Endocrine diseases make up a significant percentage of the chronic diseases that veterinarians diagnose and manage (Plummer et al, 2007). Diabetes mellitus is a complex endocrinopathy, with a pathogenesis that varies between individuals, and is associated with protracted hyperglycaemia due to loss or dysfunction of insulin secretion by pancreatic beta cells, diminished insulin sensitivity in tissues, or both. In the dog, beta-cell loss tends to be rapid and progressive, and is usually due to immune-mediated destruction, vacuolar degeneration or pancreatitis (Davison et al, 2003), while in the cat, loss or dysfunction of beta cells is the result of insulin resistance, islet amyloidosis or chronic lymphoplasmacytic pancreatitis (Goossens et al, 1998). This article provides an overview of diabetes mellitus in dogs and cats and discuss the complications that can arise in the management of this disease.
Aetiology and pathogenesis
Diabetes mellitus impairs the body's ability to produce or respond to the hormone insulin, resulting in abnormal metabolism of carbohydrates and elevated levels of glucose in the blood and urine (Niaz et al, 2018). The aetiology and pathogenesis of the disease remains poorly understood (Shields et al, 2015). However, irrespective of the underlying aetiology, diabetes mellitus is reported to occur as a result of the interplay between environmental and genetic factors (Mattin et al, 2014) and researchers continue to redefine and reclassify the different aetiologies responsible for the development of diabetes mellitus in dogs and cats (Gilor et al, 2016).
In veterinary medicine, human nomenclature of diabetic types cannot be applied as accurately to dogs and cats; however, both type 1 and type 2 diabetes do seem to occur (Randels, 2012).
Type 1 results from the destruction of beta cells, which is often immune-mediated but may be idiopathic. There is generally a progressive and complete loss of insulin secretion. These patients may have a sudden onset of signs and usually require insulin treatment from the outset
Type 2 can result from a combination of insulin resistance, dysfunctioning beta cells (producing less insulin) and increased hepatic gluconeogenesis. Insulin secretion may be high, low or normal, but will be insufficient to overcome the insulin resistance in the patient. They may either be insulin- (treated with insulin injections) or non-insulin- (treated with therapies other than insulin injections) dependent. Most cats with diabetes mellitus have features of type 1 and type 2 diabetes. As a result, insulin production is reduced, and insulin resistance makes the cat's insulin less effective than normal. If the causes of insulin resistance can be determined and reversed, many cats will go into diabetic remission (Schmeltzer, 2012). Prevalence in cats appears to be approximately 1 in 100 to 1 in 500 cats (Feldman and Nelson, 2004). Diabetes mellitus is most common in male neutered cats of any age, but most are generally older than 6 years old.
Diabetes mellitus has been reported to affect approximately one in 300 dogs (Mattin et al, 2014). Dogs with diabetes mellitus are generally between 4 and 14 years old with a peak incidence in those 7–9 years old (Wingfield and Raffe, 2002). The average age of dogs that develop diabetes mellitus is approximately 7 years (Davison et al, 2005). Female dogs are affected twice as often as males [AQ6: any evidence why?]. Intact female dogs may be transiently or permanently diabetic due to the insulin-resistant effects of the dioestrus phase (Goossens et al, 1998). In dogs, breeds such as the Samoyed and Tibetan terrier are over-represented in diabetic cohorts (Catchpole et al, 2013) suggesting an underlying genetic predisposition. However, it is not clear whether the pathogenesis of the disease varies between or within breeds (Gilor et al, 2016).
Secondary diabetes is where the patient develops carbohydrate intolerance secondary to concurrent insulin resistant disease, such as pregnancy, hyperadrenocorticism or acromegaly. This can result in permanent diabetes, and insulin dependent diabetes mellitus (IDDM) typically develops – IDDM is most similar to type 1 diabetes in humans. Almost all dogs and 50–70% of cats are IDDM (Randels, 2012). Approximately 30–50% of cats are non-insulin dependent diabetes mellitus (NIDDM) (most similar to type 2 diabetes in humans), which is very uncommon in dogs, and obesity, genetics, islet amyloidosis and abnormal insulin response are possible causes (Randels, 2012). Cats with NIDDM often progress to IDDM if not quickly treated due to the effects of glucose toxicity and subsequent pancreatic islet exhaustion, apoptosis and fibrosis (Randels, 2012).
