Signs presented by cats with diabetes

Clinical signs exhibited by cats with diabetes reflect the underlying pathological mechanisms of the disease and aid diagnosis. Laboratory tests are also needed to confirm a diagnosis.

Clinical pictures in cats suffering from diabetes mellitus:

• Uncomplicated diabetes
• Complicated by ketoacidosis
• Hyperosmolar syndrome

Clinical signs of uncomplicated diabetes in cats include:

• Polyuria (PU)
• Polydipsia (PD)
• Polyphagia
• Weight loss
• Increased susceptibility to infections (e.g. urinary tract infections).

Differential diagnoses of common clinical signs

Diabetes mellitus is a very common cause of polyuria, polydipsia and polyphagia, but there are many other differential diagnoses to consider. Occasionally, two conditions may present concurrently with similar clinical signs, and both must be managed.

The algorithms shown below may help to determine the differential diagnoses:

Signs of diabetes mellitus complicated by ketoacidosis

If feline diabetes is undetected and left untreated, a dangerous and sometimes fatal metabolic acidosis or diabetic ketoacidosis (DKA) may develop. In cats with untreated diabetes, excessive ketones are produced which results in ketonuria and DKA accompanied by electrolyte imbalances. Ketoacidosis is a serious condition that can ultimately lead to an acidotic coma and death.

In addition to the classic clinical signs of diabetes, cats affected by DKA may present with:

• Loss of appetite
• Lethargy and depression
• Vomiting
• Diarrhoea
• Weakness
• Dehydration
• Dyspnoea
• Collapse or coma

Signs of hyperosmolar syndrome

Hyperosmolar syndrome is an uncommon complication of untreated diabetes mellitus. In animals in which target tissue resistance to insulin plays a role in the disease, insulin levels can be elevated. In these cases, ketosis is suppressed and plasma glucose concentrations can become very high. Hyperosmolar syndrome represents an emergency situation. Affected cats will become progressively weaker, anorexic, lethargic and drink less. Ultimately, blood glucose levels become so high that osmosis shifts water from brain cells and coma results.

Appearance & management of uncomplicated diabetes

Two types of patients can be categorised as uncomplicated:

1. Cats presented after the owner notes the appearance of clinical signs without general deterioration or diabetic ketoacidosis (DKA). These are non-emergency cases.
2. Cats that have stabilised after initial presentation and successful treatment for DKA.

During consultation:

• Perform a thorough examination and weigh and body condition score the patient.
• Evaluate laboratory test results including complete blood count, urinalysis (including sediment examination/culture) and serum biochemistry profile (including TT4).
• Rule out hyperthyroidism, renal failure, inflammatory bowel disease, pancreatitis and exocrine pancreatic insufficiency, hyperadrenocorticism, neoplasia and hepatic disease.

Once diabetes mellitus is confirmed, and the decision has been made to treat with Caninsulin:

• Thoroughly explain to the cat owner about diabetes mellitus, that achieving stabilisation may take 3-6 months and what the implications are for the family. Make sure the owner understands what management involves and that the cat should be able to live a happy, healthy life with consistent treatment. This is crucial, as complete cooperation of the owner is essential to treatment success.
• Treat existing infections or other medical conditions. Any disease will affect insulin metabolism.
• Introduce appropriate diet.
• Begin treatment with Caninsulin (porcine insulin zinc suspension).

Initial therapy with Caninsulin:  Steps in clinic^1,2

• Weigh the cat to obtain a benchmark for future weight gain or loss.
• Start the cat on 1 to 2 IU injections of Caninsulin given twice daily. Administer injections at `the same time as, or right after meals, fed twice daily. No change in feeding schedule is needed for grazing.
• Hospitalise the cat for the day to verify that the starting dose does not cause hypoglycaemia with a blood glucose curve
• Instruct owner on:
  • How to administer injections.
  • How to identify and treat hypoglycaemia.
  • Parameters to monitor at home.
  • Preferred diet and frequency of meals.
• Discharge cat to owner’s care for 7 to 21 days. This allows the cat and owner to acclimate to the injection regimen. Offer the owner further support regarding injections over the first few days.

Tasks for clients at home

• Monitor and record water and food consumption.
• Maintain starting dose and frequency of administration for 7 to 21 days, unless there’s evidence of hypoglycaemia.
• Bring the cat in for re-evaluation 7 to 21 days after starting Caninsulin treatment.
• Ensure the pet owner is signed up to the Pet Diabetes Tracker App and understands how to use it at home, sharing the results with the clinic on a regular basis.

