Generic placeholder image

Current Cardiology Reviews

Editor-in-Chief

ISSN (Print): 1573-403X
ISSN (Online): 1875-6557

Review Article

Insulin Resistance, Hyperinsulinemia and Atherosclerosis: Insights into Pathophysiological Aspects and Future Therapeutic Prospects

Author(s): Georgios S. Papaetis*, Anastasia Sacharidou, Ioannis C. Michaelides, Konstantinos C. Mikellidis and Stylianos A. Karvounaris

Volume 21, Issue 1, 2025

Published on: 16 October, 2024

Article ID: e1573403X314035 Pages: 19

DOI: 10.2174/011573403X314035241006185109

Price: $65

TIMBC 2026
Abstract

Insulin resistance describes the lack of activity of a known quantity of insulin (exogenous or endogenous) to promote the uptake of glucose and its utilization in an individual, as much as it does in metabolically normal individuals. On the cellular level, it suggests insufficient power of the insulin pathway (from the insulin receptor downstream to its final substrates) that is essential for multiple mitogenic and metabolic aspects of cellular homeostasis. Atherosclerosis is a slow, complex, and multifactorial pathobiological process in medium to large arteries and involves several tissues and cell types (immune, vascular, and metabolic cells). Inflammatory responses and immunoregulation are key players in its development and progression. This paper examines the possible pathophysiological mechanisms that govern the connection of insulin resistance, hyperinsulinemia, and the closely associated cardiometabolic syndrome with atherosclerosis, after exploring thoroughly both in vitro and in vivo (preclinical and clinical) evidence. It also discusses the importance of visualizing and developing novel therapeutic strategies and targets for treatment, to face this metabolic state through its genesis.

Keywords: Insulin, insulin resistance, hyperinsulinemia, atherosclerosis, cardiovascular disease, glucose.

