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Biomedical subjects

J S Rand

Publications and source records attributed to J S Rand.

At least 19 recordsLinked to original sources

Separation of serum glycated proteins by agarose gel electrophoresis and nitroblue tetrazolium staining in diabetic and normal cats.

BACKGROUND: The total glycated protein (fructosamine) concentration in serum consists mainly of glycated albumin and lipoproteins. Measurement of fructosamine is used to diagnose and monitor diabetes mellitus in cats. OBJECTIVE: The aims of this study were to measure glycated proteins in diabetic and healthy (nondiabetic) cats using a semiquantitative technique and to determine whether measurement of any of the fractions of glycated protein could be potentially advantageous for the diagnosis and monitoring of diabetic cats. METHODS: Serum samples from 6 cats with diabetes mellitus and 10 clinically healthy adult cats were assayed for total glycated protein using a nitroblue tetrazolium (NBT) fructosamine assay. Serum proteins were separated by agarose gel electrophoresis and stained with NBT to identify individual glycated proteins within the bands. Gels were scanned by densitometry at 525 nm and the glycated protein content was calculated with reference to the total glycated protein content of the sample. RESULTS: Diabetic cats with increased total fructosamine concentrations had higher concentrations of glycated albumin and glycated alpha- and beta-lipoproteins compared with healthy cats. The concentration of glycated proteins in each of the fractions had a positive linear association with the total glycated protein content of serum, but there was large variation in the relative contributions of the 3 protein fractions to the total glycated protein concentration. CONCLUSIONS: Based on the results of this study, measurement of individual glycated fractions does not seem to offer any potential diagnostic advantage over measurement of total glycated protein (fructosamine) concentration alone. In some diabetic and healthy cats, glycated lipoproteins formed the major part of the total glycated protein, whereas in other cats albumin was the major contributor.

Animals↗

Basal plasma insulin and homeostasis model assessment (HOMA) are indicators of insulin sensitivity in cats.

The objective of this study was to compare simpler indices of insulin sensitivity with the minimal model-derived insulin sensitivity index to identify a simple and reliable alternative method for assessing insulin sensitivity in cats. In addition, we aimed to determine whether this simpler measure or measures showed consistency of association across differing body weights and glucose tolerance levels. Data from glucose tolerance and insulin sensitivity tests performed in 32 cats with varying body weights (underweight to obese), including seven cats with impaired glucose tolerance, were used to assess the relationship between Bergman's minimal model-derived insulin sensitivity index (S(I)), and various simpler measures of insulin sensitivity. The most useful overall predictors of insulin sensitivity were basal plasma insulin concentrations and the homeostasis model assessment (HOMA), which is the product of basal glucose and insulin concentrations divided by 22.5. It is concluded that measurement of plasma insulin concentrations in cats with food withheld for 24 h, in conjunction with HOMA, could be used in clinical research projects and by practicing veterinarians to screen for reduced insulin sensitivity in cats. Such cats may be at increased risk of developing impaired glucose tolerance and type 2 diabetes mellitus. Early detection of these cats would enable preventative intervention programs such as weight reduction, increased physical activity and dietary modifications to be instigated.

Animals↗

Dietary chromium tripicolinate supplementation reduces glucose concentrations and improves glucose tolerance in normal-weight cats.

