Evaluation of a continuous glucose monitoring system for use in dogs, cats, and horses

OBJECTIVE: To evaluate a continuous glucose monitoring system (CGMS) for use in dogs, cats, and horses. DESIGN: Prospective clinical study. Animals-7 horses, 3 cats, and 4 dogs that were clinically normal and 1 horse, 2 cats, and 3 dogs with diabetes mellitus. PROCEDURE: Interstitial glucose concentrations were monitored and recorded every 5 minutes by use of a CGMS. Interstitial glucose concentrations were compared with whole blood glucose concentrations as determined by a point-of-care glucose meter. Interstitial glucose concentrations were also monitored in 2 clinically normal horses after oral and i.v. administration of glucose. RESULTS: There was a positive correlation between interstitial and whole blood glucose concentrations for clinically normal dogs, cats, and horses and those with diabetes mellitus. Events such as feeding, glucose or insulin administration, restraint, and transport to the clinic were recorded by the owner or clinician and could be identified on the graph and associated with time of occurrence. CONCLUSIONS AND CLINICAL RELEVANCE: Our data indicate that use of CGMS is valid for dogs, cats, and horses. This system alleviated the need for multiple blood samples and the stress associated with obtaining those samples. Because hospitalization was not required, information obtained from the CGMS provided a more accurate assessment of the animal's glucose concentrations for an extended period, compared with measurement of blood glucose concentrations. Use of the CGMS will promote the diagnostic and research potential of serial glucose monitoring.     

Continuous glucose monitoring in dogs and cats

Use of continuous glucose monitoring in veterinary medicine is gaining popularity. Through use of a commercially available continuous glucose monitor system, insights into daily glucose changes in dogs and cats are achievable. The continuous glucose monitoring system measures glucose concentrations in the interstitial fluid of the subcutaneous space by use of a small, flexible probe. When placed in the subcutaneous tissue, the probe is connected to a recording device that is attached to the animal and records the interstitial fluid glucose concentration every 5 minutes (288 readings per 24 hours). Once attached and properly calibrated, the instrument can remain in place for several days, hospitalization of the patient is not necessary, and the normal daily routine of the animal can be maintained. The data from the recording device are then downloaded and a very detailed picture of the interstitial fluid glucose concentration over that time period can be obtained. Subcutaneous interstitial fluid glucose concentrations have a good correlation to blood glucose concentrations within a defined range. The continuous glucose monitoring system has distinct advantages over traditional blood glucose curves and is a valuable tool for managing diabetic dogs and cats. In addition, other clinical uses for continuous glucose monitoring are being developed. This review is designed to outline the technology behind the continuous glucose monitoring system, describe the clinical use of the instrument, provide clinical examples in which it may be useful, and discuss future directions for continuous glucose monitoring in dogs and cats.     

Home monitoring of blood glucose concentration by owners of diabetic dogs

The objective of this study was to investigate whether home monitoring of blood glucose of diabetic dogs by owners would be possible on a long-term basis. The owners of 12 diabetic dogs were each asked to generate four glucose curves by taking capillary blood samples from their dog's ear, at three- to four-week intervals. Within one week of each curve being produced by the owner, an additional curve was produced by a veterinarian in the hospital. Ten owners were able to generate blood glucose curves; three of them needed a second demonstration, and two telephoned for further guidance. The blood glucose concentrations obtained from the first two 'hospital' curves were significantly lower than those measured at home. Overall, in 42 per cent of cases, the treatment based on the hospital curves would have been different from that based on 'home' curves. The results of this study indicate that the majority of owners were able and willing to perform long-term monitoring of the blood glucose concentrations of their dogs.     

