Metabolic syndrome in childhood: Association with birth weight, maternal obesity, and gestational diabetes mellitus
Metabolic syndrome in childhood: Association with birth weight, maternal obesity, and gestational diabetes mellitus
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DOI：
10.1542/peds.2004-1808
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发表时间：
2005-03-01
期刊：
影响因子：
8
通讯作者：
Vohr, BR
中科院分区：
文献类型：
--
作者：
Boney, CM;Verma, A;Vohr, BR
Objective.儿童肥胖导致儿童2型糖尿病和代谢综合征（MS）发病率增加。宫内暴露于糖尿病和出生时的大小是2型糖尿病的危险因素，但它们与儿童期MS的相关性尚未得到证实。我们研究了大于胎龄（LGA）和适于胎龄（阿加）儿童MS的发展。MS的主要组成部分（肥胖、高血压、血脂异常和葡萄糖耐受不良）在一项纵向队列研究中进行了评估，研究对象为6、7、9和11岁的LGA（n = 84）或阿加（n = 95）子女，其母亲患有或不患有妊娠期糖尿病（GDM）。队列包括4组，即对照母亲的LGA后代、GDM母亲的LGA后代、对照母亲的阿加后代和GDM母亲的阿加后代。在6岁、7岁、9岁和11岁时进行生物统计学和人体测量。生化测试包括测量餐后葡萄糖和胰岛素水平和高密度脂蛋白（HDL）胆固醇水平在6年和7年，空腹血糖，胰岛素，甘油三酯和HDL胆固醇水平在9年和11年。我们将MS的组成部分定义为：（1）肥胖（BMI >年龄的第85百分位数），（2）舒张压或收缩压>年龄的第95百分位数，（3）餐后血糖水平>140 mg/dL或空腹血糖水平>110 mg/dL，（4）甘油三酯水平>年龄的第95百分位数，（5）11岁时高密度脂蛋白水平（第85百分位数）在25%-35%的儿童中存在，但LGA和阿加后代之间的比率没有差异。LGA/GDM组的胰岛素抵抗发生率（定义为≥ 2个MS组分的空腹葡萄糖/胰岛素比值> 50%）有较高的趋势，显著高于LGA/对照组（29%）、阿加/GDM组（21%）和阿加/对照组（18%）。LGA/GDM组11岁时MS ≥ 3个组分的患病率为15%，而其他组为3.0%至5.3%。进行考克斯回归分析，以确定发生MS的独立危险（风险）归因于出生体重，性别，母亲孕前肥胖，GDM。对于考克斯分析，我们将MS定义为以下4种组分中的≥ 2种：肥胖、高血压（收缩压或舒张压）、葡萄糖耐受不良和血脂异常（甘油三酯水平升高或HDL水平降低）。LGA状态和母亲肥胖使MS的风险增加约两倍，风险比分别为2.19（95%CI：1.25-3.82）和1.81（95%CI：1.03-3.19）。GDM和性别没有独立意义。为了确定MS随时间的累积风险，我们根据LGA或阿加类别绘制了对照组和GDM组6年至11年的风险，并进行了考克斯回归分析。在对照组中，LGA和阿加后代发生MS的风险随时间的变化无显著差异，但在GDM组中，LGA和阿加后代发生MS的风险有显著差异，LGA儿童11岁时发生MS的风险是对照组的3.6倍。我们发现，糖尿病母亲的LGA后代在儿童时期患MS的风险很大。其他组的MS患病率与1988-1994年全国健康和营养检查调查中白色青少年的患病率（4.8%）相似。LGA与母亲GDM对儿童MS的这种影响先前在皮马印第安儿童中得到证实，但在一般人群中没有。我们还发现，母亲肥胖的儿童患MS的风险增加，这表明不符合GDM临床标准的肥胖母亲可能仍然有影响胎儿生长和产后结局的代谢因素。出生时LGA并暴露于糖尿病或母体肥胖的宫内环境的儿童患MS的风险增加。鉴于肥胖患病率增加，这些发现对延续肥胖，胰岛素抵抗及其后果在后代中的循环具有影响。
Objective. Childhood obesity has contributed to an increased incidence of type 2 diabetes mellitus and metabolic syndrome (MS) among children. Intrauterine exposure to diabetes and size at birth are risk factors for type 2 diabetes mellitus, but their association with MS in childhood has not been demonstrated. We examined the development of MS among large-for-gestational-age (LGA) and appropriate-for-gestational age (AGA) children.Study Design. The major components of MS (obesity, hypertension, dyslipidemia, and glucose intolerance) were evaluated in a longitudinal cohort study of children at age 6, 7, 9, and 11 years who were LGA (n = 84) or AGA (n = 95) offspring of mothers with or without gestational diabetes mellitus (GDM). The cohort consisted of 4 groups, ie, LGA offspring of control mothers, LGA offspring of mothers with GDM, AGA offspring of control mothers, and AGA offspring of mothers with GDM. Biometric and anthropometric measurements were obtained at 6, 7, 9, and 11 years. Biochemical testing included measurements of postprandial glucose and insulin levels and high-density lipoprotein (HDL) cholesterol levels at 6 and 7 years and of fasting glucose, insulin, triglyceride, and