Effect of glipizide on serum insulin and glucose concentrations in healthy cats.

With the recent identification of non-insulin-dependent diabetes mellitus (NIDDM) in cats, new possibilities arise for the use of oral hypoglycaemic agents in the treatment of feline NIDDM, similar to their use in humans. To identify the future applicability of the oral hypoglycaemic agent, glipizide, in the treatment of feline NIDDM, its effects on serum insulin and glucose concentrations in healthy cats was examined. In addition, adverse effects seen clinically or on bloodwork following short-term use of the drug were looked for. Serum insulin and glucose concentrations were evaluated after the oral administration of 2.5, 5.0 and 10.0 mg glipizide and placebo in 10 healthy cats. For each drug trial, blood was obtained five minutes before, immediately before, and 7.5, 15, 30, 45, 60, 90 and 120 minutes after glipizide or placebo administration. Mean serum insulin concentration increased after glipizide administration, with peak mean serum insulin concentration occurring 15 minutes after administration and declining to baseline by 60 minutes. There was no significant difference in peak mean serum insulin concentration, mean serum insulin concentration at 60 minutes after glipizide administration, or mean total insulin secretion between the three glipizide dosages. Mean serum glucose concentration decreased within 15 minutes of glipizide administration, with the glucose nadir occurring 60 minutes after glipizide administration. Placebo trials showed no significant change in mean serum insulin or glucose concentrations from baseline concentrations.     

Effect of clomipramine on the electrocardiogram and serum thyroid concentrations of healthy cats

Clomipramine is a tricyclic antidepressant (TCA) commonly used to treat anxiety related behavioral disorders in companion animals. Tricyclic antidepressants (TCAs) have the potential to cause arrhythmias in humans and companion animals. The effect of the TCAs, clomipramine, and amitriptyline, at therapeutic dosages on cardiac rhythm has been evaluated in dogs. The effect of clomipramine on the cardiac rhythm of cats has not been reported. In Experiment 1, 7 healthy cats were selected to evaluate the effect of clomipramine on their cardiac rhythm using an electrocardiogram. A baseline electrocardiogram was carried out before (Day 0) and repeated (Day 29) after 4 weeks (28 days) of daily clomipramine (10 mg/cat PO) administration. Significant changes in the electrocardiogram were not found after 28 days of daily clomipramine administration. In Experiment 2, 7 healthy cats were enrolled in the study to evaluate the effect of clomipramine administration on the serum thyroid concentrations in cats. Clomipramine (10 mg/cat PO daily) was administered to all cats beginning on Day 1, and continued for 28 days. Serum total thyroxine (T₄), triiodothyronine (T₃), and free thyroxine (fT₄) concentrations were measured before (Day 0) and repeated (Day 29) after 4 weeks (28 days) of daily clomipramine administration. Statistically significant decreases in serum thyroid concentrations (T_4, T₃, and fT₄) were noted between pre and post clomipramine administration. A decrease of 25, 24, and 16% in serum T₄, T₃, and fT₄ concentrations, respectively, may lead to a misdiagnosis of euthyroidism in a subclinical hyperthyroid patient. A longer duration of drug treatment might further suppress thyroid function when used as a single agent, with concomitantly administered drugs, or in conjunction with euthyroid sick syndrome.     

Effect of dietary soy on serum thyroid hormone concentrations in healthy adult cats

OBJECTIVE: To compare effects of short-term administration of a soy diet with those of a soy-free diet on serum thyroid hormone concentrations in healthy adult cats. ANIMALS: 18 healthy adult cats. PROCEDURE: Cats were randomly assigned to receive either a soy or soy-free diet for 3 months each in a crossover design. Assays included CBC, serum biochemical profile, thyroid hormone analysis, and measurement of urinary isoflavone concentrations. RESULTS: Genistein, a major soy isoflavone, was identified in the urine of 10 of 18 cats prior to dietary intervention. Compared with the soy-free diet, cats that received the soy diet had significantly higher total thyroxine (T4) and free T4 (fT4) concentrations, but unchanged total triiodothyronine (T3) concentrations. The T3/fT4 ratio was also significantly lower in cats that received the soy diet. Although the magnitudes of the increases were small (8% for T4 and 14% for fT4), these changes resulted in an increased proportion of cats (from 1/18 to 4/18) that had fT4 values greater than the upper limit of the laboratory reference range. There was no significant effect of diet on any other measured parameter. CONCLUSIONS AND CLINICAL RELEVANCE: Short-term administration of dietary soy has a measurable although modest effect on thyroid hormone homeostasis in cats. Increase in T4 concentration relative to T3 concentration may result from inhibition of 5'-iodothyronine deiodinase or enhanced T3 clearance. Soy is a common dietary component that increases serum T4 concentration in cats.     

