillary permeability.

Glucose should be undetectable in the urine of normoglycemic patients. In these patients, all glucose filtered at the glomerulus is reabsorbed in the tubules; as a result, no glucose is excreted in the urine. Any elevation in glucose can cause glucosuria, including transient stress-related hyperglycemia. In hyperglycemic patients, the amount of glucose filtered in the glomerulus exceeds the amount that can be reabsorbed by the tubules, resulting in glucose spilling into the urine and positive results on urine glucose tests. Glucosuria can also occur with proximal tubular damage or defects, resulting in decreased reabsorptive capacity in the tubules, such as in Fanconi's syndrome, heavy metal toxicity, and aminoglycoside toxicity.

PAIN INDEXThe degree of pain associated with sample collection for blood glucose measurement varies with the type of sample required for the monitor used and the skill and experience of the person collecting the sample. Collection of venous samples requires restraint and venipuncture, whereas capillary blood collection and sample collection through an indwelling sampling catheter can often be done without restraint and is barely noticed by many patients (see technique description on page 9). Pain should be minimized because it contributes to stress hyperglycemia and patient aversion to restraint and handling. Minimally invasive and noninvasive sampling methods are current areas of focus for human diabetes research.

Diagnosis

BLOOD GLUCOSE MONITORSThe most common types of blood glucose monitors currently used in veterinary medicine include PBGMs, POC analyzers, color test strips, and automated chemistry analyzers.

Related Article: Blood Glucose Monitors

Portable Blood Glucose Monitors (PBGMs)Recent publications have compared the suitability of various PBGMs in veterinary medicine (see Table). In general, these monitors have the advantage of using small quantities of blood, have a low cost per test, and quickly yield results. They can work well with capillary samples. Many clients are able to use PBGMs at home.

Point-of-Care (POC) AnalyzersThe POC monitors are in-clinic analyzers that typically use cartridges and small quantities of blood to measure blood glucose as well as blood gases, blood pH, electrolytes, and coagulation and other biochemical variables. The iSTAT (HESKA Corporation, Fort Collins, CO) is a POC monitor currently used in many practices. These monitors are more expensive than PBGMs and are designed for use by health care professionals, but also require a small sample size and give quick, accurate results.

Color Test StripsColor test strips have a square on which blood is placed. A colorimetric reaction occurs, and the blood is rinsed from the test square. The color change is compared with a color chart, and the blood glucose level is estimated according to the closest color match. These tests are cheap and fast. However, they provide only a ballpark measurement of the blood glucose level-not a numerical readout-and are subject to interpretation.

Related Article: Diagnostic Considerations for Glucose Monitoring

Automated Chemistry AnalyzersAutomated chemistry analyzers are not available in many clinic settings; these analyzers are most commonly used by diagnostic laboratories. They require larger quantities of blood and are more expensive than PBGMs. Automated chemistry analyzers have the advantage of being able to perform other biochemical assays.

Blood glucose monitors in most veterinary settings typically use venous, capillary, or arterial blood for measurement. It is important to read the equipment insert to ensure that the type of sample and anticoagulant are appropriate for the equipment being used. The clinician should be familiar with the factors that can affect the monitor's accuracy.

Blood glucose readings can be artificially low in samples from polycythemic animals because of the decreased fluid portion of the blood. They can also be artificially low in whole blood samples not used immediately after collection due to continued glucose use by red blood cells.

Glycemic control over a long period (weeks) as opposed to immediate blood glucose determination is best assessed through use of laboratory tests, such as serum fructosamine and glycosylated hemoglobin measurement. Limitations of these tests include the inability to assess the response of blood glucose levels to insulin administration on an hour-to-hour basis and inability to determine glucose nadir.

URINE GLUCOSEUrine glucose is most often measured with dipsticks. Granules that change color in the presence of glucose are also available for placement in the litter for detection of glucosuria at home.

Related Article: Diagnose & Treat Feline Diabetes Mellitus

Follow-up

INPATIENT OR OUTPATIENTOwners can easily and successfully perform the capillary ear prick technique at home to evaluate blood glucose levels over a longer period than is practical in the clinic. Capillaries yield an acceptable blood sample for glucose determination by PBGMs.

Blood glucose levels have been shown to vary considerably on a daily basis. Single measurements or multiple measurements made on a single day in the hospital may not accurately depict the animal's glycemic control in its normal environment. Owners can assist in evaluation of their animal's glycemic control through measurement of blood glucose levels at home.

Urine glucose is easily measured at home through the use of urine dipsticks or glucose-detecting granules placed in the litter. Some clients collect urine through use of an empty litterbox, a plastic layer placed over the litter, or free catch. Urine dipsticks can also be placed in the litter, but timing of the test is important so the cat must be watched so the dipstick can be retrieved immediately after urination.

CLIENT EDUCATIONClients who are monitoring blood glucose levels at home for diabetic animals must be instructed never to adjust insulin doses based on their results. They should communicate frequently with their veterinarian for appropriate adjustments to be made.

Clients may need frequent communication and support when beginning home glucose monitoring.

Future ConsiderationsCurrent advances in human glucose monitoring that may have future applications in veterinary medicine include continuous glucose monitoring systems, minimally invasive sampling, and noninvasive monitoring of blood glucose.

