Endocrinology-Diabetology Department, University-Hospital, Dijon, France.
Inserm UMR 1231, Medical School, University of Burgundy-Franche Comté, Dijon, France.
Diabetologia. 2022 Oct;65(10):1587-1600. doi: 10.1007/s00125-022-05765-8. Epub 2022 Jul 30.
Postprandial hyperlipidaemia is an important feature of diabetic dyslipidaemia and plays an important role in the development of cardiovascular disease in individuals with type 2 diabetes. Postprandial hyperlipidaemia in type 2 diabetes is secondary to increased chylomicron production by the enterocytes and delayed catabolism of chylomicrons and chylomicron remnants. Insulin and some intestinal hormones (e.g. glucagon-like peptide-1 [GLP-1]) influence intestinal lipid metabolism. In individuals with type 2 diabetes, insulin resistance and possibly reduced GLP-1 secretion are involved in the pathophysiology of postprandial hyperlipidaemia. Several factors are involved in the overproduction of chylomicrons: (1) increased expression of microsomal triglyceride transfer protein, which is a key enzyme in chylomicron synthesis; (2) higher stability and availability of apolipoprotein B-48; and (3) increased de novo lipogenesis. Individuals with type 2 diabetes present with disorders of cholesterol metabolism in the enterocytes with reduced absorption and increased synthesis. The increased production of chylomicrons in type 2 diabetes is also associated with a reduction in their catabolism, mostly because of a reduction in activity of lipoprotein lipase. Modification of the microbiota, which is observed in type 2 diabetes, may also generate disorders of intestinal lipid metabolism, but human data remain limited. Some glucose-lowering treatments significantly influence intestinal lipid absorption and transport. Postprandial hyperlipidaemia is reduced by metformin, pioglitazone, alpha-glucosidase inhibitors, dipeptidyl peptidase 4 inhibitors and GLP-1 agonists. The most pronounced effect is observed with GLP-1 agonists, which reduce chylomicron production significantly in individuals with type 2 diabetes and have a direct effect on the intestine by reducing the expression of genes involved in intestinal lipoprotein metabolism. The effect of sodium-glucose cotransporter 2 inhibitors on intestinal lipid metabolism needs to be clarified.
餐后高脂血症是糖尿病脂代谢紊乱的一个重要特征，在 2 型糖尿病患者心血管疾病的发生发展中起重要作用。2 型糖尿病的餐后高脂血症继发于肠上皮细胞生成乳糜微粒增加，以及乳糜微粒和乳糜微粒残粒的代谢缓慢。胰岛素和一些肠激素（如胰高血糖素样肽-1[GLP-1]）影响肠道脂质代谢。在 2 型糖尿病患者中，胰岛素抵抗和 GLP-1 分泌减少可能参与了餐后高脂血症的病理生理学过程。多种因素参与乳糜微粒的过度生成：（1）微粒体甘油三酯转移蛋白表达增加，该酶是乳糜微粒合成的关键酶；（2）载脂蛋白 B-48 的稳定性和可利用性更高；（3）从头合成脂肪酸增加。2 型糖尿病患者的肠上皮细胞胆固醇代谢紊乱，表现为吸收减少和合成增加。2 型糖尿病患者乳糜微粒生成增加，同时其代谢也减少，主要是由于脂蛋白脂肪酶活性降低。在 2 型糖尿病中观察到的肠道微生物群改变也可能导致肠道脂质代谢紊乱，但人类数据仍然有限。一些降糖治疗方法显著影响肠道脂质的吸收和转运。二甲双胍、吡格列酮、α-葡萄糖苷酶抑制剂、二肽基肽酶 4 抑制剂和 GLP-1 激动剂可降低餐后高脂血症。其中 GLP-1 激动剂的作用最为显著，可显著减少 2 型糖尿病患者的乳糜微粒生成，并通过降低参与肠道脂蛋白代谢的基因表达对肠道产生直接作用。钠-葡萄糖共转运蛋白 2 抑制剂对肠道脂质代谢的影响尚需阐明。
