同种异体胰腺组织微块移植治疗糖尿病小鼠的研究

目的探讨同种异体胰腺组织微块移植对糖尿病(DM)小鼠的治疗效果及移植物在宿主体内的存活情况。方法把海藻酸钠微囊包被的正常KM小鼠胰腺组织微块移植入链脲佐菌素诱导的DM小鼠腹腔,连续监测空腹血糖(FPG)水平。结果海藻酸钠微囊包被的胰腺组织微块可有效降低DM小鼠的FPG,且移植物在宿主体内可存活12 d以上。结论海藻酸微囊包被的胰腺组织微块移植在DM治疗中有应用潜能。     

Immune Mechanisms in the Etiology of lnsulin-Dependent Diabetes Mellitus

Different environmental factors such as virus infections or toxic agents may play a role in the etiology of insulin-dependent diabetes mellitus, but it is evident that hereditary factors also are important. These two basic components can be unified into one common etiological mechanism, the immunological. Several facts support this hypothesis, which is reviewed in this paper. The theory now seems strong enough to justify trials to interfere with the immune response at the onset of diabetes in an effort to change the gradual loss of beta cell function.     

Epidemilogy of Insulin-Dependent Diabetes Mellitus in Korea

The prevalence of diabetes mellitus in the age group5–16 years, determined from 13,152 subjects residing in Kwangju, Chonnam Provice was 0.099 per cent or 98.9/100,000 in a study performed from December, 1976 to June 1977. On the other hand an epidemiologic study carried out on 254,835 subjects in the age groups14–15 and17–18 years from March 1981 to March 1982 in Seoul City revealed on overall prevalence of 7.85/100,000. In a retrospective study, 88.0/100,000 or out of a total of 10,228 pediatric inpatients were confirmed casesw of insulin-dependent diabetes mellitus, during 7 years and 2 months (from january 1974 to March 1981) at a general hospital located in Jeonju City. The wide range in the prevalence and incidence figures of diabetes mellitus in Korean children probably resulted from lack of uniformity in epidemiological methodology and the degree of ascertainment. The adge distribution at onset of diabetes mellitus showed a gradual incdrease and peak incidences at 3,8 and 12 years of age. The4 sex difference in incidence was not obvious, though girls slightly outnumbered boys. Seasonal variation at onset of diabetes mellitus showed the highest frequency of new cases in winter and spring months.     

腺病毒介导胰岛素样生长因子-1基因对链脲佐菌素诱发1型糖尿病大鼠的保护作用

目的观察腺病毒介导胰岛素样生长因子-1(IGF-1)基因对链脲佐菌素(STZ)诱导SD大鼠1型糖尿病(T1DM)的预防保护作用,比较肌肉注射、腹腔注射及胰腺被膜下注射3种不同注射途径的效果。方法4～6周龄SD雄性大鼠90只,随机分为糖尿病对照组(A组)、空白对照组(B组)、腺病毒空载体对照组(C组)、肌肉注射含有IGF-1基因的重组腺病毒(Ad-rIGF-1)组(D组)、腹腔注射Ad-rIGF-1组(E组)、胰腺被膜下注射Ad-rIGF-1组(F组),每组各15只。A组、B组不做任何处理,C组注射含空载体(Ad-eGFP)的重组腺病毒液0.1mL,D组、E组、F组注射含Ad-rIGF-1的重组腺病毒液0.1mL。1周后,A组、D组、E组及F组腹腔注射STZ50mg.kg-1诱发糖尿病,每周测定体质量、血糖。5周后,处死大鼠,取其胰腺做病理切片及免疫组织化学法观察胰腺炎症浸润程度和IGF-1局部表达程度;取下腔静脉血,测定IGF-1和胰岛素水平。结果D组、E组、F组与A组比较,糖尿病发病率低,平均血糖水平低,但血糖水平明显高于B组和C组。胰腺切片HE染色显示D组、E组、F组胰腺炎症浸润程度较A组轻,但明显重于B...     

