Evaluation of a Quality‐of‐Life Tool for Cats with Diabetes Mellitus

Background: Success in management of diabetes mellitus (DM) is defined as improvement of blood glucose concentrations and clinical signs. However, the psychological and social impact of DM and its daily treatment regimen on quality of life (QoL) of both animal and owner is uncertain. Hypothesis/Objectives: To design, validate, and apply a diabetic pet and owner‐centered, individualized measure of impact of DM (DIAQoL‐pet). Animals/Subjects: Two hundred and twenty‐one owners of insulin‐treated diabetic cats were recruited to complete the DIAQoL‐pet. Methods: Discussions and pilot surveys with clinicians and owners of diabetic cats led to the design of 29 specific DM‐associated QoL questions. Owners of diabetic cats completed the finalized survey. Each item was scored according to impact frequency and perceived importance. An item‐weighted impact score (IWIS) for each item was calculated, as was an average‐weighted impact score (AWIS) by averaging all IWISs. Principal component analysis and Cronbach's α calculation assessed the measure's reliability. Two overview questions measured overall QoL and diabetes‐dependent QoL. Results: The DIAQoL‐pet showed high reliability (Cronbach α 0.83). The AWIS was ?1.76 ± 2.4 (mean ± SD). Areas reported as most negatively impacting QoL included: “boarding difficulties” (IWIS ± SD: ?4.67 ± 5.3), “owner wanting more control” (?4.34 ± 4.7), “difficulties leaving cat with friends or family” (?4.21 ± 4.7), “worry” (?4.10 ± 3.9), “worry hypo” (?3.67 ± 3.5), “social life” (?3.48 ± 3.9), “costs” (?3.04 ± 3.8), and “work life” (?3.03 ± 3.7). Forty‐one percent of owners believed their cat's life would be “a little better” without DM. Conclusions and Clinical Importance: The DIAQoL‐pet proved robust and identified specific areas most negatively impacting on diabetic cats and their owners' QoL. This tool warrants further investigation for use in clinical or research settings.     

The Influence of Restricted Feeding on Glucagon‐Like Peptide‐1 (GLP‐1)‐Containing Cells in the Chicken Small Intestine

The influence of restricted feeding on the distribution of glucagon‐like peptide‐1 (GLP‐1)‐containing endocrine cells in the chicken small intestine was investigated using immunohistochemical and morphometrical techniques. This study demonstrated that the restricted feeding had an influence on the activity of GLP‐1‐immunoreactive cells in the chicken small intestine. There were differences in the localization and the frequency of occurrence of GLP‐1‐immunoreactive cells in the small intestine between control and restricted groups, especially 25% feed supply group provided with 25% of the intake during the adapting period. GLP‐1‐immunoreactive cells in the control chickens were mainly located in epithelium from crypts to the lower part of intestinal villi. Those in restricted groups, however, tended to be located from crypts to the middle part of intestinal villi. The frequency of occurrence of GLP‐1‐immunoreactive cells was lowest in the control group, medium in 50% feed supply group and highest in 25% feed supply group at each intestinal region examined in this study, that is, increased with the advancement of restricting the amount of feed supply. These data show that the quantity of food intake is one of signals that have an influence on the secretion of GLP‐1 from L cells in the chicken small intestine.     

Computed Tomographic Angiography of the Pancreas in Cats with Chronic Diabetes Mellitus Compared to Normal Cats

Background

Diabetes mellitus (DM) is a common endocrinopathy in cats. No known diagnostic test or patient characteristic at the time of diagnosis can predict likely disease course, unlike in people in whom computed tomographic angiography (CTA) is used. No published data exist regarding the CTA appearance of the pancreas in cats with DM, and thus, it is unknown what if any CTA variables should be further assessed for associations with pancreatic endocrine function.

Hypothesis/Objectives

A significant difference in pancreatic attenuation, volume, and size will be identified between normal cats and those with chronic DM on CTA.

Animals

Ten healthy control cats and 15 cats with naturally occurring DM present for >12 months.

Methods

Prospective cross‐sectional study comparing pancreatic attenuation, enhancement pattern, size, volume, pancreatic volume‐to‐body weight ratio (V:BW), pancreatic arterial: portal phase ratio (A:P), time‐to‐arterial enhancement, and time‐to‐peak portal enhancement on CTA between sedated healthy control cats and those with chronic DM.

Results

The pancreas in cats with chronic DM was significantly larger, had higher volume, higher V:BW, and shorter time‐to‐peak portal enhancement on CTA when compared to normal cats.

Conclusions and Clinical Importance

Peak portal enhancement time, pancreatic size, pancreatic volume, and V:BW can be used to differentiate normal sedated cats from those with chronic DM by CTA. These variables warrant further investigation to identify possible associations with endocrine function.     

