Tenneti Nikhil, Dayal Devi, Sharda Sheetal, Panigrahi Inusha, Didi Mohammed, Attri Savita Verma, Sachdeva Naresh, Bhalla Anil Kumar
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J Pediatr Endocrinol Metab. 2017 Aug 28;30(8):831-837. doi: 10.1515/jpem-2016-0422.
Recent data indicates that adults with Down syndrome (DS) are at increased risk for cardiovascular disease (CVD) that significantly contributes to their morbidity and mortality. Although identification of cardiometabolic risk factors during childhood is desirable to design preventive interventions, the data on such risk factors in children with DS is scarce. The aim of this study was to study the cardiometabolic risk factors such as insulin resistance (IR), leptin and adiponectin concentrations, lipid abnormalities and leptin resistance in non-obese children with DS.
This cross-sectional case control study included karyotype confirmed trisomy-21 DS children aged 2-12 years and their matched healthy controls. After detailed anthropometry, weight, height and body mass index (BMI) standard deviation scores (SDSs) were calculated with reference data. Laboratory evaluation included determination of fasting lipid parameters, insulin, glucose, leptin and adiponectin concentrations. The homeostasis model assessment method (HOMA-IR) was used to assess IR and the ratio of leptin to BMI was used as an index of leptin resistance.
Seventy-seven children (39 with DS and 38 controls) comprised the study cohort. The anthropometric parameters were similar in the two groups. Children with DS showed significantly higher mean leptin concentrations (2.098±1.68 ng/mL vs. 1.44±0.52 ng/mL, p-value: 0.00) and higher indices of leptin resistance (0.127±0.085 vs. 0.09±0.03, p-value: 0.001) as compared to controls. Fasting adiponectin concentrations were lower (20.64±19.87 ng/mL vs. 32.58±34.25 ng/mL, p-value: 0.21) and fasting glucose higher (89.25±8.12 mg/dL vs. 85.71±5.52 mg/dL, p-value: 0.06) in the DS group as compared to the controls but the differences did not reach statistical significance. The concentrations of insulin, various lipid parameters and calculated HOMA-IR values were similar in the two groups. In the DS group, five children were identified to have high (>75th centile) leptin levels and four as impaired fasting glucose as compared to none in the controls.
Alterations of several cardiometabolic risk factors, in particular, leptin concentrations and leptin resistance are present in children with DS. The presence of hyperleptinemia without hyperinsulinemia suggests a probable inherent genetic basis for increased leptin resistance in patients with DS. There is a need for larger studies to further understand increased leptin resistance in DS that may contribute to increased CVD related morbidity and mortality in these patients.
近期数据表明，患有唐氏综合征（DS）的成年人患心血管疾病（CVD）的风险增加，这对其发病率和死亡率有显著影响。尽管在儿童期识别心脏代谢危险因素对于设计预防干预措施是可取的，但关于DS患儿此类危险因素的数据却很匮乏。本研究的目的是研究非肥胖DS患儿的心脏代谢危险因素，如胰岛素抵抗（IR）、瘦素和脂联素浓度、血脂异常及瘦素抵抗。
这项横断面病例对照研究纳入了经核型确认的2至12岁的21三体DS患儿及其匹配的健康对照。在进行详细的人体测量后，根据参考数据计算体重、身高和体重指数（BMI）标准差评分（SDS）。实验室评估包括测定空腹血脂参数、胰岛素、葡萄糖、瘦素和脂联素浓度。采用稳态模型评估法（HOMA-IR）评估IR，瘦素与BMI的比值用作瘦素抵抗指数。
77名儿童（39名DS患儿和38名对照）组成了研究队列。两组的人体测量参数相似。与对照组相比，DS患儿的平均瘦素浓度显著更高（2.098±1.68 ng/mL对1.44±0.52 ng/mL，p值：0.00），瘦素抵抗指数也更高（0.127±0.085对0.09±0.03，p值：0.001）。与对照组相比（p值：0.21），DS组的空腹脂联素浓度较低（20.64±19. ... ng/mL对32.58±34.25 ng/mL），空腹血糖较高（89.25±8.12 mg/dL对85.71±5.52 mg/dL，p值：0.06），但差异未达到统计学意义。两组的胰岛素浓度、各种血脂参数及计算得出的HOMA-IR值相似。在DS组中，有5名儿童被确定瘦素水平高（>第75百分位数），4名儿童空腹血糖受损，而对照组中无此情况。
DS患儿存在多种心脏代谢危险因素的改变，尤其是瘦素浓度和瘦素抵抗。高瘦素血症而无高胰岛素血症的存在提示DS患者瘦素抵抗增加可能有潜在的遗传基础。需要进行更大规模的研究以进一步了解DS患者中瘦素抵抗增加的情况，这可能导致这些患者心血管疾病相关发病率和死亡率的增加。
