犬糖尿病发病情况调查与临床诊疗研究
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。
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 China
By 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 mellitus
The 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 Alloxan
The10dogs 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 diabetes
The6adult 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 treatment
4dogs 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 mellitus
The 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
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。
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 China
By 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 mellitus
The 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 Alloxan
The10dogs 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 diabetes
The6adult 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 treatment
4dogs 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 mellitus
The 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
引文
[1]王小龙,王哲,郭定宗,等.兽医内科学[M].北京：中国农业大学出版社,2004：303-305
[2]项英,叶俊华.宠物医生手册[M],第2版.沈阳：辽宁科学技术出版社,2009：512
[3]Mattheeuws D, Rottiers R, Kaneko JJ, Vermeulen A. Diabetes mellitus in dogs:relationship of obesity to glucose tolerance and insulin response. Am J Vet Res 1984;45(1):98-103
[4]郭定宗.兽医内科学[M],第2版.北京：高等教育出版社,2010.5：214
[5]http://www.who.int/mediacentre/factsheets/fs312/zh/index.html
[6]Shoback, edited by David G. Gardner, Dolores (2011). Greenspan's basic & clinical endocrinology (9th ed.). New York:McGraw-Hill Medical, pp. Chapter 17
[7]Catchpole, B., Ristic, J.M., Fleeman, L.M., Davison, L.J. (2005). "Canine diabetes mellitus:can old dogs teach us new tricks?".Diabetologica.Retrieved 25 January 2011.pp 1948-1956
[8]张丽红,张盈盈,吴玄光.犬糖尿病研究进展[J].中国兽医杂志,2008,44(8)：64-65
[9]Davison LJ, Herrtage ME, Catchpole B. Study of 253 dogs in the United Kingdom with diabetes mellitus. Vet Rec 2005;156(15):467-471
[10]梁永春.小型犬糖尿病的病因学与临床诊疗[J].中国畜牧兽医,2010,37(2)：197-199
[11]Alberti, KGMM; Aschner, P., et. al (1999). "Definition, Diagnosis and Classification of Diabetes Mellitus". World Health Organization. Retrieved 17 March 2010
[12]Vetsulin. "Difference Between Type 1 and Type 2 Diabetes". Intervet. Retrieved 17 March 2010
[13]Catchpole, B., Ristic, J.M., Fleeman, L.M., Davison, L.J. (2005). "Canine diabetes mellitus:can old dogs teach us new tricks?". Diabetologica. Retrieved 25 January 2011. (PDF)
[14]Catchpole, B., Ristic, J.M., Fleeman, L.M., Davison, L.J. (2005). "Canine diabetes mellitus:can old dogs teach us new tricks?". Diabetologica. Retrieved 25 January 2011. pp 1948-1956
[15]高得仪.犬猫疾病学[M].2版.北京：中国农业大学出版社,2001：223-227
[16]Norman F.Cheville.Cell Pathology.2nd ed.Iowa:The Iowa State University Press,1983,608-615
[17]John W.Kramer, et al.Inheritance of diabetes mellitus in Keeshond dogs.Am J Vet Res,1988,49(3):428-431
[18]王光力,董君艳.犬病临床指南.吉林：吉林科学技术出版社,1991,489-492
[19]Jubo K V,et al.Pathology of Domestic Animalls.Volume 2.3rd ed.Orland:Academic Press Inc,1985,323-325
[20]Thomas Carlyle Jones,Ronald duncan Hunt. Veterinary Pathology.5th ed.Philadelphia:Lea &Febiger,1983,1438-1439
[21]Stogdale L.Definition of diabetes mellitus.Cornell Vet,1986,76(2):156-174
[22]A.G. Gowa, D.J. Gowb,1, R. Bellb, H. Evansc, R.J. Mellanbya Insulin concentrations in dogs with hypoadrenocorticism.Research in Veterinary Science Volume 93, Issue 1, August 2012, Pages 97-99
[23]John W.Kramer, et al.Inheritance of diabetes mellitus in Keeshond dogs.Am J Vet Res,1988,49(3):428-431
[24]Peters A,Klose O,Hefty R,et al.The influence of insulin antibodies on the pharmacokinetics of NPH insulin in patients with type 1 diabetes treated with human insulin[J].Diabet Med,1995,12(10):925-930
[25]Hara K,Tobe K,Uchigata Y,et al.Antibody-mediated insulin resistance treatedby cessation of insulin administration[J].Intern Med,2000,39(2):143-145
[26]项英,叶俊华.宠物医生手册[M],第2版.沈阳：辽宁科学技术出版社,2009：513
[27]Cooke DW, Plotnick L (November 2008). "Type 1 diabetes mellitus in pediatrics". Pediatr Rev 29 (11):374-84; quiz 385. doi:10.1542/pir.29-11-374. PMID 18977856.
[28]Rafael Barrera, et al.Keratoconjunctivitis sicca and diabetes mellitus in a dog.J Am Vet Med Assoc, 1992,200(15):1967-1968
[29]Thelma Lee Gross, et al.Glucagon-Producing pancreatic endocrine tumors in two dogs with superficial necrolytic dermatitis. J Am Vet Med Assoc,1990,197(12):1619-1622
[30]Alex Gough小动物医学鉴别诊断[M].夏兆飞,袁占奎主译.北京：中国农业大学出版社,2010：1-3
[31]郭定宗.兽医内科学[M],第2版.北京：高等教育出版社,2010.5：P215
[32]Rhea V.Morgan小动物临床手册[M].施振声主译.北京：中国农业大学出版社,2005：457-461
[33].徐小平,陈慧雯.糖化血清蛋白检测对糖尿病监测的意义.检验医学,2006,21(2)：136-139
[34].赵树铭,李祝全.糖化血红蛋白AIC的测定与临床意义.中国检验医学与临床,2000,1(2)：75-76
[35]Kawamoto M, et al.Relation of fructosamine to serum protein,albumin,and glucose concentrations inhealthy and diabetic dogs.Am J Vet Res,1992,53(6):851-855
[36]A.G. Gowa, D.J. Gowb,1, R. Bellb, H. Evansc, R.J. Mellanbya Insulin concentrations in dogs with hypoadrenocorticism.Research in Veterinary Science Volume 93, Issue 1, August 2012, Pages 97-99
[37]Begue P, Coste T C, JannotM F, et a.l C-peptide Na+-K+-ATPase and diabetes[J].ExperimentalDiab Res,2004,5:37-50
[38]van Haeften T W.Clinical significance of insulin antibodies in insulin-treated diabetic patients[J].Diabetes Care,1989,12(9):641-648
[39]Sapin R.Ant-i insulin antibodies in insulin immunometric assays:a still possible pitfall[J].Eur J Clin ChemClin Biochem,1997,35(5):365-367
[40]Sapin R,Le Galudec V,Gasser F,et al.Elecsys insulin assay:free insulindetermination and the absence of cross-reactivity with insulin lispro[J].Clin Chem,2001,47(3):602-605
[41]梁先明,秦华.猫、犬用抗糖尿病药C anin sulin [J]中国兽药杂志,2004,38(10)：43-46
[42]Francielli M. de S. S., Mario H. R. A. da S., Adelar B., et al. Effects of metformin on glucose metabolism of perfused rat livers[J]. Molecular and Cellular Biochemistry.9 March 2010][Dr Garry G. Graham, Jeroen Punt, Manit Arora, et al. Clinical Pharmacokinetics of Metformin[J]. Clinical Pharmacokinetics,2011,50(2):81-98