Characterization of Diabetes Mellitus in Japanese Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is frequently associated with marked obesity and diabetes mellitus (DM). Although the overall frequency of DM in PWS ranges from 7–20%, there is only limited data available on Japanese patients. This study evaluated five factors associated with DM in PWS: 1) frequency, 2) age of onset, 3) risk factors, 4) long-term complications and 5) treatment. Sixty-five patients, ranging in age from 10 to 53 yr, were studied retrospectively. The frequency of DM in patients over 10 yr of age was 26.2% (17/65 patients). The age of DM onset ranged from 10 to 29 yr with a median age of 15 yr. The body mass index (BMI) was significantly higher in the DM group in comparison with the non-DM group. The number of patients using growth hormone (GH) in the DM group was significantly lower than the number that did not. Proteinuria (urinary excretion of albumin/creatinine at spot collection: U-Alb/Cr ≥300 mg/gCr) was observed in 1/17 patients (5.9%), microalbuminuria (U-Alb/Cr 30–300 mg/gCr) was observed in 4/17 patients (23.5%) and nonproliferative retinopathy was observed in 2/17 patients (11.8%). Among oral hypoglycemic agents, alpha-glucosidase inhibitors (α-GI) were most often used in our patients (10/17, 58.8%). Eleven out of 17 patients (64.7%) had been treated with insulin.     

Pancreatic Islets in Older Patients with Cystic Fibrosis with and without Diabetes Mellitus: Morphometric and Immunocytologic Studies

Forty patients with cystic fibrosis (CF), including 34 who died above age 10 years without having developed clinical diabetes mellitus and 6 who died with both cystic fibrosis and diabetes mellitus, were studied. The mean age of the female patients with CF but not diabetes was 15.8± 5.6 years; of males without diabetes, 17.2± 6.4 years; of female patients with CF and diabetes mellitus, 20.2± 6.9 years; and of males with CF and diabetes, 21.3± 6.6 years. The mean number of pancreatic islets in microscopic sections for patients with cystic fibrosis but not diabetes was 4.18± 2.76/mm², and the value for patients with both cystic fibrosis and diabetes mellitus was 2.61± 2.07/mm². The lowest density of pancreatic islets (1.69± 0.48/mm²) for cystic fibrosis was found in patients with the latest-stage pathologic lesion. Nesidioblastosis (presence of ductuloinsular complexes) was identified in 14 of 38 cystic fibrosis patients, both with and without diabetes mellitus. The pancreatic islets of both diabetic and nondiabetic patients with CF showed hypertrophy; the mean volume of the three largest pancreatic islets for CF only was 0.0117± 0.00657³ mm and that for cystic fibrosis and diabetes was 0.00795± 0.00599 mm³, both values being larger than normal. Ratios of the amounts of islet endocrine cells, A cells, B cells, and D cells, were determined by peroxidase-anti-peroxidase labeled antibody staining. The B cells composed 43.0% of endocrine cell mass in cystic fibrosis alone and 30.1% in cystic fibrosis with diabetes mellitus, which were lower than normal proportions. The D cell values, 11.9% in cystic fibrosis and 15.1% in cystic fibrosis with diabetes mellitus, on the other hand, were greater than normal ratios.     

儿童1型糖尿病90例

目的探讨儿童1型糖尿病(IDDM)的发病情况、临床特点、远期并发症及酮症酸中毒(DKA)的治疗。方法回顾性分析1993～2003年我院90例IDDM患儿的发病情况,临床特点,远期并发症,并探讨DKA的治疗。结果10～16岁儿童发病率最高,感染是诱发DKA的常见原因,未长期坚持胰岛素治疗易导致IDDM远期并发症的发生。结论小剂量胰岛素持续静滴、纠正水电解质紊乱、调节酸碱平衡是抢救DKA的关键;坚持长期胰岛素治疗是防治远期并发症IDDM的关键。     

Urinary C-Peptide Excretion at Onset of Insulin Dependent Diabetes Mellitus in Children

ABSTRACT. The 24-hour urinary excretion of C-peptide and the plasma C-peptide concentration were measured at the onset of insulin dependent diabetes mellitus (IDDM) in children. The excretion of C-peptide was twice as high as that found in normal control subjects, whereas the plasma C-peptide values were markedly lower, indicating increased urinary leakage of C-peptide in this phase of the disease. In the diabetic children under seven years of age the mean value of C-peptide excretion was clearly lower than in the older children.     

Classification of Diabetes Mellitus by Studies of C-Peptide Secretory Capacity

Residual pancreatic B-cell function was investigated in children with diabetes mellitus in whom classification of the type of disease was difficult at the first visit. Intravenous glucagon tests were performed at the first visit and subsequently, the C-peptide responses compared. Based on our data on a limited number of patients, we propose C-peptide concentrations of 3.0 to 3.5 ng/ml at the peak or at 6 min after injection of glucagon, as the critical level which distinguishes non-insulin dependent from insulin-dependent diabetes mellitus. However, the degree of obesity, clinical stage and other factors also need to be considered in the classification of diabetes mellitus.     

