What's in a Name? Classification of Diabetes Mellitus in Veterinary Medicine and Why It Matters.

Diabetes Mellitus (DM) is a syndrome caused by various etiologies. The clinical manifestations of DM are not indicative of the cause of the disease, but might be indicative of the stage and severity of the disease process. Accurately diagnosing and classifying diabetic dogs and cats by the underlying disease process is essential for current and future studies on early detection, prevention, and treatment of underlying disease. Here, we review the current etiology-based classification of DM and definitions of DM types in human medicine and discuss key points on the pathogenesis of each DM type and prediabetes. We then review current evidence for application of this etiology-based classification scheme in dogs and cats. In dogs, we emphasize the lack of consistent evidence for autoimmune DM (Type 1) and the possible importance of other DM types such as DM associated with exocrine pancreatic disease. While most dogs are first examined because of DM in an insulin-dependent state, early and accurate diagnosis of the underlying disease process could change the long-term outcome and allow some degree of insulin independence. In cats, we review the appropriateness of using the umbrella term of Type 2 DM and differentiating it from DM secondary to other endocrine disease like hypersomatotropism. This differentiation could have crucial implications on treatment and prognosis. We also discuss the challenges in defining and diagnosing prediabetes in cats.

Treatment of ionized hypercalcemia in 12 cats (2006-2008) using PO-administered alendronate.

BACKGROUND: Long-term treatment of cats with ionized hypercalcemia using alendronate has not been evaluated. HYPOTHESIS/OBJECTIVES: Alendronate is well tolerated in treatment of ionized hypercalcemia in cats. ANIMALS: A total of 12 cats with ionized hypercalcemia. METHODS: Prospective study of 12 cats with ionized hypercalcemia of idiopathic origin was identified by telephone and email communication with a convenience sample of consulting veterinarians. Cats were treated with alendronate at a dose of 5-20 mg per feline PO q7d. Serum ionized calcium concentration (iCa) was measured before beginning treatment with alendronate, and after 1, 3, and 6 months of treatment. Alendronate dosage was adjusted according to iCa. Evaluation included physical examination, CBC, biochemistry profile, and diagnostic imaging. The owners and referring veterinarians were questioned about any observed adverse effects. The Wilcoxon matched-pairs signed rank test was used to compare baseline iCa to iCa at different time periods. RESULTS: Alendronate treatment resulted in a decrease in iCa in all 12 cats. The median percentage change in iCa was -13.2%, -15.9%, and -18.1% (range, -29.6 to +7.6; -30.5 to -1.9; -45.8 to +1.5%) at the 1, 3, and 6 month time points, respectively. Baseline iCa was significantly different from 1 month (P = .0042), 3 months (P = .0005), and 6 months (P = .0015). No adverse effects were reported for any of the cats. CONCLUSIONS AND CLINICAL IMPORTANCE: Alendronate was well tolerated and decreased iCa in most cats for the 6-month period of observation.

Arterial blood pressure, proteinuria, and renal histopathology in clinically healthy retired racing greyhounds.

BACKGROUND: Physiologic peculiarities of Greyhounds as compared to other dogs make interpretation of laboratory results in this breed challenging for veterinarians. Hypertension in retired racing Greyhounds (RRG) can contribute to microalbuminuria (MA), overt proteinuria, and renal histologic lesions. OBJECTIVES: To evaluate clinicopathologic findings, hemodynamic status, and renal histology in a population of healthy RRG. ANIMALS: RRG presented to Ohio State University College of Veterinary Medicine for inclusion in a spay and neuter program. METHODS: Cross-sectional study. RRG were classified as normotensive (<160 mmHg) or hypertensive (>160 mmHg) based on blood pressure (BP) determinations using Doppler and oscillometric methods. Of the dogs evaluated, 62% (n = 29) were hypertensive and 38% (n = 18) were normotensive. Health status was evaluated using routine clinicopathologic tests (CBC, serum biochemistry, urinalysis) as well as evaluation of fractional excretion of electrolytes and MA determinations. Adequate renal biopsy specimens (n = 15) were evaluated using light, immunofluoresence, and electron microscopy. RESULTS: All serum biochemistry results were normal in 45/49 dogs, but MA was more common in hypertensive (84% positive for MA) as compared with normotensive (18% positive for MA) RRG. Observed renal lesions were mild and renal biopsy scores were low in this sample of RRG. CONCLUSIONS: Hypertension is common in RRG and might be breed-related. It is associated with MA, but observed renal lesions are mild. Whether or not hypertension and MA in RRG leads to progressive renal damage requires longitudinal study.

