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.     

Evaluation of circulating IGF-I and IGFBP-3 as biomarkers for tumors in dogs

BackgroundSerum-based parameters are considered non-invasive biomarkers for cancer detection. In human studies, insulin-like growth factor-I and II (IGF-I and IGF-II) and insulin-like growth factor binding protein-3 (IGFBP-3) are useful as diagnostic or prognostic markers and potential therapeutic targets.ObjectivesThis study examined the diagnostic utility of circulating IGF-I, IGF-II, and IGFBP-3 levels in healthy dogs and dogs with tumors.MethodsThe serum concentrations of these biomarkers in 86 dogs with tumors were compared with those in 30 healthy dogs using an enzyme-linked immunosorbent assay (ELISA).ResultsThe ELISA results showed no difference between healthy dogs and dogs with tumors in the serum IGF-II concentrations. On the other hand, there was a significant difference in the circulating IGF-I and IGFBP-3 levels between healthy dogs and dogs with tumors. The concentrations of serum IGF-I (median [interquartile range], 103.4 [59.5–175] ng/mL) in dogs with epithelial tumors were higher than those (58.4 ng/mL [43.5–79.9]) in healthy dogs. Thus, the concentrations of serum IGFBP-3 (43.4 ng/mL [33.2–57.2]) in dogs with malignant mesenchymal tumors were lower than those (60.8 ng/mL [47.6–70.5]) in healthy dogs.ConclusionsThe serum IGF-I and IGFBP-3 levels can be used as diagnostic biomarkers in dogs with tumors.     

Evaluation and Diagnostic Potential of Serum Ghrelin in Feline Hypersomatotropism and Diabetes Mellitus

Background

Ghrelin is a growth hormone secretagogue. It is a potent regulator of energy homeostasis. Ghrelin concentration is down‐regulated in humans with hypersomatotropism (HS) and increases after successful treatment. Additionally, ghrelin secretion seems impaired in human diabetes mellitus (DM).

Hypothesis

Serum ghrelin concentration is down‐regulated in cats with HS‐induced DM (HSDM) compared to healthy control cats or cats with DM unrelated to HS and increases after radiotherapy.

Animals

Cats with DM (n = 20) and with HSDM (n = 32), 13 of which underwent radiotherapy (RT‐group); age‐matched controls (n = 20).

Methods

Retrospective cross‐sectional study. Analytical performance of a serum total ghrelin ELISA was assessed and validated for use in cats. Differences in serum ghrelin, fructosamine, IGF‐1 and insulin were evaluated.

Results

Ghrelin was significantly higher (P < .001) in control cats (mean ± SD: 12.9 ± 6.8 ng/mL) compared to HSDM‐ (7.9 ± 3.3 ng/mL) and DM‐cats (6.7 ± 2.3 ng/mL), although not different between the HSDM‐ and DM‐cats. After RT ghrelin increased significantly (P = .003) in HSDM‐cats undergoing RT (from 6.6 ± 1.9 ng/mL to 9.0 ± 2.2 ng/mL) and the after RT ghrelin concentrations of HSDM cats were no longer significantly different from the serum ghrelin concentration of control cats. Serum IGF‐1 did not significantly change in HSDM‐cats after RT, despite significant decreases in fructosamine and insulin dose.

Conclusion and Clinical Importance

Ghrelin appears suppressed in cats with DM and HSDM, although increases after RT in HSDM, suggesting possible presence of a direct or indirect negative feedback system between growth hormone and ghrelin. Serum ghrelin might therefore represent a marker of treatment effect.     

