Chinese Journal of Tissue Engineering Research ›› 2019, Vol. 23 ›› Issue (35): 5682-5689.doi: 10.3969/j.issn.2095-4344.1891
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Society for Prevention and Control of Tissue Inflammation and Injury of Chinese Preventive Medicine Association; Society of Parenteral and Enteral Nutrition of Chinese Medical Association; Diabetic Foot Group, Committee of Peripheral Vascular Disease, China Society of Integrated Traditional Chinese and Western Medicine
Received:
2019-08-05
Online:
2019-12-18
Published:
2019-12-18
CLC Number:
Society for Prevention and Control of Tissue Inflammation and Injury of Chinese Preventive Medicine Association, Society of Parenteral and Enteral Nutrition of Chinese Medical Association, Diabetic Foot Group, Committee of Peripheral Vascular Disease, China Society of Integrated Traditional Chinese and Western Medicine. Medical nutrition treatment guideline for diabetic foot[J]. Chinese Journal of Tissue Engineering Research, 2019, 23(35): 5682-5689.
4 能量 Energy 所有糖尿病患者均应接受经临床营养师专业评估后制定的个体化能量平衡计划,其目标既要满足达到或维持理想体重的要求,又要符合不同情况下的营养需要[1]。对于糖尿病足患者而言,这种特殊的营养需求主要集中在创面合并严重感染时,补充机体代谢消耗,增加机体抵御风险能力;在感染控制、创面恢复期,提供所需能量;在创面愈合后,实现能量平衡/负平衡,达到/维持理想体重,维持血糖平稳,控制HbA1c达标。不推荐糖尿病及足病患者长期接受极低能量(<3 348.7 kJ/d,相当于800 kcal/d)营养治疗。 5 宏量营养素 Macronutrients 5.1 碳水化合物 碳水化合物的摄入量及其引起的胰岛素分泌反应是引起血糖变化的关键因素,对摄入的碳水化合物精确/经验计量,是控制血糖达标的重要手段[17]。目前,尚缺乏相关证据指出糖尿病及合并足部病变患者每日所需理想碳水化合物摄入量[15],这可能与食物中提供的各种碳水化合物对机体血糖负荷不同有关[19]。且有研究证实,在合并创面患者机体中,适量碳水化合物的摄入可有效促进纤维母细胞合成,并在白细胞抗炎过程中起重要作用[41]。因此,推荐在碳水化合物的摄入中尽可能选择高质量碳水化合物,即高营养密度、富含膳食纤维、维生素及矿物质、少/不伴添加糖、脂肪及盐的碳水化合物[15-16]。虽然,“升糖指数(glycemic index,GI)”这一概念的提出,可以很好预测进食后血糖波动峰值及变化趋势[42],但有系统回顾研究指出摄入低GI碳水化合物对改善HbA1c无益,且对空腹血糖的影响不尽一致[43]。