Comparison of signalment, clinicopathologic findings, histologic diagnosis, and prognosis in dogs with glomerular disease with or without nephrotic syndrome.

BACKGROUND: Nephrotic syndrome (NS) develops most commonly in people with glomerular diseases associated with marked albuminuria. Hypernatremia, hypertension, and progressive renal failure are more prevalent in nephrotic than nonnephrotic human patients. HYPOTHESIS/OBJECTIVES: Dogs with NS have higher serum cholesterol, triglyceride, and sodium concentrations, higher urine protein:creatinine ratios (UPC) and systolic blood pressure, and lower serum albumin concentrations than dogs with nonnephrotic glomerular disease (NNGD). NS is associated with membranous glomerulopathy and amyloidosis. Affected dogs are more likely to be azotemic and have shorter survival times. ANIMALS: Two hundred and thirty-four pet dogs (78 NS dogs, 156 NNGD dogs). METHODS: Multicenter retrospective case-control study comparing time-matched NS and NNGD dogs. NS was defined as the concurrent presence of hypoalbuminemia, hypercholesterolemia, proteinuria, and extravascular fluid accumulation. Signalment, clinicopathologic variables, histopathologic diagnoses, and survival time were compared between groups. RESULTS: Age, serum albumin, chloride, calcium, phosphate, creatinine, and cholesterol concentrations, and UPC differed significantly between NS and NNGD dogs. Both groups were equally likely to be azotemic at time of diagnosis, and NS was not associated with histologic diagnosis. Median survival was significantly shorter for NS (12.5 days) versus NNGD dogs (104.5 days). When subgrouped based on serum creatinine (< or ≥1.5 mg/dL), survival of NS versus NNGD dogs was only significantly different in nonazotemic dogs (51 versus 605 days, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Presence of NS is associated with poorer prognosis in dogs with nonazotemic glomerular disease. Preventing development of NS is warranted; however, specific interventions were not evaluated in this study.

Uroendoscopy. Evaluation of the lower urinary tract.

Recent advances in uroendoscopy have allowed diagnostic evaluation of the lower urinary tract in most of our canine and feline patients. By providing a magnified view of the luminal surfaces of the lower urinary tract, uroendoscopy provides useful diagnostic information that is not readily available even by more invasive techniques.

Simplified methods for estimation of 99mTc-pentetate and 131I-orthoiodohippurate plasma clearance in dogs and cats.

The purpose of this study was to evaluate simplified methods for estimation of Technetium Tc 99m (99mTc)-pentetate and orthoiodohippurate I 131 (131I-OIH) plasma clearance in dogs and cats with 1 and 2 blood samples. Plasma clearances were calculated after a bolus injection of 1.85-11.1 MBq of 99mTc-pentetate and 131I-OIH with a 2-compartment model based on a 12-point curve as a reference method in 21 dogs and 18 cats. Three 2-sample and 3 single-sample methods were investigated. The method yielding the smallest standard deviation of the difference between the reference method and the simplified method was selected as the optimal one. Linear regression analysis was performed between the reference method and the simplified method and coefficient of determination (R2) was calculated. For 99mTc-pentetate plasma clearance, the optimal 2-sample method was the one with a mono-compartment model with samples taken at specific times. For 131I-OIH plasma clearance, the estimation was improved slightly by raising the clearance calculated with a mono-compartment model to the power of an empirically determined parameter. The optimal single-sample method was the one with a linear quadratic regression between the volume of distribution of the tracer at a specific time and the clearance calculated with 12 samples. Two-sample methods performed significantly better than did single-sample methods. The conclusion is made that 99mTc-pentetate and 131I-OIH plasma clearances can be estimated in dogs and cats with 1 or 2 blood samples with a reasonable margin of error compared to plasma clearances calculated with a 2-compartment model and 12 blood samples.

Idiopathic hypercalcemia in cats.

