Richard W. Nelson

Successful reversal of spontaneous diabetes in dogs by intraperitoneal microencapsulated islets.

Long-term euglycemia by intraperitoneal transplantation of microencapsulated islets has not been described in the diabetic large animal model. In this study, we report the successful long-term reversal of diabetes by this method in spontaneous diabetic dogs. We have identified fundamental mechanism (s) associated with alginate-based microcapsule fibrosis, and have devised methods to ameliorate this problem. These include the use of purified alginate of low mannuronic acid content and cytokine suppression. Ten insulin-dependent, spontaneous diabetic dogs (insulin requirement 1–4 units/kg/day; absence of circulating C-peptide and diabetic K-values of 0.6±0.4) were entered into the study. Islets from mongrel donor pancreata were isolated and transplanted intraperitoneally either as free islet controls (n=3) or as microencapsulated islet allografts (n=7). In all seven encapsulated islet recipients, euglycemia was achieved within 24 hr (serum glucose falling from 304±117 to 116±72 mg/dl). IVGTT performed 14 days after islet transplant demonstrated normalization of K-values changing from a pretransplant level of 0.6±0.4 to 2.6±0.6. All animals receiving encapsulated islets remained euglycemic, free of the need for exogenous insulin, for a period of 63–172 days, with a median insulin-independence for 105 days. In contrast, recipients receiving free islets rejected their graft within seven days of implantation. In conclusion, this is the first report of long-term successful reversal of spontaneous diabetes in the large animal model by an intraperitoneal injection of encapsulated islets. The potential exists for this form of therapy to be explored in the treatment of type I diabetes in man.

Diagnosis of Spontaneous Canine Hyperadrenocorticism: 2012 ACVIM Consensus Statement (Small Animal)

This report offers a consensus opinion on the diagnosis of spontaneous canine hyperadrenocorticism. The possibility that a patient has hyperadrenocorticism is based on the history and physical examination. Endocrine tests should be performed only when clinical signs consistent with HAC are present. None of the biochemical screening or differentiating tests for hyperadrenocorticism are perfect. Imaging can also play a role. Awareness of hyperadrenocorticism has heightened over time. Thus, case presentation is more subtle. Due to the changes in manifestations as well as test technology the Panel believes that references ranges should be reestablished. The role of cortisol precursors and sex hormones in causing a syndrome of occult hyperadrenocorticism remains unclear.

Relative Adrenal Insufficiency in Dogs with Sepsis

BACKGROUND A syndrome of relative adrenal insufficiency has been identified in septic humans, and is associated with hypotension and death. Relative adrenal insufficiency is generally associated with basal serum cortisol concentration within or above the reference range and a blunted cortisol response to adrenocorticotropic hormone administration. It is unknown whether relative adrenal insufficiency occurs in septic dogs. HYPOTHESIS That relative adrenal insufficiency occurs in septic dogs, and that relative adrenal insufficiency is associated with hypotension and mortality. ANIMALS Thirty-three septic dogs admitted to a small animal intensive care unit. METHODS Dogs were included in the study if they had a known or suspected infectious disease and had systemic inflammatory response syndrome. Dogs were excluded if they had disease or medication history expected to affect the hypothalamic-pituitary-adrenal axis. Serum cortisol and endogenous plasma adrenocorticotropic hormone concentrations were measured before, and serum cortisol concentration measured 1 hour after, intramuscular administration of 250 microg of cosyntropin/dog. The change in cortisol concentration (delta-cortisol) before and after cosyntropin administration was determined in each dog. RESULTS Hypotension was associated with lower delta-cortisol values (OR 1.3; CI 1.0-1.9; P = .029). delta-Cortisol cutoff of 3.0 microg/dL was most accurate for predicting hypotension, survival to discharge, and 28-day survival. The rate of death in dogs with delta-cortisol < or = 3 microg/dL was 4.1 times that of dogs with delta-cortisol > 3 microg/dL (RR 4.1; CI 1.5-12.3; P = .01). CONCLUSIONS AND CLINICAL RELEVANCE Delta-cortisol < or = 3 microg/dL after adrenocorticotropic hormone administration is associated with systemic hypotension and decreased survival in septic dogs.