Response to Insulin Treatment and Survival in 104 Cats with Diabetes Mellitus (1985–1995)

Medical records of 104 cats with diabetes mellitus were reviewed. Information from 54 cats that had multiple blood glucose concentrations evaluated at least 5 times over a minimum of 3 months, beginning at the time insulin treatment was initiated, was used to evaluate the efficacy of insulin in treating diabetes mellitus. Fourteen of 54 cats were treated with protamine zinc insulin (PZI), 26 with ultralente insulin, and 14 with lente insulin. Six, 29, and 19 cats had good, mediocre, and poor glycemic control, respectively, based on mean blood glucose concentrations, whereas 31, 21, and 2 owners thought clinical response was good, mediocre, and poor, respectively. No significant difference was found in glycemic control among cats treated with PZI, ultralente, or lente insulin. Glycemic control was significantly (P < .05) better in 33 cats without than in 21 cats with concurrent disease. All 104 cats were used to calculate survival data. Fifty-one of 104 cats were alive at the time of the study. Mean (± standard deviation [SD]) and median survival times were 24 (± 16) and 20 months, respectively, in the 51 cats still alive at the end of the evaluation, and 25 (± 4) and 17 months, respectively, in the 53 cats that had died during the period of evaluation. Pancreatic abnormalities identified in 37 cats that underwent necropsy included chronic pancreatitis (n = 17), acute to subacute pancreatitis (n = 2), exocrine pancreatic adenocarcinoma (n = 7) and adenoma (n = 1), islet cell atrophy and vacuolar degeneration (n = 27), and islet amyloidosis (n = 8). No association was found between glycemic control and islet amyloidosis or exocrine pancreatic neoplasia, or between survival time and chronic pancreatitis, islet amyloidosis, or exocrine pancreatic neoplasia. In conclusion, diabetic cats evaluated in this study showed a variable response to exogenously administered insulin, ranging from excellent to poor. By maintaining mean blood glucose concentrations under 300 mg/dL, clinical signs were improved, and owners were satisfied with insulin treatment. Concurrent potentially insulin-antagonistic diseases were common and deleteriously affected glycemic control and survival time.     

Metabolomic profiling reveals differential effects of glucagon‐like peptide‐1 and insulin on nutrient partitioning in ovine liver

This study was conducted to identify the insulin‐independent actions of glucagon‐like peptide‐1 (GLP‐1 (7‐36 amide)) in partitioning nutrient metabolism in ovine liver. Four Suffolk wethers (60.0 ± 6.7 kg body weight (BW)) were used in a repeated‐measure design under euglycemic‐‐hyperinsulinemic and hyper ‐GLP‐1 clamps for 150 min with intravenous infusion of insulin (0.5 mU/kg BW/min; from 0 to 90 min), GLP‐1 (0.5 µg/kg BW/min; from 60 to 150 min) and both hormones co‐administered from 60 to 90 min. Liver biopsies were collected at 0, 60, 90 and 150 min to represent the metabolomic profiling of baseline, insulin, insulin plus GLP‐1, and GLP‐1, respectively, and were analyzed for metabolites using Capillary Electrophoresis Time‐of‐Flight Mass Spectrometer. Metabolomics analysis reveals 51 metabolites as being significantly altered (P < 0.05) by insulin and GLP‐1 infusion compared to baseline values. Insulin infusion enhanced glycolysis, lipogenesis, oxidative stress defense and cell proliferation pathways, but reduced protein breakdown, gluconeogenesis and ketogenesis pathways. Conversely, GLP‐1 infusion promoted lipolytic and ketogenic pathways accompanied by a lowered lipid clearance from the liver as well as elevated oxidative stress defense and nucleotide degradation. Despite further research still being warranted, our data suggest that GLP‐1 may exert insulin‐antagonistic effects on hepatic lipid and nucleotide metabolism in ruminants.     

Distribution of insulin receptor and insulin‐like growth factor‐1 receptor in the digital laminae of mixed‐breed ponies: An immunohistochemical study

