Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität (LMU Munich, Germany;
Am J Physiol Endocrinol Metab. 2013 Nov 1;305(9):E1059-70. doi: 10.1152/ajpendo.00208.2013. Epub 2013 Aug 27.
Moderate low-carbohydrate/high-fat (LC-HF) diets are widely used to induce weight loss in overweight subjects, whereas extreme ketogenic LC-HF diets are used to treat neurological disorders like pediatric epilepsy. Usage of LC-HF diets for improvement of glucose metabolism is highly controversial; some studies suggest that LC-HF diets ameliorate glucose tolerance, whereas other investigations could not identify positive effects of these diets or reported impaired insulin sensitivity. Here, we investigate the effects of LC-HF diets on glucose and insulin metabolism in a well-characterized animal model. Male rats were fed isoenergetic or hypocaloric amounts of standard control diet, a high-protein "Atkins-style" LC-HF diet, or a low-protein, ketogenic, LC-HF diet. Both LC-HF diets induced lower fasting glucose and insulin levels associated with lower pancreatic β-cell volumes. However, dynamic challenge tests (oral and intraperitoneal glucose tolerance tests, insulin-tolerance tests, and hyperinsulinemic euglycemic clamps) revealed that LC-HF pair-fed rats exhibited impaired glucose tolerance and impaired hepatic and peripheral tissue insulin sensitivity, the latter potentially being mediated by elevated intramyocellular lipids. Adjusting visceral fat mass in LC-HF groups to that of controls by reducing the intake of LC-HF diets to 80% of the pair-fed groups did not prevent glucose intolerance. Taken together, these data show that lack of dietary carbohydrates leads to glucose intolerance and insulin resistance in rats despite causing a reduction in fasting glucose and insulin concentrations. Our results argue against a beneficial effect of LC-HF diets on glucose and insulin metabolism, at least under physiological conditions. Therefore, use of LC-HF diets for weight loss or other therapeutic purposes should be balanced against potentially harmful metabolic side effects.
适度低碳水化合物/高脂肪（LC-HF）饮食被广泛用于诱导超重人群减肥，而极端生酮 LC-HF 饮食则用于治疗儿科癫痫等神经疾病。LC-HF 饮食改善葡萄糖代谢的用途存在很大争议；一些研究表明 LC-HF 饮食改善了葡萄糖耐量，而其他研究则未能确定这些饮食的积极作用，或报告称其损害了胰岛素敏感性。在这里，我们在一种经过充分特征描述的动物模型中研究了 LC-HF 饮食对葡萄糖和胰岛素代谢的影响。雄性大鼠喂食等热量或低热量的标准对照饮食、高蛋白“阿特金斯式”LC-HF 饮食或低蛋白、生酮、LC-HF 饮食。两种 LC-HF 饮食均导致空腹血糖和胰岛素水平降低，同时伴有胰岛β细胞体积减小。然而，动态挑战测试（口服和腹腔内葡萄糖耐量测试、胰岛素耐量测试和高胰岛素正葡萄糖钳夹）显示，LC-HF 限食大鼠表现出葡萄糖耐量受损和肝及外周组织胰岛素敏感性受损，后者可能是由肌内甘油三酯升高介导的。通过将 LC-HF 组的内脏脂肪量调整为对照组，即减少 LC-HF 饮食的摄入量至限食组的 80%，但不能预防葡萄糖耐量受损。综上所述，这些数据表明，尽管 LC-HF 饮食可降低空腹血糖和胰岛素浓度，但缺乏膳食碳水化合物会导致大鼠出现葡萄糖不耐受和胰岛素抵抗。我们的结果表明，LC-HF 饮食对葡萄糖和胰岛素代谢至少在生理条件下没有有益作用。因此，LC-HF 饮食用于减肥或其他治疗目的时，应权衡其潜在的有害代谢副作用。
