Efficacy of protamine zinc insulin for treatment of diabetes mellitus in cats

OBJECTIVE: To evaluate effects of protamine zinc insulin (PZI) on control of glycemia in cats with newly diagnosed diabetes mellitus or poorly controlled diabetes. DESIGN: Clinical trial. ANIMALS: 67 diabetic cats. PROCEDURE: 34 cats with newly diagnosed diabetes and 33 cats with poorly controlled diabetes were treated with PZI twice daily for 45 days. Control of glycemia was assessed on days 7, 14, 30, and 45 by evaluation of clinical response, change in body weight, serum fructosamine concentration, blood glucose concentration measured 1, 3, 5, 7, and 9 hours after administration of PZI, lowest blood glucose concentration, and mean blood glucose concentration during the 9-hour period after administration. Adjustments in dosage of PZI were made as needed to attain control of glycemia. RESULTS: For all cats, a significant increase in mean dosage of PZI and significant decreases in 9-hour mean blood glucose concentration, lowest mean blood glucose concentration, and mean serum fructosamine concentration were detected. For cats with poorly controlled diabetes, 9-hour mean blood glucose concentration and mean serum fructosamine concentration were significantly decreased on day 45, compared with day 0. Ninety percent of owners reported improvement or resolution of clinical signs by day 45. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that PZI was effective for control of glycemia in cats with newly diagnosed or poorly controlled diabetes and may be used as an initial treatment or as an alternative treatment in cats that do not respond to treatment with other types of insulin.     

Systolic blood pressure in cats with diabetes mellitus

OBJECTIVE: To determine the prevalence of systemic hypertension in cats with diabetes mellitus and establish ranges for echocardiographic variables in diabetic cats. DESIGN: Prospective study. ANIMALS: 14 cats with diabetes mellitus and 19 healthy control cats. PROCEDURE: Systolic blood pressure was measured indirectly with a noninvasive Doppler technique. Ophthalmic and echocardiographic examinations were performed, and urine protein concentration was measured. Cats were considered to have hypertension if they had systolic blood pressure > 180 mm Hg and at least 1 other clinical abnormality typically associated with hypertension (eg, hypertensive retinopathy, left ventricular hypertrophy, or proteinuria). RESULTS: None of the diabetic or control cats had systolic blood pressure > 180 mm Hg. One diabetic cat had left ventricular hypertrophy, but systolic blood pressure was 174 mm Hg. None of the cats had evidence of hypertensive retinopathy or proteinuria. Mean values for echocardiographic variables for the diabetic cats were not significantly different from published values for healthy cats. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that hypertension does not occur or occurs in only a small percentage of cats with diabetes mellitus.     

Generalized demodicosis associated with diabetes mellitus in two cats

Generalized demodicosis with concurrent diabetes mellitus was diagnosed in 2 cats. Both cats had generalized alopecia and a bilateral brown aural exudate. Mites were seen microscopically in skin scrapings and ear swab specimens. Histologic examination of the skin showed the follicular orientation of the mites. Abnormal results on oral dexamethasone suppression tests, clinical findings, and bilateral adrenal hyperplasia found on necropsy of one of the cats suggested concurrent hyperadrenocorticism.     

Determination of serum fPLI concentrations in cats with diabetes mellitus

Diabetes mellitus (DM) is one of the most common feline endocrinopathies. Pancreatitis is a reported cause for poor control of DM in cats; however, its prevalence in diabetic cats is unknown. Measurement of serum feline pancreatic lipase immunoreactivity (fPLI) has been proposed as a sensitive and specific test for the detection of pancreatitis in cats. The aim of this study was to assess fPLI concentrations in diabetic cats and compare these with non-diabetic cats of similar age. Samples from 29 cats with DM and 23 non-diabetic cats were analysed. Serum fPLI concentrations were significantly higher in samples from diabetic cats (P<0.01). A weak association was found between serum fructosamine and fPLI concentrations (R(2)=0.355, P=0.015), but there was no association between fPLI concentrations and the degree of diabetic control. There were no significant differences in reported clinical signs between cats with or without DM regardless of serum fPLI concentration. This is the first study to demonstrate elevated serum fPLI concentrations in cats with DM, suggesting that pancreatitis could be a significant comorbidity in these cats.     

