Neutrophil adherence and movement in poorly and well-controlled diabetic dogs

Neutrophil adherence, random movement, and chemotaxis were quantitated in healthy nondiabetic dogs and in dogs with experimentally induced diabetes mellitus. On the basis of glycosylated serum protein values, the diabetic dogs were subdivided into well-controlled and poorly controlled groups. Neutrophil adherence was decreased significantly in poorly controlled diabetic dogs, but significant differences in neutrophil adherences were not found between nondiabetic and well-controlled diabetic dogs. Significant differences in neutrophil random or chemotactic movements were not found between non-diabetic and diabetic dogs. The decreased neutrophil adherence observed in poorly controlled diabetic dogs may predispose these animals to bacterial infection. Therefore, stringent regulation of blood glucose concentrations may decrease the frequency of secondary bacterial infections in spontaneous diabetes mellitus in dogs.     

Advances in canine diabetes mellitus research: etiopathology and results of islet transplantation

Histopathologic and immunocytochemical alterations in the pancreas of 18 dogs with spontaneous diabetes mellitus were evaluated. In 5 of 18 dogs (28%), extensive pancreatic damage appeared to be responsible for the development of diabetes mellitus. In the other 13 dogs, there was substantial reduction in the number of well-granulated beta cells, but the number of well-granulated alpha and delta cells was normal in 70% and 85% of the dogs, respectively. Also, insulitis lesions composed of infiltrating mononuclear cells, predominantly lymphocytes, were observed in 6 of 13 dogs (46%), but evidence of islet-directed humoral autoimmunity was not detected. Each pancreas had dense Ia (class II antigen) expression on ductal epithelia but not on islet endocrine cells. The importance of the insulitis lesions and class II antigen expression on ductal epithelial cells remains unclear. Of the 18 dogs, 8 received multidonor intrahepatic islet allografts. Allograft rejection was prevented by administration of cyclosporin. Five dogs were administered cyclosporin continuously. One dog with an allograft failed to sustain euglycemia at 231 days after transplantation, and one dog with fasting euglycemia died of pneumonia at 186 days after transplantation. In the other dogs, euglycemia was sustained for periods that ranged from 253 to 716 days.     

Study of 253 dogs in the United Kingdom with diabetes mellitus

Clinical information and blood samples were collected from 253 dogs with naturally occurring diabetes mellitus. Over half of them were labrador retrievers, collies, Yorkshire terriers or crossbred dogs, and approximately 80 per cent of them were diagnosed between the ages of five and 12 years. The majority of the dogs were receiving insulin therapy once a day, but in the dogs receiving insulin injections twice a day there was a trend for lower serum fructosamine concentrations, suggesting better glycaemic control. The proportion of female dogs with diabetes was lower than in previous surveys. The disease was diagnosed more commonly in the winter months, a seasonal pattern also observed in human beings with diabetes, suggesting that similar environmental factors might be involved in the disease.     

Clinical evaluation of methoximorpholino-doxorubicin (FCE 23762) in dogs with spontaneous malignancies

We conducted a clinical evaluation of FCE 23762, a methoxymorpholino analog of doxorubicin, in 48 dogs with metastatic, nonresectable, or chemotherapy-resistant spontaneous malignancies at an initial dosage of 50-60 microg/kg IV every 3 weeks. Clinical evidence of toxicity was minimal; 6 dogs developed grades I, II, and III hematologic toxicities after the 1st treatment, and 1 dog developed grade II gastrointestinal toxicity. One dog became pancytopenic 4 months after discontinuation of FCE 23762. No other adverse effects were noted. Partial or complete remissions were observed in 32% of the dogs. Responses were observed both in previously untreated dogs and in those that had received prior chemotherapy, including doxorubicin. FCE 23762 is a promising new antineoplastic agent that can be used safely in dogs with cancer; doses higher than those used in this study may be used eventually in practice.     

