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Feline Diabetes Mellitus Updates on Diagnosis & Treatment David Bruyette, DVM, Diplomate ACVIM, and Karen Eiler, DVM, MS, Diplomate ACVIM

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Feline Diabetes Mellitus Updates on Diagnosis & Treatment David Bruyette, DVM, Diplomate ACVIM, and Karen Eiler, DVM, MS, Diplomate ACVIM PEER REVIEWED FELINE DIABETES MELLITUS Updates on Diagnosis & Treatment David Bruyette, DVM, Diplomate ACVIM, and Karen Eiler, DVM, MS, Diplomate ACVIM Feline Friendly Article iabetes mellitus (DM) is a commonly encoun- tinction to Type II DM in which the cause of insulin tered feline endocrine disease.1 DM is defined resistance is often unknown. as persistent hyperglycemia and glycosuria Ddue to an absolute or relative insulin defi- PATHOGENESIS ciency. The most common causes of feline DM are: Amylin, also known as islet amyloid polypeptide • Islet cell amyloidosis (IAPP), is synthesized in the Islets of Langerhans and • Obesity co-secreted with insulin. In cats with insulin resis- • Chronic pancreatitis. tance, amylin and insulin secretion increase concur- rently. Over time, amylin overproduction progresses CLASSIFICATION to diabetes due to 2 phenomena: Insulin is secreted exclusively from beta cells in the 1. Amylin can be enzymatically converted to amyloid, pancreas’ Islets of Langerhans. Insulin deficiency which has a direct cytotoxic effect on islet cells.5 occurs when beta cells are destroyed or their function 2. In addition, amylin itself inhibits further insulin impaired, and the pathogenesis of beta cell dysfunc- secretion in a paracrine effect.5 tion is used to classify DM. Both contribute to initial glucose intolerance and, In humans, DM is classified as: eventually, overt hyperglycemia and glucosuria. • Type I (insulin dependent): Results from autoim- mune damage to the Islets; associated with complete DIAGNOSIS lack of insulin DM is diagnosed based on clinical signs and laboratory • Type II (noninsulin dependent): Characterized by testing. abnormal insulin secretion and peripheral insulin resistance Clinical Signs • Gestational, congenital, neonatal, or monogenic. DM is typically diagnosed once blood glucose (BG) Most feline diabetics have type II DM,2 and may have exceeds renal threshold (mean threshold, 290 mg/dL6), underlying susceptibilities to this type due to genetic resulting in osmotic diuresis and compensatory poly- predisposition and decreased insulin sensitivity (seen dipsia. Other classical clinical signs include polyphagia with obesity).3,4 and weight loss. Type III DM is similar to impaired glucose tolerance in humans. Medications or diabetogenic hormones Basic Laboratory Evaluation (epinephrine, cortisol, glucagon, and growth hormone) Baseline laboratory evaluation should include a serum interfere with the action of insulin, result in glucose biochemistry profile, CBC, urinalysis, and urine cul- intolerance, and ultimately lead to DM. This is in dis- ture. Diabetic patients frequently have urinary tract 10 Today’s Veterinary Practice July/August 2013 FELINE DIABETES MELLITUS: UPDATES ON DIAGNOSIS & TREATMENT | detemir (Levemir, novonordisk-us.com) TABLE 1. Feline Diabetes Mellitus: Common • Long acting: Human recombinant prot- Biochemical Abnormalities & Causes amine zinc (PZI) (ProZinc, boehringer-ingel- heim.com) Test Abnormalities Cause • Intermediate acting: Lente (Vetsulin, Complete Often unremarkable Dehydration merck.com), which was recently reintro- Blood Count Hemoconcentration duced to the veterinary market, and neu- Serum Elevated alanine Biliary disease/ tral protamine Hagedorn (NPH) (Humulin Biochemical transaminase pancreatitis N, lilly.com, or Novolin N, novonordisk-us. Profile Elevated alkaline Hepatic lipidosis/ com). phosphatase hepatitis For dosing recommendations, see Table 2, Elevated bilirubin Pancreatitis/lipidosis page 12. Hyperglycemia Urinalysis Active sediment Urinary tract infection ULTRA LONG-ACTING INSULINS (indicating infection) Blood glucose in excess Glargine Glucosuria of renal threshold Glargine is a long-acting insulin analogue Ketonuria Ketogenesis that is designed to provide basal insulin con- centrations in humans. It remains soluble in acidic solutions but forms precipitates in the infections even in the absence of active urine sediment neutral environment of subcutaneous tissue. The change (Table 1).7 in pH associated with precipitation contraindicates dilut- Transient hyperglycemia may be caused by stress, dia- ing or mixing glargine for administration. betogenic hormones, and post prandially in animals with Efficacy. Glargine has been shown to be effective in glucose intolerance. Cats are particularly sensitive to stress felines with DM. A recent study compared the glycemic hyperglycemia due to catecholamine release.8 control and remission probabilities in 24 newly diagnosed diabetic cats treated twice daily with either glargine, PZI, Fructosamine Evaluation or lente insulin and