Ketone measurements using dipstick methodology in cats with diabetes mellitus

O bjectives : To compare the results of urine and plasma ketone dip test in a group of diabetic cats with possible ketosis or ketoacidosis, using laboratory plasma β-hydroxybutyrate measurements as the gold standard.
M ethods : According to clinical examinations, plasma β-hydroxybutyrate measurements and venous blood gas analysis, 54 cats with diabetes mellitus were classified as non-ketotic (n=3), ketotic (n=40) or ketoacidotic (n=11). Plasma and urine acetoacetate concentrations were determined using urine reagent strips.
R esults : Although there was a significant positive correlation between blood and urine ketone measurements (r=0·695, P<0·001), the results differed significantly (Z=−3·494, P<0·001). Using the differential positive rates, the best cut-off value to detect cats with ketoacidosis was 1·5 mmol/l for urine and 4 mmol/l for plasma. The sensitivity/specificity was 82/95 per cent for urine and 100/88 per cent for plasma, respectively.
C linical S ignificance : The urine and plasma ketone dip tests have a different diagnostic accuracy, and results have to be interpreted differently. Because of its high sensitivity, the plasma ketone dip test performs better than the urine ketone dip test to identify cats with impending or established ketoacidosis.     

Use of insulin glargine in dogs with diabetes mellitus

The objective of this study was to evaluate the safety and efficacy of insulin glargine in dogs with diabetes mellitus (DM). Twelve client-owned dogs with DM were included. All dogs received insulin glargine every 12 hours for at least six months, re-evaluations were performed after one, two, four, eight, 12 and 24 weeks and included clinical signs, blood glucose curves (BGCs) and measurement of serum fructosamine concentrations. Mean blood glucose concentrations were significantly lower after two weeks of treatment and remained significantly lower for the duration of the study. By week 24, polyuria/polydipsia had improved in 91 per cent of the dogs. No clinical signs that could have been caused by hypoglycaemia were observed. Based on BGCs and remission of the clinical signs for judging the success of the treatment, 58, 33 and 8 per cent of the dogs attained good, moderate and poor glycaemic control by week 24 of the study, respectively. Insulin glargine administered subcutaneously twice daily is a possible and safe method of treatment for dogs with naturally occurring DM. Although only a few studies are available on the use of other types of insulin in dogs, their success rate is somewhat greater than that with insulin glargine.     

Stress hyperglycemia in cats

It may be difficult to differentiate the possible causes of hyperglycemia in the cat. The following investigation was on transient hyperglycemia in 320 cats. The frequency and degree of stress-hyperglycemia and its relation to different types of primary diseases was proven. Animals with overt diabetes mellitus or pancreatic diseases were not included in this study. Plasma glucose was analyzed with the o-Toluidine- or with the glucose oxidase-method. Plasma immune-reactive insulin (IRI) was estimated by RIA. A glucose concentration of greater than or equal to 140 mg/dl (7.77 mmol/l) in the fasted animal was defined as hyperglycemia. The results of the retrospective investigation show in cats transient hyperglycemia occurs more often (3.2%) than permanent hyperglycemia (0.57%). Contrary to overt diabetes mellitus there is no sex- or age-related predisposition. Glucose values above 300 mg/dl (16.65 mmol/l) with maximal values up to 620 mg/dl (34.42 mmol/l) were estimated in 12% of the animals. In 12 from 19 hyperglycemic animals the basal IRI values were between 4 and 14 microU/ml, 11 animals had a lowered I/G ratio. In the following order of frequency the primary diseases found in combination with transient hyperglycemia were: dys- and stranguria, viral and bacterial infections, gastrointestinal diseases, neoplasia, renal insufficiency, cardiopathies etc. With improvement of the underlying disturbance the stress-related hyperglycemia normalized without insulin therapy within a few days. In conclusion, it is necessary to initially identify basic diseases that may trigger the onset of stress-hyperglycemia in the cat. Neither the extent of the glucose level nor a single plasma-insulin-value are valid indicators of confirming the diagnosis of diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of a continuous glucose monitoring system in cats with diabetes mellitus

A continuous glucose monitoring system (CGMS) was evaluated in 14 cats with naturally occurring diabetes mellitus. The device measures interstitial fluid glucose continuously, by means of a sensor placed in the subcutaneous tissue. All cats tolerated the device well and a trace was obtained on 15/16 occasions. There was good correlation between the CGMS values and blood glucose concentration measured using a glucometer (r=0.932, P<0.01). Limitations to the use of the CGMS are its working glucose range of 2.2-22.2 mmol/l (40-400 mg/dl) and the need for calibration with a blood glucose measurement at least every 12 h. When compared to a traditional blood glucose curve, the CGMS is minimally invasive, reduces the number of venepunctures necessary to assess the kinetics of insulin therapy in a patient and provides a truly continuous glucose curve.     

