Aortic Intima-Media Thickness and Mean Platelet Volume in Children With Type 1 Diabetes Mellitus

Background:

Diabetes mellitus type 1 is the most common endocrine metabolic disorder occurring in childhood and adolescence due to the autoimmune destruction of pancreatic beta cells as a result of various environmental factors interacting with an underlying genetic predisposition. Diabetes is a risk factor for early onset atherosclerosis, and the high mortality rate seen in these patients is partially related to cardiovascular diseases.

Objectives:

This study was conducted to compare mean platelet volume as a marker of early atherosclerosis with aortic intima-media thickness in children with type 1 diabetes and to identify its correlation with known cardiovascular risk factors.

Patients and Methods:

The study included 27 patients between age range of 6 and 17 years that were diagnosed with type 1 diabetes and 30 healthy children of the same age range who did not have any chronic disease. In both groups, we used the color Doppler ultrasound to measure children’s aortic intima-media thickness and identify their mean platelet volumes.

Results:

There was no significant difference between the groups regarding gender distribution, age, High-Density Lipoprotein (HDL) and Low-Density Lipoprotein (LDL) cholesterol levels (P > 0.05). Also no significant difference could be documented between the patient and control groups regarding the aortic intima-media thickness and mean platelet volume (P > 0.05). However, there was a significant correlation between aortic intima-media thickness and mean platelet volume (r = 0.351; P < 0.05).

Conclusions:

In the present study, there was no evidence of early atherosclerosis in children with type 1 diabetes. However, mean platelet volume having a significant correlation with aortic intima-media thickness may be useful as an early marker of atherosclerosis.     

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.     

Adiponectin is a Good Marker for Metabolic State among Type 1 Diabetes Mellitus Patients

Objective

Adiponectin is secreted from adipose tissue. This hormone has a fundamental role in pathogenesis of insulin resistance, and has anti-inflammatory and anti-atherogenic effects. The objectives of this study were to compare serum adiponectin level between type 1 diabetics and healthy people and to assess its related factors, and also to determine the relationship between adiponectin and metabolic state.

Methods

This was a case control study involving 60 diabetics (25 good and 35 poor metabolic controlled) and 28 healthy persons (younger than 18 years old). The data about demographic (age and sex), clinical and paraclinical characteristics [body mass index (BMI), duration of disease, puberty state, and glycosylated hemoglobin (HbA1c) and adiponectin level in serum] were collected. Determinants of adiponectin were assessed using univariate and multiple linear regression analyses.

Findings

Mean (±SD) serum adiponectin level in healthy persons, good-controlled and poor-controlled type 1 diabetes mellitus patients were 9.16 (±4.2) µg/cc, 10.89 (±4.48)µg/cc, and 15.92 (±8.26)µg/cc, respectively. Post hoc analysis revealed that differences of adiponectin between poor- and good-controlled type 1 diabetes mellitus patients (P=0.01) and between healthy persons and poor controlled type 1 diabetes mellitus (P<0.0001) were statistically significant. Adiponectin level was associated with puberty state and BMI in healthy persons. It was associated with puberty state and HbA1c in type 1 diabetic persons.

Conclusion

Serum level of adiponectin was higher in type 1 diabetics than in healthy persons and it can be used as a good marker for metabolic control state among diabetics.     

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。     

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.     

新诊断儿童1型糖尿病109例的临床特征

目的探讨近年新诊断儿童1型糖尿病的临床特征。方法对1999年1月1日～2005年4月30日浙江大学医学院附属儿童医院住院且为首次发病的109例1型糖尿病的临床资料进行回顾性分析,按照有无酮症酸中毒和有无低钾血症分别进行分组比较,正态分布的数据用x±s表示,采用为卡方及t检验,非正态分布的资料用中位数表示,采用Mann-WhiteyU检验进行组间比较。结果新诊断1型糖尿病儿童非酮症酸中毒(DKA)组病程明显较DKA组长,平均住院时间和糖化血红蛋白明显低于DKA组。入院时有感染诱因者21例(19.3%);伴低钾血症48例(44%),非低钾血症61例(56%);DKA组低钾血症的比率为26/47(55.3%),明显高于非DKA组的22/62(35.5%)。低钾组出现心悸、胸闷及倦怠症状出现频率为39.6%、35.4%,而非低钾组上述症状的频率分别是11.5%、16.4%,两组差异有显著性。所有患儿无1例死亡,出院后治疗依从性不一致。结论感染可能导致患儿糖尿病的进展和临床表现的出现。低钾血症组的症状较重。可能是临床症状的不典型导致了糖尿病不能及时被发现。     

三种胰岛素输注装置在1型糖尿病患儿中的应用

目的 比较一次性胰岛素注射器、胰岛素笔、胰岛索泵3种胰岛索输汴装置在1型糖尿病患儿应用中的准确性、精密度及方便性.方法 采用对照研究设计,比较3种胰岛素输注装置在注射小剂量胰岛素时的准确性和精密度.用称晕法检测实际注射剂量,用相对离差绝对值来评价准确性,用变异系数来评价精密度.由1型糖尿病患儿父母对3种装置的方便性进行评分.结果 当注射目标剂量为1 IU时,一次性胰岛素注射器、胰岛素笔、胰岛素泵的准确性及精密度差异均有统计学意义(P<,a><0.01).4 IU时,仍呈现相似的结果.10 IU时,三者准确性和精密度的差异均有统计学意义(P<,a><0.05).在使用方便性上,注射器低于胰岛素笔及胰岛素泵(P<0.01),胰岛素笔与胰岛素泵间差异无统计学意义.结论 在1 IU及4 IU时,三种注射装置比较,准确性和精确性胰岛素泵均优于胰岛素笔,胰岛素笔优于一次性胰岛素注射器.在10 IU时,三种注射装置的准确性和精密度趋于接近,而注射器的方便性不如胰岛素笔及胰岛素泵.     