The effect of dietary chromium supplementation on glucose and insulin metabolism in healthy, non-obese cats was evaluated. Thirty-two cats were randomly divided into four groups and fed experimental diets consisting of a standard diet with 0 ppb (control), 150 ppb, 300 ppb, or 600 ppb added chromium as chromium tripicolinate. Intravenous glucose tolerance, insulin tolerance and insulin sensitivity tests with minimal model analysis were performed before and after 6 weeks of feeding the test diets. During the glucose tolerance test, glucose concentrations, area under the glucose concentration-time curve, and glucose half-life (300 ppb only), were significantly lower after the trial in cats supplemented with 300 ppb and 600 ppb chromium, compared with values before the trial. Fasting glucose concentrations measured on a different day in the biochemistry profile were also significantly lower after supplementation with 600 ppb chromium. There were no significant differences in insulin concentrations or indices in either the glucose or insulin tolerance tests following chromium supplementation, nor were there any differences between groups before or after the dietary trial.Importantly, this study has shown a small but significant, dose-dependent improvement in glucose tolerance in healthy, non-obese cats supplemented with dietary chromium. Further long-term studies are warranted to determine if the addition of chromium to feline diets is advantageous. Cats most likely to benefit are those with glucose intolerance and insulin resistance from lack of exercise, obesity and old age. Healthy cats at risk of glucose intolerance and diabetes from underlying low insulin sensitivity or genetic factors may also benefit from long-term chromium supplementation.

Animals↗

Plasma leptin concentrations are independently associated with insulin sensitivity in lean and overweight cats.

This study investigated relationships between plasma leptin, insulin concentrations, insulin sensitivity and glucose tolerance in lean and overweight cats. Leptin concentrations were measured in 16 cats during glucose tolerance tests before and after gaining weight, and after feeding a test meal in overweight cats. An important finding of this study is that in both lean (r=-0.79) and overweight (r=-0.89) cats, the higher the leptin concentrations, the more insulin resistant the cat, independent of the degree of adiposity. Leptin concentrations at baseline and after consuming a meal tended to be higher in overweight cats with glucose intolerance, compared to overweight cats with normal glucose tolerance, although the difference was not significant. After feeding the test meal to overweight cats in the early morning, plasma leptin concentrations initially decreased before subsequently rising to peak 15 h later, which coincided with late evening. The leptin peak occurred 9 h after the insulin peak following ingestion of the test meal. Importantly, this study suggests that increased leptin concentrations may contribute to the diminished insulin sensitivity seen in overweight cats. Alternatively, the compensatory hyperinsulinaemia found with insulin resistance in overweight cats could stimulate leptin production.

Animals↗

Management of canine diabetes.

The majority of diabetic dogs appear to have a form of type 1 diabetes analogous to the latent autoimmune diabetes of adults (LADA) in humans. Evidence of acute or chronic pancreatitis occurs in about 40% of diabetic dogs. Blindness caused by cataract formation eventually occurs in the majority of diabetic dogs and is not dependent on glycemic control. Insulin is the mainstay of therapy for diabetic dogs, and a conservative approach to insulin therapy is crucial. Most diabetic dogs require twice-daily dosing with lente or NPH insulin to adequately control their clinical signs. The diet fed should primarily be palatable and nutritionally balanced. Improved glycemic control may be achieved in some dogs if the diet contains increased insoluble fiber.

Age Factors↗

Management of feline diabetes mellitus.

Up to one quarter of diabetic cats can be well controlled with oral hypoglycemic drugs, although at least 75% require insulin therapy. Most available insulins provide good clinical control but only moderate glycemic control. Because mild to moderate hyperglycemia is well tolerated by cats receiving insulin but hypoglycemia can be life threatening, conservative insulin dosing is recommended. Clinical signs and water intake indicate whether a dose adjustment is required, but serial blood glucose measurements are usually needed to determine the direction of the adjustment. Starting doses of 0.3 to 0.5 IU/kg administered twice daily (rounded down to the nearest whole unit) are usually safe. Dose adjustments should not exceed 1 IU per cat every 2 to 4 weeks unless clinical hypoglycemia has occurred. Cats with clinical hypoglycemia need to be reassessed to see if they are in remission. If not, a 50% to 75% reduction in dose is advised. Approximately 30% of cats go into diabetic remission 1 to 4 months after an adequate treatment protocol is instituted.

Animals↗

Pharmacology of a 40 IU/ml porcine lente insulin preparation in diabetic cats: findings during the first week and after 5 or 9 weeks of therapy.

