The Study of HLA, ICA and Autoantibodies in Japanese Type 1 Diabetes Mellitus

HLA, ICA (islet cell antibody) and autoantibodies were studied in 65 Japanese patients with type 1 diabetes mellitus to elucidate the existence of immuno-genetic heterogeneity. Patients with autoantibodies had increased frequencies of HLA DRw9 antigen and of HLA haplotype of Bw61-DRw9, and a slow decay of ICA, while patients without autoantibodies had increased frequencies of HLA DR4 antigen and of HLA haplotype of Bw54-DR4, and a rapid decay of ICA. These findings support the concept of immunogenetic heterogeneity in Japanese type 1 diabetes mellitus.     

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.     

A Randomized Clinical Trial of Insulin Glargine and Aspart,Compared to NPH and Regular Insulin in Children with Type 1 Diabetes Mellitus

Objective

Appropriate treatment of patients with Type 1 diabetes mellitus (T1DM) is necessary to avoid further complications. This study was performed to compare the efficacy of insulin Glargine and Aspart with NPH insulin and regular insulin regimen in a group of children with T1DM.

Methods

Forty patients with T1DM were enrolled in this study. During run-in, all subjects were treated with conventional therapy consisting of twice-daily NPH and thrice-daily regular. Following randomization, 20 subjects received Glargine and Aspart and 20 subjects received NPH and Regular insulin.

Findings

Mean HbA1c was 8.8% and 8.6% at first and 8.4% and 8.2% at the end of study for subjects randomized initially to Glargine and Aspart and for those randomized to NPH and Regular, respectively (P>0.05). Mean fasting blood glucose (FBS) of the subjects randomized initially to Glargine and Aspart was 217±101 mg/dL, with no significant difference to 196±75 mg/dL for those randomized to NPH and Regular (P=0.48). This was also true at the end of the study. The difference in total cholesterol and triglyceride between the two groups in the beginning of study and at the end did not show any significance.

Conclusion

The current study showed no significant difference in glycemic control [Glycated hemoglobin (HbA1c) and FBS] and lipid profile (total cholesterol and triglyceride) between two regimes.     

HLA A Class II (DR, DQ) in Japanese Patients with Type 1 Diabetes Mellitus

DNA restriction fragment length polymorphism (RFLP) typing of HLA-DR and DQ alleles of 60 Japanese type 1 (insulin dependent) diabetic patients and 115 controls was performed. RFLP typing of DRB1 showed increased frequency of DR9 and decreased frequencies of DR2 and DRW6 among patients compared to controls. In the RFLP typing of BamHI- digested DNA to DQ β probe (BamHI-DQB1), the incidence of the 10.26 kb fragment, which represents either DQW4, DQW8 or DQW9, was markedly elevated in the patients, whereas the incidence of DQW6 was reduced. The predicted DR-DQ haplotype study revealed that DR4-DQW4 or DQW8, DRW8-DQW4 or DQW8 and DR9-DQW9 may contribute to susceptibility to type 1 diabetes. When serological typing of the 13 DRW8 patients was performed, all the 11 DRW8 patients carrying DQW4 or DQW8 (BamHI-10.26 kb) were positive for DQW3.
These results indicated that the HLA-DQ locus may play an important role in the development of type 1 diabetes in the Japanese as well as other ethnic groups and that the DRW8- DQW8 haplotype may predispose to the disease in Japan.     

