中华预防医学杂志    2018年01期 膳食营养干预预防妊娠期糖尿病    PDF     文章点击量:392    
中华预防医学杂志2018年01期
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文章信息

杨振宇
YangZhenyu
膳食营养干预预防妊娠期糖尿病
Diet and nutrition interventions prevent gestational diabetes mellitus
中华预防医学杂志, 2018,52(1)
http://dx.doi.org/10.3760/cma.j.issn.0253-9624.2018.01.020

文章历史

投稿日期: 2017-08-21
上一篇:中国孕妇营养与健康状况十年回顾
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膳食营养干预预防妊娠期糖尿病
杨振宇     
杨振宇 100050 北京,中国疾病预防控制中心营养与健康所 国家卫生计生委微量元素营养重点实验室
摘要: 妊娠期糖尿病(GDM)是孕期常见的并发症之一,近年来呈现上升趋势。膳食营养素(蛋白质、脂肪和脂肪酸、碳水化合物、维生素D、维生素E、铁、锌、硒和肌醇等)的摄入量、膳食模式和益生菌等可能与GDM的发生相关。膳食因素是预防GDM重要的可控因素。本文综述了这些膳食因素在预防GDM的作用。以植物性食物为主的健康膳食模式有可能降低GDM的风险。高动物蛋白质、高脂肪和低碳水化合物的膳食模式可能增加GDM风险。营养素补充预防GDM值得进一步研究。倡导我国孕妇食物多样,以植物性食物和谷类为主,孕期保持适宜体重增长。
关键词 :糖尿病,妊娠;膳食;营养
Diet and nutrition interventions prevent gestational diabetes mellitus
YangZhenyu     
National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention; Key Laboratory of Trace Element Nutrition, National Health and Family Planning Commission, Beijing 100050, China
Corresponding author: Yang Zhenyu, Email: yang_zhenyuid@126.com
Abstract:Gestational diabetes mellitus (GDM) is one of the most common complications during pregnancy, with rising trend over the years. Dietary nutrient intake (protein, fat and fatty acids, carbohydrate, vitamin D, vitamin E, iron, zinc, selenium and inositol et al.), dietary pattern and probiotics may be related to GDM occurrence. Dietary factors are modifiable factors for preventing GDM. The study reviewed the roles of these dietary factors in preventing GDM. Results showed that plant-based dietary pattern may lower the risk of GDM and dietary pattern characterized with high animal protein, high fat and low carbohydrate may increase the risk of GDM. It warrants further studies that nutrient supplementation may prevent pregnant women from GDM. Diverse diet based on plant and cereal food should be promote for healthy and appropriate weight gain during pregnancy.
Key words :Diabetes, gestational;Diet;Nutrition
全文

妊娠期糖尿病(gestational diabetes mellitus,GDM)是孕期常见的并发症之一,指妊娠期首次发生或诊断的糖耐量异常,不包括糖尿病患者的妊娠。母亲高血糖可通过胎盘转运至胎儿,使胎儿血糖水平升高,胰岛素水平升高,促进蛋白质和脂肪储存,造成分娩巨大儿的风险增加。分娩后,新生儿低血糖及成年期发生超重和肥胖的风险均明显增加。对母亲而言,GDM增加早产、先兆子痫、剖宫产和肩难产等高危妊娠的风险,远期使母亲和子代患2型糖尿病的风险升高。随着2型糖尿病的发病率上升,GDM呈现上升趋势。全球GDM越来越值得关注,且不同地区GDM患病率差异明显。2016年,亚洲地区(中亚北非、东南亚、东亚和太平洋地区等)GDM患病率较高(11.7%~12.9%),而欧洲患病率较低(5.8%)[1]。中国天津的一项调查结果显示,与1999年相比,2008年GDM的患病率增加2.8倍[2],2010—2012年天津GDM患病率增加了3.5倍[3]。基于国际糖尿病和妊娠联合研究组(International Association of Diabetes and Pregnancy Study Group,IDPSG)新的诊断标准,天津市GDM患病率已达到9.3%。2017年一项研究显示北京市GDM的患病率高达19.7% [4]
        GDM的影响因素主要包括母亲年龄、母亲孕前肥胖、孕期增重、既往GDM史、家族糖尿病史、膳食营养、身体活动等。母亲年龄、既往GDM史、家族糖尿病史等属于短期内不易控制的危险因素。特别是随着全面"二孩"政策的实施,高龄产妇的比例期望增加,具有既往GDM史的产妇增加。随着糖尿病发病率升高,具有家族糖尿病史产妇比例亦可能增加。我们目前面临GDM发病上升的时代。因此亟待开展在孕期和围孕期可实施的干预措施,如控制母亲孕前肥胖和孕期增重,促进合理膳食营养和身体活动等来预防GDM。本文集中讨论GDM的膳食营养预防,而不考虑孕前已患糖尿病的膳食营养预防和GDM的膳食营养治疗。

