CN105998058A - 用于预防和改善胰岛素抵抗的营养组合物及其应用 - Google Patents
用于预防和改善胰岛素抵抗的营养组合物及其应用 Download PDFInfo
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Abstract
本发明公开了一种用于预防和改善胰岛素抵抗的营养组合物，包括VB3、甘氨酸、谷氨酸、胱氨酸、铬、VB1、VB12、VC、VE、VA、硒；通过改善糖尿病前期人群的糖脂代谢，促进机体外周组织对葡糖糖的摄取和利用，增加机体的葡萄糖氧化利用，促进肝脏糖代谢，降低IGR人群的空腹血糖水平，改善糖耐量，减轻胰岛素抵抗，改善血脂水平，改善机体周围组织对胰岛素的敏感性，减轻胰岛素抵抗，以改善其糖脂代谢、延缓和降低糖类吸收，调整肠道菌群结构，扶持有益肠道菌，清除条件致病菌，恢复肠道微生态，保证肠道的正常生理功能，缓解慢性炎症。
Description
技术领域
本发明涉及一种，特别涉及一种用于预防和改善胰岛素抵抗的营养组合物。
背景技术
糖尿病(DM)是以高血糖为主要特征的慢性代谢性疾病，它的特点是患病率高、医疗花费高和死亡率高。糖尿病前期(Pre-diabetes)也称糖调节受损(IGR)，是处于糖代谢正常与糖尿的异常状态，包括空腹血糖受损(IFG)、糖耐量减低(IGT)、空腹血糖受损合并量减低。我国成人IGR发生率高达50.1％，并逐年上升。IGR是DM发生前要移行期，是DM的预警信号，其以每年8％～10％的转化率进展为DM，20年DM发病率高达93％。IGR人群比一般人群发生DM的相对危险度明显增高IGR患者已出现胰岛素敏感性下降和胰岛素分泌障碍等代谢问题，并可显著增心血管疾病、肾脏疾病、视网膜病变、恶性肿瘤等的风险，报道显示其发生管疾病的风险已达糖尿病患者的1/3，患癌症风险比正常人增加15％。但IGR度可逆的，若及早进行干预，就可将异常糖代谢逆转为正常；若不及时采取干施，大量的IGR人群会在未来几年到十几年内发展成DM，而DM是不可逆的，而且DM的一系列并发症也将发生。且有研究表明对IGR者进行合理干预不仅可以降低其向DM的转化率，还能减少心血管病等慢性代谢性疾病的发病率。因此，应该特别重视血糖筛查，加强对肥胖、高糖、高脂饮食等高危人群的血糖监测，尽早发现IGR者并及时干预，争取从源头上控制DM，缓解其在世界更大范围的流行，同时减少或延缓心血管病等疾病的发生。DM患者肠道内存在菌群失调，与正常人相比，肠道内大肠杆菌等条件致病菌数量增加，双歧杆菌、乳酸杆菌等有益菌数量减少。肠道菌群组成最主要受饮食影响，不合理的膳食构成破坏了肠道菌群结构，产生免疫毒素，破坏肠道屏障功能，造成毒素入血，引起机体系统的慢性炎症，引发胰岛素抵抗、脂肪过度积累，最终形成DM等疾病。现有技术中，虽然二甲双胍能有效降低血糖，降低研究对象向DM的转变率，提高其向正常血糖的转变率，并可显著降低体重，尽管药物干预对IGR人群或许有效，但进行药物干预必定会大幅度增加医疗卫生支出，且IGR人群长期服药的依从性难以保证，目前并没有足够的证据表明药物干预具有长期疗效及卫生经济学益处，也并不了解药物是否能彻底改变IGR发展的自然病程，并且药物存在副作用。
发明内容
有鉴于此，本发明的目的在于提供一种用于预防和改善胰岛素抵抗的营养组合物，通过改善糖尿病前期人群的糖脂代谢，改善机体周围组织对胰岛素的敏感性，减轻胰岛素抵抗，以改善其糖脂代谢、延缓和降低糖类吸收，调整肠道菌群结构，扶持有益肠道菌，清除条件致病菌，恢复肠道微生态，保证肠道的正常生理功能，缓解慢性炎症，进一步提高胰岛素敏感性，恢复代谢损伤，减少或延缓糖尿病等慢性代谢性疾病的发生与发展。
