Diabetes mellitus is a common endocrine disease in dogs and cats. Clinical signs—characterized by polyphagia, polyuria and polydipsia, and weight loss—reflect hyperglycemia with resultant glucosuria. Diagnosis is based on the documentation of persistent hyperglycemia and glucosuria. Measurement of fructosamine in cats can be helpful to distinguish stress-induced hyperglycemia from diabetes. In both dogs and cats, the treatment is administration of insulin, along with modification of the diet. Remission is possible in cats; in dogs the disease, in the absence of a predisposing disease, is generally lifelong.
Diabetes mellitus is a chronic disorder of carbohydrate metabolism due to relative or absolute insulin deficiency. Most cases of spontaneous diabetes occur in middle-aged dogs and middle-aged to older cats.
In dogs, certain small breeds—such as Yorkshire Terrier, Border Terrier, Cavalier King Charles Spaniel, Bichon Frise, and West Highland White Terrier—are predisposed to diabetes mellitus; however, any dog breed can be affected.
Cats with a body weight > 4 kg seem to have diabetes mellitus more commonly than do cats with a body weight < 4 kg. Breeds such as Tonkinese, Norwegian Forest Cat, Burmese, Russian Blue, and Abyssinian appear predisposed to the disease.
Etiology and Pathogenesis of Diabetes Mellitus in Dogs and Cats
The pathogenic mechanisms responsible for decreased insulin production and secretion are multiple; usually, however, they are related to the destruction of islet cells, secondary to either immune destruction or severe pancreatitis (in dogs) or amyloidosis (in cats). Chronic relapsing pancreatitis with progressive loss of both exocrine and endocrine cells and their replacement by fibrous connective tissue results in diabetes mellitus.
As diabetes mellitus progresses, the pancreas becomes firm and multinodular and often contains scattered areas of hemorrhage and necrosis. Later in the course of the disease, a thin, fibrous band of tissue near the duodenum and stomach may be all that remains of the pancreas. In some cases the number of beta cells is decreased, and the cells become vacuolated; in chronic cases, the islets are difficult to find.
Insulin resistance and secondary diabetes mellitus also occur in many dogs that have spontaneous hyperadrenocorticism or that have been chronically administered glucocorticoids or progestins. Pregnancy and diestrus also can predispose an animal to diabetes mellitus. In dogs, but not cats, progesterone leads to the release of growth hormone from mammary tissue, resulting in hyperglycemia and insulin resistance. Obesity also predisposes both dogs and cats to insulin resistance.
Cats with diabetes mellitus usually have specific degenerative lesions localized selectively in the islets of Langerhans, while the remainder of the pancreas appears normal. The selective deposition of amyloid in islets, with degenerative changes in beta cells, is the most common pancreatic lesion in many cats with diabetes. The amyloid appears to arise from islet-associated polypeptide (IAPP), which is secreted together with insulin from the beta cells.
Cats are unable to process IAPP normally, leading to excessive accumulation and conversion into amyloid. As cats age, a greater percentage of their islets contain amyloid. In cats with diabetes, a greater percentage of islets are affected, with larger amounts of amyloid than in age-matched cats without diabetes. Amyloid or IAPP (or both) leads to physical disruption of beta cells and insulin resistance, resulting in diabetes.
In humans, certain cases of rapidly developing diabetes mellitus have been suggested to be caused by selective islet damage or pancreatitis due to infection with certain viruses. A similar pathogenesis has yet to be documented in dogs or cats.
The selective degeneration and necrosis of beta cells is accompanied by infiltration of the islets by lymphocytes and macrophages. Stress, obesity, and administration of corticosteroids or progestogens may increase the severity of clinical signs.
Complete expression of the complex metabolic disturbances in diabetes mellitus appears to be the result of a bihormonal abnormality. Although a relative or absolute deficiency of insulin action in response to a rising extracellular glucose concentration has long been recognized as the major hormonal abnormality in diabetes mellitus, the importance of an absolute or relative increase of glucagon secretion has come to be understood more recently.
Hyperglucagonemia in diabetes may be the result of the increased secretion of pancreatic glucagon, enteroglucagon, or both. Increased glucagon appears to contribute to the development of severe hyperglycemia by mobilizing hepatic stores of glucose, and to the development of ketoacidosis by increasing the oxidation of fatty acids in the liver.
