Diabetes mellitus

From Felipedia

Major physiological disturbances in feline diabetes mellitus.

Regulation of insulin secretion by glucose in pancreatic beta-cells

Adult onset diabetes mellitus (DM) is a complex and common endocrine disorder in the cat that results in excess blood glucose (hyperglycaemia; the converse being hypoglycaemia). It is clinically distinct from central diabetes insipidus (CDI), which often occurs in young animals.

DM is caused either by insufficient production of the hormone, insulin, by the pancreas (Type 1 diabetes) or by inadequate response of the body's cells to insulin secretion (Type 2 diabetes). Obesity is a common cause of insulin resistance which leads to diabetes and therefore, nutrition plays a pivotal role in prevention and treatment of this disease^[1].

Because diabetic cats are not able to utilize glucose properly, they ultimately develop hyperglycaemia (high blood sugar levels) and subsequent glucosuria (sugar in the urine). The glucosuria leads to polyuria (excessive urination) and polydipsia (excessive thirst). In spite of maintaining a good appetite, diabetic cats lose weight because the body's tissues are unable to utilize glucose properly. Progression of the disease ultimately leads to further metabolic disturbances and causes vomiting, loss of appetite, weakness, and dehydration. Although affecting cats of any breed, sex, or age, diabetes mellitus most often occurs in older, obese individuals; males are more commonly afflicted than females. The exact cause of the disease in cats is not known, although genetic predisposition, obesity, pancreatic disease, hormonal imbalances, and certain medications have all been incriminated. After a period of time, a small percentage of diabetic cats lose their requirement for specific therapy with either insulin or hypoglycaemic medications^[2].

In human diabetes, Type 1 refers to the condition seen in people who are generally lean, young and prone to ketogenesis. Type 2 DM usually occurs in older humans who are often obese but is less prone to the development of ketogenesis.. Type 1 DM patients require insulin therapy while Type 2 may be controlled at least initially with weight loss, diet and oral hypoglycaemic agents.

In cats, the classification is not as clear. Generally, diabetes is a disorder of the older, often overweight cat, more similar to the Type 2 DM in humans. However, often by the time the diagnosis of diabetes is made, the cats are insulin dependant although most are not prone to ketogenesis. In addition to these differences, cats may develop diabetes secondary to primary pancreatic disease, endocrinopathies (acromegaly or hyperadrenocorticism), or drug therapy (glucocorticoids and progestins). Insulin resistant diabetes may develop as a consequence of hyperadrenocorticism, acromegaly and pituitary adenomas^[3].

In Type 1 DM, there is beta cell depletion, resulting in absolute insulin deficiency. In Type 2 DM, the problem is one of insulin receptor and post-receptor defects, causing impaired insulin uptake by tissues. This insulin resistance and associated hyperglycaemia causes the beta cells to produce more insulin. This state is one of relative insulin deficiency. Obese cats appear to have a defect in insulin secretion along with a lower tissue sensitivity to insulin. Weight loss results in an improvement in tissue sensitivity, thus weight loss is not only helpful but also imperative in treatment.

Etiology

Until the 1970s, diabetes mellitus was a relatively rare disease in cats. The relationship between commercial high-carbohydrate diet and the onset of diabetes mellitus cannot be ignored.

Oxidative stress is thought to be a key component in the pathophysiology of type 2 DM in humans. As one source of an increase in the production of oxidative free radicals is the metabolic response to hyperglycemia, the use of high protein-low carbohydrate diets in diabetic cats may lead to a significant reduction in oxidative stress (Webb & Falkowsji, 2009). Oxidative stress may affect neutrophil lifespan, and phagocytic cell function may be negatively impacted by oxidative stress in patients with DM, resulting in a decrease in their ability to prevent or eliminate infection.

• Diabetes and glucocorticoids
• Glucose metabolism in cats
• Physiology of diabetes
• Transient diabetes in cats
• Somogyi Effect in feline diabetes mellitus
• Glucotoxicity, Lipotoxicity, and Glucolipotoxicity
• Glucagon's role in diabetes mellitus
• Amylin in diabetes mellitus
• Pancreatic amyloidosis

Clinical Signs

Polyuria, polydipsia, increased appetite, and weight loss are hallmark signs of diabetes mellitus in cats. In the earlier stages of the disease, cats remain active and alert with few other signs of disease. However as the disease progresses, poor skin and hair coat, liver disease, and secondary bacterial infections become more common.