本发明的用于预防和改善胰岛素抵抗的营养组合物，包括以下组分：100～300mgVB3、1～2g甘氨酸、1～2g谷氨酸、1～2g胱氨酸、150～250ug铬、10～30mg VB1、50～400ugVB12、1～2g VC、300～500mg VE、1200～2500ug VA、150～220ug硒；
进一步，所述改善剂包括以下组分：
200～300mg VB3、1～2g甘氨酸、1～2g谷氨酸、1～2g胱氨酸、150～200ug铬、15～30mg VB1、150～350ug VB12、1～2g VC、400～500mgVE、1300～2000ug VA、150～200ug硒；
进一步，所述改善剂包括以下组分：所述改善剂包括以下组分：
250mg VB3、1.5g甘氨酸、1.5g g谷氨酸、1.5g g胱氨酸、180ug铬、16mg VB1、250ugVB12、1.5g VC、450mgVE、1600ug VA、180ug硒；
进一步，可加入药学、食品学、保健品学上能够接受的载体制成制剂。
本发明还公开一种用于预防和改善胰岛素抵抗的营养组合物在制备改善胰岛素抵抗的食品、药品学、保健品中的应用。
本发明的有益效果：本发明的用于预防和改善胰岛素抵抗的营养组合物及其应用，床研究显示糖耐量因子(GTF)主要功能是加强胰岛素促进糖代谢和脂代谢。其具体机制可能是加强了葡萄糖的膜运输和细胞内葡萄糖的代谢途径。临床研究显示，GTF减少或缺乏导致的胰岛素活性降低是糖尿病的发病机制之一。目前发现GTF的主要成分为铬、烟酸、甘氨酸、谷氨酸和胱氨酸，因此，补充上述几种营养素有助于增加GTF的含量和活性，预防糖尿病的发生；通过改善糖尿病前期人群的糖脂代谢，促进机体外周组织对葡糖糖的摄取和利用，增加机体的葡萄糖氧化利用，促进肝脏糖代谢，降低IGR人群的空腹血糖水平，改善糖耐量，减轻胰岛素抵抗，改善血脂水平，改善机体周围组织对胰岛素的敏感性，减轻胰岛素抵抗，以改善其糖脂代谢、延缓和降低糖类吸收，调整肠道菌群结构，扶持有益肠道菌，清除条件致病菌，恢复肠道微生态，保证肠道的正常生理功能，缓解慢性炎症，进一步提高胰岛素敏感性，恢复代谢损伤，减少或延缓糖尿病等慢性代谢性疾病的发生与发展，安全无毒副作用，具有长期、稳定的效果，可替他日常膳食使用。而上述效果的实现，与各组分的配伍关系以及用量比优直接的关系，必须精确的选择个组分的用量使各组分充分发挥自己的优势作用。各组分的用量与其效果并不是相互叠加的关系，各组分的用量与组分之间的关系是一个有机的组合，上述各组分的用量使营养素达到一个最佳的平衡也不是通过有限次的试验就能获知的，而是需要考虑各组分的自身特点，组分之间的相互作用(抑制或协同)，营养素的供能比，外源性营养素与人体内的营养素之间的关系等因素控制各组分的用量达到经济与效果的最佳结合点，避免过犹不及，这是需要付出创造性劳动的。
VB1(硫胺素)作为能量代谢过程中必需的辅酶，促进葡萄糖、脂肪、蛋白质的正常氧化供能，此外，对维持神经、肌肉特别是心肌的正常功能，以及维持正常食欲、胃肠蠕动和消化分泌方面也有重要作用。
VB3(烟酸)，在体内以烟酰胺形式存在，是辅酶Ⅰ(NAD)和辅酶Ⅱ(NADP)的组成部分，参与体内能量代谢和氨基酸代谢，是糖耐量因子的组成部分之一，增加葡萄糖在体内的利用和促进葡萄糖转化为脂肪的作用，此外，烟酰胺还可以保护胰腺β细胞免于自身免疫破坏，对潜伏期和发生早期的糖尿病有很好的疗效。
甘氨酸、谷氨酸、胱氨酸作为人体的非必需氨基酸，它们是谷胱甘肽的合成原料，是糖耐量因子的组成部分之一，促进葡萄糖在体内的利用。胱氨酸使用剂量：1～2g/d，谷氨酸使用剂量：1～2g/d。其中甘氨酸也是一种较好的器官、组织、细胞保护剂。甘氨酸可抑制脂肪组织NF－κB、促炎因子表达，可减轻外周与中枢炎症和胰岛素抵抗(IR)。使用剂量：1～2g/d。。