Continuous monitoring systemsContinuous glucose monitoring systems involve subcutaneous placement of a sensor that is attached to a cord and a recording device. The system detects glucose levels in the venous blood or interstitial fluid and records hundreds of measurements taken minutes apart. This technique avoids multiple venipunctures and/or intravenous catheter placement for multiple blood collections. The system can be temporarily attached to the patient with a halter, harness, or bandage for monitoring and data collection in the patient's home environment, or the data can be transmitted with wireless technology. These systems must be calibrated to whole blood glucose measurements on an individual basis.

A recent study has shown that these devices are valid for use in cats, dogs, and horses and that they are well tolerated. They essentially perform a glucose curve with minimal stress on the animal and can be used to determine the effect of insulin therapy on blood glucose levels and glucose nadir. The devices can also be used for data collection in oral and intravenous glucose tolerance tests and in critically ill patients. Limitations include the animal's tolerance of placement of the system, current availability, cost, and range of glucose measurements.

Minimally invasive sampling techniqueReverse iontophoresis is a minimally invasive sampling technique that measures glucose levels in interstitial fluid by extracting small amounts of fluid transdermally without pain or tissue disruption. This has been studied to a limited extent in veterinary patients but will probably be the subject of future studies and discussions. This method is currently used for monitoring glucose in human diabetic patients.

Noninvasive technologyNear infra-red spectroscopy is the most-studied noninvasive glucose monitoring technology in humans. Glucose absorption peaks are measured through transmission or reflectance of light through tissues, such as the fingertip. Currently, precision has not been proven accurate enough for routine clinical use, although a system is currently marketed for veterinary use in the United States.

Other current monitoring techniques under development for humans include a contact lens with glucose monitoring capability.

AcknowledgmentThe author thanks Dr. Deborah Greco for the opportunity to write this article, her assistance in its preparation, and for providing the table on portable monitors.

ADVANCES IN GLUCOSE MONITORING • Susan A. Meeking

Suggested ReadingPortable glucose monitorsAssessment of five portable blood glucose meters, a point-of-care analyzer, and color test strips for measuring blood glucose concentration in dogs. Cohn L, McCaw D, Tate D, Johnson J. JAVMA 216:198-202, 2000.Evaluation of five portable glucose meters for use in dogs. Wess G, Reusch C. JAVMA 216:203-209, 2000.Portable blood glucose meters as a means of monitoring blood glucose concentrations in dogs and cats with diabetes mellitus. Stein J, Greco D. Clin Tech Small Anim Pract 17:70-72, 2002.

Continuous glucose monitorsContinuous glucose monitoring system for diabetic cats. Ristic J, Herrtage M, Slater L, et al. Vet Rec 152:28, 2003.Evaluation of a continuous glucose monitoring system for use in dogs, cats, and horses. Wiedmeyer CE, Johnson PJ, Cohn LA, et al. JAVMA 223:987-992, 2003.Evaluation of a continuous glucose monitoring system in cats with diabetes mellitus [Abstract]. Ristic J, Herrtage M, Walti S, et al. Proc ECVIM, 2003.Evaluation of a continuous glucose monitoring system in diabetic dogs. Davison L, Slater L, Herrtage M, et al. J Small Anim Prac_t 44:435-442, 2003.Use of continuous blood glucose monitoring for animals with diabetes mellitus. DeClue A, Cohn L, Kerl M, et al. JAAHA 40:171-173, 2004._www.glumetrics.com

Noninvasive glucose monitorsEvaluation of reverse iontophoresis as a method of non-invasive glucose monitoring in dogs and cats. Lurye J, Behrend E, Kemppainen R, et al. J Vet Intern Med 16:559, 2002.In vivo glucose sensing for diabetes management: Progress towards non-invasive monitoring. Pickup J, McCartney L, Rolinski O, et al. BMJ 319:1289, 1999.www.glucowatch.com

Ear-prick techniqueComparison of glucose concentration in blood samples obtained with a marginal ear vein nick technique versus a peripheral vein in healthy cats and cats with diabetes mellitus. Thompson MD, Taylor SM, Adams VJ, et al. JAVMA 221:389-392, 2002.Ear vein blood glucose monitoring. Thompson M. Textbook of Veterinary Internal Medicine, 6th ed-St. Louis: Elsevier Saunders, 2005, pp 308-310.Measurement of capillary blood glucose concentrations by pet owners: A new tool in the management of diabetes mellitus. Casella M, Wess G, Reusch CE. JAAHA 38:239-245, 2002.www.felinediabetes.com; this site includes a video of the ear-prick technique

OtherEvaluation of day-to-day variability of serial blood glucose concentration curves in diabetic dogs. Fleeman L, Rand J. JAVMA 222:317-321, 2003.Evaluation of long-term home monitoring of blood glucose concentrations in cats with diabetic mellitus: 26 cases (1999-2002). Kley S, Casella M, Reusch CE. JAVMA 225:261-266, 2004.Monitoring techniques for diabetes mellitus in the dog and cat. Bennett N. Clin Tech Small Anim Pract 17:65-69, 2002.Retrospective study of owners' perception of home monitoring of blood glucose in diabetic dogs and cats [Abstract]. Van de Maele I, Daminet S, Rogier N, et al. Proc ECVIM, 2003.