Graphical Abstract
[1]
Lebovitz H. Insulin resistance: Definition and consequences. Exp Clin Endocrinol Diabetes 2001; 109 (Suppl. 2): S135-48.
[http://dx.doi.org/10.1055/s-2001-18576] [PMID: 11460565]
[2]
Ginsberg HN. Insulin resistance and cardiovascular disease. J Clin Invest 2000; 106(4): 453-8.
[http://dx.doi.org/10.1172/JCI10762] [PMID: 10953019]
[3]
Abdul-Ghani MA, DeFronzo RA. Pathogenesis of insulin resistance in skeletal muscle. J Biomed Biotechnol 2010; 2010: 1-19.
[http://dx.doi.org/10.1155/2010/476279] [PMID: 20445742]
[4]
Papaetis GS, Papakyriakou P, Panagiotou TN. State of the art paper Central obesity, type 2 diabetes and insulin: Exploring a pathway full of thorns. Arch Med Sci 2015; 3(3): 463-82.
[http://dx.doi.org/10.5114/aoms.2015.52350] [PMID: 26170839]
[5]
Yaribeygi H, Farrokhi FR, Butler AE, Sahebkar A. Insulin resistance: Review of the underlying molecular mechanisms. J Cell Physiol 2019; 234(6): 8152-61.
[http://dx.doi.org/10.1002/jcp.27603] [PMID: 30317615]
[6]
Papaetis GS. Empagliflozin and the Diabetic Kidney: Pathophysiological Concepts and Future Challenges. Endocr Metab Immune Disord Drug Targets 2021; 21(9): 1555-89.
[http://dx.doi.org/10.2174/1871530321999201214233421] [PMID: 33319678]
[7]
Wysham C, Shubrook J. Beta-cell failure in type 2 diabetes: Mechanisms, markers, and clinical implications. Postgrad Med 2020; 132(8): 676-86.
[http://dx.doi.org/10.1080/00325481.2020.1771047] [PMID: 32543261]
[8]
Libby P. The changing landscape of atherosclerosis. Nature 2021; 592(7855): 524-33.
[http://dx.doi.org/10.1038/s41586-021-03392-8] [PMID: 33883728]
[9]
Chistiakov DA, Melnichenko AA, Myasoedova VA, Grechko AV, Orekhov AN. Mechanisms of foam cell formation in atherosclerosis. J Mol Med (Berl) 2017; 95(11): 1153-65.
[http://dx.doi.org/10.1007/s00109-017-1575-8] [PMID: 28785870]
[10]
Walker ARP, Isaacson C, Segal I. Fatty streaks and atherogenesis. Lancet 1980; 316(8201): 974.
[http://dx.doi.org/10.1016/S0140-6736(80)92127-3] [PMID: 6107609]
[11]
Alonso-Herranz L, Albarrán-Juárez J, Bentzon JF. Mechanisms of fibrous cap formation in atherosclerosis. Front Cardiovasc Med 2023; 10: 1254114.
[http://dx.doi.org/10.3389/fcvm.2023.1254114] [PMID: 37671141]
[12]
Cardoso L, Weinbaum S. Microcalcifications, their genesis, growth, and biomechanical stability in fibrous cap rupture. Adv Exp Med Biol 2018; 1097: 129-55.
[http://dx.doi.org/10.1007/978-3-319-96445-4_7] [PMID: 30315543]
[13]
Stout RW, Vallance-Owen J. Insulin and atheroma. Lancet 1969; 293(7605): 1078-80.
[http://dx.doi.org/10.1016/S0140-6736(69)91711-5] [PMID: 4181737]
[14]
Laakso M, Sarlund H, Salonen R, et al. Asymptomatic atherosclerosis and insulin resistance. Arterioscler Thromb 1991; 11(4): 1068-76.
[http://dx.doi.org/10.1161/01.ATV.11.4.1068] [PMID: 2065028]
[15]
Bressler P, Bailey SR, Matsuda M, DeFronzo RA. Insulin resistance and coronary artery disease. Diabetologia 1996; 39(11): 1345-50.
[http://dx.doi.org/10.1007/s001250050581] [PMID: 8933003]
[16]
Després JP, Lamarche B, Mauriège P, et al. Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med 1996; 334(15): 952-8.
[http://dx.doi.org/10.1056/NEJM199604113341504] [PMID: 8596596]
[17]
Gast KB, Tjeerdema N, Stijnen T, Smit JWA, Dekkers OM. Insulin resistance and risk of incident cardiovascular events in adults without diabetes: Meta-analysis. PLoS One 2012; 7(12): e52036.
[http://dx.doi.org/10.1371/journal.pone.0052036] [PMID: 23300589]
[18]
Kilpatrick ES, Rigby AS, Atkin SL. Insulin resistance, the metabolic syndrome, and complication risk in type 1 diabetes: “Double diabetes” in the Diabetes Control and Complications Trial. Diabetes Care 2007; 30(3): 707-12.
[http://dx.doi.org/10.2337/dc06-1982] [PMID: 17327345]
[19]
Gaggini M, Morelli M, Buzzigoli E, DeFronzo R, Bugianesi E, Gastaldelli A. Non-alcoholic fatty liver disease (NAFLD) and its connection with insulin resistance, dyslipidemia, atherosclerosis and coronary heart disease. Nutrients 2013; 5(5): 1544-60.
