Efficacy and safety of a purified porcine insulin zinc suspension for managing diabetes mellitus in dogs

The objective of this study was to evaluate the safety and efficacy of a purified porcine insulin zinc suspension for treating dogs with uncomplicated diabetes mellitus. Fifty-three dogs were treated for 60 days after an initial dose determination period. The means of the blood glucose concentrations during 12-hour glucose curves and the means of the blood glucose nadir concentrations during 12-hour glucose curves for all dogs were determined before beginning insulin therapy (time 0), at the end of the dose determination period (time 1), 30 days after time 1 (time 2), and 60 days after time 1 (time 3). Presence of polyuria, polydipsia, and ketonuria was determined at each time point. Adequacy of control of hyperglycemia was based on 12-hour blood glucose curves and improvement in clinical variables (results of physical examinations, historic information, polyuria, polydipsia, and ketonuria). Safety was evaluated by questionnaire, performance of physical examination, CBC, serum chemistry profile, and urinalysis. The means of the blood glucose concentrations during 12-hour glucose curves and the means of the blood glucose nadir concentrations during 12-hour glucose curves for all dogs at times 1, 2, and 3 were significantly lower compared with time 0 (P < .0001). There was a reduction in the proportion of dogs with polyuria, polydipsia, and ketonuria of 82, 86, and 80%, respectively. All of the dogs had adequate glycemic control at time 1, 66% at time 2, and 75% at time 3. At time 3, 66% of dogs required insulin injections q12h. Other than hypoglycemia, there were no important adverse effects of insulin administration. The insulin, was safe and efficacious for reducing blood glucose and clinical signs in dogs with diabetes mellitus.     

Evaluation of day-to-day variability of serial blood glucose concentration curves in diabetic dogs

OBJECTIVE: To evaluate day-to-day variability of serial blood glucose concentration curves in dogs with diabetes mellitus. DESIGN: Prospective clinical study. ANIMALS: 10 dogs with diabetes mellitus. PROCEDURE: Paired 12-hour serial blood glucose concentration curves performed during 2 consecutive days were obtained on 3 occasions from each dog. Dogs received the same dose of insulin and meal every 12 hours on both days. For each pair of curves, comparison was made between the results of days 1 and 2. RESULTS: Mean absolute difference (without regard to sign) between days 1 and 2 for each parameter was significantly > 0, disproving the hypothesis that there is minimal day-to-day variability of serial blood glucose concentration curves when insulin dose and meals are kept constant. Coefficient of variation of the absolute difference between days 1 and 2 for each parameter ranged from 68 to 103%. Evaluation of the paired curves led to an opposite recommendation for adjustment of the insulin dose on day 2, compared with day 1, on 27% of occasions. Disparity between dosage recommendations was more pronounced when glucose concentration nadir was < 180 mg/dL (10 mmol/L) on 1 or both days. In this subset of 20 paired curves, an opposite recommendation for dosage adjustment was made on 40% of occasions. CONCLUSIONS AND CLINICAL RELEVANCE: There is large day-to-day variation in parameters of serial blood glucose concentration curves in diabetic dogs. Day-to-day variability of serial blood glucose concentration curves has important clinical implications, particularly in dogs with good glycemic control.     

Effects of dietary fiber supplementation on glycemic control in dogs with alloxan-induced diabetes mellitus.

