载脂蛋白E基因多态性对儿童血脂的影响

目的：　研究载脂蛋白E(APOE)基因多态性是否影响了中国学龄儿童的血脂水平。方法：　检测214名本地的两所小学四年级和五年级儿童的血脂,其中男116名,女98名,年龄8～12岁。用多聚酶链反应检测APOE基因型。结果：　APOE的基因型分布为E3/ 3148例 (6 9.2 %) ,E4/ 34 1例 (19.1% ) ,E2 / 32 0例 (9.3% ) ,E4/ 45例 (2 .4% ) ,E 2/4和E2/ 2未检测到;血清总胆固醇和低密度脂蛋白胆固醇及载脂蛋白B按E4>E3>E2的顺序减低,且有统计学意义(P<0.05),高密度脂蛋白胆固醇和载脂蛋白A1,甘油三酯则按上述顺序升高,但均无统计学意义 (P>0.05)。结论：　APOE基因多态性对血脂的影响在中国汉族学龄儿童中存在。     

肾病综合征患儿血载脂蛋白E变化及与中分子尿蛋白关系的研究

目的　研究原发性肾病综合征 (INS)患儿血载脂蛋白E(ApoE)的变化及与中分子尿蛋白的关系。 方法　检测 5 0例INS患儿血ApoE及血胆固醇 (TC)、甘油三酯 (TG)、高密度脂蛋白胆固醇 (HDL C)、低密度脂蛋白胆固醇 (LDL C)、载脂蛋白A1(ApoA1)、载脂蛋白B(ApoB)及血清总蛋白 (TP)、白蛋白 (Alb)、2 4h尿蛋白 (TUP)。用HYDRASYSLC(Sebia)全自动电泳分析系统测定INS患儿尿蛋白分子质量大小以确定其尿蛋白类型。以 5 0例年龄、性别相匹配的健康儿童为对照组。结果　活动期INS患儿血ApoE及血TC、TG、HDL C、LDL C、ApoB显著高于对照组 (均P <0 0 1)。 92 %INS患儿有高ApoE血症。血ApoE及血TC、TG、LDL C、ApoB与血TP、Alb呈显著负相关 (P <0 0 1) ,而血ApoE、TC、TG、LDL C、ApoB与TUP无相关。选择性中分子蛋白尿 (SMUP)组血ApoE显著高于非选择性蛋白尿 (NSUP)组 (P <0 0 1)。结论　INS患儿血ApoE明显升高 ,高ApoE血症广泛存在于INS患儿 ,血ApoE升高不能作为脂蛋白肾小球病的特异性诊断指标。中分子尿蛋白是INS患儿血ApoE升高的一个重要原因。     

Effects of guar on plasma viscosity and related parameters in diabetic children

Ten diabetic children supplemented their normal diets with 0.45 g/kg/day guar gum for 4 weeks. They experienced a decrease in (1) plasma fibrinogen, (2) insulin requirement, (3) serum osmolality and (4) plasma viscosity; and an increase in serum albumin and total serum protein concentrations.The decrease in plasma viscosity, which was statistically significant, depended on the increase of albumin and the decrease of fibrinogen and may have some significance to the development of diabetic microangiopathy. The sequence of events eventually leading to a decrease of plasma viscosity is possibly mediated by gip and glucagon, consecutively.     

Carbohydrate intake, serum lipids and apolipoprotein E phenotype show association in children