Diabetic ketoacidosis (DKA) is a form of decompensated diabetes mellitus in which cells use free fatty acids as an energy source because absolute or relative insulin deficiency blocks their access to glucose. In the presence of elevated glucagon and other counterregulatory hormones, free fatty acids are broken down into ketoacids. The accumulation of ketoacids and glucose in the blood leads to metabolic disturbances that can be profound and life-threatening.
Hyperosmolar hyperglycemic state (HHS) is a syndrome of decompensated diabetes mellitus that has a pathophysiology similar to that of DKA. Historically, HHS was distinguished from DKA on the basis of a lack of detectable ketonemia or ketonuria. HHS is now defined as a syndrome of severe hyperglycemia (serum glucose concentration> 600 mg/dL) and hyperosmolality (> 320 mOsm/kg). This syndrome is less common than DKA.
Clinical Findings of Diabetes Mellitus in Dogs and Cats
The onset of diabetes mellitus is often insidious, and the clinical course chronic. Disturbances in water metabolism develop primarily because of an osmotic diuresis. The renal threshold for glucose (ie, the serum glucose concentration above which glucosuria develops) is approximately 180 mg/dL in dogs and approximately 280 mg/dL in cats.
Common clinical signs include the following:
polyuria
polydipsia
polyphagia
weight loss
cataracts (dogs)
weakness
Some dogs and up to 50% of cats with diabetes mellitus have a decreased appetite. Other clinical signs include hepatomegaly, lethargy, cataract formation (dogs), and diabetic neuropathy (mainly cats). Signs are usually slowly progressive over weeks to months.
Diabetic animals have decreased resistance to bacterial and fungal infections and often develop chronic or recurrent infections such as cystitis, prostatitis, bronchopneumonia, and dermatitis. This increased susceptibility to infection may be related in part to impaired chemotactic, phagocytic, and antimicrobial activity associated with decreased neutrophil function.
Radiographic evidence of emphysematous cystitis (rare) due to infections with glucose-fermenting organisms such as Proteus sp, Aerobacter aerogenes, and Escherichia coli, which results in gas formation in the wall and lumen of the bladder, suggests diabetes mellitus. Emphysema also may develop in the wall of the gallbladder in dogs with diabetes.
Hepatomegaly due to lipid accumulation is common with diabetes in dogs and cats. The fatty liver is a result of increased fat mobilization from adipose tissue. Individual liver cells are greatly enlarged by the accumulation of multiple droplets of neutral lipid. In cats, hepatic lipidosis may occur in conjunction with diabetes mellitus.
Cataracts develop frequently in dogs (but not cats) with poorly controlled diabetes mellitus. The lenticular opacities appear initially along the suture lines of lens fibers and are stellate (asteroid) in shape. Cataract formation in dogs is related to the unique sorbitol pathway by which glucose is metabolized in the lens, which leads to edema of the lens and disruption of normal light transmission. Although the same sorbitol pathway seems to be present in cats, cats rarely develop cataracts.
Other extrapancreatic lesions associated with diabetes mellitus in humans, such as nephropathy, retinopathy, and micro- and macrovascular angiopathy, are rare in dogs and cats.
In DKA, as ketoacids and glucose accumulate in the blood, metabolic disturbances include dehydration, hypovolemia, elevated anion gap, metabolic acidosis, electrolyte disturbances, azotemia, elevated liver enzymes, hyperlactatemia, and clinical signs of vomiting and anorexia.
HHS is characterized by profound hyperglycemia (serum glucose concentration > 600 mg/dL) and hyperosmolality (> 320 mOsm/kg), with a normal pH and no or mild ketonemia or ketonuria. In the classical form, animals show no ketosis or acidosis; however, mixed forms occur with severe hyperosmolality compounded by ketoacidosis.
Diagnosis of Diabetes Mellitus in Dogs and Cats
Persistent hyperglycemia
Glucosuria
Elevated serum fructosamine concentration
A diagnosis of diabetes mellitus is based on persistent hyperglycemia and glucosuria. The normal blood glucose concentration in dogs and cats is 75–120 mg/dL (measured after food withholding). In cats, stress-induced hyperglycemia is a common problem, and multiple blood and urine samples may be required to confirm the diagnosis.
