The pancreas is a complex organ comprising both an exocrine and an endocrine function. The endocrine pancreas involves the area called the islets of Langerhans which contain β-cells; it is from these cells that insulin is produced (Kipperman and Rogers, 2012). Insulin is responsible for maintaining blood glucose levels within a normal range, and in healthy patients, receptors in the pancreas monitor blood glucose levels informing the β-cells to increase or decrease the amount of insulin accordingly.
Diabetes mellitus is an endocrine disorder that results from either insufficient insulin production by the pancreas or an ineffectiveness of insulin at peripheral tissues resulting in persistent hyperglycaemia (Yin, 2010). Various studies have been performed to determine the prevalence of diabetes mellitus and it has been estimated that approximately 0.43% of feline patients are affected (Reusch, 2014), while it is reported to affect around 0.3% of canine patients (Tardo et al, 2019).
Diabetes mellitus in canine and feline patients
Traditionally, classification of diabetes mellitus has mirrored that of the human disorder and is categorised into type-1 like and type-2 like diabetes mellitus.
Type-1/insulin dependent diabetes mellitus is characterised by a reduced level of insulin production by the pancreas because of β cell destruction and requires daily insulin administration (Kipperman and Rogers, 2012). Causes can include pancreatitis, immune destruction of β cells and amyloidosis (Yin, 2010). Insulin dependent diabetes mellitus is the most common type diagnosed in canine patients (Tardo et al, 2019).
Type-2/non-insulin dependent diabetes mellitus occurs when the pancreas is producing sufficient levels of insulin, but this insulin is unable to have the desired effect on the body due to peripheral insulin resistance (Yin, 2010). Patients with this type may go into remission with the correct management. It is thought that feline patients more frequently suffer from a type-2 like diabetes mellitus and risk factors for development of the disorder include obesity and inactivity, being of male gender, being neutered and increasing age (Reusch, 2010).
Once the patient has been diagnosed, the veterinary surgeon (VS) will choose an appropriate treatment regimen and will work with the owners to ensure the patient receives this. The veterinary nurse (VN) plays a key role at this point with the educating of owners and can play a key role in demonstrating how to administer medications, discussing dietary options and in helping the VS in the explanation of which adverse clinical symptoms to monitor for. Usually there is a fine balance between the diet, medication and exercising of these patients and sometimes it does not require much to cause the patient to destabilise. In the veterinary practice, VNs may be the initial point of contact for owners and should know what advice to provide to owners in the event of diabetic complications.
Iatrogenic hypoglycaemic crisis
Hypoglycaemia is a low blood glucose level and has been defined as <3.3 mmol/litre (Idowu and Heading, 2018). Hypoglycaemia can occur in diabetic patients because of exogenous insulin overdose or mishandling, which may be as a result of incorrect storage or syringe type, strenuous exercise or as a result of the patient becoming inappetant or vomiting and still receiving the prescribed dosage of insulin (Morgan et al, 2018). Clinical symptoms can vary depending on the degree of hypoglycaemia and have been summarised in Table 1.
Table 1. Common clinical symptoms of hypoglycaemia
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Hypoglycaemic crises tend to arise in the home environment and the owners should be guided as to what action should be taken in this event. Initial guidance is to offer food or administer sugar water if the patient is able to swallow and/or apply a glucose gel or honey (Figure 1) to the patient's oral mucous membranes (MM) and to contact their VS. A recent study by Holt et al (2019) concluded that MM application of oral glucose products could take 15 minutes to have an effect so it may be prudent to warn the owners of this. The patient should be transported to the veterinary clinic as soon as possible for examination and may require emergency intervention if neurological symptoms are present.
Emergency treatment in the hospital environment for hypoglycaemia involves administration of a dextrose constant rate infusion (CRI) to restore euglycaemia and the VS may opt to administer a bolus, prior to starting the CRI, depending on the clinical status of the patient. It is important to remember that a dextrose concentration <5% must be administered via peripheral intravenous catheters, if the concentration is >5% a central venous catheter must be used bevause of the risk of thrombophlebitis (Skelly, 2018). Table 2 demonstrates how to prepare the dextrose solutions to different concentrations. The VS will likely stop insulin administration until euglycaemia is restored but it is important to remember to restart it once the patient is stabilised. Depending on the cause of the hypoglycaemia the insulin dosage may require adjusting, further investigation warranted, or the owner may require extra support and guidance with regard to diabetic management.
Table 2. How to make different dextrose concentration solutions
| % dextrose solution to make | Fluid bag size | Amount fluid to remove | Amount dextrose to add | Total amount fluid |
|---|---|---|---|---|
| 2.5% | 250 ml | 12.5 ml | 12.5 ml of 50% dextrose | 250 ml |
| 2.5% | 500 ml | 25 ml | 25 ml of 50% dextrose | 500 ml |
| 2.5% | 1000 ml | 50 ml | 50 ml of 50% dextrose | 1000 ml |
| 5% | 250 ml | 25 ml | 25 ml of 50% dextrose | 250 ml |
| 5% | 500 ml | 50 ml | 50 ml of 50% dextrose | 500 ml |
| 5% | 1000 ml | 100 ml | 100 ml of 50% dextrose | 1000 ml |
Diabetic ketoacidosis
Diabetic ketoacidosis is a life-threatening diabetic emergency which requires prompt diagnosis and treatment (Bolton et al, 2016). Patients presenting with diabetic ketoacidosis may have a previous diagnosis of diabetes mellitus and have decompensated, or this may be their first presentation and they are subsequently diagnosed with diabetes mellitus.
