口服年龄限制改善代谢综合征肥胖个体的胰岛素抵抗：一项随机对照试验。
Oral AGE restriction ameliorates insulin resistance in obese individuals with the metabolic syndrome: a randomised controlled trial.
作者信息
Vlassara Helen, Cai Weijing, Tripp Elizabeth, Pyzik Renata, Yee Kalle, Goldberg Laurie, Tansman Laurie, Chen Xue, Mani Venkatesh, Fayad Zahi A, Nadkarni Girish N, Striker Gary E, He John C, Uribarri Jaime
机构信息
Department of Geriatrics, Division of Experimental Diabetes and Aging, The Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY, 10029, USA.
Department of Medicine, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
出版信息
Diabetologia. 2016 Oct;59(10):2181-92. doi: 10.1007/s00125-016-4053-x. Epub 2016 Jul 29.
AIMS/HYPOTHESIS: We previously reported that obese individuals with the metabolic syndrome (at risk), compared with obese individuals without the metabolic syndrome (healthy obese), have elevated serum AGEs that strongly correlate with insulin resistance, oxidative stress and inflammation. We hypothesised that a diet low in AGEs (L-AGE) would improve components of the metabolic syndrome in obese individuals, confirming high AGEs as a new risk factor for the metabolic syndrome.
METHODS
A randomised 1 year trial was conducted in obese individuals with the metabolic syndrome in two parallel groups: L-AGE diet vs a regular diet, habitually high in AGEs (Reg-AGE). Participants were allocated to each group by randomisation using random permuted blocks. At baseline and at the end of the trial, we obtained anthropometric variables, blood and urine samples, and performed OGTTs and MRI measurements of visceral and subcutaneous abdominal tissue and carotid artery. Only investigators involved in laboratory determinations were blinded to dietary assignment. Effects on insulin resistance (HOMA-IR) were the primary outcome.
RESULTS
Sixty-one individuals were randomised to a Reg-AGE diet and 77 to an L-AGE diet; the data of 49 and 51, respectively, were analysed at the study end in 2014. The L-AGE diet markedly improved insulin resistance; modestly decreased body weight; lowered AGEs, oxidative stress and inflammation; and enhanced the protective factors sirtuin 1, AGE receptor 1 and glyoxalase I. The Reg-AGE diet raised AGEs and markers of insulin resistance, oxidative stress and inflammation. There were no effects on MRI-assessed measurements. No side effects from the intervention were identified. HOMA-IR came down from 3.1 ± 1.8 to 1.9 ± 1.3 (p < 0.001) in the L-AGE group, while it increased from 2.9 ± 1.2 to 3.6 ± 1.7 (p < 0.002) in the Reg-AGE group.
CONCLUSIONS/INTERPRETATION: L-AGE ameliorates insulin resistance in obese people with the metabolic syndrome, and may reduce the risk of type 2 diabetes, without necessitating a major reduction in adiposity. Elevated serum AGEs may be used to diagnose and treat 'at-risk' obesity.
TRIAL REGISTRATION
ClinicalTrials.gov NCT01363141 FUNDING: The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (DK091231).
目的/假设：我们之前报道过，患有代谢综合征的肥胖个体（处于风险中）与未患代谢综合征的肥胖个体（健康肥胖者）相比，血清晚期糖基化终末产物（AGEs）升高，且与胰岛素抵抗、氧化应激和炎症密切相关。我们假设低AGEs饮食（L-AGE）可改善肥胖个体的代谢综合征组分，从而证实高AGEs是代谢综合征的一个新风险因素。
方法
对患有代谢综合征的肥胖个体进行了一项为期1年的随机试验，分为两个平行组：L-AGE饮食组和常规饮食组（习惯性高AGEs饮食，Reg-AGE）。使用随机排列区组随机将参与者分配到每组。在基线和试验结束时，我们获取了人体测量变量、血液和尿液样本，并进行了口服葡萄糖耐量试验（OGTT）以及腹部内脏和皮下组织及颈动脉的磁共振成像（MRI）测量。只有参与实验室检测的研究人员对饮食分配不知情。对胰岛素抵抗（HOMA-IR）的影响是主要结局。
结果
61人被随机分配到Reg-AGE饮食组，7人被随机分配到L-AGE饮食组；2014年研究结束时分别分析了49人和51人的数据。L-AGE饮食显著改善了胰岛素抵抗；适度降低了体重；降低了AGEs、氧化应激和炎症；并增强了保护因子沉默调节蛋白1、AGE受体1和乙二醛酶I。Reg-AGE饮食增加了AGEs以及胰岛素抵抗、氧化应激和炎症的标志物。对MRI评估的测量结果无影响。未发现干预的副作用。L-AGE组的HOMA-IR从3.1±1.8降至1.9±1.3（p<0.001），而Reg-AGE组从2.9±1.2升至3.6±1.7（p<0.002）。
结论/解读：L-AGE可改善患有代谢综合征的肥胖者的胰岛素抵抗，并可能降低2型糖尿病风险，而无需大幅降低肥胖程度。血清AGEs升高可用于诊断和治疗“有风险”的肥胖症。
试验注册
ClinicalTrials.gov NCT01363141 资助：该研究由美国国立糖尿病、消化和肾脏疾病研究所（DK091231）资助。
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