硒：在人体内主要以含硒蛋白质形式存在，它是谷胱甘肽过氧化物酶及磷脂过氧化氢谷胱甘肽没的组成成分，该酶在人体内起抗氧化作用，能催化GSH与胞液中的过氧化物反应，防止过氧化物对机体的损伤。硒还具有抗癌、抗病毒等作用。推荐剂量。
铬：是人体必需的微量元素，是糖耐量因子的组成部分之一，它通过促进胰岛素与细胞受体的结合，增加胰岛素的生物学效应，对调节体内糖代谢、维持体内正常的葡萄糖耐量起重要作用。此外，铬具有调节脂类代谢和核酸(DNA和RNA)合成的作用。
VC、VE是具有抗氧化作用，两者具有协同作用，可防止胰岛细胞氧化损伤，维持细胞正常功能。
VC：作为电子供体具有抗氧化，还是强还原剂，它作为体内维持羟化酶活性所必需的辅助因子，参与体内许多重要物质的合成与代谢，如胶原蛋白、5-羟色胺、去甲肾上腺素等，此外还具有解毒、提高机体抵抗力的作用。
VE：主要生理功能是抗氧化作用，是体内最重要的脂溶性抗氧化剂和自由基清除剂。主要对抗生物膜上过氧化所产生的自由基，保护生物膜的结构与功能，使细胞膜维持正常的流动性，其作用机制是与过氧化脂质自由基形成反应性较低且相对稳定的生育酚自由基，后者可在VC或谷胱甘肽的作用下还原称非自由基产物生育酚。VE可调控多种基因表达，如生育酚代谢相关基因、与动脉粥样硬化发生发展相关基因、细胞黏附与抗炎的相关基因、细胞信号转导和细胞周期调节的相关基因等。因此，VE具有除抗氧化作用以外的多种功能，如具有抗炎、维持正常免疫功能和抑制细胞增殖的作用，预防动脉粥样硬化、抗衰老等作用。
VB12又称钴胺素，是唯一含金属元素的维生素，其中甲基钴胺素与5-脱氧腺苷钴胺素是体内活性辅酶形式参与机体的蛋氨酸、四氢叶酸、脂肪酸的合成与代谢，预防巨幼细胞贫血和维持中枢神经系统髓鞘的结构正常。
维生素A是一种脂溶性维生素,它的活性型包括视黄醇、视黄醛和维甲酸。其中全反式视黄酸作为胰岛素分泌促进剂增加胰岛素合成，参与葡萄糖诱导的胰岛素分泌；诱导肝葡萄糖激酶基因表达并提高该酶活性；此外，还可能通过减轻白细胞介素1及干扰素γ介导的细胞毒作用，延缓β细胞的损伤，对胰岛β细胞具有保护作用。
具体实施方式
实施例一
本实施例的用于预防和改善胰岛素抵抗的营养组合物，包括以下组分：100mgVB3、1g甘氨酸、1g谷氨酸、1g胱氨酸、150ug铬、10mg VB1、50ug VB12、1g VC、300mg VE、1200ug VA、150ug硒。
实施例二
本实施例的用于预防和改善胰岛素抵抗的营养组合物，包括以下组分：300mgVB3、2g甘氨酸、2g谷氨酸、2g胱氨酸、250ug铬、30mg VB1、400ug VB12、2g VC、500mg VE、2500ug VA、220ug硒。
实施例三
本实施例的用于预防和改善胰岛素抵抗的营养组合物，包括以下组分：
200mg VB3、1g甘氨酸、1g谷氨酸、1g胱氨酸、150ug铬、15mg VB1、150ug VB12、1gVC、400mgVE、1300ug VA、150ug硒。
实施例四
本实施例的用于预防和改善胰岛素抵抗的营养组合物，包括以下组分：
300mg VB3、2g甘氨酸、2g谷氨酸、2g胱氨酸、200ug铬、30mg VB1、350ug VB12、2gVC、500mgVE、2000ug VA、200ug硒。
实施例五
本实施例的用于预防和改善胰岛素抵抗的营养组合物，包括以下组分：
200mg VB3、2g甘氨酸、1g谷氨酸、2g胱氨酸、150ug铬、30mg VB1、150ug VB12、2gVC、400mgVE、2000ug VA、150ug硒。