[http://dx.doi.org/10.3390/nu5051544] [PMID: 23666091]
[20]
Papaetis GS. SGLT2 Inhibitors and diabetic kidney disease: Targeting multiple and interrelated signaling pathways for renal protection. Curr Mol Pharmacol 2023; 17: e18761429261105.
[http://dx.doi.org/10.2174/0118761429261105231011101200] [PMID: 37904562]
[21]
Papaetis GS, Filippou PK, Constantinidou KG, Stylianou CS. Liraglutide: New perspectives for the treatment of polycystic ovary syndrome. Clin Drug Investig 2020; 40(8): 695-713.
[http://dx.doi.org/10.1007/s40261-020-00942-2] [PMID: 32583294]
[22]
Li M, Chi X, Wang Y, Setrerrahmane S, Xie W, Xu H. Trends in insulin resistance: Insights into mechanisms and therapeutic strategy. Signal Transduct Target Ther 2022; 7(1): 216.
[http://dx.doi.org/10.1038/s41392-022-01073-0] [PMID: 35794109]
[23]
Papaetis G. GLP-1 receptor agonists, SGLT-2 inhibitors, and obstructive sleep apnoea: Can new allies face an old enemy? Arch Med Sci Atheroscler Dis 2023; 8(1): 19-34.
[http://dx.doi.org/10.5114/amsad/161170] [PMID: 37153372]
[24]
Li JW, He SY, Liu P, Luo L, Zhao L, Xiao YB. Association of Gestational Diabetes Mellitus (GDM) with subclinical atherosclerosis: A systemic review and meta-analysis. BMC Cardiovasc Disord 2014; 14(1): 132.
[http://dx.doi.org/10.1186/1471-2261-14-132] [PMID: 25266849]
[25]
Kim Y, Han E, Lee JS, et al. Cardiovascular risk is elevated in lean subjects with nonalcoholic fatty liver disease. Gut Liver 2022; 16(2): 290-9.
[http://dx.doi.org/10.5009/gnl210084] [PMID: 34238770]
[26]
Kasuga M, Karlsson FA, Kahn CR. Insulin stimulates the phosphorylation of the 95,000-dalton subunit of its own receptor. Science 1982; 215(4529): 185-7.
[http://dx.doi.org/10.1126/science.7031900] [PMID: 7031900]
[27]
White MF, Shoelson SE, Keutmann H, Kahn CR. A cascade of tyrosine autophosphorylation in the beta-subunit activates the phosphotransferase of the insulin receptor. J Biol Chem 1988; 263(6): 2969-80.
[http://dx.doi.org/10.1016/S0021-9258(18)69163-X] [PMID: 2449432]
[28]
Sun XJ, Rothenberg P, Kahn CR, et al. Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature 1991; 352(6330): 73-7.
[http://dx.doi.org/10.1038/352073a0] [PMID: 1648180]
[29]
Skolnik EY, Lee CH, Batzer A, et al. The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS1 and Shc: Implications for insulin control of ras signalling. EMBO J 1993; 12(5): 1929-36.
[http://dx.doi.org/10.1002/j.1460-2075.1993.tb05842.x] [PMID: 8491186]
[30]
Paz K, Voliovitch H, Hadari YR, Roberts CTJ Jr, LeRoith D, Zick Y. Interaction between the insulin receptor and its downstream effectors. Use of individually expressed receptor domains for structure/function analysis. J Biol Chem 1996; 271(12): 6998-7003.
[http://dx.doi.org/10.1074/jbc.271.12.6998] [PMID: 8636129]
[31]
Kolterman OG, Insel J, Saekow M, Olefsky JM. Mechanisms of insulin resistance in human obesity: Evidence for receptor and postreceptor defects. J Clin Invest 1980; 65(6): 1272-84.
[http://dx.doi.org/10.1172/JCI109790] [PMID: 6997333]
[32]
Bryant NJ, Govers R, James DE. Regulated transport of the glucose transporter GLUT4. Nat Rev Mol Cell Biol 2002; 3(4): 267-77.
[http://dx.doi.org/10.1038/nrm782] [PMID: 11994746]
[33]
Saxton RA, Sabatini DM. mTOR signaling in growth, metabolism, and disease. Cell 2017; 168(6): 960-76.
[http://dx.doi.org/10.1016/j.cell.2017.02.004] [PMID: 28283069]
[34]
Kamagate A, Qu S, Perdomo G, et al. FoxO1 mediates insulin-dependent regulation of hepatic VLDL production in mice. J Clin Invest 2008; 118(6): 2347-64.
[http://dx.doi.org/10.1172/JCI32914] [PMID: 18497885]
[35]
Altomonte J, Cong L, Harbaran S, et al. Foxo1 mediates insulin action on apoC-III and triglyceride metabolism. J Clin Invest 2004; 114(10): 1493-503.