[43]严小惠,姚苏宁.糖尿病社区治疗药物及经济学评价.中国全科医学,2004,7(14)：259-260
[44]陈敏矜,严棠,陈玉驹.20例低血糖昏迷临床分析[J].新医学,1992,23(8)：410
[45]赵子华,范虹.优降糖致老年糖尿病患者低血糖昏迷[J].中级医刊,1995,30(9)：525
[46]章乐虹,杨学伟,陈德基,等.微囊化猪胰岛肝动脉内移植治疗犬1型糖尿病[J].中华肝胆外科杂志,2004,10(8)：549-551
[47]Rebecka S H, Philip H K, Th omas J, et al. Associat ion betw een Di abet es Mell itus, H ypothyroidism or Hyperadrenocort icism and Atheroscl erosis in Dogs [J]. J Vet Int ern Med,2003,17: 489-494
[48]Nicole B. M on it orin g Techniqu es f or Diabet es M ellitu s in the Dog and the Cat [J]. Clinical Techn iqu es in Smal 1 Animal Pract ice,2002,17(2):65-69
[1]安铁洙,谭建华,韦旭斌.犬解剖学[M].长春：吉林科学技术出版社,2003：60
[2]Theresa Welch Fossum,CherylS.Hedlund,DonaldA.Hulse,etal.Small Animal Surgery[M]张海滨,夏兆飞,林德贵.译.2版.北京：中国农业大学出版社,2008.1：483-484
[3]Jensen RT. Pancreatic endocrine tumors:recent advances. Ann Oncol 1999; 10:170-176
[4]扬秀平.动物生理学[M].北京：高等教育出版社,2002
[5]Pasieka JL, Hershfield N. Pancreatic polypeptide hyperplasia causing watery diarrhea syndrome:A case report. Can J Surg 1999;42:55-58
[6]B. F. Hansen, P. Jensen, E. Nepper-Christensen. Effects of glucagon-like peptide-1 (7-36)amide on insulin stimulated rat skeletal muscle glucose transport[J].Acta Diabetologica,1998,35(2):101-103
[7]B. F. Hansen, P. Jensen, E. Nepper-Christensen,etal. Effect of Doses of Glucagon Used to Treat Food Impaction on Esophageal Motor Function of Normal Subjects[J].Dysphagia,1999,14(1):27-30
[8]Giorgio Radetti, Lino Gentili, Claudio Paganini. Cholelithiasis in a newborn following treatment with the somatostatin analogue octreotide[J].European Journal of Pediatrics,2000,159(7):550
[9]王玉中,孙素珍,林玲.葡萄糖诱导胰岛素合成分泌机制与特点[J].医学综述,2009,15(11)：1690-1611
[10]Clark SA, Quaade C, Constandy H,et al. Novel insulinoma cell lines produced by iterative engineering ofGLUT2, glucokinase, and human insulin expression[J].Diabetes,1997,46(6):958-967
[10]TakahashiN,KadowakiT,YazakiY,et al. Post-priming actions of ATP on Ca2+-dependent exocytosis in pancreatic beta cellsf J]. ProcNatlAcad SciUSA,1999,96(2):760-765
[11]DuekworthWC.EndoerRev1988:9:319
[12]李晨钟.胰岛素降解酶研究新进展[J].重庆医科大学学报,1999,24(2)：208-209
[13]邓尚平.临床糖尿病学[M].成都：四川科学技术出版社,2000：17-18
[14]Kelpe CL, Johnson LM, PoitoutV. Increasing triglyceride synthesis inhibits glucose-induced insulin secretion in isolated rat islets of langerhans:a study using adenoviral expression of diacylglycerol acyltransferase[J].Endocrinology,2002,143(9):3326-3332
[15]EvansMH, Pace CS, Clements RS Jr. Endogenous prostaglandin synthesis and glucose-induced insulin secretion from the adult rat pancreatic islet[J].Diabetes,1983,32(6):509-515
[16]Persaud SJ,MullerD, BelinVD,etal.The role of arachidonic acid and itsmetabolites in insulin secretion from human islets of langer-hans[J].Diabetes,2007,56(1):197-203
[17]SacksD. Posibion sbabtement on the use of the ankle brachial index in the evaluation of Patients with Peripheral vascular disease, J vase InterRadiol 2002; 13:353.
[18]朱惠,陆颖理,张惠新,等.腹型肥胖与2型糖尿病患者胰高血糖素关系的研究[J].实用糖尿病杂志,2011,6(3)：16-18
[19]廖二元,超楚生.内分泌学[M].北京：人民卫生出版社,2001：1388-1392
[20]Handbook of Small Animal Practice, Fifth Edition,473
[21]郝光浩.胰岛素泵的临床应用及注意事项[J].实用糖尿病杂志,2005,1(5)：64
[22]Norgaard K.A nationwide study of continous subcutaneous insulin. infusion(CSII) in Denmark[J].Diabet Med,2003,20(4):307
[1]杜冠华,李学军,张永祥,等译.药理学实验指南—新药发现和药理学评价[M].北京：科学出版社,2001：698-712
[2]王彦.两种链尿佐菌素实验性2型糖尿病模型的研究[J].中国实用医药,2013,8(4)：254-255
[3]Iizuka S, Suzuki W, Tabuchi M,etal. Diabetic complications in a new animal model (TSODmouse) of spontaneous NIDDM with obesity. Exp Anim 2005;54:71-83
[4]Takasu N, Komiya I, Asawa T, et al. Streptozocin and alloxan-induced H2O2generation and DNA fragmentation in pancreatic islets[J]. Diabetes,1991,40(9):1141-1145
[5]潘竞锵,韩超,刘惠纯,等.菌陈蒿汤对正常和多种糖尿病模型动物血糖的影响[J].中药材,2001,24(2)：128-131
[6]Miura T, Suzuki W, Ishihara E,etal. Impairment of insulin-stimulated GLUT4 translocation in skeletalmuscle and adipose tissue in the Tsumura Suzuki obese diabeticmouse:A new genetic animal model of type 2 diabetes. Eur J Endocrinol2001;145:785-790
[7]嵇扬,张癸荣,王文俊.建立四氧嘧啶糖尿病模型的研究[J].中医药学刊.2003,21(7)：1126
[8]韦耀东,何正松,农嵩.建立四氧嘧啶糖尿病动物模型的研究[J]右江民族医学院学报,2004,26(3)：322-323
[9]徐叔云.药理学试验方法学[M].北京：人民卫生出版社,1996：813-815
[10]郭啸华,刘志红,李恒,等.高糖高脂饮食诱导的2型糖尿病大鼠模型及其肾病特点[J].中国糖尿病杂志,2002,10(5)：290-294
[11]沈亚非,徐焱成.高糖高脂膳食和链尿佐菌素诱导2型糖尿病模型的建立[J].实用诊断与治疗杂志,2006,20(9)：649-650
[12]Thulesen J, Orskov C, Holst JJ, et al. Short-term insulin treatment prevents the diabetogenic action of streptozo-tocin in rats [J]. Endocrinology,1997,138 (1):62
[13]陈道瑾,黄建花,孙维佳,等.狗全胰切除制作实验性糖尿病模型[J].中国实验外科杂志,1992,9(1)：30
[14]彭芳,杨远华.实验性糖尿病动物模型制备及指标测定评价[J].大理学院学报,2003,2(1)1
[15]艾昭东,刘晟,叶斌,等.狗胰腺次全切除制作1型糖尿病模型研究[J].现代医药卫生,2008,24(21)：3169-3170
[16]董叫云,陈志龙.糖尿病动物模型制作及进展[J].中华国际医学杂志,2001,7(2)：148-150
[17]施新猷.现代医学实验动物学[M].北京：人民军医出版社,2000：482-484
[18]关子安,孙茂欣,关大顺,等.现代糖尿病学[M].天津：天津科学技术出版社,2001：63-68,56-59
[19]张均田.现代药理学实验方法[M].北京：北京医科大学中国协和医科大学联合出版社,1998：981-988
[20]Hao L, Chan SM, Lafferty K J, et al. Mycophenolate mofetil can prevent the development of d iab etes in BB rats[J]. AnnN YA cad Sci,1993,969 (6):328-332
[21]SainiKS, Thom pson C, W in terford CM,etal.Streptozotocin at lowdoses inducesapoptos is and at high dosescauses necrosis inam urine pancreaticbeta celllin e, INS1 [J]. Biochem Mol Biol Int, 1996,39(6):1229-1236
[22]U eda H, Ikegam iH, Y am ato E, et al. The NSY m ouse:a new an im almodel of spontaneousN IDDM withmod erate obesity[J]. Diabetlogia,1995,38 (5):503-508
[23]Pciarel BF. Im pariedinsul in secretion and excess ivehepatic glucose production are both earLy events in the diabet ic GK rat[J]. Am J Physiol,1996,271 (4p t1):E755-E762
[24]Shao JH, Yam ash ita H, Qiao LP, et al. Phosphatidylinos itol 3k inase red is tribution is associated with skeletal muscle insu1 in resistance in gestation al diabetes mellitus [J]. Diabetes, 2002,51(1):1929