The aim of this study was to measure the pharmacokinetics and pharmacodynamics of subcutaneously injected 40 IU/ml porcine lente insulin preparation (Caninsulin, Intervet BV, The Netherlands) in diabetic cats. The pharmacological properties of the insulin in poorly controlled or untreated cats were compared with those after several weeks of treatment, to determine if improved diabetic stability altered the pharmacology of this insulin. In addition, the pharmacological properties of intravenously injected 100 IU/ml regular porcine insulin (Actrapid MC, NovoNordisk, Denmark) were measured. Serial plasma samples were collected after subcutaneous injection of porcine lente insulin from 25 diabetic cats in the first week of admission to a 12-month diabetic treatment trial. Samples were also collected after 4 or 8 weeks of treatment, in those cats which had not achieved diabetic remission by this time. At this time, serial plasma samples were also collected from these cats after intravenous injection of porcine regular insulin. Plasma samples were assayed for glucose, anti-insulin antibodies were extracted using a PEG technique, and samples were assayed for insulin using an RIA kit with low sensitivity for endogenous feline insulin, but high sensitivity for exogenous porcine insulin in feline plasma. Caninsulin injected subcutaneously in diabetic cats led to a peak insulin concentration in plasma after 1.7+/-0.1 h, and a nadir of blood glucose after 4.1+/-0.3 h. Insulin and glucose concentrations returned to baseline within 12 h. There was no significant change in the onset or duration of Caninsulin action between the first week of treatment and 5 or 9 weeks of treatment. Actrapid MC injected intravenously had a peak insulin at 0.36+/-0.03 h, and a nadir of blood glucose at 1.9+/-0.3 h. Insulin and glucose returned to baseline within 6 h. It was concluded that Caninsulin injected subcutaneously has suitable pharmacological properties for the twice-daily treatment of diabetes mellitus in cats. In addition, Actrapid MC insulin injected intravenously has suitable pharmacological properties for injection every 4-6 h in diabetic cats.

Animals↗

Insulin sensitivity decreases with obesity, and lean cats with low insulin sensitivity are at greatest risk of glucose intolerance with weight gain.

This study quantifies the effects of marked weight gain on glucose and insulin metabolism in 16 cats which increased their weight by an average of 44.2% over 10 months. Significantly, the development of feline obesity was accompanied by a 52% decrease in tissue sensitivity to insulin and diminished glucose effectiveness. In addition, glucose intolerance and abnormal insulin response occurred in some cats. An important finding was that normal weight cats with low insulin sensitivity and glucose effectiveness were at increased risk of developing impaired glucose tolerance with obesity. High basal insulin concentrations or low acute insulin response to glucose also independently increased the risk for developing impaired glucose tolerance. Male cats gained more weight relative to females and this, combined with their tendency to lower insulin sensitivity and higher insulin concentrations, may explain why male cats are at greater risk for diabetes. Results suggest an underlying predisposition for glucose intolerance in some cats, which is exacerbated by obesity. These cats may be more at risk of progressing to overt type 2 diabetes mellitus.

Animals↗

Determination of reference values for glucose tolerance, insulin tolerance, and insulin sensitivity tests in clinically normal cats.

OBJECTIVE: To determine reference values and test variability for glucose tolerance tests (GTT), insulin tolerance tests (ITT), and insulin sensitivity tests (IST) in cats. ANIMALS: 32 clinically normal cats. PROCEDURE: GTT, ITT, and IST were performed on consecutive days. Tolerance intervals (ie, reference values) were calculated as means +/- 2.397 SD for plasma glucose and insulin concentrations, half-life of glucose (T1/2 glucose), rate constants for glucose disappearance (Kglucose and Kitt), and insulin sensitivity index (Si). Tests were repeated after 6 weeks in 8 cats to determine test variability. RESULTS: Reference values for T1/2glucose, Kglucose, and fasting plasma glucose and insulin concentrations during GTT were 45 to 74 minutes, 0.93 to 1.54 %/min, 37 to 104 mg/dl, and 2.8 to 20.6 microU/ml, respectively. Mean values did not differ between the 2 tests. Coefficients of variation for T1/2glucose, Kglucose, and fasting plasma glucose and insulin concentrations were 20, 20, 11, and 23%, respectively. Reference values for Kitt were 1.14 to 7.3%/min, and for SI were 0.57 to 10.99 x 10(4) min/microU/ml. Mean values did not differ between the 2 tests performed 6 weeks apart. Coefficients of variation for Kitt and SI were 60 and 47%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: GTT, ITT, and IST can be performed in cats, using standard protocols. Knowledge of reference values and test variability will enable researchers to better interpret test results for assessment of glucose tolerance, pancreatic beta-cell function, and insulin sensitivity in cats.