fed a low-carbohydrate diet.9 Fructosamine is formed when glucose reacts with amino • Probability of remission was substantially higher for cats acids of serum proteins, such as albumin. In hyperglyce- with lower mean 12 H BG concentrations on day 17, mic states, levels of fructosamine increase. Fructosamine irrespective of insulin type.9 levels can be used for several purposes: • In this small study, cats treated with glargine had better • To help confirm a diagnosis of DM glycemic control and higher probability of remission • To monitor persistent hyperglycemia; levels above than those treated with PZI or lente insulin.9 However, the reference range indicate persistent hyperglycemia further studies with larger numbers of cats are needed and, therefore, help differentiate diabetes from other before it can be concluded that glargine is more effec- causes of transient hyperglycemia. tive at achieving remission than other insulins. • To evaluate response to treatment; in well-controlled • In a different study of owner responses on an online diabetics, fructosamine is often in the low end of the forum, a remission rate of 84% was noted in patients reference range or normal. treated with glargine within 6 months of diagnosis; cats treated with glargine 6 months after diagnosis achieved Total Thyroxine Evaluation a 35% remission rate. Caution should be exercised not Total thyroxine levels should be evaluated to rule out to overinterpret owner reports that were not confirmed hyperthyroidism as a cause for insulin resistance. by a veterinarian.10 INSULIN OVERVIEW Several types of insulin are available for use in diabetic GOALS OF TREATMENT cats. • Minimize clinical signs • Ultra long acting: Glargine (Lantus, sanofi.us) and • Avoid complications, such as diabetic ketoacidosis and peripheral neuropathy CLINICAL SIGNS OF CONCURRENT/ • Avoid symptomatic SECONDARY DISEASE hypoglycemia • Cats may present with icterus due to concur- • Maintain owner rent hepatic lipidosis or pancreatitis. compliance with treatment • A plantigrade stance may be noted secondary regimen and follow-up to prolonged or severe hyperglycemia, result- • Achieve patient quality of life ing in a peripheral neuropathy. • If possible, achieve diabetic remission July/August 2013 Today’s Veterinary Practice 11 | FELINE DIABETES MELLITUS: UPDATES ON DIAGNOSIS & TREATMENT » Pre-insulin BG concentration is < 180 mg/dL and/or Diabetic remission is defined as the ability to » Nadir BG concentration is 54 to 90 mg/dL (4-hour maintain euglycemia without insulin for 2 to 4 weeks post insulin injection). after insulin therapy has been discontinued, without » If the nadir BG concentration is < 54 mg/dL, the next the reappearance of clinical signs of diabetes. dose of insulin can be skipped rather than taking Remission appears more likely to occur if: the chance of an overdose. If the total insulin dose is • Blood glucose levels are strictly controlled using already 1 unit Q 12 H, stop the insulin (or administer insulin 1 unit Q 24 H) and evaluate for diabetic remission. • Cats are fed a low-carbohydrate diet. Additional Notes. The manufacturer recommends dis- At least 25% to 30% of cats that have achieved carding opened vials after 4 weeks of use; however, if refrig- remission subsequently relapse into overt diabetes erated, opened vials can be used for 6 months (unless and need reinstitution of insulin treatment. In these discoloration is noted). cats, a second remission is unlikely to be achieved and permanent insulin therapy is usually needed. DETEMIR Good glycemic control soon after diagnosis is Detemir, like glargine, is a basal human insulin analogue associated with increased probability of remission and binds reversibly to albumin, resulting in a long dura- and should be the goal of insulin therapy.10,11 tion of action. It has been demonstrated to be effective in the treatment of feline DM and is also associated with remis- sion in cats that receive at-home, intensive BG monitoring. Monitoring. Because glargine is a basal insulin, 4-hour Efficacy. Another recent study of owner results collected post injection BG monitoring can be performed. If per- through an online forum evaluated detemir and a protocol forming a 12-hour BG curve (BGC), samples can be drawn of intensive BG control with home monitoring in diabetic cats, and compared the results with a previous study that every 4 hours. This type of monitoring is inappropriate for used the same protocol with glargine.12 nonbasal insulins, such as NPH or recombinant PZI. • The study included 18 cats diagnosed with diabetes and • Increase insulin dose by 1 unit Q 12 H if: previously treated with other insulins. » Pre-insulin BG concentration is > 216 mg/dL and/or • No significant differences were identified between the » Nadir BG concentration is > 180 mg/dL (often at glargine and detemir studies, with the exception of 3 4-hour post insulin injection). possibly interrelated
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