基础加餐时胰岛素治疗儿童1型糖尿病的疗效

目的 观察应用基础加餐时胰岛素治疗儿童1型糖尿病(T1DM)的临床效果.方法 15例T1DM患儿采用传统治疗方案治疗平均16个月:双时相低精蛋白锌胰岛素30/70,2/3量早餐前30 min皮下注射,1/3量晚餐前30 min皮下注射;之后采用基础加餐时治疗方案治疗至少12个月:3餐前0～15 min门冬胰岛素皮下注射,睡前甘精胰岛素皮下注射.观察基础加餐时方案治疗后糖化血红蛋白(HbA1c)水平、胰岛素用量和低血糖发生情况.结果 15例T1DM患儿应用基础加餐时胰岛素类似物治疗后3、6、9、12个月的HbA1c与传统治疗相比降低(t=7.15、4.88、3.46、5.28,Pa<0.01),3、6、9、12个月的HbA1c相互间比较差异无统计学意义(t=2.08、1.64、1.73、1.85、1.96、1.66,Pa>0.05).胰岛素用量差异无统计学意义(t=1.56,P>0.05).传统方法治疗期间,7例发生严重低血糖,改用基础加餐时胰岛素治疗方案后,无一例发生严重低血糖.发生轻中度低血糖的次数亦显著减少(t=13.31,P<0.001).结论 应用基础加餐时胰岛素治疗儿童T1DM可使患儿获得较好的血糖控制,同时减少低血糖发生,而胰岛素用量并无增加,并可改善患儿的治疗满意度及生活质量.     

Thyroid Disorders in Children and Adolescents with Type 1 Diabetes Mellitus in Isfahan,Iran

Objective

Studies in different populations have shown great variation in the prevalence of thyroid diseases in patients with type 1 diabetes mellitus (T1DM). Our aim was to study the prevalence of thyroid disorders such as autoimmunity of thyroid (AIT), thyroid dysfunction, and goiter in children and adolescents with T1DM, compared with age- and sex-matched healthy controls in Isfahan.

Methods

One hundred patients with T1DM who were referred to Isfahan Endocrine and Metabolism Research Center and 184 healthy schoolchildren matched for age and sex were included. They were examined for goiter by two endocrinologists. Thyroid function test and serum thyroid antibodies (anti-TPO Ab and anti-Tg Ab) were measured.

Findings

The prevalence of subclinical hypothyroidism was high in both groups (18%). T1DM patients had lower frequency of goiter (21% vs. 38%, P=0.001), and higher prevalence of positive AIT (22% vs. 8%, P=0.001), anti-TPO Ab positivity (19.3% vs. 5.3%, P=0.000), and anti-Tg Ab (11.1% vs. 6.4%, P=0.1) in comparison with the control group. Being positive for AIT in diabetic patients meant an odds ratio of 5 (CI 95%: 1.5-15.6) for thyroid dysfunction. There was no association between age, sex, duration of diabetes and HbA_1C with serum anti-TPO Ab and anti-Tg Ab concentrations in this group.

Conclusion

Our results demonstrated the high prevalence of AIT and thyroid dysfunction in patients with T1DM. We suggest regular thyroid function and antibody testing in these patients.     

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。     

胰岛素泵治疗儿童1型糖尿病并酮症或酮症酸中毒26例

目的观察胰岛素泵持续皮下注射胰岛素对儿童1型糖尿病并酮症或酮症酸中毒(DK/DKA)的疗效。方法本院内分泌科2003~2005年收治的1型糖尿病并DK/DKA患儿43例,分为治疗组26例和对照组17例。治疗组予胰岛素泵治疗,对照组予小剂量胰岛素持续静脉滴注。比较二组患儿血糖、尿酮体、血pH值变化,住院时间长短。结果1.治疗组血糖下降相对稳定,纠正酸中毒后无反复。2.治疗过程中治疗组未出现低血糖,对照组2例出现。3.住院时间治疗组[(11.92±4.72)d]较对照组[(17.35±4.83)d]治疗组较对照组明显缩短(P<0.001)。结论胰岛素泵持续皮下注射胰岛素治疗儿童1型糖尿病并DK/DKA是安全有效的。     

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。     

Diet Therapy for Poorly Controlled Type 2 (Non-insulin-dependent) Diabetes Mellitus