Evaluation of serum chondroitin sulfate and hyaluronan: biomarkers for osteoarthritis in canine hip dysplasia

Hip dysplasia (HD) is one of the most important bone and joint diseases in dogs. Making the radiographic diagnosis is sometime possible when the disease has markedly progressed. Chondroitin sulfate (CS) and hyaluronan (HA) are the most important cartilage biomolecules that are elevated in the serum taken from dogs with osteoarthritis. The serum CS and HA can be detected by an ELISA technique, with using monoclonal antibodies against CS epitope 3B3 and WF6 and the HA chain as the primary antibodies. The aim of this study was to compare the levels of serum CS (both epitopes) and HA in non-HD and HD dogs. All 123 dogs were categorized into 2 groups. The non-HD group was composed of 98 healthy dogs, while the HD group was comprised of 25 HD dogs. Blood samples were collected for analyzing the serum CS and HA levels with using the ELISA technique. The results showed that the average serum level of the CS epitope WF6 in the HD group (2,594 ± 3,036.10 ng/ml) was significantly higher than that in the non-HD group (465 ± 208.97 ng/ml) (p < 0.01) while the epitope 3B3 in the HD group (105 ± 100.05 ng/ml) was significantly lower than that in the non-HD group (136 ± 142.03 ng/ml) (p < 0.05). The amount of serum HA in the HD group (134.74 ± 59.71 ng/ml) was lower than that in the non HD group (245.45 ± 97.84 ng/ml) (p < 0.05). The results indicate that the serum CS and HA levels might be used as biomarkers for osteoarthritis in HD dogs.     

Circadian variations of serum thyroxine, free thyroxine and 3,5,3'triiodothyronine concentrations in healthy dogs

This study was to determine the daily fluctuation of serum thyroxine (tT₄), free thyroxine (fT₄), 3,5,3''-triiodothyronine (T₃) concentrations in healthy dogs. Thyroid function of these dogs was evaluated on the basis of results of TSH response test. Samples for the measurement of serum tT₄, fT₄, and T₃ concentrations were obtained at 3-hour intervals from 8 : 00 to 20 : 00. Serum tT₄, fT₄, and T₃ concentrations were measured by the enzyme chemiluminescent immunoassay (ECLIA). Mean T₃ concentrations had no significant differences according to the sample collection time during the day. Mean tT₄ and fT₄ concentrations at 11 : 00 were 3.28 ± 0.86 µg/dl and 1.30 ± 0.37 ng/dl, respectively and mean tT₄ and fT₄ at 14:00 were 3.54 ± 1.15 µg/dl and 1.35 ± 0.12 ng/dl, respectively. These concentrations were significantly high compared with tT₄ and fT₄ concentrations at 8:00, which were 1.75 ± 0.75 µg/dl and 0.97 ± 0.25 ng/dl, respectively (p < 0.05). According to the sample collection time, mean tT₄ and fT₄ concentrations changed with similar fluctuation during the day. Based on these results, it was considered that measurement of serum tT₄ and fT₄ concentrations from 11 : 00 to 14 : 00 might more easily diagnose the canine hypothyroidism in practice.     

Reliability of history and physical examination findings for assessing control of glycemia in dogs with diabetes mellitus: 53 cases (1995-1998)

OBJECTIVE: To evaluate the reliability of history and physical examination findings for assessing control of glycemia in insulin-treated diabetic dogs. DESIGN: Retrospective study. ANIMALS: 53 insulin-treated dogs with diabetes mellitus. PROCEDURE: Medical records of insulin-treated diabetic dogs from June 1995 to June 1998 were reviewed, and information on owner perception of their dog's response to insulin treatment, physical examination findings, body weight, insulin dosage, and concentrations of food-withheld (i.e., fasting) blood glucose (FBG), mean blood glucose (MBG) during an 8-hour period, blood glycosylated hemoglobin (GHb), and serum fructosamine was obtained. Owner's perception of their dog's response to insulin treatment, physical examination findings, and changes in body weight were used to classify control of glycemia as good or poor for each dog. The FBG, MBG/8 h, blood GHb, and serum fructosamine concentrations were compared between well-controlled and poorly controlled insulin-treated diabetic dogs. RESULTS: Presence or absence of polyuria, polydipsia, polyphagia, lethargy, and weakness were most helpful in classifying control of glycemia. Mean FBG and MBG/8 h concentrations, blood GHb concentrations, and serum fructosamine concentrations were significantly decreased in 25 well-controlled diabetic dogs, compared with 28 poorly controlled diabetic dogs. Most well-controlled diabetic dogs had concentrations of FBG between 100 and 300 mg/dl, MBG/8 h < or = 250 mg/dl, blood GHb < or = 7.5%, and serum fructosamine < or = 525 mumol/L, whereas most poorly controlled diabetic dogs had results that were greater than these values. CONCLUSIONS AND CLINICAL RELEVANCE: Reliance on history, physical examination findings, and changes in body weight are effective for initially assessing control of glycemia in insulin-treated diabetic dogs.     

