Diabetes Mellitus - An Update on Where We Are in 2014
World Small Animal Veterinary Association World Congress Proceedings, 2015
David B. Church1
1The Royal Veterinary College, University of London, London, UK

Introduction

Diabetes mellitus is not a single disease but a manifestation of various pathophysiological processes. Diabetes mellitus is perhaps best defined as clinically significant glucose intolerance caused by an absolute or relative lack of insulin. In any individual patient, the degree of insulin deficiency can fluctuate over time. These changes may be influenced by many factors. For example any animal with pancreatitis may develop clinically significant impaired insulin secretion. This is generally reversible and resolves as the inflammation subsides. Perhaps more obscurely, any condition resulting in chronic insulin resistance results in hyperinsulinism that may lead to so called "islet exhaustion" in susceptible individuals. This may be variably reversible depending on the length of time the islets have been exposed to this increased secretory demand and the presence of inherent individual susceptibility to the damaging effects of chronic insulin "hypersecretion."

Clinical Signs

Most diabetic animals will present with various combinations of polydipsia, polyuria, polyphagia and weight loss. This is particularly true in dogs and less so in cats. Physical examination may reveal varying degree of muscle wasting (although some animals can be obese at the time of presentation), hepatomegaly and cataracts (almost exclusively dogs). Additionally if they are becoming ketoacidotic they may present with signs of dehydration, depression, inappetence, vomiting and diarrhoea. They will also have a ketotic breath although only a proportion of humans can detect the ketotic odour.

It is vitally important to remember that, in the absence of marked ketoacidosis, diabetes mellitus is unlikely to be the explanation for an animal presenting with inappetence or varying degrees of gastrointestinal dysfunction or depression and lethargy.

The presence of this sort of clinical picture in the absence of moderate to marked ketoacidosis suggests the concurrent presence of subnormal islet reserves and some other disease process causing the observed clinical signs. Consequently if an explanation is not apparent further targeted investigation to uncover the explanation is almost always warranted.

Diagnosis

Generally in the dog a diagnosis of diabetes mellitus is confirmed by the presence of fasting hyperglycaemia of greater than around 14 mmol/L. In the cat elevations in blood glucose of this magnitude or higher can be a result of stress due to any illness and further corroborating evidence should be obtained. In both dogs and cats with glucosuria, hyperglycaemia should be confirmed before treatment is considered.

Blood glucose estimations provide an estimate of the blood glucose concentration at the time of sampling. An elevated fasting blood glucose is likely to be an indication of persisting hyperglycaemia (especially if there are concurrent consistent clinical signs) however in cats that are unwell or 'stressed' fasting hyperglycaemia may be a transient phenomenon. If the clinician is in any doubt as to the significance of the hyperglycaemia it is possibly worth determining the glycosylated haemoglobin or plasma fructosamine level. Both of these parameters estimate the proportion of haemoglobin and albumin respectively that has glucose bound to it in a non-enzymatic irreversible way. As the process is both non-enzymatic and irreversible the proportion of the relatively constant protein that is "glycated" is an estimate of the "average" blood glucose concentration over a preceding period that appears to be somewhat variable depending upon whether we are dealing with cats or dogs.

In the dog the fructosamine concentration probably reflects the blood glucose levels over the last 2–4 weeks. In the cat the accuracy of the fructosamine as a reflection of previous blood glucose levels appears to be more variable and more a reflection of the blood glucose levels over the previous five to 10 days.

Regardless of these differences, clearly plasma fructosamine levels can be helpful in differentiating short-term hyperglycaemia from persistent hyperglycaemia. However it should be remembered that in the cat many disorders can cause an elevated blood glucose thus an increase in fructosamine should not be considered diagnostic for diabetes mellitus. It is simply an indication of a subacute or chronic moderate to marked blood glucose elevation.

Where glycosylated haemoglobin and fructosamine estimations are most valuable is in evaluating effective management of the diabetic patient. In many patients the need for repeated blood glucose estimations (glucose curves) can be avoided by a single blood sample for a glycosylated haemoglobin or fructosamine estimation. Of course a glucose curve can still be valuable in those animals proving difficult to manage.