Diagnosis and management of diabetes mellitus in five cats with somatotrophic abnormalities

The clinical findings and management of five cats with abnormalities consistent with acromegaly were examined retrospectively. Growth hormone (GH) concentrations were elevated in four cats. In one, a minimal elevation of GH was accompanied by a marked elevation in insulin-like growth factor-1 (IGF-1). Insulin-like growth factor-1 concentrations supported the diagnosis in three of four cats measured, but was not elevated initially in one cat, despite a markedly elevated GH concentration. These findings suggest that elevated IGF-1 concentrations are a reliable indicator of acromegaly, but that values within the reference range do not exclude such a diagnosis. Clinical signs of acromegaly were similar to those previously reported, although upper respiratory stridor occurred in one cat, and insulin-resistant diabetes mellitus was not a consistent feature. Despite the lack of a widely available definitive treatment for acromegaly, good control of the clinical signs of diabetes mellitus can be achieved for long periods despite high doses of insulin often being required.     

Absorption kinetics of regular insulin in dogs with alloxan-induced diabetes mellitus

The absorption kinetics of porcine regular insulin following IV, IM, and SC administration were evaluated in 10 dogs with alloxan-induced diabetes mellitus. Plasma immunoreactive insulin (IRI) concentrations were evaluated immediately prior to and at 10, 20, 30, 45, 60, 90, 120, 180, and 240 minutes following IV administration; and immediately prior to and every 30 minutes for 2 hours and then every hour for 6 hours following IM and SC administration of 0.55 U of porcine regular insulin/kg of body weight. Model-independent pharmacokinetic analysis was performed on each data set. Plasma IRI concentration declined rapidly after IV administration of regular insulin and then returned to baseline IRI concentration by 3.2 +/- 0.8 hours. The absorption kinetics following IV administration of regular insulin were similar to those found in earlier studies in healthy dogs and human beings. The IM and SC routes of regular insulin administration resulted in a pharmacologic concentration of IRI at 30 minutes. The peak mean (+/- SD) plasma IRI concentration was significantly (P less than 0.05) greater following SC administration than it was following IM administration of regular insulin (263 +/- 185 and 151 +/- 71 I microU/ml, respectively). The time of the peak plasma IRI concentration (68 +/- 31 minutes and 60 +/- 30 minutes) and the time to return to baseline plasma IRI concentration (5.8 +/- 1.2 hours and 5.8 +/- 1.3 hours) were not significantly different following SC and IM administration of regular insulin, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Growth hormone excess and the effect of octreotide in cats with diabetes mellitus

In this prospective study 16 cats with diabetes mellitus were examined for concurrent acromegaly by measuring plasma growth hormone (GH) and insulin-like growth factor-I concentrations, and magnetic resonance imaging (MRI) of the pituitary fossa. Additionally, the effects of octreotide administration on the plasma concentrations of glucose, GH, α-melanocyte-stimulating hormone (α-MSH), adrenocorticotrophic hormone (ACTH), and cortisol were measured.Five cats were diagnosed with hypersomatotropism. The pituitary was enlarged in these 5 cats and in 2 other cats. Six cats that required a maximum lente insulin dosage ≥1.5 IU/kg body weight per injection had pituitary enlargement and 5 of these cats had acromegaly. Plasma concentrations of GH, ACTH, and cortisol decreased significantly after single intravenous administration of the somatostatin analogue octreotide in the acromegalic cats. The effect on GH concentrations was more pronounced in some of the acromegalic cats than in others. In the non-acromegalic cats only ACTH concentrations decreased significantly. In both groups plasma glucose concentrations increased slightly but significantly, whereas α-MSH concentrations were not significantly affected.In conclusion, the incidence of hypersomatotropism with concomitant pituitary enlargement appears to be high among diabetic cats with severe insulin resistance. Some of these cats responded to octreotide administration with a pronounced decrease in the plasma GH concentration, which suggests that octreotide administration could be used as a pre-entry test for treatment with somatostatin analogues.     