Aim:  To study the association between carbohydrate intake and serum lipids in children, and influence of apolipoprotein E phenotype (apoE) on the association.
Subjects/methods:  A total of 644 children from a prospective, randomized atherosclerosis prevention trial (STRIP) participated in this longitudinal study at age 5 (n = 644), 7 (n = 585) and 9 (n = 550) years. ApoE phenotype, fasting triglyceride, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol concentrations and 4-day food records were analysed.
Results:  An increase in the total carbohydrate intake by 1 E% (percentage of total daily energy intake) associated with a decrease in HDL cholesterol by 0.006 mmol/L (p < 0.001) when adjusted for saturated, monounsaturated and polyunsaturated fatty acid, age, gender, body mass index and STRIP study group. The inverse association between total carbohydrate intake and HDL cholesterol was evident in children with apoE3 (p < 0.001) or apoE4 (p < 0.001), but not in those with apoE2 (p = 0.78). An increase in total carbohydrate intake by 1 E% increased triglycerides by 0.02 mmol/L (p < 0.001) independently of apoE phenotype, while 1 E% increase in sucrose intake increased triglycerides by 0.01 mmol/L (p < 0.001).
Conclusion:  Carbohydrate intake has a relatively small effect on serum lipids in children. Children with the apoE3 or E4 but not with E2 phenotype show reduction in HDL cholesterol with increasing carbohydrate intake indicating that genetic and environmental factors interact with children's lipoprotein metabolism.     

Diagnosis and treatment of diabetic ketoacidosis in children and adolescents

Diabetic ketoacidosis (DKA) continues to be a common presentation of both type 1 and type 2 diabetes in children and adolescents. Early recognition and treatment in patients with new-onset diabetes are essential to the prevention of this potentially life-threatening complication of diabetes. DKA management protocols for paediatric patients differ from adult protocols, and therefore, it is important to have clear written guidelines and that in-patient care occur in centres with experience in the management of paediatric DKA. The present article outlines recommendations regarding the diagnosis and management of DKA. It also discusses management guidelines for intercurrent illness, with a view to reducing the frequency of DKA in children and adolescents with established diabetes.     

Anticardiolipin antibodies in children and adolescents with insulin-dependent diabetes mellitus

Anticardiolipin antibodies were determined in 29 diabetic children and adolescents, aged 3.9–26.8 years, with disease duration from 1 month to 19 years. Anti-islet cell antibodies (ICA-IgG and CF-ICA), anti-insulin antibodies (IAA), antithyroid antibodies and non organ-specifc (NOSA) antibodies were also determined. Patients were grouped according to insulin-dependent diabetes mellitus (IDDM) duration: group I (n=11)<6 months, and group II (n=18)>5 years. Eleven of group II patients showed precocious signs of micro-angiopathic complications. Forty-two age- and sex-matched healthy subjects served as controls. IgG and IgM anticardiolipin antibodies were evaluated by ELISA and their results expressed as arbitrary units (AU). IgG anticardiolipin antibodies were found in 7 patients (24%), while IgM anticardiolipin antibodies were absent in all. IgG anticardiolipin antibodies were more frequent in IDDM patients than in controls (P<0.005) and group I (in 6 out of 11 patients; 54.5%) than in group II (in 1 out of 18 patients; 5.5%) (P<0.025). In five out of six group I patients with IgG anticardiolipin antibodies, ICA-IgG and/or CF-ICA were also found. No correlation was observed between anticardiolipin and other auto-antibodies, micro-angiopatic complications, and HLA typing.     

Polyunsaturated fatty acids in plasma lipids of diabetic children during and after diabetic ketoacidosis