ABSTRACT. Poorly controlled type 2 diabetes represents a major therapeutic problem. A classification of the disease, based on body weight and presence or absence of adequate insulin-secretion capacity, may be helpful in the choice of correct treatment. Calorie reduction is the most important therapeutic intervention in overweight patients. In the diabetic diet digestible carbohydrates should comprise at least 50 energy % , while the fat content should be reduced below 30 energy % . Controlled clinical studies show that the blood glucose control can be improved and the urinary glucose excretion be diminished by addition of dietary fibre. In obese type 2 diabetics supplemented fasting may be usehrl to achieve a rapid weight loss and an improved metabolic control. Although our knowledge with regard to the patho-physiology of type 2 diabetes and the effects of dietary treatment has increased during recent years, several important questions remain unanswered. Also there is a great need for education and training programmes to achieve improved compliance to the dietary advice given.     

儿童I型糖尿病青春发育前及青春期血清IGF-I和IGFBP-3水平监测

目的：研究儿童Ⅰ型糖尿病青春发育前及青春期血清胰岛素样生长因子I(IGF-I),胰岛素样生长因子结合蛋白3(IGFBP-3)水平变化,探讨生长激素 胰岛素样生长因子I(GH-IGF-I)轴与血糖控制的关系。方法：分别采用ELISA和免疫放射法测定63例Ⅰ型糖尿病患儿和47例正常对照血清IGF-I,IGFBP-3水平,用胶乳凝集法测定Ⅰ型糖尿病患儿的糖化血红蛋白(HbAIC)。结果：①青春发育前糖尿病患儿血IGF-I为(75.4±26.6) ng/ml,IGFBP-3为(2 756.1±763.8) ng/ml,与对照组［(103.9±46.5) ng/ml,(2 717.1±480.2 ng/ml)相比无统计学差异(P>0.05);但青春期糖尿病患儿血IGF-I和IGFBP-3［(178.2±65.9) ng/ml,(2 956.0±847.6) ng/ml］均低于对照组［(229.6±54.5) ng/ml,(3 393.2±748.9) ng/ml］］P<0.05。②新发病的I型糖尿病患儿胰岛素治疗后血IGF-I为(143.0±67.5) ng/ml,IGFBP-3为(2 740.0±449.8) ng/ml,较治疗前［(54.8±44.3) ng/ml, (2 233.8±336.2) ng/ml］明显升高(P<0.05)。③糖尿病组HbA IC与血IGF-I,IGFBP-3之间存在负相关关系(r=-0.32,-0.29,P<0.01或0.05)。④糖尿病组青春期HbAIC为(9.0±1.8)%,每日胰岛素用量为(0.86±0.30)U/kg,均高于青春期前［(7.8±1.8) %,(0.64±0.38) U/kg］(P<0.05)。结论：儿童Ⅰ型糖尿病血IGF-I,IGFBP-3水平较正常儿降低,尤其青春期患儿比正常同龄儿降低的程度更为显著,提示此类患者青春期存在GH IGF-I轴的严重紊乱,可能是导致这一时期血糖控制不良的重要原因。     

Analysis of HLA-DQA1 in Japanese Patients with Type 1 Diabetes Mellitus, Using DNA-PCR-RFLP Typing

DNA-polymerase chain reaction(PCR)-RFLP(restriction fragment length polymorphism) typing of the DQA1 gene was performed on 39 patients with type 1 diabetes and 30 controls. Analysis of the frequency of the subtypes of DQA1 alleles, using the DNA-PCR-RFLP typing technique, showed that the DQA1*0301 subtype was most strongly associated with the disease (97.4% vs 56.7%, R.R. = 19.8, pc < 0.00005). These results indicated that DQA1*0301 may determine the disease susceptibility in the Japanese. In addition, we analyzed the frequency of the subtypes of DQA1 genes in the ten patients carrying the DRW8-DQW8 haplotype, and found that at least eight of them (80%) were classified as having DQA1*0301. The DRYV8-DQW8-DQA1*0301 may be one of the susceptible haplotypes among the Japanese.     