Animals↗

Plasma leptin concentrations in cats: reference range, effect of weight gain and relationship with adiposity as measured by dual energy X-ray absorptiometry.

The aims of our study were to determine a reference range for plasma leptin in healthy, normal-weight cats and to measure the effect of weight gain on plasma leptin levels. To increase our understanding of the association between leptin and feline obesity, we investigated the relationship between plasma leptin and measures of adiposity in cats. Twenty-six normal-weight cats were used to determine the reference range for feline leptin using a multispecies radioimmunoassay. In the second part of the study, plasma leptin concentrations were determined in 16 cats before and after approximately 10 months of spontaneous weight gain. Dual energy X-ray absorptiometry scans (DEXA) were performed after weight gain. The tolerance interval for plasma leptin concentrations was 0.92-11.9 ng/ml Human Equivalent (HE) with a mean concentration of 6.41+/-2.19 ng/ml HE. In part two of the study, 16 cats gained on average 44.2% bodyweight over 10 months. The percentage of body fat in obese cats ranged from 34.2 to 48.7%. Mean plasma leptin concentrations increased from 7.88+/-4.02 ng/ml HE before weight gain to 24.5+/-12.1 ng/ml HE after weight gain, (P<0.001). Total body fat and body fat per cent were the strongest predictors of plasma leptin in obese cats (r=0.8 and r=0.78, P<0.001, respectively). In conclusion, plasma leptin concentrations increased three-fold in cats as a result of weight gain and were strongly correlated with the amount of adipose tissue present. Despite elevated leptin levels, cats continued to eat and gain weight, suggesting decreased sensitivity to leptin. This investigation into the biology of leptin in cats may aid the overall understanding of the role of leptin and the development of future treatments to help prevent and manage feline obesity.

Absorptiometry, Photon↗

Insulin sensitivity in normal and diabetic cats.

Estimates of in vivo insulin sensitivity (S(I)) can be derived from minimal model analysis of a frequently sampled intravenous glucose tolerance test (FSIVGTT). Modification of the FSIVGTT by the injection of insulin allows insulin sensitivity to be measured in diabetics. To establish and compare reference values for insulin sensitivity in clinically normal and diabetic cats, we subjected 10 clinically normal cats and five diabetic cats to the insulin-modified FSIVGTT with minimal model analysis. Diabetic cats had a significantly lower insulin sensitivity than clinically normal cats (P<0.05). Mean insulin sensitivity in clinically normal cats was 3.22x10(-4)/min/microU/ml (range 1.71-5.23x10(-4)/min/microU/ml). In contrast, the mean insulin sensitivity in diabetic cats was 0.58x10(-4)/min/microU/ml (range 0.136-0.88x10(-4)/min/microU/ml), or approximately six times less insulin sensitive than clinically normal cats. Mean glucose effectiveness in clinically normal cats was 0.030/min (range 0.021-0.045/min). Mean glucose effectiveness in diabetic cats was 0.014/min (range 0.008-0.021/min). Our data demonstrate that insulin resistance is a feature of feline diabetes mellitus and that diabetic cats have a similar relative decrease in insulin sensitivity to humans with type 2 diabetes.

Animals↗

Food intake and blood glucose in normal and diabetic cats fed ad libitum.