但仍推荐糖尿病足病患者在高质量碳水化合物范围内选择GI较低的品类,主要是因为:①血糖波动(平均及最大幅度)经证实与糖尿病下肢血管病变显著相关[44],而选择低GI碳水化合物可有效减小进食后血糖波动,从而减少对缺血性糖尿病足病患者的下肢血管的进一步损害;②低GI碳水化合物对血糖影响较小,可相应减少血糖依赖性胰岛素分泌及对外源注射用胰岛素需求量,从而减少胰岛素介导的抑制脂肪动员、促进脂肪及胆固醇合成的作用,达到控制体重的目的[45]。此外,患者应避免饮用包含果汁在内的各种含糖饮料,最新研究指出,果糖摄入过多,亦可明显增加体重,且此时的增重以脂肪为主[46]。关于是否需要特异性增加膳食纤维摄入量的问题,由于在实际临床研究过程中,在增加膳食纤维摄入的同时多增加低GI碳水化合物摄入占比[47],故高膳食纤维(>50 g/d)饮食与血糖控制的相关性无法一概而论,且高膳食纤维饮食常见胃肠胀气及腹泻等不适,所以,推荐糖尿病及合并足病患者,其膳食纤维摄入量与健康人群摄入量至少保持一致[15],为(14 g/4 185.8 kJ,相当于14 g/1 000 kcal),或为女性25 g/d,男性38 g/d[48]。 5.2 蛋白质 对于无糖尿病肾病风险患者,传统认为,应保证每日0.8 g/kg蛋白质摄入量。而ADA 2019年最新发布的糖尿病医学管理标准及医学营养治疗专家共识中指出,目前并无证据支持推荐蛋白质最佳摄入量,应以个体健康状况及需求为参考,制定科学摄入计划[14-15]。有研究提出该类患者每日蛋白质摄入量应为1.0-1.5 g/kg,或至少达到全部热卡来源的15%[49]。而对于合并肾脏风险患者,考虑减少蛋白质摄入并不会在改善血糖、预防心血管事件、延缓肾小球滤过率下降病程等方面获益[50-53],故并不推荐限制蛋白质摄入[54]。在实际临床工作中,常见糖尿病合并足部病变患者也常合并有不同程度肾脏损害,对于该类患者,减少蛋白质摄入不仅无益于其肾病进展,还可能影响其足部创面愈合。有综述性文献总结后支持对于确诊合并营养不良的糖尿病足病患者,应给予1.0-2.0 g/kg蛋白质,并特异性补充谷氨酰胺及精氨酸,有助于创面愈合[55]。因此,推荐糖尿病足患者,尤其伴持续不愈合足部溃疡患者,在不减少蛋白质摄入的基础上,调整蛋白质供应比例,充分重视优质蛋白质供应,并特异性补充于创面预后有益的谷氨酰胺及精氨酸。由于蛋白质可引起不依赖血糖升高的促胰岛素分泌反应[56],故以蛋白质供能治疗或预防低血糖无效,也因此不推荐有低血糖风险因素患者选择各种形式的高蛋白质饮食方式。 5.3 脂肪 推荐根据患者具体情况设定每日脂肪摄入量,相比于摄入量,摄入脂肪的质量更加重要[14]。虽然,人体所需必须脂肪酸较多为长链脂肪酸,但有较多可信度确实的研究指出,高单不饱和脂肪酸饮食(供能比10%-20%)有助于血糖控制及改善CVD风险[57-58],这可能也是以单不饱和脂肪酸食物作为重要组件的地中海饮食方式得到广泛推崇的主要原因之一。因此,结合中国营养学会相关指南推荐[59-60],长链饱和脂肪酸、单不饱和脂肪酸及多不饱和脂肪酸摄入比例以1∶1∶1为宜。中链脂肪酸结构特异性,更易经人体利用代谢生成酮体,结合糖尿病足患者实际情况,有增加其继发酮症及代谢性酸中毒可能的风险,故在其医学营养治疗中,无额外添加中链脂肪酸必要性。虽然综合目前研究结果,尚无法确定加强ω-3脂肪酸补充对糖尿病患者有改善血糖控制及减少CVD风险的显著效果;但一项最新的随机对照研究结果指出,对糖尿病足患者在一段时间(3个月)内特异性补充亚麻籽油来源ω-3脂肪酸(1 000 mg,2次/d)可使患者足部创面面积及深度明显减小[61],分析这可能与ω-3脂肪酸减少炎症因子产 生[62]、通过抑制核因子活化B细胞κ轻链增强子活化减少炎症反应与氧化应激有关[63-64],提示对糖尿病足患者可以考虑短期内特异性补充ω-3脂肪酸,有助创面愈合及感染控制。避免摄入反式脂肪酸。 6 微量营养素 Micronutrients 虽然无相关证据表明特异性补充微量营养素(维生素及微量矿物质)可使糖尿病患者显著获益,相关指南均推荐糖尿病患者各种微量营养素摄入量与健康群体保持一致[1,14-17]。但针对糖尿病足病患者,有较多临床研究提示特异性补充微量营养素,可显著促进足部创面愈合。 