Pharmacokinetics of selamectin following intravenous,oral and topical administration in cats and dogs

The pharmacokinetics of selamectin were evaluated in cats and dogs, following intravenous (0.05, 0.1 and 0.2 mg/kg), topical (24 mg/kg) and oral (24 mg/kg) administration. Following selamectin administration, serial blood samples were collected and plasma concentrations were determined by high performance liquid chromatography (HPLC). After intravenous administration of selamectin to cats and dogs, the mean maximum plasma concentrations and area under the concentration-time curve (AUC) were linearly related to the dose, and mean systemic clearance (Clb) and steady-state volume of distribution (Vd(ss)) were independent of dose. Plasma concentrations after intravenous administration declined polyexponentially in cats and biphasically in dogs, with mean terminal phase half-lives (t(1/2)) of approximately 69 h in cats and 14 h in dogs. In cats, overall Clb was 0.470 +/- 0.039 mL/min/kg (+/-SD) and overall Vd(ss) was 2.19 +/- 0.05 L/kg, compared with values of 1.18 +/- 0.31 mL/min/kg and 1.24 +/- 0.26 L/kg, respectively, in dogs. After topical administration, the mean C(max) in cats was 5513 +/- 2173 ng/mL reached at a time (T(max)) of 15 +/- 12 h postadministration; in dogs, C(max) was 86.5 +/- 34.0 ng/mL at T(max) of 72 +/- 48 h. Bioavailability was 74% in cats and 4.4% in dogs. Following oral administration to cats, mean C(max) was 11,929 +/- 5922 ng/mL at T(max) of 7 +/- 6 h and bioavailability was 109%. In dogs, mean C(max) was 7630 +/- 3140 ng/mL at T(max) of 8 +/- 5 h and bioavailability was 62%. There were no selamectin-related adverse effects and no sex differences in pharmacokinetic parameters. Linearity was established in cats and dogs for plasma concentrations up to 874 and 636 ng/mL, respectively. Pharmacokinetic evaluations for selamectin following intravenous administration indicated a slower elimination from the central compartment in cats than in dogs. This was reflected in slower clearance and longer t(1/2) in cats, probably as a result of species-related differences in metabolism and excretion. Inter-species differences in pharmacokinetic profiles were also observed following topical administration where differences in transdermal flux rates may have contributed to the overall differences in systemic bioavailability.     

Association of Vitamin D Status and Clinical Outcome in Dogs with a Chronic Enteropathy

Background

Dogs with a chronic enteropathy (CE) have a lower vitamin D status, than do healthy dogs. Vitamin D status has been associated with a negative clinical outcome in humans with inflammatory bowel disease.

Objectives

To examine the relationship between serum 25 hydroxyvitamin D (25(OH)D) concentrations at diagnosis and clinical outcome in dogs with a CE.

Animals

Forty‐one dogs diagnosed with CE admitted to the Royal Dick School of Veterinary Studies, Hospital for Small Animals between 2007 and 2013.

Methods

Retrospective review. Serum 25(OH)D concentrations were compared between dogs which were alive at follow up or had died because of non‐CE‐related reasons (survivors) and dogs which died or were euthanized due to their CE (non‐survivors). A binary logistic regression analysis was performed to determine significant predictors of death in dogs with CE.

Results

Serum concentrations of 25(OH)D at the time a CE was diagnosed were significantly lower in nonsurvivors (n = 15) (median nonsurvivors 4.36 ng/mL, interquartile range 1.6–17.0 ng/mL), median survivors (n = 26) (24.9 ng/mL interquartile range 15.63–39.45 ng/mL, P < .001). Serum 25(OH)D concentration was a significant predictor of death in dogs with CE (odds ratio 1.08 [95% CI 1.02–1.18)]).

