DIABETES MELITUS

Overview

 

• Diabetes mellitus is a condition that is shaped by the body’s inability to regulate sugar in the bloodstream. This disease is caused by a deficiency in the hormone insulin.  

• Insulin is secreted by the pancreas, an organ in the digestive system, to control the amount of sugar (glucose) going into cells that need it for energy. Without enough insulin, sugar stays in the bloodstream, leading to higher blood sugar levels (hyperglycemia). The body’s cells then become starved for energy, and so they start making energy by breaking down stores of protein and fat.  

• Over time, uncontrolled high blood sugar can lead to cataracts (cloudy eye lenses), or a life-threatening condition called diabetic ketoacidosis (DKA). This is a medical emergency that causes the dog's blood to become too acidic (acidosis), and without prompt treatment, DKA can be fatal. 

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Symptoms and Types

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 is approximately 180 mg/dL in dogs and approximately 240 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. 

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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.

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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.

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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.

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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.

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Other extrapancreatic lesions associated with diabetes mellitus in humans, such as nephropathy, retinopathy, and micro- and macrovascular angiopathy, are rare in dogs and cats.

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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.

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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.

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Diagnosis

• 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

• Insulin

• Oral hypoglycemic agents

• Dietary management​

  • Successful treatment of diabetes mellitus depends on the following factors:

  • 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.

    • 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.

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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

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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.

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Numerous insulin regimens have been used in the treatment of DKA, including insulin constant-rate infusion (CRI) and intermittent dosing.

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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.

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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.

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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.

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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.

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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.

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References

1. 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

2. 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.

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

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