[http://dx.doi.org/10.1172/JCI200419992] [PMID: 15546000]
[36]
Sánchez-Margalet V. Stimulation of glycogen synthesis by insulin requires S6 kinase and phosphatidylinositol-3-kinase in HTC-IR cells. J Cell Physiol 2000; 182(2): 182-8.
[http://dx.doi.org/10.1002/(SICI)1097-4652(200002)182:2<182:AID-JCP6>3.0.CO;2-X] [PMID: 10623881]
[37]
Tzivion G, Dobson M, Ramakrishnan G. FoxO transcription factors; Regulation by AKT and 14-3-3 proteins. Biochim Biophys Acta Mol Cell Res 2011; 1813(11): 1938-45.
[http://dx.doi.org/10.1016/j.bbamcr.2011.06.002] [PMID: 21708191]
[38]
Krycer JR, Sharpe LJ, Luu W, Brown AJ. The Akt–SREBP nexus: Cell signaling meets lipid metabolism. Trends Endocrinol Metab 2010; 21(5): 268-76.
[http://dx.doi.org/10.1016/j.tem.2010.01.001] [PMID: 20117946]
[39]
Rebrin K, Steil GM, Mittelman SD, Bergman RN. Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs. J Clin Invest 1996; 98(3): 741-9.
[http://dx.doi.org/10.1172/JCI118846] [PMID: 8698866]
[40]
Jaworski K, Sarkadi-Nagy E, Duncan RE, Ahmadian M, Sul HS. Regulation of Triglyceride Metabolism.IV. Hormonal regulation of lipolysis in adipose tissue. Am J Physiol Gastrointest Liver Physiol 2007; 293(1): G1-4.
[http://dx.doi.org/10.1152/ajpgi.00554.2006] [PMID: 17218471]
[41]
Rieusset J, Andreelli F, Auboeuf D, et al. Insulin acutely regulates the expression of the peroxisome proliferator-activated receptor-gamma in human adipocytes. Diabetes 1999; 48(4): 699-705.
[http://dx.doi.org/10.2337/diabetes.48.4.699] [PMID: 10102684]
[42]
Draznin B. Molecular mechanisms of insulin resistance: Serine phosphorylation of insulin receptor substrate-1 and increased expression of p85alpha: The two sides of a coin. Diabetes 2006; 55(8): 2392-7.
[http://dx.doi.org/10.2337/db06-0391] [PMID: 16873706]
[43]
Stentz FB, Kitabchi AE. De novo emergence of growth factor receptors in activated human CD4+ and CD8+ T lymphocytes. Metabolism 2004; 53(1): 117-22.
[http://dx.doi.org/10.1016/j.metabol.2003.07.015] [PMID: 14681852]
[44]
Entezari M, Hashemi D, Taheriazam A, et al. AMPK signaling in diabetes mellitus, insulin resistance and diabetic complications: A pre-clinical and clinical investigation. Biomed Pharmacother 2022; 146: 112563.
[http://dx.doi.org/10.1016/j.biopha.2021.112563] [PMID: 35062059]
[45]
Liang CP, Han S, Okamoto H, et al. Increased CD36 protein as a response to defective insulin signaling in macrophages. J Clin Invest 2004; 113(5): 764-73.
[http://dx.doi.org/10.1172/JCI19528] [PMID: 14991075]
[46]
Iida KT, Suzuki H, Sone H, et al. Insulin inhibits apoptosis of macrophage cell line, THP-1 cells, via phosphatidylinositol-3-kinase-dependent pathway. Arterioscler Thromb Vasc Biol 2002; 22(3): 380-6.
[http://dx.doi.org/10.1161/hq0302.105272] [PMID: 11884278]
[47]
Pina AF, Borges DO, Meneses MJ, et al. Insulin: Trigger and Target of Renal Functions. Front Cell Dev Biol 2020; 8: 519.
[http://dx.doi.org/10.3389/fcell.2020.00519] [PMID: 32850773]
[48]
Abel ED. Insulin signaling in the heart. Am J Physiol Endocrinol Metab 2021; 321(1): E130-45.
[http://dx.doi.org/10.1152/ajpendo.00158.2021] [PMID: 34056923]
[49]
Blázquez E, Velázquez E, Hurtado-Carneiro V, Ruiz-Albusac JM. Insulin in the brain: Its pathophysiological implications for States related with central insulin resistance, type 2 diabetes and Alzheimer’s disease. Front Endocrinol (Lausanne) 2014; 5: 161.
[http://dx.doi.org/10.3389/fendo.2014.00161] [PMID: 25346723]
[50]
Luo J, Field SJ, Lee JY, Engelman JA, Cantley LC. The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complex. J Cell Biol 2005; 170(3): 455-64.
[http://dx.doi.org/10.1083/jcb.200503088] [PMID: 16043515]
[51]
Häring HU. The insulin receptor: Signalling mechanism and contribution to the pathogenesis of insulin resistance. Diabetologia 1991; 34(12): 848-61.
[http://dx.doi.org/10.1007/BF00400192] [PMID: 1663881]