Evaluation of a continuous glucose monitoring system in diabetic dogs

The generation of a blood glucose curve is important for assessing the response to insulin therapy in diabetic dogs. Disadvantages of this technique include patient discomfort and the potential for missing transient hypo- or hyperglycaemic episodes. The aim of the current study was to evaluate a continuous glucose monitoring system (CGMS) for use in diabetic dogs. Interstitial fluid glucose concentrations were recorded in 10 diabetic dogs, every five minutes for up to 48 hours, using a subcutaneous sensor attached to the CGMS device. Blood glucose concentrations were measured simultaneously using a glucometer. The correlation between interstitial fluid and blood glucose values was 0.81 (P < 0.01). The largest discrepancies between the two sets of data were seen during the one- to three-hour period following feeding, suggesting that postprandial hyperglycaemia might not be reflected in the interstitial fluid. The authors conclude that the CGMS is a potentially valuable tool in the management of canine diabetic patients.     

Fructosamine and glycated hemoglobin in the assessment of glycaemic control in dogs

Fructosamine and glycated hemoglobin (HbA1c) concentrations were measured simultaneously in 222 dogs (96 healthy and 126 sick dogs). The dogs were divided into 3 groups according to the glucose concentration: hypo, hyper and euglycaemic dogs. Serum fructosamine concentrations were measured by the reduction test with nitroblue tetrazolium. A turbidimetric inhibition immunoassay and specific polyclonal antibodies were used to evaluate glycated hemoglobin concentrations. A significant correlation was found between glucose concentration and either fructosamine (r = 0.63, p < 0.0001) or glycated hemoglobin (r = 0.82, p < 0.0001). The correlation was higher in hyperglycaemic dogs for fructosamine (r = 0.80, p < 0.0001) and in hypoglycaemic dogs for glycated hemoglobin (r = 0.91, p < 0.005). We found a significant correlation between serum fructosamine and glycated hemoglobin (r = 0.65, p < 0.0001 ) when all the dogs were studied. A significant correlation was observed between serum fructosamine and glycated hemoglobin only in hyperglycaemic dogs (r = 0.82, p < 0.0003). Thus, fructosamine and HbA1c may be considered for use in screening tests for diabetes mellitus in dogs and clinical tests for monitoring control and evaluation of the diabetic animal's response to treatment. The choice of the analytical assay depends on the characteristic and analytical opportunities of the laboratory, as well as the number of serum samples to be analysed.     

Measurement of capillary blood glucose concentrations by pet owners: a new tool in the management of diabetes mellitus

Recently a new method for capillary blood sampling from the ears of dogs and cats was described, which allows the measurement of glucose concentration by means of portable glucose meters. The authors of this report evaluated the suitability of this method for use by pet owners and the potential technical problems. The owners of seven healthy dogs and seven healthy cats were asked to perform two glucose curves (measuring blood glucose concentration every 2 hours for a total of 12 hours). All dog owners and three cat owners were able to perform a reliable blood glucose curve. The most frequently encountered problems were inadequate formation of a blood drop due to excessive digital pressure on the pinna, repeatedly depressing the plunger of the lancet device instead of allowing the negative pressure to slowly build up, and failure to fill the test strip up to the mark. The authors conclude that these steps of the procedure need to be stressed during technique demonstration and that home monitoring of blood glucose concentrations may serve as a new tool in the management of diabetic dogs and cats.     

Accuracy of a continuous glucose monitoring system in dogs and cats with diabetic ketoacidosis

