• ISSN 16748301
  • CN 32-1810/R
Volume 33 Issue 1
Jan.  2019
Article Contents


Postprandial hyperglycemia and postprandial hypertriglyceridemia in type 2 diabetes

  • Postprandial glucose level is an independent risk factor for cardiovascular disease that exerts effects greater than glucose levels at fasting state, whereas increase in serum triglyceride level, under both fasting and postprandial conditions, contributes to the development of arteriosclerosis. Insulin resistance is a prevailing cause of abnormalities in postabsorptive excursion of blood glucose and postprandial lipid profile. Excess fat deposition renders a vicious cycle of hyperglycemia and hypertriglyceridemia in the postprandial state, and both of which are contributors to atherosclerotic change of vessels especially in patients with type 2 diabetes mellitus. Several therapeutic approaches for ameliorating each of these abnormalities have been attempted, including various antidiabetic agents or new compounds targeting lipid metabolism.
  • 加载中
  • [1] Group TDS, and the The DECODE Study Group. Group on behalf of the EDE. Is the current definition for diabetes relevant to mortality risk from all causes and cardiovascular and noncardiovascular diseases[J]? Diabetes Care, 2003, 26(3):688-696.
    [2] Levitan EB, Song Y, Ford ES, et al. Is nondiabetic hyperglycemia a risk factor for cardiovascular disease[J]? Arch Intern Med, 2004, 164(19):2147-2155.
    [3] DECODE Study Group, and the European Diabetes Epidemiology Group. Glucose tolerance and cardiovascular mortality:comparison of fasting and 2-hour diagnostic criteria[J]. Arch Intern Med, 2001, 161(3):397-405.
    [4] Sone H, Tanaka S, Tanaka S, et al. Serum level of triglycerides is a potent risk factor comparable to LDL cholesterol for coronary heart disease in Japanese patients with type 2 diabetes:Subanalysis of the Japan Diabetes Complications Study (JDCS)[J]. J Clin Endocrinol Metab, 2011, 96(11):3448-3456.
    [5] Nakamura H, Arakawa K, Itakura H, et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study):a prospective randomised controlled trial[J]. Lancet, 2006, 368(9452):1155-1163.
    [6] Iso H, Imano H, Yamagishi K, et al. Fasting and non-fasting triglycerides and risk of ischemic cardiovascular disease in Japanese men and women:the Circulatory Risk in Communities Study (CIRCS)[J]. Atherosclerosis, 2014, 237(1):361-368.
    [7] Zilversmit DB. Atherogenesis:a postprandial phenomenon[J]. Circulation, 1979, 60(3):473-485.
    [8] Monnier L, Colette C, Dunseath GJ, et al. The loss of postprandial glycemic control precedes stepwise deterioration of fasting with worsening diabetes[J]. Diabetes Care, 2007, 30(2):263-269.
    [9] Kodama K, Tojjar D, Yamada S, et al. Ethnic differences in the relationship between insulin sensitivity and insulin response:A systematic review and meta-analysis[J]. Diabetes Care, 2013, 36(6):1789-1796.
    [10] Wu L, Parhofer KG. Diabetic dyslipidemia[J]. Metabolism, 2014, 63(12):1469-1479.
    [11] Node K, Inoue T. Postprandial hyperglycemia as an etiological factor in vascular failure[J]. Cardiovasc Diabetol, 2009, 8(1):23.
    [12] Tomkin GH, Owens D. Dyslipidaemia of diabetes and the intestine[J]. World J Diabetes, 2015, 6(7):970-977.
    [13] Ceriello A, Genovese S. Atherogenicity of postprandial hyperglycemia and lipotoxicity[J]. Rev Endocr Metab Disord, 2016, 17(1):111-116.
    [14] Rizza RA. Pathogenesis of fasting and postprandial hyperglycemia in type 2 diabetes:Implications for therapy[J]. Diabetes, 2010, 59(11):2697-2707.
    [15] Ginsberg HN. Review:Efficacy and mechanisms of action of statins in the treatment of diabetic dyslipidemia[J]. J Clin Endocrinol Metab, 2006, 91(2):383-392.