The effect of a high insoluble-fiber (IF) diet containing 15% cellulose in dry matter, high soluble-fiber (SF) diet containing 15% pectin in dry matter, and low-fiber (LF) diet on glycemic control in 6 dogs with alloxan-induced insulin-dependent diabetes mellitus was evaluated. Each diet contained greater than 50% digestible carbohydrate in dry matter. A crossover study was used with each dog randomly assigned to a predetermined diet sequence. Each dog was fed each diet for 56 days. Caloric intake was adjusted weekly as needed to maintain each dog within 1.5 kg of its body weight measured prior to induction of diabetes mellitus. All dogs were given pork lente insulin and half of their daily caloric intake at 12-hour intervals. Mean (+/- SEM) daily caloric intake was significantly (P less than 0.05) less when dogs consumed the IF diet vs the SF and LF diets (66 +/- 3 kcal/kg, 81 +/- 5 kcal/kg, and 79 +/- 4 kcal/kg, respectively). Serum alkaline phosphatase activity was significantly (P less than 0.05) higher when dogs consumed the LF diet vs the IF and SF diets (182 +/- 37 IU/L, 131 +/- 24 IU/L, and 143 +/- 24 IU/L, respectively). Mean postprandial plasma glucose concentration measured every 2 hours for 24 hours, beginning at the time of the morning insulin injection, was significantly (P less than 0.05) lower at most blood sampling times in dogs fed IF and SF diets, compared with dogs fed the LF diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

The use of isophane insulin for the control of diabetes mellitus in dogs.

For this study 54 dogs with diabetes mellitus verified by anamnesis, clinical examinations and laboratory analyses were selected in 13 Danish and Swedish small animal clinics. After instruction the owners gave isophane insulin ("Insulin Protaphan Human") injections to the dogs morning and evening followed by a commercial or homemade meal rich in fibers. The veterinarians examined the treated dogs 5 times or more in the 90 day treatment period, preferably in the morning before injection and meal. In all 54 dogs the clinical symptoms disappeared a few days after isophane insulin injections, and 54% of the dogs were clinically healthy within 8 days. Within a month 96% of the dogs were normalized after therapy. Simultaneously the blood glucose levels were normalized in 64% of the dogs within 14 days and in further 21% within 30 days. The urine glucose levels were normalized in 64% of the dogs within 14 days and for further 19% within 30 days. At the end of the study 48 out of the 54 diabetic dogs were clinically healthy, alert and free from symptoms of diabetes. The average dose of isophane insulin was for greater dogs 0.44 units per kg bw twice a day, for small dogs 0.79. Six dogs had been destroyed in the trial period for various reasons. One owner had injection troubles. Another owner was hospitalized and had to get rid of the dog. One dog developed advanced breast cancer, 1 went fierce and 2 developed cataracts. Four dogs had by 1 or 2 occasions shown hypoglycemic symptoms, which quickly disappeared after appropriate adjustments of insulin dosing, feeding schedule and exercise programme.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oral chromium picolinate and control of glycemia in insulin-treated diabetic dogs

Chromium is an essential dietary trace mineral involved in carbohydrate and lipid metabolism. Chromium is required for cellular uptake of glucose, and chromium deficiency causes insulin resistance. Chromium supplementation may improve insulin sensitivity and has been used as adjunct treatment of diabetes mellitus in humans. In this study, 13 dogs with naturally acquired diabetes mellitus were treated with insulin for 3 months, then with insulin and chromium picolinate for 3 months. Dogs weighing <15 kg (33 lb: n = 9) were administered 200 microg of chromium picolinate PO once daily for I month, then 200 microg of chromium picolinate twice daily for 2 months. Dogs weighing >15 kg (n = 4) received 200 microg of chromium picolinate once daily for 2 weeks, then 200 microg twice daily for 2 weeks, then 400 microg twice daily for 2 months. Type of insulin, frequency of insulin administration, and diet were kept constant, and insulin dosage was adjusted, as needed, to maintain optimal control of glycemia. Mean body weight, daily insulin dosage, daily caloric intake, 10-hour mean blood glucose concentration, blood glycated hemoglobin concentration, and serum fructosamine concentration were not markedly different when dogs were treated with insulin and chromium picolinate, compared with insulin alone. Adverse effects were not identified with chromium picolinate administration. Results of this study suggest that, at a dosage range of 20-60 microg/kg/d, chromium picolinate caused no beneficial or harmful effects in insulin-treated diabetic dogs.     