Conclusions

Serum 25(OH)D concentrations at diagnosis are predictive of outcome in dogs with CE. The role of vitamin D in the initiation and outcome of chronic enteropathies in dogs is deserving of further study.     

Serum concentrations of leptin and adiponectin in dogs with chronic kidney disease

BackgroundAn imbalance in adipokines is associated with the progression of chronic kidney disease (CKD) in humans. However, alterations in adipokines in dogs with CKD remain unclear.ObjectivesTo examine whether adipokine concentrations in serum differ between healthy dogs and dogs with CKD and to determine the correlation between serum adipokine concentrations and CKD severity in dogs.AnimalsTwenty dogs with CKD and 10 healthy dogs.MethodsIn this cross‐sectional study, serum concentrations of leptin, adiponectin, interleukin (IL)‐6, IL‐10, IL‐18, and tumor necrosis factor (TNF)‐α were measured in healthy dogs and dogs with CKD, which were classified according to the International Renal Interest Society guidelines.ResultsSerum leptin concentrations were positively correlated with systolic arterial blood pressure (r = .41), creatinine concentrations (r = .39), and symmetric dimethylarginine concentrations (r = .73). Serum adiponectin concentrations (median [range]) in CKD dogs with borderline or non‐proteinuric (20.25 [14.9‐45.8] ng/mL) were significantly higher than those in proteinuric CKD dogs (13.95 [6.4‐22.1] ng/mL; P = .01). Serum IL‐6 (median [range]; 43.27 [24.30‐537.30] vs 25.63 [6.83‐61.03] pg/mL; P = .02), IL‐18 (median [range]; 25.98 [11.52‐280.55] vs 10.77 [3.53‐38.45] pg/mL; P = .01), and TNF‐α (median [range]) concentrations (11.44 [8.54‐38.45] vs 6.105 [3.97‐30.68] pg/mL; P = .02) were significantly different between proteinuric and borderline or non‐proteinuric CKD dogs.Conclusions and Clinical Importanceleptin and adiponectin concentrations in serum might be associated with severity of CKD and proteinuria in dogs with CKD, respectively.     

Influence of gonadotropins on insulin- and insulin-like growth factor-I (IGF-I)-induced steroid production by bovine granulosa cells

To determine the effect of gonadotropins on insulin- and insulin-like growth factor (IGF-I)-induced bovine granulosa cell functions, granulosa cells from bovine ovarian follicles were cultured for 2 days in the presence of 10% fetal calf serum (FCS), and then cultured for an additional 2 days in serum-free medium with added hormones. In the presence of 0 or 1 ng/mL of insulin or IGF-I, FSH had little or no effect (P>0.05) on estradiol production by granulosa cells from both small (1–5 mm) and large (≥8 mm) follicles. However, in the presence of ≥3 ng/mL of insulin, FSH increased (P<0.05) estradiol production by granulosa cells from small and large follicles such that the estimated dose (ED₅₀) of insulin necessary to stimulate 50% of the maximum estradiol production was decreased by 2- to 3-fold from 22 to 28 ng/mL in the absence of FSH to 7–14 ng/mL in the presence of FSH. Similarly, in the presence of ≥3 ng/mL of IGF-I, FSH increased (P<0.05) estradiol production by granulosa cells from small and large follicles such that the ED₅₀ of IGF-I for estradiol production was decreased by 4- to 5-fold from 25 to 36 ng/mL in the absence of FSH to 5–6 ng/mL in the presence of FSH. In the presence of FSH, the maximal effect of insulin on estradiol production was much greater than that of IGF-I (137- versus 12-fold increase) and were not additive; when combined, 100 ng/mL of IGF-I completely blocked the stimulatory effect of 100 ng/mL of insulin. In the absence of FSH, the maximal effect of insulin and IGF-I on estradiol production was similar. Concomitant treatment with 30 ng/mL of LH reduced (P<0.05) insulin-stimulated estradiol production by 52% on day 1 and 19% on day 2 of treatment. Insulin, IGF-I and FSH also increased (P<0.05) granulosa cell numbers and progesterone production but their maximal effects were less (i.e., <4-fold increase) than their effects on estradiol production. In conclusion, insulin and IGF-I synergize with FSH to directly regulate ovarian follicular function in cattle, particularly granulosa cell aromatase activity.     