[52]
Aguirre V, Werner ED, Giraud J, Lee YH, Shoelson SE, White MF. Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action. J Biol Chem 2002; 277(2): 1531-7.
[http://dx.doi.org/10.1074/jbc.M101521200] [PMID: 11606564]
[53]
Qiao L, Zhande R, Jetton TL, Zhou G, Sun XJ. In vivo phosphorylation of insulin receptor substrate 1 at serine 789 by a novel serine kinase in insulin-resistant rodents. J Biol Chem 2002; 277(29): 26530-9.
[http://dx.doi.org/10.1074/jbc.M201494200] [PMID: 12006586]
[54]
Gao Z, Zhang X, Zuberi A, et al. Inhibition of insulin sensitivity by free fatty acids requires activation of multiple serine kinases in 3T3-L1 adipocytes. Mol Endocrinol 2004; 18(8): 2024-34.
[http://dx.doi.org/10.1210/me.2003-0383] [PMID: 15143153]
[55]
Summers S. Ceramides in insulin resistance and lipotoxicity. Prog Lipid Res 2006; 45(1): 42-72.
[http://dx.doi.org/10.1016/j.plipres.2005.11.002] [PMID: 16445986]
[56]
Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 2004; 350(7): 664-71.
[http://dx.doi.org/10.1056/NEJMoa031314] [PMID: 14960743]
[57]
Schubert KM, Scheid MP, Duronio V. Ceramide inhibits protein kinase B/Akt by promoting dephosphorylation of serine 473. J Biol Chem 2000; 275(18): 13330-5.
[http://dx.doi.org/10.1074/jbc.275.18.13330] [PMID: 10788440]
[58]
Stratford S, Hoehn KL, Liu F, Summers SA. Regulation of insulin action by ceramide: Dual mechanisms linking ceramide accumulation to the inhibition of Akt/protein kinase B. J Biol Chem 2004; 279(35): 36608-15.
[http://dx.doi.org/10.1074/jbc.M406499200] [PMID: 15220355]
[59]
Özcan U, Yilmaz E, Özcan L, et al. Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes. Science 2006; 313(5790): 1137-40.
[http://dx.doi.org/10.1126/science.1128294] [PMID: 16931765]
[60]
Hurrle S, Hsu WH. The etiology of oxidative stress in insulin resistance. Biomed J 2017; 40(5): 257-62.
[http://dx.doi.org/10.1016/j.bj.2017.06.007] [PMID: 29179880]
[61]
Dröge W. Free radicals in the physiological control of cell function. Physiol Rev 2002; 82(1): 47-95.
[http://dx.doi.org/10.1152/physrev.00018.2001] [PMID: 11773609]
[62]
Taniyama Y, Hitomi H, Shah A, Alexander RW, Griendling KK. Mechanisms of reactive oxygen species-dependent downregulation of insulin receptor substrate-1 by angiotensin II. Arterioscler Thromb Vasc Biol 2005; 25(6): 1142-7.
[http://dx.doi.org/10.1161/01.ATV.0000164313.17167.df] [PMID: 15802620]
[63]
Jia G, Lockette W, Sowers JR. Mineralocorticoid receptors in the pathogenesis of insulin resistance and related disorders: From basic studies to clinical disease. Am J Physiol Regul Integr Comp Physiol 2021; 320(3): R276-86.
[http://dx.doi.org/10.1152/ajpregu.00280.2020] [PMID: 33438511]
[64]
Andreozzi F, Laratta E, Sciacqua A, Perticone F, Sesti G. Angiotensin II impairs the insulin signaling pathway promoting production of nitric oxide by inducing phosphorylation of insulin receptor substrate-1 on Ser312 and Ser616 in human umbilical vein endothelial cells. Circ Res 2004; 94(9): 1211-8.
[http://dx.doi.org/10.1161/01.RES.0000126501.34994.96] [PMID: 15044323]
[65]
Reyna SM, Ghosh S, Tantiwong P, et al. Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. Diabetes 2008; 57(10): 2595-602.
[http://dx.doi.org/10.2337/db08-0038] [PMID: 18633101]
[66]
Hill MA, Yang Y, Zhang L, et al. Insulin resistance, cardiovascular stiffening and cardiovascular disease. Metabolism 2021; 119: 154766.
[http://dx.doi.org/10.1016/j.metabol.2021.154766] [PMID: 33766485]
[67]
Zeng G, Quon MJ. Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells. J Clin Invest 1996; 98(4): 894-8.
[http://dx.doi.org/10.1172/JCI118871] [PMID: 8770859]
[68]
Gimbrone MA Jr, García-Cardeña G. Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis. Circ Res 2016; 118(4): 620-36.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.306301] [PMID: 26892962]
[69]