Diabetic ketoacidosis occurs because an increasing in-sulin deficiency or resistance, along with excessive levels of counter-regulatory hormones including glucagon, cortisol and growth hormone, cause a persistent hyperglycaemia and over-production of ketones (Schaer, 2010). The insulin deficiency or resistance leads to decreased cellular uptake of glucose causing the body to start breaking down fat stores to release more glucose into the system to obtain energy, a waste product of this fat breakdown is ketones (Kipperman and Rogers, 2012). As more fat is broken down both glucose and ketone levels increase eventually overwhelming the body's buffering systems leading to electrolyte imbalances and metabolic acidosis (Bolton et al, 2016). In patients previously diagnosed with diabetes mellitus they may have developed a concurrent disease causing this insulin deficiency or resistance, for example pancreatitis, urinary tract infection (UTI) or hyperadrenocorticism (Bolton et al, 2016).
Common clinical symptoms of diabetic ketoacidosis include vomiting, inappetance, depression and weakness (Schaer, 2010), but symptoms are variable, and some may be a clue to an underlying condition, for example abdominal pain if the patient is suffering from pancreatitis and the owner may have observed stranguria if a UTI is present.
The aim of management is to treat the immediate life-threatening electrolyte and acid–base derangements, restore hydration, control the ketone and glucose levels and to establish any underlying disorders that require attention to allow the patient to be stabilised (Kipperman and Rogers, 2012). Dehydration deficits should be calculated along with daily maintenance requirements and ongoing losses (Box 1) to ensure fluid therapy requirements are met for each individual patient (Schaer, 2010), and the VS will choose a suitable isotonic crystalloid, either sodium chloride 0.9% or Hartmann's solution, and will decide if initial fluid bolusing is required. In these patients a central venous catheter is invaluable, for both fluid/medication administration and the repeated blood sampling these patients require, but if this is not possible the widest bore peripheral catheter should be placed (Skelly, 2018). Potassium levels should be measured at admission and frequently monitored as although they may appear normal or even increased at presentation they can quickly deplete when fluid therapy and insulin administration are implemented (Kipperman and Rogers, 2012). Skelly (2018) explained this normokalaemia as an effect of ‘solvent drag’ whereby potassium and water are drawn out of the cells because of the high extracellular glucose levels, but once fluid replacement and insulin therapy are started the potassium returns into the cell causing a hypokalaemia, which will require supplementation.
Box 1.Calculating fluid requirements
- Calculate fluid deficit: % dehydration x bodyweight (kg) x 10
- Calculate daily maintenance requirements: 50mls x bodyweight
- Calculate ongoing losses (e.g. vomit/diarrhoea) Estimate 50ml per episode of vomit Estimate 100ml per episode of diarrhoea
Daily fluid requirement = deficit + maintenance + ongoing losses(Boag and Hughes, 2018)
Rapid acting soluble (neutral) insulin will be prescribed to treat hyperglycaemia by encouraging cellular uptake of glucose, which will in turn reduce ketone production and encourage ketone metabolism (Skelly, 2010). Soluble insulin is administered until ketosis has resolved and the patient is eating and is clinically well. Ketosis resolution can be monitored by measuring urine with a dipstick, but be aware that a dipstick can only asses the presence of acetoacetate and not beta-hydroxybutyrate (Kipperman and Rogers, 2012), which is measured in blood. Ketosis may take longer to resolve than hyperglycaemia, but soluble insulin should be continued until it is resolved, which can cause the patient to develop a hypoglycaemia; therefore, it may be necessary to implement a dextrose CRI alongside insulin administration (Skelly, 2018). Two methods of soluble insulin administration may be chosen, and these have been summarised in Table 3.
Table 3. Two methods for insulin administration
| Intramuscular bolus injection | Intravenous constant rate infusion |
|---|---|
| Treatment begins with initial bolus injection and then hourly injections after this | Soluble insulin is diluted with sodium chloride 0.9% |
| Aim to keep blood glucose between 8–15 mmol/litre and check hourly | Run alongside crystalloid fluids in separate syringe driver to allow adjustment of each individually |
| If becomes hypoglycaemic may need to administer dextrose concurrently | Insulin binds to plastic tubing so important to run through 50ml of the insulin solution to avoid this |
| Blood glucose is checked an hour after starting infusion and every 1–2 hours after this | |
| Aim to maintain blood glucose between 8–15 mmol/litre and may have to administer dextrose if hypoglycaemia occurs |
Once the initial crisis has been managed, the VS will look at discontinuing the soluble insulin protocol and reintroducing the patient's daily insulin regimen, and will decide if the dosage or type needs to be altered while also looking at implementing any other medications if concurrent conditions have been diagnosed.