Pasireotide for the Medical Management of Feline Hypersomatotropism

Background

Feline hypersomatotropism (HST) is a cause of diabetes mellitus in cats. Pasireotide is a novel multireceptor ligand somatostatin analog that improves biochemical control of humans with HST.

Hypothesis/Objectives

Pasireotide improves biochemical control of HST and diabetes mellitus in cats.

Animals

Hypersomatotropism was diagnosed in diabetic cats with serum insulin‐like growth factor‐1 (IGF‐1) concentration >1,000 ng/mL by radioimmunoassay and pituitary enlargement.

Methods

Insulin‐like growth factor 1 was measured and glycemic control assessed using a 12‐hour blood glucose curve on days 1 and 5. On days 2, 3, and 4, cats received 0.03 mg/kg pasireotide SC q12h. IGF‐1, insulin dose, and estimated insulin sensitivity (product of the area under the blood glucose curve [BGC] and insulin dose) were compared pre‐ and post treatment. Paired t‐tests or Wilcoxon signed rank tests were employed for comparison where appropriate; a linear mixed model was created to compare BGC results.

Results

Insulin‐like growth factor 1 decreased in all 12 cats that completed the study (median [range] day 1: 2,000 ng/mL [1,051–2,000] and day 5: 1,105 ng/mL [380–1,727], P = .002, Wilcoxon signed rank test). Insulin dose was lower on day 5 than on day 1 (mean reduction 1.3 [0–2.7] units/kg/injection, P = .003, paired t‐test). The product of insulin dose and area under the BGC was lower on day 5 than day 1 (difference of means: 1,912; SD, 1523; u × mg/dL × hours, P = .001; paired t‐test). No clinically relevant adverse effects were encountered.

Conclusions

Short‐acting pasireotide rapidly decreased IGF‐1 in cats with HST and insulin‐dependent diabetes. The decrease in IGF‐1 was associated with increased insulin sensitivity.     

Cardiac troponin I in the normal dog and cat

Cardiac troponin I (cTnI) has proven to be a highly specific and sensitive marker for myocardial cellular damage in many mammalian species. The structure of cTnI is highly conserved across species, and assays for human cTnI (including the one used in the current study) have been validated in the dog. Blood concentrations of cTnI rise rapidly after cardiomyocyte damage, and assay of cTnI potentially may be valuable in many clinical diseases. The purpose of this study was to establish the normal range of cTnI in heparinized plasma of dogs and cats. Forty one clinically normal dogs and 21 cats were included in the study. One to 3 milliliters of blood were collected by venipuncture into lithium heparin vacutainers for analysis of cTnI (Stratusz CS). The range of plasma cTnI concentrations in dogs was <0.03 to 0.07 ng/mL with a mean of 0.02 ng/mL, with the upper tolerance limit (0.07 ng/mL) at the 90th percentile with 95% confidence. In cats, the range was <0.03 to 0.16 ng/mL with a mean of 0.04 ng/mL, and the upper tolerance limit (0.16 ng/mL) at the 90th percentile as well with 90% confidence. This study establishes preliminary normal ranges of plasma cTnI in normal dogs and cats for comparison to dogs and cats with myocardial injury or disease.     

Serum Erythropoietin Concentrations Measured by Radioimmunoassay in Normal, Polycythemic, and Anemic Dogs and Cats

