Prevalence and risk factors for the development of diabetes mellitus in Swedish cats

Background

The prevalence and risk factors for the development of feline diabetes mellitus (FDM) in Swedish cats have not previously been reported. The objective of the present pilot study was to indicate prevalence and possible risk factors for FDM in Swedish cats. Twenty diabetic cats from the database at the University Animal Hospital in Uppsala participated in the study, and these were matched with 20 healthy controls on sex and age. A mail-and-telephone questionnaire focusing on diet, activity and obesity was used.

Results

The prevalence of FDM during the years 2000–2004 based on the results of the hospital records in the present study was 21 per 10,000 cats. The diabetic cats were on average 9 years old when the disease signs were discovered (median, min-max 2–15). Among FDM cases, it was more common to be male (n=17 males vs n=3 females; P≤0.05). Ten out of twenty owners to cases (50%) reported their cats to be obese at the time of the diagnosis (median 9 years, min-max 2–15), as compared to five out of twenty (25%) controls at the same age. The median BW at the time for diagnosis was 5.5 kg (min-max 2.0-9.0) for cases, and 5.0 kg (min-max 3.0-8.0 kg) for controls, respectively. Despite that both cases and controls had the same median age at the time of the study (13 years, min-max 3–18), a significantly higher number of controls were alive at that age (n=16 controls vs 8 cases; P≤0.05). A significantly higher proportion of cases that were obese at the time of the FDM diagnosis were dead at the time of the study compared to the proportion of controls that were obese at a similar age (P≤0.05).The diets given at the time for diagnosis for cases compared to diet of the controls at a similar time were mainly commercial foods, and controls consumed a higher proportion of dry foods compared to cases (medians 79 vs 44% of DM intake/d, respectively; P≤0.05). Cases were less active compared to the controls (2.3 and 3.2 h/d, respectively; P≤0.05).

Conclusions

The results indicate that the proportions of dry foods in the diet, to perform low activity and to be obese could be identified as preliminary risk factors for FDM in Swedish cats, and should be taken into account in preventive measures as well as in the design of future epidemiological studies in this population.     

Over representation of Burmese cats with diabetes mellitus

Objective To determine if Burmese cats in Queensland have an increased risk of diabetes mellitus.
Design A retrospective study of diabetic and nondiabetic cats that had blood submitted to a veterinary clinical laboratory over a 22 month study period.
Sample population 4402 cats
Procedure Cats were considered diabetic if blood glucose concentration was > 11 mmol/L and fructosamine was > 406 μmol/L or hydroxybutyrate was >1 mmol/L. Cats were grouped into Burmese and non-Burmese. Adjusted odds ratios of diabetes were calculated for breed, gender and age group amongst cats with blood glucose > 11 mmol/L.
Results Burmese cats comprised 20% of 45 diabetic cats of known breed, which was higher (P < 0.001) than among the normoglycemic reference population of 2203 cats (7% Burmese). There were more females among the diabetic Burmese (62%), but this did not differ (P > 0.05) from the Burmese reference population (45% females). In contrast, males seemed to predominate among diabetic non-Burmese (63%), although this also did not differ (P > 0.05) from the reference population (55%) or from diabetic Burmese (38% males). The majority (90%) of diabetic cats were older than 6 years, irrespective of breed (median age 12 years, interquartile range 10 to 13 years). This was higher (χ²= 8.13, P < 0.005) than among the normoglycaemic reference population, where 69% were older than 6 years.
Conclusions Burmese cats were significantly over represented among cats with diabetes mellitus. Irrespective of breed, the risk of diabetes in the study population increased with age.     

Malate dehydrogenase activities are lower in some types of peripheral leucocytes of dogs and cats with type 1 diabetes mellitus

The activities of the enzymes in the malate-aspartate shuttle were measured in peripheral leucocytes of spontaneous type 1 diabetic dogs and cats treated with insulin injections. In the diabetic dogs and cats, fasting plasma glucose concentrations were three- or fourfold greater than the control levels in spite of insulin injections and the activities of cytosolic malate dehydrogenase (MDH), one of pivotal enzymes in the malate-aspartate shuttle, were remarkably lower than the controls. Depressed expression of cytosolic MDH mRNA was confirmed by RT-PCR analysis in the diabetic animals. The cytosolic ratio of MDH/lactate dehydrogenase (LDH) activity (M / L ratio) in leucocytes of the diabetic animals was significantly lower than that of normal control animals. The smaller M / L ratio appeared to reflect depression of energy metabolism in the diabetic animals. Intrinsically lower and further decreased MDH activities may be factors that induce insulin resistance observed in diabetic cats.     