In-clinic re-evaluation

• Verify adequate injection technique and offer further support as necessary
• Evaluate owner's monitoring of clinical signs and glycosuria.
• Weigh and body condition score the patient.
• Evaluate glycaemia via a blood glucose curve or fructosamine evaluations.
• Adjust insulin dose if necessary, according to clinical signs and blood glucose values/fructosamine assessment. An interval of 7 to 21 days between dosage increments is ideal (unless there’s evidence of hypoglycaemia).

Stabilisation

Repeat procedures listed above at regular intervals until clinical signs and weight/body condition score are satisfactory and stable.

When regulation is achieved (no clinical signs; satisfied owners), schedule rechecks every 2 to 4 months:

• Perform a complete physical examination.
• Revise home monitoring if necessary.
• Evaluate blood glucose as necessary (e.g. glucose curve, fructosamine).

Problems

If clinical signs resume, laboratory results are not satisfactory or overall health deteriorates, causes must be identified.

• Perform a complete physical exam.
• Recheck:
  • Injection technique and insulin quality control.
  • Feeding and exercise.
  • Changes to the environment or lifestyle of the patient.
• Perform a blood glucose curve.
• Evaluate complete blood count, urinalysis (including sediment examination), and serum biochemistry profile (including T4).

Additional testing procedures may be required. Cats with diabetes may develop other concurrent diseases, such as pancreatitis, or infections that will interfere with the action of insulin.

Diabetic ketoacidosis (DKA) is potentially life-threatening

If a diagnosis of DKA is found as a complication in diabetic cats, it must be treated immediately.

Diagnosis

Diagnosis is based on the presence of ketonuria with clinical signs.

Management guidelines

Goals of treatment for diabetic ketoacidosis include correcting fluid deficits and acid- base and electrolyte imbalances, reducing blood glucose and ketonuria, initiating insulin therapy and treating concurrent diseases. The use of intravenous fluid therapy with isotonic fluids to correct fluid deficits and acid-base and electrolyte imbalances is recommended^3,4.

Many protocols for the treatment of DKA exist, but IV fluids and fast-acting (or regular) insulin must be administered immediately to decrease hyperglycaemia. Once the blood glucose has decreased to 14 mmol/L, using regular insulin, it is important to add dextrose to the fluids and continue with regular insulin until the cat is no longer vomiting, is eating and no longer has ketones in the urine. At this point, the regular insulin along with the dextrose in the fluids can be discontinued and Caninsulin (porcine insulin zinc suspension) therapy can be initiated².

Evaluation of treatment

When evaluating the regulation of insulin therapy, it is important to consider several areas including the evaluation of glycaemia, urine monitoring, routine rechecks and glycated protein evaluations.

Evaluation of the glycaemia

Creating a blood glucose curve is the most accurate way to evaluate glycaemia in order to adjust the Caninsulin dose.

Indications for creating a blood glucose curve are:

• First, to establish the insulin dose, dosing interval and insulin type when beginning stabilisation
• Second, to evaluate stabilisation especially if problems occur
• Third, when rebound hyperglycaemia (Somogyi effect) is suspected

Contraindications for creating a blood glucose curve are:

• Concurrent administration of drugs affecting glycaemia
• Presence of a known infection or disease
• Stressed animal

Procedural response

The most accurate way to assess the response to management is to generate a blood glucose curve. Ideally, take the first blood sample just prior to or immediately following the first Caninsulin^® administration. Thereafter, take blood samples every 2 hours throughout the day for 12 hours.

For one-off or ‘spot’   blood glucose measurements, single blood samples (or a series of samples) can be taken around the time of the expected nadir (this may have been determined following a blood glucose curve conducted during stabilisation). If this information is not available, a sample (or series of samples) can be taken any time from midday until late in the afternoon, shortly before the second meal is fed. However, this is less precise as some problems could be missed (e.g. Somogyi overswing). For this reason, it is not recommended to increase the dose of Caninsulin based on a single blood glucose sample (spot check).

Urine monitoring

A urine sample will only test positive for glucose if the blood glucose concentration remains above the renal threshold for a substantial period of time. Therefore, urine monitoring is not a very reliable method by which to adjust a cat's insulin dose and should only be used when it’s impossible to take blood samples or to monitor for ketones in the urine.