6.1 维生素A 糖尿病足创面的愈合过程主要分为血小板聚集、白细胞参与抗感染、纤维母细胞迁移/增殖及肌纤维细胞重塑4个阶段[65],而维生素A的重要作用,可谓贯穿创面愈合全程:在抗感染阶段,维生素A缺乏可影响B细胞及T细胞功能,使抗体合成大幅减少[66];在纤维母细胞增殖及肌纤维细胞重塑阶段,维生素A缺乏又将影响上皮细胞产生、胶原蛋白连结以及肉芽组织形成[67]。故推荐有条件的患者,在短期内特异性补充维生素A 10 000-25 000 IU/d[68]。 6.2 维生素B 维生素B由硫胺素、核黄素、吡哆醇、叶酸、泛酸盐和钴胺素组成,是参与白细胞形成的酶反应和创面愈合的合成代谢过程中必不可少的辅因子。其中硫胺素、核黄素、吡哆醇和钴胺素也是合成胶原蛋白所必需的[7]。因此,维生素B缺乏将直接影响创面愈合,减少发生感染相关并发症风险[69]。其中维生素B9,即叶酸,在糖尿病创面动物模型中观察到经特异性补充 3 mg/(kg·d),可使创面愈合时间明显缩短,创面愈合率明显升高,这可能与其抗氧化作用有关[70]。其在糖尿病足患者中的作用尚有待临床试验进一步证实。在各种B族维生素的搭配组合中,有纤维母细胞体外划痕实验证实,维生素B3、B5、B6、B10及维生素B9、B12,和维生素B3、B5、B7的组合可在细胞培养24-48 h是划痕面积明显缩小[71]。且维生素B12衍生物甲钴胺可有效改善糖尿病相关神经病变引起的下肢感觉异常[20]。推荐补充复合维生素B族使糖尿病足患者广泛获益。 6.3 维生素C 维生素C除参与免疫细胞形成巨噬细胞过程[72],还可胶原纤维间形成额外胶连,以增加胶原蛋白的强度及稳定性[73]。一项应用灌胃大剂量维生素C[1.2 g/(kg·d)]治疗糖尿病创面小鼠模型的研究指出,大剂量维生素C对创面愈合的积极作用可能与其促进创面毛细血管再生相关[41]。目前推荐维生素C补充量在单纯创面患者为500 mg/d,在复杂创面患者为2 g/d[66],但结合动物试验研究结果,可能该推荐量尚趋于保守。 6.4 维生素D 虽然目前尚无证据证明常规或特异性补充维生素D有益于糖尿病足创面治疗,但在静脉性下肢溃疡、经检测合并维生素D缺乏患者特异性补充维生素D,可使创面面积明显缩小[74]。 6.5 锌 皮肤是人体中含锌量居第3位的组织结构[75],锌缺乏必将导致皮肤组织结构的改变和破坏,引起皮肤屏障功能减退,形成创面,甚至溃疡。伊朗学者Larijani等[76]观察发现糖尿病合并足部创面患者群体血清锌水平明显低于单纯糖尿病患者,提示特异性补充锌或可帮助创面愈合。目前关于推荐锌补充量尚无定论,但须注意,锌超量将影响其他微量矿物质,如铜、铁的吸收利用,导致其他生理问题。 6.6 铁 铁剂补充对于糖尿病足患者的显著增益,主要体现在3个方面:其一,铁通过参与脯氨酸及赖氨酸的羟基化过程,促进胶原蛋白合成[77];其二,糖尿病足患者由于营养不良、创面渗血等多种原因合并有不同程度贫血,最新数据提示贫血在糖尿病足患者中发生率高达85.3%,且缺铁原因导致贫血占该患者群体一半以上[78],在血源紧缺、输血不良反应发生、患者拒绝输血治疗等特殊情况下,铁剂补充或成为改善患者贫血状况的有效方式;最后,铁可以与糖蛋白结合,形成乳铁蛋白,经腺上皮细胞分泌后,起效于创面感染阶段,抑制机体对新鲜肉芽组织及再生上皮的过分免疫应答[75],促进胶原蛋白合成所需的纤维母细胞及角化细胞迁移行为[79]。关于补充剂量推荐,建议结合患者血液常规及铁代谢化验结果,制定个体化补充目标,予口服或/和静脉补充。 7 随访 Follow-up 营养治疗应贯穿糖尿病足病患者疾病管理始终,对于创面治疗有效患者,建议其营养治疗应以门诊复诊、持续随访方式进行,可与创面门诊复诊同时进行。随访内容包括每日营养日记、体重变化、人体代谢成分变化、自我血糖监测结果等。其中自我血糖监测结果是评价营养治疗效果的重要指标。推荐严格自我血糖监测7次/d,分别测定空腹、三餐前后及睡前指血血糖并记录。考虑患者可耐受程度及操作难度,推荐持续血糖监测,可使患者在HbA1c改善、减小血糖波动及避免低血糖事件方面显著获益[80]。"
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