Clinical signs and management
The main clinical feature of diabetes mellitus is thought to be the failure of beta-cells to produce sufficient insulin for the metabolic pathway of the body organisms. The onset of diabetes mellitus depends on different factors (Ganguly, 2014):
At this time, there is not a standard definition for subclinical diabetes mellitus in veterinary medicine or any validated testing to determine which patients are at risk for developing diabetes mellitus (Behrend et al, 2018).
Regardless of the underlying aetiology, classic clinical signs of polyuria, polydipsia, polyphagia and weight loss result from protracted hyperglycaemia and glucosuria. Increased fat mobilisation leads to hepatic lipidosis, hepatomegaly, hypercholesterolemia, hypertriglyceridemia and increased catabolism (Behrend et al, 2018).
Clinical signs are present once blood glucose concentrations exceed 14–16 mmol/dl (250–290 mg/dl) in both cats and dogs. In cats, stress can also increase blood glucose levels; however, it normally returns to normal after a couple of hours. Fructosamine levels are becoming increasingly used as standard in evaluating glucose levels (Randals 2010).
As a result of the marked stress hyperglycaemia response in cats, fructosamine levels are becoming standard in evaluating control of glucose levels (Randels, 2012). Fructosamine concentrations are directly related to blood glucose levels, but are not affected by acute situations, such as stress, as glucose is. In cats, normal serum fructosamine will vary somewhat by laboratory but are generally 225–360 μmol/l. Values >500 μmol/l suggest inadequate control of diabetes mellitus. Low fructosamine levels indicate probable periods of hypoglycaemia, even if clinical signs are not present. Checking fructosamine levels in the fractious, excitable or stressed patient is advantageous over glucose curves due to the hyperglycaemic response to these stresses (Randels, 2012).
Management of diabetes mellitus is often complicated. Success requires understanding of current scientific evidence and sound clinical judgment. As different aetiologies become better understood, treatment can be more specifically tailored to the individual patient. Treatment that is more specific to the underlying aetiology will presumably lead to better control of clinical signs of diabetes mellitus and possibly increase remission rates (Behrend et al, 2018). Studies have shown that cats with diabetes have remission rates that have been reported to be variable (15–100%) Remission rates are believed to be around 30–40%, with the highest chance of this within the first 6 months of treatment. After 6 months, the chance of remission rapidly reduces and this may not be achieved despite treating the cause of insulin resistance.
Because remission can occur, cat owners may be advised that remission is a possibility when treated with a combination of diet and insulin (Caney, 2013; Bloom and Rand, 2014).
To best treat patients and maintain their quality of life, it is necessary to examine the whole patient and consider all potential clinical manifestations (Plummer et al, 2007). Each patient requires an individualised treatment plan, frequent reassessment and modification of that plan based on the patient's response (Behrend et al, 2018). The long-term goal is to control the clinical signs, which is achieved by managing the blood glucose level so that it remains within the normal range, or as close to normal as possible. This is accomplished with insulin, diet and careful glucose monitoring (Schmeltzer, 2012). Veterinary nurses can play a key role in educating owners with diabetic dogs and cats and supporting them and, where possible, specific diabetes veterinary nursing clinics can provide significant support to owners (Ackerman et al, 2018).
Complications
Management of patients with diabetes mellitus is vital to minimise complications that are associated with the disease, and this includes dietary measures, exercise, control of concurrent disease, oral hypoglycaemic drugs and/or insulin treatment. The goals of treatment are to eliminate signs and the life-threatening effects of hyperglycaemia (Randels, 2012). If left untreated or inadequately controlled, ketonemia, ketonuria and ketoacidosis develop and result in progressive compromise of the patient's health (Behrend et al, 2018).
Iatrogenic hypoglycaemia
Iatrogenic hypoglycaemia is one of the most common side effects of insulin therapy and is clinically defined as a blood glucose level <60 mg/dl. Clinical signs will vary as they are dependent on the rate and magnitude of the decrease of blood glucose levels, but can include lethargy, nervousness, anxiety, weakness, ataxia, seizures, coma and death (Randels, 2012). The severity of the signs is dependent on the severity of hypoglycaemia and the rate of decrease of blood glucose. Table 1 shows the factors that can contribute to hypoglycaemia.
| Insulin related |
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| Other |
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Diabetic ketoacidosis
Diabetic ketoacidosis is a common endocrine emergency affecting dogs and cats, which can be fatal. Concurrent diseases, such as chronic pancreatitis, pneumonia, hyperadrenocorticism, urinary tract infection or congestive heart failure, may predispose the patient to developing diabetic ketoacidosis (Randels, 2012). The preliminary signs of patients presenting with diabetic ketoacidosis are polydipsia, polyuria, polyphagia and weight loss, which have usually gone unnoticed by the owner. Patients may live for up to 6 months with no serious adverse effects; however, once diabetic ketoacidosis starts, the patient will become severely ill within 1–7 days. The nursing management and care of these patients can be both challenging and time consuming and the veterinary nurse can play an invaluable role in the successful outcome of these cases.