Pulmonary lesions in cats with diabetes mellitus

Diabetes mellitus (DM) is a common endocrinopathy of cats and humans. Although few studies have examined the effects of DM on the pulmonary system, changes in pulmonary function and immunology in humans with type I and II diabetes, and pulmonary lesions in a murine diabetic model have been documented. Our objective was to determine whether pulmonary lesions occurred in cats with DM. Medical records and necropsy evaluations of 42 cats with DM were compared with those of 45 age-matched, nondiabetic cats for the presence of clinical evidence of respiratory disease and pulmonary histopathological findings at the time of necropsy. No statistical difference was noted in the presence of clinical evidence of respiratory disease between cats with diabetes and control cats. Nevertheless, there was a significant association between the presence of abnormal pulmonary histopathology and DM (P = .018, odds ratio = 3 inclusive of all cats; P = .005, odds ratio = 5 when non-DM cats with overt clinical evidence of respiratory disease were excluded). Pulmonary abnormalities detected by histopathological examination in cats with diabetes included congestion and edema, histiocytosis, pneumonia, smooth muscle hypertrophy, fibrosis, mineralization, neoplasia, and type II pneumocyte hyperplasia. The observed association between DM and pulmonary lesions in cats, independent of clinical evidence of respiratory disease, emphasizes the need for careful assessment of the respiratory tract in sick cats with diabetes.     

IGF-1和IGF-1R基因在辽宁绒山羊皮肤组织中的表达

为了研究类胰岛素生长因子1(IGF-1)和类胰岛素生长因子1受体(IGF-1R)基因在绒山羊绒毛生长不同阶段皮肤组织中的表达差异,试验采用实时荧光定量PCR技术对非产绒期和产绒期辽宁绒山羊皮肤中IGF-1和IGF-1R基因的表达进行了测定。结果表明:辽宁绒山羊皮肤中IGF-1和IGF-1R mRNA的表达量在产绒期均极显著高于非产绒期(P<0.01),产绒期IGF-1、IGF-1RmRNA的表达水平分别是非产绒期的8.30倍和7.49倍。说明IGF-1和IGF-1R基因可能与山羊绒周期性生长有关。     

Serum insulin-like growth factor-I concentration in cats with diabetes mellitus and acromegaly

BACKGROUND: Serum insulin-like growth factor-I (IGF-I) has been used in place of serum growth hormone quantification for identifying acromegaly in diabetic cats. The utility of IGF-I as a screening test for acromegaly has not been critically evaluated. This retrospective study was performed to evaluate the usefulness of serum IGF-I concentration for identifying acromegaly. HYPOTHESIS: Serum IGF-I is a useful screening test for acromegaly in diabetic cats. ANIMALS: A review was made of the medical records of 74 diabetic cats that had serum IGF-I quantified. The diabetes was classified as well controlled (15 cats), poorly controlled because of problems with the insulin treatment regimen, concurrent disease, or both (40), or poorly controlled with clinical findings consistent with acromegaly (19). METHODS: A review of medical records was made. RESULTS: Serum IGF-I concentration was significantly (P < .0001) increased in acromegalic diabetic cats, compared with well-controlled and poorly controlled diabetic cats. Sensitivity and specificity for serum IGF-I concentration were 84% (95%/ confidence interval [CI] = 60.4-96.6%) and 92% (95% CI = 81.3-97.2%), respectively. There was no significant correlation between serum IGF-I concentration and duration of insulin treatment (r = 0.23, P = .089), insulin dosage (r = 0.14, P = .30), age (r = 0.16, P = .12), and pituitary volume (r = 0.40, P = .11), but a modest correlation was found between serum IGF-I concentration and body weight (r = 0.48, P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Results support the use of serum IGF-I concentration as a screening test for acromegaly in diabetic cats that have clinical findings supportive of the disease.     