格列苯脲对4例永久性新生儿糖尿病的疗效

目的 探讨格列本脲治疗永久性新生儿糖尿病( PNDM)的疗效.方法 选取2008年2月- 2009年5月本院收治并确诊的PNDM患儿4例,应用格列本脲对患儿进行试验性治疗2～3周,对格列本脲治疗有效的患儿进行长期随访,并对其疗效进行分析.结果 4例PNDM患儿中例1对格列本脲治疗有效,完全用格列本脲取代了胰岛素治疗.例4部分有效,运用格列本脲和胰岛素联合进行治疗.例2和例3对格列本脲治疗无效.对格列本脲有效及部分有效的患儿进行长期随访,血糖控制良好,未发现明显不良反应.结论 部分PNDM患儿对格列苯脲治疗有效.对临床考虑为PNDM的患儿应尽早进行遗传学分析,以利于临床治疗方案的选择.     

Neonatal Macrosomia and Hypoglycaemia in Children of Mothers with Insulin-Treated Gestational Diabetes Mellitus

ABSTRACT. All newborn children to mothers with gestational diabetes mellitus (GDM) in the county of Örebro were investigated during a one year prospective study. Neonatal macrosomia (birthweight > 3 SD) was observed in 27% of children of mothers with GDM and was significantly correlated to the cord C-peptide concentration. Hypoglycaemia (B-glucose <1.5 mmol/l) was observed in 38% of the children, most frequently two hours after delivery. Hypoglycaemia was not more common in macrosomic children and could not be predicted by the blood glucose concentration of the mother at delivery or by the cord C-peptide level. It is concluded that mothers with GDM must be intensively treated in order to avoid the occurrence of macrosomia in their infants and that the newborn child must be carefully observed and treated in order to avoid neonatal hypoglycaemia.     

Report of a Japanese Girl with Marfan Syndrome Associated with Insulin-Dependent Diabetes Mellitus

A 3 year old girl was admitted to hospital in an emaciated condition and with polydipsia in October 1974. Following the diagnosis of diabetes mellitus, she Received treatment with insulin. On the first admission, a systolic murmur was noted at the apex of the heart. In 1981, the murmur was found to be continuous with a systolic click, and echocardiography demonstrated a mitral valve prolapse. In 1982, electrocardiography revealed left ventricular hypertrophy, and the patient's X-ray showed vertebral kyphoscoliosis. Ophthalmological examination revealed slightly impaired visual acuity and a mild case of cataracts in 1986. The patient grew to be tall and thin with arachnodactylia of the hands, fingers, feet and toes. These symptoms and findings were compatible with Marfan syndrome, although the ophthalmological findings are not specific for this disease. This patient is the first case in Japan of Marfan syndrome associated with insulin-dependent diabetes mellitus, although the relation between Marfan syndrome and IDDM remains unclear.     

C-Peptide/Creatinine Ratio in Early Morning Urine as an Indicator of Residual B-Cell Function in Insulin-Dependent Diabetes

The C-peptide/creatinine (Cr) ratio in early morning urine was evaluated to assess B-cell function. The subjects were 12 boys and 36 girls with insulin-dependent diabetes mellitus (IDDM). The controls were 130 boys and 137 girls aged 4–15 years. There was a significant inverse correlation of this ratio with the duration of insulin therapy (r = -0.5807, P<0.01). The daily insulin dose in U/kg was significantly different among the following groups: 1.22 ± 0.31 U/kg in group 1 with undetectable C-peptide, 0.94 ± 0.37 in group 2 with a decreased ratio and 0.45 ± 0.28 in group 3 with a normal ratio. HbAl levels were 11.3 ±1.6% in group 1 and 9.2 ± 1.1% in group 3. The difference was significant. The result shows that the C-peptide/ Cr ratio in early morning urine is useful for assessing B-cell function in diabetic children.     

Transient Neonatal Diabetes Mellitus in a Pair of Twins

ABSTRACT. The occurrence of transient neonatal diabetes mellitus in male twins with almost identical courses of illness is reported. A trial with chlorpropamide treatment of twin A had no obvious influence on the insulin consumption or on duration of treatment. Very low values of plasma C-peptide and serum proinsulin with no detectable insulin antibodies supports the theory of delayed maturation of the beta-cell.     