Concurrent diabetes mellitus and hypoadrenocorticism in the dog: Diagnosis and management of eight cases

Eight cases of concurrent diabetes mellitus and hyperadrenocorticism are described. In all but one dog diabetes mellitus was the first condition recognised and, in these, clinical signs attributable to hyperadrenocorticism developed further while the dogs received replacement insulin therapy. The most common signs were resistance to exogenous insulin with daily insulin replacement dosage requirements exceeding 2 iu/kg, erratic insulin requirements, continuing polydipsia/polyuria and weight loss. Lethargy and muscle weakness were variable and dermatological abnormalities were present in only four cases. Six dogs were treated with op'DDD and clinical signs resolved with improvement of glycaemic control.     

Evaluation of an insulin zinc suspension for control of naturally occurring diabetes mellitus in dogs

OBJECTIVE: To evaluate duration of action of an insulin zinc suspension (Caninsulin, Intervet) in spontaneously occurring cases of canine diabetes mellitus and suitability of its use as a once daily administered insulin for treatment of this disease. DESIGN: Eight client-owned canine diabetics were included in a prospective pilot study. All dogs had been treated with Caninsulin for a minimum of 2 months and were considered on clinical grounds to be adequately stabilised. PROCEDURE: Dogs were hospitalised for 24 h and blood collected every 2 h via indwelling venous catheters for blood glucose determination. RESULTS: Once daily Caninsulin administration failed to maintain glycaemic control for greater than 13 h in five of eight dogs, but acceptable blood glucose concentrations were maintained for 22 h and greater than 24 h in two others. One dog became distressed during hospitalisation and the blood glucose curve did not show an identifiable response to the insulin. CONCLUSION: Most diabetic dogs may require twice daily administration of Caninsulin for satisfactory glycaemic control, but once daily administration may be adequate in some animals. More comprehensive investigation into duration of activity of Caninsulin is warranted.     

An Investigation of the Action of Neutral Protamine Hagedorn Human Analogue Insulin in Dogs with Naturally Occurring Diabetes Mellitus

Background: Neutral Protamine Hagedorn human analogue insulin (Humulin N) is commonly used for treatment of canine diabetes mellitus (DM). However, blood glucose and serum insulin concentrations in Humulin N-treated dogs with naturally occurring DM have not been reported.
Objective: To investigate blood glucose and serum insulin concentrations in the clinical setting of client-owned Humulin N-treated dogs with naturally occurring, well-regulated DM.
Animals: Ten client-owned dogs with naturally occurring, well-regulated DM.
Methods: In this clinical study, blood glucose and serum insulin concentrations were measured when dogs received food and insulin (T₀), at approximately every half hour for the next 2 hours, and then approximately every 2 hours for an additional 8 hours. Insulin duration of action was defined as the number of hours from T₀ to the lowest blood glucose concentration and until blood glucose concentration returned to an interpolated value of 70% of basal blood glucose concentration (Glucose_b).
Results: Mean percent of insulin-induced blood glucose suppression was 49.9 ± 17.1% (median, 46%; range, 29–78%). Insulin duration of action ranged from 4 to 10 hours. Blood glucose concentration increased initially and returned to Glucose_b within 0.6–2.2 hours after T₀ in 5 dogs. This initial blood glucose surge then was followed by blood glucose suppression in all 5 dogs.
Conclusions and Clinical Importance: These results suggest that Humulin N administered SC twice daily is an effective mode of treatment for dogs with naturally occurring DM. Postprandial hyperglycemia is present in some well-regulated diabetic dogs treated with Humulin N.     

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.     

Funduscopic findings following cataract extraction by means of phacoemulsification in diabetic dogs: 52 cases (1993-2003)

