Richard W. Nelson, DVM, DACVIM
The basic objective of insulin therapy is to eliminate the clinical signs of diabetes mellitus while avoiding the common complications associated with the disease. The devastating chronic complications of human diabetes require several decades to develop and are uncommon in diabetic dogs and cats. As such, the need to establish near normal blood glucose concentrations is not necessary in diabetic dogs and cats. Most owners are happy and most dogs and cats are healthy and relatively asymptomatic if most blood glucose concentrations are kept between 100 and 250 mg/dl (5.6 and 14 mmol/l).
The most important initial parameters to assess when evaluating control of glycemia are the owner's subjective opinion of severity of clinical signs and overall health of their pet, findings on physical examination, and stability of body weight. If the owner is happy with results of treatment, the physical examination is supportive of good glycemic control, and the body weight is stable, the diabetic dog or cat is usually adequately controlled and a serial blood glucose curve performed in the hospital is not recommended. A serum fructosamine concentration can be performed to corroborate the status of glycemic control. Fructosamines result from an irreversible, non-enzymatic, insulin-independent binding of glucose to serum proteins and are used as a marker of the average blood glucose concentration during the previous 2 to 3 weeks. The higher the average blood glucose concentration during the preceding 2 to 3 weeks, the higher the serum fructosamine concentration, and vice versa.
In our laboratory, the normal reference range for serum fructosamine is 200 to 375 µmol/L; a range determined in healthy dogs and cats with normal blood glucose concentrations. Interpretation of serum fructosamine in a diabetic dog or cat must take into consideration the fact that hyperglycemia is common, even in well-controlled diabetics. Most owners are happy with their pet's response to insulin treatment if serum fructosamine concentrations can be kept between 350 and 450 µmol/L. Values greater than 500 µmol/L suggest inadequate control of the diabetic state and values greater than 600 µmol/L indicate serious lack of glycemic control. Serum fructosamine concentrations in the lower half of the normal reference range or below the normal reference range should raise concern for significant periods of hypoglycemia. Increased serum fructosamine concentrations (i.e., > 500 µmol/L) suggest poor control of glycemia and a need for insulin adjustments; however, increased serum fructosamine concentrations do not identify the underlying problem.
Poor control of glycemia should be suspected if the owner reports clinical signs of hyper- or hypoglycemia, the physical examination identifies problems consistent with poor control of glycemia (e.g., thin or emaciated, poor hair coat, peripheral neuropathy), the dog or cat is losing weight, or a serum fructosamine concentration is greater than 500 µmol/L. A serial blood glucose curve is indicated in the poorly-controlled diabetic dog or cat to gain insight into the actions of the insulin in that animal and guidance in making the adjustment in insulin therapy. Stress-induced hyperglycemia can result in misinterpretation of the blood glucose curve. If stress-induced hyperglycemia is suspected, a switch from reliance on serial blood glucose curves generated in the veterinary hospital to reliance on blood glucose results generated by the owner in the less-stressful home environment (e.g., the marginal ear vein prick technique) or evaluation of sequential serum fructosamine concentrations should be done, in addition to the history and physical examination findings.
When generating a serial blood glucose curve in the veterinary hospital, the insulin and feeding schedule used by the owner should be followed and blood should be obtained every 1 to 2 hours throughout the day for glucose determination. It is more important to maintain the pet's daily treatment routine than to risk inaccurate blood glucose results caused by inappetence in the hospital or insulin administration at an unusual time. Blood glucose concentrations are typically determined by either a point-of-care bench top glucose analyzer or hand-held portable blood glucose monitoring device. Blood glucose values determined by many portable blood glucose monitoring devices are typically lower than actual glucose values determined by bench-top methodologies. This may result in an incorrect diagnosis of hypoglycemia or the misperception that glycemic control is better than it actually is. Failure to consider this "error" could result in insulin underdosage and the potential for persistence of clinical signs despite "acceptable" blood glucose results.
By evaluating serial blood glucose measurements every 1 to 2 hours throughout the day, the clinician will be able to determine if the insulin is effective and to identify the glucose nadir, time of peak insulin effect, duration of insulin effect, and severity of fluctuation in blood glucose concentrations in that particular diabetic dog or cat; information which is critical when deciding how to change insulin therapy. Obtaining only 1 or 2 blood glucose concentrations has not been reliable for evaluating the effect of a given insulin dose. The ideal goal of insulin therapy in diabetic dogs and cats is to maintain the blood glucose concentration between 100 mg/dl and 250 mg/dl (5.6 and 14 mmol/l) throughout the day and night.