[25]Bali D. Anim almodel for maturity onset diabetes of the young generated by disruption of the mouse glucok inase gene[J]. J Biol Chem,1995,270(10):21464-21467
[26]Bruning JC. Development of a novel polygen icmodel ofN IDDM in mice heterozygous for IR and IRS1 null alleles [J]. Cell,1997,88(11):561572
[1]Karen J.Wolfsheimer.Insulin-resistant diabetes mellitus. In:Robert W.Kirk.Current Veterinary Therapy X:Small Ani-mal Practice. Philadelphia:W.B.Saunders Company,1989,1012-1019
[2]Mattheeuws D, Rottiers R, Kaneko JJ, Vermeulen A. Diabetes mellitus in dogs:relationship of obesity to glucose tolerance and insulin response. Am J Vet Res 1984;45(1):98-103
[3]黄志宏.犬猫糖尿病[J].西南民族学院学报.1996,22(2)：211-216
[4]Rieder, J.,Seipel, J., Biermann, K, et al. Canine and feline diabetes mellitus:a retrospective epidemiological study (1996-2006)[J], TIERAERZTLICHE PRAXIS AUSGABE KLEINTIERE HEIMTIERE,2008,36(3):169-175
[5]郭定宗.兽医内科学[M],第2版.北京：高等教育出版社,2010.5：P214
[6]Goodman-Gruen D, Barrett-ConnorE. Sex differencesin the association of endogenous sex hormone levels andglucose tolerance status in oldermenandwomen[J].Dia-betesCare,2000;23(5):912-918
[7]MullerM, Grobbee DE, den Tonkelaar I, et a.lEndoge-nous sex hormones and metabolic syndrome in aging men[J].JClin EndocrinolMetab,2005;90(5):2618-2623
[8]梁永春.小型犬糖尿病的病因学与临床诊疗[J].中国畜牧兽医,2010,37(2)：197-199
[9]Nelson R W, Feldman E C.Canine diabetes mellitus.In:RobertW.Kirk.Current Veterinary TherapyⅨ:Small Animal Practice.Philadelphia:W.B.Saunders Company,1986,991-999
[10]R ebecka S H, Phili p H K, T homas J, et al. A ssociat ion be-t ween D iabetes M ellitus, H ypothyroidism or Hyperadrenocor-t icism, and A t h eroscleros is in D ogs [J]. J V et In tern M ed,2003, 17:489-494.
[11]Jubo K V,etal.Pathology of Domestic Animalls.Volume 2.3rd ed.Orland:Academic Press Inc,1985,323-325
[12]StogdaleL.Definition of diabetes mellitus.Cornell Vet,1986,76(2):156-174
[13]Cooke DW, Plotnick L (November 2008). "Type 1 diabetes mellitus in pediatrics". Pediatr Rev 29 (11):374-84; quiz 385. doi:10.1542/pir.29-11-374. PMID 18977856.
[14]项英,叶俊华.宠物医生手册[M],第2版.沈阳：辽宁科学技术出版社,2009：513
[15]张丽红,张盈盈,吴玄光.犬糖尿病研究进展[J].中国兽医杂志,2008,44(8)：64-65
[16]张士元.我国白内障的流行病学调查资料分析[J].中华眼科杂志,1999,35(5)：336-339.
[17]郭秉宽.中国医学百科全书—眼科学[M].上海：上海科学技术出版社,1985.9
[18]李德馨,王思玲,苏德森.白内障的发病机制与药物治疗.沈阳药科大学学报,2002,19(4)：300-307
[19]Huang P, Jiang Z, Teng S, et al, Synergism between phospholipase D2 and sorbitol accumulation in diabetic cataract formation through modulation of Na, K-ATPase activity and osmotic stress [J]. Exp Eye Res,2006; 83(4):939-48
[20]Bettelheim FA,ZengFF,BiaY,etal.Lens hydrationin transgenic mice containing HIV-1 protease linked tothe lensAA-crystalilin promoter [J]. Arch BiochemBiophys,1995,324(2):223-227
[21]Ahmed N.Advancedglycationendproducts-role in pathology of diabeticcomplications. DiabetesResClinPract,2005,67:3-21
[1]王哲,郭定宗,李家奎.糖尿病[A].王小龙.兽医内科学[M].北京：中国农业大学出版社,2004.303-305
[2]Mattheeuws D, Rottiers R, Kaneko JJ, Vermeulen A. Diabetes mellitus in dogs:relationship of obesity to glucose tolerance and insulin response. Am J Vet Res 1984;45(1):98-103
[3]Alex Gough小动物医学鉴别诊断[M].夏兆飞,袁占奎主译.北京：中国农业大学出版社,2010：1-3
[3]Luppi P, Geng X, Cifarelli V, et al. C-peptide is internalised in human endothelial and vascular smooth muscle cells via early endosomes. Diabetologia.2009;52(10):2218-2228
[4]Rubenstein AH, Clark JL, Melani F, Steiner DF. Secretion of proinsulin C-Peptide by pancreatic β cells and its circulation in blood. Nature.1969;224(5220):697-699
[5]Munte CE, Vilela L, Kalbitzer HR, Garratt RC. Solution structure of human proinsulin C-peptide. The FEBS Journal.2005;272(16):4284-4293
[6]Flatt PR, Swanston-Flatt SK, Hampton SM,et al. Specific binding of the C-peptide of proinsulin to cultured B-cells from a transplantable rat islet cell tumor. Bioscience Reports.1986;6(2):193-199
[7]Chaisiri K, Pongpaew P, Tungtrongchitr R, et al. Prevalence and abnormal glucose tolerance in Khon Kaen province and validity of urine stick and fasting blood sugar as screening tools. J Thai Med Assoc.1997;80:363-371
[8]Selvin E, Steffes MW, Zhu H, et al. "Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults". N. Engl. J. Med.362 (9):800-11. doi:10.1056/NEJMoa0908359. PMC 2872990. PMID 20200384
[9]Tahara Y, Shima K. Kinetics of HbAlc, glycated albumin, and fructosamine and analysis of their weight functions against preceding plasma glucose level. Diabetes Care.1995;18:440-447
[10]Dungan KM, Buse JB, Largay J, Kelly MM, Button EA, Kato S, et al.1,5-Anhydroglucitol and Postprandial Hyperglycemia as Measured by Continuous Glucose Monitoring System in Moderately Controlled Patients With Diabetes. Diabetes Care.2006;29:1214-1219
[11]Santaguida PL, Balion C, Hunt D,et al. "Diagnosis, Prognosis, and Treatment of Impaired Glucose Tolerance and Impaired Fasting Glucose". Summary of Evidence Report/Technology Assessment, No. 128. Agency for Healthcare Research and Quality. Retrieved 2008-07-20
[12]郭定宗.兽医内科学[M],第2版.北京：高等教育出版社,2010.5：P215
[13]Rhea V.Morgan小动物临床手册[M].施振声主译.北京：中国农业大学出版社,2005：457-461
[14]Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia:report of a WHO/IDF consultation. World Health Organization.2006. p.21. ISBN 978-92-4-159493-6
[15]McGarry JD (2002) Banting lecture 2001:dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 51:7-18
[16]The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med.1993;329:977-86
[17]American Diabetes Association. Standards of medical care in diabetes—2012. Diabetes Care.2012;35(Suppl 1):S11-63
[18]Patel A, MacMahon S, Chalmers J, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med.2008;358:2560-72
[19]Jacobson GJ, Ramos GA, Ching JY,et al. Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization. Am J ObstetGynecol.2005;193:118-124.