    [16] Bonora E, Corrao G, Bagnardi V, et al. Prevalence and correlates of post-prandial hyperglycaemia in a large sample of patients with type 2 diabetes mellitus[J]. Diabetologia, 2006, 49(5):846-854.
    [17] Pratley RE, Weyer C. The role of impaired early insulin secretion in the pathogenesis of Type Ⅱ diabetes mellitus[J].Diabetologia, 2001, 44(8):929-945.
    [18] Fineman MS, Koda JE, Shen LZ, et al. The human amylin analog, pramlintide, corrects postprandial hyperglucagonemia in patients with type 1 diabetes[J]. Metabolism, 2002, 51(5):636-641.
    [19] Koda JE, Fineman M, Rink TJ, et al. Amylin concentrations and glucose control[J]. Lancet, 1992, 339(8802):1179-1180.
    [20] Holst JJ, Gromada J. Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans[J]. Am J Physiol Endocrinol Metab, 2004, 287(2):E199-E206.
    [21] Toft-Nielsen MB, Damholt MB, Madsbad S, et al. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients[J]. J Clin Endocrinol Metab, 2001, 86(8):3717-3723.
    [22] Meier JJ, Nauck MA. Is the diminished incretin effect in type 2 diabetes just an epi-phenomenon of impaired beta-cell function[J]? Diabetes, 2010, 59(5):1117-1125.
    [23] Little TJ, Pilichiewicz AN, Russo A, et al. Effects of intravenous glucagon-like peptide-1 on gastric emptying and intragastric distribution in healthy subjects:relationships with postprandial glycemic and insulinemic responses[J]. J Clin Endocrinol Metab, 2006, 91(5):1916-1923.
    [24] Drucker DJ, Nauck MA. The incretin system:glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes[J]. Lancet, 2006, 368(9548):1696-1705.
    [25] Haller H, Lindschau C, Quass P, et al. Differentiation of vascular smooth muscle cells and the regulation of protein kinase C-alpha[J]. Circ Res, 1995, 76(1):21-29.
    [26] Goetze S, Xi XP, Kawano Y, et al. TNF-alpha-induced migration of vascular smooth muscle cells is MAPK dependent[J]. Hypertension, 1999, 33(1):183-189.
    [27] Anderson TJ. Assessment and treatment of endothelial dysfunction in humans[J]. J Am Coll Cardiol, 1999, 34(3):631-638.
    [28] Giacco F, Brownlee M. Oxidative stress and diabetic complications[J]. Circ Res, 2010, 107(9):1058-1070.
    [29] Wu J, Xia S, Kalionis B, et al. The role of oxidative stress and inflammation in cardiovascular aging[J]. BioMed Res Int, 2014(2):615312.
    [30] Harrison DG. Cellular and molecular mechanisms of endothelial cell dysfunction[J]. J Clin Invest, 1997, 100(9):2153-2157.
    [31] Monnier L, Mas E, Ginet C, et al. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes[J]. JAMA, 2006, 295(14):1681-1687.
    [32] Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients:Variations with increasing levels of HbA1c[J]. Diabetes Care, 2003, 26(3):881-885.
    [33] Ceriello A, Falleti E, Motz E, et al. Hyperglycemia-induced circulating ICAM-1 increase in diabetes mellitus:the possible role of oxidative stress[J]. Horm Metab Res, 1998, 30(3):146-149.
    [34] Shuto Y, Asai A, Nagao M, et al. Repetitive glucose spikes accelerate atherosclerotic lesion formation in C57BL/6 mice[J]. PLoS One, 2015, 10(8):e0136840.
    [35] Mandosi E, Giannetta E, Filardi T, et al. Endothelial dysfunction markers as a therapeutic target for Sildenafil treatment and effects on metabolic control in type 2 diabetes[J]. Expert Opin Ther Targets, 2015, 19(12):1617-1622.
    [36] Firth RG, Bell PM, Marsh HM, et al. Postprandial hyperglycemia in patients with noninsulin-dependent diabetes mellitus. Role of hepatic and extrahepatic tissues[J]. J Clin Invest, 1986, 77(5):1525-1532.