Clinical Significance of Urinary C-Peptide Excretion in Children with Insulin-Dependent Diabetes Mellitus

ABSTRACT. In order to evaluate the accuracy of urinary C-peptide determination and the clinical significance of C-peptiduria for the early course of insulin-dependent diabetes (IDDM), the rate of urinary excretion of C-peptide was determined in 32 children and adolescents with IDDM and correlated with serum C-peptide concentration, urinary excretion of albumin and β-mic-rogloublin and with the glomerular filtration rate (GFR) measured in terms of the clearance of ⁹⁹mTc-DTPA. The age of the subjects ranged from 9.1 to 17.1 years (mean 13.1) and the duration of diabetes from 0.3 to 11.9 years (mean 4.6). There was a good correlation between postprandial serum C-peptide concentration and the 24-hour urinary C-peptide excretion rate ( r =0.81; p <0.001). GFR and urinary albumin excretion were slightly elevated in the diabetic patients as compared with non-diabetic subjects ( p <0.05 and p <0.001, respectively), but C-peptide excretion was unrelated to the degree of hyperfiltration or albuminuria, neither was there any correlation between the excretion rate of β₂-microglobulin and C-peptide. Glycaemic control was poorer in the diabetic children who had only trace amounts of C-peptide in their urine (<0.05 nmol/m²/24 h) than in those with minimal (0.05–1.0 nmol/m²) or moderate 24-hour urinary C-peptide excretion (>1.0 nmol/m²). It is concluded that urinary C-peptide excretion serves very well to reflect residual β-cell function and is unrelated to the slight renal hyperfunction and albuminuria often seen in diabetic subjects. Even minimal C-peptide excretion ranging from 0.05 to 1.0 nmol/m²/24 h still seems to indicate clinically significant insulin secretion.     

持续皮下胰岛素输注在儿童1型糖尿病治疗中的应用

胰岛素泵(CSII)可减少严重低血糖、改善黎明现象、降低糖化血红蛋白(HbAlc),但花费大、有皮肤损害、活动时部分患者感觉不便。因此,需要更多、更经常和更严格的监测,进行糖尿病知识教育,掌握不当反而易发生糖尿病酮症酸中毒。建议选择适用患者为主动寻求降低血糖和HbAlc、寻求减少低血糖危险、寻求改善生活方式、愿意尝试CSII治疗和应有现实合理期望值的患者。同时他们应有良好的自我管理能力,按时随访,会计算碳水化合物,每日监测4次以上血糖,有可靠的成人监督,掌握CSII治疗的各项技术技能,能主动与糖尿病治疗专家沟通等。作者就1型糖尿病患儿CSII使用和调节剂量的方法进行介绍。     

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。     

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.     

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。     

CLEC16A基因与中国儿童1型糖尿病遗传易感性及临床表现的相关性

目的研究CLEC16A基因与中国儿童1型糖尿病(T1DM)易感性及临床表现的关联。方法提取131例无血缘关系的T1DM患儿(T1DM组,均符合1999年WHOT1DM的诊断标准)及121例无血缘关系的成年健康献血员(健康对照组)的外周血基因组DNA(饱和盐析法),选取CLEC16A基因17个具有单核甘酸多态性(SNPs)的位点,运用飞行质谱技术对CLEC16A基因与中国儿童T1DM遗传易感性及临床表现的相关性进行研究。结果1.在17个CLEC16ASNPs位点多态性中,只有rs12921922和rs12931878位点的等位基因的频率在T1DM组中显著增加,其他等位基因的频率分布在T1DM组与健康对照组中无统计学差异。rs12921922的等位基因为C与T,其中T等位基因的频率在T1DM组为90.8%,健康对照组为85.0%,二组比较有统计学差异(P=0.0440)。rs12931878的等位基因为A与C,其中A等位基因的频率在T1DM组为90.1%,健康对照组为84.0%,二组比较有统计学差异(P=0.0435)。2.CLEC16A易感性基因在中国T1DM患儿不同临床表现分组中的频率分布无统计学差异。结论C...     

不同血钾水平1型糖尿病175例的临床特征

目的了解不同血钾水平儿童及青少年1型糖尿病临床特征。方法1型糖尿病患者175例根据血钾水平将其分为3组：A组血钾〈4 mmol/L,C组血钾≥5 mmol/L,B组血钾正常（4~5 mmol/L）。对3组性别、年龄、住院时间、伴发呕吐、感染、酮症酸中毒（DKA）的比例及生化指标等临床特征进行观察。分析血钾紊乱和不同临床表现之间的关系及可能原因。结果血钾异常组较易发生代谢紊乱及伴发症状。A组40例,其发生酮症酸中毒及感染比例比B组要高。A组血氯水平最高。C组36例,发生呕吐比例比B组高,其患儿年龄较A组小,C组入院时血糖水平在3组中最高。结论糖尿病发生代谢紊乱和急性并发症时,易并血钾异常,治疗方面应积极纠正血钾紊乱。     

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.