一、营养素与GDM  胰岛β细胞分泌不足、孕期炎性反应、氧化应激等可能是胰岛素抵抗和GDM的重要原因。膳食营养素(蛋白质、碳水化合物、脂肪及脂肪酸、维生素和矿物质)摄入和营养状况与胰岛素分泌、炎性因子和氧化应激息息相关,可能影响GDM的发生发展。

1.蛋白质:  膳食蛋白质和氨基酸是葡萄糖代谢的重要调控因子,高膳食蛋白质摄入常伴有胰岛素抵抗。有研究结果显示,膳食蛋白质摄入量和种类可能与GDM的发生发展相关[5]。美国护士队列Ⅱ是一项纵向追踪的大型队列研究,从1989年开始对25~44岁妇女进行了定期追踪,研究对象多数为白人。在10年追踪过程中,15 294名妇女中共有21 457次单胎怀孕,发现870余名GDM新发病例。该队列研究中高膳食蛋白质组中蛋白质供能比为23.3%,其中动物性蛋白质的供能比为18.6%。低膳食蛋白质组蛋白质的供能比为15.2%,与我国孕妇膳食蛋白质推荐摄入量相近。该研究发现高动物性蛋白质摄入组,特别是高红肉蛋白质摄入,其随后GDM发生率增加1.49倍[RR(95%CI):1.49(1.03~2.17)],而植物性蛋白质摄入,特别是坚果摄入与GDM发生率呈负相关[RR(95%CI):0.69(0.50~0.97)]。用蛋白质取代碳水化合物摄入可显著增加GDM的发病率,用植物蛋白质取代动物蛋白质可降低GDM的发生率[5]。新加坡的一项亚裔人群横断面研究结果提示,高膳食蛋白质摄入量(平均供能比为19.9%)显著增加GDM患病比[OR(95%CI):2.15(1.27~3.62)][6],其低蛋白质组的蛋白质供能比为11.4%,同我国普通人群的蛋白质平均供能比相似。

2.碳水化合物:  碳水化合物种类(如膳食纤维、添加糖等)在2型糖尿病的预防控制中获得较好的效果。美国护士队列Ⅱ研究发现,膳食纤维,特别是谷类和水果类膳食纤维摄入量是GDM发病的保护因素[RR(95%CI):0.70(0.52~0.96)]。高血糖载荷(食物碳水化合物的量与其生糖指数的乘积)食物组的GDM发病率是低血糖载荷食物组的1.61倍[7]。含糖饮料摄入与2型糖尿病的关系一直是人们关注的热点。美国护士队列研究团队报道了高摄入含糖类可乐(≥5份/周)也会增加GDM的发病率1.22倍,而摄入其他含糖饮料与GDM无显著关联[8]。日本的一项队列研究结果显示,碳水化合物摄入量与GDM筛查阳性呈负相关[9]