AAHA Diabetes Management Guidelines for Dogs and Cats

Diabetes mellitus (DM) is a treatable condition that requires a committed effort by veterinarian and client. This document provides current recommendations for the treatment of diabetes in dogs and cats. Treatment of DM is a combination of art and science, due in part to the many factors that affect the diabetic state and the animal’s response. Each animal needs individualized, frequent reassessment, and treatment may be modified based on response. In both dogs and cats, DM is caused by loss or dysfunction of pancreatic beta cells. In the dog, beta cell loss tends to be rapid and progressive, and it is usually due to immune-mediated destruction, vacuolar degeneration, or pancreatitis.1 Intact females may be transiently diabetic due to the insulin-resistant effects of the diestrus phase. In the cat, loss or dysfunction of beta cells is the result of insulin resistance, islet amyloidosis, or chronic lymphoplasmacytic pancreatitis.2 Risk factors for both dogs and cats include insulin resistance caused by obesity, other diseases (e.g., acromegaly in cats, hyperadrenocorticism in dogs), or medications (e.g., steroids, progestins). Genetics is a suspected risk factor, and certain breeds of dogs (Australian terriers, beagles, Samoyeds, keeshonden3) and cats (Burmese4) are more susceptible. Regardless of the underlying etiology, diabetic dogs and cats are hyperglycemic and glycosuric, which leads to the classic clinical signs of polyuria, polydipsia (PU/PD), polyphagia, and weight loss. Increased fat mobilization leads to hepatic lipidosis, hepatomegaly, hypercholesterolemia, hypertriglyceridemia, and increased catabolism. Eventually, hyperketonemia, ketonuria, and ketoacidosis develop and result in progressive compromise of the animal.

Frequency and Risk Factors for Urinary Tract Infection in Cats with Diabetes Mellitus

BACKGROUND Identification and control of infections are important in the management of diabetic cats. Urinary tract infections have not been well characterized in diabetic cats. This retrospective study was performed to review and characterize urinary tract infections in diabetic cats. HYPOTHESIS Urinary tract infections are common in diabetic cats. ANIMALS A review was made of the medical records of 141 diabetic cats that had had urine obtained for culture by antepubic cystocentesis and that had not been treated with antibiotics, undergone urinary tract catheterization or urinary tract surgery within 2 weeks of urine collection or had urethral obstruction at the time of urine collection. METHODS A review of medical records. RESULTS Urinary tract infection was identified in 18 of 141 diabetic cats. Escherichia coli was the most common isolate (67%). Female cats were at increased risk (prevalence odds ratios [POR], 3.7; 95% confidence interval [CI], 1.3 to 10.2; P = .013). Clinical signs of lower urinary tract disease and findings on urine sediment examination were good predictors of positive urine cultures. CONCLUSIONS AND CLINICAL IMPORTANCE Urinary tract infections are common in diabetic cats regardless of status of diabetic control, suggesting routine monitoring with urine sediment exams or urine culture is warranted.

Evaluation of urine specific gravity and urine sediment as risk factors for urinary tract infections in cats

BACKGROUND It has been suggested that diseases that promote isosthenuria predispose to urinary tract infections because of a lack of the common bacteriostatic properties present in concentrated urine. OBJECTIVES The purpose of this study was to assess the clinicopathologic risk factors for positive urine culture outcome in cats with chronic kidney disease (CKD), diabetes mellitus (DM), uncontrolled hyperthyroidism (HT), or lower urinary tract disease (LUTD). METHODS For this retrospective study, medical records of all cats in which a urinalysis and aerobic bacterial urine culture were performed between January 1995 and December 2002 were reviewed. Signalment, body weight, and clinicopathologic data were recorded. Based on the medical records, cats were diagnosed with CKD, DM, HT, or LUTD. Prevalence odds ratios and 95% confidence intervals were calculated using logistic regression. Multivariate models were created for each variable of interest while controlling for the confounding effect of disease group. RESULTS Six hundred fourteen cats met the criteria for inclusion in the study. Overall, positive urine cultures were identified in 16.9% of cats with CKD, 13.2% of cats with DM, 21.7% of cats with HT, and 4.9% of cats with clinical signs of LUTD. Decreasing urine specific gravity was not associated with positive urine culture when controlled for disease but pyuria, bacteriuria, and hematuria were all associated with positive urine culture outcome. Persians, females, increasing age, and decreasing body weight were all associated with positive urine culture outcome. CONCLUSIONS Performing a urine culture sample based solely on the presence of isosthenuria does not seem warranted. Further studies are warranted to help identify host predisposing factors for urinary bacterial colonization in cats with these diseases.

Evaluation of twice-daily, low-dose trilostane treatment administered orally in dogs with naturally occurring hyperadrenocorticism