    [37] Unger RH, Orci L. The essential role of glucagon in the pathogenesis of diabetes mellitus[J]. Lancet, 1975, 1(7897):14-16.
    [38] Kawamori D, Kurpad AJ, Hu J, et al. Insulin signaling in alpha cells modulates glucagon secretion in vivo[J]. Cell Metab, 2009, 9(4):350-361.
    [39] Ahren B. Beta-and alpha-cell dysfunction in subjects developing impaired glucose tolerance:outcome of a 12-year prospective study in postmenopausal Caucasian women[J]. Diabetes, 2009, 58(3):726-731.
    [40] Henquin JC, Rahier J. Pancreatic alpha cell mass in European subjects with type 2 diabetes[J]. Diabetologia, 2011, 54(7):1720-1725.
    [41] Kubota N, Kubota T, Itoh S, et al. Dynamic functional relay between insulin receptor substrate 1 and 2 in hepatic insulin signaling during fasting and feeding[J]. Cell Metab, 2008, 8(1):49-64.
    [42] Kubota T, Kubota N, Kumagai H, et al. Impaired insulin signaling in endothelial cells reduces insulin-induced glucose uptake by skeletal muscle[J]. Cell Metab, 2011, 13(3):294-307.
    [43] The Diabetes Control and Complications Trial Research Group. The Effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus[J]. N Engl J Med, 1993, 329(14):977-986.
    [44] UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)[J]. Lancet, 1998, 352(9131):837-853.
    [45] Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus:a randomized prospective 6-year study[J]. Diabetes Res Clin Pract, 1995, 28(2):103-117.
    [46] Turner RC, Millns H, Holman RR, et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus:United Kingdom prospective diabetes study (UKPDS:23)[J]. BMJ, 1998, 316(7134):823-828.
    [47] Tominaga M, Eguchi H, Manaka H, et al. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose. The Funagata Diabetes Study[J]. Diabetes Care, 1999, 22(6):920-924.
    [48] Nakagami T, Qiao Q, Tuomilehto J, et al. Screen-detected diabetes, hypertension and hypercholesterolemia as predictors of cardiovascular mortality in five populations of Asian origin:the DECODA study[J]. Eur J Cardiovasc Prev Rehabil, 2006, 13(4):555-561.
    [49] Hanefeld M, Cagatay M, Petrowitsch T, et al. Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients:meta-analysis of seven long-term studies[J]. Eur Heart J, 2004, 25(1):10-16.
    [50] Ceriello A, Esposito K, Piconi L, et al. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients[J]. Diabetes, 2008, 57(5):1349-1354.
    [51] de Vries M, Klop B, Castro Cabezas M. The use of the nonfasting lipid profile for lipid-lowering therapy in clinical practice-point of view[J]. Atherosclerosis, 2014, 234(2):473-475.
    [52] Rosenson RS, Davidson MH, Hirsh BJ, et al. Genetics and causality of triglyceride-rich lipoproteins in atherosclerotic cardiovascular disease[J]. J Am Coll Cardiol, 2014, 64(23):2525-2540.
    [53] White KT, Moorthy MV, Akinkuolie AO, et al. Identifying an optimal cutpoint for the diagnosis of hypertriglyceridemia in the nonfasting state[J]. Clin Chem, 2015, 61(9):1156-1163.
    [54] Langsted A, Nordestgaard BG. Nonfasting Lipid Profiles:The Way of the Future[J]. Clin Chem, 2015, 61(9):1123-1125.
    [55] Syvänne M, Taskinen MR. Lipids and lipoproteins as coronary risk factors in non-insulin-dependent diabetes mellitus[J]. Lancet, 1997, 350(Suppl):SI20-SI23.
    [56] Adiels M, Boren J, Caslake MJ, et al. Overproduction of VLDL1 driven by hyperglycemia is a dominant feature of diabetic dyslipidemia[J]. Arterioscler Thromb Vasc Biol, 2005, 25(8):1697-1703.
    [57] Bansal S, Buring JE, Rifai N, et al. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women[J]. JAMA, 2007, 298(3):309-316.