OBJECTIVE: To determine prevalence of retinal hemorrhages and microaneurysms in dogs with diabetes mellitus following cataract extraction by means of phacoemulsification and identify potential risk factors. DESIGN: Retrospective study. PROCEDURE: Medical records of dogs undergoing phacoemulsification between 1993 and 2003 were reviewed, and information was recorded on signalment, history, physical examination findings, ophthalmic examination findings, results of laboratory testing, electroretinographic findings, and surgical findings. Glycemic control was classified as poor, intermediate, or good on the basis of baseline blood glucose concentration, perioperative body weight loss, daily insulin dosage, and presence of glucosuria and ketonuria. Data from diabetic and nondiabetic dogs were analyzed to determine prevalence and risk factors for development of retinal hemorrhages or microaneurysms following phacoemulsification. RESULTS: 11 of the 52 (21%) dogs with diabetes mellitus developed ophthalmoscopic signs of retinal hemorrhages or microaneurysms, compared with 1 of the 174 (0.6%) nondiabetic dogs. Median time from onset of diabetes mellitus to diagnosis of retinopathy was 1.4 years (range, 0.5 to 3.2 years). No risk factors for development of retinopathy were identified. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that retinal hemorrhages and microaneurysms may be more common and develop earlier in diabetic dogs than previously reported. This may affect treatment, as diabetic dogs survive longer with improved glycemic control.     

Effects of insoluble and soluble dietary fiber on glycemic control in dogs with naturally occurring insulin-dependent diabetes mellitus

OBJECTIVE: To evaluate the effects of diets differing in type and quantity of fiber on glycemic control in dogs with naturally occurring insulin-dependent diabetes mellitus. DESIGN: Prospective randomized crossover controlled trial. ANIMALS: 7 dogs with well-regulated naturally occurring insulin-dependent diabetes mellitus. PROCEDURE: Dogs were fed 1 of 3 diets for 1 month each in 1 of 6 randomized diet sequences. Diets included a low-fiber diet (LF) and 2 high-fiber diets; 1 contained only insoluble fiber (HIF), and 1 contained soluble fiber in addition to insoluble fiber (HSF). Caloric intake was unchanged throughout the study. Glycemic control was assessed after each feeding trial by measuring serum fructosamine concentration and performing 5 serial measurements of blood glucose concentration every 2 hours after the morning feeding and insulin injection. RESULTS: Significant differences were not detected in body weight, required insulin dosage, or albumin concentration among dogs fed the HIF, HSF, and LF diets. Mean and maximum blood glucose concentrations and area under the blood glucose curve were significantly lower in dogs fed the HIF diet, compared with values in the same dogs fed the HSF or LF diet. Fructosamine concentration was significantly lower in dogs fed the HIF or HSF diet, compared with values in the same dogs fed the LF diet. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with naturally occurring insulin-dependent diabetes mellitus, a dry, high insoluble-fiber diet may aid in glycemic control.     

Pharmacokinetics of a porcine insulin zinc suspension in diabetic dogs

Ten dogs with naturally occurring diabetes mellitus were injected with a highly purified porcine insulin zinc suspension at a dose according to their expected requirement. Plasma insulin and glucose concentrations were measured at two-hourly intervals over 24 hours following injection. There were either one or two peaks in plasma insulin concentration: one at about four hours (mean 4.3 21.3 [SD]) and another at about 11 hours (mean 11 pM1-85) after the injection. The second insulin peak was seen in only eight dogs. Persistence of elevated plasma insulin concentrations ranged from 14 to 24 hours (mean 17.4 pM 3.65). These results compare favourably with those published for other intermediate-acting insulin preparations used to treat canine diabetes mellitus and suggest that this preparation has useful properties for the successful management of many canine diabetics.     

一例犬糖尿病的诊断与治疗

犬糖尿病是犬的常发疾病,其临床症状为多饮、多食、多尿、体重下降。持续的血糖升高导致机体代谢紊乱,出现如白内障、胰腺炎、肾上腺皮质机能亢进等继发症,对犬的生活质量及生命健康造成严重的威胁。论文对1例Ⅰ型糖尿病犬进行详细分析,通过测量血糖、尿糖确诊为糖尿病,并通过实验室检查包括血细胞计数、血清生化检测及血气分析,排除并发症。治疗过程与主人共同配合,使用外源性胰岛素结合食物疗法与运动疗法。目前该犬的血糖稳定并接近正常值,身体状况得到改善,生活质量提高,主人对治疗效果满意。持续治疗方法是根据犬的身体情况及血糖变化适当调整胰岛素的剂量。     