Unexplained hypercalcemia has been increasingly recognized in cats since 1990. In some instances, hypercalcemia has been associated with calcium oxalate urolithiasis, and some affected cats have been fed acidifying diets. We studied the laboratory findings, clinical course, and treatment of 20 cats with idiopathic hypercalcemia. Eight (40%) of the cats were longhaired and all 14 cats for which adequate dietary history was available had been fed acidifying diets. Clinical signs included vomiting (6 cats), weight loss (4 cats), dysuria (4 cats), anorexia (3 cats), and inappropriate urinations (3 cats). Hypercalcemia was mild to moderate in severity. and serum parathyroid hormone concentrations were normal or low. Serum concentrations of phosphorus, parathyroid hormone-related peptide, 25-hydroxycholecalciferol, and calcitriol were within the reference range in most cats. Diseases commonly associated with hypercalcemia (eg, neoplasia, primary hyperparathyroidism) were not identified despite thorough medical evaluations and long-term clinical follow-up. Azotemia either did not develop (10 cats) or developed after the onset of hypercalcemia (3 cats), suggesting that renal failure was not the cause of hypercalcemia in affected cats. Seven of 20 cats (35%) had urolithiasis, and in 2 cats uroliths were composed of calcium oxalate. Subtotal parathyroidectomy in 2 cats and dietary modification in 11 cats did not result in resolution of hypercalcemia. Treatment with prednisone resulted in complete resolution of hypercalcemia in 4 cats.

Ureteral obstruction after ureteroneocystostomy in dogs assessed by technetium TC 99m diethylenetriamine pentaacetic acid (DTPA) scintigraphy.

OBJECTIVE: To use technetium Tc 99m diethylenetriamine pentaacetic acid (99mTc-DTPA) renal scintigraphy to monitor ureteral obstruction after ureteroneocystostomy in a canine model of partial ureteral obstruction. STUDY DESIGN: Experimental study. ANIMALS: Eight normal adult dogs. METHODS: Partial ureteral obstruction was created in 8 dogs by incomplete ligation of the terminal right ureter. Two weeks later, ureteroneocystostomy was performed in 7 dogs with unilateral partial ureteral obstruction and in 1 dog that had developed bilateral partial ureteral obstruction. 99mTc-DTPA scintigraphy was performed intermittently for 2 weeks after ureteroneocystostomy. Renal transit time of each kidney, as assessed by the time to maximal uptake (time of peak), and glomerular filtration rate, as assessed by percentage of kidney uptake of the radiopharmaceutical between 1 and 3 minutes, were estimated. Comparison between affected and nonaffected kidneys was performed with the Wilcoxon rank sum test. RESULTS: Unilateral partial ureteral obstruction was induced successfully in 7 dogs. In 1 dog, bilateral partial obstruction was induced inadvertently. After ureteroneocystostomy, percentage of kidney uptake of 99mTc-DTPA was low in 4 affected kidneys. The uptake returned to within normal limits in 2 of the kidneys during the observation period. The time activity curve had a more rounded appearance or was increasing continuously for all affected kidneys. A significant increase in renal transit time was observed 2 and 4 days after ureteroneocystostomy. Transit time progressively returned to normal by 4 to 11 days for all affected kidneys except 1. CONCLUSION: Ureteroneocystostomy resulted in persistent partial ureteral obstruction for 4 to 11 days as determined by 99mTc-DTPA scintigraphy. CLINICAL RELEVANCE: 99mTc-DTPA scintigraphy may be a useful procedure for monitoring renal function and ureteral obstruction after ureteroneocystostomy. Persistent partial ureteral obstruction may be seen 1 to 2 weeks after ureteral reimplantation in dogs with previously existing dilated ureters.

Effect of sample number and time on determination of plasma clearance of technetium Tc 99m pentetate and orthoiodohippurate sodium I 131 in dogs and cats.

OBJECTIVE: To determine the effect of number of blood samples and sampling times on plasma clearance of technetium Tc 99m pentetate (Tc99mP) and orthoiodohippurate sodium I 131(OIH). ANIMALS: 20 dogs and 14 cats. PROCEDURE: Plasma clearances of OIH and Tc99mP were calculated by use of a 2-compartment model, on the basis of a 12-point curve as a reference method. Plasma clearance was calculated by use of all possible combinations of 4 to 11 samples. Time schedule yielding the smallest difference from the reference method was considered to be optimal. Regression analysis was performed between the 12-point model and models using a reduced number of samples. RESULTS: SD of the difference between the 12-point clearance and the models with reduced numbers of samples increased when the number of samples decreased. The SD of the difference between 12-point clearance and 4-point clearance was 4.17 ml/min for OIH and 0.94 ml/min for Tc99mP in dogs and 0.45 ml/min for OIH and 0.11 ml/min for Tc99mP in cats. Optimal schedules were distributed logarithmically and included an early sample at 5 or 10 minutes, a late sample at 2.5, 3, 4, or 5 hours for OIH, and a late sample at 4 or 5 hours for Tc99mP. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma clearances of OIH and Tc99mP can be accurately calculated in dogs and cats by use of a single-injection 2-compartment pharmacologic model with a reduced number of blood samples, resulting in an acceptable margin of error.