    [58] Harchaoui KEL, Visser ME, Kastelein JJP, et al. Triglycerides and cardiovascular risk[J]. Curr Cardiol Rev, 2009, 5(3):216-222.
    [59] Eberly LE, Stamler J, Neaton JD. Relation of triglyceride levels, fasting and nonfasting, to fatal and nonfatal coronary heart disease[J]. Arch Intern Med, 2003, 163(9):1077-1083.
    [60] Yao Z, Wang Y. Apolipoprotein C-Ⅲ and hepatic triglyceride-rich lipoprotein production[J]. Curr Opin Lipidol, 2012, 23(3):206-212.
    [61] Gaudet D, Brisson D, Tremblay K, et al. Targeting APOC3 in the Familial Chylomicronemia Syndrome[J]. N Engl J Med, 2014, 371(23):2200-2206.
    [62] Gaudet D, Alexander VJ, Baker BF, et al. Antisense Inhibition of Apolipoprotein C-Ⅲ in Patients with Hypertriglyceridemia[J]. N Engl J Med, 2015, 373(5):438-447.
    [63] Graham MJ, Lee RG, Bell TA, et al. Antisense oligonucleotide inhibition of apolipoprotein c-iii reduces plasma triglycerides in rodents, nonhuman primates, and humans[J]. Circ Res, 2013, 112(11):1479-1490.
    [64] TG and HDL Working Group of the Exome Sequencing Project, National Heart, Lung, and Blood Institute, Crosby J, et al. Loss-of-function mutations in APOC3, triglycerides, and coronary disease[J]. N Engl J Med, 2014, 371(1):22-31.
    [65] Caron S, Verrijken A, Mertens I, et al. Transcriptional activation of apolipoprotein CⅢ expression by glucose may contribute to diabetic dyslipidemia[J]. Arterioscler Thromb Vasc Biol, 2011, 31(3):513-519.
    [66] Gleeson A, Anderton K, Owens D, et al. The role of microsomal triglyceride transfer protein and dietary cholesterol in chylomicron production in diabetes[J]. Diabetologia, 1999, 42(8):944-948.
    [67] Qin B, Qiu W, Avramoglu RK, et al. Tumor necrosis factor-α induces intestinal insulin resistance and stimulates the overproduction of intestinal apolipoprotein b48-containing lipoproteins[J]. Diabetes, 2007, 56(2):450-461.
    [68] Zoltowska M, Ziv E, Delvin E, et al. Cellular aspects of intestinal lipoprotein assembly in Psammomys obesus:a model of insulin resistance and type 2 diabetes[J]. Diabetes, 2003, 52(10):2539-2545.
    [69] Phillips C, Bennett A, Anderton K, et al. Intestinal rather than hepatic microsomal triglyceride transfer protein as a cause of postprandial dyslipidemia in diabetes[J]. Metabolism, 2002, 51(7):847-852.
    [70] Phillips C, Mullan K, Owens D, et al. Intestinal microsomal triglyceride transfer protein in type 2 diabetic and non-diabetic subjects:the relationship to triglyceride-rich postprandial lipoprotein composition[J]. Atherosclerosis, 2006, 187(1):57-64.
    [71] Lally S, Tan CY, Owens D, et al. Messenger RNA levels of genes involved in dysregulation of postprandial lipoproteins in type 2 diabetes:the role of Niemann-Pick C1-like 1, ATPbinding cassette, transporters G5 and G8, and of microsomal triglyceride transfer protein[J]. Diabetologia, 2006, 49(5):1008-1016.
    [72] Sparks JD, Chamberlain JM, O'Dell C, et al. Acute suppression of apo B secretion by insulin occurs independently of MTP[J]. Biochem Biophys Res Commun, 2011, 406(2):252-256.
    [73] Sarwar N, Gao P, Seshasai SRK, et al., and the The Emerging Risk Factors Collaboration. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease:a collaborative meta-analysis of 102 prospective studies[J]. Lancet, 2010, 375(9733):2215-2222.
