Proceedings of the Southern European Veterinary Conference - SEVC -

Transcription

1 Proceedings of the Southern European Veterinary Conference - SEVC - Sep. 29-Oct. 2, 2011, Barcelona, Spain Next SEVC Conference: Oct , Barcelona, Spain Reprinted in the IVIS website with the permission of the SEVC - AVEPA

2 FELINE DIABETES MELLITUS: TYPES AND TREATMENT Dolores Perez Alenza Universidad Complutense de Madrid Diabetes mellitus is an endocrine disease becoming more common in cats. Not all cats initially have the same type of diabetes and it is useful to know the different types because the treatment and outcome may be different. Type I diabetes or insulin-dependent results from destruction, probably autoimmune, of pancreatic β -cell, is characterized by the inability to produce insulin and is irreversible. Type II diabetes is characterized by hyperglycaemia and insulin resistance, but there is still some capacity for insulin secretion. This type of diabetes is more common in cats and its frequency is increasing, as in humans, because the lifestyles are changing: a sedentary lifestyle and a diet rich in carbohydrates promote the onset of obesity, which is the most important factor for its development. It can be non-insulin dependent or insulin-dependent. It may be reversible if diagnosed early and treated properly. Type III diabetes or secondary occurs because of various factors such as diseases (e.g. pancreatitis, hyperadrenocorticism or acromegaly) and medications (e.g. glucocorticoids or progestins) and may be reversible after correction of the triggering cause. It tends to be insulin-dependent. On the other hand, and according to the clinical presentation, diabetes is considered uncomplicated or complicated depending on its severity. In uncomplicated diabetes, cats show symptoms of diabetes, hyperglycaemia, glucosuria, even ketones in the urine, but they are not unbalanced (they are dehydrated, they can eat, without vomiting, diarrhoea...) and usually can be treated at home. In the complicated presentation, cats are unbalanced, they are dehydrated, have poor appetite or anorexia, vomiting and there are urine ketones, all indicative of diabetic ketoacidosis that should be handled in the hospital, with urgent treatment based on fluids, electrolyte replacement and regular insulin. The diagnosis of diabetes mellitus is based on the presence of persistent hyperglycaemia and glycosuria with classic symptoms of diabetes (polyuria, polydipsia and weight loss). Occasionally, it may be difficult in cats with stress hyperglycaemia (due to concurrent illnesses). Hyperglycaemia in a cat with no symptoms of diabetes warrants the measurement of fructosamine levels and monitoring of glycosuria to help in the diagnosis. The goals of the treatment of uncomplicated diabetes are to make symptoms vanish, avoid long-term complications (ketoacidosis, peripheral neuropathy), control of the risk factors (obesity, chronic infections) and prevent the occurrence of hypoglycaemia. An additional objective, unique for cats with newly diagnosed type II diabetes, is the remission of the disease (the reversal of the sick cat to a non-insulin-dependent status). There are several key aspects to achieve these: the administration of a proper diet, exercise, insulin administration, control of concurrent diseases and monitoring of the disease. A good communication and collaboration with the owner are essential to achieve these objectives. Diet and Exercise. In type II diabetic cats, exercise plays a key role; we can increase the activity level by dividing their daily food in small quantities and place them in different parts of the house. It has been shown that cats who live exclusively indoors and without the company of other cats, have a less active lifestyle and are predisposed to obesity and diabetes. The goal of the diet is to achieve and maintain a desirable body weight and minimize postprandial hyperglycaemia. In general, prescribed diets for diabetic dogs (rich in fibre and