Routine rechecks

After the pet is successfully stabilised, routine rechecks should be performed at regular intervals of 2 to 4 months. Recheck evaluations sometimes show a slight hypo- or hyperglycaemia and if all other parameters (urine, appetite, water uptake, general conditions, etc.) are normal, a repeat blood glucosecurve the following day is recommended before making any dose adjustment.

Glycosylated proteins^5,6

Measurement of the glycosylated proteins, serum fructosamine (SF) and glycosylated haemoglobin (GHb), is another way to evaluate stabilisation. The level of these proteins reflects the chronic hyperglycaemia characteristic of diabetes mellitus and is not affected by stress, medication or recent feeding. SF is most frequently used and reflects the regulation of mean blood glucose levels for 1-3 weeks before the blood sample.

Blood samples to assess SF levels in the cat can be taken at any time of day and only a single sample is required, however they do have limitations and results should be interpreted accordingly:

• Fructosamine analysis will not detect short term or transient abnormalities, such as transient daily episodes of hypoglycaemia (which would require blood glucose analysis) or Somogyi overswing, requiring serial measurement of blood glucose concentrations.
• Hyperthyroid cats with concurrent diabetes mellitus may have decreased fructosamine levels because of an increase in the protein turnover rate (decreased protein half-life) resulting from increased thyroid hormone concentrations. It is important to rule this condition out or ensure it is well managed.
• Dehydration is not uncommon in cats with unregulated diabetes and this can lead to the appearance of hyperproteinaemia and higher than expected fructosamine values. Dehydration should be corrected before evaluating serum fructosamine levels.
• Globulin and fructosamine concentrations are correlated in cats. Hypoglobulinaemia will result in decreased fructosamine concentration—the laboratory performing the analysis should be consulted as to whether a correction is required and whether this has been done.

Proper management to avoid complications⁷

Hyperosmolar syndrome is an uncommon complication of untreated feline diabetes mellitus. In animals in which target tissue resistance to insulin plays a role in the disease, insulin levels can be elevated. In these cases, ketosis is suppressed and plasma glucose concentrations can become very high.

Diagnosis

Physical examination often reveals profound dehydration and the cat is typically lethargic, extremely depressed or comatose. The severity of the hyperosmolality correlates directly with the severity of these signs.

Hyperosmolar syndrome represents an emergency situation. Affected cats will become progressively weaker, anorexic, lethargic and drink less. Ultimately, blood glucose levels become so high that osmosis shifts water from brain cells and coma results.

Management guidelines

The goals of management include:

• Correcting fluid deficits and electrolyte balance associated with severe dehydration
• Reducing blood glucose via insulin therapy
• Correcting the hyperglycaemic, hyperosmolar state
• Managing concurrent diseases

Fluid therapy is critical to alleviate this syndrome, especially in the first 4 to 6 hours of management. The goal is to reduce blood glucose at the rate of 3 mmol/l. When the blood glucose approaches 16.5 mmol/l, the IV fluid selection should be changed to a 5% dextrose solution.

Intravenous isotonic fluid and insulin therapy usually resolve hyperosmolality but must be administered slowly to minimise the shift of water from the extracellular to the intracellular compartment.

Delay insulin therapy (typically 4–6 hours) until fluid therapy has improved the cat’s condition, corrected dehydration and improved urine production, hyperglycaemia, hyperosmolality and electrolyte levels.

Evaluation of management

When evaluating the effectiveness of fluid therapy, also monitor:

• Urine output
• Blood pressure
• Blood glucose
• Serum electrolytes
• BUN and urine glucose

Diseases that may contribute to the development of feline diabetes

Obesity

The number of cats suffering from obesity is growing at a rapid rate – yet it is a condition that can easily be controlled by pet owners, with help from their veterinary surgeon. In obese cats, lipids are preferentially deposited in muscle tissue, causing the insulin sensitivity of tissue receptors to decrease, leading to a greater demand for insulin, which eventually results in the exhaustion of the islets of Langerhans^8,9,10.  Obese cats can occasionally become non-insulin dependent when a normal weight is achieved. Weight loss should be gradual but consistent and the insulin dose adapted accordingly (following appropriate blood glucose analysis) to avoid loss of diabetic stability.

