Institut de Recherches Cliniques de Montréal (IRCM), Montreal, Quebec, Canada.
Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Am J Clin Nutr. 2018 Jul 1;108(1):62-76. doi: 10.1093/ajcn/nqy070.
To optimize the prevention of type 2 diabetes (T2D), high-risk obese subjects with the best metabolic recovery after a hypocaloric diet should be targeted. Apolipoprotein B lipoproteins (apoB lipoproteins) induce white adipose tissue (WAT) dysfunction, which in turn promotes postprandial hypertriglyceridemia, insulin resistance (IR), and hyperinsulinemia.
The aim of this study was to explore whether high plasma apoB, or number of plasma apoB lipoproteins, identifies subjects who best ameliorate WAT dysfunction and related risk factors after a hypocaloric diet.
Fifty-nine men and postmenopausal women [mean ± SD age: 58 ± 6 y; body mass index (kg/m2): 32.6 ± 4.6] completed a prospective study with a 6-mo hypocaloric diet (-500 kcal/d). Glucose-induced insulin secretion (GIIS) and insulin sensitivity (IS) were measured by 1-h intravenous glucose-tolerance test (IVGTT) followed by a 3-h hyperinsulinemic-euglycemic clamp, respectively. Ex vivo gynoid WAT function (i.e., hydrolysis and storage of 3H-triolein-labeled triglyceride-rich lipoproteins) and 6-h postprandial plasma clearance of a 13C-triolein-labeled high-fat meal were measured in a subsample (n = 25).
Postintervention first-phase GIISIVGTT and total C-peptide secretion decreased in both sexes, whereas second-phase and total GIISIVGTT and clamp IS were ameliorated in men (P < 0.05). Baseline plasma apoB was associated with a postintervention increase in WAT function (r = 0.61) and IS (glucose infusion rate divided by steady state insulin (M/Iclamp) r = 0.30) and a decrease in first-phase, second-phase, and total GIISIVGTT (r = -0.30 to -0.35) without sex differences. The association with postintervention amelioration in WAT function and GIISIVGTT was independent of plasma cholesterol (total, LDL, and HDL), sex, and changes in body composition. Subjects with high baseline plasma apoB (1.2 ± 0.2 g/L) showed a significant increase in WAT function (+105%; P = 0.012) and a decrease in total GIISIVGTT (-34%; P ≤ 0.001), whereas sex-matched subjects with low plasma apoB (0.7 ± 0.1 g/L) did not, despite equivalent changes in body composition and energy intake and expenditure.
High plasma apoB identifies obese subjects who best ameliorate WAT dysfunction and glucose-induced hyperinsulinemia, independent of changes in adiposity after consumption of a hypocaloric diet. We propose that subjects with high plasma apoB represent an optimal target group for the primary prevention of T2D by hypocaloric diets. This trial was registered at BioMed Central as ISRCTN14476404.
为了优化 2 型糖尿病（T2D）的预防，应该针对代谢恢复最佳的高危肥胖人群进行干预。载脂蛋白 B 脂蛋白（apoB 脂蛋白）会诱导白色脂肪组织（WAT）功能障碍，进而导致餐后高甘油三酯血症、胰岛素抵抗（IR）和高胰岛素血症。
本研究旨在探讨高血浆 apoB 或 apoB 脂蛋白数量是否可以识别出在低热量饮食后 WAT 功能障碍和相关危险因素改善最佳的人群。
59 名男性和绝经后女性[平均 ± 标准差年龄：58 ± 6 岁；体重指数（kg/m2）：32.6 ± 4.6]完成了一项前瞻性研究，为期 6 个月的低热量饮食（-500 千卡/天）。通过 1 小时静脉葡萄糖耐量试验（IVGTT）后测量葡萄糖诱导的胰岛素分泌（GIIS）和胰岛素敏感性（IS），然后进行 3 小时高胰岛素-正常血糖钳夹。在亚组（n=25）中测量女性臀肌 WAT 功能（即 3H-三油精标记的富含甘油三酯的脂蛋白的水解和储存）和 13C-三油精标记的高脂肪餐的 6 小时餐后血浆清除率。
干预后，两性的第一时相 GIIS-IVGTT 和总 C 肽分泌均下降，而男性的第二时相和总 GIIS-IVGTT 以及钳夹 IS 得到改善（P <0.05）。基线时血浆 apoB 与干预后 WAT 功能（r=0.61）和 IS（葡萄糖输注率除以稳态胰岛素（M/Iclamp）r=0.30）的增加以及第一时相、第二时相和总 GIIS-IVGTT 的减少相关（r=-0.30 至-0.35），且无性别差异。与干预后 WAT 功能和 GIIS-IVGTT 改善相关的关联独立于血浆胆固醇（总胆固醇、LDL 和 HDL）、性别和身体成分的变化。基线时血浆 apoB 较高（1.2±0.2 g/L）的受试者 WAT 功能显著增加（增加 105%；P=0.012），总 GIIS-IVGTT 降低（-34%；P≤0.001），而血浆 apoB 较低的匹配性别受试者（0.7±0.1 g/L）则没有，尽管身体成分和能量摄入和消耗有相同的变化。
高血浆 apoB 可识别出肥胖人群，这些人群在低热量饮食摄入后 WAT 功能障碍和葡萄糖诱导的高胰岛素血症改善最佳。我们提出，高血浆 apoB 的受试者代表通过低热量饮食进行 T2D 一级预防的最佳目标人群。该试验在生物医学中心注册为 ISRCTN14476404。