BACKGROUND AND AIM: Previously we reported significantly higher plasma values of the essential fatty acids but significantly lower values of their longer-chain metabolites in diabetic children than in healthy controls. Here, we report data on the acute effect of diabetic ketoacidosis (DKA) on the fatty acid composition of plasma lipids. METHODS: Diabetic children (n=9; age: 16.1 [3.3] y; duration of diabetes: 5.0 [5.3.] y; daily insulin dose: 0.87 [0.66] unit/kg body weight/d; glycated haemoglobin: 13.4 [2.8] %; median [IQR]) were investigated at admission for DKA (during DKA) and at the end of the treatment of DKA (after DKA). Fatty acid composition of plasma lipid classes was determined by high-resolution capillary gas-liquid chromatography. RESULTS: Blood glucose (27.0 [8.5] vs 6.5 [1.6] mmol/l), pH (7.28 [0.35] vs 7.36 [0.06]) and base excess (-8.9 [15.1] vs -2.2 [6.3] mmol/l) were grossly abnormal during but not after DKA. Values of linoleic acid were significantly lower after than during DKA (non-esterifed fatty acids (NEFA): 15.55 [1.47] vs 12.27 [5.74] % wt/wt; triacylglycerols (TG): 20.84 [9.23] vs 17.40 [5.78]; p<0.05). In contrast, values of gamma-linolenic acid (NEFA: 0.87 [0.54] vs 2.34 [1.85]; p<0.05) and arachidonic acid (TG: 1.37 [0.71] vs 1.74 [0.57]; p<0.05) were significantly lower during than after DKA. The product/substrate ratios for delta-6 desaturation were significantly lower during than after DKA. CONCLUSION: Successful treatment of diabetic ketoacidosis is associated with a significant increase of long-chain polyunsaturated fatty acid values in blood plasma in diabetic children. This observation suggests that disturbances of essential fatty acid metabolism in diabetic children are related not only to diet but to hypoinsulinaemia as well.     

Serum lipids in epileptic children treated with carbamazepine and valproate

Serum total cholesterol (TC), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) and very low-density lipoprotein cholesterol, triglyceride, apolipoproteins A1 and B levels were studied in 57 healthy children and in 39 children with epilepsy who had been receiving carbamazepine (CBZ) (23 children) for 1.58 ± 1.10 years or valproic acid (VPA) (16 children) for 1.34 ± 1.11 years. In patients receiving CBZ, mean TC level, mean LDL-C level, mean TC/HDL-C ratio and mean LDL-C/HDL-C ratio were significantly higher than controls. None of the mean levels of serum lipids evaluated in patients receiving VPA was significantly different from the corresponding control group mean. Changes in serum lipids correlated with neither duration of therapy or plasma antiepileptic levels nor age or gender. Conclusion Our results suggested that CBZ, a hepatic-enzyme-inducing drug, affects serum lipid status. Long-term prospective studies are necessary to determine whether chronic CBZ therapy is a risk factor for atherosclerotic disorders. Received: 15 October 1996 / Accepted: 5 February 1997     

Increased high density lipoproteins in diabetic children

Serum lipoprotein lipid and apolipoprotein concentrations were determined in 27 diabetic children (5–18 years old) and 13 matched healthy controls. The serum cholesterol concentrations in the diabetics were slightly higher than in the controls (P<0.05) due to a significantly higher level of the high density lipoprotein cholesterol (P<0.01). Also the serum concentration of apolipoprotein A-I, the major protein constituent of the high density lipoprotein fraction, was higher in the diabetic children (P=0.05). There were no significant differences between the groups with regard to the serum triglyceride concentrations or the apolipoprotein C-II and C-III concentrations. Neither the lipoprotein lipid nor the apolipoprotein levels were significantly correlated with variables related to the degree of regulation of the diabetic disease. No obvious explantation, based on the present data, can be given for the increased high density lipoprotein cholesterol concentrations in insulin-treated diabetics in comparison with the healthy children. It is possible, however, that the increased high density lipoprotein cholesterol concentration may be caused by an increased level of insulin in the circulation of insulin-treated diabetic children.     

肥胖儿童载脂蛋白E基因多态性的研究

目的 探讨单纯性肥胖儿童载脂蛋白Ｅ（ＡｏｐＥ）基因多态性的分布及其对血脂、脂蛋白、载脂蛋白的影响。方法 采用改良的聚合酶链式反应－限制性片段长度多态性方法分析肥胖及健康儿童ＡｐｏＥ基因型。结果 肥胖儿童Ａｐｏε４等位基因频率（０．１２２９）较健康儿童（０．０６１８）增高（Ｐ〈０．０５）。ＡｐｏＥ基因多态性影响健康儿童的血脂水平。在单纯性肥胖儿童,ε２,ε３,ε４等位基因携带者的血甘油三酯（ＴＧ）、     