Acromegaly¹¹

Acromegaly (hypersomatotropism) is an endocrine disease caused by excessive secretion of growth hormone by the pituitary gland. In cats, acromegaly results from a pituitary tumour which secretes growth hormone. It is estimated that 25% of cats in the UK with diabetes may also by hypersomatotropic.

Acromegaly is characterized by chronic overgrowth of connective tissue, bone and viscera. Clinical signs of acromegaly in cats include:

• Insulin-resistant diabetes
• Enlargement of soft tissue organs
• Proliferation of gum tissue

Management of acromegaly

• Hypophysectomy (surgical removal of the pituitary gland) has been successfully carried out in cats across a number of U.K. surgical referral centres. Complete excision of the tumour usually results in a diabetic cure and can be an ideal solution for many cats (although lifelong oral hormone supplementation will be required).
• Conventional fractionated radiotherapy has been shown to be partially effective for management of pituitary tumours in cats that cause acromegaly and diabetes mellitus, but recently, stereotactic radiation therapy (SRT) has been shown to be safe and effective for treating cats with acromegaly. Cats treated with SRT have an improved survival time and better control of their DM when compared to patients treated with conventional radiotherapy¹².

Feline hyperthyroidism 

Hyperthyroidism is the most common endocrine disorder affecting cats. It causes a wide range of clinical signs resulting from the overproduction of thyroid hormone from the thyroid gland. This condition often presents concurrently with diabetes mellitus.

Common clinical signs of hyperthyroidism include:

• Weight loss
• Polyphagia
• Polyuria
• Polydipsia
• Vomiting
• Diarrhoea
• Hyperactivity
• Matted or greasy haircoat

Over time, excessive thyroid hormone secretion can cause heart disease and cats may exhibit:

• Heart murmur
• Difficulty breathing
• Tachycardia
• Arrhythmias

Diagnosis of feline hyperthyroidism

In most cats, laboratory measurement of the thyroid hormone, T4, will confirm the presence of hyperthyroidism. A small percentage of cats with hyperthyroidism will show normal T4 levels. In these cases, if hyperthyroidism is still suspected, conduct:

• Follow-up total T4 measurement 3 or more weeks later
• Free T4 measurement (by equilibrium dialysis)
• T3 suppression test

Treatment of feline hyperthyroidism

After confirming a hyperthyroidism diagnosis, 4 treatment options exist including:
 

• Surgical thyroidectomy
• Radioactive-iodine therapy
• Anti-thyroid medications
• Low iodine thyroid diet

Pancreatitis 

Pancreatitis causes digestive enzymes to leak into and damage the surrounding pancreatic tissues. In most cases, the cause of pancreatitis is idiopathic, however risk factors include:

• High-fat, low-protein diet
• Breed—Siamese cats are at higher risk
• Cholangiohepatitis
• Toxoplasmosis
• Feline leukaemia virus
• Feline herpesvirus
• Obesity
• Diabetes mellitus
• Cushing's disease
• Chronic renal failure
• Neoplasia

Acute pancreatitis or pancreatic neoplasia may produce temporary diabetes mellitus. If extensive pancreatic necrosis occurs, diabetes may become a permanent condition.

Pancreatic neoplasia

Pancreatic neoplasia is relatively rare in the cat but cases of insulinoma are seen. The tumour secretes insulin, leading to a fall in blood glucose and hypoglycaemia. At this point, cats show behavioural signs such as seizures and weakness. However, as the secretion of insulin in not continuous, clinical signs may be sporadic.

Other, rarer, pancreatic tumours may have a secondary impact by destroying pancreatic tissue and insulin secreting islet cells.

Exocrine pancreatic insufficiency (EPI) 

EPI is a congenital or acquired condition that can affect both dogs and cats, although it is more common in dogs. EPI in cats is very rare and typically manifests as the final stage of pancreatitis. EPI may occur concurrently with diabetes mellitus, if both the exocrine and endocrine pancreas are damaged.

EPI pathophysiology

• Digestive enzymes are not secreted normally by the pancreas
• Food is not sufficiently digested and processed
• Diarrhoea and weight loss occur despite normal or increased appetite

EPI diagnosis and treatment

EPI is diagnosed based on blood tests and is managed with pancreatic enzyme replacements and dietary management, which usually improve clinical signs. However, if EPI is a result of chronic pancreatitis, accompanied by diabetes mellitus, it can be more difficult to treat.