OBJECTIVE To evaluate the effects of twice-daily oral administration of a low-dose of trilostane treatment and assess the duration of effects after once-daily trilostane administration in dogs with naturally occurring hyperadrenocorticism (NOH). DESIGN Prospective study. ANIMALS 28 dogs with NOH. PROCEDURES 22 dogs received 0.5 to 2.5 mg of trilostane/kg (0.23 to 1.14 mg/lb) orally every 12 hours initially. At intervals, dogs were reevaluated; owner assessment of treatment response was recorded. To assess drug effect duration, 16 of the 22 dogs and 6 additional dogs underwent 2 ACTH stimulation tests 3 to 4 hours and 8 to 9 hours after once-daily trilostane administration. RESULTS After 1 to 2 weeks, mean trilostane dosage was 1.4 mg/kg (0.64 mg/lb) every 12 hours (n = 22 dogs; good response [resolution of signs], 8; poor response, 14). Four to 8 weeks later, mean dosage was 1.8 mg/kg (0.82 mg/lb) every 12 or 8 hours (n = 21 and 1 dogs, respectively; good response, 15; poor response, 5; 2 dogs were ill). Eight to 16 weeks after the second reevaluation, remaining dogs had good responses (mean dosages, 1.9 mg/kg [0.86 mg/lb], q 12 h [n = 13 dogs] and 1.3 mg/kg [0.59 mg/lb], q 8 h [3]). At 3 to 4 hours and 8 to 9 hours after once-daily dosing, mean post-ACTH stimulation serum cortisol concentrations were 2.60 and 8.09 Pg/dL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE In dogs with NOH, administration of trilostane at low doses every 12 hours was effective, although 2 dogs became ill during treatment. Drug effects diminished within 8 to 9 hours. Because of potential adverse effects, lower doses should be evaluated.

Predictive Factors and the Effect of Phenoxybenzamine on Outcome in Dogs Undergoing Adrenalectomy for Pheochromocytoma

BACKGROUND Some studies in dogs undergoing adrenalectomy for pheochromocytoma suggest that anesthetic complications and perioperative mortality are common. In humans, surgical outcome has improved with the use of phenoxybenzamine (PBZ) before adrenalectomy. HYPOTHESIS Dogs treated with PBZ before adrenalectomy have increased survival compared with untreated dogs. ANIMALS Forty-eight dogs that underwent adrenalectomy for pheochromocytoma. METHODS A retrospective medical record review for dogs that underwent adrenalectomy for pheochromocytoma at a veterinary medical teaching hospital over the period from January 1986 through December 2005. RESULTS Twenty-three of 48 dogs were pretreated with PBZ (median dosage: 0.6 mg/kg PO q12h) for a median duration of 20 days before adrenalectomy. Duration of anesthesia and surgery, percentage of dogs with pheochromocytoma involving the right versus left adrenal gland, size of tumor, and presence of vascular invasion were similar for PBZ-treated and untreated dogs. Thirty-three (69%) of 48 dogs survived adrenalectomy in the perioperative period. PBZ-treated dogs had a significantly (P = .014) decreased mortality rate compared with untreated dogs (13 versus 48%, respectively). Additional significant prognostic factors for improved survival included younger age (P = .028), lack of intraoperative arrhythmias (P = .0075), and decreased surgical time (P = .0089). CONCLUSIONS AND CLINICAL IMPORTANCE Results from this retrospective study support treatment with PBZ before surgical removal of pheochromocytoma in dogs.

Evaluation of six portable blood glucose meters for measuring blood glucose concentration in dogs

OBJECTIVE To evaluate accuracy of 6 portable blood glucose meters (PBGMs) by comparing results of these meters with results obtained with a reference chemistry analyzer. DESIGN Evaluation study. ANIMALS 49 dogs (158 blood samples). Procedures-Venous blood samples were tested with the 6 PBGMs, and results were compared with results of a commercially available analyzer that used a reference method based on the hexokinase reaction. RESULTS Plasma glucose concentrations obtained with the reference analyzer ranged from 41 to 639 mg/dL. There were significant correlations between blood glucose concentrations obtained with the 6 PBGMs and plasma glucose concentrations obtained with the reference analyzer (r > or = 0.96). However, for all 6 PBGMs, results differed from results for the reference analyzer, with the difference increasing as plasma glucose concentration increased. Significant differences in bias were found among meters. For 142 samples classified as hypoglycemic, euglycemic, or hyperglycemic on the basis of results of the reference analyzer, the percentage of samples that were misclassified on the basis of results of the PBGMs ranged from 2.1% to 38.7%. CONCLUSIONS AND CLINICAL RELEVANCE Results of the present study suggested that there were substantial differences in the accuracy of currently available PBGMs when used to determine blood glucose concentration in dogs.

ANIMAL MODELS OF DISEASE: Classification and etiology of diabetes in dogs and cats

Diabetes mellitus is a common disease in dogs and cats. The most common form of diabetes in dogs resembles type 1 diabetes in humans. Studies suggest that genetics, an immune-mediated component, and environmental factors are involved in the development of diabetes in dogs. A variant of gestational diabetes also occurs in dogs. The most common form of diabetes in cats resembles type 2 diabetes in humans. A major risk factor in cats is obesity. Obese cats have altered expression of several insulin signaling genes and glucose transporters and are leptin resistant. Cats also form amyloid deposits within the islets of the pancreas and develop glucotoxicity when exposed to prolonged hyperglycemia. This review will briefly summarize our current knowledge about the etiology of diabetes in dogs and cats and illustrate the similarities among dogs, cats, and humans.