3 low in fat) are also useful in the diabetic cat, unless it is very thin. In these cases, use higher calorie diets and less fibre initially. However, it has been shown that the most appropriate diet for the diabetic cat is a diet low in carbohydrates and high in protein. Cats are obligate carnivores and better adapted to metabolize protein-rich diets. Diets rich in carbohydrates may exacerbate hyperglycaemia and muscle loss, whereas diets low in carbohydrates and high in protein, help to prevent hyperglycaemia and maintain muscle mass. The benefits of these diets are more evident in cats with early diabetes, when they maintain the capacity of insulin secretion and its use increases the likelihood of remission of the diabetes up to 30-50% of cats. In cats with longstanding diabetes, it is less likely to achieve remission; even so, these diets favour the regulation of diabetes. It is recommended to reduce de insulin dose by 25-50% after switching to this diets in cats who are already receiving insulin. Diets low in carbohydrates and high in protein are also recommended for diabetic cats with normal or low weight as they can promote weight loss or gain depending of the daily ration. Currently, diets rich in fibre are only recommended in diabetic cats that have concurrent illnesses that respond to the fibre, such as constipation, or in those where a high protein diet is contraindicated or in cats with renal failure. Oral hypoglycaemic agents. Oral hypoglycaemic agents (e.g. sulfonylureas) stimulate pancreatic insulin secretion and some cats with uncomplicated diabetes mellitus, with suspected Type II diabetes (obesity and lack of ketone bodies) can be occasionally controlled with the diet and oral hypoglycaemic agents; however, they are not recommended for long term use because they may enhance the formation of amyloid deposition in the pancreas. In general, they are not recommended except in cases in which the owner refused the treatment with insulin and is considering euthanasia. The most widely used sulfonylurea in cats is glipizide, and should always be used with a proper diet. It is given at mg/kg, up to a maximum of 5 mg every 12 hours. Vomiting and anorexia, hypoglycaemia and jaundice may occur. The drug should be withdrawn if the cat does not respond to glipizide in a few weeks or if it develops ketoacidosis or side effects and, therefore, insulin should be used. Insulin. There are different types of insulin according to the duration of action and origin (human, cattle, porcine). Regular insulin is the fastest acting, short and powerful, used for complicated feline diabetes (ketoacidosis) and can be used intramuscularly or intravenously. Intermediate-acting insulins (NPH) have a longer action, although this variable duration (4-14 hours). Slow-acting insulins (Lente, PZI) and ultralente (glargine) are the insulins of choice in cats because their duration after subcutaneous administration is longer. Depending on the origin, in Spain we have human-derived NPH insulin and porcine slow insulin (Caninsulin, Intervet). In other countries, sells PZI bovine insulin or human origin, which have proven highly effective in the management of feline diabetes is not complicated, but not sold in some countries. In recent years, human insulin analogues with long effect duration (glargine and detemir) designed to achieve a prolonged and predictable absorption are becoming available in many countries. In general, we recommend starting the treatment of uncomplicated feline diabetes with a diet low in carbohydrates and rich in protein and low doses of lente insulin (Caninsulin), 1 IU/cat every 12 hours in cats <4 kg and IU/12h in cats> 4 kg, or to start with 0.2 to 0.5 IU/kg/12h. Start with a conservative dose of insulin and gradually adapt it as necessary to avoid hypoglycaemia. In cats with recently diagnosed diabetes, the change of the diet may also promote its remission and, thus, it is very important to ensure an accurate monitoring of treatment and that the owner plays an active role. We must show them the proper handling of insulin, subcutaneous injection technique, reading the strips for urine

4 glucose and ketone bodies and the identification and treatment of hypoglycaemia. It is worth remembering that Caninsulin is marketed at 40 u/ml, while human insulins are all 100 u/ml so we must prevent confusion and do not use U100 syringes to calculate units of Caninsulin U40. Alternatively, or as first choice in recently diagnosed cats, you can begin the treatment with insulin glargine. Insulin Glargine (Lantus ) is a synthetic analogue of human insulin. After being subcutaneously injected, it causes a microprecipitate that causes a continuous and relatively slow absorption, so it should not be diluted because it would alter the rate of absorption. In normal cats, the duration of action is around 23 hours; however, a better effect is obtained using 0.25 IU/kg/12 hours instead of 0.5 IU/kg/24 hours. In a study, different types of insulin were followed for 4 months, and insulin glargine obtained the remission of diabetes in the 8 cats treated with it, whereas other insulin-treated cats had a lower remission rate (2 / 8 in cats treated with insulin lente and 3 / 8 of the cats treated with PZI insulin). However, studies with larger numbers of cats and a long-term monitoring to assess the efficacy of this insulin are needed. Once the treatment is scheduled, we must recheck the diabetic cats, initially weekly, then monthly. The owner should evaluate the clinical response (polyuria and polydipsia and activity) and measure levels of glycosuria and ketones in urine, initially once a day. The veterinarian will then adjust the insulin dose according to the glycosuria and the clinical response. A given dose should be maintained between 3 and 4 days before being considered inadequate. If we start the treatment with a low dose of 0.2 IU insulin/kg, we must increase this dose a 10-25% in most occasions. In many cats, an adequate control is eventually achieved with a dose of U/kg of insulin (Caninsulin or glargine). Some cats, however, are controlled with very low doses of insulin and we must always bear in mind that diabetes can be transient. At check-ups, especially those made monthly, the levels of fructosamine must be determined. If symptoms persist in the successive revisions, i.e. blood glucose levels are elevated > 250 mg/dl at any time of day or are > 125 mg/dl between 6-8 h after insulin administration (nadir), the levels of fructosamine are elevated (> 450 mmol/l) and there is persistent glucosuria, especially if you are already using high doses of insulin (> 0.7 to 1 IU/kg), it suggests a of poor control of the disease. Faced with a poorly controlled disease, we must always re-check the patient (for concurrent diseases that cause insulin resistance), the diet, the therapeutic schedule, type of insulin and its administration and, if we cannot find the cause, perform a glucose curve. In cats, blood glucose curves can be done at home or at the hospital. Currently, it is recommended to do them at home because the animal is less stressed and the results are more reliable. Recently, the use of a continuous glucose monitor that is placed under the skin has been described, and it is very useful for the glucose curves, although not yet available in Spain. The results of the glucose curve may be affected by stress and lack of appetite. Although these problems can be minimized with good management, we must interpret these glucose curves with caution because there is great variability in the results of curves made two consecutive days apart in the same animal and under the same conditions. The glucose curve is drawn determining glucose levels every 2 hours for 12 hours while maintaining the usual feeding and insulin injections. If blood glucose is <100 mg/dl at any time, then blood glucose should be determined every hour. Blood glucose levels should remain between 100 and 250 mg/dl at least in 80-90% of the interval between 2 injections of insulin. The nadir of glucose (lowest blood sugar level) indicates whether the insulin dose is adequate, and should be between 110 and 145 mg/dl. If the nadir is below 110 mg/dl, the risk of causing a rebound hyperglycaemia (Somogyi effect) secondary to hypoglycaemia. The Somogyi effect then causes a severe hyperglycaemia, which can be confused with a low dose of insulin or insulin resistance if hypoglycaemia has not been noticed previously. In this case, the dose of insulin should be reduced.