Autoantibodies to pancreatic islet cells in canine diabetes mellitus

Indirect immunofluorescence on normal canine pancreatic tissue fixed in Bouin's solution was used to detect islet cell antibodies in dogs with diabetes mellitus, other endocrine diseases, and pancreatitis. 18 of 25 dogs with diabetes mellitus alone, 2 of 8 dogs with diabetes mellitus and concurrent pancreatitis, and 2 of 2 dogs with diabetes mellitus and concurrent pancreatic exocrine insufficiency were positive for autoantibody. 2 of 12 dogs with hypoadrenocorticism, 3 of 6 dogs with hyperadrenocorticism, 6 of 28 dogs with hypothyroidism and one of 19 dogs with pancreatitis alone were also antibody positive. None of 20 healthy dogs or 20 dogs with disorders other than those of the pancreas or endocrine organs were antibody positive. Islet cell antibodies were demonstrated in dogs with diabetes mellitus and other endocrine disorders. The possibility of autoimmune involvement in the development of diabetes mellitus in the dog should be considered.     

Renal clearance, insulin secretion and glucose tolerance in spontaneous diabetes mellitus of dogs.

A standard intravenous glucose tolerance test (IVGTT) and the insulin response to the glucose loads were studied in 14 cases of diabetes mellitus in dogs. In addition, urinary glucose excretion, and clearances of urea, creatinine and phosphate were also determined in these dogs. All diabetic dogs were characterized by glucose intolerance as expressed by an abnormal half-time (T 1/2) or fractional clearance rate (k-value) and were further classified as Types I, II or III diabetes on the basis of their insulin responses. Renal functional impairment was observed in about 60 percent of the cases and was generally mild. There appeared to be no apparent relationship between advanced chronic renal disease and severity of diabetes in dogs.     

Prevalence of malignancy when solitary versus multiple lesions are detected during abdominal ultrasonographic examination of dogs with spontaneous hemoperitoneum: 31 cases (2003–2008)

Objective – To compare the histopathologic diagnosis in dogs with spontaneous hemoperitoneum when abdominal ultrasonographic examination detects a solitary versus multiple lesions.
Design – Retrospective cross-sectional study.
Setting – Private veterinary hospital.
Animals – Client-owned dogs presented with spontaneous hemoperitoneum between March 1, 2003 and June 1, 2008.
Interventions – Dogs were divided into 2 groups based on presence of a solitary or multiple abdominal ultrasonographic lesions. Prevalences were compared between groups for malignancy and specifically hemangiosarcoma.
Measurements and Main Results – Ten of 31 (32%) dogs had a solitary abdominal ultrasonographic lesion and 21 of 31 (68%) had more than 1 lesion. The bleeding tissue was characterized as malignant in 8 of 10 (80%) dogs with solitary lesions and 17 of 21 (81%) dogs with multiple lesions; there was no significant difference ( P =1.0) between groups. In this study no association ( P =0.26) was found between the number of abdominal ultrasonographic lesions observed and subsequent diagnosis of hemangiosarcoma.
Conclusions – Solitary abdominal ultrasonographic lesions in dogs with spontaneous hemoperitoneum do not necessarily indicate a lower prevalence of malignancy.     

Transnasal laryngoscopy for the diagnosis of laryngeal paralysis in dogs

Four dogs with clinical signs of laryngeal paralysis and three normal dogs were evaluated with transnasal laryngoscopy. Six of these dogs subsequently underwent standard laryngoscopy. For transnasal laryngoscopy, a video endoscope was passed through the left nasal passage after intramuscular sedation and topical anesthesia. The laryngeal opening was observed during spontaneous ventilation. Laryngeal paralysis was diagnosed in four dogs and was confirmed with traditional laryngoscopy in three dogs. Normal motion of the arytenoid cartilages was present in the other three dogs; however, two required mechanical stimulation of the laryngeal mucosa for full evaluation. Transnasal laryngoscopy provided a means for diagnosing laryngeal paralysis in dogs without general anesthesia.     

Surgical and nonsurgical management of and selected risk factors for spontaneous pneumothorax in dogs: 64 cases (1986-1999)