Montagnani M, Ravichandran LV, Chen H, Esposito DL, Quon MJ. Insulin receptor substrate-1 and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells. Mol Endocrinol 2002; 16(8): 1931-42.
[http://dx.doi.org/10.1210/me.2002-0074] [PMID: 12145346]
[70]
Förstermann U, Xia N, Li H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ Res 2017; 120(4): 713-35.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.309326] [PMID: 28209797]
[71]
Barrett EJ, Liu Z. The endothelial cell: An “early responder” in the development of insulin resistance. Rev Endocr Metab Disord 2013; 14(1): 21-7.
[http://dx.doi.org/10.1007/s11154-012-9232-6] [PMID: 23306779]
[72]
Tanigaki K, Chambliss KL, Yuhanna IS, et al. Endothelial fcγ Receptor IIB Activation Blunts Insulin Delivery to Skeletal Muscle to cause insulin resistance in mice. Diabetes 2016; 65(7): 1996-2005.
[http://dx.doi.org/10.2337/db15-1605] [PMID: 27207525]
[73]
Guo YJ, Pan WW, Liu SB, Shen ZF, Xu Y, Hu LL. ERK/MAPK signalling pathway and tumorigenesis. Exp Ther Med 2020; 19(3): 1997-2007.
[PMID: 32104259]
[74]
Carel K, Kummer JL, Schubert C, Leitner W, Heidenreich KA, Draznin B. Insulin stimulates mitogen-activated protein kinase by a Ras-independent pathway in 3T3-L1 adipocytes. J Biol Chem 1996; 271(48): 30625-30.
[http://dx.doi.org/10.1074/jbc.271.48.30625] [PMID: 8940037]
[75]
Zhang W, Liu HT. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res 2002; 12(1): 9-18.
[http://dx.doi.org/10.1038/sj.cr.7290105] [PMID: 11942415]
[76]
Cubbon RM, Rajwani A, Wheatcroft SB. The impact of insulin resistance on endothelial function, progenitor cells and repair. Diab Vasc Dis Res 2007; 4(2): 103-11.
[http://dx.doi.org/10.3132/dvdr.2007.027] [PMID: 17654443]
[77]
Metzler B, Hu Y, Dietrich H, Xu Q. Increased expression and activation of stress-activated protein kinases/c-Jun NH(2)-terminal protein kinases in atherosclerotic lesions coincide with p53. Am J Pathol 2000; 156(6): 1875-86.
[http://dx.doi.org/10.1016/S0002-9440(10)65061-4] [PMID: 10854211]
[78]
Hu Y, Dietrich H, Metzler B, Wick G, Xu Q. Hyperexpression and activation of extracellular signal-regulated kinases (ERK1/2) in atherosclerotic lesions of cholesterol-fed rabbits. Arterioscler Thromb Vasc Biol 2000; 20(1): 18-26.
[http://dx.doi.org/10.1161/01.ATV.20.1.18] [PMID: 10634796]
[79]
Rahaman SO, Lennon DJ, Febbraio M, Podrez EA, Hazen SL, Silverstein RL. A CD36-dependent signaling cascade is necessary for macrophage foam cell formation. Cell Metab 2006; 4(3): 211-21.
[http://dx.doi.org/10.1016/j.cmet.2006.06.007] [PMID: 16950138]
[80]
Muslin AJ. MAPK signalling in cardiovascular health and disease: Molecular mechanisms and therapeutic targets. Clin Sci (Lond) 2008; 115(7): 203-18.
[http://dx.doi.org/10.1042/CS20070430] [PMID: 18752467]
[81]
Abu-Elheiga L, Matzuk MM, Kordari P, et al. Mutant mice lacking acetyl-CoA carboxylase 1 are embryonically lethal. Proc Natl Acad Sci USA 2005; 102(34): 12011-6.
[http://dx.doi.org/10.1073/pnas.0505714102] [PMID: 16103361]
[82]
Ferré P, Foufelle F. SREBP-1c transcription factor and lipid homeostasis: Clinical perspective. Horm Res 2007; 68(2): 72-82.
[PMID: 17344645]
[83]
Stout RW. Insulin and atheroma. 20-yr perspective. Diabetes Care 1990; 13(6): 631-54.
[http://dx.doi.org/10.2337/diacare.13.6.631] [PMID: 2192848]
[84]
Lechner K, McKenzie AL, Kränkel N, et al. High-risk atherosclerosis and metabolic phenotype: The roles of ectopic adiposity, atherogenic dyslipidemia, and inflammation. Metab Syndr Relat Disord 2020; 18(4): 176-85.
[http://dx.doi.org/10.1089/met.2019.0115] [PMID: 32119801]
[85]
Steinberg H, Baron A. Vascular function, insulin resistance and fatty acids. Diabetologia 2002; 45(5): 623-34.
[http://dx.doi.org/10.1007/s00125-002-0800-2] [PMID: 12107742]
[86]
Andronico G, Ferraro-Mortellaro R, Mangano M, et al. Insulin resistance and glomerular hemodynamics in essential hypertension. Kidney Int 2002; 62(3): 1005-9.
