【作者】 谢伟东；

【导师】 黄克和；

【作者基本信息】 南京农业大学 ， 兽医， 2013， 博士

【摘要】 犬糖尿病以胰腺β细胞破坏为基础,导致该细胞不能正常分泌胰岛素。胰岛素的不足造成机体细胞不能利用葡萄糖,从而造成高血糖。持续的高血糖引起碳水化合物、蛋白质、脂肪等的代谢障碍,临床表现出多饮、多尿、多食及体重减轻的临床症状。犬作为宠物,健康监护还未引起足够重视,还没有形成定期体检的意识,症前高血糖很容易被忽视,从而延误了治疗时机。目前犬糖尿病发病率不高,大约为0.005-1.5%。随着人们生活水平的提高,宠物犬饲养量不断上升,由于犬的生存周期大约10-15年,老龄犬数量将会不断增多。同时宠物犬作为伴侣犬,享受衣食无忧的待遇,更作为宅犬束缚屋内,缺乏必要的运动,随着肥胖犬的不断增多,随之而来犬的代谢性、老年性疾病,也越来越多,糖尿病的发病率有不断增高趋势。因此,犬糖尿病应引起我们的足够重视。本论文通过犬糖尿病发病情况调查与临床诊疗研究,了解犬糖尿病的发病情况,探讨出犬糖尿病的诊断程序和胰岛素治疗方法。1中国部分地区犬糖尿病发病情况调查通过对8个地区14家宠物医院2009-2011年就诊犬的个案资料进行统计,汇总共获得有效个案资料45112例。统计各年就诊犬数、糖尿病数及各年糖尿病占当年就诊犬数的百分率这3个指标趋势逐年升高,糖尿病患犬的增长幅度大于就诊犬数的增长。近3年诊断为糖尿病的犬数为212只,占总就诊犬数的0.47%(212/45112)。小串、京巴、雪纳瑞的发病率最高,分别占糖尿病患犬的26.89%、20.75%及14.62%。金毛、泰迪、杜宾、腊肠的发病率较低,均低于1.89%(0.09‰)。公母犬之间发病率差异具有统计学意义(P<0.05),说明母犬比公犬更容易发生糖尿病。55.67%(29.25%+26.42%)的患犬发病时间集中在7-10岁,5岁以下及15岁以上发病率低(<5%)。经济发达的城市发病率明显高于内陆经济相对落后的城市,其中以北京、上海一线城市发病率最高(0.76%和0.67%),这说明经济越发达,人民生活水平越高的地方,犬患糖尿病的概率也越高。78.31%的糖尿病犬血糖水平集中在15.1-25.0段,平均19.1±3.7mmol/L。全部犬表现出多饮或(及)多尿的症状,白内障是犬糖尿病最易发生的并发症,占糖尿病犬数的72.64%,其双眼白内障的发生率达到78.57%。2犬糖尿病27例临床诊疗分析采取病史回顾法对本院确诊的27例犬糖尿病病例的临床诊疗情况进行分析。结果显示犬糖尿病的主要症状是多饮多尿(100%)、体重下降(92.6%)、食欲增加(48.1%)及精神状沉郁(33.3%)。犬糖尿病并发白内障的概率很高(88.9%),运动机能障碍达到22.2%。25只犬体重有不同程度的下降,3只下降达到30%以上,说明糖尿病属于营养消耗性疾病。24只白内障患犬中,17只双眼白内障,说明糖尿病性白内障一般为双侧性,但存在单侧发作病例。6只犬有运动机能障碍,说明糖尿病对犬神经系统有损害。糖尿病犬中48.1%的患犬存在炎症,33.3%的患犬存在贫血情况。大部分犬ALKP升高,部分犬ALT及BUN升高,提示肝、肾功能受损。TP降低说明蛋白质不足,严重营养不良。尿分析显示尿糖(GLU)、尿比重(SG)、酮体(KET)、尿胆红素(BIL)出现异常。治疗结果表明,单纯通过常规清创和抗感染的治疗方法,无一例治愈,改为胰岛素治疗后,血糖得到控制,创口逐步愈合。单独口服降糖药组血糖变化不明显,创口无愈合趋势,改为降糖药+胰岛素治疗方案后,症状缓解,但出现药物反应及肝损伤。RI治疗组血糖下降最快,可以迅速缓解高血糖引发的急性并发症,但容易发生低血糖。NPH组血糖波动大,不易控制,容易出现低血糖。N30R与N30比较,均能较好的控制血糖,但N30比N30R平稳,用量相对较小。3胰动脉注射四氧嘧啶法制作犬糖尿病模型的研究10只犬随机分为单血管注射组和多血管注射组,以30mg/kg勺剂量通过胰动脉注射四氧嘧啶进行糖尿病造模。结果显示单动脉注射组成模率只有20%(1/5)。多血管注射组成模率达到80%(4/5)。肝功能指标两组犬ALT及ALKP在正常范围,而AST活性高于正常范围。肾功能指标两组犬用药前后,BUN与Crea均在正常范围。胰腺功能上,两组AMYL酶活性均升高,单动脉组给药前后,胰岛素浓度差异不显著(P<0.05),而多动脉组胰岛素浓度差异极显著(P<0.01)。表明多动脉注射组具有成模率高,血糖稳定,对胰腺功能损伤严重,肝功能损伤轻微,而对肾功能无影响。4四氧嘧啶型糖尿病犬皮肤创面愈合情况研究6只成年犬随机分为成年健康组和成年糖尿病组,6只老年犬随机分为老年健康组和老年糖尿病组,每组各3只。糖尿病组通过四氧嘧啶诱导成糖尿病犬。12只犬腹部造缝合创,肩背部造皮肤缺损创,并观察创口愈合情况。结果显示糖尿病对老年犬(9岁)缝合创的愈合有明显影响,但对青年糖尿病犬(2岁)影响不显著,青年糖尿病犬与健康犬之间缝合创的拆线时间无明显差异。拆线时间从长到短,依次为老年糖尿病组、成年糖尿病组、老年健康组、成年健康组。糖尿病犬皮肤愈合率显著低于健康犬,存在年龄(2岁与9岁)差异。随着时间的增加,各组间愈合率差别越大。5治疗犬糖尿病胰岛素制剂的筛选四氧嘧啶型糖尿病犬4只,随机分成不同胰岛素组和不同剂量组,每组各2只。不同胰岛素组犬轮流注射3种胰岛素制剂(NN、N30R及N30)中的一种,不同剂量组犬各按照0.1U/kg、0.2U/kg及0.4U/kg体重的剂量轮流注射胰岛素类似物(N30),两组犬注射前及注射后2、4、6、8、10、12小时采血测血糖值。结果显示,不同胰岛素组中,同只犬对不同胰岛素的血糖变化不一致,降糖能力从强到弱依次为N30>N30R>NN.不同犬对相同胰岛素相同剂量下血糖反应也不一致,波动幅度从大到小依次为NN>N30R>N30。不同剂量组中,同只犬3个胰岛素浓度下,浓度越大,曲线越低,对血糖的控制越明显。结果说明N30降糖作用强,血糖控制比较稳定、波动小。6双时相低精蛋白锌胰岛素在犬糖尿病临床治疗上的应用并发白内障及乳腺肿瘤糖尿病犬使用双时相低精蛋白锌胰岛素(30%RI+70%NPH)进行治疗。结果显示,采取胰岛素小剂量逐步调整的方法,胰岛素用量调整到1.4U(早)及0.9U(晚)后,血糖基本控制在5.3～8.2mmol/L范围。血糖降下后,进行乳腺摘除手术及白内障治疗。结果显示,术后皮肤能达到1期愈合,但使用苄达赖氨酸及吡诺克辛钠治疗白内障未见明显效果。更多还原

【Abstract】 Canine diabetes mellitus is based on the autoimmune processes which destroy the pancreatic beta-cells that synthesize insulin, and causing a nearly complete absence of this hormone. An insulin deficiency prevents the body’s cells to absorb glucose in the blood, and results in hyperglycemia (high blood glucose). Sustained hyperglycemia causes the metabolic disorders of carbohydrates, proteins and fats, with clinical symptoms as polydipsia, polyuria, polyphagia and weight loss. Dogs as pets, have not been paid enough attentions on their