Measurement of serum fructosamine concentration can assist in differentiating between stress-induced hyperglycemia and diabetes mellitus. In cases of stress-induced hyperglycemia, the fructosamine concentrations are normal. In all cases, a thorough history should be taken to rule out exposure to drugs or diseases that predispose to diabetes.
Treatment of Diabetes Mellitus in Dogs and Cats
Insulin
Oral hypoglycemic agents
Dietary management
Successful treatment of diabetes mellitus depends on the following factors:
Excellent client communication. Up to 25% of patients with diabetes are euthanized on day 1 of diagnosis, for reasons that can often be mitigated with education about diabetes and goals of treatment.
The administration of basal insulins or oral hypoglycemic agents in cats to improve remission rates.
Appropriate dietary management.
Frequent monitoring, which is often best performed at home.
Longterm success in treating diabetes mellitus depends on the understanding and cooperation of the owner. The treatment consists of a combination of weight loss, dietary management, insulin, and possibly oral hypoglycemics.
Dietary management and weight loss alone will not control diabetes mellitus, so initial treatment with insulin is required.
Treatment of Diabetes Mellitus in Dogs
In general, either neutral protein Hagedorn (NPH) or lente is the initial insulin of choice (starting dosage 0.25–0.5 U/kg, SC, every 12 hours) in dogs. Most dogs require two doses of insulin per day. With twice-daily injections, two meals of equal calories are given, each one immediately before insulin administration.
For dogs with poor glycemic control that are being given NPH or lente insulin, administration of the basal insulin detemir (0.1 U/kg, SC, every 12 hours) should be considered. Because of detemir's potency, clinical signs and glycemic control should be reassessed 1 week after the drug is administered.
In dogs, diets high in fiber and complex carbohydrates are preferred. Diets high in simple sugars (semimoist foods) should be avoided.
It is recommended to spay intact diabetic canine females to achieve insulin regulation.
Treatment of Diabetes Mellitus in Cats
Insulin administration is the treatment of choice for diabetes mellitus in cats. For cats with newly diagnosed diabetes, protamine zinc insulin (PZI; starting dosage 0.25 U/kg [1 U/cat], SC, every 12 hours) and insulin glargine (starting dosage 0.25–0.5 U/kg [1–2 U/cat], SC, every 12 hours) are the most common insulins used (1, 2). They produce comparable glycemic control and remission rates.
Estimated ideal body weight, not actual weight, is used to calculate insulin dosages; starting doses should be conservative, not exceeding 2 U/cat. Cats should be reevaluated 5–7 days after starting treatment before adjustments are made to the insulin dosage, unless hypoglycemia develops. Insulin dosages should not be increased more often than every 1–2 weeks.
The use of NPH or porcine zinc lente insulin as initial treatment for diabetes mellitus is not recommended in cats, because of the short duration of action and poor control of clinical signs in many cats. These treatments may be tried when other alternatives have failed (starting dosage 1–3 U/cat, SC, every 12 hours).
In addition to insulin treatment, a high-protein, low-carbohydrate diet should be initiated in cats with diabetes mellitus. Canned foods are preferred over dry foods.
When treated with a combination of diet modification and insulin, many cats achieve diabetic remission and no longer need insulin treatment.
The administration of oral hypoglycemic agents such as glipizide (2.5 mg/cat, PO, every 12 hours) in combination with dietary management has been evaluated in cats with diabetes. Glipizide is a sulfonylurea that stimulates the release of insulin from functional beta cells. Glipizide should not be administered to thin cats or cats with ketonuria, which are likely to have absolute insulin deficiency and require exogenous insulin administration.
Clinical response to glipizide is observed at 3–4 weeks. Short-term success occurs in 50% of treated cats; the longterm success rate (> 1 year) is approximately 15%.
Other sulfonylureas may also be administered to treat diabetes mellitus in cats—eg, glimepiride (2 mg/cat, PO, every 24 hours) and glyburide (0.625 mg/cat, PO, every 24 hours). Treatment with oral sulfonylureas will likely be eclipsed by treatment with oral SGLT2 inhibitors.
Acarbose (12.5–25 mg/cat, PO, every 12 hours), an alpha-glucosidase inhibitor, has also been used in cats to control hyperglycemia, in conjunction with dietary management and insulin administration.
In 2022, a new class of drugs, known as sodium-glucose transport protein 2 (SGLT2) inhibitors, was licensed for the treatment of cats with diabetes.