[http://dx.doi.org/10.1046/j.1523-1755.2002.00529.x] [PMID: 12164884]
[87]
DeFronzo RA. Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: The missing links. The Claude Bernard Lecture 2009. Diabetologia 2010; 53(7): 1270-87.
[http://dx.doi.org/10.1007/s00125-010-1684-1] [PMID: 20361178]
[88]
Raz I. Exogenous hyperinsulinemia and atherosclerosis in type 1 diabetic patients. J Diabetes Complications 2013; 27(1): 2-3.
[http://dx.doi.org/10.1016/j.jdiacomp.2012.10.003] [PMID: 23151316]
[89]
Matteucci E, Giampietro O, Covolan V, Giustarini D, Fanti P, Rossi R. Insulin administration: Present strategies and future directions for a noninvasive (possibly more physiological) delivery. Drug Des Devel Ther 2015; 9: 3109-18.
[http://dx.doi.org/10.2147/DDDT.S79322] [PMID: 26124635]
[90]
Schwartz SS, Jellinger PS, Herman ME. Obviating much of the need for insulin therapy in type 2 diabetes mellitus: A re-assessment of insulin therapy’s safety profile. Postgrad Med 2016; 128(6): 609-19.
[http://dx.doi.org/10.1080/00325481.2016.1191955] [PMID: 27210018]
[91]
Jandeleit-Dahm KAM, Gray SP. Insulin and cardiovascular disease: Biomarker or association? Diabetologia 2012; 55(12): 3145-51.
[http://dx.doi.org/10.1007/s00125-012-2729-4] [PMID: 23052054]
[92]
Wang MY, Yu X, Lee Y, et al. Iatrogenic hyperinsulinemia in type 1 diabetes: Its effect on atherogenic risk markers. J Diabetes Complications 2013; 27(1): 70-4.
[http://dx.doi.org/10.1016/j.jdiacomp.2012.08.008] [PMID: 23079124]
[93]
Draznin B. Mechanism of the mitogenic influence of hyperinsulinemia. Diabetol Metab Syndr 2011; 3(1): 10.
[http://dx.doi.org/10.1186/1758-5996-3-10] [PMID: 21668983]
[94]
Muis MJ, Bots ML, Grobbee DE, Stolk RP. Insulin treatment and cardiovascular disease; friend or foe? A point of view. Diabet Med 2005; 22(2): 118-26.
[http://dx.doi.org/10.1111/j.1464-5491.2004.01416.x] [PMID: 15660727]
[95]
Henry RR, Gumbiner B, Ditzler T, Wallace P, Lyon R, Glauber HS. Intensive Conventional Insulin Therapy for Type II Diabetes: Metabolic effects during a 6-mo outpatient trial. Diabetes Care 1993; 16(1): 21-31.
[http://dx.doi.org/10.2337/diacare.16.1.21] [PMID: 8422777]
[96]
Gupta S, Wang H, Skolnik N, et al. Treatment dosing patterns and clinical outcomes for patients with type 2 diabetes starting or switching to treatment with insulin glargine (300 units per milliliter) in a real-world setting: A retrospective observational study. Adv Ther 2018; 35(1): 43-55.
[http://dx.doi.org/10.1007/s12325-017-0651-3] [PMID: 29313285]
[97]
Church TJ, Haines ST. Treatment approach to patients with severe insulin resistance. Clin Diabetes 2016; 34(2): 97-104.
[http://dx.doi.org/10.2337/diaclin.34.2.97] [PMID: 27092020]
[98]
Ovalle F. Clinical approach to the patient with diabetes mellitus and very high insulin requirements. Diabetes Res Clin Pract 2010; 90(3): 231-42.
[http://dx.doi.org/10.1016/j.diabres.2010.06.025] [PMID: 20724017]
[99]
Pontiroli AE, Miele L, Morabito A. Increase of body weight during the first year of intensive insulin treatment in type 2 diabetes: Systematic review and meta-analysis. Diabetes Obes Metab 2011; 13(11): 1008-19.
[http://dx.doi.org/10.1111/j.1463-1326.2011.01433.x] [PMID: 21645195]
[100]
McFarlane SI. Insulin therapy and type 2 diabetes: Management of weight gain. J Clin Hypertens (Greenwich) 2009; 11(10): 601-7.
[http://dx.doi.org/10.1111/j.1751-7176.2009.00063.x] [PMID: 19817944]
[101]
Brown A, Guess N, Dornhorst A, Taheri S, Frost G. Insulin‐associated weight gain in obese type 2 diabetes mellitus patients: What can be done? Diabetes Obes Metab 2017; 19(12): 1655-68.
[http://dx.doi.org/10.1111/dom.13009] [PMID: 28509408]
[102]
Papaetis G, Kyriacou A. GLP-1 receptor agonists, polycystic ovary syndrome and reproductive dysfunction: Current research and future horizons. Adv Clin Exp Med 2022; 31(11): 1265-74.