Ten diabetic cats were studied at intervals for up to 12 months with twice-daily insulin injections. Ten clinically healthy cats were also studied. Diets fed were based on the individual cat's performance, using mainly commercial dry or canned cat foods and fresh meat. In most cases more than one food was offered. Food was given fresh twice daily, and the cats allowed to eat ad libitum. The food intake and blood glucose were measured every 2 h in diabetic cats after insulin injection and in diabetic and normal cats without insulin injections. Food was quantified by the energy consumed (kJ ME), crude protein (g), crude fat (g), and carbohydrate (g). The blood glucose in 10 diabetic cats was measured for 2 h following a 20-min meal. Both diabetic cats and normal cats showed similar patterns of eating, with a higher food intake in the 2 h after fresh food was placed. Both groups of cats ate multiple small meals spread through the day and night. There was little or no correlation between the blood glucose and the amount of food consumed over the previous 2-h period, in insulin- or non-insulin-treated diabetic cats, or in normal cats. An overnight fast did not significantly alter morning blood glucose in diabetic cats. No demonstrable appetite stimulation occurred following an occurrence of low blood glucose; however, recorded incidences were few. No post-prandial hyperglycaemia was seen in the 10 diabetic cats during a 2-h period following the ingestion of typical cat foods.

Animals↗

The effect of interday variation and a short-term stressor on insulin sensitivity in clinically normal cats.

To determine whether there is a day-to-day variation in insulin sensitivity in cats, we subjected six clinically normal cats to four insulin-modified frequently sampled intravenous glucose tolerance tests (FSIVGTTs) over 7 days. The insulin-modified FSIVGTTs were analysed by the minimal model method. Minimal model insulin sensitivity (S(I)) averaged 2.9+/-0.4 x 10(-4) min(-1)/microU/ml (range 1.9-4.6 x 10(-4) min(-1)/microU/ml), with a mean interday coefficient of variation (CV) of 35.4+/-6.4% (range 12.8-58.5%). Glucose effectiveness (S(G)) averaged 0.029+/-0.002 min(-1)(range 0.024-0.037 min(-1)), and showed less interday variability with a mean CV of 24.7+/-4.3% (range 7.9-39.3%). Insulin sensitivity was also measured after a short-term stressor (5-min spray bath) of sufficient magnitude to elevate blood glucose levels. The mean insulin sensitivity after the stressor was 3.6+/-0.8 x 10(-4) min(-1)/microU/ml (range 1.6-7.3 x 10(-4) min(-1)/microU/ml), which was not significantly different to the mean insulin sensitivity before the short-term stressor (P=0.237). The mean glucose effectiveness after the stressor was 0.046+/-0.004 min(-1)(range 0.032-0.057 min(-1)), which was significantly different from mean glucose effectiveness before the short-term stressor (P=0.003). We conclude that insulin sensitivity is highly variable from day to day in normal cats, and that hyperglycaemia in response to short-term stressors is probably due to increased hepatic glucose production, rather than peripheral insulin resistance.

Animals↗

Evaluation of a polyurethane jugular catheter in cats placed using a modified Seldinger technique.

OBJECTIVE: To describe and evaluate the placement of a new design of polyurethane jugular catheter in cats using a modification of the technique of Seldinger. The maintenance and use of these catheters for repeated blood sampling over several days in healthy and diabetic cats is reported. PROCEDURE: Thirty polyurethane jugular catheters were placed in 10 clinically healthy cats and 10 cats with diabetes mellitus using the modified Seldinger technique. Catheters were placed while the cats were under general anaesthesia. RESULTS: The catheters remained in place for a range of 2 to 14 days (median 5 days) with no major complications. In all cats patency of the catheters was maintained until removal. All cats examined had patent jugular veins when assessed 4 or more weeks after the catheters were removed. CONCLUSIONS: These polyurethane jugular catheters, when placed by a modified Seldinger technique, are effective and safe in cats, and jugular patency returns after the catheters are removed.