Reasons for performing study: Hyperinsulinaemia has been implicated in the pathogenesis of laminitis; however, laminar cell types responding to insulin remain poorly characterised. Objectives: To identify laminar cell types expressing insulin receptor (IRc) and/or insulin‐like growth factor‐1 receptor (IGF‐1R); and to evaluate the effect of dietary nonstructural carbohydrate (NSC) on their expression. Methods: Mixed‐breed ponies (n = 22) received a conditioning hay chop diet (NSC ～6%); following acclimation, ponies were stratified into lean (n = 11, body condition score [BCS]≤4) or obese (n = 11, BCS ≥7) groups and each group further stratified to remain on the low NSC diet (n = 5 each for obese and lean) or receive a high NSC diet (total diet ～42% NSC; n = 6 each for obese and lean) for 7 days. Laminar samples were collected at the end of the feeding protocol and stained immunohistochemically for IRc and IGF‐1R. The number of IRc(+) cells was quantified; distribution of IGF‐1R was qualitatively described. Laminar IRc content was assessed via immunoblotting. Results: The number of IRc(+) cells was greater in the laminae of high NSC ponies than low NSC ponies (P = 0.001); there was a positive correlation between the change in serum insulin concentration and number of IRc(+) cells (r²= 0.74; P<0.0001). No epithelial IRc(+) cells were observed; IRc(+) cells were absent from the deep dermis. Analysis of serial sections identified IRc(+) cells as endothelial cells. The distribution of IGF‐1R was more extensive than that of IRc, with signal in vascular elements, epithelial cells and fibroblasts. Conclusions: Increased dietary NSC results in increased laminar endothelial IRc expression. Laminar keratinocytes do not express IRc, suggesting that insulin signalling in laminar epithelial cells must be mediated through other receptors (such as IGF‐1R). Potential relevance: Manipulation of signalling downstream of IRc and IGF‐1R may aid in treatment and prevention of laminitis associated with hyperinsulinaemia.     

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.     

Characterization of the clinical characteristics, electrolytes, acid–base, and renal parameters in male cats with urethral obstruction

Objective: To characterize the clinical characteristics, electrolyte changes, acid–base changes, and renal parameters in a consecutive population of cats with urethral obstruction. Design: Retrospective clinical study. Setting: University Veterinary Teaching Hospital. Animals: Two hundred and twenty‐three male cats that presented consecutively with urethral obstruction between 1997 and 1999. Interventions: None. Measurements and main results: The medical records of 223 cats with urethral obstruction were reviewed for signalment, previous medical history, indoor/outdoor status, body weight, clinical signs, physical examination findings, renal function tests (blood urea nitrogen and creatinine), and blood gas and electrolyte analysis. The majority of cats were relatively stable without serious metabolic derangements. Only 12% (24/199) of cats had severe hyperkalemia (>8.0 mmol/L). Hyperkalemia did not occur in isolation; the majority of these cats had concurrent acidemia and low ionized calcium concentrations. Potassium was significantly inversely correlated with pH, bicarbonate, pCO₂, sodium, chloride, and ionized calcium, but positively correlated with blood urea nitrogen and creatinine. Ionized calcium was positively correlated with pH and bicarbonate. Of the animals with a potassium concentration greater than 8.0 mmol/L, 75% (18/24) had an ionized calcium concentration of less than 1.0 mmol/L. Seventy‐nine percent (19/24) of cats with a potassium concentration greater than 8.0 mmol/L had a blood pH<7.20. Similarly, 74% (23/31) of cats with a pH<7.20 had an ionized calcium concentration <1.00 mmol/L. Conclusions: The majority of cats with urethral obstruction presented with mild electrolyte and blood gas changes and were relatively stable, although 12% of cats had multiple, life‐threatening metabolic derangements. Of 219 cats in this study, 205 (93.6%), where it could be determined, survived to discharge from the hospital, supporting the fact that most cats with urethral obstruction survive the acute episode with emergency treatment.     

Effect of Feeding an Iodine‐Restricted Diet in Cats with Spontaneous Hyperthyroidism

Background

Exclusive feeding of an iodine‐restricted diet has been proposed as a method for controlling clinical manifestations of hyperthyroidism in hyperthyroid cats.

Objectives

To determine the effect of feeding an iodine‐restricted diet on TT4 concentrations and clinical signs in cats with spontaneous hyperthyroidism.

Animals

Forty‐nine client‐owned cats with spontaneous hyperthyroidism.

Methods

Retrospective case series. Hyperthyroid cats were exclusively fed a commercially available iodine‐restricted diet. Clinical response was assessed by change in weight and heart rate and serum TT4, blood urea nitrogen (BUN), and creatinine concentrations at various times during dietary management (21–60 days, 60–180 days).

Results

Serum TT4 normalized in 20/48 cats (42%) and 39/47 cats (83%) at 21–60 days and 61–180 days, respectively. Cats in which the TT4 concentrations were still above reference range at 21–60 days had a significantly higher starting TT4 than those that normalized their TT4 levels during the same time period (P = .038). Body weight did not significantly increase (P = .34) nor heart rate decrease (P = .64) during the study. There was a significant decrease in serum creatinine (P = .028). Cats in the low reference range for serum TT4 concentrations did not have a significant increase in body weight (P = .41) nor creatinine (P = .54) when compared to those with high reference range.