Evaluation of ionized and total serum magnesium concentrations in hyperthyroid cats

Hyperthyroidism can increase the renal excretion of magnesium and thus cause hypomagnesemia in various species. Anaerobically collected blood samples from 15 hyperthyroid and 40 normal, healthy cats were analyzed with an ion-selective electrode analyzer and a serum biochemical analyzer. There was no significant difference in ionized or total serum magnesium concentration between the 2 groups, but there was a significant difference (P = 0.004) in the ratio of ionized to total serum magnesium concentrations between the healthy cats and the hyperthyroid cats with thyroxine (T4) concentrations at or above the median. There was a significant correlation (r = 0.894, P = 0.000) between the ionized and total magnesium concentrations in the hyperthyroid cats. The hyperthyroid cats had a significantly lower (P = 0.003) total serum protein concentration than the healthy cats. A significant negative correlation (r = -0.670, P = 0.006) was detected between the ionized magnesium and logarithmically transformed total T4 concentrations in the hyperthyroid cats, which suggests that the severity of hyperthyroidism may contribute to a decrease in the ionized magnesium concentration.     

Comparison of three commercially available prescription diet regimens on short-term post-prandial serum glucose and insulin concentrations in healthy cats

Dietary therapy is an important treatment component for diabetes mellitus (DM). In this study, the impact of three different commercially available diet regiments (1 general use and 2 aimed for treating obesity and DM) on short-term post-prandial serum glucose and insulin concentrations of five healthy cats to better understand what impact each of these diets may have for diabetic cats. The diet regiments used in this study were as follows: C/D dry (General Use- Low protein, High fat, High carbohydrate, and Low fiber), M/D dry (DM- High protein, High fat, Low carbohydrate, and High Fiber), and W/D dry (DM- Low Protein, Low Fat, High Carbohydrate, and High Fiber). No significant difference in post-prandial serum glucose levels were observed with the C/D (84.6 ± 1.5 mg/dl) and W/D (83.8 ± 1.4 mg/dl) dry diets when compared to pre-prandial fasting levels (83.9 ± 1.4 mg/dl). However, a significant reduction was observed with the M/D diet (78.9 ± 0.8 mg/dl) which had 50-60% less carbohydrates than either C/D or W/D diet. Unlike what was observed with post-prandial glucose levels, an interesting pattern emerged with post-prandial insulin levels, which were increasing with W/D, C/D, and M/D diets in that order (1.1 ± 0.2, 1.7 ± 0.2, and 2.3 ± 0.2 ng/ml respectively). Most surprising, though, was the fact that the W/D diet did not seem to stimulate insulin secretion as compared to pre-prandial levels (1.1 ± 0.1 ng/ml) in healthy cats. Interestingly, the W/D diet had high levels of carbohydrate and low levels of protein. Coincidentally, the only diet (M/D) which had a significant reduction in post-prandial glucose also showed the highest increase in post-prandial insulin in healthy cats. Therefore, dietary amounts of carbohydrate, fat, protein and fiber can all have an individual impact on post-prandial glycemia and subsequent insulin requirement levels. Just as concepts regarding dietary management of people with DM are evolving, investigators are reassessing what constitutes the ideal diet for the diabetic feline. As such, having a better understanding for each dietary component, may lead us to better understand how we can synergize certain dietary components to aid in DM management.     