Objective – (1) To determine the ability of a continuous interstitial glucose monitoring system (CGMS) to accurately estimate blood glucose (BG) in dogs and cats with diabetic ketoacidosis. (2) To determine the effect of perfusion, hydration, body condition score, severity of ketosis, and frequency of calibration on the accuracy of the CGMS. Design – Prospective study. Setting – University Teaching Hospital. Animals – Thirteen dogs and 11 cats diagnosed with diabetic ketoacidosis were enrolled in the study within 24 hours of presentation. Interventions – Once BG dropped below 22.2 mmol/L (400 mg/dL), a sterile flexible glucose sensor was placed aseptically in the interstitial space and attached to the continuous glucose monitoring device for estimation of the interstitial glucose every 5 minutes. Measurements and Main Results – BG measurements were taken with a portable BG meter every 2–4 hours at the discretion of the primary clinician and compared with CGMS glucose measurements. The CGMS estimates of BG and BG measured on the glucometer were strongly associated regardless of calibration frequency (calibration every 8 h: r=0.86, P<0.001; calibration every 12 h: r=0.85, P<0.001). Evaluation of this data using both the Clarke and Consensus error grids showed that 96.7% and 99% of the CGMS readings, respectively, were deemed clinically acceptable (Zones A and B errors). Interpatient variability in the accuracy of the CGMS glucose measurements was found but was not associated with body condition, perfusion, or degree of ketosis. A weak association between hydration status of the patient as assessed with the visual analog scale and absolute percent error (Spearman's rank correlation, ρ=?0.079, 95% CI=?0.15 to ?0.01, P=0.03) was found, with the device being more accurate in the more hydrated patients. Conclusions – The CGMS provides clinically accurate estimates of BG in patients with diabetic ketoacidosis.     

Serum glycated albumin: Potential use as an index of glycemic control in diabetic dogs

Measurements of serum fructosamine, glycated hemoglobin, and glycated albumin (GA) complement serum glucose concentration for better management of diabetes mellitus (DM). Especially, the serum fructosamine test has long been used for diagnosing and monitoring the effect of treatment of DM in dogs. However, fructosamine tests are currently not performed in veterinary medicine in Japan. GA and fructoasmine levels have been shown to strongly correlate. However, the clinical implications of using GA remain to be elucidated. Therefore, the purpose of the current study was threefold: 1) Determine whether GA% is altered by acute hyperglycemia in normal dogs, simulating stress induced hyperglycemia; 2) Demonstrate that GA% does not dynamically change with diurnal variation of blood glucose concentration in diabetic dogs; and 3) Investigate whether GA% is capable of providing an index of glycemic control for 1–3 weeks in diabetic dogs as is the case with diabetic human patients. Our study demonstrated that serum GA% remains very stable and unaltered under acute hyperglycemic conditions (intravenous glucose injection) and in spite of diurnal variation of blood glucose concentration. Furthermore, serum GA% can reflect long-term changes (almost 1–3 weeks) in blood glucose concentration and the effect of injected insulin in diabetic dogs.     

Evaluation of the effect of cephalexin and enrofloxacin on clinical laboratory measurements of urine glucose in dogs

OBJECTIVE: To determine the effects of cephalexin and enrofloxacin on results of 4 commercially available urine glucose tests in dogs. ANIMALS: 6 healthy adult female dogs. PROCEDURE: In a crossover design, cephalexin (22 and 44 mg/kg [10 and 20 mg/lb], p.o., q 8 h) or enrofloxacin (5 and 10 mg/kg [2.3 and 4.5 mg/lb], p.o., q 12 h) was administered to dogs for 1 day. Urine samples were tested for glucose at 0, 6, and 24 hours after drug administration. In vitro, dextrose was added to pooled glucose-negative canine urine samples containing either no antimicrobial or known concentrations of either antimicrobial; urine samples were then tested for glucose. RESULTS: In vivo, false-positive results were obtained by use of a tablet test in the presence of both antimicrobials and by use of a strip test in the presence of cephalexin. In vitro, false-positive results were obtained with the tablet test at the highest urine concentration of cephalexin (2,400 microg/mL) and with a strip test at the highest concentration of enrofloxacin (600 microg/mL). Enrofloxacin in urine samples containing dextrose caused the urine glucose tests to underestimate urine glucose concentration. CONCLUSIONS AND CLINICAL RELEVANCE: Cephalexin and enrofloxacin at dosages used in clinical practice may result in false-positive or false-negative urine glucose results, and care should be taken when using urine as a basis for identifying or monitoring diabetic animals.     