health cares, and there are lacks of recognitions on regular medical examinations for pet dogs, an early high blood sugar can be easily overlooked, and the timing of treatment will be delayed. Recently, the canine diabetes mellitus morbidity is not high, and it is about0.005～1.5%. As people’s living standards improved, the amount of pet dog breeding keeps on rising. Consider the lifetime of dogs is about10-15years, thus, the number of aging dogs will be continually increased. At the meantime, pet dogs as companion dogs, enjoy a comfortable living, shackled as a house dog with less exercises, and it shows a great increase of dog obesity that accompanied with increased metabolic and age-related diseases. Moreover, there is a constant increase in canine diabetes mellitus morbidity. Therefore, more attentions should be paid on canine diabetes mellitus.This paper studies the morbidity of canine diabetes mellitus, by carrying out the research of canine diabetes mellitus morbidity with a study on clinical diagnosis and treatment, and then explores the diagnostic procedures and insulin treatments of canine diabetes mellitus.1The morbidity research of canine diabetes mellitus in some regions of ChinaBy collecting the statistics on visit dog cases among14pet hospitals in8regions, from year2009-2011,45112cases have been collected as valid. The three statistics indicators, which include the numbers of visit dogs each year, the numbers of dogs with diabetes mellitus and the percentage that dogs with diabetes mellitus accounts for, have shown an increased trend year by year, and the growth rate of dogs with diabetes mellitus is greater than the growth in the number of visit dogs. In the past3years, the number of dogs diagnosed with diabetes mellitus is212, accounts for0.47%of the total number of visit dogs (212/45112). The small-sized hybrid, Pekingese and Schnauzer have had the highest morbidities, each accounted for26.89%,20.75%and14.62%of total numbers of diabetic dogs. The morbidities are lower among Golden Retriever, Teddy, Doberman and Sausage, they are all below1.89%(0.09%o). The morbidity difference between the male and female dogs is statistically significant (P<0.05), which indicates the female dogs are more prone to diabetes than male dogs.55.67%(29.25%+26.42%) dogs have shown an onset in middle to old age-about7-10years, younger (less than5years old) and elderly dogs (over15years old) have shown a lower morbidity rate (<5%). The morbidities of economically developed cities are significantly higher than inland cities with less developed economies. Among these, the first-tier cities like Beijing and Shanghai have had the highest rates (0.76%and0.67%), which indicates the more developed the economy, the higher the people’s living standards, the higher the probability of dogs suffering from diabetes. The blood glucose levels of78.31%dogs with diabetes mellitus are in15.1-25.0stage, the average is19.1±3.7mmol/L. All the dogs with diabetes mellitus show polydipsia or (and) polyuria symptom, and cataract is very prone to incident, which accounts for72.64%of the total numbers of dogs with diabetes mellitus, the cataract morbidity in both eyes has reached78.57%.2The analysis on clinical diagnosis and treatment of27cases of canine diabetes mellitusThe