Evaluation of IGF-1 levels in cats with transient and permanent diabetes mellitus

It was investigated if IGF-1 levels in cats which experience diabetic remission (i.e. transient diabetes mellitus) differ from those in cats with permanent disease. Thirteen of 32 diabetic cats showed remission within 16 weeks after initiating insulin therapy, 19 cats continued to need insulin therapy. IGF-1 concentrations were measured before (t(0)), 1-3 (t(1)) and 4-8 (t(2)) weeks after initiating insulin therapy. No difference in IGF-1 levels was found between cats with transient and permanent diabetes at any point in time. In both groups of cats IGF-1 concentrations were significantly lower compared to those of controls before insulin administration. After starting insulin therapy IGF-1 increased significantly in both groups. In cats with transient diabetes IGF-1 levels were not different from controls already at t(1), whereas in cats with permanent diabetes it took until t(2). Although IGF-1 levels seem to normalize faster in cats with transient diabetes mellitus, measurement is not helpful to predict the course of the disease.     

Measurements of growth hormone and insulin-like growth factor 1 in cats with diabetes mellitus

Serum concentrations of insulin-like growth factor 1 (IGF-1) and growth hormone were measured in 25 cats with untreated diabetes mellitus (11 of which were used for follow-up measurements, one to three, four to eight, nine to 12 and 13 to 16 weeks after their treatment with insulin began), 14 diabetic cats that had previously been treated with insulin, and seven diabetic cats that also had hypersomatotropism, two of which had not previously been treated with insulin; 18 healthy cats were used as controls. In the untreated diabetic cats the concentration of IGF-1 ranged from 13.0 to 433.0 ng/ml (median 170.5 ng/ml), which was significantly lower than the concentrations in the control cats (196.0 to 791.0 ng/ml, median 452.0 ng/ml). Their IGF-1 concentrations increased significantly when they were treated with insulin and after four to eight weeks were not different from those in the control cats. In the diabetic cats that had previously been treated with insulin the IGF-1 concentrations were 33.0 to 476.0 ng/ml (median 316.0 ng/ml), which was significantly lower than the concentrations in the control cats, but significantly higher than in the untreated diabetic cats. The IGF-1 concentrations in the two previously untreated diabetic cats with hypersomatotropism were low and low-normal but increased markedly after treatment with insulin. In the five previously treated cats with hypersomatotropism the concentration of IGF-1 was above the normal range. The concentrations of growth hormone in the treated and untreated diabetic cats without hypersomatotropisms were not significantly different and there was an overlap in its concentrations in the diabetic cats with and without hypersomatotropism.     

Urinary tract infections in cats with hyperthyroidism, diabetes mellitus and chronic kidney disease

The prevalence of urinary tract infections (UTIs) in cats with hyperthyroidism (n=90), diabetes mellitus (DM) (n=57) and chronic kidney disease (CKD) (n=77) was evaluated retrospectively. It was found to be 12% in cats with hyperthyroidism and DM, respectively, and 22% in cats with CKD. Associations between UTIs and clinical signs, biochemical markers in serum and urinalyses were investigated. Many of the cats with UTIs had no clinical signs of lower urinary tract disease or changes in their laboratory values indicative of infection. Therefore, a urinalysis alone should not be used to exclude UTIs in these cats. UTIs are relatively common in cats with hyperthyroidism, DM and CKD, and urine cultures are recommended as part of the basic diagnostic plan for cats suspected of suffering from these conditions.     

Day-to-day variability of blood glucose concentration curves generated at home in cats with diabetes mellitus

OBJECTIVE: To evaluate day-to-day variability in blood glucose curves (BGCs) generated at home and at the clinic for cats with diabetes mellitus. DESIGN: Prospective study. ANIMALS: 7 cats with diabetes mellitus. Procedures-BGCs generated at home on 2 consecutive days and within 1 week at the clinic were obtained twice. On each occasion, insulin dose, amount of food, and type of food were consistent for all 3 BGCs. Results of curves generated at home were compared with each other and with the corresponding clinic curve. RESULTS: Differences between blood glucose concentration determined after food was withheld (fasting), nadir concentration, time to nadir concentration, maximum concentration, and mean concentration during 12 hours had high coefficients of variation, as did the difference between fasting blood glucose and nadir concentrations and area under the curve of home curves. Differences between home curve variables were not smaller than those between home and clinic curves, indicating large day-to-day variability in both home and clinic curves. Evaluation of the paired home curves led to the same theoretical recommendation for adjustment of insulin dose on 6 of 14 occasions, and evaluation of home and clinic curves resulted in the same recommendation on 14 of 28 occasions. Four of the 6 paired home curves in cats with good glycemic control and 2 of the 8 paired home curves in cats with poor glycemic control led to the same recommendation. CONCLUSIONS AND CLINICAL RELEVANCE: Considerable day-to-day variability was detected in BGCs generated at home. Cats with good glycemic control may have more reproducible curves generated during blood collection at home than cats with poorer control.