Activities of Enzymes in the Malate–Aspartate Shuttle in the Peripheral Leukocytes of Dogs and Cats

The activities of the enzymes involved in the malate–aspartate shuttle and the expression of malate dehydrogenase (MDH), a rate-limiting enzyme in the NADH shuttle that produces ATP in glucose metabolism in leukocytes, were determined to investigate the differences in this shuttle system in the peripheral leukocytes of dogs and cats. There were no significant differences between dogs and cats in plasma glucose, immunoreactive insulin, free fatty acid or triglyceride concentrations. The activities of cytosolic and mitochondrial MDH and of mitochondrial glutamate dehydrogenase (GLDH) in canine leukocytes were significantly higher than in feline leukocytes. High activities of MDH in canine leukocytes were confirmed by RT-PCR analysis on the total RNA extracted from leukocytes. It was concluded that there were significant differences between dogs and cats in the NADH shuttle system.     

Home monitoring of blood glucose concentrations by owners of diabetic dogs and cats

Generation of blood glucose curves is essential to monitor glycemic control in dogs and cats with diabetes mellitus. Up till now blood collection and blood glucose measurements could only be performed in a hospital. However, glucose concentrations measured in a hospital environment can markedly differ from concentrations measured at home, due to reduced appetite, different activity level and stressful handling. At the Clinic of Small Animal Internal Medicine, University of Zurich, a new method to collect capillary blood from the ear and to measure blood glucose by means of a portable glucose meter has been developed. This method enables owners of diabetic dogs or cats to determine blood glucose concentrations and generate blood glucose curves at home. Three cases demonstrate, how much blood glucose concentrations at home may differ from those in the hospital and how home monitoring can help to establish diabetic control in dogs and cats.     

High-fat feeding and staphylococcus intermedius infection impair beta cell function and insulin sensitivity in mongrel dogs

As obesity is a state of low-grade inflammation, we aimed to investigate the combined effect of high-fat diet and bacterial infection on β-cell function and insulin sensitivity in dogs. We used 20 healthy, male, mongrel dogs randomly divided into four groups: control group—healthy, non-obese dogs; infected group—non-obese dogs with experimentally induced infection (Staphylococcus intermedius); obese group—obese dogs (after 90 day high-fat diet) and obese-infected group—obese dogs with experimentally induced infection (Staphylococcus intermedius). To evaluate insulin sensitivity and β-cell function an intravenous glucose tolerance test (IVGTT) was performed. Plasma insulin increased in all group after glucose infusion. The lowest values were found in obese-infected group. Blood glucose also increased on 3 min after glucose infusion and then gradually decreased. In obese-infected group glucose concentration on 30 min was still significantly higher than initial levels, while in other groups glucose concentration returned to the initial values. The lowest rate of glucose elimination was found in infected group. In dogs of obese group and obese-infected group AUC_{ins 0–60 min} was lower compared to controls. AUC_{glucose 0–60 min} values were lowest in infected group, while in obese-infectd group values were the highest. Levels of ∆I/∆G in dogs of obese-infected group were significantly lower compared to controls and infected group. In conclusion, these results reveal that infection in obese dogs leads to impaired glucose tolerance, which is result of impairment in both insulin secretion and insulin sensitivity.     

Capillary blood sampling from the ear of dogs and cats and use of portable meters to measure glucose concentration

Two new methods for collection of capillary blood from the ear of dogs and cats for the measurement of blood glucose concentration using portable blood glucose meters (PBGMs) are described. The first method uses a lancing device after pre-warming the ear, while the second employs a vacuum lancing device. Both methods generated blood drops of adequate size, although the latter method was faster and easier to perform. Accuracy of the two PBGMs was evaluated clinically and statistically. Although assessment of statistical accuracy revealed differences between the PBGMs and the reference method, all of the PBGM readings were within clinically acceptable ranges. Measurement of capillary blood glucose concentration is easy to perform, inexpensive and fast. It may be used by owners to determine blood glucose concentrations at home, and could serve as a new tool for monitoring diabetic dogs and cats.     

Outcome of surgical versus medical treatment of dogs with beta cell neoplasia: 39 cases (1990-1997).