OBJECTIVE: To compare results of surgical versus nonsurgical treatment of spontaneous pneumothorax in dogs. DESIGN: Retrospective study. ANIMALS: 64 dogs with pneumothorax without any history of antecedent trauma. PROCEDURE: Information on signalment, thoracic radiographic findings, treatment, histologic findings, and outcome was obtained from the medical records. Signalment of affected dogs was compared with signalment of a control population of 260 dogs examined by the emergency service for reasons other than pneumothorax during the study period. RESULTS: Siberian Huskies were overrepresented in the case population, compared with the control population of dogs examined by the emergency service for other reasons. Twenty-eight dogs were treated without surgery (ie, thoracocentesis or tube thoracostomy with or without cage rest), and 36 were treated with surgery. Information regarding final outcome was available for 33 dogs treated with surgery (median follow-up time, 485 days) and 15 dogs treated without surgery (median follow-up time, 366 days). Dogs that underwent surgery had significantly lower recurrence (1/30) and mortality (4/33) rates, compared with dogs treated without surgery (6/12 and 8/15, respectively). A definitive diagnosis was obtained for 38 dogs, including 34 of 36 dogs undergoing surgery; 26 had bullous emphysema and 4 had neoplasia. Two dogs developed spontaneous pneumothorax secondary to migration of plant foreign bodies. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that recurrence and mortality rates for dogs with spontaneous pneumothorax managed surgically were significantly lower than rates for dogs managed by nonsurgical means alone. Early surgical intervention is recommended for definitive diagnosis and treatment of dogs with spontaneous pneumothorax.     

Basal and Glucagon-Stimulated Plasma C-PeDtide Concentrations in Healthy Dogs, Dogs With Diabetes Millitus, and Dogs With Hyperadrenocorticism

Serum glucose and plasma C-peptide response to IV glucagon administration was evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs with insulin-treated diabetes mellitus, and 8 dogs with naturally acquired hyperadrenocorticism. Serum insulin response also was evaluated in all dogs, except 20 insulin-treated diabetic dogs. Blood samples for serum glucose, serum insulin, and plasma C-peptide determinations were collected immediately before and 5,10,20,30, and (for healthy dogs) 60 minutes after IV administration of 1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated changes in plasma C-peptide and serum insulin concentrations were identical, with single peaks in plasma C-peptide and serum insulin concentrations observed approximately 15 minutes after IV glucagon administration. Mean plasma C-peptide and serum insulin concentrations in untreated diabetic dogs, and mean plasma C-peptide concentration in insulin-treated diabetic dogs did not increase significantly after IV glucagon administration. The validity of serum insulin concentration results was questionable in 10 insulin-treated diabetic dogs, possibly because of anti-insulin antibody interference with the insulin radioimmunoassay. Plasma C-peptide and serum insulin concentrations were significantly increased (P < .001) at all blood sarnplkg times after glucagon administration in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Five-minute C-peptide increment, C-peptide peak response, total C-peptide secretion, and, for untreated diabetic dogs, insulin peak response and total insulin secretion were significantly lower (P < .001) in diabetic dogs, compared with healthy dogs, whereas these same parameters were significantly increased (P < .011 in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Although not statistically significant, there was a trend for higher plasma C-peptide concentrations in untreated diabetic dogs compared with insulin-treated diabetic dogs during the glucagon stimulation test. Baseline C-peptide concentrations also were significantly higher (P < .05) in diabetic dogs treated with insulin for less than 6 months, compared with diabetic dogs treated for longer than 1 year. Finally, 7 of 42 diabetic dogs had baseline plasma C-peptide concentrations greater than 2 SD (ie, >0.29 pmol/mL) above the normal mean plasma C-peptide concentration; values that were significantly higher, compared with results in healthy dogs (P < .001) and with the other 35 diabetic dogs (P < .001). In summary, measurement of plasma C-peptide concentration during glucagon stimulation testing allowed differentiation among healthy dogs, dogs with impaired β-cell function (ie, diabetes mellitusl, and dogs with increased β-cell responsiveness to glucagon (ie, insulin resistance). Plasma C-peptide concentrations during glucagon stimulation testing were variable in diabetic dogs and may represent dogs with type-1 and type-2 diabetes or, more likely, differences in severity of β-cell loss in dogs with type-1 diabetes. J Vet Intern Med 1996;10:116–122. Copyright © 1996 by the American College of Veterinary Internal Medicine.     