EGF和IGF-1对水牛卵母细胞体外成熟培养的影响

作者研究了在培养液中添加不同浓度的EGF、IGF-1以及EGF联合IGF-1对水牛卵母细胞体外成熟的影响。结果表明：①添加各种浓度的EGF都可以提高水牛卵母细胞的成熟率，其中50 ng/ml EGF有显著影响(P＜0.05)。②10、20 ng/ml的IGF 1对水牛卵母细胞体外成熟无显著影响(P＞0.05)； 30 ng/ml的IGF-1能显著提高水牛卵母细胞体外成熟率(P＜0.05)。③添加20 ng/ml EGF+30 ng/ml IGF-1组卵母细胞体外成熟率高于添加30 ng/ml的IGF-1组，显著高于添加20 ng/ml EGF组和对照组(P＜0.05)。可见，EGF和IGF-1对水牛卵母细胞体外成熟有协同作用。     

The prevalence of microalbuminuria and proteinuria in cats with diabetes mellitus

The prevalence of microalbuminuria (MA) and proteinuria was evaluated in 66 cats with diabetes mellitus (DM), 35 nondiabetic cats with other illness, and 11 healthy nondiabetic cats with use of the E.R.D.-HealthScreen Feline Urine Test. The MA prevalence was higher in the diabetic than in the nondiabetic sick and healthy control cats (70%, 39%, and 18% respectively, P < .0001). In addition, prevalence of proteinuria defined by a protein/creatinine ratio (UPC) > 0.4 was significantly higher in the diabetic cat than in the control cats (70%, 35%, and 9% respectively, P < .0001). There was a significant but weak correlation between the results of MA and UPC (P < .0001, r = 0.43). Our results showed that MA is common in cats with DM. Further studies are required to evaluate the prognostic value of the presence and the severity of MA in cats with DM.     

蓝塘仔猪IGF-1水平与组织IGF-1、GHR基因的表达

32头不同日龄(出生、3、21、35d)蓝塘仔猪,由前腔静脉采血后剖杀,取肝脏、背最长肌样品。用RIA法测血液、组织中IGF 1浓度,用放射受体法(RBA)检测肝脏、肌肉组织中GHR结合活性,用实时荧光定量PCR法检测IGF 1、GHRmRNA的表达水平。结果表明:(1)血液中IGF 1在出生日显著高于其它时期(P<0 05)。肌肉组织中IGF 1含量高于肝脏组织,肌肉组织IGF 1含量在3、21、35日龄时都显著高于出生日(P<0 05)。(2)肝脏细胞膜GHR结合活性在出生日显著高于3、21日龄(P<0 05),肝脏细胞膜GHR结合活性高于肌肉组织。(3)肝脏组织IGF 1、GHRmRNA的表达量均显著高于肌肉组织(P<0 05)。肝脏IGF 1mRNA的表达在出生日、21日龄时显著高于3、35日龄(P<0 05),GHRmRNA的表达在出生日显著高于其它日龄(P<0 05)。肌肉IGF 1、GHRmRNA的表达在出生日均显著高于其它日龄(P<0 05)。     

限饲和自由采食条件下色氨酸对断奶仔猪血清IGF-1浓度的影响

IGF-1是动物出生后生长调节的重要因子,试验采用2×3因子试验设计,研究了饲喂方式(自由采食和限饲)和日粮色氨酸水平(0.12%、0.19%或0.26%)对仔猪血清IGF-1水平的影响,旨在探讨色氨酸对仔猪生长的调节途径。试验选用48头28日龄断奶、初始体重为(8.6±0.13)kg的二元杂交(长白×大白)阉公猪,按照随机区组的原则分成6个处理,每个处理8个重复。试验第10天,仔猪空腹12h,采血,制备血清,测定IGF-1浓度。结果表明:色氨酸具有改善仔猪生长性能、促进血清IGF-1浓度上升(P<0.01)的作用,饲喂方式和日粮色氨酸水平对血清IGF-1有互作效应(P<0.01),这表明色氨酸促进仔猪生长可能与血液中IGF-1水平升高有关。     

新扬州鸡IGF-1基因5''调控区PstⅠ位点多态性与繁殖性状关系的研究

采用PCR-RFLP技术,对207只新扬州鸡的胰岛素样生长因子-1(IGF-1)基因的5'端调控区进行遗传多态性研究,发现该调控区的扩增产物经PstⅠ酶切后出现AA、AB和BB 3种基因型.x2检验的结果表明:新扬州鸡在IGF-1基因PstⅠ位点上均处于Hardy-Weinberg平衡状态(P＞0.05).分析基因型与产蛋性状的关系时,发现基因型对新扬州鸡开产蛋重、第30周和40周蛋重以及40周产蛋量有显著影响(P＜0.05),而对新扬州鸡30、40、50和60周产蛋数、开产体重、开产日龄、开产胸骨长、开产胫长和蛋壳重影响不显著(P＞0.05).在所研究的指标中,新扬州鸡的BB基因型效应均大于AB和AA基因型.     

