Medical and Nutritional Management of Diabetes Mellitus
World Small Animal Veterinary Association World Congress Proceedings, 2014
Stijn J.M. Niessen1, DVM, PhD, DECVIM, PGCertVetEd, FHEA, MRCVS; Marge Chandler2, DVM, MS, MANZCVSc, DACVN, DACVIM, DECVIM-CA, MRCVS
1Senior Lecturer Internal Medicine, Royal Veterinary College, University of London, London, UK; Research Associate, Newcastle Medical School, Newcastle, UK; Consultant, Veterinary Information Network, Davis, CA, USA; 2Royal (Dick) School of Veterinary Studies
Roslin, UK

Internist View On Canine Diabetes Management (Dr. Niessen)

The staple ingredients of current canine diabetes treatment have not changed and still consist of combining the most appropriate insulin regimen with the most appropriate diet regimen in order to mimic the lost function of the endocrine pancreas. However, significant shifts in the relative importance and understanding of details of these ingredients have taken place. Twice daily insulin injections currently remain the mainstay of canine diabetes treatment. Since diabetic remission is not a treatment goal in (neutered) diabetic dogs and diabetic complications such as cataract seem to appear despite excellent diabetic control, near euglycemic control is not necessary and increases the risk of dangerous hypoglycaemia with detrimental physical and emotional consequences. The treatment goal therefore remains ensuring good quality of life by reducing glucose to a level that there is minimal or absent polyuria, polydipsia, polyphagia, weight loss or risk for diabetic ketoacidosis, whilst preventing dangerous hypoglycemia. The choice of suitable insulin types ranges from porcine insulin (35% amorphous and 65% crystalline) (Caninsulin/Vetsulin®, MSD Animal Health) to NPH (various manufacturers), glargine (Lantus®, Sanofi Aventis), PZI (various manufacturers) and detemir (Levemir®, Novo Nordisk) insulin. NPH has been especially popular given its availability and its price. This insulin type can indeed prove satisfactory in diabetic dogs when used twice daily, although unfortunately suffers from a short duration of action in a frustratingly high proportion of cases. If the latter is encountered, clinicians would be advised to consider a change in insulin type or a change in the timing of food provision and insulin injection. Indeed, this latter "trick" is worthwhile considering with any insulin type, since postprandial hyperglycemia occurs more rapidly than that semi-lente, lente or Ultralente type insulin types reach peak activity after injection. If we can better match the timing of onset of peak insulin activity (± 2–10 hours) and the onset of postprandial hyperglycemia (± 10–30 minutes after eating), a more effective insulin regimen will be established. In the author's clinic, whenever possible, insulin is therefore given prior to feeding. This can range from 30 minutes to 90 minutes prior to food, resulting in the use of lower insulin doses with superior efficacy. When dealing with a diabetic dog with variable appetite, two factors can be consider. Firstly, the variable appetite needs to be explained, since diabetes mellitus alone, should not result in inappetence (unless diabetic ketoacidosis is present). Secondly, if no underlying reason for the variable appetite can be found and this seems more an inherent characteristic of the patient's character, 25% of food could be given at the same time as injecting the insulin and the remaining 75% could be given at the later time point. When switching to a pre-food insulin protocol it is wise to reduce the insulin dose to a conservative starting dose (0.25–0.5 units/kg BID), rather than maintaining an already established higher dose, given the possible superior efficacy of a lower dose with the new regimen. Since we are trying to mimic the lost function of the endocrine pancreas and we therefore want to match the twice daily insulin injections with twice daily meals, palatability of diet is absolutely crucial, ensuring reliable uptake of a steady amount of calories at regular intervals. An alternative option is to consider a different insulin type and of the types available using Caninsulin/Vetsulin® (the initial go-to insulin in most countries for canine diabetes) or Detemir® has been shown to be very potent in dogs and clinicians are therefore advised to start with a dose of 0.1 unit per kilogram twice daily. Its use in small dog breeds is therefore problematic and discouraged given the high chance of hypoglycaemia as well as associated lack of ability to fine-tune the dose. Unfortunately preliminary assessments of PZI and glargine insulin have proven underwhelming in most dogs with diabetes mellitus, although might still be useful in a minority of individual dogs or if future data proves more rewarding. Finally, in order to achieve the best outcome in each patient, clinicians are encouraged to be flexible in their insulin treatment protocols, adapting each diabetic protocol to each individual patient and its owner. This means that, although for all insulin types twice daily injections constitute the minimal needed frequency to be effective in 95% of cases, once daily injections should be considered when an owner refuses to comply with such BID regimen. Equally, TID injections should be considered when encountering a particularly short duration of action in a particular patient. Using a short acting (neutral or soluble) insulin together with a lente or ultra-lente insulin, could also be considered in others where lack of glycemic control results in poor quality of life or risk for diabetic ketoacidosis. The overall message remains: no two owners or two diabetic dogs are the same; why should each diabetic protocol therefore be the same? The need for such individualised diabetic care is especially emphasised when studying quality of life research results, recently obtained from diabetic dog owners, which highlights the significant impact on owners life and its impact on long-term compliance and success rates. The use of quantitative QoL-measurement tools designed for diabetic dogs in the shape of standardised surveys is therefore encouraged in order to achieve this individualised and optimised diabetic care.