Serum erythropoietin (Epo) concentrations were measured by radioimmunoassay (RIA) in normal, polycythemic, and anemic dogs and cats. The serum Epo concentration in normal dogs ( n = 25) ranged from 7 to 37 mU/mL (median, 20 mU/mL); and in normal cats ( n = 11) ranged from 9 to 38 mU/mL (median, 18 mU/mL). Polycythemic animals (PCV < 55% in dogs, > 45% in cats) were classified as those with primary (polycythemia vera), secondary, or polycythemia of uncertain etiology. Dogs with polycythemia vera (PV, n = 8) had a median serum Epo concentration in the normal range (17 mU/mL); cats with PV ( n = 7) also had a median serum Epo concentration that was within the normal range (10 mU/mL). In the category of secondary polycythemias, dogs ( n = 7) (median, 30.7 mU/mL) and cats ( n = 2) had normal Epo concentrations. The median serum Epoconcentration was significantly decreased ( P > .05) in dogs with PV compared with dogs with secondary polycythemias. The median serum Epo concentrations in dogs ( n = 13) and cats ( n = 5) with anemias not due to chronic renal disease were significantly increased ( P > .05) compared with normal dogs and cats. In cats with anemias due to chronic renal disease ( n = 5) the median serum Epo concentration was not significantly different from normal cats. The measurement of the serum EPO concentration may be useful in assessment of anemia or polycythemia but the overlap of values with the normal range in all groups evaluated limit its diagnostic use.     

Glycemic Status and Predictors of Relapse for Diabetic Cats in Remission

Background

It is unknown if diabetic cats in remission have persistent abnormalities of glucose metabolism and should be considered prediabetic, or have normal glucose tolerance.

Objective

To characterize glycemic status of diabetic cats in remission and to determine predictors of relapse.

Animals

A total of 21 cats in diabetic remission and 28 healthy control cats.

Methods

At a median of 107 days after remission, screening blood glucose concentration was measured on entry to the clinic. After a 24‐hour fast in hospital, fasting blood glucose, fructosamine and feline pancreatic lipase concentrations were measured, and 3 hours later, a simplified IV glucose tolerance test (1 g glucose/kg) performed. Twenty cats were monitored for relapse for at least 9 months.

Results

Of the 21 cats in remission, 19% (4/21) had impaired fasting glucose concentration and 76% (16/21) had impaired glucose tolerance. Of cats followed up for 9 months after testing, 30% (6/20) had relapsed and required insulin treatment. Fasting blood glucose concentration ≥7.5 mmol/L (≥135 mg/dL) (odds ratio [OR] = 12.8) and severely impaired glucose tolerance (≥5 hours to return to <6.5 mmol/L or <117 mg/dL; OR = 15.2) were significantly associated with relapse. Blood glucose concentration >14 mmol/L; 252 mg/dL at 3 hours was significantly associated with relapse (OR = 10.1).

Conclusion and Clinical Importance

Most cats in diabetic remission have impaired glucose tolerance and a minority have impaired fasting glucose concentration and should be considered prediabetic. More severe glucose intolerance and impaired fasting glucose concentration are predictors of relapse. Ongoing glucose monitoring of diabetic cats in remission is recommended.     

Incidence,Severity and Prognosis Associated with Hypernatremia in Dogs and Cats

Background

Hypernatremia has been associated with substantial morbidity and death in human patients. The incidence and importance of hypernatremia in dogs and cats has not been determined.

Hypothesis/Objectives

To describe the incidence of and prognosis associated with hypernatremia in dogs and cats at a university teaching hospital.

Animals

A total of 16,691 dogs and 4,211 cats with measured blood or serum sodium concentration.

Methods

Retrospective study. Medical records of animals with a blood or serum sodium concentration measured during a 60‐month period were reviewed to determine the severity of hypernatremia and its associated case fatality rate. Cases with moderate (11–15 mmol/L above the reference range) or severe hypernatremia (≥16 mmol/L above the reference range) were further reviewed.

Results

A total of 957 dogs (5.7%) and 338 cats (8.0%) were diagnosed with hypernatremia. Case fatality rates of dogs and cats with hypernatremia was 20.6 and 28.1%, respectively compared to 4.4 and 4.5% with a normal blood or serum sodium concentration (P < .0001). The magnitude of hypernatremia was linearly associated with a higher case fatality rate (P < .0001). Hypernatremia was associated with a higher case fatality rate than hyponatremia. Among the animals with moderate or severe hypernatremia, 50% of dogs and 38.5% of cats presented with community‐acquired hypernatremia, and 50% of dogs and 61.5% of cats developed hospital‐acquired hypernatremia.

Conclusions and clinical importance

Hypernatremia was found infrequently in this population but was associated with increased case fatality rates in dogs and cats. Presence and severity of hypernatremia might be useful as a prognostic indicator.     