IGF-1 receptor signaling pathways and effects of AMPK activation on IGF-1-induced progesterone secretion in hen granulosa cells

IGF-1 plays a key role in the proliferation and differentiation of granulosa cells. However, the molecular mechanism of IGF-1 action in avian granulosa cells during follicle maturation is unclear. Here, we first studied IGF-1 receptor (IGF-1R) expression, IGF-1-induced progesterone production and some IGF-1R signaling pathways in granulosa cells from different follicles. IGF-1R (mRNA and protein) was higher in fresh or cultured granulosa cells from the largest follicles (F1 or F2) than in those from smaller follicles (F3 or F4). In vitro, IGF-1 treatment (10(-8)M, 36h) increased progesterone secretion by four-fold in mixed F3 and F4 (F3/4) granulosa cells and by 1.5-fold in F1 granulosa cells. IGF-1 (10(-8)M, 30min)-induced increases in tyrosine phosphorylation of IGF-1R beta subunit and phosphorylation of ERK were higher in F1 than in F3/4 granulosa cells. Interestingly, IGF-1 stimulation (10(-8)M, 10min) decreased the level of AMPK Thr172 phosphorylation in F1 and F3/4 granulosa cells. We have recently showed that AMPK (AMP-activated protein kinase) is a protein kinase involved in the steroidogenesis in chicken granulosa cells. We then studied the effects of AMPK activation by AICAR (5-aminoimidazole-4-carboxamide ribonucleoside), an activator of AMPK, on IGF-1-induced progesterone secretion by F3/4 and F1 granulosa cells. AICAR treatment (1mM, 36h) increased IGF-1-induced progesterone secretion, StAR protein levels and decreased ERK phosphorylation in F1 granulosa cells. Opposite data were observed in F3/4 granulosa cells. Adenovirus-mediated expression of dominant negative AMPK totally reversed the effects of AICAR on IGF-1-induced progesterone secretion, StAR protein production and ERK phosphorylation in both F3/4 and F1 granulosa cells. Thus, a variation of energy metabolism through AMPK activation could modulate differently IGF-1-induced progesterone production in F1 and F3/4 granulosa cells.     

四种黄羽肉鸡IGF-1多态性与生产性能相关分析

采用PCR-SSCP技术测定了4个黄羽肉鸡品种IGF-1基因2个SNP位点,并分析了它们对不同周龄体重及产蛋性状的遗传效应.结果显示,2个SNP位点分别发生了T→A、G→A的单碱基突变,各有3种基因型,京海黄鸡P1位点偏离Hardy-Weinberg平衡状态(P<0.01).最小二乘方差分析表明,京海黄鸡、江村黄鸡从型个体具有较高的300日龄产蛋量,与AB、BB型间差异显著(P<0.05),江村黄鸡从型具有较高的12周龄和300日龄体重,石岐杂鸡AA型300日龄体重显著高于BB型(P<0.05),表明A为产蛋及体重增效基因;不同黄鸡品种均表现出CC型个体具有较高的300日龄体重和产蛋数(P>0.05).     

子宫蓄脓对犬子宫内膜组织中IGF-2及IGF-1R蛋白表达的影响

探讨IGF-2及IGF-1R蛋白质在子宫蓄脓的表达及与子宫蓄脓发病的相关性。采用免疫组织化学PV法与Western blotting检测5例正常子宫内膜(对照组)、19例子宫蓄脓(试验组)子宫内膜组织中IGF-2及IGF-1R的表达情况。结果表明,免疫组化与Western blotting检测结果一致,IGF-2和IGF-1R在蓄脓子宫组中的表达量极显著高于正常子宫(P<0.01)。对子宫蓄脓组中IGF-1R与IGF-2进行相关性分析,免疫组化结果表明IGF-1R与IGF-2之间低度相关(ｒ=0.423),Western blotting结果显示IGF-1R与IGF-2之间高度相关(ｒ=0.927)。结果提示,IGF-2阳性表达上调及IGF-1R的异常高表达,在子宫蓄脓的发生和发展过程中可能具有重要作用。     