Treatment of Uncomplicated Diabetes Mellitus

Clearly whenever underlying explanations for insulin resistance can be identified it is important to correct these whenever practicable as this may well result in resolution of clinical signs and indeed result in the patient no longer requiring insulin. Additionally, some obese diabetic cats may initially require insulin injections but requirement may diminish or cease when their body weight normalises.

However, especially in dogs, in many cases the clinically significant glucose intolerance will not resolve with the reduction in insulin resistance-inducing factors and the clinician will have to consider implementing insulin therapy.

Which Insulin Is Best?

Insulins such as NPH, protamine zinc and lente insulins have been the mainstay of insulin therapy of cats and dogs for some time. Over the last few years the synthetic insulin analogues, insulin glargine and insulin detemir, have been recommended for use as a twice daily exogenous insulin in cats. The perceived advantages of these two insulins is a relatively "peakless" profile and longer duration of action than is seen with insulin lente or PZI. It is possible that these products' relatively "peakless activity profile" may make them more a more suitable insulin for those cats that are keen to "graze."

However when studies are "corrected" for diet, currently there is no substantial clinical data that suggests cats receiving twice daily glargine or detemir are any better controlled or any more likely to go into remission than cats receiving twice daily lente or protamine-zinc insulins.

Remember the overall aim of insulin therapy is to administer the insulin so that its time of peak activity corresponds to the peak demand, i.e., when the blood glucose is rising after feeding. The aim is to lower blood glucose concentration over the 24 hour period and to minimise fluctuations.

Feeding and Exercising the Diabetic Patient (Dog or Cat)

The diet must be consistent - the animal should consume the same caloric intake morning and night and from day to day. The food should be controlled and consistent:

 Commercial canned preparations with variable amounts of dry food are a convenient food type for diabetics as their caloric content is relatively predictable and consistent. However they may not be attractive to all patients, particularly if they have not been a traditional part of the animal's diet.

 When using relatively short duration insulins it is vital that all the offered food is consumed within a short space of time. In other words, caloric content and palatability are equally important. As a result, some diabetic dogs and cats need to be stabilised on standardised portions of their usual diets.

 Whatever the form of the calories fed to the diabetic patient, the timing and the caloric content must remain consistent. Any changes in the animal's diet can only be made if the overall caloric content remains unchanged.

 No snacks should be provided unless they have virtually no calories.

 As a general guide feed 50–70 kcal/kg body weight.

 There is no evidence that adding fibre to a diabetic's diet is likely to significantly improve poor diabetic control.

Low Carbohydrate, High Protein Diet - Good or Bad?

Lowering the overall carbohydrate intake by feeding a diet low in carbohydrate and high in protein may theoretically lower insulin requirements and/or improve diabetic control. Over the last few years numerous clinical trials have demonstrated improved diabetic control and reduced insulin requirements in diabetic cats fed a low carbohydrate-high protein diet. In a number of these studies the 'control' group were fed a high fibre (& hence high carbohydrate) diet of differing starch sources (which may have an impact on the glycaemic index). Certainly in the cat the results of all the studies strongly suggest feeding cats commercial diets more closely resembling the composition of their natural carnivorous diet to which they have become effectively adapted will increase diabetic remission rates, especially in those cats with marked insulin resistance through obesity. It is certainly a more theoretically sound principle than attempting to increase the amount of fibre they are being fed. The proportion of cats with uncomplicated diabetes mellitus likely to achieve a state where they no longer require exogenous insulin after receiving a combination of exogenous insulin and being switched to a high protein, restricted carbohydrate diet is still a point of conjecture. However it is generally accepted that up to 30% of early diabetics may be able to be managed without exogenous insulin.

Exercise

Generally exercise has the capacity to lower insulin requirements hence exercise should be consistent and encouraged. As diabetics are usually older animals that have been obese due to overfeeding and lack of exercise, over-exercise is not usually a problem.

  

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

David B. Church
The Royal Veterinary College
University of London
London, UK


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