SGLT2 proteins are expressed in the proximal tubules of the kidney and are responsible for the resorption of 90% of the glucose from the glomerular filtrate in healthy animals. The SGLT2 inhibitors velagliflozin (1 mg/kg, PO, every 24 hours) and bexagliflozin (15 mg/cat [in cats weighing at least 3 kg], PO, every 24 hours) increase urinary glucose excretion by inhibiting glucose resorption in the proximal renal tubule.
Both velagliflozin and bexagliflozin cause a rapid decrease in blood glucose, decrease the fructosamine concentration, and improve clinical signs of diabetes mellitus in newly diagnosed diabetic cats; however, velagliflozin has been reported to have slightly better results. In one study, glucose and fructosamine were within normal limits at day 180 in > 80% of cats, with 90% of cats showing improvement in polyuria, and 75% showing improvement in polyphagia (3).
SGLT2 inhibitors should be used only in newly diagnosed diabetic cats, because they are most likely to be non–insulin dependent and to have the capacity to secrete some endogenous insulin. SGLT2 inhibitors are contraindicated for cats that were previously treated with insulin and for cats with concurrent diseases like hepatic disease, renal disease, or pancreatitis.
Pearls & Pitfalls
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Blood Glucose Monitoring
Clinical signs and serial blood glucose determinations are used to monitor treatment after initial stabilization at home for 5–7 days. Blood glucose testing is best performed at home to avoid changes in the pet's routine and to minimize the stress of in-hospital testing. Studies in both dogs and cats have shown that at-home monitoring of diabetes mellitus improves glycemic control in both species and increases the likelihood of obtaining remission in cats.
Although blood glucose curves (see Glucose Curve Calculator) can aid in detecting subclinical hypoglycemia, considerable day-to-day variability and the potential for nondetection of nocturnal hypoglycemia complicate their interpretation.
Continuous glucose monitoring (CGM) systems offer a solution by recording interstitial glucose concentrations over extended periods, facilitating the identification of hypoglycemia during the night and providing a more comprehensive assessment of daily trends. At-home CGM systems do not require pet owners to prick the ears or lips of their pets to collect blood, making them easier to use and less stressful for the animals.
CGM systems measure interstitial glucose concentration every 15 minutes for up to 14 days. Although CGM is not specifically calibrated for veterinary patients, it has been successful in both dogs and cats, providing accurate readings in general. However, some patients show marked differences between CGM and blood glucose readings, especially when glucose readings are low. It is therefore advisable to confirm low CGM readings with a blood glucose reading.
Treatment of Diabetic Ketoacidosis
Treatment of DKA focuses on the following:
correcting dehydration by administering IV fluids, such as saline (0.9% NaCl) solution or lactated Ringer’s solution
decreasing hyperglycemia and ketosis by administering crystalline zinc (regular) insulin
maintaining serum electrolyte concentrations, especially potassium and phosphorus, by administering appropriate supplemental electrolyte solutions
identifying and treating underlying and complicating diseases, such as acute pancreatitis or infections
Regular insulin (a potent, short-acting insulin) is most commonly used for acute management of DKA. Patients with DKA are critically ill, and absorption of insulin administered IM and SC depends on factors such as the patient's hydration status. Regular insulin has the advantages of being able to be dosed IV, IM, or SC and enabling doses to be titrated to effect. Insulin lispro (another short-acting insulin) has also been used successfully in dogs and cats with DKA (4, 5, 6, 7).
Numerous insulin regimens have been used in the treatment of DKA, including insulin constant-rate infusion (CRI) and intermittent dosing.
An example protocol for regular insulin infusion in dogs (up to 2.2 U/kg, IV CRI, every 24 hours, titrated to effect) or cats (up to 1.1 U/kg, IV CRI, every 24 hours, titrated to effect) is summarized in the table Regular Insulin Constant-Rate Infusion for Diabetic Ketoacidosis in Dogs and Cats.
In the intermittent dosing regimen, regular insulin is administered at intervals (initial dose 0.2 U/kg, IM, then 0.1 U/kg, IM, every 60 minutes). Once the serum glucose concentration is < 250 mg/dL, a lower dosage (0.1–0.3 U/kg, SC, every 4–6 hours) is administered until glycemic control is achieved. Serum glucose concentration should be closely monitored (measured every 1–2 hours).
