Strategies for monitoring diabetes mellitus in dogs (Sponsored by Intervet/Schering-Plough Animal Health)

Monitoring the effectiveness of therapy is an important part of managing canine diabetes mellitus. The success of treatment for this disorder greatly depends on the complete cooperation of the pet owner, as the majority of day-to-day patient care is done at home. The pet owner must be trained to carefully observe and even interpret signs of possible illness. Monitoring must be frequent enough to be effective, but not so frequent as to discourage client compliance. It is also essential to foster a strong veterinarian-client relationship at the time of diagnosis and maintain that relationship throughout the pet's lifetime. The time and effort the veterinarian devotes to client education will improve the client's ability to accurately relate what is observed at home and to monitor the dog according to the veterinarian's instructions—both of which facilitate the veterinarian's ability to assess the long-term efficacy of treatment.

Variables in choosing a monitoring program

The goals of a monitoring program are improvement and maintenance of patient health through optimization of antidiabetic therapy and minimization of diabetic complications. Several published clinical reviews outline the various clinical and laboratory measures available to veterinarians for monitoring diabetic dogs.1,2 Unfortunately, few published studies are available to guide clinicians' recommendations as to the best monitoring strategy to achieve these goals.

An effective monitoring strategy should provide sufficient information and room for adjustments until the dog is free of clinical signs for the majority of each day. For example, a moderate monitoring program, the strategy veterinarians most commonly recommend, might have as its endpoint the suppression of clinical signs of diabetes. An intensive monitoring program, on the other hand, might gather the detailed physiologic and metabolic information needed to achieve specific endpoints associated with excellent diabetic control. Evidence from human medicine indicates that intensive diabetic monitoring is associated with improved long-term results in clinical variables and reduced rates of diabetic complications. Unfortunately, intensive diabetic monitoring is also associated with a higher frequency of severe hypoglycemic episodes in people.3 A relationship between the optimization of clinical endpoints via intensive monitoring and improved clinical results has not been shown in veterinary medicine. Given the increased morbidity and diminished quality of life that might result from chronic or recurrent hypoglycemia, veterinarians must carefully consider the pros and cons of intensive monitoring and management before routinely recommending such a strategy for canine diabetics. Table 1 summarizes a comparison of moderate and intensive monitoring approaches.

Table 1. Comparison of select features of moderate and intensive canine diabetes monitoring programs

Clinical and laboratory parameters

Clinical signs

Common signs of diabetes in dogs, particularly polyuria and polydipsia, are directly related to hyperglycemia and glucosuria, which in turn are direct consequences of absolute or relative insulin deficiency. One or more of the clinical signs of diabetes are usually listed among the major complaints at the time of diagnosis. Owners may be taught to observe these clinical signs at home to monitor the effectiveness of diabetic therapy. For dogs with long-term diabetes, owner observations of clinical signs and physical examination findings correlate well with objective criteria of glucose management, such as the serum fructosamine level and mean eight-hour blood glucose concentration.4

As part of the monitoring program, instruct the owner to observe the dog for specified clinical signs of diabetes and record the observations for later review. Water consumption, urination habits, appetite, activity level, and body weight are usually the easiest parameters for most dog owners to observe at home. Because glucosuria occurs once the threshold for renal resorption of glucose is exceeded, polyuria roughly corresponds to the degree of hyperglycemia. Likewise, polydipsia is related to the degree of hyperglycemia. Polydipsia results from activation of thirst mechanisms by plasma hypertonicity and mild volume reduction caused, respectively, by hyperglycemia and increased renal fluid loss. Polyphagia or the preservation of appetite is a common finding in dogs with uncomplicated diabetes. In untreated dogs, weight loss may occur despite adequate nutritional intake as a result of the catabolic state induced when circulating insulin is deficient. Thus, an increase in body weight or maintenance of body weight is expected during insulin therapy. Persistence of polyphagia and failure to gain or maintain body weight are indirect indicators of inadequate blood glucose regulation in an otherwise uncomplicated diabetic dog.

Urine monitoring

Some clinicians recommend at-home monitoring of glucose and ketone concentrations in urine as part of a diabetic monitoring program. Recommendations for the frequency of urine testing vary from weekly to multiple times daily.2,5 Although its effectiveness has not been firmly established by research studies, the rationale for urine testing is improvement of patient management by alerting owners to changes in diabetic status before clinical signs appear. Metabolic changes relevant to patient management that may be detected in urine before clinical signs appear include large fluctuations in glucosuria, sudden absence of glucosuria, or development of ketonuria. Potential drawbacks of urine testing as a monitoring tool include:5

• It may be difficult to obtain a sample for testing.

• Urine metabolite concentrations may not reflect serum levels at the time of testing.

• Test strip results are only semiquantitative.

• It may be difficult for owners to discern color differences on test strips.