Conclusions and Clinical Importance

Restricted‐iodine diets were effective at maintaining serum TT4 concentrations within reference ranges for a majority of cats with spontaneous hyperthyroidism over 1 year, although not all clinical signs of hyperthyroidism improved.     

N-乙酰-L-半胱氨酸抗1型糖尿病模型比格犬晶状体上皮氧化损伤的作用

本研究旨在探讨N-乙酰-L-半胱氨酸(NAC)对1型糖尿病模型比格犬晶状体上皮氧化损伤的影响。将40只2～3岁比格犬随机分为对照组(CON组)、糖尿病模型组(DM组)、胰岛素治疗组(INS组)、NAC联合胰岛素治疗组(NAC+INS组)和NAC治疗组(NAC组),每组8只,各治疗组试验犬模型建立持续120 d。在造模前及造模后按试验设定时间对犬进行空腹血糖监测、胰岛素释放试验、房水葡萄糖测定、用裂隙灯进行白内障等级评定。对眼晶状体上皮进行病理组织学观察的同时,利用ELISA、RT-PCR等方法对晶状体内氧化应激指标进行检测。试验结果显示：空腹血糖监测和胰岛素释放试验显示,成功建立了1型糖尿病比格犬模型;与CON组相比,DM组犬在试验结束时,血清及房水葡萄糖显著升高(P<0.05),晶状体功能明显下降;裂隙灯结果显示,DM组犬的晶状体混浊等级在试验结束时达Ⅳ级,其余4组并未出现明显皮质混浊迹象,且DM组的晶状体上皮出现细胞核固缩和坏死小体等较为明显的病理变化;NAC、INS和NAC+INS组血糖虽呈下降趋势,但仍高于CON组,其中,NAC+INS组血糖较DM组显著下降(P<0...     

Evaluation of Pax5 expression and comparison with BLA.36 and CD79αcy in feline non‐Hodgkin lymphoma

Paired box gene 5 (Pax5) is a widely used B‐cell marker for human and canine non‐Hodgkin's lymphoma (nHL); however, in the literature there is only one case report using Pax5 in a cat B‐cell lymphoma. The purposes of this study were to investigate the expression and detection of B‐cell specific activator protein (BSAP) using a monoclonal anti‐Pax5 antibody in feline nHL (FnHL) tissue samples to evaluate its diagnostic relevance as a B‐cell marker. A total of 45 FnHL samples in 45 cats were evaluated. B‐cell lymphoma was the most common immunophenotype (51.1%) for all the samples and T‐cell the most common immunophenotype (64.3%) for the gastrointestinal (GI) form. Pax5 stained 82.6% of all B‐cell lymphomas and no expression was found in any of the T‐cell lymphomas. Anti‐Pax5 antibody staining in FnHL is similar to that reported in human and canine counterparts and may offer an excellent B‐cell marker in cats.     

A Polymorphism in the Melanocortin 4 Receptor Gene (MC4R:c.92C>T) Is Associated with Diabetes Mellitus in Overweight Domestic Shorthaired Cats

Background

Feline diabetes mellitus (DM) shares many pathophysiologic features with human type 2 DM. Human genome‐wide association studies have identified genes associated with obesity and DM, including melanocortin 4 receptor (MC4R), which plays an important role in energy balance and appetite regulation.

Hypothesis/Objectives

To identify single nucleotide polymorphisms (SNPs) in the feline MC4R gene and to determine whether any SNPs are associated with DM or overweight body condition in cats.

Animals

Two‐hundred forty domestic shorthaired (DSH) cats were recruited for the study. Of these, 120 diabetics were selected (60 overweight, 60 lean), along with 120 nondiabetic controls (60 overweight and 60 lean). Males and females were equally represented.

Methods

A prospective case‐control study was performed. Genomic DNA was extracted from blood samples and used as template for PCR amplification of the feline MC4R gene. The coding region of the gene was sequenced in 10 cats to identify polymorphisms. Subsequently, genotyping by restriction fragment length polymorphism (RFLP) analysis assessed MC4R:c.92C > T allele and genotype frequencies in each group of cats.

Results

No significant differences in MC4R:c.92C>T allele or genotype frequencies were identified between nondiabetic overweight and lean cats. In the overweight diabetic group, 55% were homozygous for the MC4R:c.92C allele, compared to 33% of the lean diabetics and 30% of the nondiabetics. The differences between the overweight diabetic and the nondiabetics were significant (P < .01).

Conclusions and Clinical Importance

We identified a polymorphism in the coding sequence of feline MC4R that is associated with DM in overweight DSH cats, similar to the situation in humans.