[20]Francielli M. de S. S., Mario H. R. A. da S., Adelar B., et al. Effects of metformin on glucose metabolism of perfused rat livers[J]. Molecular and Cellular Biochemistry.9 March 2010
[21]Feldman EC, Nelson RW. Canine and Feline Endocrinology and Reproduction.3rd ed. St. Louis, Missouri:Elsevier; 2004. pp.581-615
[1]全国临床检验操作规程,第3版.中华人民共和国卫生部医政司,东南大学出版社,2009：1009-1014
[2]韩德恩,江启俊,蔡全忠,等.利用全胰切除术制造狗的糖尿病模型[J].哈尔滨医科大学学报,1983,3：40-43
[3]艾昭东,刘晟,叶斌,等.狗胰腺次全切除制作Ⅰ型糖尿病模型研究[J].现代医药卫生,2008,24(21)：3169-3171
[4]刘晟,王维,罗贤明,等.药物诱导狗Ⅰ型糖尿病的研究[J].湖南医科大学学报,2000,25(2)：125-128
[5]关子安,孙茂欣,关大顺,等.现代糖尿病学[M].天津：天津科学技术出版社,2001：56-68
[6]Lenzen,S.,The mechanisms of alloxan-and streptozotocin-induced diabetes.Diabetologia 2008,51:216-226
[7]A.Pimentel Morales, E.Gomez Conde, M.G.Delgado Lopez, et al. An improved method of 90% pancreatectomy using a low dose of streptozotocin at the pancreaticoduodenal artery results in a rapid diabetic stage in dogs[J].Acta Diabetol,2005,42:153-155
[8]周贤用,傅红兴,刘云西,等.1例Beagle犬的糖尿病建模分析[J],中国医药科学,2011,1(15)：46-47
[9]史文博,梁圣保.低剂量四氧嘧啶局部动脉注射制作犬糖尿病模型[J].中华器官移植杂志,1992,13(1)：16-17
[10]李聪然,游雪甫,蒋建东.糖尿病动物模型及研究进展[J].中国比较医学杂志,2005,15(1)：59-63
[11]Pciarel BF. Im paried insul in secret ion and excess ive hepat ic glucose produ ct ion are both earLy events in the d iabet ic GK rat[J]. Am J Physiol,1996,271 (4p t1):E755-E762
[12]M. Ader, J.M. Richey, R. N. Bergman. Evidence for direct action of alloxan to induce insulin resistance at the cellular level[J]. Diabetologia,1998,41:1327-1336
[13]Black HE, Rosenblum IY, Charles CC.Chemically induced (streptozotocinalloxan) diabetes mellitus in the dog biochemical and ultrastructural studies[J]. AM J Path,1980,98(2):295-305.
[14][德]H.G沃格尔,[美]W.H沃格尔.药理学实验指南—新药发现和药理学评价.(杜冠华,李学军,张永祥译).北京：科学出版社,2001：699
[15]何学令,尹海林.四氧嗜睫剂量和给药途径对制作大鼠糖尿病模型的影响.四川动物,2003,22(40)：255-257
[16]嵇扬,张癸荣,王文俊.建立四氧嘧啶糖尿病模型的研究[J].中医药学刊,2003,21(7)：1125-6
[17]辛晓林.四氧嗜咤对小鼠肝指数和MDA含量的影响.青海师范大学学报(自然科学 版),2001：53-54
[18]张炯,王永川,吉倩梅,等.14C-四氧嘧啶在小鼠体内分布的研究[J].核技术.1988,11(1)：58
[1]铁璐,伊利夏提·肖开提,王宪,等.糖尿病伤口愈合的分子机制[J].生理科学进展,2010,41(6)：407-411
[2]刘晟,王维,罗贤明,等.药物诱导狗Ⅰ型糖尿病的研究[J].湖南医科大学学报,2000,25(2)：125-128
[3]史文博,梁圣保.低剂量四氧嘧啶局部动脉注射制作犬糖尿病模型[J].中华器官移植杂志,1992,13(1)：16-17
[4]付小兵,王德文.现代创伤修复学[M].北京：人民军医出版社,1999：1-10
[5]汪世昌,陈家璞.家畜外科学[M].北京,中国农业出版社,第三版,1998：18-20
[6]林炜栋,陆树良,青春,等.糖尿病难愈创面与晚期糖基化终末产物的关系[J].中国临床康复,2003,6(8)：370
[7]林源,王润秀,农庆文,等.糖尿病创面愈合过程的动态组织学特征[J].中国临床康复,2005,9(3)：118：120
[8]Bhora FY, Dunkin BJ, Batzri S, et al. Effect of growth factors on cell proliferation and epithelialization in human skin. J Surg Res,1995,59(2):236-244
[9]Cohen S and Carpenter G. Human epidermal growth factor isolation and chemical and biological properties. Proc Natl Acad Sci,1975,72(4):1317-1321
[10]Esch F, Baird A, Ling N, et al. Primary structure of bovine pituitary basic fibroblast growth factor(FGF) and comparison with the amino-terminal sequence of bovine brain acidic FGF. Proe Natl Acad Sci USA,1985,82(19):6507-6511
[11]Wang HJ, Wan HL, Yang TS et al. Acceleration of skin graft healing by growth factors. Burns,1996,22(1):10-14
[12]Roberts AB, Anzano MA, Wakefield LM, et al. Type beta transforming growth factor a bifunctional regulator of cellular growth. Proc Natl Acad Sci USA,1985,82(1):119-123
[13]Micera A, Vigneti E, Pickholtz D, Et al. Nerve growth factor displays stimulatory effects on human skin and lung fibroblasts, demonstrating a direct role for this factor in tissue repair. Proc Natl Acad Sci USA,2001,98(11):6162-6167
[15]Rudman SM, Philpott MP, Thomas GA, et al. The role of IGF-I in human skin and its ppendages; morphogen as well as mitogen? J Invest Dermatol,1997,109:770-777
[1]Feldman, E.C., Nelson, R.W.,2004. Diabetes mellitus. In:Canine and Feline Endocrinology and Reproduction, third ed. W.B. Saunders, Philadelphia, pp.486-538
[2]William E. Monroe, David Laxton, Edward A. Fallin, et al. Efficacy and Safety of a Purified Porcine Insulin Zinc Suspension for Managing Diabetes Mellitus in Dogs[J]. J Vet Intern Med 2005,19:675-682
[3]梁先明,秦华.猫、犬用抗糖尿病药[J].中国兽药杂志,2004,38(10)：43-46
[4]Chen Gilor, DVM, Thomas K. Graves, DVM, PhD, Synthetic Insulin Analogs and Their Use in Dogs and Cats。 Veterinary Clinics of North America:Small Animal Practice Volume 40, Issue 2, March 2010, Pages 297-307
[5]Torrance, A.G., and Mooney, C.T.,2001. Canine diabetes mellitus. In:Manual of small Animal Endocrinology.2nd edn.,(British Small Animal Veterinary Association, Cheltenham) 83-96
[6]Behrend, E.N.2006. Update on drugs used to treat endocrine diseases in small animals. The Veterinary clinics of North America. Small animal practice,36,1087-1105
[7]Reusch C. E., Robben J. H. & Kooistra H. S. (2010) Endocrine pancreas. In Clinical Endocrinology of Dogs and Cats.2nd edn. Eds Rijnberk A.Kooistra H. S.. Schlutersche. pp 155-185
[8]Rebecka S. Hess, Cynthia R. Ward. Effect of insulin dosage on glycemic response in dogs with diabetes mellitus:221 cases (1993-1998)[J]. Journal of the American Veterinary Medical Association, 2000,216(2):217-211
[1]项英,叶俊华.宠物医生手册[M],第2版.沈阳：辽宁科学技术出版社,2009：512
[2]Rhea V.Morgan小动物临床手册[M].施振声主译.北京：中国农业大学出版社,2005：457-461
[3]迟家敏.实用糖尿病学[M],第3版.北京：人民卫生出版社,2009：505
[4]Davison LJ, Ristic JM, Herrtage ME, et al. Anti-insulin antibodies in dogs with naturally occurring diabetes mellitus. Vet Immunol Immunopathol 2003;91:53-60
[5]Lucy J. Davisona, Jelena M.E. Risticb, Michael E. Herrtageb, etal. Anti-insulin antibodies in dogs with naturally occurring diabetes mellitus. Veterinary Immunology and Immunopathology 2003;91:53-60
[6]L.J.Davison, B.Walding, M.E. Herrtage, etal. Anti-Insulin Antibodies in Diabetic Dogs Before and After Treatment with Different Insulin Preparations. J Vet Intern Med 2008;22:1317-1325
[7]基斯.巴耐特,克里斯汀.亨里奇,简.桑塞姆,犬眼科学[M],Canine Ophthalmology.吴炳憔主译.沈阳：辽宁科学技术出版社,2008：107
[2]项英,叶俊华.宠物医生手册[M],第2版.沈阳：辽宁科学技术出版社,2009：512
[3]Mattheeuws D, Rottiers R, Kaneko JJ, Vermeulen A. Diabetes mellitus in dogs:relationship of obesity to glucose tolerance and insulin response. Am J Vet Res 1984;45(1):98-103
[4]郭定宗.兽医内科学[M],第2版.北京：高等教育出版社,2010.5：214
[5]http://www.who.int/mediacentre/factsheets/fs312/zh/index.html