    [74] Kadowaki S, Okamura T, Hozawa A, et al. Relationship of elevated casual blood glucose level with coronary heart disease, cardiovascular disease and all-cause mortality in a representative sample of the Japanese population. NIPPON DATA80[J]. Diabetologia, 2008, 51(4):575-582.
    [75] Fujishima M, Kiyohara Y, Kato I, et al. Diabetes and Cardiovascular Disease in a Prospective Population Survey in Japan:The Hisayama Study[J]. Diabetes, 1996, 45(Supplement 3):S14-S16.
    [76] Nakamura K, Miyoshi T, Yunoki K, et al. Postprandial hyperlipidemia as a potential residual risk factor[J]. J Cardiol, 2016, 67(4):335-339.
    [77] Gordin D, Saraheimo M, Tuomikangas J, et al. Influence of postprandial hyperglycemic conditions on arterial stiffness in patients with type 2 diabetes[J]. J Clin Endocrinol Metab, 2016, 101(3):1134-1143.
    [78] Hokanson JE, Austin MA. Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level:a meta-analysis of populationbased prospective studies[J]. J Cardiovasc Risk, 1996, 3(2):213-219.
    [79] Labreuche J, Touboul PJ, Amarenco P. Plasma triglyceride levels and risk of stroke and carotid atherosclerosis:a systematic review of the epidemiological studies[J]. Atherosclerosis, 2009, 203(2):331-345.
    [80] Noda H, Iso H, Saito I, et al. The impact of the metabolic syndrome and its components on the incidence of ischemic heart disease and stroke:the Japan public health center-based study[J]. Hypertens Res, 2009, 32(4):289-298.
    [81] Patel A, Barzi F, Jamrozik K, et al. Serum triglycerides as a risk factor for cardiovascular diseases in the Asia-Pacific region[J]. Circulation, 2004, 110(17):2678-2686.
    [82] Sarwar N, Danesh J, Eiriksdottir G, et al. Triglycerides and the risk of coronary heart disease:10,158 incident cases among 262,525 participants in 29 Western prospective studies[J]. Circulation, 2007, 115(4):450-458.
    [83] Gæde P, Lund-Andersen H, Parving HH, et al. Effect of a multifactorial intervention on mortality in type 2 diabetes[J]. N Engl J Med, 2008, 358(6):580-591.
    [84] Ma KL, Varghese Z, Ku Y, et al. Sirolimus inhibits endogenous cholesterol synthesis induced by inflammatory stress in human vascular smooth muscle cells[J]. Am J Physiol Heart Circ Physiol, 2010, 298(6):H1646-H1651.
    [85] Zhao L, Chen Y, Tang R, et al. Inflammatory stress exacerbates hepatic cholesterol accumulation via increasing cholesterol uptake and de novo synthesis[J]. J Gastroenterol Hepatol, 2011, 26(5):875-883.
    [86] Walenbergh SMA, Koek GH, Bieghs V, et al. Non-alcoholic steatohepatitis:The role of oxidized low-density lipoproteins[J]. J Hepatol, 2013, 58(4):801-810.
    [87] Tanaka M, Ikeda K, Suganami T, et al. Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis[J]. Nat Commun, 2014, 5:4982.
    [88] Itoh M, Kato H, Suganami T, et al. Hepatic crown-like structure:A unique histological feature in non-alcoholic steatohepatitis in mice and humans[J]. PLoS One, 2013, 8(12):e82163.
    [89] Brenner C, Galluzzi L, Kepp O, et al. Decoding cell death signals in liver inflammation[J]. J Hepatol, 2013, 59(3):583-594.
    [90] Chiasson JL, Josse RG, Gomis R, et al. Acarbose for the prevention of Type 2 diabetes, hypertension and cardiovascular disease in subjects with impaired glucose tolerance:facts and interpretations concerning the critical analysis of the STOP-NIDDM Trial data[J]. Diabetologia, 2004, 47(6):969-975., discussion 976-977.
    [91] Barrett ML, Udani JK. A proprietary alpha-amylase inhibitor from white bean (Phaseolus vulgaris):a review of clinical studies on weight loss and glycemic control[J]. Nutr J, 2011, 10(1):24.
