Diabetes mellitus is estimated to affect around 1 in 200 cats and is the second most common endocrinopathy, after hyperthyroidism. It is believed that the prevalence of this disease is increasing. Risk factors include genetic factors, obesity, gender and neuter status, lifestyle and medication history. A recent UK study reported an increased risk of diabetes in certain breeds including Tonkinese, Burmese and Norwegian Forest (O’Neill et al., 2016). Diagnosis can be made more challenging by the stress hyperglycaemia phenomenon that cats are vulnerable to and presence of concurrent diseases which may make interpretation of laboratory parameters more difficult.
The majority of diabetic cats are non-ketotic, and their diabetes is analogous to human type 2 diabetes mellitus, characterised by insulin resistance, obesity and pancreatic amyloid deposition. Ketoacidotic diabetic cats need to be treated urgently, with attention being paid to electrolyte imbalances, fluid therapy and reversing the hyperglycaemia and ketoacidosis.
Treatment of diabetes mellitus should aim to achieve diabetic remission if possible. Additional aims include resolution of clinical signs associated with diabetes mellitus (eg polyuria, polydipsia, polyphagia and weight loss), maintaining blood glucose levels below the renal threshold (between 12 and 14mmol/l) for the majority of the time. This should be associated with prevention and/or minimisation of ketoacidosis and the development of other long-term complications of diabetes such as peripheral neuropathies (Figure 1). Hypoglycaemia should also be avoided by maintaining blood glucose levels above 5mmol/l.
Early diagnosis and aggressive treatment increases the chances of diabetic remission. Efforts should therefore be concentrated on:
- Insulin therapy and dietary management: resolution of glucose toxicity greatly increases the chance of achieving diabetic remission. Glucose toxicity describes the situation whereby prolonged hyperglycaemia suppresses insulin secretion by the β-cells of the pancreas. As glucose toxicity resolves, the β-cells may recover some ability to produce and secrete insulin leading to improved glycaemic control and diabetic remission in some patients
- Where possible, withdrawing any diabetogenic drugs the cat may be receiving (eg glucocorticoids). If not possible to withdraw then consider replacing with less diabetogenic alternatives (eg using inhaled corticosteroids for asthma; Figure 2)
- Managing obesity, where present (Figure 3). Obesity causes insulin resistance and is an important risk factor for the development of feline diabetes. A weight loss regime resulting in 1 percent loss of bodyweight per week is recommended. A low carbohydrate diet fed at an appropriate caloric intake for weight loss is often an ideal choice for an overweight diabetic cat
- Identifying and supporting pancreatitis, where present. Many diabetic cats are thought to have pancreatitis which may be subclinical but may still have an impact on diabetic stability and likelihood of achieving diabetic remission (Zini et al., 2015; Shaefer et al., 2017)
- Identifying and addressing other underlying conditions. All inflammatory, infectious and neoplastic conditions have the potential to increase insulin resistance and destabilise diabetic control. Successful resolution of these may be enough to result in diabetic remission. For example, dental disease should be addressed early in the course of treatment for diabetes. Acromegaly may be more prevalent than once thought – a recent study indicated that the prevalence of this may be as high as 25 percent of UK diabetic cats (Niessen et al., 2015)
- Identifying and managing concurrent illnesses which may be linked to the diabetes. For example, urinary tract infections are a potential complication of diabetes and will increase insulin requirements and complicate stabilisation. Reported prevalence of bacterial UTIs in cats with diabetes mellitus has varied from 7 percent to 14.3 percent (Bailiff et al., 2006; Mayer-Roenne et al., 2007; Michiels et al., 2008; Bailiff et al., 2008). Urine culture is recommended as a priority in all newly diagnosed diabetic cats and those whose diabetic control has recently deteriorated
- Increasing physical activity increases insulin effectiveness and is especially beneficial in aiding weight loss in an obese inactive cat
Typically, a third to half of diabetic cats treated with insulin may achieve diabetic remission, and are able to maintain normoglycaemia without insulin therapy or use of other glucose-lowering drugs (Michiels et al., 2008; Gostelow et al., 2014; Hazuchova et al., 2018). There is evidence that early intensive management with long-acting insulin (glargine or detemir) and dietary management can increase this figure to greater than 80 percent in some situations (Roomp et al., 2009; Marshall et al., 2009; Roomp et al., 2012; Gostelow et al., 2014).