Assessment of glomerular filtration rate with dynamic computed tomography in normal Beagle dogs

The objective of our study was to determine individual and global glomerular filtration rates (GFRs) using dynamic renal computed tomography (CT) in Beagle dogs. Twenty-four healthy Beagle dogs were included in the experiment. Anesthesia was induced in all dogs by using propofol and isoflurane prior to CT examination. A single slice of the kidney was sequentially scanned after a bolus intravenous injection of contrast material (iohexol, 1 mL/kg, 300 mgI/mL). Time attenuation curves were created and contrast clearance per unit volume was calculated using a Patlak plot analysis. The CT-GFR was then determined based on the conversion of contrast clearance per unit volume to contrast clearance per body weight. At the renal hilum, CT-GFR values per unit renal volume (mL/min/mL) of the right and left kidneys were 0.69 ± 0.04 and 0.57 ± 0.05, respectively. No significant differences were found between the weight-adjusted CT-GFRs in either kidney at the same renal hilum (p = 0.747). The average global GFR was 4.21 ± 0.25 mL/min/kg and the whole kidney GFR was 33.43 ± 9.20 mL/min. CT-GFR techniques could be a practical way to separately measure GFR in each kidney for clinical and research purposes.     

Analytical determination and pharmacokinetics of robenacoxib in the dog

An analytical method was developed and validated for the measurement of the novel analgesic and anti-inflammatory drug robenacoxib in blood and plasma of dogs and cats. To prevent nonreproducible carry-over effects, an initial solid phase extraction procedure was followed by high pressure liquid chromatography analysis for samples with concentrations in the range 500 to 20 000 ng/mL. To improve accuracy, samples of concentration 3 to 100 ng/mL were analyzed by liquid chromatography-mass spectrometry. Applying these methods, blood concentration-time profiles and pharmacokinetic variables of robenacoxib in dogs were determined in a four-phase cross-over study, which compared different routes of administration of the drug, including intravenous (i.v.) injection, oral application with and without feed, and subcutaneous (s.c.) application. After i.v. administration the mean clearance from blood was 0.81 L/kg/h, the volume of distribution was 0.77 L/kg for the elimination phase and 0.24 L/kg for steady-state, and the terminal half-life in blood was 0.63 h. Maximum blood concentrations were obtained in less than 1 h following oral or s.c. application. Absolute bioavailability was 88% after s.c. injection, 84% after oral administration to fasted dogs, but was reduced to 62% when applied orally to fed dogs. In canine and feline plasma the degree of binding of robenacoxib to plasma protein in vitro was greater than 98%. The blood:plasma concentration ratio was 0.44:1 in the dog and 0.65:1 in the cat. In conclusion analytical methods for the quantification of robenacoxib in blood and plasma in the dog and cat were developed and validated. In dogs, robenacoxib has good bioavailability after oral (84%) and subcutaneous (88%) administration.     

Incidence,Severity and Prognosis Associated with Hyponatremia in Dogs and Cats

Background

Hyponatremia is a common electrolyte abnormality in human patients and is associated with substantial morbidity and death. The incidence and importance of hyponatremia in dogs and cats has not been determined.

Hypothesis/Objectives

To describe the incidence of and prognosis associated with hyponatremia in dogs and cats at a university teaching hospital.

Animals

Of 16,691 dogs and 4,211 cats with measured blood or serum sodium concentration.

Methods

Retrospective study. Medical records of animals with a blood or serum sodium concentration measured during a 60‐month period were reviewed to determine the severity of hyponatremia and its associated fatality rate. Cases with moderate (11–15 mmol/L below the reference range) or severe hyponatremia (≥16 mmol/L below the reference range) were further reviewed.

Results

Of 4,254 dogs (25.5%) and 2,081 cats (49.4%) were diagnosed with hyponatremia. Case fatality rates of dogs and cats with hyponatremia were 13.7% and 11.9%, respectively, compared to 4.4% and 4.5% with a normal blood or serum sodium concentration (P < 0.0001). The magnitude of hyponatremia was linearly associated with a higher case fatality rate (P < 0.0001). Hyponatremia was associated with a lower case fatality rate than hypernatremia in the same population. Among the animals with moderate or severe hyponatremia, 92.1% of dogs and 90.6% of cats presented with community‐acquired hyponatremia, and 7.9% of dogs and 9.4% of cats developed hospital‐acquired hyponatremia.