Plasma, tissue, and urine carnitine concentrations in healthy adult cats and kittens

Mean carnitine concentrations [( carnitine]) were higher (P less than 0.05) in adult cats than in kittens for skeletal muscle (total and free carnitine), myocardium (free carnitine), and urine (total and free carnitine). The free/total carnitine ratio was lower (P less than 0.05) in kittens than in adults for liver, myocardium, and urine. Carnitine concentrations were similar between genders in kittens, but in adult cats, [carnitine] in plasma (total, free, and esterified carnitine) and liver (total and free carnitine) were higher (P less than 0.05) in female than in male cats. Total and free plasma [carnitine] were correlated to total and free liver [carnitine], respectively. Skeletal muscle [carnitine] was not correlated to plasma [carnitine]. Correlations in [carnitine] between plasma and myocardium, kidney, or urine were inconsistent.     

Evaluation of serum and urine 1,5-anhydro-D-glucitol and myo-inositol concentrations in healthy dogs

1,5-anhydro-D-glucitol (1,5AG) is a pyranoid polyol compound found in human circulating blood. Myo-inositol (MI) is a stereoisomer of inositol and serves as a precursor of inositol phospholipids. 1,5AG and MI are filtered by the glomerulus and almost completely reabsorbed through the renal tubules. However, under hyperglycemic conditions, reabsorption through the renal tubules is competitively inhibited because the structures of 1,5AG and MI resemble that of glucose. In this study, we investigated the kinetics of serum and urine 1,5AG and MI levels in healthy dogs. We demonstrated that 1,5AG and MI exist in canine serum and urine by gas chromatography-mass spectrometry. Under continuous hyperglycemic conditions, the serum 1,5AG concentration in healthy dogs decreased while the serum MI concentration remained unchanged. Urinary excretion of 1,5AG and MI increased significantly after blood glucose concentrations reached 200 to 220 mg/dl. A significant negative correlation was observed between serum 1,5AG and glucose concentrations during hyperglycemia. However, no significant correlation was observed between serum MI and glucose concentrations. In this study, we demonstrated that serum and urine 1,5AG and MI levels were changed by blood glucose concentrations. The serum 1,5AG concentration was decreased by continuous hyperglycemia. However, the serum MI concentration does not reflect hyperglycemia.     

Effect of glimepiride and nateglinide on serum insulin and glucose concentration in healthy cats

Glimepiride and nateglinide are two common oral hypoglycemic agents currently being used with humans suffering from Type 2 diabetes mellitus. Neither drug has been tested with cats thus far and it is currently unknown whether either of these drugs exert any effect in cats or not. The objective of this study was to determine the effect of glimepiride and nateglinide on glucose and insulin responses in healthy control cats, in order to determine their potential use in diabetic cats. The intravenous glucose tolerance tests was carried out since it is an excellent test for evaluating pancreatic β-cell function for insulin secretion. Alterations in the insulin secretion pattern can be perceived as the earliest sign of β-cell dysfunction in many species, including cats. Nateglinide demonstrated a quick action/short duration type effect with serum glucose nadiring and insulin response peaking at 60 and 20 minutes, respectively. Alternatively, glimepiride is medium-to-long acting with serum glucose nadiring and insulin response peaking at 180 minutes and 60 minutes, respectively. Nateglinide’s potency was evident allowing it to induce a 1.5–2 higher preliminary insulin peak (3.7?±?1.1 pg/ml) than glimepiride’s (2.5?±?0.1 pg/ml), albeit only for a short period of time. Because glimepiride and nateglinide have a shared mode of action, no significant differences in overall glucose AUC_0-360min (24,435?±?2,940 versus 24,782?±?2,354 mg min/dl) and insulin AUC_0-360min (410?±?192 versus 460?±?159) in healthy control cats were observed. These findings may provide useful information when choosing a hypoglycemic drug suited for the treatment of diabetic cats depending on the degree of diabetes mellitus the cat is suffering from.     

Myocardial taurine concentrations in cats with cardiac disease and in healthy cats fed taurine-modified diets.