Radiotelemetry catheter implantation: surgical technique and results in cats.

Arterial blood pressure in cats can be measured by direct or indirect techniques. Most direct measurement techniques require sedation or anesthesia, which decreases blood pressure. The restraint and human intervention needed for indirect techniques cause blood pressure to increase. These limitations make the accurate assessment of blood pressure and the response to antihypertensive medications difficult to interpret. Radiotelemetry allows for direct measurement of the arterial blood pressure and heart rate without sedation, anesthesia, or animal handling during measurement. A surgical technique for the placement of radiotelemetry catheters and the complications associated with the technique have not been described in cats. Our purpose is to provide a detailed description of the placement of the modified implant model TA11PA-C40 (Data Sciences International), with accompanying illustrations, and to discuss complications associated with the procedure. Radiotelemetry catheters were surgically placed in the left femoral artery of 12 cats. The surgical procedure was completed within 50 min, and no surgical complications occurred in any cat. The radiotelemetry catheters were used for an average of 6.5 weeks (range, 5.5 to 9.5 weeks). This technique allows for long-term monitoring of ambulatory blood pressure and heart rate in the research setting. This methodology is especially useful for studies of the pathophysiology of hypertension and assessment of the efficacy of antihypertensive medications.

Renal transit time of 99mTc-diethylenetriaminepentacetic acid (DTPA) in normal dogs.

The transit time of 99mTc-DTPA in the kidneys is an indicator of renal function that has been used in humans for the diagnosis of renal obstruction, renal artery stenosis, and rejection of renal transplants. Its use, however, has not been reported in the dog. 99mTc-DTPA scintigraphy was performed in 8 normal dogs and the time of peak was calculated as the time between the injection and the maximum renal uptake. Deconvolution analysis was performed to estimate the renal retention function using 3 different techniques, i.e. the matrix method, the fast Fourier transform (FFT) method, and the constrained least square method. The parenchymal and whole kidney mean transit times were calculated from the deconvolved renogram using alternatively the thorax and the aorta as the input function. Average mean transit times ranged from 137 to 184 seconds. Parenchymal mean transit time was significantly shorter than whole kidney mean transit time (P<0.03). Mean transit time calculated with the thorax as the input function was significantly longer than mean transit time calculated with the aorta (P<0.001). No differences were observed between mean transit time calculated with the matrix, FFT and constrained least square methods.

Effect of partial ureteral obstruction on results of renal scintigraphy in dogs.

OBJECTIVE: To use scintigraphy to determine the effects of partial ureteral obstruction on renal transit time and induction of diuresis in dogs. ANIMALS: 8 adult dogs. PROCEDURE: Scintigraphy was performed, using technetium Tc 99m diethylenetriaminepentacetic acid (Tc 99m-DTPA), before and within 2 weeks after surgical induction of unilateral partial ureteral obstruction. Time of peak (TOP) for the parenchyma (pTOP) and whole kidney (wTOP) and mean-transit time (MTT) for the parenchyma (pMTT) and whole kidney (wMTT) were determined by evaluation of renal time-activity curves before and after deconvolution analysis. Percentage uptake for each kidney between 1 and 3 minutes after injection of Tc 99m-DTPA was determined and used to indicate glomerular filtration rate. The effect of diuresis was determined by measuring the slope of decrease in activity after i.v. administration of furosemide. Obstruction was documented by direct inspection of the ureter. RESULTS: There was a concomitant increase in pTOP, wTOP, pMTT, and wMTT of the kidney with the partially obstructed ureter in all dogs at various times between 2 and 9 days after surgery. Concurrently, renal time-activity curves changed shape. Percentage renal uptake of the affected kidney was decreased in 2 dogs. Response to furosemide injection was inconsistent for kidneys before surgery and for kidneys with obstructed and nonobstructed ureters after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Scintigraphy may be a useful procedure for the evaluation of renal function in dogs with ureteral obstruction. Induction of diuresis appears to be of little value for differentiating renal function in dogs with obstructed and nonobstructed ureters.