Urinary tract infections develop in about 15% of diabetic patients^[4].

Life-threatening diabetic ketoacidosis (DKA), hyperosmolar hyperglycaemic state (HHS) and insulin-induced hypoglycaemia may develop in some diabetic cats. Without proper and prompt treatment, this condition ultimately proves fatal. Risk factors include body weight >7kg, older age (>10 years), male gender and neutered. Unlike humans, cats do not normally have hypertension associated with diabetes^[5].

Other clinical signs associated with feline diabetes mellitus include:

• diabetic neuropathy
• diabetic retinopathy and cataract
• metabolic epidermal necrosis
• sorbitol accumulation

Diagnosis

Diabetes mellitus is diagnosed based on the cat's clinical signs, physical examination findings, laboratory test results, and the persistent presence of abnormally high amounts of sugar in the blood and urine. In stressed patients, adrenalin release causes hyperglycaemia and glucosuria. It is essential to differentiate between stress response and diabetes^[6].

• Urinalysis

The presence of glucose in the urine (glucosuria) is associated with a blood glucose level greater than 15 mmol/L. any glucose in the urine is abnormal and often is an indicator of diabetes. Other conditions such as fanconi syndrome can also cause glucosuria.

• Blood sugar

Blood sugar reading below 10 mmol/L are considered normal. Levels of glucose >10mmol/L may be seen in severe physiological stress but may be an indicator of diabetes.

• Fructosamine assay^[7].

Treatment

• Diet
• Oral hypoglycaemic drugs - rarely used in cats, and shown to be poorly effective at regulating hyperglycaemic states
• Acarbose - the alpha-glucosidase inhibitors (eg, acarbose) reduce intestinal glucose absorption (Greco 1999) and are generally not effective in the treatment of feline diabetes alone, but can be used in conjunction with insulin and/or other oral agents to gain better glycemic control . Cats given acarbose and fed a low carbohydrate diet had a reduced insulin requirement and improved glycaemic control, but similar results were achieved feeding the low carbohydrate diet alone.
• Insulin - recent studies show that treatment with Glargine (Lantus) results in a higher probability of remission compared to PZI or lente insulin^[8].
• Problems cats that fail to stabilise on insulin

A diabetic cat may live many healthy years with owners who are willing to put forth the effort of monitoring the cat's condition daily. Cats tend to be difficult to maintain on the same regimen for long periods of time, and increases or decreases may need to be made in drug dosages.

References

1. ↑ Miller E (1995) Long-term monitoring of the diabetic dog and cat. Clinical signs, serial blood glucose determinations, urine glucose, and glycated blood proteins. Vet Clin N Am Small Anim Pract 24:571-585
2. ↑ Nelson R (2000) Diabetes Mellitus. In: Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine. Diseases of the Dog and Cat, 5th ed. Philadelphia, W.B. Saunders Co. p. 1443
3. ↑ Scherk, M (2007) Focus on feline medicine, PGFVSc Conference proceedings, University of Sydney, NSW, Australia
4. ↑ Bailiff, NL et al (2006) Frequency and risk factors for urinary tract infection in cats with diabetes mellitus. J Vet Intern Med 20:850
5. ↑ Hess, RS (2010) Diabetic emergencies. In August, JR (Ed): Consultations in feline internal medicine. Vol 6. Elsevier Saunders, Philadelphia. pp:297
6. ↑ Webb, CB & Falkowski, L (2009) Oxidative stress and innate immunity in feline patients with diabetes mellitus: the role of nutrition. JFMS 11:271-276
7. ↑ Graham PA, Mooney CT, Murray M (1999) Serum fructosamine concentrations in hyperthyroid cats. Res Vet Sci 67:171-175
8. ↑ Rand, JS (2010) Use of long-acting insulin in the treatment of diabetes mellitus. In August, JR (Ed): COnsultations in feline internal medicine. Vol 6. Elsevier Saunders, Philadelphia. pp:286