Treatment of 46 cats with porcine lente insulin--a prospective, multicentre study

This prospective, multicentre, non-blinded, open study followed 46 cats with diabetes mellitus during treatment with porcine lente insulin (also known as porcine insulin zinc suspension, Caninsulin, Intervet) for 16+/-1 weeks (stabilization phase), with additional monitoring of some cats (n=23) for a variable period. At least three of the following were present at initial presentation: appropriate history of clinical signs consistent with diabetes mellitus, glucosuria, blood glucose greater than 15 mmol/l and fructosamine greater than 380 micromol/l. Insulin treatment was started at a dose rate of 0.25-0.5 IU/kg body weight twice daily, with a maximum starting dose of 2 IU/injection. Twenty-eight of the cats were classed as reaching clinical stability during the study, in 23 of these cats this was during the stabilization phase. Seven cats went into remission during the stabilization phase and one of the cats in week 56. Clinical signs of hypoglycaemia, significantly associated with a dose of 3 units or 0.5 IU/kg or more per cat (twice daily), were observed in nine of the 46 cats during the stabilization phase and concomitant biochemical hypoglycaemia was recorded in most cases. Biochemical hypoglycaemia, recorded in 6% of the blood glucose curves performed during the stabilization phase, was significantly associated with a dose rate of 0.75 IU/kg or more twice daily. This further highlights the need for cautious stepwise changes in insulin dose. The protocol used in the present study is suitable for and easy to use in practice. This study confirmed the efficacy and safety of porcine lente insulin (Caninsulin) in diabetic cats under field conditions.     

Effect of the alpha-glucosidase inhibitor acarbose on control of glycemia in dogs with naturally acquired diabetes mellitus

OBJECTIVE: To evaluate effect of acarbose on control of glycemia in dogs with diabetes mellitus. DESIGN: Prospective randomized crossover controlled trial. ANIMALS: 5 dogs with naturally acquired diabetes mellitus. PROCEDURE: Dogs were treated with acarbose and placebo for 2 months each: in 1 of 2 randomly assigned treatment sequences. Dogs that weighed < or = 10 kg (22 lb; n = 3) or > 10 kg (2) were given 25 or 50 mg of acarbose, respectively, at each meal for 2 weeks, then 50 or 100 mg of acarbose, respectively, at each meal for 6 weeks, with a 1-month interval between treatments. Caloric intake, type of insulin, and frequency of insulin administration were kept constant, and insulin dosage was adjusted as needed to maintain control of glycemia. Serum glucose concentrations, blood glycosylated hemoglobin concentration, and serum fructosamine concentration were determined. RESULTS: Significant differences in mean body weight and daily insulin dosage among dogs treated with acarbose and placebo were not found. Mean preprandial serum glucose concentration, 8-hour mean serum glucose concentration, and blood glycosylated hemoglobin concentration were significantly lower in dogs treated with insulin and acarbose, compared with insulin and placebo. Semisoft to watery feces developed in 3 dogs treated with acarbose. CONCLUSIONS AND CLINICAL RELEVANCE: Acarbose may be useful as an adjunctive treatment in diabetic dogs in which cause for poor glycemic control cannot be identified, and insulin treatment alone is ineffective.     

Spontaneously obese dogs exhibit greater postprandial glucose, triglyceride, and insulin concentrations than lean dogs