Classification of Type 1 and Type 2 Diabetes Mellitus from Studies of ICA, HLA and Insulin Secretory Capacity

We studied ICA, HLA and insulin secretory capacity in 87 children with positive urinary screening and more than 2 points in the oral glucose tolerance test in order to establish criteria by which they could be classified into type 1 or type 2 diabetes mellitus. Fifty-five non-obese, ketosis-prone insulin dependent diabetic children were used as controls for type 1 diabetes mellitus. Our conclusions were as follows: 1. Type 1 diabetics were non-obese (on insulin therapy), ICA positive, ketosis-prone, had an insulin secretory capacity (Z IRI) of less than 100/nU/ml, and most of them possessed HLA-Bw54-DR4 or DRw9, DRw53 but did not possess Bw52-DR2 haplotype. 2. In the patients who were treated by dietary regimens alone for certain periods, however, insulin secretory capacities gradually deteriorated and they finally became insulin dependent. The children of this group who were not obese during insulin therapy and possessed an HLA haplotype identical to that in type 1 diabetes, regardless of ICA, might be classified as having slowly progressive type 1 diabetes. 3. The major difference between type 1 and slowly progressive type 1 diabetes was a family history of diabetes. Genetic factors might modify the clinical course of type 1 diabetes mellitus. 4. If the sensitivity of ICA or related autoantibodies to islet cells can be detected more readily, it should become easier to distinguish between type 1 and 2 diabetes.     

Incidence of Childhood Diabetes Mellitus in Austria 1979–1984

ABSTRACT. The mean annual incidence of childhood diabetes mellitus in Austria was 7.22 cases per 100 000 with a year to year variation of 6.09–8.67 per 100 000. A seasonal variation of onset, with peaks in autumn and winter and with lower rates in summer in children older than 4 years, could be observed. The peak incidence in girls occurred at 11–12 years and preceeded the highest incidence in boys by 1–2 years. Both sexes showed a small peak around 6 years of age. The male to female ratio was 1.2/1. Compared to epidemiologic studies in north-west-ern Europe the incidence of childhood diabetes in Austria is low, however higher than in France or Italy.     

Histopathological Changes of the Placenta in Diabetes Induced by Maternal Administration of Streptozotocin during Pregnancy in the Rat

Abstract The objective of this investigation was to find out the histopathological changes of the placenta and to correlate them with fetal malformations and growth retardation in experimental diabetes. Diabetes was induced in Wistar rats at different stages of gestation by intraperitoneal injection of streptozotocin (STZ). The controls were either buffer treated or injected with STZ followed by 2–6 IU insulin until term. All fetuses and placentae were collected on day 20 of gestation. Fetuses of diabetic rats were significantly growth retarded. Maxillary hypoplasia, edema, gastroschisis, exencephaly and septal defects of the heart were the major malformations. Most of the experimental placentae weighed heavier relative to their body mass. Toluidine blue stained sections of the placentae revealed severe histological abnormalities. The unusually large sized placentae had extensive cystic degeneration, often with an increased population of leucocytes. Giant cells were very numerous. Perivascular fibrosis, persistence of fetal mesenchyme, edema, infarcts and vacuolisation were observed in the labyrinths. In the small placentae, the glycogen cells were fewer and the glycogen in them remained unutilized. Reduction of labyrinthine zone, hypovascularity, constriction of vessels, perivascular edema and platelet aggregation characterized these placentae. The placentae of externally malformed fetuses showed cystic degeneration; their labyrinths contained constricted and less extensive vascular network. Phagocytic giant cells, polymorphs and platelet aggregation were also marked. Placentae of externally normal looking fetuses also presented cystic degeneration, reduction in fetal vasculature, dilated maternal sinusoids and giant cell proliferation. Insulin treatment resulted in the preservation of most of the normal histology of the placenta which correlated well with the reduced fetal malformations.     

2型糖尿病儿童8例临床分析及综合治疗随访

目的探讨2型糖尿病(T2DM)儿童的临床特点及诊治方法。方法对2002年5月-2008年2月本院8例住院T2DM患儿的临床资料进行回顾性分析,包括临床症状、体质量指数、血压、血脂、合并症、家族史、口服葡萄糖耐量试验、胰岛素释放试验。予饮食、运动、行为纠正和药物综合治疗及疗效随访。结果8例中仅1例有典型症状;均为肥胖儿,体质量指数为31.4±2.7;并脂肪肝7例,并原发性高血压、代谢综合征各4例,并高三酰甘油血症、黑棘皮病各3例,并酮症酸中毒1例;4例有肥胖家族史;3例通过饮食、运动和行为纠正治疗2个月后血糖有效控制,1例予胰岛素治疗1周后改为二甲双胍,余服用二甲双胍,2周后血糖有效控制。结论儿童T2DM起病隐匿,肥胖症是其重要危险因素,易并原发性高血压、脂质代谢异常、血管病变及靶器官损伤,需采取饮食、运动和药物治疗、教育及自我监控相结合的综合治疗措施。