3.脂肪:  脂肪酸在葡萄糖代谢发挥关键作用。正常妊娠时胎盘催乳素、孕酮和雌激素等激素水平升高可能引起机体脂肪动员,血中游离脂肪酸水平升高,促进胰岛素分泌增加,出现生理性胰岛素抵抗,来确保胎儿获得充足的葡萄糖供给。美国护士队列Ⅱ研究结果提示,随着动物脂肪摄入量的增加,GDM发病风险增加。用植物性脂肪取代动物性脂肪,GDM发病风险降低[10]。不同类型脂肪酸对GDM的影响可能不同。中国上海的一项研究结果显示,多不饱和脂肪酸摄入量是GDM的保护性因素,特别是对于BMI较高的人群影响更为明显[11]。大豆油是该人群重要的多不饱和脂肪酸来源(≥67%的多不饱和脂肪酸来源于大豆油),大豆油富含n-3多不饱和脂肪酸(α-亚麻酸)。多不饱和脂肪酸具有抗炎抗氧化的功能,可能会降低胰岛素抵抗和增加胰岛素敏感度。α-亚麻酸作为前体可以合成二十二碳六烯酸(DHA)。DHA可能改善胰岛素抵抗,降低血清胰岛素水平和HOMA-IR指数[12]。因此n-3多不饱和脂肪酸摄入量可能与GDM患病率呈负相关。然而在澳大利亚一项孕妇DHA随机双盲对照试验中,从孕20周左右开始给予800 mg/d DHA直到分娩,DHA补充组GDM发生率与对照组差异无统计学意义[13]。一项系统综述评价了n-3多不饱和脂肪酸补充对GDM的预防效果,未证实n-3多不饱和脂肪酸补充可以预防GDM的发生[14]

4.维生素D:  近年来人群维生素D缺乏问题越来越得到关注。2013年我国乳母维生素D缺乏和不足的比例(<20 ng/ml)高达70.6% [15]。维生素D营养状况与GDM关系的研究日益增多。一项巢式病例对照研究结果提示,GDM孕妇的血清25-OH维生素D3水平低于正常孕妇(23.9 ng/ml比26.7 ng/ml)[16],但调整了相关混杂因素后,维生素D营养状况与GDM的关联无统计学意义。西班牙的一项纵向研究分析了孕早期维生素D不足或缺乏状况(25-OH维生素D3<30 ng/ml)与GDM的关系,也未发现两者间存在相关[17]。但当血清25OHD3水平在20~29 ng/ml之间,同血清25-OH维生素D3水平<20 ng/ml相比,患GDM的OR(95%CI)值为0.53 (0.29~0.97)。澳大利亚一项维生素D补充随机对照试验,从孕20周前开始补充维生素D 5 000 IU/d,对照组补充400 IU/d维生素D直至分娩;每日补充5 000 IU维生素D未对GDM发病有显著影响(8%比13%,P=0.250);在每日补充400 IU维生素D组,基线维生素D水平与空腹血糖和糖耐量试验2 h血糖水平呈反比,即孕妇基线时25-OH维生素D3水平较低,其孕26~28周的空腹血糖和糖耐量试验2 h血糖水平较高[18]。一项包括20项观察性研究的系统综述评价了维生素D营养状况与GDM的关系,发现维生素D缺乏孕妇患GDM的OR(95%CI)值为1.53(1.33~1.75)。GDM孕妇的血清25-OH维生素D3水平约比非GDM孕妇低约2 ng/ml [19]。孕期维生素D补充可能会降低妊娠并发症(早产/妊娠期高血压综合征),但文中没有报道对GDM的影响[20]。一项Cochrane荟萃分析纳入2项维生素D补充随机对照试验,总样本量共219名孕妇。该研究结果提示,维生素D补充可能与GDM发生无关[OR(95%CI):0.43(0.05~3.45)][21,22]。其他荟萃分析结果也未发现维生素D补充对GDM的保护作用[23]