method of medical history review has been used to analyze the clinical diagnosis and treatment of27diabetes cases which have been diagnose by our hospital. The results shown the main symptoms of canine diabetes mellitus are polydipsia/polyuria (100%), weight loss (92.6%), increased appetite (48.1%) and melancholy (33.3%). The probability of canine diabetes cataract is high (88.9%), and22.2%shown motility disorders.25dogs have different degrees of body weight loss,3of them have a decline of more than30%, which indicate diabetes mellitus is a nutrition consumption disease. Among24cataract dogs,17of them have both eyes cataract, which indicates diabetic cataract is usually bilateral, while unilateral cases also exist.6dogs have mobility disorders, which indicate diabetes brings damages to dogs’ nervous systems.48.1%of diabetic dogs have inflammation, and33.3%dogs have anemia. Most dogs have an increased ALKP, and some of them have an increased ALT and BUN, which prompt damages in liver and kidney functions. The decreased TP indicates the lack of protein, which means a severe malnutrition. Urine analysis reveals that glucose in urine (GLU), specific gravity of urine (SG), ketone bodies (KET) and urine bilirubin (BIL) have shown an abnormality. The treatment results declare that simply by using conventional debridement and anti-infection treatment, none of cases have been cured, and after swapping for insulin treatment, the blood glucose is under control, and the wounds are gradually healed. The group that only take oral hypoglycemic agents shows no significant changes in blood glucose, and the wounds appear no trend of healing, after applying hypoglycemic agents plus insulin treatment, the symptom has been relieved, while drug reactions and liver damages occurred. The RI treatment group has a quicker decline of blood glucose, the acute complications caused by high blood sugar can be quickly relieved, but hypoglycemia can be easily happened. The NPH group has a larger fluctuation of blood glucose which is difficult to control, and hypoglycemia can be easily happened as well. The comparison between N30R and N30indicates that both of them are able to offer a better control of blood glucose, while N30is more stable with a relative small using amount.3The research of canine diabetes modeling by using pancreatic artery injection of AlloxanThe10dogs are randomly divided into single-vascular injection group and multi-vascular injection group, modeling diabetes mellitus through pancreatic artery injection of Alloxan with30mg/kg dose. The results reveal that the molded rate of single-vascular injection group is only20%(1/5), and such rate of multi-vascular injection group has reached80%(4/5). The liver function indicators of dogs in two groups show that ALT and ALKP are in normal range, while AST activity is higher than normal range. The kidney function indicators of dogs in two groups show that BUN and Crea are all in normal range, before and after medications. For functions of pancreas, the AMYL enzyme activity has increased in both groups, insulin concentration has no significant difference (P<0.05) in single-vascular injection group, before and after medications, while there is a significant difference (P<0.01) of insulin concentration in multi-vascular injection group. This indicates a higher molded rate in multi-vascular injection group, with a stable blood glucose, but causes a severe damage to pancreas functions, while there is a slight damage to liver function, and no impact on kidney function. 