    [92] Fujitani Y, Fujimoto S, Takahashi K, et al. Effects of linagliptin monotherapy compared with voglibose on postprandial blood glucose responses in Japanese patients with type 2 diabetes:Linagliptin Study of Effects on Postprandial blood glucose (L-STEP)[J]. Diabetes Res Clin Pract, 2016, 121:146-156.
    [93] Pratley RE, Hagberg JM, Dengel DR, et al. Aerobic exercise training-induced reductions in abdominal fat and glucosestimulated insulin responses in middle-aged and older men[J]. J Am Geriatr Soc, 2000, 48(9):1055-1061.
    [94] Pratley RE, Weyer C. The role of impaired early insulin secretion in the pathogenesis of Type Ⅱ diabetes mellitus[J]. Diabetologia, 2001, 44(8):929-945.
    [95] Teva, Product Information:Glyburide (Glibenclamide), 2009, https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/017532s030lbl.pdf.
    [96] Sanofi-Aventis, Product Information:Glimepiride, 2012., www.accessdata.fda.gov/drugsatfda.../020496s018s019lbl. pdf.
    [97] Hu S, Boettcher B, Dunning B. The mechanisms underlying the unique pharmacodynamics of nateglinide[J]. Diabetologia, 2003, 46(S1):M37-M43.
    [98] Prasad-Reddy L, Isaacs D. A clinical review of GLP-1 receptor agonists:efficacy and safety in diabetes and beyond[J]. Drugs Context, 2015, 4(212283):1-19.
    [99] Fisman E, Tenenbaum A. Antidiabetic treatment with gliptins:focus on cardiovascular effects and outcomes[J]. Cardiovasc Diabetol, 2015, 14(1):129.
    [100] Green J, Bethel M, Armstrong P, et al. Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes[J]. N Engl J Med, 2015, 373(3):232-242.
    [101] Zannad F, Cannon C, Cushman W, et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE:a multicentre, randomised, double-blind trial[J]. Lancet, 2015, 385(9982):2067-2076.
    [102] The ACCORD Study Group, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes[J]. N Engl J Med, 2011, 364(9):818-828.
    [103] Colhoun, Helen Met al.. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS):multicentre randomised placebo-controlled trial[J]. Lancet,2004, 364(9435):685-696.
    [104] Sever PS, Poulter NR, Dahlof B, et al. Reduction in cardiovascular events with atorvastatin in 2,532 patients with type 2 diabetes:Anglo-Scandinavian Cardiac Outcomes Trial-lipid-lowering arm (ASCOT-LLA)[J]. Diabetes Care, 2005, 28(5):1151-1157.
    [105] Borén J, Matikainen N, Adiels M, et al. Postprandial hypertriglyceridemia as a coronary risk factor[J]. Clin Chim Acta, 2014, 431:131-142.
    [106] Scott R, O'Brien R, Fulcher G, et al. Effects of fenofibrate treatment on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome:the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study[J]. Diabetes Care, 2009, 32(3):493-498.
    [107] Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and Safety of Evolocumab in Reducing Lipids and Cardiovascular Events[J]. N Engl J Med, 2015, 372(16):1500-1509.
    [108] Blom DJ, Hala T, Bolognese M, et al. A 52-Week PlaceboControlled Trial of Evolocumab in Hyperlipidemia[J]. N Engl J Med, 2014, 370(19):1809-1819.
    [109] Chandler CE, Wilder DE, Pettini JL, et al. CP-346086:an MTP inhibitor that lowers plasma cholesterol and triglycerides in experimental animals and in humans[J]. J Lipid Res, 2003, 44(10):1887-1901.
    [110] Mera Y, Kawai T, Ogawa N, et al. JTT-130, a novel intestinespecific inhibitor of microsomal triglyceride transfer protein, ameliorates lipid metabolism and attenuates atherosclerosis in hyperlipidemic animal models[J]. J Pharmacol Sci, 2015, 129(3):169-176.
    [111] Filippov S, Pinkosky SL, Newton RS. LDL-cholesterol reduction in patients with hypercholesterolemia by modulation of adenosine triphosphate-citrate lyase and adenosine monophosphate-activated protein kinase[J]. Curr Opin Lipidol, 2014, 25(4):309-315.