Transient diabetes
Approximately 20% of cats with diabetes will have transient diabetes (Feldman and Nelson, 2004). These cats will often be subclinical until a stressful event occurs, which can include systemic inflammation, systemic disease, or administration of an insulin-antagonistic drug. Psychological stress may also act as a precursor to the onset of clinical signs. The hyperglycaemic response mimics type 1 diabetes (Randels, 2012). It should be noted that this is rare in cats and dogs and there is limited literature to support evidence of this. It is not always detected in every episode of hypoglycaemia.
Somogyi phenomenon
Somogyi phenomenon, a rebound high blood glucose level in response to low blood glucose, can occur when hypoglycaemia is not detected, resulting in the rebound release of cortisol and growth hormone, which will result in insulin resistance. Typically, patients will have episodes of hypoglycaemia, followed by rebound hyperglycaemia, and close monitoring of serial blood glucose curves is key to diagnosis (Randels, 2012).
Hyperosmolar coma
Hyperosmolar coma is an uncommon condition which can occur in patients with gastrointestinal abnormalities along with neurologic issues, such as weakness that may be progressive, anorexia, vomiting and lethargy. Clinical signs include profound dehydration, hypothermia, lethargy, extreme depression, and possibly coma (Randels, 2012).
Bacterial cystitis and pancreatitis
In cats, bacterial cystitis and pancreatitis are known causes of insulin resistance. A urine culture may be requested because many cats with diabetes mellitus have a bacterial urinary tract infection (Schmeltzer, 2012). A blood test for pancreatitis (feline pancreatic lipase immunoreactivity (fPLI)) may also be ordered, as it has been found that 50% of newly diagnosed feline diabetics have this disease (Schmeltzer, 2012).
Cataract formation
Cataract formation is the most common ocular complication and the most consistent ocular manifestation of diabetes in dogs, occurring in 75% of dogs within the first 12 months of the disease (Beam et al, 1999). Almost all dogs with diabetes develop cataracts at some point during the course of the disease, so it is crucial to recognise this and appropriately educate clients. Cataracts also occur in diabetic cats but much less frequently than in dogs, and the reason for this difference is probably related to the pathogenesis of cataract formation (Plummer et al, 2007). The rate at which cataracts mature in diabetic patients is variable and has previously been linked to the degree of glycaemic control. Some cataracts may develop slowly over months, while others may progress rapidly, resulting in complete blindness in 1–2 weeks. Lens capsule rupture in the equatorial region has even been reported in diabetic dogs (Plummer et al, 2007). The only treatment for the cataracts is surgical removal.
When cataracts form, there is associated uveitis. Lens proteins that leak into the eye from within the lens capsule elicit an inflammatory reaction, which may manifest with various degrees of low intraocular pressure, miosis, aqueous flare and cells, episcleral injection, corneal oedema, blepharospasm and epiphora (van der Woerdt et al, 1992). Because chronic uveitis can result in secondary glaucoma, vision loss and ocular pain, intraocular inflammation should be addressed, even if cataract surgery is not pursued (Plummer et al, 2007). Poor corneal wound healing, corneal neuropathy, altered lipid metabolism and retinal lesions are also potential consequences of diabetes in dogs and cats (Plummer et al, 2007).
Conclusions
Diabetes mellitus is a complex endocrinopathy affecting dogs and cats. While there has been an attempt to classify diabetes mellitus according to type (1 and 2) as in human medicine, this is not accurate in the veterinary medicine. Early diagnosis and regular monitoring are key to the successful management of these cases, and owner education, particularly with dogs and cats that are clinically obese, is key to maintaining a good quality of life for these patients. There are many complications that can arise when treating dogs and cats with diabetes mellitus and it is important that an individualised plan is determined on a case by case basis. Owners will need support if they are to be able to successfully manage their dog and cats’ health, and veterinary nurses play an important role providing diabetes mellitus nursing consults to facilitate this.