4The study of skin wound healing of dogs with Alloxan diabetesThe6adult dogs are randomly divided into healthy adult group and adult diabetic group, and the6elderly dogs are randomly divided into healthy elderly group and elderly diabetic group, each group with3dogs. The dogs in diabetic groups are induced to diabetes by Alloxan injection. Abdomen sutures have been made among12dogs with skin defect wounds in shoulders and backs, and the healing conditions will be observed. The results imply that diabetes has significant impact on the sutures healing of old dog (9years old), but shows no significant influence on younger diabetic dog (2years old), days to take out the stitches between young diabetic dogs and healthy dogs show no significant differences. As the timeline from long to short, it is followed by elderly diabetic group, adult diabetic group, elderly healthy group, adult healthy group. The skin wound healing rate of diabetic dogs is significantly lower than healthy dogs, and age differences exist (2years old and9years old). As time increased, the healing rate shows a greater difference among groups.5Screening of insulin preparations for canine diabetes mellitus treatment4dogs with Alloxan diabetes are randomly divided into group of different insulin and group of different dose, each group with2dogs. The dogs in group of different insulin inject one of three kinds of insulin preparations (NN, N30R and N30) in turns, while dogs in group of different dose inject insulin analogues (N30) in turns according to0.1U/kg,0.2U/kg and0.4U/kg weight dose. Before the injections and2,4,6,8,12hours after the injections, blood tests are carried out among two groups of dogs. The results show in group of different insulin, the same dog presents inconsistent changes in blood glucose with different insulin, and the hypoglycemic capacity, from strong to light, is followed by N30>N30R>NN. The different dogs show different blood glucose reactions with same insulin and same dose, fluctuations from largest to smallest are followed by NN>N30R>N30. In group of different dose, the same dog with3insulin concentrations, the higher the concentration, the lower the curve, and more significant in blood glucose control. The results indicate N30has a strong hypoglycemic capacity, with a relative stable glycemic control and small fluctuations.6The application of dual-phase Isophane insulin in clinical treatment of canine diabetes mellitusThe dual-phase Isophane insulin will be used to treat cataract and breast tumors diabetic dogs. The result indicates, by applying small dose of insulin with gradual adjustment, after adjusting the amount of insulin to1.4U (morning) and0.9U (night), the blood glucose has been controlled in5.3～8.2mmol/L range. Breast removal surgery and cataract treatment has been carried out after the blood glucose lowered. The results show that the postoperative skin can reach a healing, while there is no significant effect in cataract treatment by using Bendazac Lysine and Pirenoxine Sodium更多还原