Diabetic remission is also possible for patients presenting in diabetic ketoacidosis. Remission typically occurs within one to three months of initiation of treatment, although relapse occurs transiently or permanently in around a quarter of these. Remission from relapse is generally much harder to achieve. Most patients in diabetic remission have reduced pancreatic function as a result of β-cell loss and damage resulting from glucose toxicity, as well as any underlying pancreatic pathology which contributed to diabetes development in the first place. Other clinical problems are often present in these cases and also may account for the patient’s predisposition to diabetic relapse through increasing insulin requirements. Common concurrent illnesses include gingivitis, obesity, hyperthyroidism, concurrent diabetogenic drugs and renal disease.
Dietary management of diabetes mellitus
Studies have shown benefits to glycaemic control by feeding diabetic cats a low carbohydrate diet. These studies reported diabetic remission rates between 33 and 100 percent when using a combination of dietary management and insulin therapy (Roomp et al., 2009; Marshall et al., 2009; Roomp and Rand, 2012).
There are now a number of specially formulated veterinary prescription diets available for this purpose. Wet diets are generally recommended over dry because these often contain lower carbohydrate levels. The lower energy density and greater water content is also useful for managing obesity. Use of low carbohydrate diets may reduce or eliminate the need for insulin therapy in the long term.
In those cats where the diet is changed following diagnosis of diabetes, it is important to do this slowly and to monitor the patient carefully since insulin requirements can change very quickly. Low carbohydrate diets are suitable for use in diabetic cats of all weights – whether needing weight loss or gain. Since cats have a very prolonged postprandial glycaemia, timing of meals is not critical for management of most feline diabetic patients.
Insulin therapy
Insulin therapy is required to stabilise most diabetic cats. In general, twice daily insulin therapy is associated with better results than once daily, regardless of the insulin preparation chosen although there is considerable inter-cat variation in duration of action and response to insulin. Longer-acting insulins are generally recommended for treatment of diabetic cats where possible (Sparkes et al., 2015; Behrend et al., 2018).
The two veterinary licensed insulins in the UK are:
- Longer-acting protamine zinc insulin (Prozinc, Boehringer Ingelheim): a recombinant human insulin in a 40iu/ml formulation and typical duration of 13 to 24 hours. Some studies have indicated improved glycaemic control when using twice daily protamine zinc insulin compared to twice daily lente insulin (Gostelow et al., 2018) and this should be prioritised for cats with a short duration of action on lente
- Medium-acting lente insulin (Caninsulin, MSD Animal Health): this is a porcine insulin zinc suspension with an insulin concentration of 40iu/ml and typical duration of 8 to 10 hours. Caninsulin provides good to excellent clinical control of diabetes in the majority of patients
When using 40iu/ml preparations it is essential to also use 40iu/ml syringes. Use of a magnifying glass or reading spectacles can be helpful for care providers with poor eyesight, especially when low doses are prescribed. Caninsulin is available in a pen doser which accurately dispenses insulin in 0.5iu increments (VetPen, MSD Animal Health). Pens facilitate more accurate dosing, especially when a low dose is required, helping to reduce the risk of hypoglycaemia (Thompson et al., 2015). Use of pens is associated with fewer “needle stick” injuries although carers do not always find them easier to use (Albuquerque et al., 2019).
Most cats require only small doses of insulin. Non-ketotic diabetic cats should be started on insulin at a dose of around 0.25 to 0.5 units per kg bodyweight per injection (maximum starting dose 2iu per cat). The dose of insulin should not be increased more often than every five days as it takes several days for the effects of a new dose to “settle out”. Detailed guidelines for diabetic stabilisation and monitoring are available elsewhere (Sparkes et al., 2015; Behrend et al., 2018).
Future therapies
Diabetes mellitus is an area of much active research in cats with several current strands of investigation. Future therapies currently being assessed include incretin analogues. Incretins are hormones released by enterocytes in response to small intestine nutrient content; use of incretin analogues such as exenatide may improve diabetic remission rates and reduce/avoid the need for insulin therapy (Gilor et al., 2016; Behrend et al., 2018).
Conclusions
Many cases of diabetes are straightforward to stabilise although it may take several weeks or months to identify an optimal insulin regime. Dietary management ideally involving feeding a therapeutic diet improves patient outcome. Early diagnosis and treatment increase the chances of diabetic remission. Detailed survival statistics for diabetic cats are not available but a recent study reported a median survival time of 516 days with almost half of the cats living for more than two years (Callegari et al., 2013).
