Use of Continuous Blood Glucose Monitoring for Animals With Diabetes Mellitus

Introduction

Therapeutic monitoring of blood glucose concentration in diabetic animals can be a frustrating experience for veterinarians. The two primary goals of insulin therapy when treating diabetics are resolution of clinical signs and avoidance of insulin-induced hypoglycemia. Clinical signs such as polyuria, polydipsia, polyphagia, weight loss, weakness, and attitude changes should alert the clinician to a potential problem with glycemic control. Ideally, blood glucose concentrations are maintained between 100 to 250 mg/dL and 100 to 300 mg/dL in diabetic dogs and cats, respectively. With the described goals in mind, diabetic monitoring usually focuses on history, physical examination, and ideally, testing that allows identification of not only glycemic control, but also the glucose nadir. In addition, monitoring should be relatively inexpensive, minimally labor intensive, and induce little or no stress for the animals.

Currently, a 12- to 24-hour glucose concentration curve is considered the gold standard of diabetic monitoring. Glucose concentration curves allow the veterinarian to evaluate peak and nadir blood glucose concentrations, as well as the duration of action and efficacy of the insulin used. Typically, these glucose curves are conducted in a hospital setting by obtaining blood samples every 2 to 3 hours. The time and labor commitment, combined with the stress of hospitalization, restraint, and multiple needle punctures or jugular catheter placement make this method less than ideal. Additionally, stress-induced hyperglycemia may result in inaccurate results, and peak and trough glucose concentrations may be missed depending on their relationship to the timing of the blood sampling.

With the recognition of the possible pitfalls of in-hospital glucose measurements, at-home blood glucose concentration monitoring has become popular. This latter method circumvents the stress-induced inaccuracies of in-clinic testing, but it requires the pet owner to master certain technical skills. Few owners are willing or able to obtain blood samples every few hours. Both in-hospital and at-home blood glucose concentration curves also fail to give a complete blood glucose concentration profile, since the samples are taken intermittently.

Methods of analyzing concentrations of substances other than blood glucose have been used as surrogates for monitoring glycemic control. Urine glucose concentrations may also be monitored at home, often in conjunction with monitoring for urine ketones. This form of monitoring may alert a clinician to a potential problem when negative or very elevated glucose concentrations are detected consistently or when ketones are noted, but further investigation is warranted prior to treatment alteration. Measurement of the glycated products of serum proteins (fructosamine) or hemoglobin (glycosylated hemoglobin) provides an estimate of average glycemic control over weeks to months, respectively. While these measurements have the advantage of requiring only a single blood sample, they only indicate general trends in glycemic control and cannot detect the blood glucose nadir. Clinicopathological tests always should be evaluated and interpreted in light of the clinical signs.

Continuous Glucose Monitoring System

Continuous glucose monitoring is a new option for periodic assessment of insulin therapy. A continuous glucose monitoring system (CGMS) has received approval by the Federal Drug Administration for use in human diabetic patients [Figure 1]. The system uses a novel sensor and calibration method for measuring glucose concentrations in the interstitial space within the subcutaneous tissue. The system consists of a recording device and a flexible electrode sensor. The sensor detects an electric signal produced by a reaction between interstitial glucose and glucose oxidase.¹ The interstitial glucose concentration is recorded in mg/dL every 10 seconds. The data is then downloaded onto a personal computer and displayed as a graph of the average interstitial glucose concentration every 5 minutes [Figures 2A, 2B]. Glucose concentrations within the range of 40 to 400 mg/dL are detected by the instrument.²

Interstitial fluid glucose concentration mimics that of blood glucose concentration in people, dogs, and rats.^1–3 The time delay between changes in the blood and interstitial fluid compartment glucose concentrations is <10 minutes.³ Two studies have evaluated the Medtronic Minimed CGMS for use in animals (dog, cat, and horse) with excellent results.¹² In one study, the correlations between interstitial fluid and blood glucose concentrations were 0.997 and 0.0974 in dogs and cats, respectively, while the second study found a correlation of 0.81 in dogs.¹² Optimal accuracy for this device is achieved when the correlation is >0.79.¹

Placement and Calibration

After the sensor is placed in the animal, interstitial glucose concentrations can be monitored for up to 72 continuous hours. The small, flexible sensor is inserted into the subcutaneous tissues using a stylet or spring-loaded device. The external portion of the sensor is attached to the skin with cyanoacrylate adhesive or tape. Since the insertion needle is small (approximately 24 gauge), sensor insertion is minimally invasive and well tolerated [Figure 3]. Once the sensor is placed, it is attached to the 170-g recording device, and the whole apparatus is attached to the animal with either a harness or bandage [Figure 4]. After a 1-hour initialization period, three blood glucose determinations are required to calibrate the instrument. These three determinations can be conducted at any time during the monitoring period. For clients that have been trained to perform at-home blood glucose monitoring, the calibration may be done outside of the hospital using a standard glucometer.

Clinical Application

The CGMS enables veterinarians to interpret a glucose curve with values provided every 5 minutes, providing a more accurate depiction of blood glucose fluctuations. Although most useful for diabetic monitoring, the CGMS may be utilized with oral or intravenous glucose tolerance tests for the diagnosis of intestinal absorptive diseases or diabetes mellitus, respectively.² Because the procedure is quick and painless and most of the monitoring time is spent in the animal’s own home, use of the CGMS helps circumvent inaccuracies associated with the stress of hospitalization, repeated venipunctures, dietary changes, and variations in insulin administration by hospital staff. Multiple studies have demonstrated marked day-to-day variations in glucose curves obtained by standard methods, despite similar administration of insulin and feeding schedules.⁴ Because the sensor can be left in the animal for up to 3 days, a more accurate representation of glucose control may be obtained as compared to a single 12- or 24-hour monitoring period.

Despite the many advantages of the CGMS, there are shortcomings with the device. Because of the limited working glucose range, interstitial glucose concentrations >400 mg/dL are inappropriately recorded as 400 mg/dL [Figure 2A]. As a result, use of the CGMS is not recommended for diabetics with obvious evidence of poor glycemic control. Because the unit does not provide real-time glucose concentrations, marked hypoglycemia goes undetected until the monitor is removed from the animal and downloaded, preventing immediate recognition of the hypoglycemic event. Recording of glucose concentrations can be interrupted by detachment of the sensor from the skin or from the recorder unit. Occasionally, although no obvious detachment is observed, the sensor fails to read glucose concentrations. Such an event remains undetected until the monitoring unit is downloaded onto a computer. Finally, the initial cost of the equipment may limit its use to facilities that manage a large number of diabetic animals [see Table].

Conclusion

Current diabetic monitoring tools all have advantages and disadvantages. Most clinicians assess multiple tests and clinical history in making treatment decisions. As veterinarians strive for decreased morbidity in diabetic animals, more precise methods of glucose monitoring are necessary. Continuous glucose monitoring has improved diabetic monitoring and, concomitantly, patient management in human medicine.⁵ While more research is necessary, continuous glucose monitoring may also help bridge the gap between current monitoring modalities and the therapeutic goals in animal diabetics.