1型糖尿病并低三碘甲状腺氨酸综合征201例

目的探讨1型糖尿病(T1DM)及糖尿病酮症酸中毒(DKA)患儿并低三碘甲状腺氨酸(T3)综合征的临床特点。方法采用放射免疫分析法检测91例T1DM并DKA患儿(DKA组)及110例单纯T1DM患儿(非DKA组)血清T3、甲状腺素(T4)、促甲状腺激素(TSH)水平,观察2组T3、T4下降例数及水平,并将DKA组分为轻、中、重3个亚组,观察不同组别中甲状腺激素变化特点。结果 DKA组易发生T3、T4下降,DKA组T3[(0.54±0.51)μg.L-1]、T4[(5.65±2.80)μg.L-1]与非DKA组T3[(1.02±0.38)μg.L-1]、T4[(9.28±2.85)μg.L-1]比较,差异均有统计学意义(Pa<0.000 1)。中、重度DKA组与非DKA组T3比较,差异有统计学意义(Pa<0.000 1),轻、中、重度DKA组与非DKA组T4比较,差异均有统计学意义(Pa<0.000 4,0.000 1)。DKA组与非DKA组TSH比较,差异无统计学意义(P>0.05)。结论 T1DM患儿甲状腺激素检测的结果主要表现为T3降低,部分伴T4降低,其疾病的严重程度与甲状腺激素降低程度一致,T1DM并DKA患儿的T3、T4水平均有明显下降,提示T1DM患儿需重视甲状腺激素的检测,利于早期防治。     

HLA class II genetic association of type 1 diabetes mellitus in Czech children

Abstract:  To examine human leukocyte antigen (HLA) class II association of type 1 diabetes mellitus (DM) in Czech children, we performed a case–control study of 261 patients diagnosed before the age of 15 and 289 non-diabetic control children. Complete HLA-DQA1, DQB1 genotyping and DRB1*04 subtyping were carried out by polymerase chain reactions with sequence-specific primers. The effect of the DRB1*04 subtypes was studied in DRB1*04 alleles carried on DQB1*0302-DQA1*03 haplotypes. The risk was statistically evaluated by testing 2 × 2 tables, considering corrected p-values < 0.05 significant. The DQB1*0302 (odds ratio, OR = 9.0), DQB1*0201 (OR = 3.4) and DQA1*03 (OR = 7.5) alleles were significantly associated with diabetes risk, while the DQB1*0602 (OR = 0.02), DQB1*0301 (OR = 0.08), DQB1*0503 (OR = 0.13), DQB1*0603 (OR = 0.20), DQA1*01 (OR = 0.28) and DQA1*02 (OR = 0.26) alleles were significantly protective. Of the DQA1-DQB1 genotypes, we point out the extremely high risk of OR = 116 conferred by HLA-DQA1*05-DQB1*0201/DQA1*03-DQB1*0302. Among DRB1*04 subtypes, DRB1*0403 was significantly protective (OR = 0.05, CI 95% 0.01–0.45). Since none of the remaining DRB1*04 subtypes was associated with type 1 DM, our study may present another piece of evidence that the DRB1*0401 and DRB1*0404 alleles do not modify type 1 diabetes risk generally in European populations.     

Type 2 diabetes,polycystic ovary syndrome and the insulin resistance syndrome in adolescents: Are they one big iceberg?

Obesity in children may cause overt clinical disease in childhood. The complex endocrine and metabolic changes of obesity and insulin resistance in adolescents result in hyperinsulinemia, dyslipidemia, hypertension, steatohepatitis, glucose intolerance, type 2 diabetes, acanthosis nigricans and ovarian hyperandrogenemia, commonly known as polycystic ovarian syndrome (PCOS). Type 2 diabetes and PCOS in adolescents are new endocrine diseases in this age group that require unique approaches to diagnosis and treatment. The direct correlation between duration of disease and control of the disease, and subsequent long term complications of these two diseases, predict serious morbidity in young adult life for the affected adolescents. Pediatricians have an important role in the prevention, diagnosis and treatment of obesity, insulin resistance syndrome, type 2 diabetes and PCOS.     

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...