儿童原发性肾病综合征载脂蛋白E 基因检测及临床意义

目的　研究原发性肾病综合征 (INS)患儿血浆载脂蛋白E(ApoE)基因多态性分布及对血脂代谢的影响。方法　选择 2 0 0 0年 1月至 2 0 0 3年 9月潍坊市人民医院收治的 5 2例INS患儿 ,并选择 6 9名健康儿童作为对照组 ,测定其血清胆固醇 (TC)、甘油三酯 (TG)、高密度脂蛋白 (HDL)、低密度脂蛋白 (LDL)、载脂蛋白AI及载脂蛋白B10 0 (ApoAI,ApoB10 0 )水平 ,用聚合酶链反应 限制性片段长度多态性 (PCR RFLP)检测ApoE基因型。结果　与对照组相比 ,INS患儿血清TC、TG、LDL、HDL、ApoAI和ApoB10 0水平增高 (P <0 0 1) ;其Apoε等位基因频率分布不均 ,ε2、ε3、ε4等位基因携带者的TC、TG、ApoB10 0水平差异有显著性意义 (P <0 0 5 )。与ε3等位基因携带者相比 ,ε2携带者TG水平较高 ,LDL水平较低 (P <0 0 5 ) ;ε4携带者TC水平较高 ,TG水平较低 (P <0 0 5 )。ε2、ε3、ε4等位基因与TC、LDL浓度呈正相关 (P <0 0 5 )。难治性肾病综合征 (RNS)患儿Apoε2等位基因频率较对照组显著增高 (P <0 0 5 )。结论　INS患儿Apoε等位基因频率分布与对照组无差异 ,RNS患儿Apoε2等位基因频率显著增高 ,脂质代谢紊乱持续存在 ,易发生肾脏损害 ,应及早加用降血脂药物治疗。     

Relationship of apolipoprotein E phenotypes to serum lipid and lipoprotein levels in Japanese schoolchildren

The distribution of apolipoprotein (apo) E phenotypes was investigated in Japanese schoolchildren and an attempt was made to determine whether the apoE phenotypes influence the serum levels of lipid and lipoprotein. The subjects were 289 children from ajunior high school (145 M, 144 F, aged 12–13 y). TheE_3/3 phenotype was demonstrated in 69.9%, E_4/3 in 18.7%, E_2/3 in 9.0%, E_4/2 in 1.4%, E_4/4 in 0.7% and E_5/4 in 0.3%. E_2/2 was not detected. Serum levels of total cholesterol and low-density lipoprotein-cholesterol were progressively lower in the phenotypes E_4/3, E_3/3 and E_2/3. The serum level of high-density lipoprotein-cholesterol showed a progressive increase in the same order. In conclusion, Japanese schoolchildren with E_4/3 already had an atherogenic serum lipid profile.     

Serum lipids and apolipoproteins in Spanish children and adolescents: a 5 year follow-up

This study was designed to assess "tracking" of serum lipids and apolipoproteins in three age groups of Spanish children over a 5 year period. A total of 84 6-year-old, 89 10-year-old and 64 14-year-old children were evaluated in 1989 (with measurement of serum total cholesterol, triglycerides, lipoproteins and apolipoproteins A1 and B), and re-evaluated in 1994. Correlation coefficients between initial and final lipid and apolipoprotein values were as follows: total cholesterol, 0.66; low-density lipoprotein (LDL) cholesterol, 0.65; high-density lipoprotein (HDL) cholesterol, 0.61; triglycerides, 0.61; apolipoprotein A1, 0.60; apolipoprotein B, 0.66. When age groups were analysed separately, children who were 14 years old at the beginning of the study showed higher correlation coefficients, particularly for total cholesterol and LDL cholesterol (> 0.7 in both cases). More than 70%, of children who were in the top quintile of total, LDL or HDL cholesterol as well as apolipoprotein A1 or B in 1989 remained in the top quintile 5 years later.     

