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    Diabetes in dogs: complications and association with other hormones

    Diabetes mellitus (DM) is a common endocrine disease in dogs characterised by chronic hyperglycaemia resulting from a deficit in insulin secretion, a decline in its action or both.

    Diabetes in dogs: causes

    Diabetes in dogs causes hyperglycaemia because the body cannot balance the amount of glucose it receives, either because the pancreas does not produce enough insulin or the cells in the target tissues and organs do not recognise and respond correctly to the hormone’s action.It is one of the most common health problems in veterinary practiceand affects 1 in 500 dogs.

    Type 1 diabetes is a common disease in dogs and, although its causes are unknown, it has been associated with the total destruction of endocrine pancreas cells which translates into a complete absence of insulin production. In fact, it is estimated that approximately 50% of dogs with diabetes have immune-mediated destruction of pancreatic islets.

    Dogs can also develop type 2 diabetes, which is due to an increasing resistance to the action of insulin in peripheral tissues. 

    Diabetes is most commonly diagnosed in middle-aged and elderly dogs aged 5 to 12 years. 

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    It has been suggested that there is a genetic predisposition both for and against the development of diabetes in dogs. Genetic predisposition plays an important role in the development of diabetes. Medium-sized and intact female dogs are more likely to suffer from this diabetes, although certain breeds are more prone than others (Beagle, Poodle, Smooth-Haired Dachshund, Miniature Schnauzer and Miniature Pinscher).

    However, some environmental factors, such as a poor diet or infectious agents that stimulate an abnormal immune response, can trigger diabetes.

    Obesity, for example, is a risk factor for pancreatitis and, therefore, diabetes. This means that a diet containing too much fat can alter lipid metabolism, encouraging the development of pancreatitis and diabetes in canine patients. In fact, 28% of dogs with diabetes are known to have significant pancreatic damage, probably due to chronic pancreatitis. 

    It is more common among females.  

    In some cases, diabetes in dogs is due to increased levels of progesterone and growth hormone during dioestrous. Given that progesterone induces insulin resistance by reducing the number of insulin receptors or their expression rate, it should not come as a surprise that this phase of the oestrous cycle has been associated with diabetes in dogs. Furthermore, blood glucose levels are higher during dioestrous than in the rest of the oestrous cycle. In addition to this, growth hormone acts as a powerful insulin antagonist.

    Diabetes in dogs: complications

    Diabetes mellitus in dogs can have a high rate of mortality if it is not detected and treated in time. Below is an explanation of the hormonal and acid–base imbalances that underlie diabetes and details of the most appropriate diet to slow its progression.

    Once diabetes is diagnosed, dogs have a mean survival time of 3 years, with the highest peak in mortality occurring within the first 6 months. In fact, 64% of dogs that survive after their condition is initially stabilised also survive the first year. It is therefore essential to diagnose the disease as soon as possible and start treatment.

    Serum ketone and glucose concentrations were significantly higher in dogs with diabetes than in healthy dogs. The anion gap, a parameter connected to metabolic acidosis, was much higher in diabetic dogs and correlated with hyperosmolar syndrome. There are no apparent differences in venous blood pH or acid–base balance. Moreover, the serum bicarbonate concentration was significantly lower in dogs with diabetes.

    One study revealed a significant linear relationship between the indicators of acid–base balance and serum ketone concentration, and also between the latter and the serum insulin:glucagon ratio, serum cortisol levels and plasma norepinephrine concentrations. In fact, serum beta-hydroxybutyrate levels, which are expressed as a percentage of the serum ketone concentration, were found to decrease as serum ketone concentration increased. These results suggest that ketosis in diabetic dogs is linked to the insulin:glucagon ratio, as ketosis can be prevented with just low concentrations of insulin. Acidosis in dogs with ketosis was largely attributed to high serum ketone concentrations.

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    Concurrent hyperadrenocorticism and diabetes in dogs

    Diabetes usually has a high rate of comorbidity with other diseases, one of the most significant being hyperadrenocorticism. Better known as Cushing’s syndrome, this condition is caused by excess cortisol. It is most common among dogs aged 7 to 12 years.

    A study published in Research in Veterinary Science4 analysed the coexistence of diabetes and hyperadrenocorticism, as well as the risk factors involved. After studying 235 dogs with hyperadrenocorticism, the authors reported a 13.61% concurrence with diabetes.