Effect of Canine Pyometra on IGF-2, IGF-1R Proteins Expressions of Endometria

To investigate the expression of IGF-2 and IGF-1R protein in endometria of canine pyometra and analyze the possible correlation with the incidence of canine pyometra.Immunohistochemistry PV method and Western blotting were used to measure the IGF-2 and IGF-1R expression characteristic of 5 normal endometria and 19 endometria of canine pyometra.The results showed that the IGF-2 level of endometria from pyometra group was extremely significant higher than that of control group by immunohistochemistry and Western blotting (P<0.01).The positive expression rate of IGF-1R in endometria of canine pyometra compared with that in the normal endometria was extremely significant higher by immunohistochemistry and Western blotting (P<0.01).The correlation analysis of IGF-2 and IGF-1R in canine pyometra showed that the result of immunohistochemistry was low correlation (ｒ=0.423), the result of Western blotting was high correlation (ｒ=0.927).The data suggested that increased expression of IGF-2 and IGF-1R played an important role in occurrence of canine pyometra.     

Pregnancy-related diabetes mellitus in two dogs

CASE SUMMARIES: Two cases of diabetes mellitus occurring in bitches in association with pregnancy are reported. In the first case, a bitch with suspected acromegaly developed diabetes mellitus within 2 weeks of the due date. Despite insulin therapy, euglycaemia was not achieved. Tw o live, small pups were delivered by elective Caesarean section but died within 2 days. Signs consistent with acromegaly resolved but diabetes mellitus was permanent in the bitch. In the second case, diabetic ketosis with severe gastrointestinal disease was diagnosed 2 days after Caesarean section was performed due to dystocia. The pups delivered all died within 5 days. The bitch recovered fully from diabetes mellitus within 2 weeks and has remained euglycaemic without insulin for a period of at least 18 months.

CLINICAL RELEVANCE: These two cases demonstrate that diabetes mellitus can occur in association with pregnancy in dogs, that diabetic ketosis can occur during transient diabetes mellitus in dogs, and suggest that acromegaly may occur during pregnancy-related dioestrus in dogs. The scarcity of previous reports of this nature, however, suggests that such cases are unusual.

Lack of prompt resolution of hyperglycaemia may result in secondary diabetes mellitus becoming permanent. Management should focus on immediate insulin therapy or ovariohysterectomy to minimise this risk. Even mild hyperglycaemia should not be ignored during pregnancy. The insulin antagonistic effects of pregnancy, stressful illness, surgery and dystocia can be enough to result in diabetic ketosis in the absence of permanent insulin deficiency. Maternal hyperglycaemia may contribute to adverse fetal outcomes in dogs but further study is required regarding the nature of the risk.     

Evaluation of bexagliflozin in cats with poorly regulated diabetes mellitus

The aim of this study was to investigate the effect of bexagliflozin on glycemic control in poorly regulated diabetic cats and to evaluate for adverse events associated with this medication.Sodium-glucose cotransporter 2 inhibitors are a newer class of drugs used in the management of humans with type 2 diabetes mellitus. The objective of this study was to evaluate the effect of the orally administered drug, bexagliflozin in a group of poorly regulated diabetic cats over a 4-week study period. Five client-owned cats with poorly controlled diabetes mellitus receiving insulin therapy were enrolled. Bexagliflozin was administered once daily. Serum fructosamine, serum biochemistry profile, and 10-hour blood glucose curves were assessed at baseline (Day 0), Day 14, and Day 28. All cats had a significant reduction in insulin dose requirement (P = 0.015) and insulin was discontinued in 2 cats. There was a significant decrease in blood glucose concentration obtained from blood glucose concentration curves during the study period (P = 0.022). Serum fructosamine decreased in 4 of the 5 cats with a median decrease of 152 μmol/L (range: 103 to 241 μmol/L), which was not statistically significant (P = 0.117). No cats had any documented episodes of hypoglycemia. Adverse effects were mild. The addition of bexagliflozin significantly improved diabetic management in this group of cats.