Animals↗

Reference values for glucose tolerance and glucose tolerance status in cats.

OBJECTIVE: To determine the reference range for glucose tolerance, using a simplified glucose tolerance test (GTT), and to evaluate glucose tolerance status in cats. DESIGN: Prospective study. ANIMALS: 57 clinically normal cats. PROCEDURE: 2 catheters were placed in the cephalic veins of nonsedated cats at least 3 hours before the test. Blood samples were obtained before (0 minutes) and 2, 5, 10, 15, 30, 45, 60, 90, and 120 minutes after glucose (0.5 g/kg [0.23 g/lb] of body weight) was injected i.v. Blood glucose concentration was measured by a glucose meter. Glucose half-life (t1/2) and disappearance of glucose (Kglucose) were calculated. RESULTS: Glucose tolerance in cats was considered normal when upper limits for glucose concentration were < or = 159 mg/dl at 0 minutes, < or = 322 mg/dl at 60 minutes, < or = 238 mg/dl at 90 minutes, or < or = 171 mg/dl at 120 minutes and glucose t1/2 was < or = 94.7 minutes or Kglucose was > or = 0.41%/min. Impaired glucose tolerance in cats was defined as a glucose concentration > or = 160 mg/dl at 0 minutes, > or = 323 mg/dl at 60 minutes, > or = 239 mg/dl at 90 minutes, or > or = 172 mg/dl at 120 minutes. The frequency of impaired glucose tolerance was 2%. Five cats had stress-affected GTT. Significant differences in glucose t1/2 or Kglucose between cats < 7 and > or = 7 years old were not found. CLINICAL IMPLICATIONS: The simplified GTT and measurement of glucose concentration by a glucose meter provides a simple and low-cost method of assessing glucose tolerance status in cats that are normoglycemic after food is withheld. Use of absolute glucose concentrations overcomes the need to calculate glucose t1/2 values. The high glucose concentration at 0 minutes found in this study may reflect a more realistic concentration to use in assessing client-owned cats in a hospital environment.

Aging↗

Evaluation of a simplified intravenous glucose tolerance test and a reflectance glucose meter for use in cats.

A simplified intravenous glucose tolerance test has been developed for use in domestic cats and the results compared with those obtained using the standard test. The simplified test used two cephalic catheters, implanted in unsedated, unanaesthetised cats three hours before the test. Blood samples were collected before and after intravenous administration of glucose (0.5 g/kg bodyweight). Blood glucose concentration was measured with a reflectance glucose meter and an automated chemistry analyser. There were no significant differences between the results derived from the two tests. Because the simplified glucose tolerance test is easier to perform, requires no anaesthesia, uses only cephalic catheters and can be done on an outpatient basis, it is more cost effective and more clinically applicable. There were no significant differences between the results of glucose measurements with the two machines and the simplified glucose tolerance test can therefore be carried out with the reflectance glucose meter.

Animals↗

Detection of amyloid deposition in various regions of the feline pancreas by different staining techniques.

Deposition of islet amyloid is a common finding in the pancreas of diabetic cats and it may contribute to the deterioration of glucose tolerance. Three techniques for detecting pancreatic amyloid deposition were compared in cats not known to be diabetic. Congo red (CR) staining was used for histological sections (35 cats) and tissue smear preparations (crush and smear [CS] technique; 35 cats, and an immunohistochemical method (18 cats) was used for the detection of amyloid derived from amylin. Six diabetic cats were used as positive controls for the immunohistochemical method. The amount of pancreatic amyloid demonstrated immunohistochemically was significantly correlated with that shown by CR staining in histological sections but not in CS preparations, which were less satisfactory. However, the amount of amyloid determined immunohistochemically was slightly but significantly higher than that seen in CR-stained sections. There was no difference in the amount of amyloid between the left limb middle segment and right limb of the pancreas. Amylin labelling was seen in about 70 to 80% of islet cells, mainly those located in the islet periphery and the labelling was most intense in the cell periphery.

Amyloid↗