The Nutritionist View on Canine Diabetes Management (Dr. Chandler)

Can diet modification help in treatment of canine diabetes? Insulin is the primary treatment of canine diabetes mellitus (DM) as dogs remain insulin dependent, but diet can help in management. Obesity in dogs does cause insulin resistance (but not usually Type II DM) so weight control is important. Low calorie, low fat, high fibre diets are often used for DM and weight control. Further, the nutrients of the diet and the feeding management both play a role in the uptake and utilization of glucose.

Feeding Schedule

Many protocols have been proposed for the number and timing of meals for diabetic dogs. As the insulin peak and duration of activity for an individual is hard to determine (blood glucose curves vary daily even with the same dose and treatment schedule), the exact feeding time is not crucial if food is available or in the digestive tract during periods of high insulin concentrations. If possible (e.g., dogs that are not greedy eaters) providing dry food free choice helps avoid hypoglycaemic episodes. If required, an owner or an automated feeding providing a small meal mid-afternoon (or early morning) can help prevent an excessive drop in blood glucose during that time.

Fibre

Although several studies in diabetic dogs indicate that high-fibre (cv low-fibre) diets improve glycaemic control, no measurable benefit has been shown in high fibre cv moderate-fibre diets. There is a marked variation in the glycaemic responses of individual diabetic dogs to dietary fibre, i.e., some show an improvement and some do not.

Carbohydrate

The amount of dietary starch is a major determinant of the glycaemic response. Rice-based diets may result in higher postprandial glucose and insulin responses. Sorghum results in the lowest postprandial glucose response and barley produces the lowest insulin response; but more work is needed before specific recommendations can be made.

Fat

While altered lipid metabolism occurs with insulin deficiency, little is known about the influence of dietary fat on diabetic dogs. Diabetes can occur secondary to exocrine pancreatic disease, and DM may be a risk factor for pancreatitis. High-fat diets and hyper-triglyceridaemia are potential inciting causes of canine pancreatitis; low-fat diets are recommended for chronic canine pancreatitis. Feeding low fat diets to diabetic dogs may improve insulin sensitivity, especially if they result in weight loss in fat animals, but low calorie diets are not appropriate for thin dogs.

Carnitine

Carnitine is a conditionally essential nutrient that plays a pivotal role in fatty acid metabolism. Supplemental carnitine suppresses acidosis and ketogenesis during starvation in dogs and diets for DM containing carnitine are worth considering.

Chromium

Chromium tripicolinate is a mineral that increases the blood clearance rate of glucose by about 10% in healthy dogs. Supplementation may only be beneficial in deficient individuals. Dietary chromium levels of most people in industrialized countries are low, but similar information is not available for dogs. Chromium would theoretically be useful in DM dogs; however, so far supplementing with chromium picolinate has not been found to improve glycaemic control.

The Internist View on Feline Diabetes Management (Dr. Niessen)