OBJECTIVE: To compare outcome of surgical versus medical treatment of dogs with beta cell neoplasia. DESIGN: Retrospective study. ANIMALS: 39 dogs with clinical signs of hypoglycemia and serum glucose and insulin concentrations consistent with a diagnosis of beta cell neoplasia. PROCEDURE: Information on signalment; clinical history; physical examination findings; results of CBC, serum biochemical analyses, and urinalysis; serum glucose and insulin concentrations; results of thoracic radiography and abdominal ultrasonography; treatment and treatment complications; survival time; and cause of death were obtained from medical records. RESULTS: 26 dogs underwent exploratory celiotomy and partial pancreatectomy; 13 dogs were treated medically (i.e., dietary change and prednisone). Median survival time was significantly longer for dogs treated surgically than for dogs treated medically. Significant differences were not found in mean age, body weight, duration of clinical signs prior to diagnosis, serum glucose and insulin concentration, or results of other serum biochemical tests between dogs treated surgically and dogs treated medically; also, there was no significant correlation between any of these parameters and survival time for either group of dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that exploratory celiotomy and partial pancreatectomy are indicated once a tentative diagnosis of beta cell neoplasia is established in dogs.     

Comparison of peritoneal fluid and peripheral blood pH,bicarbonate, glucose,and lactate concentration as a diagnostic tool for septic peritonitis in dogs and cats

OBJECTIVE: To establish a reliable diagnostic tool for septic peritonitis in dogs and cats using pH, bicarbonate, lactate, and glucose concentrations in peritoneal fluid and venous blood. STUDY DESIGN: Prospective clinical study. ANIMALS: Eighteen dogs and 12 cats with peritoneal effusion. METHODS: pH, bicarbonate, electrolyte, lactate, and glucose concentrations were measured on 1- to 2-mL samples of venous blood and peritoneal fluid collected at admission. The concentration difference between blood and peritoneal fluid for pH, bicarbonate, glucose, and lactate concentrations were calculated by subtracting the peritoneal fluid concentration from the blood concentration. Peritoneal fluid was submitted for cytologic examination and bacterial culture. Peritonitis was classified as septic or nonseptic based on cytology and bacterial culture results. RESULTS: In dogs, with septic effusion, peritoneal fluid glucose concentration was always lower than the blood glucose concentration. A blood-to-fluid glucose (BFG) difference > 20 mg/dL was 100% sensitive and 100% specific for the diagnosis of septic peritoneal effusion in dogs. In 7 dogs in which it was evaluated, a blood-to-fluid lactate (BFL) difference < -2.0 mmol/L was also 100% sensitive and specific for a diagnosis of septic peritoneal effusion. In cats, the BFG difference was 86% sensitive and 100% specific for a diagnosis of septic peritonitis. In dogs and cats, the BFG difference was more accurate for a diagnosis of septic peritonitis than peritoneal fluid glucose concentration alone. CONCLUSIONS: A concentration difference > 20 mg/dL between blood and peritoneal fluid glucose concentration provides a rapid and reliable means to differentiate a septic peritoneal effusion from a nonseptic peritoneal effusion in dogs and cats. CLINICAL RELEVANCE: The difference between blood and peritoneal fluid glucose concentrations should be used as a more reliable diagnostic indicator of septic peritoneal effusion than peritoneal fluid glucose concentration alone.     

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.     

The amended insulin to glucose ratio and diagnosis of insulinoma in dogs

Amended insulin to glucose ratios were calculated from the concentrations of serum insulin and blood glucose measured concurrently during either a glucagon tolerance test or after feeding in healthy dogs. Values greater than 30 𝛍U/mg which are supportive of a diagnosis of insulinoma were obtained at certain times during the test period. Amended insulin to glucose ratios calculated from serum insulin and blood glucose concentrations obtained during a glucagon tolerance test and an oral glucose tolerance test on a dog with an insulinoma were less than 30 𝛍U/mg, or equivocal, at different times during the test period. This indicates that under some circumstances healthy dogs may have elevated amended insulin to glucose ratios, and dogs with insulinoma may have a normal amended insulin to glucose ratio. Care is essential for interpretation of amended insulin to glucose ratios, and a diagnosis of insulinoma using the ratio must be made in conjunction with appropriate clinical signs of hvnoglvcaemia.     