5.铁:  孕期铁缺乏十分普遍,全球范围内约19.2%的孕妇患有缺铁性贫血。2010—2012年中国孕妇贫血患病率为17.2% [24]。WHO推荐孕期给予铁补充剂来预防铁缺乏发生。然而铁作为氧化剂,机体储存过多的铁,可能造成胰岛β细胞受损,进而引起糖代谢异常。美国护士队列Ⅱ研究结果显示,高血红素铁摄入可显著增加患GDM风险[RR(95%CI):1.58(1.21~2.08)][25,26]。芬兰一项队列研究报道,对于孕早期非贫血孕妇,增加总铁摄入量可能会增加GDM发生风险,其调整RR(95%CI)为2.35(1.13~4.92)[27]。然而最近一项综述结果显示[28],在中国香港和芬兰进行的两项孕期铁补充随机干预试验发现孕期铁补充对GDM发病率无明显影响[29,30],虽然该结果可能受研究对象铁营养状况的影响。

6.肌醇:  肌醇是一个环己醇,可能具有增加胰岛素敏感性的功能。肌醇同葡萄糖的化学结构相似,在高血糖水平下,葡萄糖可能竞争性抑制细胞摄取肌醇。意大利的研究团队研究了不同GDM高危因素下(超重、肥胖、2型糖尿病家族史)肌醇补充的效果。结果显示,从孕早期开始每日两次给予2 g肌醇(4 g/d肌醇)可以显著降低GDM的发病率,其RR值分别0.33和0.34 [31,32]。孕早期或孕中期空腹血糖升高孕妇给予肌醇补充后,GDM发生率显著低于安慰剂组(OR=0.127)[33]。意大利和英国的系统性综述评价了肌醇补充对GD的影响,结果显示肌醇补充可降低GDM发生风险[34,35,36,37]

7.其他微量营养素:  一项横断面调查发现,GDM孕妇的膳食锌和硒的摄入低于正常孕妇,维生素摄入差异无统计学意义[38]。另一项病例-对照研究提示,GDM患者维生素C摄入量和血中抗坏血酸浓度均低于对照组[39]。另一项横断面研究报道,在孕中期补充多种微量营养素孕妇中,高维生素E摄入,其孕30周时空腹血糖水平和胰岛素抵抗指数较低[40]
        宏量营养素的质与量(如动物性蛋白质、植物性蛋白质、膳食纤维、动物性脂肪、植物油等)的摄入可能与GDM的发病相关。然而目前关于DHA、维生素D和铁补充预防GDM的效果仍不明确。肌醇补充可能预防GDM,有必要开展大样本研究来证实其有效性。除这几种营养素外,锌、硒、维生素C和维生素E营养状况与GDM的关系也需进一步研究来证实。

二、食物、膳食模式与GDM  单个食物与GDM的关系更容易受其他食物等混杂因素的影响,而且GDM可能是孕妇在多种食物长期暴露环境下的结局。膳食模式与GDM的关系可以综合反映膳食对GDM的影响。通过膳食指导预防GDM,可以明确膳食干预方法。功能性食物成分如益生菌和肌醇在GDM控制中受到关注。

