Canine Diabetes
Diabetes mellitus is a common endocrinopathy in middle-aged and older dogs and is a complex disorder of carbohydrate, protein and lipid metabolism1. This disorder, which is the result of a relative or absolute insulin deficiency and / or of peripheral cell insensitivity to insulin, is characterised by high blood glucose concentrations such that the renal threshold is exceeded. As a result, glucose is excreted in the urine.
The osmotic action of glucose leads to polyuria and, through loss of fluid, to polydipsia. In addition, metabolism is impaired so that the general condition of the animal deteriorates. If left unmanaged, diabetes mellitus can be fatal.
The role of insulin
Insulin is synthesised and released from beta cells in the pancreatic islets. Insulin assists with cellular uptake of glucose from the bloodstream, thus exerting a hypoglycaemic effect. Within cells, insulin promotes anabolism (such as synthesis of glycogen, fatty acids and proteins) and counters catabolic events (reduces gluconeogenesis and inhibits fat and glycogen breakdown).
Whereas insulin lowers blood glucose, there are opposing hormones (glucagon, cortisol, progesterone, adrenaline, thyroid hormone and growth hormone) that act to increase blood glucose. It is important to consider these counter-regulatory hormones, because changes in their blood concentrations will interfere with the action of insulin.
Changes in these hormones can occur in natural physiological conditions, in disease states, or as a consequence of drug administration.
In the absence of sufficient insulin, dogs with diabetes will switch from glucose to fat metabolism for cellular energy. While this is initially beneficial, fat metabolism in unrecognised or untreated diabetics typically progresses to ketoacidosis and ultimately can be fatal.
Diabetes mellitus is not related to diabetes insipidus, an uncommon condition that occurs when the kidneys are unable to regulate fluids in the body. Diabetes insipidus is characterised by a deficiency or inadequate response to a hormone called vasopressin.
Disease prevalence and risk factors
Estimates of the prevalence of diabetes mellitus in dogs is up to 1 in 300 1,2.
Certain breeds appear to be at greater risk for developing canine diabetes1:
- Cocker Spaniels
- Dachshunds
- Doberman Pinschers
- German Shepherds
- Golden Retrievers
- Labrador Retrievers
- Keeshond
- Pomeranians
- Terriers
- Toy Poodles
- Miniature Schnauzers
- Samoyeds
Diabetes typically occurs when dogs are between 4 to 14 years old. Entire female dogs are at least twice as likely as male dogs to suffer from diabetes1,3.
Obesity may play a factor in breeds already predisposed to diabetes, so it is worth discussing weight management with owners of these breeds before clinical signs develop4.
Management and prognosis
The prognosis for diabetes mellitus depends mainly on the cause, early diagnosis and adequate therapy. In general, the prognosis is very good, provided that diagnosis is made at an early stage and therapy is administered properly.
Most forms of diabetes can be successfully managed with insulin, the cornerstone of successful management, but dietary adjustments and a regular lifestyle are also important.
Open communication between the pet owner and their veterinary practice is also extremely important. Veterinary encouragement will largely influence the dog owner’s motivation and compliance with therapy. Clients need to fully understand the disease to help achieve and maintain good diabetic stability and be highly motivated and committed to the management of their dog.
The clinical staff should also understand the basics of diabetes and its management.
Veterinary nurses form a vital part of the health care team and have a very important role in providing detailed client education, instruction and encouragement. They can also play a key role in the monitoring process.
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Classification
Several classification systems have been used to describe diabetes mellitus. A human classification system revised in 1997 divides the disease into three types: Type 1 (previously insulin-dependent or juvenile-onset diabetes mellitus), Type 2 (previously non–insulin-dependent or adult-onset diabetes mellitus) and other specific types of diabetes mellitus (previously secondary or Type 3 diabetes mellitus).
The most commonly recognised form in dogs shares many characteristics with the human Type 1 (insulin-dependent diabetes mellitus)5. Dogs with the insulin-dependent form of the disease require daily insulin injections to control the clinical signs and delay the associated disorders related to the diabetic disease process.
Untreated dogs commonly display severe weight loss, polydipsia and polyuria. They may experience dehydration and severe metabolic and electrolyte abnormalities if severe ketoacidosis develops. Untreated or improperly managed dogs with diabetes suffer a decreased quality of life and most die without appropriate therapy and monitoring.
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Aetiology
Primary causes of diabetes mellitus
By the time diabetes mellitus is clinically recognised in dogs, virtually all will present with type 1 or insulin-dependent disease. This is characterised by beta cell destruction (often a result of autoimmune destruction of the islets of Langerhans) and hypoinsulinaemia. Insulin secretagogues (substances which promote the secretion of insulin), such as glucose or glucagon, fail to stimulate endogenous insulin production and there is an absolute requirement for exogenous insulin injections to control blood glucose levels.
Secondary causes diabetes mellitus
Diabetes mellitus can be secondary to severe inflammation or neoplasia of exocrine pancreatic tissue, which lead to loss of islet function. In these cases, diabetes is also complicated by exocrine pancreatic insufficiency. Diabetes can also occur when there is either overproduction of counteracting hormones or insulin resistance. Excessive growth hormone production can be seen in entire, cycling bitches.
Progesterone produced during the luteal phase of the oestrous cycle induces the production of growth hormone by the mammary gland, which counteracts the action of insulin.
Dogs with hyperadrenocorticism (Cushing’s syndrome) produce excessive amounts of glucocorticosteroids that stimulate gluconeogenesis and lead to an increase in the plasma glucose concentration. This stimulates insulin synthesis, which eventually results in exhaustion of the islets of Langerhans. A small number of cases, up to 14%, of canine Cushing’s syndrome cases are complicated by diabetes mellitus6.