    The researchers noted certain risk factors predisposed the development of both diseases:

    • Fasting blood glucose > 5.6 mmol/L
    • Dyslipidaemia
    • Pituitary-dependent hyperadrenocorticism
       

    They also observed that the onset of diabetes in dogs with hyperadrenocorticism reduced their survival time. Both diseases cause metabolic imbalances that can lead to other health problems.

    Diagnostic difficulties when faced with diabetes and hyperadrenocorticism concurrently

    Diabetes and hyperadrenocorticism are common endocrine disorders in dogs that often occur simultaneously. Since both conditions have similar clinical signs, their diagnosis and treatment can pose a challenge for veterinary practitioners. 

    The most common clinical signs of diabetes and hyperadrenocorticism in dogs are: polyuria, hepatomegaly, polyphagia, abdominal distension, alopecia of the trunk, anorexia and vomiting. Moreover, hyperadrenocorticism causes permanent hyperglycaemia, which can exacerbate the clinical course of diabetes. However, as they yield similar clinical and laboratory findings, hyperadrenocorticism is often overlooked during the early stages. 

    The clinical signs and moderate hyperglycaemia observed in patients with hyperadrenocorticism are both due to cortisol’s antagonism of various functions of insulin; this also causes pancreatic beta cells to secrete more insulin, eventually leading to beta-cell depletion and the onset of diabetes. An article published in Research in Veterinary Science3 looked at changes in carbohydrate metabolism in 60 dogs with untreated hyperadrenocorticism by measuring basal plasma glucose and insulin concentrations and performing glucose and insulin tolerance tests.

    How diet can help keep diabetes in dogs under control

    The evolution of diabetes in dogs depends to a large extent on their diet, so it is important they consume foods specifically formulated to control blood glucose levels. ADVANCE VETERINARY DIETS DIABETES is a complete food for adult dogs with diabetes, it has a total sugars content of just 1.8% and the right amount of starch, which is a decisive factor in the postprandial glycaemic response.

    Its high protein content also helps maintain muscle mass and reduce the animal’s fat deposits. With soluble and fermentable fibres, the diet improves glucose tolerance and facilitates intestinal transit, as demonstrated by a study published in The Journal of Nutrition4, because these ingredients improve the gut’s ability to transport glucose and impact on peptide synthesis in a similar manner to glucagon in type 1 diabetes, and also on insulin secretion.

    Furthermore, the diet is highly palatable, which guarantees its regular and spontaneous consumption, and enriched with an antioxidant supplement to address the oxidative stress underlying the pathophysiology of diabetes in dogs.

    Gastrointestinal physiology of cats and dogs - Parte 3

    References
    Behrend E, Holford A, Lathan P, Rucinsky R, Schulman R. 2018 AAHA Diabetes Management Guidelines for Dogs and Cats. J Am Anim Hosp Assoc. 2018 Jan/Feb;54(1):1-21. doi: 10.5326/JAAHA-MS-6822. PMID: 29314873.
    Davison L. J., Herrtage M. E. & Catchpole B. (2005) Study of 253 dogs in the United Kingdom with diabetes mellitus. Vet. Rec 156: 467-471.
    Graham P. A. & Nash A. S. (1997) Metestrus-associated diabetes mellitus in the dog. Procc. 15th ACVIM Forum.
    Fall T. et al. (2010) Diabetes Mellitus in Elkhounds is Associated with Diestrus and Pregnancy. J Vet Intern Med 24: 1322–1328.
    Gilor C, Niessen SJ, Furrow E, DiBartola SP. What’s in a Name? Classification of Diabetes Mellitus in Veterinary Medicine and Why It Matters. J Vet Intern Med. 2016 Jul;30(4):927-40. doi: 10.1111/jvim.14357. PMID: 27461721; PMCID: PMC5108445.
    Tardo AM, Del Baldo F, Dondi F, Pietra M, Chiocchetti R, Fracassi F. Survival estimates and outcome predictors in dogs with newly diagnosed diabetes mellitus treated in a veterinary teaching hospital. Vet Rec. 2019 Dec 7;185(22):692. doi: 10.1136/vr.105227. Epub 2019 Oct 3. PMID: 31582571.
    Catchpole, B. et al. (2005) Canine diabetes mellitus: can old dogs teach us new tricks? Diabetologia; 48(10): 1948-1956.
    Peterson, M. E. et al. (1981) Diagnosis and management of concurrent diabetes mellitus and hyperadrenocorticism in thirty dogs. J Am Vet Med Assoc; 178(1): 66-69.
    Miceli, D. D. et al. (2017) Concurrent hyperadrenocorticism and diabetes mellitus in dogs. Res Vet Sci; 115: 425-431.