[6]Shoback, edited by David G. Gardner, Dolores (2011). Greenspan's basic & clinical endocrinology (9th ed.). New York:McGraw-Hill Medical, pp. Chapter 17
[7]Catchpole, B., Ristic, J.M., Fleeman, L.M., Davison, L.J. (2005). "Canine diabetes mellitus:can old dogs teach us new tricks?".Diabetologica.Retrieved 25 January 2011.pp 1948-1956
[8]张丽红,张盈盈,吴玄光.犬糖尿病研究进展[J].中国兽医杂志,2008,44(8)：64-65
[9]Davison LJ, Herrtage ME, Catchpole B. Study of 253 dogs in the United Kingdom with diabetes mellitus. Vet Rec 2005;156(15):467-471
[10]梁永春.小型犬糖尿病的病因学与临床诊疗[J].中国畜牧兽医,2010,37(2)：197-199
[11]Alberti, KGMM; Aschner, P., et. al (1999). "Definition, Diagnosis and Classification of Diabetes Mellitus". World Health Organization. Retrieved 17 March 2010
[12]Vetsulin. "Difference Between Type 1 and Type 2 Diabetes". Intervet. Retrieved 17 March 2010
[13]Catchpole, B., Ristic, J.M., Fleeman, L.M., Davison, L.J. (2005). "Canine diabetes mellitus:can old dogs teach us new tricks?". Diabetologica. Retrieved 25 January 2011. (PDF)
[14]Catchpole, B., Ristic, J.M., Fleeman, L.M., Davison, L.J. (2005). "Canine diabetes mellitus:can old dogs teach us new tricks?". Diabetologica. Retrieved 25 January 2011. pp 1948-1956
[15]高得仪.犬猫疾病学[M].2版.北京：中国农业大学出版社,2001：223-227
[16]Norman F.Cheville.Cell Pathology.2nd ed.Iowa:The Iowa State University Press,1983,608-615
[17]John W.Kramer, et al.Inheritance of diabetes mellitus in Keeshond dogs.Am J Vet Res,1988,49(3):428-431
[18]王光力,董君艳.犬病临床指南.吉林：吉林科学技术出版社,1991,489-492
[19]Jubo K V,et al.Pathology of Domestic Animalls.Volume 2.3rd ed.Orland:Academic Press Inc,1985,323-325
[20]Thomas Carlyle Jones,Ronald duncan Hunt. Veterinary Pathology.5th ed.Philadelphia:Lea &Febiger,1983,1438-1439
[21]Stogdale L.Definition of diabetes mellitus.Cornell Vet,1986,76(2):156-174
[22]A.G. Gowa, D.J. Gowb,1, R. Bellb, H. Evansc, R.J. Mellanbya Insulin concentrations in dogs with hypoadrenocorticism.Research in Veterinary Science Volume 93, Issue 1, August 2012, Pages 97-99
[23]John W.Kramer, et al.Inheritance of diabetes mellitus in Keeshond dogs.Am J Vet Res,1988,49(3):428-431
[24]Peters A,Klose O,Hefty R,et al.The influence of insulin antibodies on the pharmacokinetics of NPH insulin in patients with type 1 diabetes treated with human insulin[J].Diabet Med,1995,12(10):925-930
[25]Hara K,Tobe K,Uchigata Y,et al.Antibody-mediated insulin resistance treatedby cessation of insulin administration[J].Intern Med,2000,39(2):143-145
[26]项英,叶俊华.宠物医生手册[M],第2版.沈阳：辽宁科学技术出版社,2009：513
[27]Cooke DW, Plotnick L (November 2008). "Type 1 diabetes mellitus in pediatrics". Pediatr Rev 29 (11):374-84; quiz 385. doi:10.1542/pir.29-11-374. PMID 18977856.
[28]Rafael Barrera, et al.Keratoconjunctivitis sicca and diabetes mellitus in a dog.J Am Vet Med Assoc, 1992,200(15):1967-1968
[29]Thelma Lee Gross, et al.Glucagon-Producing pancreatic endocrine tumors in two dogs with superficial necrolytic dermatitis. J Am Vet Med Assoc,1990,197(12):1619-1622
[30]Alex Gough小动物医学鉴别诊断[M].夏兆飞,袁占奎主译.北京：中国农业大学出版社,2010：1-3
[31]郭定宗.兽医内科学[M],第2版.北京：高等教育出版社,2010.5：P215
[32]Rhea V.Morgan小动物临床手册[M].施振声主译.北京：中国农业大学出版社,2005：457-461
[33].徐小平,陈慧雯.糖化血清蛋白检测对糖尿病监测的意义.检验医学,2006,21(2)：136-139
[34].赵树铭,李祝全.糖化血红蛋白AIC的测定与临床意义.中国检验医学与临床,2000,1(2)：75-76
[35]Kawamoto M, et al.Relation of fructosamine to serum protein,albumin,and glucose concentrations inhealthy and diabetic dogs.Am J Vet Res,1992,53(6):851-855
[36]A.G. Gowa, D.J. Gowb,1, R. Bellb, H. Evansc, R.J. Mellanbya Insulin concentrations in dogs with hypoadrenocorticism.Research in Veterinary Science Volume 93, Issue 1, August 2012, Pages 97-99
[37]Begue P, Coste T C, JannotM F, et a.l C-peptide Na+-K+-ATPase and diabetes[J].ExperimentalDiab Res,2004,5:37-50
[38]van Haeften T W.Clinical significance of insulin antibodies in insulin-treated diabetic patients[J].Diabetes Care,1989,12(9):641-648
[39]Sapin R.Ant-i insulin antibodies in insulin immunometric assays:a still possible pitfall[J].Eur J Clin ChemClin Biochem,1997,35(5):365-367
[40]Sapin R,Le Galudec V,Gasser F,et al.Elecsys insulin assay:free insulindetermination and the absence of cross-reactivity with insulin lispro[J].Clin Chem,2001,47(3):602-605
[41]梁先明,秦华.猫、犬用抗糖尿病药C anin sulin [J]中国兽药杂志,2004,38(10)：43-46
[42]Francielli M. de S. S., Mario H. R. A. da S., Adelar B., et al. Effects of metformin on glucose metabolism of perfused rat livers[J]. Molecular and Cellular Biochemistry.9 March 2010][Dr Garry G. Graham, Jeroen Punt, Manit Arora, et al. Clinical Pharmacokinetics of Metformin[J]. Clinical Pharmacokinetics,2011,50(2):81-98
[43]严小惠,姚苏宁.糖尿病社区治疗药物及经济学评价.中国全科医学,2004,7(14)：259-260
[44]陈敏矜,严棠,陈玉驹.20例低血糖昏迷临床分析[J].新医学,1992,23(8)：410
[45]赵子华,范虹.优降糖致老年糖尿病患者低血糖昏迷[J].中级医刊,1995,30(9)：525
[46]章乐虹,杨学伟,陈德基,等.微囊化猪胰岛肝动脉内移植治疗犬1型糖尿病[J].中华肝胆外科杂志,2004,10(8)：549-551
[47]Rebecka S H, Philip H K, Th omas J, et al. Associat ion betw een Di abet es Mell itus, H ypothyroidism or Hyperadrenocort icism and Atheroscl erosis in Dogs [J]. J Vet Int ern Med,2003,17: 489-494
[48]Nicole B. M on it orin g Techniqu es f or Diabet es M ellitu s in the Dog and the Cat [J]. Clinical Techn iqu es in Smal 1 Animal Pract ice,2002,17(2):65-69
[1]安铁洙,谭建华,韦旭斌.犬解剖学[M].长春：吉林科学技术出版社,2003：60
[2]Theresa Welch Fossum,CherylS.Hedlund,DonaldA.Hulse,etal.Small Animal Surgery[M]张海滨,夏兆飞,林德贵.译.2版.北京：中国农业大学出版社,2008.1：483-484
[3]Jensen RT. Pancreatic endocrine tumors:recent advances. Ann Oncol 1999; 10:170-176
[4]扬秀平.动物生理学[M].北京：高等教育出版社,2002
[5]Pasieka JL, Hershfield N. Pancreatic polypeptide hyperplasia causing watery diarrhea syndrome:A case report. Can J Surg 1999;42:55-58
[6]B. F. Hansen, P. Jensen, E. Nepper-Christensen. Effects of glucagon-like peptide-1 (7-36)amide on insulin stimulated rat skeletal muscle glucose transport[J].Acta Diabetologica,1998,35(2):101-103
[7]B. F. Hansen, P. Jensen, E. Nepper-Christensen,etal. Effect of Doses of Glucagon Used to Treat Food Impaction on Esophageal Motor Function of Normal Subjects[J].Dysphagia,1999,14(1):27-30