5 If the nadir of blood glucose is > 145 mg/dl, it may be caused by an insufficient dose or insulin resistance. If we are using a low dose (< 0.5 IU/kg), we must increase the dose of insulin. If the dose is high (> 1 IU/kg per dose), we do usually speak of insulin resistance because that patient requires very high doses. This occurs for several reasons: sickness / concurrent disorders: obesity, infections (mouth, urinary tract), administration of progestins and / or glucocorticoids, hyperadrenocorticism, renal failure, pancreatitis, heart diseases, liver diseases, cancer, acromegaly (excess growth hormone) hyperthyroidism and, finally, the existence of anti-insulin antibodies. Hyperadrenocorticism is less common than in dogs and often results in most cases of insulin-resistant diabetes mellitus. Acromegaly is a rare condition that causes a severe insulin resistance in cats, mainly elderly and male cats, with increase in body size, especially of the head and extremities. The number of skin folds may increase and laryngeal stridor is common. Organomegaly (heart, kidneys, etc) and osteoarthritis can be detected radiologically. Feline acromegaly is caused by the increased production of growth hormone by a pituitary tumour and its diagnosis is confirmed by demonstration of raised plasma levels of GH or IGF-I (> 1000 ng / ml). A MRI is required to confirm the pituitary tumour. As the definitive treatment is pituitary hypophysectomy or radiation therapy, most cases are not effectively treated and require high doses of insulin (> 15 UI/12h/cat). A medical treatment with octreotide (Sandostatin ), a synthetic analogue of somatostatin, that decreases the synthesis of growth hormone has been described, although its effectiveness is reduced in acromegalic cats and is an expensive drug. Although the prevalence of this disease is increasing in recent years, mortality has declined from over 40% to less than 10% in the last 20 years, demonstrating that feline diabetes mellitus can be successfully treated with an early and adequate therapy. Marshall RD, Rand JS, Morton JM. Treatment of newly diagnosed diabetic cats with glargine insulin improves glycaemic control and results in higher probability of remission than protamine zinc and lente insulins. J Feline Med Surg Aug;11(8): Epub 2009 Jun 18. Michiels L, Petrie G, Thollot IG, et al. Treatment of 46 cats with porcine lente insulin a prospective, multicentre study. J Fel Med Surg : Moretti S, Tschuor F, Osto M, et al. Evaluation of a Novel Real-Time Continuous Glucose Monitoring System for use in cats. J Vet Intern Med : 24: Nelson RW, Henley K, Cole C; PZIR Clinical Study Group. Field safety and efficacy of protamine zinc recombinant human insulin for treatment of diabetes mellitus in cats. J Vet Intern Med Jul-Aug;23(4): Niessen SJ.Feline acromegaly: an essential differential diagnosis for the difficult diabetic. J Feline Med Surg Jan;12(1): Rucinsky R, Cook A, Haley S, Nelson R, Zoran DL, Poundstone M; American Animal Hospital Association. AAHA diabetes management guidelines.j Am Anim Hosp Assoc May-Jun;46(3):215-24