Whether urine glucose measurements should be used to adjust the insulin dosage is a matter of legitimate debate. The practice of having owners adjust the daily insulin dose based on urine glucose measurements has fallen from favor in veterinary medicine. The veterinarian may find urine testing results helpful for formulating a change in insulin dose; however, as with any results, these should be viewed in the context of other findings.5

Glycated serum proteins

Fructosamine is formed by a nonenzymatic glycation reaction between glucose and serum proteins (especially albumin).6 Glycated proteins circulate for approximately the lifetime of the parent protein. Albumin, the principal glycated serum protein, has a lifetime in serum of about two weeks. The serum fructosamine level in dogs reflects the mean blood glucose level for the preceding two to three weeks.6 A dog with diabetes mellitus is likely to have an elevated serum fructosamine level if clinical signs have been present for longer than three to four days. The fructosamine concentration should decrease with successful therapy, and monitoring serum fructosamine levels is an effective way to evaluate glycemic control and response to insulin in diabetic dogs;6 however, the fructosamine level can be affected by concurrent conditions. Low serum fructosamine levels are found in as many as 70% of nondiabetic dogs with hypoproteinemia or hypoalbuminemia, as well as in dogs with hyperlipidemia and azotemia.7

Glycated hemoglobin, a complex of glucose and hemoglobin, is formed similarly to fructosamine. Because of the longer serum lifetime of hemoglobin, glycated hemoglobin reflects glycemic control over the previous five to nine weeks.1 Because of its widespread availability and ability to provide a more clinically relevant window into glycemic history, the serum fructosamine test is preferred over the glycated hemoglobin test in veterinary medicine.

Blood glucose monitoring

Blood glucose monitoring is the de facto gold standard for determining daily insulin requirements in clinical patients; however, it is a poor method in many cases. Information about insulin effectiveness, onset of action, time to peak effect, peak effect, and duration of action can be derived from a properly performed glucose curve, but the method is fraught with potential error. Several options for patient glucose monitoring are available to veterinarians. The traditional blood glucose curve involves frequent glucose sampling (as often as hourly) of a hospitalized patient. New technology designed for continuous glucose monitoring has been employed in recent years and may prove superior to intermittent sampling.8 Home glucose monitoring, in which owners obtain and analyze samples, is another option for obtaining blood glucose information.9,10 One study showed that about 85% of dog owners successfully performed long-term home glucose monitoring and reported little or no difficulty performing the procedure.11 Protocols for at-home glucose monitoring in dogs have been presented in detail elsewhere.10,12

At least three sources of variability can affect a glucose curve: human error, variability in technology, and biological variability. Human error can be minimized when trained personnel perform the technique, the technology is easy to use, and minimal interventions are required to complete the testing. Veterinary studies have shown that many commercial glucometers designed for use in people are accurate enough for clinical use in dogs and cats; however, some models have performed much better than others.13 Some companies make glucometers designed for use in dogs and cats (see Reliable glucometers). When glucometers from different manufacturers were compared in dogs, the results of a single blood glucose determination would have led to an inappropriate therapy change up to 20% of the time for the most accurate units highlighting the variability inherent in technology.13 Another study examined the variability of serial glucose curves in diabetic dogs.14 Paired glucose curves from the same dog (two 12-hour glucose curves obtained 24 hours apart) were examined to determine variability in important glucose curve parameters (e.g., minimum, maximum, and mean blood glucose concentrations, time from injection to nadir). The significant confounding effect of variability on clinical decision making was readily demonstrated by the finding that treatment recommendations made after examination of each single curve in the pair did not agree in 45% of dogs. In dogs where analysis of individual curves resulted in recommendations that did not agree, the recommendations were exactly opposite 65% of the time (e.g., one curve indicated an increase in insulin dose was needed and its paired curve indicated a dose decrease was needed).14 Variability in blood glucose curves is likely to be a factor regardless of the method used to generate them. In people, day-to-day insulin absorption and activity are highly variable (15% to 50%) even under carefully controlled experimental conditions.15 This is thought to represent true biologic variability. Presumably, similar biologic variability is present in dogs.

Reliable glucometers

General health

Complete diabetic monitoring involves careful attention to the patient's overall health. Diabetes is a risk factor for cataract formation, urinary tract infection, and neuropathy in dogs.16 Concurrent disorders are relatively common in diabetic dogs, including pancreatitis, renal failure, endocrinopathy (e.g., hyperadrenocorticism or hypothyroidism), or neoplasia.16,17 Veterinarians should perform periodic evaluation and appropriate testing for disorders that may complicate diabetes as part of their diabetic monitoring regimen.

Personal perspective

Current veterinary literature does not conclusively support any one or a combination of methods to monitor canine diabetics. In my opinion, the recommended program should yield as much objective information about the level of blood glucose regulation and diabetes control as possible, yet it must be flexible enough to accommodate the needs of individual patients and owners. Individual cases may require a lesser or greater level of routine monitoring to achieve clinical success.