Myocardial taurine concentrations were measured in cats with cardiac disease and in healthy cats fed diets with various concentrations of taurine. Group 1 was composed of 26 cats with 3 categories of naturally developing cardiac disease: dilatative cardiomyopathy (group 1A), 10 cats; hypertrophic cardiomyopathy (group 1B), 9 cats; and volume overload (group 1C), 7 cats. These cats had been fed various commercial diets. Group 2 was composed of 40 healthy cats that had been fed diets varying in taurine concentration (0 to 1% taurine) for at least 2 years. Mean myocardial taurine concentrations did not differ significantly between group-1 cats with dilatative cardiomyopathy and those with hypertrophic cardiomyopathy or volume overload. Cats in group 1A had a mean myocardial taurine concentration 3 times higher than healthy cats fed a taurine-free diet (P less than 0.002). Mean myocardial taurine concentrations did not differ significantly between group-1A cats and healthy cats fed a diet containing 0.02% taurine; group-1A cats had significantly lower mean myocardial taurine concentrations than did healthy cats fed a synthetic diet containing 0.05 or 1.0% taurine (P less than 0.001). Acute oral administration of taurine in 5 group-1A cats appeared to increase mean myocardial taurine concentrations, compared with similar cats not given taurine during treatment for cardiac failure. In group-2 cats, mean myocardial taurine concentrations increased directly with percentage of dietary taurine.     

Prevalence and incidence of serum magnesium abnormalities in hospitalized cats

Total serum magnesium concentration ([Mg2+]s) was prospectively determined for 57 cats admitted to the intensive care unit (ICU) of the Cornell University Hospital for Animals. Data were collected and analyzed to determine the following: prevalence and incidence of [Mg2+] abnormalities, medical disorders associated with altered [Mg2+]s, association of altered [Mg2+]s with other electrolyte abnormalities, length of hospitalization for cats with abnormalities of [Mg2+]s versus those with normal [Mg2+]s, and survival of cats with abnormal [Mg2+)s versus those with normal [Mg2+]s. The point prevalence of magnesium abnormalities was 26%, the period prevalence was 46%, and the cumulative incidence was 23%. Hypermagnesemia was associated with abnormalities of serum potassium (P = .04) and phosphate (P = .01) concentrations. Abnormalities of [Mg2+]s were not associated with abnormal serum concentrations of Na+, Ca2+, or Cl-. On admission. hypomagnesemia was detected in cats with gastrointestinal, endocrine, and other disorders; hypermagnesemia was detected only in cats with renal disease, obstructive uropathy, or neoplastic disease. The median hospital stay for cats that developed abnormal [Mg2+]s after admission was longer than for cats that remained normomagnesemic (5 versus 4 days, respectively; P = .03). Despite the longer hospital stay, the survival of these cats was lower than that of normomagnesemic cats (54 versus 77%; P = .05). When all cats were considered, the survival of cats with abnormal [Mg2+]s also was decreased compared with normomagnesemic cats (62 versus 81%; P = .05). We conclude that abnormalities of [Mg2+]s may affect morbidity and mortality of affected cats.     

Effect of pre-calving zeolite, magnesium and phosphorus supplementation on periparturient serum mineral concentrations

The objective of this study was to test whether supplementing dry cow rations with phosphorus (P) and magnesium (Mg) would interfere with the beneficial effect of zeolite supplementation on the periparturient blood calcium (Ca) concentration in dairy cattle. Three groups (A-C) of 10 Danish Jersey cows were each given the following daily supplements from 2 weeks before the expected date of calving until actual calving: group A: zeolite, monoammonium phosphate, standard dry cow mineral and vitamin mix, containing 61g magnesium phosphate; group B: zeolite, standard mineral and vitamin mix without the magnesium phosphate and group C: standard mineral and vitamin mix, monoammonium phosphate. All cows in group B had an apparently less variable serum calcium concentration around calving with no cases of milk fever and no subclinical hypocalcaemia or hypomagnesaemia recorded. In contrast, a parturient drop in blood Ca was seen in group A as well as group C. In group A, one cow was hypocalcaemic at calving, and developed milk fever. In group C, 12 blood samples, representing six cows, were hypocalcaemic, and three of these cows were treated for milk fever. All groups remained normomagnesaemic and there were no significant differences in blood Mg across groups. In conclusion, the combined P and Mg supplementation in addition to zeolite supplementation did not increase the serum Mg level (forage Mg 16.9g/day; 0.21% of DM). Combined P and Mg supplementation reduced the zeolite-induced hypophosphataemia but also reduced the stabilising effect of zeolite on parturient serum Ca.     

