Glucose requires monitoring in the canine/feline veterinary patient
Discover the significance of glucose and the diseases, conditions and symptoms related to hypoglycemia plus methods for monitoring glucose levels in dog and cat patients.
Role of glucose
Glucose serves a vital role in cellular metabolism in almost all tissues of the body. Although it is not the only fuel source, it is the most efficient and most common. Glucose production occurs primarily in the liver and, to a lesser extent, in the renal cortex. Storage is achieved by combining multiple molecules into a polysaccharide to limit the osmotic effect in the form of glycogen. When demand increases, glycogen is enzymatically broken down into glucose molecules again in a process called glycogenolysis. Glycogen can be found throughout the body in the cytoplasm of cells, but stockpiles also are held in muscles for local usage. The largest glucose reservoir is in the liver for rapid utilization by the entire body.
Regulation of glucose
The regulation of glucose levels to achieve homeostasis occurs through multiple hormonal mechanisms. The pancreas plays a primary role in the production of the associated hormones, including insulin and glucagon. Insulin is produced in the β-cells of the pancreas and facilitates the translocation of glucose into the body’s cells, thereby lowering plasma glucose levels and providing the fuel for cellular metabolism. When plasma concentrations of glucose rise above the upper end of the normal range (>130 mg/dL), insulin release is increased, which regulates the level back into the normal range. At the other end of the spectrum is glucagon, which is produced in the α cells of the pancreas and released in response to hypoglycemia glucose levels < 60 mg/dL). These primary means of regulation are influenced by multiple other hormonal factors in the body, including cortisol, epinephrine, growth hormone, thyroxine, and endorphins. Therefore, many different disease processes and conditions can influence glucose homeostasis and affect plasma glucose levels.
Diseases and symptoms related to hypoglycemia
Generally, hypoglycemia is related to decreased production of glucose or increased utilization/removal from the blood. The liver, as the primary production plant for much of the body’s glucose, is a common link in many diseases. End-stage liver failure, acute hepatitis, portosystemic liver shunts (rarely), and various toxins can adversely affect glucose production or inhibit glycogenolysis, resulting in systemic hypoglycemia. In addition, glycogen-storage diseases, hypoadrenocorticism, and growth hormone deficiency may manifest as hypoglycemia. Increased utilization and removal of glucose from the blood may occur in other diseases such as insulinoma, or insulin-like substance secreting tumors (i.e. IGF-1 and IGF-2 in malignant canine mammary carcinoma or some renal tumors), may drive glucose into cells at an increased rate, having similar effects to insulin overdosing in patients with diabetes.
Toxins such as xylitol and oleander, systemic Bartonellosis or Babesiosis, sepsis, and renal disease all can cause hypoglycemia. Patients with mild hypoglycemia may be asymptomatic, but symptoms of acute hypoglycemia are generally neurologic. These may include ataxia, seizures, disorientation, blindness, cardiac arrhythmias, lethargy, vomiting, and shock/death if untreated or sufficiently severe.
Diseases, conditions, and symptoms related to hyperglycemia
Hyperglycemia in veterinary medicine is most associated with diabetes mellitus. However, several other diseases and physiological conditions also elevate blood glucose levels to above normal parameters. Stress hyperglycemia commonly occurs in cats but may also be observed in dogs. Postprandial glucose levels also may show a temporary increase. Growth hormone-secreting tumors (pituitary in felines, and mammary and pituitary in canines), pheochromocytoma, hyperadrenocorticism, and hyperthyroidism can cause hyperglycemia. Each of these conditions can induce hyperglycemia through the unregulated/increased production of the hormones associated with the related organs and increase glucose production.
Pancreatic disease, such as acute or chronic pancreatitis or neoplasia, can elevate blood glucose levels. Various drugs used in veterinary medicine may affect glucose production, including steroids, progestogens, β-blockers, and α-2 agonists. Furthermore, ethylene glycol toxicityand head trauma can lead to hyperglycemia.