[8]Giorgio Radetti, Lino Gentili, Claudio Paganini. Cholelithiasis in a newborn following treatment with the somatostatin analogue octreotide[J].European Journal of Pediatrics,2000,159(7):550
[9]王玉中,孙素珍,林玲.葡萄糖诱导胰岛素合成分泌机制与特点[J].医学综述,2009,15(11)：1690-1611
[10]Clark SA, Quaade C, Constandy H,et al. Novel insulinoma cell lines produced by iterative engineering ofGLUT2, glucokinase, and human insulin expression[J].Diabetes,1997,46(6):958-967
[10]TakahashiN,KadowakiT,YazakiY,et al. Post-priming actions of ATP on Ca2+-dependent exocytosis in pancreatic beta cellsf J]. ProcNatlAcad SciUSA,1999,96(2):760-765
[11]DuekworthWC.EndoerRev1988:9:319
[12]李晨钟.胰岛素降解酶研究新进展[J].重庆医科大学学报,1999,24(2)：208-209
[13]邓尚平.临床糖尿病学[M].成都：四川科学技术出版社,2000：17-18
[14]Kelpe CL, Johnson LM, PoitoutV. Increasing triglyceride synthesis inhibits glucose-induced insulin secretion in isolated rat islets of langerhans:a study using adenoviral expression of diacylglycerol acyltransferase[J].Endocrinology,2002,143(9):3326-3332
[15]EvansMH, Pace CS, Clements RS Jr. Endogenous prostaglandin synthesis and glucose-induced insulin secretion from the adult rat pancreatic islet[J].Diabetes,1983,32(6):509-515
[16]Persaud SJ,MullerD, BelinVD,etal.The role of arachidonic acid and itsmetabolites in insulin secretion from human islets of langer-hans[J].Diabetes,2007,56(1):197-203
[17]SacksD. Posibion sbabtement on the use of the ankle brachial index in the evaluation of Patients with Peripheral vascular disease, J vase InterRadiol 2002; 13:353.
[18]朱惠,陆颖理,张惠新,等.腹型肥胖与2型糖尿病患者胰高血糖素关系的研究[J].实用糖尿病杂志,2011,6(3)：16-18
[19]廖二元,超楚生.内分泌学[M].北京：人民卫生出版社,2001：1388-1392
[20]Handbook of Small Animal Practice, Fifth Edition,473
[21]郝光浩.胰岛素泵的临床应用及注意事项[J].实用糖尿病杂志,2005,1(5)：64
[22]Norgaard K.A nationwide study of continous subcutaneous insulin. infusion(CSII) in Denmark[J].Diabet Med,2003,20(4):307
[1]杜冠华,李学军,张永祥,等译.药理学实验指南—新药发现和药理学评价[M].北京：科学出版社,2001：698-712
[2]王彦.两种链尿佐菌素实验性2型糖尿病模型的研究[J].中国实用医药,2013,8(4)：254-255
[3]Iizuka S, Suzuki W, Tabuchi M,etal. Diabetic complications in a new animal model (TSODmouse) of spontaneous NIDDM with obesity. Exp Anim 2005;54:71-83
[4]Takasu N, Komiya I, Asawa T, et al. Streptozocin and alloxan-induced H2O2generation and DNA fragmentation in pancreatic islets[J]. Diabetes,1991,40(9):1141-1145
[5]潘竞锵,韩超,刘惠纯,等.菌陈蒿汤对正常和多种糖尿病模型动物血糖的影响[J].中药材,2001,24(2)：128-131
[6]Miura T, Suzuki W, Ishihara E,etal. Impairment of insulin-stimulated GLUT4 translocation in skeletalmuscle and adipose tissue in the Tsumura Suzuki obese diabeticmouse:A new genetic animal model of type 2 diabetes. Eur J Endocrinol2001;145:785-790
[7]嵇扬,张癸荣,王文俊.建立四氧嘧啶糖尿病模型的研究[J].中医药学刊.2003,21(7)：1126
[8]韦耀东,何正松,农嵩.建立四氧嘧啶糖尿病动物模型的研究[J]右江民族医学院学报,2004,26(3)：322-323
[9]徐叔云.药理学试验方法学[M].北京：人民卫生出版社,1996：813-815
[10]郭啸华,刘志红,李恒,等.高糖高脂饮食诱导的2型糖尿病大鼠模型及其肾病特点[J].中国糖尿病杂志,2002,10(5)：290-294
[11]沈亚非,徐焱成.高糖高脂膳食和链尿佐菌素诱导2型糖尿病模型的建立[J].实用诊断与治疗杂志,2006,20(9)：649-650
[12]Thulesen J, Orskov C, Holst JJ, et al. Short-term insulin treatment prevents the diabetogenic action of streptozo-tocin in rats [J]. Endocrinology,1997,138 (1):62
[13]陈道瑾,黄建花,孙维佳,等.狗全胰切除制作实验性糖尿病模型[J].中国实验外科杂志,1992,9(1)：30
[14]彭芳,杨远华.实验性糖尿病动物模型制备及指标测定评价[J].大理学院学报,2003,2(1)1
[15]艾昭东,刘晟,叶斌,等.狗胰腺次全切除制作1型糖尿病模型研究[J].现代医药卫生,2008,24(21)：3169-3170
[16]董叫云,陈志龙.糖尿病动物模型制作及进展[J].中华国际医学杂志,2001,7(2)：148-150
[17]施新猷.现代医学实验动物学[M].北京：人民军医出版社,2000：482-484
[18]关子安,孙茂欣,关大顺,等.现代糖尿病学[M].天津：天津科学技术出版社,2001：63-68,56-59
[19]张均田.现代药理学实验方法[M].北京：北京医科大学中国协和医科大学联合出版社,1998：981-988
[20]Hao L, Chan SM, Lafferty K J, et al. Mycophenolate mofetil can prevent the development of d iab etes in BB rats[J]. AnnN YA cad Sci,1993,969 (6):328-332
[21]SainiKS, Thom pson C, W in terford CM,etal.Streptozotocin at lowdoses inducesapoptos is and at high dosescauses necrosis inam urine pancreaticbeta celllin e, INS1 [J]. Biochem Mol Biol Int, 1996,39(6):1229-1236
[22]U eda H, Ikegam iH, Y am ato E, et al. The NSY m ouse:a new an im almodel of spontaneousN IDDM withmod erate obesity[J]. Diabetlogia,1995,38 (5):503-508
[23]Pciarel BF. Im pariedinsul in secretion and excess ivehepatic glucose production are both earLy events in the diabet ic GK rat[J]. Am J Physiol,1996,271 (4p t1):E755-E762
[24]Shao JH, Yam ash ita H, Qiao LP, et al. Phosphatidylinos itol 3k inase red is tribution is associated with skeletal muscle insu1 in resistance in gestation al diabetes mellitus [J]. Diabetes, 2002,51(1):1929
[25]Bali D. Anim almodel for maturity onset diabetes of the young generated by disruption of the mouse glucok inase gene[J]. J Biol Chem,1995,270(10):21464-21467
[26]Bruning JC. Development of a novel polygen icmodel ofN IDDM in mice heterozygous for IR and IRS1 null alleles [J]. Cell,1997,88(11):561572
[1]Karen J.Wolfsheimer.Insulin-resistant diabetes mellitus. In:Robert W.Kirk.Current Veterinary Therapy X:Small Ani-mal Practice. Philadelphia:W.B.Saunders Company,1989,1012-1019
[2]Mattheeuws D, Rottiers R, Kaneko JJ, Vermeulen A. Diabetes mellitus in dogs:relationship of obesity to glucose tolerance and insulin response. Am J Vet Res 1984;45(1):98-103
[3]黄志宏.犬猫糖尿病[J].西南民族学院学报.1996,22(2)：211-216
[4]Rieder, J.,Seipel, J., Biermann, K, et al. Canine and feline diabetes mellitus:a retrospective epidemiological study (1996-2006)[J], TIERAERZTLICHE PRAXIS AUSGABE KLEINTIERE HEIMTIERE,2008,36(3):169-175
[5]郭定宗.兽医内科学[M],第2版.北京：高等教育出版社,2010.5：P214
[6]Goodman-Gruen D, Barrett-ConnorE. Sex differencesin the association of endogenous sex hormone levels andglucose tolerance status in oldermenandwomen[J].Dia-betesCare,2000;23(5):912-918
[7]MullerM, Grobbee DE, den Tonkelaar I, et a.lEndoge-nous sex hormones and metabolic syndrome in aging men[J].JClin EndocrinolMetab,2005;90(5):2618-2623
[8]梁永春.小型犬糖尿病的病因学与临床诊疗[J].中国畜牧兽医,2010,37(2)：197-199
[9]Nelson R W, Feldman E C.Canine diabetes mellitus.In:RobertW.Kirk.Current Veterinary TherapyⅨ:Small Animal Practice.Philadelphia:W.B.Saunders Company,1986,991-999
[10]R ebecka S H, Phili p H K, T homas J, et al. A ssociat ion be-t ween D iabetes M ellitus, H ypothyroidism or Hyperadrenocor-t icism, and A t h eroscleros is in D ogs [J]. J V et In tern M ed,2003, 17:489-494.
