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An Urban Experience
Glucose and lipid toxicity
Once persistent hyperglycaemia occurs, insulin secretion is reduced through a phenomenon termed glucose toxicity. There is evidence that initially, suppression
of insulin secretion is functional and reversible. With hyperglycaemia of longer than 2 weeks duration, histological abnormalities are evident, including
glycogen deposition and cell death. The severity of the glucose toxicity effect is dependent on the degree of hyperglyceamia and the duration.
Increased fatty acids produce a similar effect to glucose toxicity, called lipotoxicity.
The clinical implications of glucose and lipid toxicity are very important. It is vital that hyperglycemia is reduced as soon as possible in diabetic cats, if beta cell function is to be preserved. Most cats will undergo remission of their diabetes, if the effects of glucose toxicity are minimised.
Insulin resistance and chronic hyperglycemia
Chronically elevated blood glucose also causes insulin resistance. This has implications for therapy, because once glucose concentrations are decreased with treatment, insulin sensitivity may improve.
Diabetic remission or transient diabetes
Diabetic remission occurs in up to 90% of newly diagnosed cats if treated appropriately. Remission occurs most commonly after 1 to 4 months of insulin therapy, and is more likely if glycaemic control is optimum, so beta cells can recover from glucose toxicity. Therefore, insulin therapy is recommended as the initial therapy
to maximise control of blood glucose and increase the probability of remission.
Clinical Signs and Diagnosis
There are no internationally agreed criteria for diagnosis of diabetes mellitus in cats. Clinical signs such as polydypsia/poly- uria, weight loss, or polyphagia are non-speci c, and diagnosis cannot be con rmed on clinical examination. Diagnosis in cats is often complicated by stress hyperglycaemia, which in sick non-diabetic cats may lead to glycosuria or blood glucose levels in excess of 360 mg/dL (20 mmol/L). Blood glucose in non-dia- betic unstressed client-owned cats is usually less than 171 mg/ dL (9.5 mmol/L), however struggling can transient hyperglyce- mia as high as 288 mg/dL (16 mmol/L) in normal cats. Blood glu- cose should be measured several hours after the  rst sample to con rm persistent hyperglycemia. Signs of diabetes occur once blood glucose concentration exceeds the renal threshold, which is approximately 250-288 mg/dL (14-16 mmol/L) for normal cats.
Fructosamine may be useful in assisting diagnosis, especially when typical clinical signs of diabetes are not present. However, false positive and negative results can occur. A fructosamine level of greater than 400 μmol/L in a cat strongly supports a diagnosis of diabetes.
Measurement of water intake is inexpensive and useful for con rming polydypsia once blood glucose is above the renal threshold. In normal cats, total water intake including water in food ranges from 60 to 100 mL/kg/24h, but average water drunk
is approximately 20 mL/kg or less.
If there is doubt whether the hyperglycemia 270 mg/dL (15 mmol/L) is transient and associated with stress or is from diabetes, in sick cats it is prudent to begin insulin therapy and monitor glucose concentrations carefully for the next few days. Reducing glucose concentrations with exogenous insulin reduc- es the suppressive effect of glucose toxicity and makes recov- ery of beta cells more likely. Therapy for the underlying disease can then be instituted and glucose concentrations monitored to adjust insulin dose.
Ketoacidosis occurs in approximately 12 – 37% of diabetic cats at the time of diagnosis, and a smaller percent are ketotic without acidosis. Ketoacidosis results in depression, vomiting and anorexia. Ketoacidosis
can be precipitated by concomitant disease, especially infection. However, once cats become markedly insulinopaenic, even previously normal cats progress to ketosis within 10 – 30 days. In experimentally induced diabetes, ketonaemia occurred on average 5 days before ketonuria was detected using a urine test strip. Although ketotic cats usually have low insulin concentrations, with appropriate therapy to overcome glucose and lipotoxicity, some beta cell function may return, and many of these cats achieve remission.
Principles of therapy
Therapy for diabetes should be instituted as soon as possible after diagnosis and administration of insulin and dietary modi cation are the principal therapies. The main aim of therapy is to achieve exemplary glycaemic control to facilitate remission. In cats in which remission is not possible, resolution of clinical signs and avoidance of clinical hypoglycaemia are the goals. Oral hypoglycaemic drugs are not recommended unless blood glucose is persistently elevated but in the prediabetic range (< 10 mmol/; 180 mg/dL). A recent study has shown that
if good glycaemic control is achieved early in newly diagnosed diabetic cats, very high remission rates occur within 8 weeks of treatment. Good glycaemic control reverses the glucose toxicity suppressing beta cells, and maximises the chance of preserving beta cell function and achieving diabetic remission.
Understanding the pathogenesis of feline diabetes is important for good patient management, and may help to decrease the incidence of diabetes.

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