Department of Internal Medicine, Maastricht University Medical Center, Maastricht, Netherlands.
CARIM School for Cardiovascular Diseases.
JCI Insight. 2022 Mar 22;7(6):e156950. doi: 10.1172/jci.insight.156950.
BACKGROUNDAccumulation of advanced glycation endproducts (AGEs) may contribute to the pathophysiology of type 2 diabetes and its vascular complications. AGEs are widely present in food, but whether restricting AGE intake improves risk factors for type 2 diabetes and vascular dysfunction is controversial.METHODSAbdominally obese but otherwise healthy individuals were randomly assigned to a specifically designed 4-week diet low or high in AGEs in a double-blind, parallel design. Insulin sensitivity, secretion, and clearance were assessed by a combined hyperinsulinemic-euglycemic and hyperglycemic clamp. Micro- and macrovascular function, inflammation, and lipid profiles were assessed by state-of-the-art in vivo measurements and biomarkers. Specific urinary and plasma AGEs Nε-(carboxymethyl)lysine (CML), Nε-(1-carboxyethyl)lysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were assessed by mass spectrometry.RESULTSIn 73 individuals (22 males, mean ± SD age and BMI 52 ± 14 years, 30.6 ± 4.0 kg/m2), intake of CML, CEL, and MG-H1 differed 2.7-, 5.3-, and 3.7-fold between the low- and high-AGE diets, leading to corresponding changes of these AGEs in urine and plasma. Despite this, there was no difference in insulin sensitivity, secretion, or clearance; micro- and macrovascular function; overall inflammation; or lipid profile between the low and high dietary AGE groups (for all treatment effects, P > 0.05).CONCLUSIONThis comprehensive RCT demonstrates very limited biological consequences of a 4-week diet low or high in AGEs in abdominally obese individuals.TRIAL REGISTRATIONClinicaltrials.gov, NCT03866343; trialregister.nl, NTR7594.FUNDINGDiabetesfonds and ZonMw.
晚期糖基化终产物 (AGEs) 的积累可能导致 2 型糖尿病及其血管并发症的病理生理学变化。AGEs 广泛存在于食物中，但限制 AGE 摄入是否能改善 2 型糖尿病和血管功能障碍的风险因素仍存在争议。
研究采用双盲、平行设计，将腹型肥胖但其他方面健康的个体随机分配到为期 4 周的 AGE 低或高饮食中。通过联合高胰岛素-正葡萄糖和高血糖钳夹评估胰岛素敏感性、分泌和清除率。通过最先进的体内测量和生物标志物评估微血管和大血管功能、炎症和脂质谱。通过质谱法评估特定的尿液和血浆 AGEs Nε-（羧甲基）赖氨酸 (CML)、Nε-（1-羧乙基）赖氨酸 (CEL) 和 Nδ-（5-羟-5-甲基-4-咪唑烷-2-基）-鸟氨酸 (MG-H1)。
在 73 名个体（22 名男性，平均年龄和 BMI 为 52 ± 14 岁，30.6 ± 4.0 kg/m2）中，CML、CEL 和 MG-H1 的摄入量在低和高 AGE 饮食之间相差 2.7、5.3 和 3.7 倍，导致尿液和血浆中这些 AGEs 相应变化。尽管如此，低和高饮食 AGE 组之间的胰岛素敏感性、分泌或清除率、微血管和大血管功能、整体炎症或脂质谱均无差异（所有治疗效果，P > 0.05）。
这项全面的 RCT 表明，腹型肥胖个体进行为期 4 周的低或高 AGE 饮食，其生物学后果非常有限。
Clinicaltrials.gov，NCT03866343；trialregister.nl，NTR7594。
糖尿病基金和 ZonMw。