Symptoms of hyperglycemia may be nonexistent in acute or mild cases. Glycosuria occurs when hyperglycemia exceeds the renal threshold, followed by renal tubular osmotic diuresis, and subsequent polyuria and compensatory polydipsia.This threshold varies but is approximately 180 to 200 mg/dL in canines and 200 to 280 mg/dL in felines.
Monitoring of glucose levels in canine/feline veterinary patients
Patient-side glucose monitoring in the clinic or hospital is commonly performed because of the critical need of glucose for survival, its diagnostic value, and relatively low cost. Handheld glucometers use a small drop of blood and an algorithm for species-specific adjustment related to the red blood cells and distribution of glucose to determine blood glucose levels. One of the most common is the AlphaTRAK 2 glucose monitor with canine- and feline-specific settings, but other glucometers can also be used. The iSTAT analyzer has excellent accuracy and is commonly used in emergency and general practice settings. One caveat with handheld glucometers is that hemoconcentrated patients may register artificially low glucose levels because of a higher red blood cell concentration on the algorithm associated with the actual measurement of glucose levels.
Serum analyzers in the clinic or the test results of separate samples sent elsewhere for analysis can be used to confirm diagnosis and are less susceptible to artifacts. Chemical reaction sticks, used to screen for the presence of glucose in the urine, may confirm more persistent hyperglycemia and are commonly used in veterinary hospitals. Furthermore, in-house or outsourced testing of fructosamine can give further insight into the last 2 to 3 weeks of glucose regulation. Glucose can irreversibly react with plasma proteins to produce fructosamine. Assuming normal protein levels, abnormal glucose levels can also lead to altered fructosamine levels. However, this can be influenced by thyroid conditions, hyperlipidemia, hypoproteinemia, and hemolysis, and it should not be used as a sole source of diabetes/insulin therapy management.
Sampling in the clinic is generally achieved through venipuncture. In pediatric, dehydrated, or debilitated patients, pricks of the paw pad, gums, lips, or ear margin also can be used to collect blood samples. Owing to the frequency of sampling needed in conditions such as sepsis and diabetic ketoacidosis, central lines/jugular catheters or intracatheters are preferred for patient comfort. Plotting glucose curves is a common method to determine the efficacy of insulin regulation in patients with diabetes. However, glucose curves also have the potential to give skewed results associated with stress hyperglycemia and may not reflect the typical blood glucose levels seen in a patient at home.
Various tools are available to the owners of pets with a need for long-term glucose monitoring at home. Traditionally, urine reagent strips were used to check for any glycosuria. Such strips could indicate whether blood glucose levels exceed the renal threshold and can also detect ketosis, but they give little information about the duration or severity of levels outside of the normal range. In addition, hypoglycemia is not addressed if insulin dosing is high, and reagent strips are generally no longer in common use, particularly with the increased availability of modern and superior monitoring techniques. Glucometers with lancets or needle pricks of the ear veins, paw pads, or buccal mucosa can be used, however, some patients will not tolerate regular use.
Continuous glucose monitoring systems are becoming more common. They have been used routinely in humans and their application in pets generally allow a 1- to 2-week period of real-time monitoring of glucose levels in the intracellular fluid of subcutaneous tissues without the need for repeated needle pricks. Most dogs and cats tolerate these systems, but their accuracy at lower blood glucose levels (< 100 mg/dL) is reduced. Thus, their use in the clinic or at home is generally reserved for more stable patients. Application site reactions to the adhesive may occur but are uncommon, and the glucometer’s software/app stores data from sampling to give a more accurate glucose curve without the stress of restraint, venipuncture, or a veterinary visit.
Many diseases can affect glucose regulation in pets, and there are several ways to monitor glucose levels that can facilitate correction or therapy changes. It is likely that glucose monitoring will continue to play a key role in patient wellness and care as less-invasive, more accurate tools and techniques are developed.
Dr Kelley is the emergency service head for the emergency medicine associates of BluePearl Pet Hospital in Clearwater, Florida. He is a 2003 graduate of Kansas State University College of Veterinary Medicine. With more than 15 years of experience in emergency medicine, he helps oversee one of the busiest BluePearl Emergency Services in the United States.