    [112] Lemus HN, Mendivil CO. Adenosine triphosphate citrate lyase:Emerging target in the treatment of dyslipidemia[J]. J Clin Lipidol, 2015, 9(3):384-389.
    [113] Chen JS, Chen YH, Huang PH, et al. Ginkgo biloba extract reduces high-glucose-induced endothelial adhesion by inhibiting the redox-dependent interleukin-6 pathways[J]. Cardiovasc Diabetol, 2012, 11(1):49.
    [114] Siegel G, Ermilov E, Knes O, et al. Combined lowering of low grade systemic inflammation and insulin resistance in metabolic syndrome patients treated with Ginkgo biloba[J]. Atherosclerosis, 2014, 237(2):584-588.
    [115] Zhou YH, Yu JP, Liu YF, et al. Effects of Ginkgo biloba extract on inflammatory mediators (SOD, MDA, TNF-alpha, NF-kappaBp65, IL-6) in TNBS-induced colitis in rats[J]. Mediators Inflamm, 2006, 2006(5):92642.
    [116] Xie Z, Liang G, Zhang L, et al. Molecular mechanisms underlying the cholesterol-lowering effect of Ginkgo biloba extract in hepatocytes:a comparative study with lovastatin[J]. Acta Pharmacol Sin, 2009, 30(9):1262-1275.
    [117] Schultz O, Oberhauser F, Saech J, et al. Effects of inhibition of interleukin-6 signalling on insulin sensitivity and lipoprotein (a) levels in human subjects with rheumatoid diseases[J]. PLoS One, 2010, 5(12):e14328.
    [118] Strang AC, Bisoendial RJ, Kootte RS, et al. Pro-atherogenic lipid changes and decreased hepatic LDL receptor expression by tocilizumab in rheumatoid arthritis. Atherosclerosis, 2013, 229(1):174-181.
    [119] Ridker PM. From C-reactive protein to interleukin-6 to interleukin-1:moving upstream to identify novel targets for atheroprotection[J]. Circ Res, 2016, 118(1):145-156.
    [120] Lippi G, Targher G. Optimal therapy for reduction of lipoprotein(a)[J]. J Clin Pharm Ther, 2012, 37(1):1-3.
    [121] Mohammadpour AH, Akhlaghi F. Future of cholesteryl ester transfer protein (CETP) inhibitors:a pharmacological perspective[J]. Clin Pharmacokinet, 2013, 52(8):615-626.
    [122] Kumashiro N, Beddow SA, Vatner DF, et al. Targeting pyruvate carboxylase reduces gluconeogenesis and adiposity and improves insulin resistance[J]. Diabetes, 2013, 62(7):2183-2194.
    [123] Kiyosue A, Hayashi N, Komori H, et al. Dose-ranging study with the glucokinase activator AZD1656 as monotherapy in Japanese patients with type 2 diabetes mellitus[J]. Diabetes Obes Metab, 2013, 15(10):923-930.
    [124] Lloyd DJ, St Jean DJJ, Kurzeja RJM, et al. Antidiabetic effects of glucokinase regulatory protein small-molecule disruptors[J]. Nature, 2013, 504(7480):437-440.
    [125] van Poelje PD, Potter SC, Erion MD. Fructose-1, 6-bisphosphatase inhibitors for reducing excessive endogenous glucose production in type 2 diabetes[J]. Handb Exp Pharmacol, 2011, 203:279-301.
    [126] Swarbrick MM, Havel PJ, Levin AA, et al. Inhibition of protein tyrosine phosphatase-1B with antisense oligonucleotides improves insulin sensitivity and increases adiponectin concentrations in monkeys[J]. Endocrinology, 2009, 150(4):1670-1679.
    [127] Agius L. New hepatic targets for glycaemic control in diabetes[J]. Best Pract Res Clin Endocrinol Metab, 2007, 21(4):587-605.
    [128] Baker DJ, Timmons JA, Greenhaff PL. Glycogen phosphorylase inhibition in type 2 diabetes therapy:A systematic evaluation of metabolic and functional effects in rat skeletal muscle[J]. Diabetes, 2005, 54(8):2453-2459.