Prevalence of coeliac disease in diabetic children and adolescents

Screening for coeliac disease (CD) with serum antigliadin antibodies (AGA) was performed in 1032 diabetic children and adolescents. In 8 children CD had been diagnosed before study entry. Of the remaining 1024 children, 33 had an elevated AGA titre in the first serum sample. On follow-up an elevated AGA titre was confirmed in only 17 of 31 patients. Nine of the repeatedly positive patients underwent jejunal biopsy, and CD was diagnosed in two asymptomatic patients; both were positive for IgG- and IgA-AGA. Among 10 AGA-positive patients in whom biopsies could not be performed, only 1 showed IgA-AGA and thus carried a high risk for CD. From our results we estimate a prevalence of CD in Swiss and German diabetic children between 1.1% and 1.3%. Falsepositive AGA titres occurred significantly more often in patients with diabetes duration of less than 1 year. AGA testing teached a specificity of 99% if performed at least 1 year after the onset of diabetes. Children suffering from both diabetes and CD showed a diabetes manifestation at a significantly younger age than non-coeliac patients, whereas CD tended to be diagnosed at a remarkably late age.Abbreviations AGA antigliadin antibodies - CD coeliac disease - FIST fluorescent immunosorbent test - IDDM insulindependent diabetes mellitus     

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目的探讨单纯性肥胖儿童载脂蛋白(apolipoprotein,Apo)E基因多态性的分布及其对血脂、脂蛋白、载脂蛋白的影响,及其与冠状动脉、心电图改变的关系。并对其早期预测和疾病预防提供理论依据。方法选择2002年12月至2004年12月潍坊医学院附属医院儿科的6～14岁单纯性肥胖儿童89例和健康儿童76例。抽取外周静脉血,测定血清中甘油三酯(TG),总胆固醇(TC),高密度脂蛋白胆固醇(HDLC),低密度脂蛋白胆固醇(LDLC),载脂蛋白A1(ApoA1),载脂蛋白B100(ApoB100)浓度。应用改良的聚合酶链式反应限制性片段长度多态性(PCRRFLP)分析及聚丙烯酰胺凝胶电泳测定儿童ApoE基因型。结果共检出4种ApoE基因型,E3/3、E4/3、E2/3、E4/2,以ε3为最常见。与健康儿童比较,肥胖儿童ε4等位基因频率增高,差异有显著性(P<0.05)。结论单纯性肥胖儿童有ApoE基因多态性的变化,且明显影响小儿血浆脂类代谢,肥胖儿童ApoE4与冠心病有密切相关性。     

The metabolic syndrome in children and adolescents

The metabolic syndrome is a constellation of metabolic abnormalities that result in an increased risk for type 2 diabetes mellitus and cardiovascular disease in adults. It emerges when a person’s predisposition for insulin resistance is worsened by increasing central obesity and is largely confined to the overweight population. The United States National Cholesterol Education Program’s Adult Treatment Panel III report proposed a set of criteria for the clinical diagnosis of metabolic syndrome in the adult population. A uniform definition for the paediatric population is lacking. Despite this, several studies have demonstrated that features of the syndrome develop in childhood and that the syndrome is present in up to 30% of obese children (body mass index at or above the 95th percentile). Ninety per cent of obese children meet at least one of the five criteria. The degree of abnormality is related to the body mass index, waist circumference and fasting insulin levels. There appears to be a genetic predisposition to the development of the syndrome and certain ethnic groups are at increased risk. The intrauterine environment also appears to play a role. Insulin resistance should be targeted for treatment through exercise and dietary intervention. The role of pharmacotherapeutic agents remains unclear. A uniform definition of the metabolic syndrome for paediatric patients needs to be created. Early intervention should be instituted because many of the features of the syndrome track from childhood into adulthood.     