Urinary tract infection
Patients with diabetes mellitus are more susceptible to bacterial infections, particularly UTIs, and those with a predisposing cause like diabetes mellitus are classed as having a complicated UTI which generally requires a longer antibiotic course (potentially 4–6 weeks) and sometimes multiple antibiotics (Aguirre and Darling, 2012).
Bacterial UTIs commonly arise from pathogens ascending the urinary tract from tissue and skin surrounding the external urinary opening, and if defence mechanisms of the host are weakened the bacteria are able to invade and infect (Aguirre and Darling, 2012). Patients with diabetes mellitus are at increased risk of UTI because of the presence of glucose in the urine which promotes bacterial growth (Veterinary Health Centre, 2020). If left untreated a UTI can ascend the urinary tract and lead to pyelonephritis (kidney infection), that can in turn lead to an acute kidney injury which requires emergency management (Langston, 2010).
As noted above, the presence of a UTI can lead to destabilisation of the previously well-controlled diabetic patient. Infection can cause secretion of insulin-antagonising hormones such as glucagon and cortisol leading to insulin resistance (Hackendahl and Schaer, 2006). Rapid diagnosis and treatment of UTI is essential to reduce the risk of insulin resistance or interference developing.
The mainstay of treatment for bacterial UTI is antimicriobial therapy and the VS will choose the most appropriate antimicrobial agent with gold standard being based on urine culture testing (Aguirre and Darling, 2012). Urine samples for culture must be collected in an aseptic manner, with cystocentesis recommended, and collection into a sterile container, samples should be collected prior to starting any antimicrobial therapy (Aguirre and Darling, 2012). Guidelines published by the International Society for Companion Animal Infectious Diseases (ISCAID) advise that if an initial UTI episode resolves with the appropriate course of antimicrobials then a repeat urine culture may not be required, however, if the UTI is recurrent then follow-up urine culture samples should be tested 5–7 days after the course of antimicrobials have finished, to check for either relapse with the same bacteria or reinfection with a different bacteria (Weese et al, 2019).
Diabetic neuropathy
Although most cats with diabetes mellitus will present with the typical symptoms of polyuria/polydipsia, polyphagia and weight loss, approximately 10% of cats will present with symptoms of diabetic neuropathy (Reusch, 2010), which are summarised in Table 4. It can also occur in the chronic diabetic patient with persistent hyperglycaemia that has not been well controlled. This disorder is uncommon in dogs (Nelson, 2010).
Table 4. Clinical symptoms of feline diabetic neuropathy
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The pathophysiology of diabetic neuropathy is not fully understood but is thought to be a mixture of metabolic and vascular components and no specific treatment is currently available (Reusch, 2010). Management of a patient with diabetic neuropathy involves gaining and maintain glycaemic control, which can improve and sometimes resolve clinical symptoms (Reusch, 2010); prior to this it may be beneficial for the patient to establish a physiotherapy routine dependent on the severity of clinical symptoms.
Diabetic cataracts
A cataract is an opacity in the lens of the eye causing blindness and is the most common chronic complication of diabetes mellitus in canine patients (Nelson, 2010). Cataracts form when extra circulating glucose (as a result of the hyperglycaemia) diffuses into the lens and is converted into sorbitol before metabolising to fructose (Yin, 2010). Both these sugars are very hydrophilic drawing water into the lens disrupting the lens fibres and leading to cataracts (Nelson, 2010). Dogs with poorly controlled diabetes are at increased risk of cataract formation (Nelson, 2010).
The only treatment option for cataracts is surgical intervention and no medical options to either slow or reverse the process are currently available (Ofri, 2019). The VN plays a key role in supporting the owner caring for a blind dog and some useful suggestions to the owner can include:
- Ensuring the home environment is safe and removing/securing any potential hazards
- Avoiding movement of large objects once the dog is used to navigating their home environment
- Speaking to their pet before approaching (assuming no hearing issues are also present) to avoid startling them
- Ensuring food and water bowls are kept in the same location so their pet can easily find them.
Conclusion
Diabetes mellitus is a life-long endocrine disorder that requires careful management and communication between owners and the veterinary team. Unfortunately, as with any disease or disorder, complications can arise if something changes with the patient's daily routine or an underlying condition develops. It is important that owners are educated in adverse clinical symptoms to observe for and are made aware of when to seek urgent veterinary attention as rapid diagnosis and treatment of these complications are necessary.
KEY POINTS
- Diabetes mellitus is a disorder of the endocrine system resulting from either insufficient insulin production or an ineffectiveness of the insulin that is produced leading to a persistent hyperglycaemia.
- Common complications in diabetic patients include hypoglycaemia, diabetic ketoacidosis, urinary tract infection, diabetic neuropathy and cataracts.
- Some complications of diabetes mellitus lead to presentation of emergency patients (hypoglycaemia, diabetic ketoacidosis) requiring rapid intervention whereas others may develop more gradually (cataracts).