实施例六
所述改善剂包括以下组分：所述改善剂包括以下组分：
250mg VB3、1.5g甘氨酸、1.5g g谷氨酸、1.5g g胱氨酸、180ug铬、16mg VB1、250ugVB12、1.5g VC、450mgVE、1600ug VA、180ug硒。
实施例七
本实施例的用于预防和改善胰岛素抵抗的营养组合物，包括以下组分：
200mg VB3、2g甘氨酸、1g谷氨酸、2g胱氨酸、150ug铬、30mg VB1、150ug VB12、2gVC、400mgVE、2000ug VA、150ug硒、100ug的白藜芦醇、50mg辣椒素、100mg山核桃提取物。
将上述实施例加入药学、食品学、保健品学上能够接受的载体制成制剂，可替代日常膳食使用。
将上述实施例的用于预防和改善胰岛素抵抗的营养组合物用于制备制备改善胰岛素抵抗的食品、药品学、保健品。
实验例：
方法以口服葡萄糖耐量试验(OGTT)筛查IGT患者115例，随机分成治疗组(58例)和对照组(57例)，治疗组予口服复合营养组合物(烟酸100mg/d、甘氨酸1g/d、谷氨酸1g/d、胱氨酸1g/d、铬200ug/d、VB1 50mg/d、VB12 100ug/d、VC500mg/d、VE300mg/d、VA 1500ugRE/d、硒100ug/d)，6个月；对照组不进行任何治疗。分别于治疗前后检测血糖(PG)及胰岛素(Ins)，用稳态模型评价胰岛素抵抗指数(HOMA-IR)及胰岛细胞分泌功能指数(HOMA-β)。
结果治疗组FPG、Ins及HOM-IR较试验前及对照组均明显下降，具有显著性差异(P<0.05)；HOMA-β无明显变化。对照组试验前后各项指标无明显变化。试验结束时,对照组有5例转为糖尿病(DM)，占8.7％，治疗组无DM发生。经x2检验两组DM的发生率差异无显著意义(x2＝8.7，P>0.05)。
结论复合营养组合物对IGT的胰岛素抵抗具有改善作用，减轻IR。
对象与方法
1、研究对象
从2012～2013年参加体检的人群中检出IGT患者115例，IGT的诊断根据1999年WHO标准,即口服糖耐量试验(OGTT)中,空腹血糖(FPG)<7.0mmol/L，服糖后2h血糖(2hPG)>7.8mmol/L而<11.1mmol/L者为IGT。所有IGT患者均为新诊断,未经过任何干预治疗。其中IGT合并高血压15例、高血脂17例、冠心病12例。均除外肝、肾及其他内分泌代谢性疾病。
2、试验设计
将115名IGT患者随机分成治疗组(58例)与对照组(57例)，试验前测量患者身高、体重、血压等指标；进行OGTT，检测0min及120min的血糖(PG)及胰岛素(Ins)，同时检测血清甘油三酯(TG)、胆固醇(TC)、尿素氮(BUN)及肌酐(Cr)等指标。治疗组予口服服复合营养组合物，对照组不予任何干预治疗，6个月后重复检测上述指标，试验期间两组均不进食任何营养保健品或补充剂，不改变饮食结构和习惯。
复合营养组合物来源于江苏圣协生物制剂公司生产的营养素单体，均由食物中提取而来，按照需求配制成粉末状(烟酸100mg、甘氨酸1g、谷氨酸1g、胱氨酸1g、铬200ug、VB150mg、VB12 100ug、VC 500mg、VE300mg、VA 1500ugRE、硒100ug)，每日一袋。
3、实验室检测
(1)OGTT：受试者分别于OGTT前及2h后抽取静脉血检测PG及Ins。
(2)Ins采用RIA法测定，试剂盒由第三军医大学试剂中心提供,批内C V 5.6％，批间C V 8.4％；PG采用GOD法测定；
(3)胰岛素抵抗指数(HOMA-IR)及胰岛细胞分泌功能指数(HOMA)采用稳态模型(HOMA Model)评价,计算公式为：