Glucose tolerance and insulin response in diabetes mellitus of dogs

The low dose intravenous glucose tolerance test (IVGTT) and the insulin response to the glucose load were performed in a series of twenty–two diabetic dogs. All diabetic dogs were characterized by glucose intolerance as expressed by an abnormal half time (Tl/2) or fractional turnover rate (k) for glucose clearance. On the basis of the initial insulin level (Io), the insulin peak response (Ip) and the insulinogenic index (I/G), the dogs were classified into three types. Type I dogs were characterized by a low Io, low Ip and low I/G in response to glucose, similar to the juvenile form of diabetes in humans. Type II dogs were characterized by a normal or high Io, but also with a low Ip and a low I/G which are some of the features of the maturity onset form. Type III dogs were characterized by a normal Io and a normal or delayed response to glucose as seen in chemical diabetes. It is suggested that these types represent stages in the natural history of the development of diabetes mellitus in dogs.     

Serial plasma glucose changes in dogs suffering from severe dog bite wounds

The objective of this study was to describe the changes in plasma glucose concentration in 20 severely injured dogs suffering from dog bite wounds over a period of 72 hours from the initiation of trauma. Historical, signalment, clinical and haematological factors were investigated for their possible effect on plasma glucose concentration. Haematology was repeated every 24 hours and plasma glucose concentrations were measured at 8-hourly intervals post-trauma. On admission, 1 dog was hypoglycaemic, 8 were normoglycaemic and 11 were hyperglycaemic. No dogs showed hypoglycaemia at any other stage during the study period. The median blood glucose concentrations at each of the 10 collection points, excluding the 56-hour and 64-hour collection points, were in the hyperglycaemic range (5.8- 6.2 mmol/l). Puppies and thin dogs had significantly higher median plasma glucose concentrations than adult and fat dogs respectively (P < 0.05 for both). Fifteen dogs survived the 72-hour study period. Overall 13 dogs (81.3 %) made a full recovery after treatment. Three of 4 dogs that presented in a collapsed state died, whereas all dogs admitted as merely depressed or alert survived (P = 0.004). The high incidence of hyperglycaemia can possibly be explained by the "diabetes of injury" phenomenon. However, hyperglycaemia in this group of dogs was marginal and potential benefits of insulin therapy are unlikely to outweigh the risk of adverse effects such as hypoglycaemia.     

Insulin-secreting islet cell tumors: establishing a diagnosis and the clinical course for 25 dogs

Twenty-five dogs with insulin-secreting neoplasms of the pancreas were studied. The diagnosis in each case was determined by histologic evaluation of pancreatic tissue obtained at surgery. The breed distribution revealed that German Shepherd Dogs, Irish Setters, and Collies were most commonly represented. Physical examination, complete blood counts, serum biochemical analysis, and urinalysis were of little diagnostic value, aside from the finding of hypoglycemia in 21 of 25 dogs. Radiographs of the thorax and abdomen were noncontributory to the ultimate diagnosis. Prior to surgery, fasting immunoreactive insulin concentrations and blood glucose concentrations were studied. Insulin:glucose ratios, glucose:insulin ratios, and amended insulin:glucose ratios were determined from the insulin and glucose concentrations in a single blood sample in each of 28 trials. In addition, glucagon tolerance tests were performed on 12 dogs. The amended insulin:glucose ratios proved to be the most reliable for diagnosis. Pancreatic masses were evident at surgery in 23 of 25 dogs; the remaining 2 dogs had microscopic evidence of an islet cell tumor. Nineteen of the islet cell tumors were carcinomas and 6 were simply described as "islet cell tumors." The mean life expectancy after surgery was 12.3 months. Treatment for malignant islet cell tumours included frequent feeding glucocorticoids, and diazoxide.