My preferred monitoring approach relies primarily on the results of periodic examination and owner-provided observations and includes the results of at-home urine testing. Observations recorded by the owner include daily assessment of appetite, activity level, water consumption, urine frequency and volume, and weekly measurement of body weight, if possible. I provide test strips and ask owners to perform twice weekly urine testing for glucose and ketones. I don't permit any adjustment in the insulin dose based on urine test results. Owners are provided with specific instructions about when it is necessary to contact the veterinarian. These scenarios include changes in the dog's overall health, decrease in appetite or activity, increase in the degree of polydipsia or polyuria, increase in the amount of glucosuria, absence of glucosuria, and appearance of any degree of ketonuria. I recommend weekly recheck examinations immediately after the diagnosis but gradually extend them to every three months as the diabetes is controlled. I perform laboratory tests as needed at each recheck, especially if concurrent problems are also being managed. The serum fructosamine level may be helpful for documenting trends in diabetic control or when the owner cannot supply pertinent patient information. A glucose curve can be helpful, especially if hypoglycemia is suspected. However, recent studies documenting substantial variability in glucose curves performed in dogs means that any results should be carefully interpreted in the context of other clinical and laboratory findings.14 Currently, I perform a glucose curve when I cannot obtain the information needed using a more reliable method, such as the combination of periodic examination and owner-provided information. The use of continuous blood glucose monitoring may alleviate some of the current difficulties with glucose curve data.

Effective monitoring of diabetes after initiating treatment can mean the difference between success and failure of treatment. Involving owners in the pet's healthcare to this degree means you must also ensure the owner's responsibilities are manageable. The overarching goals of treatment are a high quality of life for the patient and owner and a reduction of morbidity associated with diabetic complications. With careful planning and implementation of a monitoring strategy, veterinarians can effectively manage the majority of diabetic dogs.

References

1. Miller E. Long-term monitoring of the diabetic dog and cat: Clinical signs, serial blood glucose determinations, urine glucose, and glycated blood proteins. Vet Clin North Am Small Anim Pract 1995;25:571-584.

2. Bennett N. Monitoring techniques for diabetes mellitus in the dog and cat. Clin Tech Small Anim Pract 2002;17:65-69.

3. Epidemiology of severe hypoglycemia in the diabetes control and complications trial. The DCCT Research Group. Am J Med 1991;90:450-459.

4. Briggs CE, Nelson RW, Feldman EC, et al. Reliability of history and physical examination findings for assessing control of glycemia in dogs with diabetes mellitus: 53 cases (1995-1998). J Am Vet Med Assoc 2000;217:48-53.

5. Schaer M. A justification for urine glucose monitoring in the diabetic dog and cat. J Am Anim Hosp Assoc 2001;37:311-312.

6. Reusch CE, Liehs MR, Hoyer M, et al. Fructosamine. A new parameter for diagnosis and metabolic control in diabetic dogs and cats. J Vet Intern Med 1993;7:177-182.

7. Reusch CE, Haberer B. Evaluation of fructosamine in dogs and cats with hypo- or hyperproteinemia, azotemia, hyperlipidemia, and hyperbilirubinemia. Vet Rec 2001;148:370-376.

8. Wiedmeyer CE, DeClue AE. Continuous glucose monitoring in dogs and cats. J Vet Intern Med 2008;22:2-8.

9. Casella M, Wess G, Reusch CE. Measurement of capillary blood glucose concentrations by pet owners: a new tool in the management of diabetes mellitus. J Am Anim Hosp Assoc 2002;38:239-245.

10. Schermerhorn T. Has at-home glucose monitoring for management of diabetic dogs and cats come of age? Adv Small Anim Med Surg 2005;18:1-3.

11. Casella M, Wess G, Hässig M, et al. Home monitoring of blood glucose concentration by owners of diabetic dogs. J Sm Anim Pract 2003;44:298-305.

12. Mathes MA. Home monitoring of the diabetic pet. Clin Tech Small Anim Pract 2002;17:86-95.

13. Cohn LA, McCaw DL, Tate DJ, et al. Assessment of five portable blood glucose meters, a point-of-care analyzer, and color test strips for measuring blood glucose concentration in dogs. J Am Vet Med Assoc 2000;216:198-202.

14. Fleeman LM, Rand JS. Evaluation of day-to-day variability of serial blood glucose concentration curves in diabetic dogs. J Am Vet Med Assoc 2003;222:317-321.

15. Heinemann L. Insulin pharmacology. In: Pickup JC, Williams G, eds. Textbook of diabetes. 3rd ed. Malden, Mass: Blackwell Science Ltd., 2003;42.1-42.15.

16. Nelson RW. Diabetes mellitus. In: Ettinger SJ, Feldman EC, eds. Textbook of veterinary internal medicine. 6th ed. Philadelphia, Pa: Elsevier/Saunders Publishing Co., 2005;1563-1591.

17. Hess RS, Saunders HM, Van Winkle TJ, et al. Concurrent disorders in dogs with diabetes mellitus: 221 cases (1993-1998). J Am Vet Med Assoc 2000;217:1166-1173.