HDL cholesterol levels at 9 and 11 years. We defined the components of MS as (1) obesity (BMI >85th percentile for age), (2) diastolic or systolic blood pressure >95th percentile for age, (3) postprandial glucose level >140 mg/dL or fasting glucose level >110 mg/dL, (4) triglyceride level >95th percentile for age, and (5) HDL level 85th percentile) at 11 years was present in 25% to 35% of the children, but rates were not different between LGA and AGA offspring. There was a trend toward a higher incidence of insulin resistance, defined as a fasting glucose/insulin ratio of = 2 components of MS was 50% for the LGA/GDM group, which was significantly higher than values for the LGA/control group (29%), AGA/GDM group (21%), and AGA/control group (18%). The prevalence of >= 3 components of MS at age 11 was 15% for the LGA/GDM group, compared with 3.0% to 5.3% for the other groups. Cox regression analysis was performed to determine the independent hazard (risk) of developing MS attributable to birth weight, gender, maternal prepregnancy obesity, and GDM. For Cox analyses, we defined MS as >= 2 of the following 4 components: obesity, hypertension (systolic or diastolic), glucose intolerance, and dyslipidemia (elevated triglyceride levels or low HDL levels). LGA status and maternal obesity increased the risk of MS approximately twofold, with hazard ratios of 2.19 (95% CI: 1.25-3.82) and 1.81 (95% CI: 1.03-3.19), respectively. GDM and gender were not independently significant. To determine the cumulative hazard of developing MS with time, we plotted the risk according to LGA or AGA category for the control and GDM groups from 6 years to 11 years, with Cox regression analyses. The risk of developing MS with time was not significantly different between LGA and AGA offspring in the control group but was significantly different between LGA and AGA offspring in the GDM group, with a 3.6-fold greater risk among LGA children by 11 years.Conclusions. We showed that LGA offspring of diabetic mothers were at significant risk of developing MS in childhood. The prevalence of MS in the other groups was similar to the prevalence (4.8%) among white adolescents in the 1988-1994 National Health and Nutrition Examination Survey. This effect of LGA with maternal GDM on childhood MS was previously demonstrated for Pima Indian children but not the general population. We also found that children exposed to maternal obesity were at increased risk of developing MS, which suggests that obese mothers who do not fulfill the clinical criteria for GDM may still have metabolic factors that affect fetal growth and postnatal outcomes. Children who are LGA at birth and exposed to an intrauterine environment of either diabetes or maternal obesity are at increased risk of developing MS. Given the increased obesity prevalence, these findings have implications for perpetuating the cycle of obesity, insulin resistance, and their consequences in subsequent generations.