[11]Jubo K V,etal.Pathology of Domestic Animalls.Volume 2.3rd ed.Orland:Academic Press Inc,1985,323-325
[12]StogdaleL.Definition of diabetes mellitus.Cornell Vet,1986,76(2):156-174
[13]Cooke DW, Plotnick L (November 2008). "Type 1 diabetes mellitus in pediatrics". Pediatr Rev 29 (11):374-84; quiz 385. doi:10.1542/pir.29-11-374. PMID 18977856.
[14]项英,叶俊华.宠物医生手册[M],第2版.沈阳：辽宁科学技术出版社,2009：513
[15]张丽红,张盈盈,吴玄光.犬糖尿病研究进展[J].中国兽医杂志,2008,44(8)：64-65
[16]张士元.我国白内障的流行病学调查资料分析[J].中华眼科杂志,1999,35(5)：336-339.
[17]郭秉宽.中国医学百科全书—眼科学[M].上海：上海科学技术出版社,1985.9
[18]李德馨,王思玲,苏德森.白内障的发病机制与药物治疗.沈阳药科大学学报,2002,19(4)：300-307
[19]Huang P, Jiang Z, Teng S, et al, Synergism between phospholipase D2 and sorbitol accumulation in diabetic cataract formation through modulation of Na, K-ATPase activity and osmotic stress [J]. Exp Eye Res,2006; 83(4):939-48
[20]Bettelheim FA,ZengFF,BiaY,etal.Lens hydrationin transgenic mice containing HIV-1 protease linked tothe lensAA-crystalilin promoter [J]. Arch BiochemBiophys,1995,324(2):223-227
[21]Ahmed N.Advancedglycationendproducts-role in pathology of diabeticcomplications. DiabetesResClinPract,2005,67:3-21
[1]王哲,郭定宗,李家奎.糖尿病[A].王小龙.兽医内科学[M].北京：中国农业大学出版社,2004.303-305
[2]Mattheeuws D, Rottiers R, Kaneko JJ, Vermeulen A. Diabetes mellitus in dogs:relationship of obesity to glucose tolerance and insulin response. Am J Vet Res 1984;45(1):98-103
[3]Alex Gough小动物医学鉴别诊断[M].夏兆飞,袁占奎主译.北京：中国农业大学出版社,2010：1-3
[3]Luppi P, Geng X, Cifarelli V, et al. C-peptide is internalised in human endothelial and vascular smooth muscle cells via early endosomes. Diabetologia.2009;52(10):2218-2228
[4]Rubenstein AH, Clark JL, Melani F, Steiner DF. Secretion of proinsulin C-Peptide by pancreatic β cells and its circulation in blood. Nature.1969;224(5220):697-699
[5]Munte CE, Vilela L, Kalbitzer HR, Garratt RC. Solution structure of human proinsulin C-peptide. The FEBS Journal.2005;272(16):4284-4293
[6]Flatt PR, Swanston-Flatt SK, Hampton SM,et al. Specific binding of the C-peptide of proinsulin to cultured B-cells from a transplantable rat islet cell tumor. Bioscience Reports.1986;6(2):193-199
[7]Chaisiri K, Pongpaew P, Tungtrongchitr R, et al. Prevalence and abnormal glucose tolerance in Khon Kaen province and validity of urine stick and fasting blood sugar as screening tools. J Thai Med Assoc.1997;80:363-371
[8]Selvin E, Steffes MW, Zhu H, et al. "Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults". N. Engl. J. Med.362 (9):800-11. doi:10.1056/NEJMoa0908359. PMC 2872990. PMID 20200384
[9]Tahara Y, Shima K. Kinetics of HbAlc, glycated albumin, and fructosamine and analysis of their weight functions against preceding plasma glucose level. Diabetes Care.1995;18:440-447
[10]Dungan KM, Buse JB, Largay J, Kelly MM, Button EA, Kato S, et al.1,5-Anhydroglucitol and Postprandial Hyperglycemia as Measured by Continuous Glucose Monitoring System in Moderately Controlled Patients With Diabetes. Diabetes Care.2006;29:1214-1219
[11]Santaguida PL, Balion C, Hunt D,et al. "Diagnosis, Prognosis, and Treatment of Impaired Glucose Tolerance and Impaired Fasting Glucose". Summary of Evidence Report/Technology Assessment, No. 128. Agency for Healthcare Research and Quality. Retrieved 2008-07-20
[12]郭定宗.兽医内科学[M],第2版.北京：高等教育出版社,2010.5：P215
[13]Rhea V.Morgan小动物临床手册[M].施振声主译.北京：中国农业大学出版社,2005：457-461
[14]Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia:report of a WHO/IDF consultation. World Health Organization.2006. p.21. ISBN 978-92-4-159493-6
[15]McGarry JD (2002) Banting lecture 2001:dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 51:7-18
[16]The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med.1993;329:977-86
[17]American Diabetes Association. Standards of medical care in diabetes—2012. Diabetes Care.2012;35(Suppl 1):S11-63
[18]Patel A, MacMahon S, Chalmers J, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med.2008;358:2560-72
[19]Jacobson GJ, Ramos GA, Ching JY,et al. Comparison of glyburide and insulin for the management of gestational diabetes in a large managed care organization. Am J ObstetGynecol.2005;193:118-124.