Hyperglycemia induced by stress, aggression or excitement is the single biggest problem affecting accuracy of the serial blood glucose curve, especially in cats. Stress can override the glucose-lowering effect of the insulin injection, causing high blood glucose concentrations despite the presence of adequate amounts of insulin in the circulation and leading to a spiraling path of insulin overdosage, hypoglycemia, Somogyi phenomenon, and poor control of glycemia. The biggest factors inducing stress hyperglycemia are hospitalization and multiple venipunctures. An alternative to hospital-generated blood glucose curves is to have the owner generate the blood glucose curve at home using the marginal ear vein or lip prick technique and a portable home blood glucose monitoring device that allows the owner to touch the drop of blood on the ear with the end of the glucose-test strip. There are several web sites on the internet (e.g., http://www.sugarcats.net/sites/harry/ ) that explain in detail the marginal ear vein prick technique in layman's terms and provide information on owner's experiences with the technique and with different portable home blood glucose monitors. At the time diabetes is diagnosed, we provide a web site to the client and ask them to visit the web site and see if they would be interested in monitoring blood glucose concentrations at home. We spend time teaching the technique to those individuals willing to give it a try, advise them on how often to perform a blood glucose curve (ideally no more frequently than one day every 2 to 4 weeks), and how often to measure the blood glucose concentration on the day of the curve (typically at the time of insulin administration and 3, 6, 9 and 12 hours later). We have had very good results using the marginal ear vein prick technique in cats. Stress has been significantly reduced and accuracy of the blood glucose measurements has improved immensely. A similar approach can be used in diabetic dogs, using either the ear or lip prick technique. However, we do not push home glucose monitoring in dogs as much as cats, primarily because stress-induced hyperglycemia is not as big of a problem in diabetic dogs.
Reliance on change in serum fructosamine concentration is necessary if stress-induced hyperglycemia persists despite measurement of glucose values at home. Serum fructosamine concentrations are not affected by acute transient increases in blood glucose concentration, as occurs with stress-induced hyperglycemia, and provide reliable information on the status of glycemic control in fractious or stressed diabetic cats and dogs. In fractious or stressed cats and dogs, the clinician must make an educated guess as to where the problem lies (e.g., wrong type of insulin, low insulin dose, etc), make an adjustment in therapy, and rely on changes in serum fructosamine to assess the benefit of the change in treatment. Because serum proteins have a relatively short half-life, serum fructosamine concentration changes relatively quickly (i.e., 2 to 3 weeks) in response to a change in glycemic control. This short period for change in serum fructosamine concentration is advantageous for detecting improvement or deterioration of glycemic control quickly in fractious, stressed or scared cats and dogs in which blood glucose concentrations are unreliable. As such, serum fructosamine concentrations can be measured prior to and 2 to 3 weeks after changing insulin therapy to assess the effectiveness of the change. If changes in insulin therapy are appropriate, a decrease in serum fructosamine concentration should occur. If the serum fructosamine concentration is the same or has increased, the change was ineffective in improving glycemic control, another change in therapy based on an educated guess should be done, and the serum fructosamine measured again 2 to 3 weeks later.
Occasional monitoring of urine for glycosuria and ketonuria is helpful in those diabetic dogs and cats that have problems with recurring ketosis or hypoglycemia to determine if ketonuria or persistent negative glycosuria is present, respectively. We do not have the owner adjust daily insulin dosages based on morning urine glucose measurements in diabetic dogs, except to decrease the insulin dose in dogs with recurring hypoglycemia and persistent negative glycosuria. In our experience, the vast majority of diabetic dogs develop complications as a result of owners being misled by morning urine glucose concentrations. On occasion we recommend evaluation (e.g., on the weekends) of multiple urine samples obtained throughout the day and early evening. The well-controlled diabetic pet should have urine that is either free or has trace amounts of glucose for most of each 24-hour period. Persistent glycosuria throughout the day and night suggests a problem that may require evaluation via in-hospital or at home blood glucose determinations.