Dogs do not appear to progress from obesity-induced insulin resistance to type 2 diabetes mellitus. Both postprandial hyperglycemia and postprandial hypertriglyceridemia have been proposed to cause or maintain beta cell failure and progression to type 2 diabetes mellitus in other species. Postprandial glucose, triglyceride, and insulin concentrations have not been compared in lean and obese dogs. We measured serum glucose, triglyceride, and insulin concentrations in nine naturally occurring obese and nine age- and gender-matched lean dogs. After a 24-h fast, dogs were fed half their calculated daily energy requirement of a standardized diet that provided 37% and 40% of metabolizable energy as carbohydrate and fat, respectively. Fasting and postprandial glucose and triglyceride concentrations were greater in the obese dogs (P < 0.001), although the mean insulin concentration for this group was five times greater than that of the lean group (P < 0.001). Most of the 0.6 mM (11 mg/dL) difference in mean postprandial glucose concentrations between lean and obese dogs was attributable to a subset of persistently hyperglycemic obese dogs with mean postprandial glucose concentrations 1.0 mM (18 mg/dL) greater than that in lean dogs. Persistently hyperglycemic obese dogs had lower triglyceride (P = 0.02 to 0.04) and insulin (P < 0.02) concentrations than other obese dogs. None of the dogs developed clinical signs of diabetes mellitus during follow-up for a median of 2.6 yr. We conclude that pancreatic beta cells in dogs are either not sensitive to toxicity because of mild hyperglycemia or lack another component of the pathophysiology of beta cell failure in type 2 diabetes mellitus.     

Endogenous serum insulin concentration in dogs with diabetic ketoacidosis

Objective: To determine endogenous serum insulin concentration in dogs with diabetic ketoacidosis (DKA), and to compare it to endogenous serum insulin concentration in diabetic dogs with ketonuria but no acidosis (KDM), diabetic dogs with uncomplicated diabetes mellitus (DM) that did not have ketonuria or acidosis, and dogs with non‐pancreatic disease (NP). Design: Prospective study. Setting: Veterinary Hospital of the University of Pennsylvania. Animals: Forty‐four client‐owned dogs; 20 dogs with newly diagnosed diabetes mellitus (7 dogs with DKA, 6 dogs with KDM, and 7 dogs with DM) and 24 dogs with non‐pancreatic disease. Interventions: Blood and urine samples were obtained at the time of admission to the hospital. Measurements and main results: Signalment, clinical signs, physical examination findings, and concurrent disease were recorded for all dogs. Blood glucose concentration, venous blood pH, venous blood HCO3^? concentration, urinalysis, and endogenous serum insulin concentration were determined in all dogs. Dogs with DKA have significantly decreased endogenous serum insulin concentrations compared to dogs with DM (P = 0.03) and dogs with non‐pancreatic disease (P = 0.0002), but not compared to dogs with KDM (P = 0.2). Five of 7 dogs with DKA had detectable endogenous serum insulin concentrations, and 2 of these dogs had endogenous serum insulin concentration within the normal range. Conclusions: Diabetic dogs with ketoacidosis have significantly decreased endogenous serum insulin concentration compared to dogs with uncomplicated diabetes mellitus. However, most dogs with DKA have detectable endogenous serum insulin concentrations, and some dogs with DKA have endogenous serum insulin concentrations within the normal range.     

Paraneoplastic hypoglycemia in a diabetic dog with an insulin growth factor-2-producing mammary carcinoma

A 6-year-old intact female Labrador Retriever had diabetes mellitus, which had been difficult to control with insulin. The dog also had a solid ductal mammary carcinoma with very rapid growth, which was temporally related to onset of hypoglycemia. Eight months after initial diagnosis of diabetes, the dog had a hypoglycemic crisis. Insulin administration was stopped and serum glucose concentration returned to normal. Three months after discontinuing insulin, another hypoglycemic crisis occurred. During subsequent months, serum glucose concentrations remained at life-threatening levels (1.64-2.12 mmol/L, reference interval 4.44-6.66 mmol/L) simultaneously with an increase in the size of the mammary tumor, which reached a diameter of about 16 cm. At the time of surgery for removal of the tumor serum glucose concentration was 2.20 mmol/L and was then monitored every 3 hours after excision of the tumor. The glucose concentration continued to rise and reached 9.99 mmol/L 12 hours after the removal of the mammary tumor. Immunohistochemical staining demonstrated expression of insulin growth factor-2 by tumor cells, which apparently had caused the hypoglycemia during tumor growth even in a diabetic dog. Hyperglycemia associated with diabetes was pronounced after excision of the tumor and had been masked by the paraneoplastic effect of the tumor.     