HOMA-IR＝FIns×FPG/22.5
HOMA-β＝20×FIns/(FPG-3.5)
四、统计学方法
数据用SPSS统计软件包处理,有关变量用x±s表示，组间差异用t检验,试验结束时两组IGT、DM的发生率用x2检验。Ins、HOMA-IR及HOMA-β取其自然对数值使其正态化后进入分析。
实验结果数据
1、试验前IGT患者一般临床资料
两试验组试验前、后及两试验组间各项指标体质指数(BMI)、T G、TC、BUN及Cr无明显差异；差异均无显著意义(P>0.05)(表1)。
表1 IGT患者的一半临床资料
2、治疗前两IGT组FPG、FIns、2hPG及2hIns、HOMA-IR、HOMA-β均无明显差异。复合营养组合物治疗6个月后,IGT治疗组FPG、2hPG、FIns、2hIns、HOMA-IR较试验前及对照组均明显下降，2hIns无明显变化；各组HOMA-β无明显变化。对照组试验前、后各项指标无明显变化(表2)。
表2治疗前后IGT患者的血糖、胰岛素、HOMA-IR及HOMA-β水平(x±s)
与对照组试验后相比#P<0.05；与治疗前相比ΔP<0.05。
3、试验结束时IGT患者DM的发生率
试验结束时，IGT对照组有5例发展为糖尿病，占8.7％，IGT治疗组无糖尿病出现。两组差异无显著意义(x2＝8.7,P>0.05)。
最后说明的是，以上实施例仅用以说明本发明的技术方案而非限制，尽管参照较佳实施例对本发明进行了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的宗旨和范围，其均应涵盖在本发明的权利要求范围当中。
Claims (5)
1.一种用于预防和改善胰岛素抵抗的营养组合物，其特征在于：包括以下组分：
100～300mg VB3、1～2g甘氨酸、1～2g谷氨酸、1～2g胱氨酸、150～250ug铬、10～30mgVB1、50～400ug VB12、1～2g VC、300～500mg VE、1200～2500ug VA、150～220ug硒。
2.根据权利要求1所述的用于预防和改善胰岛素抵抗的营养组合物，其特征在于：所述改善剂包括以下组分：
200～300mg VB3、1～2g甘氨酸、1～2g谷氨酸、1～2g胱氨酸、150～200ug铬、15～30mgVB1、150～350ug VB12、1～2g VC、400～500mgVE、1300～2000ugVA、150～200ug硒。
3.根据权利要求2所述的用于预防和改善胰岛素抵抗的营养组合物，其特征在于：所述改善剂包括以下组分：所述改善剂包括以下组分：
250mg VB3、1.5g甘氨酸、1.5g g谷氨酸、1.5g g胱氨酸、180ug铬、16mg VB1、250ug VB12、1.5g VC、450mgVE、1600ug VA、180ug硒。
4.根据权利要求1-3任一所述的用于预防和改善胰岛素抵抗的营养组合物，其特征在于：可加入药学、食品学、保健品学上能够接受的载体制成制剂。
5.一种权利要求1-3任一所述的用于预防和改善胰岛素抵抗的营养组合物在制备改善胰岛素抵抗的食品、药品学、保健品中的应用。
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| EP0652012A1 (en) * | 1989-03-27 | 1995-05-10 | Albert Naito | Combination of sugars with animo acids and other drugs |
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