1.膳食模式:  虽然食物消化吸收后以营养素的形式进入体内发挥各自生理功能,但孕妇直接摄入的是食物和各种食物组合。美国护士队列Ⅱ研究发现孕前以动物性食物为主的高蛋白质、高脂肪、低碳水化合物膳食模式可能使GDM发病风险增加[OR(95%CI):1.36 (1.13~1.64)],但孕前以植物性食物为主的高蛋白质、高脂肪和低碳水化合物膳食模式与GDM发病风险无显著关联[OR(95%CI):0.84 (0.69~1.03)][41]。澳大利亚的一项队列研究结果显示,孕前以地中海膳食模式为特征的膳食可降低GDM发生率,膳食模式部分通过改变孕前BMI而影响GDM的发生。而对于未遵循地中海膳食模式孕妇,其患GDM风险增加[OR(95%CI):1.35(1.02~1.60)][42]。坚持预防高血压膳食模式(dietary approaches to stop hypertension,DASH)或地中海膳食均可以降低空腹血糖浓度、糖化血红蛋白水平和GDM的比值[43]。对于肥胖或既往GDM史的GDM高危人群,遵循北欧营养推荐,健康膳食质量指数每增加1分,可以降低GDM的比值17% [44]。健康膳食质量指数与孕期空腹血糖水平和糖耐量试验2 h血糖水平呈负相关[45]。无论是地中海膳食模式,DASH模式,还是健康膳食指数模式,坚持以植物性食物为主的饮食均可以显著降低GDM发生风险[46]。在印度低收入人群中,通过增加绿叶蔬菜、水果和奶类的摄入,从而降低患GDM风险[OR(95%CI):0.56(0.36~0.86)][47]。孕前薯类摄入高可能增加GDM风险。减少薯类摄入,增加蔬菜、豆类摄入量可降低9%~12%GDM的风险[48]。海产品的摄入与GDM无明显关联[49]。虽然适量水果摄入可能有助于维持适宜孕期体重增长,但孕中期过量摄入水果却增加患GDM风险。孕中期水果摄入较高(上四分位组)与水果摄入较低(下四分位组)相比,其OR(95%CI)值为4.82 (2.38~9.76)。水果摄入过量增加GDM风险可能是由于水果的血糖指数或水果中多酚类化合物含量的影响[50]。美国护士队列Ⅱ研究结果显示,随着孕前油炸食物摄入频率增加,GDM发生风险逐步上升。孕前每周食用7次及以上油炸食物的孕妇患GDM风险增加2.18倍[51]。空间地理模型分析结果显示,在美国西式快餐店的数量较多地区,其人群GDM患病率较高[52]。进餐的时间也可能影响孕妇的血糖反应。对于体重正常孕妇,习惯性晚间(7点以后)进餐可以增加孕妇空腹血糖水平[53]

2.膳食指导:  芬兰2008—2014年在开展了一项对GDM高危人群(既往GDM史或肥胖)随机对照干预试验。干预内容包括膳食行为干预在内的生活方式干预。结果显示,从孕20周前开始给予营养指导和身体活动干预可显著降低GDM的发病率[54]。Cochrane荟萃分析结果显示,膳食指导可降低患GDM的风险,特别是对于超重或肥胖孕妇,但该综述仅包括6项随机干预试验,而且研究质量较低[55]。对于超重肥胖孕妇,膳食干预可显著降低GDM风险[OR(95%CI):0.40(0.18~0.86)] [37];在孕15周前干预效果明显,而15周后干预效果则不显著[56]

3.益生菌:  孕晚期每日食用含益生菌(嗜酸乳杆菌LA5和动物双歧杆菌BB12)酸奶9周,其血清胰岛素水平和HOMA-IR指数低于对照组[57]。在芬兰,含益生菌酸奶干预也显著降低孕妇血糖水平和胰岛素水平[58]。给予益生菌胶囊补充(鼠李糖乳杆菌GG和乳双歧杆菌Bb12)可降低GDM的发病风险(13% vs 36%)[59]。益生菌补充可能会降低患GDM风险[RR(95%CI):0.38(0.20~0.70)][60]。而爱尔兰的一项随机干预试验给予肥胖孕妇益生菌胶囊每日1粒,共4周,未能明显改变空腹血糖水平和GDM的发病率[61]

三、结语  虽然膳食因素与GDM发生之间的因果关联仍存在一些争议,但以植物性食物为主的健康膳食模式(诸如地中海膳食、DASH膳食)都有可能降低GDM的风险。高动物蛋白质、高脂肪和低碳水化合物的膳食模式可能增加GDM风险。在孕妇膳食指导时,应坚持以植物性食物和谷类为主的我国传统膳食模式。倡导孕妇食物的多样,动物性食物选择应以鱼禽蛋为佳,控制猪牛等红肉摄入,减少高脂油炸食物和含糖饮料如可乐的摄入量。谷类食物的选择宜以富含膳食纤维和低生糖指数的食物为首选。水果摄入应适量,避免过量。当然,孕期和孕前体重控制同样至关重要。
        营养素补充预防GDM的干预试验较少,亟待在我国孕妇人群中开展相关的干预研究。目前证据尚不支持DHA、维生素D、铁以及其他微量营养素补充与GDM之间存在关联。肌醇和益生菌有可能作为预防GDM的候选功能成分,值得进一步研究。

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