Evaluation of d,l-ethionine as a mechanism for pancreatic islet regeneration in dogs

OBJECTIVE: To determine whether induction of pancreatic necrosis and islet proliferation by d,l-ethionine has potential for treating dogs with beta-cell insufficiency. DESIGN: Eighteen mixed breed dogs of both sexes were given d,l-ethionine at 100 mg/kg three times weekly for 2 weeks; 6 dogs were euthanased at 2, 14 and 28 d after the last dose. METHODS: Clinical signs during administration and recovery were assessed. Routine biochemical analyses were performed before each ethionine dose and then once weekly. Faecal samples were examined weekly for malassimilated nutrients and blood. Blood coagulation screening tests (OSPT and APTT) were determined on four dogs after ethionine administration. Intravenous glucose tolerance tests were conducted before the first and after the last ethionine dose and then fortnightly. All dogs were necropsied and pancreas, liver, kidney and jejunum were examined microscopically. RESULTS: During ethionine administration all animals displayed vomiting, inappetence, diarrhoea (often with blood), weight loss and depression. Three dogs were euthanased prematurely due to severe illness, but those allowed to recover were eating and brighter 7 d after cessation of ethionine administration. Serum concentrations of TLI, amylase and lipase increased initially, then decreased, during administration but retumed to normal during recovery. Concentrations of ALT, ALP, unconjugated and conjugated bilirubin increased during administration then decreased slowly. Histological examination revealed hepatic lipidosis and necrosis, but no renal or jejunal lesions. In most dogs, faecal examination demonstrated increased undigested starch and muscle, as well as increased digested and undigested fat, during ethionine administration or early during the recovery period, suggesting transient malassimilation. APTT was unchanged but OSPT was prolonged in all dogs. There was no impairment of insulin secretion or glucose intolerance and C-peptide concentrations were unaffected. Immediately after ethionine administration there was delayed insulin degradation and by day 43 there was evidence of increased insulin sensitivity. CONCLUSION: d,l-ethionine administration in dogs appeared not to interfere with insulin secretion, but caused clinical signs and laboratory changes indicative of pancreatic exocrine necrosis, severe hepatobiliary disease and transient malassimilation. Pancreatic and hepatic dysfunction was severe but clinical recovery occurred after ethionine administration ceased. The severe side-effects observed with d,l-ethionine should preclude its potential use for treating diabetes mellitus in dogs.     

Effect of dietary insoluble fiber on control of glycemia in cats with naturally acquired diabetes mellitus

OBJECTIVE: To evaluate effects of dietary insoluble fiber on control of glycemia in cats with naturally acquired diabetes mellitus. DESIGN: Randomized controlled crossover trial. ANIMALS: 16 cats with naturally acquired diabetes mellitus. PROCEDURE: Cats were fed a diet high in insoluble fiber (HF) containing 12% cellulose (dry-matter basis) or a diet low in insoluble fiber (LF) for 24 weeks; they were fed the other diet for the subsequent 24 weeks. Caloric intake and insulin treatment were adjusted to maintain stable body weight and control of glycemia, respectively. Cats were allowed an adaptation period of 6 weeks after initiation of a diet, after which control of glycemia was evaluated at 6-week intervals for 18 weeks. Variables assessed included serum glucose concentration measured during the preprandial state, blood glycated hemoglobin concentration, serum glucose concentration measured at 2-hour intervals for 12 hours beginning at the time of the morning insulin injection, 12-hour mean serum glucose concentration, and mean fluctuation in serum glucose concentration from the 12-hour mean serum glucose concentration. RESULTS: Mean daily caloric intake, body weight, or daily insulin dosage did not differ significantly between cats when fed HF and LF diets. Mean preprandial serum glucose concentration, most post-prandial serum glucose concentrations, and the 12-hour mean serum glucose concentration were significantly lower when cats consumed the HF diet, compared with values when cats consumed the LF diet. CONCLUSIONS AND CLINICAL RELEVANCE: These results support feeding a commercially available diet containing approximately 12% insoluble fiber (dry-matter basis) to cats with naturally acquired diabetes mellitus.