By Caitlan Koontz, DVM
Diabetes mellitus is a commonly diagnosed endocrine disorder in dogs. In humans, diabetes is classified most simply as type I or type II based on the pathophysiology of the disease and requirement for exogenous insulin. Diabetes in our canine patients most closely resembles type I diabetes, however, it is more appropriately classified as “insulin-dependent diabetes mellitus” (IDDM) as nearly all diabetic dogs necessitate daily insulin therapy.1 In the insulin-dependent diabetic dog, there is a relative or absolute deficiency of insulin. The etiologies vary but generally include a combination of genetic predisposition, immune-mediated destruction of beta islet cells, pancreatitis, and concurrent diseases and environmental factors leading to beta cell destruction and/or insulin resistance.1 A few breeds at higher risk for developing diabetes include the Schnauzer, Toy and Miniature Poodle, Terrier breeds and mixes, Beagle and Dachshund.3
The most common clinical signs of diabetes in the dog include polyuria (PU), polydipsia (PD), polyphagia and weight loss.1 Insulin deficiency and resistance lead to hyperglycemia due to decreased tissue utilization of glucose. Tissues are essentially “starved” of glucose thus stimulating hepatic gluconeogenesis and glycogenolysis, worsening the hyperglycemia. Glucose from circulation spills over into the urine as the threshold for reabsorption of glucose by the renal tubules is exceeded. Glucose in the urine acts as an osmotic diuretic, leading to polyuria and subsequent polydipsia. In the untreated or poorly regulated diabetic dog where these common clinical signs are mild or go unnoticed by the owner, diabetic ketoacidosis (DKA) may ultimately develop (DKA will be discussed further in the following paragraphs). Many canine patients often present to their general practitioner or an emergency service suffering from DKA. Common clinical signs include lethargy or weakness, hyporexia or anorexia, vomiting, labored breathing and collapse.2
Diabetes in the dog is diagnosed in a variety of situations. Hyperglycemia may be discovered incidentally on routine blood work, or a patient may be presented to their veterinarian for the common clinical signs, particularly PU/PD. In these patients, the diagnosis is ultimately made based on the presence of persistent fasting hyperglycemia and glycosuria.1 In patients who are suffering from diabetic ketosis or ketoacidosis, the diagnosis is usually rapidly made based on the presence of marked hyperglycemia, ketonuria and metabolic acidosis.2 When hyperglycemia is mild, or to clarify discrepancies on serial blood glucose (BG) measurements and differentiate stress from true hyperglycemia, serum fructosamine may be measured.1 Various other ancillary tests exist including measurement of serum insulin concentrations and anti-beta cell autoantibodies.5 Physical exam abnormalities are often absent in the otherwise healthy, non-ketotic patient, however, muscle wasting, thin body condition, cranial organomegaly, poor hair coat and mild dehydration may be present.1 In the sick, undiagnosed diabetic patient who may be suffering from diabetic ketoacidosis, additional exam findings often include more severe dehydration and evidence of hypovolemia such as tachycardia and poor pulse quality, dull mentation and generalized weakness, sweet-smelling breath that resembles acetone, nausea, abdominal pain and slow deep breathing (Kussmaul respiration).2
Treatment of the newly diagnosed diabetic dog depends on whether the patient is ketotic or not. For the purposes of this review, we will focus on beginning insulin therapy in the non-ketotic patient. For the dog suffering from diabetic ketosis or ketoacidosis, hospitalization at a 24-hour facility is recommended. These patients require short-acting regular insulin in the initial treatment period to eliminate ketones and correct what it usually a marked hyperglycemia. IV fluids and supplemental electrolytes are generally required to correct dehydration, and acid/base and electrolyte derangements. Supportive care for other clinical signs or concurrent diseases is also often required. In the non-ketotic patient, intermediate-acting insulin can be started, assuming the patient is eating well and any concurrent diseases have been identified and managed. There are several types of intermediate-acting insulins. The two most commonly used in dogs include porcine lente insulin (Vetsulin) and recombinant human NPH insulin, with porcine insulin having a slightly longer duration of action.3 Porcine insulin has the same amino acid sequence as canine insulin, and thus could be considered the more appropriate choice as it theoretically would be less likely to stimulate insulin auto-antibodies.4 However, recombinant human sourced insulin is very similar and a study showed only 5% of dogs treated with it developed antibodies.1 Determining which insulin to use ultimately depends on availability, personal preference and patient response (i.e. control of hyperglycemia and associate clinical signs at home). The recommended starting dosage for intermediate-acting insulin is 0.25U/kg twice a day, however, higher doses are often eventually required especially in patients with concurrent illnesses or environmental factors causing insulin resistance.1 Insulin therapy should be initiated in hospital and blood sugars monitored using a typical BG curve over 12-24 hours. The goal at this time is not to obtain perfect glycemic control and the client should be informed that this ultimately can take a month or longer. During the initial treatment period and first BG curve, the objective is to identify the nadir (lowest BG reading) and at what time during the day it occurs. If the nadir is less than 80mg/dL, the insulin dose should be reduced.1,3 If the nadir is greater than 150mg/dL, the dose should be increased.1,3 A safe unit of increase is approximately 1U/injection, however, the size of the dog should be considered and the exact U/kg dose calculated.6 If the dose exceeds 1U/kg without adequate glycemic control, it is likely that there are other factors such as concurrent illness or improper insulin handling at play and these causes should be investigated.3 The nadir should ideally fall between 100 – 125mg/dL.3 The duration of effect of the insulin should also be evaluated on the BG curve. If the duration is less than 10 hours, a longer acting insulin should be used (i.e. if NPH is being used, the insulin could be switched to Lente) and vice versa if the duration of action is longer than 14 hours.1,3 The long term, ideal BG concentrations in a well-controlled diabetic dog should fall between 100 and 250mg/dL.1,3 After an initial dose is determined and the patient is discharged, a recheck BG curve should be scheduled for the following week, and either weekly or biweekly thereafter until adequate glycemic control is achieved and the owner sees resolution of clinical signs at home. Gradual increases in insulin doses and close monitoring is important to avoid complications including hypoglycemia and Somogyi response. Dietary and lifestyle adjustments are also important when managing the newly diagnosed diabetic dog and should be maintained long term. Typical diets recommended for the diabetic dog are those high in fiber and low in fat. The main mechanisms by which these diets help improve glycemic control include the fiber creating a viscous gel within the intestine and thus inhibiting absorption of glucose and delayed gastric emptying; thus, delayed absorption of nutrients.1 The higher the percent crude fiber, the lower the calorie content. Therefore, these diets should be used with caution in thin or underweight diabetic dogs. However, they are important and effective in overweight or obese patients. Regular exercise should also be implemented as it helps promote weight loss and thus reduce the insulin resistance brought on by obesity, and help mobilize insulin from the site of injection.