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Glucose Toxicity & Hypoglycaemia
Glucose toxicity
Glucose toxicity occurs when insulin secretion is reduced by prolonged hyperglycaemia. Prolonged hyperglycaemia can occur as a result of several causes. The prolonged and high-dose therapeutic use of glucocorticosteroids can induce diabetes mellitus. The use of exogenous progestogens can lead to growth hormone excess. Progestogens also have an affinity for glucocorticosteroid receptors.
In obese dogs, tissue receptors have decreased insulin sensitivity. This leads to a greater demand for insulin, which can result in exhaustion of the islets of Langerhans.
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Hypoglycaemia
If the insulin dose is too high, clinical signs of hypoglycaemia may be observed. Hypoglycaemia may also be triggered by events causing a relative insulin overdose:
- Loss of appetite
- Vomiting
- Excessive exercise
The clinical signs of hypoglycaemia, in increasing order of severity, are:
- Hunger
- Restlessness and anxiety
- Muscle twitching and shivering
- Ataxia
- Disorientation
- Convulsions and coma
It is worth noting that some animals may just become very quiet and inappetent and the signs of hypoglycaemia may be missed.
Emergency treatment of hypoglycaemia
- Immediate oral administration of glucose solution or honey (1 g per kg body weight). Animals that are collapsed should not have large volumes of fluid forced into their mouths as this may result in aspiration pneumonia. Here it is preferable to rub a small amount of the glucose solution or honey onto the animal’s gums or under its tongue.
- Intravenous dextrose solution (50%) can be administered in severe cases or if oral therapy has been ineffective. Dose for hypoglycaemia 1–5 ml 50% dextrose by slow intravenous injection (over 10 minutes)7 — not aimed to correct blood glucose concentration but to reverse clinical signs.
Owners of pets with diabetes should always have a source of glucose readily available. Following the successful emergency administration of oral glucose, small amounts of food should be offered at intervals of 1–2 hours until the effects of the insulin overdose have been counteracted.
If the insulin dose is too high it should be reduced e.g. by at least 10%. It may be necessary to construct a glucose curve to enable appropriate adjustment of the insulin.
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Pathogenesis
Pathogenesis of canine diabetes mellitus
The insulin deficiency that occurs with diabetes impairs the uptake of glucose by cells, resulting in a great paradox: simultaneous extracellular hyperglycaemia (elevated blood glucose) and intracellular glucose deficiency.
To compensate for the glucose deficiency, gluconeogenesis occurs. This process stimulates the use of amino acids for glucose production, so there is a decrease in protein synthesis, subsequent weight loss and an increased risk of infections as a result of antibody loss.
The excess glucose produced accumulates in the blood, causing hyperglycaemia. Small glucose molecules are freely filtered through the glomerulus in the kidney. In normal dogs, the renal tubules will reabsorb the filtered glucose. However, if the blood glucose rises above the renal threshold of approximately 10-12 mmol/l in dogs, these tubular reabsorption mechanisms are overwhelmed, and glucose appears in the urine.
Glucose exerts an osmotic diuretic effect that leads to polyuria. To compensate, the dog experiences excessive thirst and polydipsia. Furthermore, the concentration of glucose in the bloodstream exerts an osmotic pressure and pulls fluid out of cells, resulting in cell dehydration. Without medical intervention, hyperglycaemic coma and death can occur.
Untreated or unrecognised diabetes mellitus may progress to diabetic ketoacidosis. In the absence of sufficient insulin, dogs with diabetes will switch from glucose to fat metabolism for cellular energy. While fats are initially beneficial energy sources, lipid waste products (ketone bodies) accumulate in the blood and invoke severe and potentially life-threatening metabolic abnormalities.
Dogs with ketoacidotic diabetes can present with severe clinical signs (severe depression, anorexia, vomiting, dyspnea, collapse, or coma). Clients may not have recognised or reported that the classic clinical signs of diabetes were present. Without aggressive and determined management, ketoacidotic dogs may die.
Caninsulin® 40 IU/ml Suspension for Injection contains porcine insulin.POM-V
Further information is available from the SPC, datasheet or package leaflet.
Advice should be sought from the medicine prescriber.
Prescription decisions are for the person issuing the prescription alone.
Use Medicines Responsibly.
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References
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Fall T, Hamlin H.H, Hedhammar A, Kämpe O, Egenvall A. Diabetes mellitus in a population of 180,000 insured dogs: incidence, survival, and breed distribution. J. Vet. Intern. Med. 2007;21:1209
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Mattin, M. et al. (2014). An epidemiological study of diabetes mellitus in dogs attending first opinion practice in the UK. Vet. Record 174: 349
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Guptill L., Glickman L., Glickman N., Time trends and risk factors for diabetes mellitus in dogs: Analysis of veterinary medical data base records (1970-1999). Vet J 2003; 165:240-247
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Behrend, E., Holford, A., Lathan, P., Rucinsky, R. & Schulman, R. (2018). 2018 AAHA Diabetes Management Guidelines for Dogs and Cat. www. JAAHA.org
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Mattin, M. et al. (2014). An epidemiological study of diabetes mellitus in dogs attending first opinion practice in the UK. Vet. Record 174: 349
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Miceli DD, Pignataro OP, Castillo VA. Concurrent hyperadrenocorticism and diabetes mellitus in dogs. Res Vet Sci. 2017 Dec;115:425-431.
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Petersen M. Insights into Veterinary Endocrinology. https://endocrinevet.blogspot.com/2013/05/emergency-management-of-insulinoma-and.html