Conclusions and clinical importance

Hyponatremia was found commonly in this population and was associated with increased case fatality rate. Presence and severity of hyponatremia might be useful as a prognostic indicator.     

Evaluation of serum insulin-like growth factor binding proteins (IGFBP) in Angus cattle divergently selected for serum IGF-I concentration

Postweaning serum insulin-like growth factor-I (IGF-I) concentrations and serum IGF binding proteins (IGFBP) were investigated in 68 (1992 Fall-born) and 84 (1999 Fall-born) Angus cattle selected for either high or low serum IGF-I concentrations since 1989. Relative serum levels of IGFBP were determined by [¹²⁵I]IGF-I Western ligand blotting. IGFBP species of 38–42, 34, 30, and 24 kDa were identified. The 34 kDa species was identified as IGFBP-2 by immunoblot analysis. No significant line effects were observed for any of the IGFBP. In both 1992 and 1999, heifers had higher IGFBP-2 levels than bulls (P<0.0005). In 1992 calves, relative levels of the 38–42 and 24 kDa species were significantly correlated with serum IGF-I concentration. In 1999 calves, none of the IGFBP were correlated with serum IGF-I, although IGFBP-2 was negatively correlated with several measures of body weight. No significant line effects were observed for growth or serum IGF-I traits in 1992 calves. However, 1999 high line calves had higher serum IGF-I concentrations and body weights than low line calves (P<0.05). In both 1992 and 1999 calves, bulls had higher serum IGF-I concentrations and body weights than heifers (P<0.05). Thus, while selection for high versus low serum IGF-I concentrations has resulted in divergence between the selection lines and also in changes in body weights, it has not resulted in changes in serum IGFBP levels. Furthermore, circulating IGFBP-2 appears to be higher in heifers than in bulls, and also appears to be negatively correlated with body weights.     

Effect of Chronic Administration of Phenobarbital,or Bromide,on Pharmacokinetics of Levetiracetam in Dogs with Epilepsy

Background

Levetiracetam (LEV) is a common add‐on antiepileptic drug (AED) in dogs with refractory seizures. Concurrent phenobarbital administration alters the disposition of LEV in healthy dogs.

Hypothesis/Objectives

To evaluate the pharmacokinetics of LEV in dogs with epilepsy when administered concurrently with conventional AEDs.

Animals

Eighteen client‐owned dogs on maintenance treatment with LEV and phenobarbital (PB group, n = 6), LEV and bromide (BR group, n = 6) or LEV, phenobarbital and bromide (PB–BR group, n = 6).

Methods

Prospective pharmacokinetic study. Blood samples were collected at 0, 1, 2, 4, and 6 hours after LEV administration. Plasma LEV concentrations were determined by high‐pressure liquid chromatography. To account for dose differences among dogs, LEV concentrations were normalized to the mean study dose (26.4 mg/kg). Pharmacokinetic analysis was performed on adjusted concentrations, using a noncompartmental method, and area‐under‐the‐curve (AUC) calculated to the last measured time point.

Results

Compared to the PB and PB–BR groups, the BR group had significantly higher peak concentration (C _max) (73.4 ± 24.0 versus 37.5 ± 13.7 and 26.5 ± 8.96 μg/mL, respectively, P < .001) and AUC (329 ± 114 versus 140 ± 64.7 and 98.7 ± 42.2 h*μg/mL, respectively, P < .001), and significantly lower clearance (CL/F) (71.8 ± 22.1 versus 187 ± 81.9 and 269 ± 127 mL/h/kg, respectively, P = .028).

Conclusions and Clinical Importance

Concurrent administration of PB alone or in combination with bromide increases LEV clearance in epileptic dogs compared to concurrent administration of bromide alone. Dosage increases might be indicated when utilizing LEV as add‐on treatment with phenobarbital in dogs.