Type 2 diabetes mellitus in European children and adolescents

Aim: The aim of the study was to review the published and unpublished data on type 2 diabetes in European children in order to determine how common this problem is in the dominantly Caucasian population. Methods: The MEDLINE database was searched and a questionnaire was distributed among European Childhood Obesity Group (ECOG) representatives from 16 countries. Results: One hundred and eighty-four children with type 2 diabetes were diagnosed in Europe, 144 of them of Caucasian origin. The majority of them were overweight females and, had positive family history for type 2 diabetes mellitus.

Conclusion: Because of the significant rates of type 2 diabetes in Europe, screening for it in obese children and adolescents is highly recommended.     

Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents

Introduction Randomly estimated fasting hyperglycaemia in an asymptomatic individual may represent the first sign of pancreatic β-cell dysfunction. Objective We aimed at specifying the genetic aetiology of asymptomatic hyperglycaemia in a cohort of children and adolescents.Subjects and methods We analysed the aetiological diagnosis in 82 non-obese paediatric subjects (38 males) aged 0.2-18.5 years (median: 13.1) who were referred for elucidation of a randomly found blood glucose level above 5.5 mmol/l. In addition to fasting glycaemia and circulating levels of insulin and C-peptide, the subjects were tested by an oral glucose tolerance test and an intravenous glucose tolerance test and screened for mutations in the genes encoding glucokinase (GCK), HNF-1α (TCF1), Kir6.2 (KCNJ11) (if aged <2 years) and HNF-4α (HNF4A) (those with a positive family history of diabetes). Results and discussion We identified 35 carriers of GCK mutations causing MODY2, two carriers of TCF1 mutations causing MODY3, one carrier of a HNF4A mutation causing MODY1 and one carrier of a KCNJ11 mutation causing permanent neonatal diabetes mellitus. Of the remaining patients, 11 progressed to type 1 diabetes mellitus (T1DM) and 9 had impaired glucose tolerance or diabetes mellitus of unknown origin. In 23 subjects, an impairment of blood glucose levels was not confirmed. We conclude that 39 of 82 paediatric patients (48%) with randomly found fasting hyperglycaemia suffered from single gene defect conditions, MODY2 being the most prevalent. An additional 11 patients (13%) progressed to overt T1DM. The aetiological diagnosis in asymptomatic hyperglycaemic children and adolescents is a clue to introducing an early and effective therapy or, in MODY2, to preventing any future extensive re-investigations.     

单纯性肥胖儿童外周血单核细胞载脂蛋白E基因的表达

目的　探讨单纯性肥胖儿童外周血单核细胞载脂蛋白E基因表达及其与血脂、脂蛋白、载脂蛋白的相关关系。方法　采用竞争性逆转录 聚合酶链式反应方法分析 3 2例单纯性肥胖儿童和 3 2例正常健康儿童外周血单核细胞的载脂蛋白E基因表达。结果　载脂蛋白E基因能在儿童外周血单核细胞表达 ,与健康儿童比较 ,单纯性肥胖儿童外周血单核细胞载脂蛋白E基因表达水平显著下调 (P <0 0 1) ,重度肥胖儿童尤其明显 ,载脂蛋白E基因表达水平与肥胖度呈负相关 (P <0 0 5)。肥胖儿童存在明显的血脂代谢紊乱 ,载脂蛋白E基因表达水平与低密度脂蛋白 胆固醇呈负相关 ,与血载脂蛋白E浓度呈正相关 (P <0 0 5) ,与血总胆固醇、甘油三酯、高密度脂蛋白 胆固醇、脂蛋白 (a)、载脂蛋白AⅠ水平无明显相关 (P >0 0 5)。结论　单纯性肥胖儿童外周血单核细胞载脂蛋白E基因表达水平明显下调 ,并与肥胖程度及血脂代谢异常相关联 ,提示载脂蛋白E基因表达变化可能与肥胖的发生发展及肥胖的心血管病变相关联