[20]Francielli M. de S. S., Mario H. R. A. da S., Adelar B., et al. Effects of metformin on glucose metabolism of perfused rat livers[J]. Molecular and Cellular Biochemistry.9 March 2010
[21]Feldman EC, Nelson RW. Canine and Feline Endocrinology and Reproduction.3rd ed. St. Louis, Missouri:Elsevier; 2004. pp.581-615
[1]全国临床检验操作规程,第3版.中华人民共和国卫生部医政司,东南大学出版社,2009：1009-1014
[2]韩德恩,江启俊,蔡全忠,等.利用全胰切除术制造狗的糖尿病模型[J].哈尔滨医科大学学报,1983,3：40-43
[3]艾昭东,刘晟,叶斌,等.狗胰腺次全切除制作Ⅰ型糖尿病模型研究[J].现代医药卫生,2008,24(21)：3169-3171
[4]刘晟,王维,罗贤明,等.药物诱导狗Ⅰ型糖尿病的研究[J].湖南医科大学学报,2000,25(2)：125-128
[5]关子安,孙茂欣,关大顺,等.现代糖尿病学[M].天津：天津科学技术出版社,2001：56-68
[6]Lenzen,S.,The mechanisms of alloxan-and streptozotocin-induced diabetes.Diabetologia 2008,51:216-226
[7]A.Pimentel Morales, E.Gomez Conde, M.G.Delgado Lopez, et al. An improved method of 90% pancreatectomy using a low dose of streptozotocin at the pancreaticoduodenal artery results in a rapid diabetic stage in dogs[J].Acta Diabetol,2005,42:153-155
[8]周贤用,傅红兴,刘云西,等.1例Beagle犬的糖尿病建模分析[J],中国医药科学,2011,1(15)：46-47
[9]史文博,梁圣保.低剂量四氧嘧啶局部动脉注射制作犬糖尿病模型[J].中华器官移植杂志,1992,13(1)：16-17
[10]李聪然,游雪甫,蒋建东.糖尿病动物模型及研究进展[J].中国比较医学杂志,2005,15(1)：59-63
[11]Pciarel BF. Im paried insul in secret ion and excess ive hepat ic glucose produ ct ion are both earLy events in the d iabet ic GK rat[J]. Am J Physiol,1996,271 (4p t1):E755-E762
[12]M. Ader, J.M. Richey, R. N. Bergman. Evidence for direct action of alloxan to induce insulin resistance at the cellular level[J]. Diabetologia,1998,41:1327-1336
[13]Black HE, Rosenblum IY, Charles CC.Chemically induced (streptozotocinalloxan) diabetes mellitus in the dog biochemical and ultrastructural studies[J]. AM J Path,1980,98(2):295-305.
[14][德]H.G沃格尔,[美]W.H沃格尔.药理学实验指南—新药发现和药理学评价.(杜冠华,李学军,张永祥译).北京：科学出版社,2001：699
[15]何学令,尹海林.四氧嗜睫剂量和给药途径对制作大鼠糖尿病模型的影响.四川动物,2003,22(40)：255-257
[16]嵇扬,张癸荣,王文俊.建立四氧嘧啶糖尿病模型的研究[J].中医药学刊,2003,21(7)：1125-6
[17]辛晓林.四氧嗜咤对小鼠肝指数和MDA含量的影响.青海师范大学学报(自然科学 版),2001：53-54
[18]张炯,王永川,吉倩梅,等.14C-四氧嘧啶在小鼠体内分布的研究[J].核技术.1988,11(1)：58
[1]铁璐,伊利夏提·肖开提,王宪,等.糖尿病伤口愈合的分子机制[J].生理科学进展,2010,41(6)：407-411
[2]刘晟,王维,罗贤明,等.药物诱导狗Ⅰ型糖尿病的研究[J].湖南医科大学学报,2000,25(2)：125-128
[3]史文博,梁圣保.低剂量四氧嘧啶局部动脉注射制作犬糖尿病模型[J].中华器官移植杂志,1992,13(1)：16-17
[4]付小兵,王德文.现代创伤修复学[M].北京：人民军医出版社,1999：1-10
[5]汪世昌,陈家璞.家畜外科学[M].北京,中国农业出版社,第三版,1998：18-20
[6]林炜栋,陆树良,青春,等.糖尿病难愈创面与晚期糖基化终末产物的关系[J].中国临床康复,2003,6(8)：370
[7]林源,王润秀,农庆文,等.糖尿病创面愈合过程的动态组织学特征[J].中国临床康复,2005,9(3)：118：120
[8]Bhora FY, Dunkin BJ, Batzri S, et al. Effect of growth factors on cell proliferation and epithelialization in human skin. J Surg Res,1995,59(2):236-244
[9]Cohen S and Carpenter G. Human epidermal growth factor isolation and chemical and biological properties. Proc Natl Acad Sci,1975,72(4):1317-1321
[10]Esch F, Baird A, Ling N, et al. Primary structure of bovine pituitary basic fibroblast growth factor(FGF) and comparison with the amino-terminal sequence of bovine brain acidic FGF. Proe Natl Acad Sci USA,1985,82(19):6507-6511
[11]Wang HJ, Wan HL, Yang TS et al. Acceleration of skin graft healing by growth factors. Burns,1996,22(1):10-14
[12]Roberts AB, Anzano MA, Wakefield LM, et al. Type beta transforming growth factor a bifunctional regulator of cellular growth. Proc Natl Acad Sci USA,1985,82(1):119-123
[13]Micera A, Vigneti E, Pickholtz D, Et al. Nerve growth factor displays stimulatory effects on human skin and lung fibroblasts, demonstrating a direct role for this factor in tissue repair. Proc Natl Acad Sci USA,2001,98(11):6162-6167
[15]Rudman SM, Philpott MP, Thomas GA, et al. The role of IGF-I in human skin and its ppendages; morphogen as well as mitogen? J Invest Dermatol,1997,109:770-777
[1]Feldman, E.C., Nelson, R.W.,2004. Diabetes mellitus. In:Canine and Feline Endocrinology and Reproduction, third ed. W.B. Saunders, Philadelphia, pp.486-538
[2]William E. Monroe, David Laxton, Edward A. Fallin, et al. Efficacy and Safety of a Purified Porcine Insulin Zinc Suspension for Managing Diabetes Mellitus in Dogs[J]. J Vet Intern Med 2005,19:675-682
[3]梁先明,秦华.猫、犬用抗糖尿病药[J].中国兽药杂志,2004,38(10)：43-46
[4]Chen Gilor, DVM, Thomas K. Graves, DVM, PhD, Synthetic Insulin Analogs and Their Use in Dogs and Cats。 Veterinary Clinics of North America:Small Animal Practice Volume 40, Issue 2, March 2010, Pages 297-307
[5]Torrance, A.G., and Mooney, C.T.,2001. Canine diabetes mellitus. In:Manual of small Animal Endocrinology.2nd edn.,(British Small Animal Veterinary Association, Cheltenham) 83-96
[6]Behrend, E.N.2006. Update on drugs used to treat endocrine diseases in small animals. The Veterinary clinics of North America. Small animal practice,36,1087-1105
[7]Reusch C. E., Robben J. H. & Kooistra H. S. (2010) Endocrine pancreas. In Clinical Endocrinology of Dogs and Cats.2nd edn. Eds Rijnberk A.Kooistra H. S.. Schlutersche. pp 155-185
[8]Rebecka S. Hess, Cynthia R. Ward. Effect of insulin dosage on glycemic response in dogs with diabetes mellitus:221 cases (1993-1998)[J]. Journal of the American Veterinary Medical Association, 2000,216(2):217-211
[1]项英,叶俊华.宠物医生手册[M],第2版.沈阳：辽宁科学技术出版社,2009：512
[2]Rhea V.Morgan小动物临床手册[M].施振声主译.北京：中国农业大学出版社,2005：457-461
[3]迟家敏.实用糖尿病学[M],第3版.北京：人民卫生出版社,2009：505
[4]Davison LJ, Ristic JM, Herrtage ME, et al. Anti-insulin antibodies in dogs with naturally occurring diabetes mellitus. Vet Immunol Immunopathol 2003;91:53-60
[5]Lucy J. Davisona, Jelena M.E. Risticb, Michael E. Herrtageb, etal. Anti-insulin antibodies in dogs with naturally occurring diabetes mellitus. Veterinary Immunology and Immunopathology 2003;91:53-60
[6]L.J.Davison, B.Walding, M.E. Herrtage, etal. Anti-Insulin Antibodies in Diabetic Dogs Before and After Treatment with Different Insulin Preparations. J Vet Intern Med 2008;22:1317-1325
[7]基斯.巴耐特,克里斯汀.亨里奇,简.桑塞姆,犬眼科学[M],Canine Ophthalmology.吴炳憔主译.沈阳：辽宁科学技术出版社,2008：107