During aggressive treatment with insulin, blood glucose concentrations may fall rapidly, and the addition of 2.5%–5% dextrose to IV fluids may be required.
In dogs with DKA, administration of a longer-acting insulin preparation (NPH, lente, or detemir) can be started once the patient is rehydrated and is eating and drinking voluntarily. In cats with DKA, however, studies support the administration of insulin glargine (initially 2 U/cat, SC, then 1 U/cat, IM, 2 hours later; after that, 1 U/cat, IM, every 4 hours as long as blood glucose remains > 250 mg/dL), rather than regular insulin; the results are encouraging (8, 9, 10).
When insulin treatment has been instituted, blood glucose should be checked frequently until an adequate maintenance dose has been determined. Once the animal is on maintenance treatment and its condition is stable, the treatment should be reassessed every 4–6 months.
Treatment of HHS is similar to that for DKA. However, because a rapid change in osmolality can cause cerebral edema, the goal of insulin treatment is to slowly lower glucose (no faster than 50–70 mg/dL/hour). Rehydration of patients with HHS also often requires more conservative fluid therapy. The prognosis for HHS is worse than for DKA.
Key Points
Diabetes mellitus is a common endocrine disorder encountered in clinical practice.
Client education is extremely important.
Long-acting insulins (glargine or protamine zinc insulin [PZI]) are preferred for cats; lente is the insulin of choice for dogs.
At-home monitoring improves the outcome and is well accepted by pet owners.
For More Information
American Animal Hospital Association, 2018 AAHA Diabetes Management Guidelines for Dogs and Cats
American Association of Feline Practitioners (AAFP), Diabetes Educational Toolkit
Also see pet health content regarding diabetes mellitus in dogs, cats, horses, and birds.
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;54(1):1-21. doi:10.5326/JAAHA-MS-6822
Restine LM, Norsworthy GD, Kass PH. Loose-control of diabetes mellitus with protamine zinc insulin in cats: 185 cases (2005-2015). Can Vet J. 2019;60(4):399-404.
Behrend EN, Ward CR, Chukwu V, et al. Velagliflozin, an SGLT2 inhibitor, as once-daily, oral solution, stand-alone therapy for feline diabetes mellitus. J Vet Intern Med. 2023;37(6):2638-2660. doi:10.1111/jvim.16902
Malerba E, Alessandrini F, Grossi G, Giunti M, Fracassi F. Efficacy and safety of intramuscular insulin lispro vs. continuous intravenous regular insulin for the treatment of dogs with diabetic ketoacidosis. Front Vet Sci. 2020;7:559008. doi:10.3389/fvets.2020.559008
Malerba E, Mazzarino M, Del Baldo F, et al. Use of lispro insulin for treatment of diabetic ketoacidosis in cats. J Feline Med Surg. 2019;21(2):115-123. doi:10.1177/1098612X18761696
Anderson JD, Rondeau DA, Hess RS. Lispro insulin and electrolyte supplementation for treatment of diabetic ketoacidosis in cats. J Vet Intern Med. 2019;33(4):1593-1601. doi:10.1111/jvim.15518
Sears KW, Drobatz KJ, Hess RS. Use of lispro insulin for treatment of diabetic ketoacidosis in dogs. J Vet Emerg Crit Care (San Antonio). 2012;22(2):211-218. doi:10.1111/j.1476-4431.2012.00719.x
Zeugswetter FK, Luckschander-Zeller N, Karlovits S, Rand JS. Glargine versus regular insulin protocol in feline diabetic ketoacidosis. J Vet Emerg Crit Care (San Antonio). 2021;31(4):459-468. doi:10.1111/vec.13062
Gallagher BR, Mahony OM, Rozanski EA, Buob S, Freeman LM. A pilot study comparing a protocol using intermittent administration of glargine and regular insulin to a continuous rate infusion of regular insulin in cats with naturally occurring diabetic ketoacidosis. J Vet Emerg Crit Care (San Antonio). 2015;25(2):234-239. doi:10.1111/vec.12269
Marshall RD, Rand JS, Gunew MN, Menrath VH. Intramuscular glargine with or without concurrent subcutaneous administration for treatment of feline diabetic ketoacidosis. J Vet Emerg Crit Care (San Antonio). 2013;23(3):286-290. doi:10.1111/vec.12038