    [129] Kazda CM, Ding Y, Kelly RP, et al. Evaluation of efficacy and eafety of the glucagon receptor antagonist LY2409021 in patients with type 2 diabetes:12-and 24-week phase 2 studies[J]. Diabetes Care, 2016, 39(7):1241-1249.
    [130] Girard J. The inhibitory effects of insulin on hepatic glucose production are both direct and indirect[J]. Diabetes, 2006, 55(Supplement 2):S65-S69.
    [131] Gray LR, Sultana MR, Rauckhorst AJ, et al. Hepatic mitochondrial pyruvate carrier 1 is required for efficient regulation of gluconeogenesis and whole-body glucose homeostasis[J]. Cell Metab, 2015, 22(4):669-681.
    [132] Divakaruni AS, Wiley SE, Rogers GW, et al. Thiazolidinediones are acute, specific inhibitors of the mitochondrial pyruvate carrier[J]. Proc Natl Acad Sci USA, 2013, 110(14):5422-5427.
    [133] DiTullio NW, Berkoff CE, Blank B, et al. 3-Mercaptopicolinic Acid, an Inhibitor of Gluconeogenesis[J]. Biochem J, 1974, 138(3):387-394.
    [134] Altomonte J, Richter A, Harbaran S, et al. Inhibition of Foxo1 function is associated with improved fasting glycemia in diabetic mice[J]. Am J Physiol Endocrinol Metab, 2003, 285(4):E718-E728.
    [135] Perry RJ, Kim T, Zhang XM, et al. Reversal of hypertriglyceridemia, fatty liver disease, and insulin resistance by a livertargeted mitochondrial uncoupler[J]. Cell Metab, 2013, 18(5):740-748.
    [136] Perry RJ, Zhang D, Zhang XM, et al. Controlled-release mitochondrial protonophore reverses diabetes and steatohepatitis in rats[J]. Science, 2015, 347(6227):1253-1256.
    [137] Yamauchi T, Nio Y, Maki T, et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions[J]. Nat Med, 2007, 13(3):332-339.
    [138] Iwabu M, Yamauchi T, Okada-Iwabu M, et al. Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1[J]. Nature, 2010, 464(7293):1313-1319.
    [139] Okada-Iwabu M, Yamauchi T, Iwabu M, et al. A smallmolecule AdipoR agonist for type 2 diabetes and short life in obesity[J]. Nature, 2013, 503(7477):493-499.
  • 加载中

Article Metrics

Article views(674) PDF downloads(2) Cited by()

Proportional views
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

Postprandial hyperglycemia and postprandial hypertriglyceridemia in type 2 diabetes

    Corresponding author: Toru Hiyoshi, email:toru_hiyoshi@med.jrc.or.jp
  • 1 Division of Diabetes and Endocrinology, Department of Internal Medicine, Japanese Red Cross Medical Center, Tokyo, Japan;
  • 2 Department of Laboratory Medicine, Japanese Red Cross Medical Center, Tokyo, Japan;
  • 3 Department of Biochemistry, Microbiology and Immunology, Ottawa Institute of Systems Biology, University of Ottawa, Ottawa, Ontario, K1H 8M5, Canada

Abstract: Postprandial glucose level is an independent risk factor for cardiovascular disease that exerts effects greater than glucose levels at fasting state, whereas increase in serum triglyceride level, under both fasting and postprandial conditions, contributes to the development of arteriosclerosis. Insulin resistance is a prevailing cause of abnormalities in postabsorptive excursion of blood glucose and postprandial lipid profile. Excess fat deposition renders a vicious cycle of hyperglycemia and hypertriglyceridemia in the postprandial state, and both of which are contributors to atherosclerotic change of vessels especially in patients with type 2 diabetes mellitus. Several therapeutic approaches for ameliorating each of these abnormalities have been attempted, including various antidiabetic agents or new compounds targeting lipid metabolism.


Reference (139)



DownLoad:  Full-Size Img  PowerPoint