2型糖尿病是21世纪全球最严重的公共卫生问题之一。研究表明，40%～50%的2型糖尿病患者合并脂代谢紊乱。脂代谢紊乱加速胰岛B细胞功能损伤、促进胰岛素抵抗、加重糖尿病患者大血管动脉粥样硬化。调查显示，大血管病变是糖尿病患者致残、致死的主要原因之一。因此，在有效降低血糖的基础上调节异常的脂代谢对于糖尿病的血糖控制及减缓并发症的发生有着重要的意义。在本文中作者主要阐述脂代谢紊乱对胰岛B细胞功能及胰岛素抵抗的影响机制，并着重探讨兼具糖脂代谢调节作用的控糖药物在此方面的研究进展。

[1] RABE K,LEHRKE M,PARHOFER K G,et al.Adipokines and insulin resistance[J]. Mol Med,2008,14(11/12):741-751.
[2] BHAT A,SEBASTIANI G,BHAT M.Systematic review:preventive and therapeutic applications of metformin in liver disease[J]. World J Hepatol,2015,7(12):1652-1659.
[3] ROUABHIA S,MILIC N,ABENAVOLI L.Metformin in the treatment of non-alcoholic fatty liver disease:safety,efficacy and mechanism[J]. Expert Rev Gastroenterol Hepatol,2014,8(4):343-349.
[4] TAN G D,FIELDING B A,CURRIE J M,et al.The effects of rosiglitazone on fatty acid and triglyceride metabolism in type 2 diabetes[J]. Diabetologia,2005,48:83-95.
[5] AL-MAJALI K,COOPER M B,STAELS B,et al.The effect of sensitization to insulin with pioglitazone on fasting and postprandial lipid metabolism,lipoprotein modification by lipases,and lipid transfer activities in type 2 diabetic patients[J]. Diabetologia,2006,49:527-537.
[6] CADOUDAL T,BLOUIN J M,COLLINET M,et al.Acute and selective regulation of glyceroneogenesis and cytosolicphosphoenolpyruvate carboxykinase in adipose tissue by thiazolidinediones in type 2 diabetes[J]. Diabetologia,2007,50:666-675.
[7] CHANGTING X,SATYA D,CECILIA M,et al.Gut peptides are novel regulators of intestinal lipoprotein secretion:experimental and pharmacological manipulation of lipoprotein metabolism[J]. Diabetes,2015,64:2310-2318.
[8] MONAMI M,DICEMBRINI I,NARDINI C,et al.Effects of glucagonlike peptide-1 receptor agonists on cardiovascular risk:a meta-analysis of randomized clinical trials[J]. Diabetes Obes Metab,2014,16:38-47.
[9] DAI X,WANG H,JING Z,et al.The effect of a dual combination of noninsulin antidiabetic drugs on lipids:a systematic review and network meta-analysis[J]. Curr Med Res Opin,2014,30:1777-1786.[ZK)]
[10] SUN F,WU S,WANG J,et al.Effect of glucagon-like peptide-1 receptor agonists on lipid profiles among type 2 diabetes:a systematic review and network meta-analysis[J]. Clin Ther,2015,37:225-241.
[11] BUNCK M C,CORNÉR A,ELIASSON B,et al.One-year treatment with exenatide vs.insulin glargine:effects on postprandial glycemia,lipid profiles,and oxidative stress[J]. Atherosclerosis,2010,212:223-229.
[12] KLONOFF D C,BUSE J B,NIELSEN L L,et al.Exenatide effects on diabetes,obesity,cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years[J]. Curr Med Res Opin,2008,24:275-286.
[13] HERMANSEN K,BÆKDAL T A,DÜRING M,et al.Liraglutide suppresses postprandial triglyceride and apolipoprotein B48 elevations after a fat-rich meal in patients with type 2 diabetes:a randomized,double-blind,placebo-controlled,cross-over trial[J]. Diabetes Obes Metab,2013,15:1040-1048.
[14] ZANDER M,MADSBAD S,MADSEN J L,et al.Effect of 6-week course of glucagon-like peptide 1 on glycaemic control,insulin sensitivity,and beta-cell function in type 2 diabetes:a parallel-group study[J]. Lancet,2002,359:824-830.
[15] HSIEH J,LONGUET C,BAKER L,et al.The glucagon-like peptide 1 receptor is essential for postprandial lipoprotein synthesis and ecretion in hamsters and mice[J]. Diabetologia,2010,53:552-561.
[16] TAGHIBIGLOU C,CARPENTIER A,van IDERSTINE S C,et al.Mechanisms of hepatic very low density lipoprotein overproduction in insulin resistance.Evidence for enhanced lipoprotein assembly,reduced intracellular ApoB degradation,and increased microsomal triglyceride transfer protein in a fructose-fed hamster model[J]. J Biol Chem,2000,275:8416-8425.
[17] EDWIN T P,YANAN W,JANINE J G,et al.GLP-1 receptor activation inhibits VLDL production and reverses hepatic steatosis by decreasing hepatic lipogenesis in high-fat-fed APOE*3-Leiden mice[J]. PLoS One,2012,7(11):e49152.
[18] 刘畅.新型統代谢综合征药物的筛选及发现[D]. 北京:北京协和医院,2015.
[19] 司梅梅.新型吲哚类衍生物和DPP-Ⅳ抑制剂的抗糖尿病作用及其机制研究[D]. 杭州:浙江大学,2014.
[20] CHAPMAN K,HOLMES M,SECKL J.11B-hydroxysteroid dehydrogenases:intracellular gate-keepers of tissue glucocorticoid action [J]. Physiol Rev,2013,93(3):1139-1206.
[21] MONDOK A,VARGA I,GLAZ E,et al.11beta-hydroxysteroid dehydrogenase activity in acromegalic patients with normal or impaired carbohydrate metabolism [J]. Steroids,2009,74(9):725-729.
[22] STIMSON R H,WALKER B R.The role and regulation of 11B-hydroxysteroid dehydrogenase type 1 in obesity and the metabolic syndrome [J]. Horm Mol Biol Clin Investig,2013,15(2):37-48.
[23] ROSENSTOCK J,BANARER S,FONSECA V A,et al.The 11-betahydroxysteroid dehydrogenase type 1 inhibitor INCB13739 improves hyperglycemia in patients with type 2 diabetes inadequately controlled by metformin monotherapy[J]. Diabetes Care,2010,33(7):1516-1522.
[24] KHARITONENKOV A,SHIYANOVA TL,KOESTER A,et al.FGF-21 as a novel metabolic regulator[J]. J Clin Invest,2005,115(6):1627-1635.
[25] WENTE W,EFANOV A M,BRENNER M,et al.Fibroblast growth factor-21 improves pancreatic beta-cell function and survival by activation of extra-cellular signal regulated kinase 1/2 and Akt signaling pathways [J]. Diabetes,2006,55(9):2470-2478.
[26] KHARITONENKOV A,WROBLEWSKI V J,KOESTER A,et al.The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21[J]. Endocrinology,2007,148(2):774-781.
[27] YILMAZ Y,EREN F,YONAL O,et al.Increased serum FGF21 level in patients with nonalcoholic fatty liver disese[J]. Eur J Clin Invest,2010,40(10):887-892.