Despite seemingly straight forward therapeutic recommendations, diabetes can be a very difficult disease to treat and control in dogs (and cats). As mentioned briefly above, several complications can occur. Hypoglycemia can be seen with large increases in insulin or overlap of insulin action in dogs being treated twice daily, after excessive exercise or when there is significant hyporexia/anorexia, vomiting or diarrhea. Insulin overdosage can lead to hypoglycemia and subsequently the Somogyi response which is where the body secretes insulin counter-regulatory hormones such as glucagon, cortisol and epinephrine in response to hypoglycemia.1 This leads to a profound hyperglycemia. 12-hour BG curves are important if the Somogyi response is suspected as increasing the insulin dose based on a single BG measurement where significant or worsening hyperglycemia is found can ultimately be deleterious. Correcting the Somogyi response requires decreasing the insulin dose.
Diabetic ketoacidosis is a condition more commonly encountered in the undiagnosed or untreated diabetic, but can occur in underdosed and poorly regulated diabetic dogs especially when there is concurrent illness causing insulin resistance. With DKA, the body mobilizes stored fat to be used as an energy source. The metabolism of stored fatty acids results in the production of ketone bodies, which are acidic, and accumulation can lead to a metabolic acidosis and profound illness. As discussed above, dogs suffering from DKA require hospitalization and 24-hour care to correct the acidosis and eliminate the ketones. Other complications commonly encountered when treating the diabetic dog include concurrent illnesses or conditions that induce insulin resistance. Some examples include infection such as urinary tract infections, pancreatitis, hyperadrenocorticism, hypothyroidism, diestrus in intact female dogs, and renal and liver insufficiency.3 Use of diabetogenic drugs (most commonly glucocorticoids) will also make glycemic control difficult. Thus, when diagnosing diabetes and initiating insulin therapy, a full systemic work-up and control or correction of these diseases and conditions must be made a priority.
The prognosis of dogs with diabetes depends on a variety of factors including age, ease of glycemic control, owner compliance and willingness to treat, and control or reversal of concurrent illnesses. Long term complications and quality of life are also important factors. However, with good glycemic control, proper care by the owners at home and regular veterinary rechecks, the diabetic dog can lead a generally happy and healthy life.
1 Feldman, Edward C., and Richard William Nelson. “Chapter 11: Canine Diabetes Mellitus.” Canine and Feline Endocrinology and Reproduction, 3rd ed., Saunders, 2004, pp. 486–538.
2 Feldman, Edward C., and Richard William Nelson. “Chapter 13: Diabetic Ketoacidosis.” Canine and Feline Endocrinology and Reproduction, 3rd ed., Saunders, 2004, pp. 580–615.
3 Nelson, Richard W., and C. Guillermo. Couto. “Chapter 52: Disorders of the Endocrine Pancreas.” Small Animal Internal Medicine, 5th ed., Mosby, 2014, pp. 780–815.
4 Monroe, William E., et al. “Efficacy and Safety of a Purified Porcine Insulin Zinc Suspension for Managing Diabetes Mellitus in Dogs.” Journal of Veterinary Internal Medicine, vol. 19, no. 5, 2005, pp. 675–682., doi:10.1111/j.1939-1676.2005.tb02745.x.
5 Davison, L.j., et al. “Anti-Insulin Antibodies in Diabetic Dogs Before and After Treatment with Different Insulin Preparations.” Journal of Veterinary Internal Medicine, vol. 22, no. 6, 2008, pp. 1317–1325., doi:10.1111/j.1939-1676.2008.0194.x.
6 Hess, Rebecka S., and Cynthia R. Ward. “Effect of Insulin Dosage on Glycemic Response in Dogs with Diabetes Mellitus: 221 Cases (1993â1998).” Journal of the American Veterinary Medical Association, vol. 216, no. 2, 2000, pp. 217–211., doi:10.2460/javma.2000.216.217.