Canine cataracts, diabetes mellitus and spontaneous lens capsule rupture: a retrospective study of 18 dogs

OBJECTIVE: To describe the clinical presentation and surgical outcome of diabetic canine patients with cataracts and preoperative spontaneous lens capsule rupture. ANIMALS STUDIED: A total of 20 dogs and 40 eyes were included in the retrospective evaluation. The patients' ages ranged from 5 to 14 years (mean 8.5 years). RESULTS: All dogs had clinical diabetes mellitus, with the duration since diagnosis ranging from 30 to 240 days (mean 123 days). Cataracts were bilateral and noted to have been present for 14-112 days (mean 39 days). Of the 40 eyes affected with cataracts, 30 had a spontaneous rupture of the lens capsule prior to surgery. The capsular rupture was diagnosed on clinical examination in 28/30 eyes and was noted intraoperatively in 2/30. The location of the capsular rupture was equatorial in 29/30 and posterior in 1/30 eyes. Surgery was performed in 38/40 eyes, with one case lost to follow-up without surgical intervention. Prior to surgery, routine diagnostic ophthalmic examination, ocular ultrasound, electroretinography, and systemic evaluation were performed in all dogs. Surgical procedures included phacoemulsification in 28/40 eyes, with IOL placement performed in 20/28 eyes. Intrascleral prosthesis placement or enucleation was performed in 8/40 and 2/40 eyes, respectively, due to a significantly reduced ERG or secondary glaucoma. CONCLUSIONS: The duration of clinical follow-up (19/20 dogs) ranged from 1 to 36 months (mean 12.9 months). All eyes that had cataract surgery with or without IOL placement were sighted at the time of the last follow-up examination. Spontaneous lens capsule rupture associated with diabetes mellitus, cataract and rapid lens intumescence occurs in the dog. Early surgical intervention, prior to secondary complications of glaucoma and loss of retinal function, is associated with a favorable outcome.     

A retrospective-cohort study on the development of cataracts in dogs with diabetes mellitus: 200 cases

The objective of the study was to determine the incidence and estimated median time to cataract formation in dogs with diabetes mellitus. The animals studied were 200 dogs with diabetes mellitus which were referred to a university teaching hospital between 1985 and 1995. Medical records from dogs with a diagnosis of diabetes mellitus were reviewed and, where necessary, further follow-up information was gathered from the referring veterinarian. Incidence rate and median time to diabetic cataract formation was calculated using survival-analysis techniques in a retrospective cohort study design. Among the 200 dogs in the study population, 23 had cataracts at the time of diabetes diagnosis that were presumed to be related to other disease processes. Of the remaining 177 dogs, 132 had documented cataract development with features suggestive as being secondary to diabetes. Twenty-three dogs did not have obvious cataracts at the time of their last examination while 22 dogs did not have cataracts at the time they were lost to follow-up. These 55 cases contributed to the statistical models as noncases of cataracts until the last date for which an examination was available. Half of the population had developed cataracts by the 170th day postdiagnosis of diabetes mellitus, while 75% and 80% of the population developed cataracts by 370 days and 470 days, respectively. The results of this study suggest that the majority of dogs with diabetes will develop cataracts within 5–6 months from the time of diagnosis of the disease, and that approximately 80% of dogs will develop cataracts within 16 months of diagnosis.     

Clinical significance of plasma mannose concentrations in healthy and diabetic dogs

Circulating levels of monosaccharides can act as a reflection of systemic glucose/ energy metabolism. Characteristic changes observed in these levels can be seen in patients with diabetes and other metabolic disorders. There have been a few reports describing the significance of mannose metabolism as an energy source under physiological and pathological conditions. However, the relationship between circulating levels of mannose and the pathophysiology of diabetes mellitus are unknown in dogs. This study examined circulating levels of mannose between healthy control and diabetic dogs and evaluated the clinical significance of mannose levels in dogs. Diabetic dogs demonstrated a higher circulating level of mannose in comparison to normal healthy control dogs. Plasma mannose was positively correlated with plasma glucose and fructosamine, respectively. Interestingly, plasma mannose levels were affected by plasma insulin levels. In the context of feeding and glucose tolerance tests, plasma mannose levels responded to changes in circulating insulin levels. Circulating plasma mannose levels decreased after feeding in both control and diabetic animals in spite of observed insulin level differences. However, when glucose tolerance tests were given, a positive correlation between mannose levels and insulin levels was observed. Therefore, plasma mannose levels obtained via glucose tolerance testing may be used as a new diagnostic method for evaluating insulin resistance or deficiency in diabetic dogs.     