In recent years a focus has arisen on remission as a treatment goal in the diabetic cat. Few randomized studies have been conducted to truly determine how to achieve this, leaving us currently guessing what the best treatment recipe is. Diabetic remission seems to occur more frequently in cats that become diabetic later in life. Secondly, remission also seems more likely in newly diagnosed cats which are treated effectively (which does not necessarily mean aggressively). Various initial papers reported a wide range of remission rates albeit in small case-number studies (20–100%). Probably however, a rate of 50% is a more realistic expectation in a population representative of the newly diagnosed Type 2 diabetics seen by first opinion practitioners. In these cats remission occurs most commonly after 1–4 months of insulin therapy. Once persistent hyperglycemia occurs, insulin secretion is reduced through the phenomenon of glucose toxicity. There is evidence that initially, this suppression of insulin secretion is reversible and not associated with actual lesions in the beta-cells. However, with hyperglycemia of longer than two weeks duration, histological abnormalities become evident, including glycogen deposition and cell death. The severity of the glucose toxicity effect seems dependent on the degree of hyperglycemia and the duration. Chronically elevated blood glucose also causes insulin resistance, which further complicates matters. Additionally, increased fatty acids produce a similar effect to glucose toxicity (lipotoxicity). The clinical implications of the above will be at least two-fold: 1). we could improve both beta-cell function and insulin sensitivity and possibly induce diabetic remission by treating the hyperglycemia; 2). we know from the situation in human diabetics that even if complete diabetic remission does not occur, the patients' glycaemia might be easier to control with insulin if there is still residual beta-cell function. In line with this and based on world-wide experience, remission seems more likely if glycemic control is optimal, suggesting that beta-cells in the diabetic cat can indeed recover from the glucose- and lipotoxicity. Therefore, if a specific owner-diabetic cat combination strongly desires induction of remission, immediate insulin therapy using an effective insulin-type and protocol, as well as adequate monitoring are recommended. Additionally, a trial with an oral hypoglycaemic could therefore be contraindicated, since this might lead to losing time and thereby losing beta-cells. Initial studies documented remarkably high diabetic remission rates in cats treated with glargine, suggesting that diabetic remission was more easily obtained using this insulin type. However, dietary management and the rapid treatment after initial onset could also have accounted for these phenomenal remission rates. Since these initial studies, further data have been published that suggest a range of remission rates can be achieved when using insulin glargine, some documenting a higher rate than with other insulin types, others documenting similar rates across insulin types. In view of this, it seems likely that a high remission-rate is not in fact primarily associated with the employed insulin-type, but with the level of achieved glycemic control. Although various protocols have been proposed, some quite intense and with day-to-day or even within-day dose changes, clinicians should be aware of the potential for dangerous hypoglycemia with intense protocols, as well as the significant animal and owner burden inflicted by these protocols. Adding to this, the still lacking unbiased evidence that proves intense protocols are unquestionable associated with higher remission rates, it seems appropriate to at least have a discussion with owners on the various available protocols (ranging from intense to relaxed) and their practical implications. At this moment the author, in the average case, still often recommends that when using any lente, PZI or synthetic insulin-type, it is used as a BID treatment, without too frequent dose changes (unless hypoglycemia forces a dose change); the full effect of any dose change of a longer-acting insulin-type might still be best evaluated 7–10 days after that change using the clinical image (PU/PD, polyphagia, weight change) and a blood glucose curve.

The Nutritionist's View on Feline Diabetes Management (Dr. Chandler)

As mentioned earlier the main goal for treatment of diabetes mellitus in cats is to attain remission. Diet plays a major role in this achievement.

Protein, Fat and Carbohydrates

Studies in diabetic cats treated with insulin and fed a high protein, low carbohydrate diet have shown that this diet is associated with reduced insulin requirement and a better chance of remission. A diet with 46% of the calories from protein results in lower postprandial glucose concentrations than diets with 47% of the calories from fat or carbohydrates. High protein diets more closely mimic cats' natural diet than high carbohydrate diets.

Does feeding dry food to cats cause diabetes mellitus due to the high carbohydrate content?

Cats are obligate carnivores and are less efficient than some other mammals at metabolizing large amounts of carbohydrates. They will choose a low carbohydrate diet, but be capable of digesting them. Intake of commercial dry or canned cat foods has not been found to alter blood glucose concentrations. Overweight cats do show insulin resistance on a high carbohydrate, low protein diet. Proven risk factor for type 2 diabetes in cats include indoor confinement, low physical activity and neutering but not the proportion of dry diet or high dietary carbohydrates. Increased body fat is more likely than the diet type to induce a pre-diabetic condition.

Feeding Schedule

It is important to allow cats to adhere to their usual feeding schedule whenever possible. Most cats eat small meals frequently during the day, and having free choice food available will help avoid hypoglycaemic episodes; however, obese cats may need to be meal fed.

Fibre

Increased dietary fibre reduces post-prandial glycaemia in humans by modulating the absorption of glucose from the intestines; however, cats appear to have a different pattern of post-prandial glycaemia than people (and dogs). Several older studies showed improved diabetic control in cats on high fibre diets compared with controls, suggesting that other factors might affect glycaemic control. High fibre diets are often lower in calories, which may be beneficial.

Chromium

Chromium supplementation in healthy, non-obese cats has shown a small but significant, dose-dependent improvement in glucose tolerance. Cats most likely to benefit are those with glucose intolerance and insulin resistance from lack of exercise, obesity and old age. Healthy cats at risk of glucose intolerance and diabetes from underlying low insulin sensitivity or genetic factors may also benefit from long-term chromium supplementation.

L-Carnitine

Cats benefit from the lean body mass preservation effects of carnitine. It is beneficial in overweight feline weight loss due to its protective effect on liver function and benefits cats with hepatic lipidosis. Most commercial feline diets for weight loss and for DM contain added L-carnitine.

Obesity and Diabetes Mellitus

Obesity decreases sensitivity to insulin and contributes to the risk of diabetes mellitus in cats. Overweight cats have twice the risk of developing diabetes mellitus, and obese cats have 8 times the risk. In overweight cats, weight loss will aid in DM remission.

  

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

Marge Chandler, DVM, MS, MANZCVSc, DACVN, DACVIM, DECVIM-CA, MRCVS
Royal (Dick) School of Veterinary Studies
Roslin, UK

Stijn J.M. Niessen, DVM, PhD, DECVIM, PGCertVetEd, FHEA, MRCVS
Royal Veterinary College
University of London
London, UK


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