Serum cobalamin concentrations in healthy cats and cats with non-alimentary tract illness in Australia

Objective   To determine a reference range for serum cobalamin concentration in healthy cats in Australia using a chemiluminescent enzyme immunoassay and to prospectively investigate the prevalence of hypocobalaminaemia in cats with non-alimentary tract disease.
Design   Prospective study measuring serum cobalamin concentrations in clinically healthy cats and cats with non-alimentary tract illness.
Procedure   Blood was collected from 50 clinically healthy cats that were owned by staff and associates of Veterinary Specialist Services or were owned animals presented to Creek Road Cat Clinic for routine vaccination. Blood was collected from 47 cats with non-alimentary tract illness presented at either clinic. Serum cobalamin concentration was determined for each group using a chemiluminescent enzyme immunoassay.
Results   A reference range for Australian cats calculated using the central 95th percentile in the 50 clinically healthy cats was 345 to 3668 pg/mL. Median serum cobalamin concentration in 47 cats with non-alimentary tract illness (1186 pg/mL; range 117–3480) was not significantly different to the median serum cobalamin of the 50 healthy cats (1213 pg/mL, range 311–3688). Using the calculated reference range one sick cat with non-alimentary tract illness had a markedly low serum cobalamin concentration.
Conclusion   Although hypocobalaminaemia is uncommon in sick cats with non-alimentary tract illness in Australia, its occurrence in this study warrants further investigation.     

Presence of anti-insulin natural autoantibodies in healthy cats and its interference with immunoassay for serum insulin concentrations

A substance interfering with the enzyme-linked immunosorbent assay (ELISA) for feline insulin concentration was investigated in healthy cats. An insulin-binding substance isolated from feline serum showed 2 bands at 25 and 50 kDa in SDS-PAGE, suggesting the presence of immunoglobulin G (IgG). Insulin-binding IgG from healthy cats indeed reduced insulin immunoreactivity in the ELISA for determining insulin concentration. The insulin-binding IgG was polyclonal/polyreactive and showed certain specificity, high affinity, and high binding capacity, which was evaluated by liquid-phase radioimmunoassay with Scatchard plot analysis. Epitope analysis revealed that the insulin-binding IgG showed significant binding at residues A1-5 and B20-30 of the insulin molecule. Removal of the antibodies from serum enabled the determination of serum insulin concentrations by ELISA. Our data indicated that serum from healthy cats contained substantial amounts of natural autoantibodies combined with insulin, and that the antibodies interfered with the heterologous immunoassay for serum insulin concentration.     

Effect of sodium bicarbonate infusion on serum osmolality, electrolyte concentrations, and blood gas tensions in cats.

The effects of single IV injections of sodium bicarbonate (0.5 mEq/kg of body weight, 1 mEq/kg, 2 mEq/kg, and 4 mEq/kg) on serum osmolality, serum sodium, chloride, and potassium concentrations, and venous blood gas tensions in 6 healthy cats were monitored for 180 minutes. Serum osmolality increased and remained significantly (P less than 0.05) increased for 120 minutes in cats given 4 mEq of sodium bicarbonate/kg. Serum sodium was increased significantly (P less than 0.05) for 30 minutes in cats given 4 mEq of sodium bicarbonate/kg. Serum sodium decreased and remained significantly (P less than 0.05) decreased for 120 minutes in cats given 1 g of 20% mannitol/kg, and serum osmolality was significantly (P less than 0.05) decreased at 30 and 60 minutes. Serum chloride decreased significantly (P less than 0.05) for 10 minutes in cats given 1 mEq of sodium bicarbonate/kg, and was significantly decreased for 30 minutes in cats given 2 mEq and 4 mEq of sodium bicarbonate/kg. Serum chloride decreased and remained significantly (P less than 0.05) decreased for 30 minutes in cats given 1 g of 20% mannitol/kg. Serum sodium and serum osmolality did not change significantly (P less than 0.05) in cats given 4 ml of 0.9% sodium chloride/kg. Serum potassium decreased significantly (P less than 0.05) for 10 minutes in cats given 1 mEq of sodium bicarbonate/kg, and for 120 minutes in cats given 2 mEq/kg or 4 mEq/kg. There was a significantly (P less than 0.05) greater decrease in serum potassium that lasted for 30 minutes after given sodium bicarbonate at the dosage of 4 mEq/kg, compared with other dosages given.(ABSTRACT TRUNCATED AT 250 WORDS)