Neurologic manifestations associated with hypothyroidism in four dogs

Hypothyroidism was believed responsible for peripheral and central neurologic abnormalities in 4 dogs. Clinical signs consisted of abnormalities of gait and postural reactions and dysfunction of multiple cranial nerves in all 4 dogs. Circling, hypermetria, and spontaneous verticle nystagmus were observed in some of the dogs. Hypothyroidism was diagnosed in all 4 dogs on the basis of low resting serum thyroxine concentration and inadequate response to thyroid stimulating hormone. After thyroid hormone supplementation, resolution of neurologic abnormalities was complete in 2 dogs and partial in the other 2 dogs.     

Evaluation of plasma-ionized magnesium concentration in 122 dogs with diabetes mellitus: a retrospective study

The goal of this study was to evaluate plasma-ionized magnesium (iMg2+) concentration in a large group of dogs with naturally occurring diabetes mellitus and to determine whether dogs with diabetes mellitus have hypomagnesemia, as reported in diabetic humans and cats. Plasma iMg2+ concentrations were retrospectively evaluated at the time of initial examination of 122 diabetic dogs at the Matthew J. Ryan Veterinary Hospital of the University of Pennsylvania. Diabetic dogs were defined as having uncomplicated diabetes mellitus (DM, 78 dogs) diabetic ketoacidosis (DKA, 32 dogs), or ketotic nonacidotic diabetes mellitus (DK, 12 dogs) on the basis of presence or absence of metabolic acidosis or ketonuria. Twenty-two control dogs were used to determine reference values for plasma iMg2+ concentration in healthy dogs. Plasma iMg2+ concentration also was evaluated in 19 nondiabetic dogs with acute pancreatitis because many of the dogs with DKA had concurrent acute pancreatitis. Plasma iMg2+ concentration was significantly higher in dogs with DKA (median 0.41 mmol/L, reference range 0.14-0.72 mmol/L) than in dogs with DM (0.33 mmol/L, 0.17-0.65 mmol/L; P = .0002) or the control group (0.32 mmol/L, 0.26-0.41 mmol/L; P = .006). There were no significant differences between plasma iMg2+ concentrations in dogs with DM or DK compared with control dogs. We conclude that dogs with naturally occurring diabetes mellitus do not have marked hypomagnesemia on initial examination at a tertiary care center.     

Retrospective evaluation of urinary tract infection in 42 dogs with hyperadrenocorticism or diabetes mellitus or both

A retrospective study was performed to determine the proportion of dogs with hyperadrenocorticism or diabetes mellitus or both that had urinary tract infection (UTI) and to describe clinical and laboratory findings. Dogs with these endocrine disorders were included if results of quantitative urine culture were available and dogs were not receiving antimicrobials. Dogs with positive urine cultures were considered to have UTI and dogs with negative urine cultures were used as controls. Information including history, clinical signs, physical examination findings, and results of laboratory tests and urine culture was extracted from all records. Findings in dogs with UTI were compared with control dogs. There were 101 dogs with hyperadrenocorticism or diabetes mellitus or both that met inclusion criteria; 42 (41.6%) had UTI and 59 (58.4%) did not. UTI was present in 46% of dogs with hyperadrenocorticism, 37% of dogs with diabetes mellitus, and 50% of dogs with both endocrine disorders. There was no association between endocrine group and occurrence of UTI. Escherichia coli was the most common bacteria isolated, and cultures from 29 dogs (69%) showed growth of this organism. Of dogs with UTI, <5% had stranguria, pollakiuria, or discolored urine, whereas 60% had pyuria and 69% had bacteriuria. We conclude that UTIs are common in dogs with hyperadrenocorticism, diabetes mellitus, or both diseases. Clinical signs of UTI, however, are uncommon and results of urinalysis may be normal. Therefore, it is appropriate to recommend urine culture as part of the evaluation of dogs with these endocrine disorders.     

Urinary corticoids in the diagnosis of canine hyperadrenocorticism

In 20 healthy experimental dogs the 24 hour urinary corticoid excretion as measured by cortisol radioimmunoassay on two consecutive days varied from 0.5 to 3.3 nmol/kg/24 hours and from 0.3 to 3.6 nmol/kg/24 hours. In 20 dogs with otherwise proven spontaneous hyperadrenocorticism these values varied from 4.4 to 35.7 nmol/kg/24 hours and from 3.6 to 26.8 nmol/kg/24 hours respectively. Corticoid/creatinine ratios in morning urine samples of 28 healthy pet dogs were 1.2 to 6.9 X 10(-6). In 27 dogs with spontaneous hyperadrenocorticism all ratios exceeded the range observed in the healthy pet dogs.     

The role of vasopressin in dogs with polyuria

Polyuria and polydipsia (PUPD) occur frequently in dogs and may be caused by a variety of endocrine, metabolic, and renal disturbances. The studies described in this PhD Thesis, which was defended in January 2004 in Utrecht, investigated the role of the antidiuretic hormone vasopressin (VP) in the pathogenesis of different forms of canine polyuria. Experiments in healthy dogs demonstrated that the ranges of urine specific gravity and urine osmolality are much larger than previously thought. A water deprivation test is not required in all polyuric dogs, because serial measurements of urine osmolality may already lead to the diagnosis of primary polydipsia, in some cases. In dogs with primary polydipsia a wide variation in VP responses to hypertonic stimulation can be found, including a hyperresponse, a hyporesponse, and a non-linear response. The significance of the VP response to hypertonic saline infusion as the 'gold standard' for a diagnosis of canine polyuria is discussed. In the dog, VP is secreted in a pulsatile fashion with a wide variation in the number of VP pulses, VP pulse duration, and VP pulse amplitude and height. The occurrence of spontaneous VP pulses may severely hamper the interpretation of the curve describing the relationship between plasma osmolality and plasma VP concentration during osmotic stimulation. A radioimmunoassay to measure the VP-dependent water channel aquaporin-2 (AQP2) in urine was developed in dogs. In healthy dogs, urinary AQP2 excretion closely reflects changes in collecting duct exposure to VP. Measurement of urinary AQP2 excretion in polyuric dogs may be helpful to distinguish between central diabetes insipidus, nephrogenic diabetes insipidus, and primary polydipsia.     

Fat absorption in dogs with diabetes mellitus or hypothyroidism

Quantitative fat absorption was studied in normal dogs and in dogs with hypothyroidism and diabetes mellitus. The serum triglyceride concentrations of diabetic and hypothyroid dogs were significantly higher at each sampling time than those of normal dogs. The fat absorption curve of hypothyroid dogs peaked at 180 minutes and though significantly raised was parallel to that of normal dogs whereas the fat absorption curve of diabetic dogs continued to rise up to 240 minutes. These results provide evidence for impaired plasma clearance of triglyceride in canine diabetes mellitus and hypothyroidism.     

Effect of insulin dosage on glycemic response in dogs with diabetes mellitus: 221 cases (1993-1998)

OBJECTIVE: To evaluate glycemic response to insulin treatment in dogs with diabetes mellitus. DESIGN: Retrospective study. ANIMALS: 221 dogs with diabetes mellitus. PROCEDURE: Type and dosage of insulin used, minimum and maximum blood glucose concentrations, time of blood glucose concentration nadir, and optimal duration of action of insulin were determined on the basis of data obtained prior to initial examination at the teaching hospital (127 dogs), at the time of initial examination (212 dogs), at the time a second follow-up blood glucose curve was performed (59 dogs), and at the time of clinical control of diabetes mellitus (83 dogs). RESULTS: Prior to examination, 69 of 127 dogs (54%) received 1 s.c. insulin injection daily. Thirty-one dogs (24%) received a high dose of insulin (i.e., > 1.5 U/kg [0.7 U/lb] of body weight); 27 of these dogs (87%) received 1 injection/d. Eleven of 16 dogs (69%) that were hypoglycemic (blood glucose concentration < 80 mg/dl) also received 1 injection/d. However, optimal duration of action of insulin was > 12 hours in only 5 of 83 dogs (6%) evaluated at the time diabetes mellitus was clinically controlled. At that time, only 1 dog (1%) received a high dose of insulin, and the dog received 2 injections/d. Moreover, 8 of 10 dogs (80%) with hypoglycemia received 1 injection/d. CONCLUSIONS AND CLINICAL RELEVANCE: Most dogs with diabetes mellitus are clinically regulated with 2 daily insulin injections. Administration of a high dose of insulin or development of hypoglycemia may be more common in diabetic dogs that receive insulin once daily, compared with dogs that receive insulin twice daily.