[http://dx.doi.org/10.17219/acem/151695] [PMID: 35951627]
[103]
Biesenbach G, Raml A, Alsaraji N. Weight gain and insulin requirement in type 2 diabetic patients during the first year after initiating insulin therapy dependent on baseline BMI. Diabetes Obes Metab 2006; 8(6): 669-73.
[http://dx.doi.org/10.1111/j.1463-1326.2005.00552.x] [PMID: 17026491]
[104]
Mendez CE, Walker RJ, Eiler CR, Mishriky BM, Egede LE. Insulin therapy in patients with type 2 diabetes and high insulin resistance is associated with increased risk of complications and mortality. Postgrad Med 2019; 131(6): 376-82.
[http://dx.doi.org/10.1080/00325481.2019.1643635] [PMID: 31311382]
[105]
Gerstein HC, Bosch J, Dagenais GR, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 2012; 367(4): 319-28.
[http://dx.doi.org/10.1056/NEJMoa1203858] [PMID: 22686416]
[106]
Marso SP, McGuire DK, Zinman B, et al. Efficacy and safety of degludec versus glargine in type 2 diabetes. N Engl J Med 2017; 377(8): 723-32.
[http://dx.doi.org/10.1056/NEJMoa1615692] [PMID: 28605603]
[107]
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). Lancet 1998; 352(9131): 837-53.
[http://dx.doi.org/10.1016/S0140-6736(98)07019-6] [PMID: 9742976]
[108]
Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 2005; 353(25): 2643-53.
[http://dx.doi.org/10.1056/NEJMoa052187] [PMID: 16371630]
[109]
Purnell JQ, Braffett BH, Zinman B, et al. Impact of excessive weight gain on cardiovascular outcomes in type 1 diabetes: Results from the diabetes control and complications trial/epidemiology of diabetes interventions and complications (DCCT/EDIC) study. Diabetes Care 2017; 40(12): 1756-62.
[http://dx.doi.org/10.2337/dc16-2523] [PMID: 29138273]
[110]
Masrouri S, Shapiro MD, Khalili D, Hadaegh F. Impact of coronary artery calcium on mortality and cardiovascular events in metabolic syndrome and diabetes among younger adults. Eur J Prev Cardiol 2024; 31(6): 744-53.
[http://dx.doi.org/10.1093/eurjpc/zwae039] [PMID: 38323650]
[111]
Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group. Intensive Diabetes Treatment and Cardiovascular Outcomes in Type 1 Diabetes: The DCCT/EDIC Study 30-Year Follow-up. Diabetes Care 2016; 39(5): 686-93.
[http://dx.doi.org/10.2337/dc15-1990] [PMID: 26861924]
[112]
Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988; 37(12): 1595-607.
[http://dx.doi.org/10.2337/diab.37.12.1595] [PMID: 3056758]
[113]
Norton L, Shannon C, Gastaldelli A, DeFronzo RA. Insulin: The master regulator of glucose metabolism. Metabolism 2022; 129: 155142.
[http://dx.doi.org/10.1016/j.metabol.2022.155142] [PMID: 35066003]
[114]
Reaven GM. Insulin resistance, the insulin resistance syndrome, and cardiovascular disease. Panminerva Med 2005; 47(4): 201-10.
[PMID: 16489319]
[115]
Reaven GM. Insulin resistance, cardiovascular disease, and the metabolic syndrome: How well do the emperor’s clothes fit? Diabetes Care 2004; 27(4): 1011-2.
[http://dx.doi.org/10.2337/diacare.27.4.1011] [PMID: 15047666]
[116]
Castro JP, El-Atat FA, McFarlane SI, Aneja A, Sowers JR. Cardiometabolic syndrome: Pathophysiology and treatment. Curr Hypertens Rep 2003; 5(5): 393-401.
[http://dx.doi.org/10.1007/s11906-003-0085-y] [PMID: 12948432]
[117]
Lastra G, Manrique C, McFarlane SI, Sowers JR. Cardiometabolic syndrome and chronic kidney disease. Curr Diab Rep 2006; 6(3): 207-12.
[http://dx.doi.org/10.1007/s11892-006-0036-5] [PMID: 16898573]
[118]
Gill H, Mugo M, Whaley-Connell A, Stump C, Sowers JR. The key role of insulin resistance in the cardiometabolic syndrome. Am J Med Sci 2005; 330(6): 290-4.
[http://dx.doi.org/10.1097/00000441-200512000-00006] [PMID: 16355013]
[119]
Whaley-Connell A, Sowers JR. Basic science. J Am Soc Hypertens 2014; 8(8): 604-6.
[http://dx.doi.org/10.1016/j.jash.2014.07.003] [PMID: 25151323]
[120]
Hu G, Qiao Q, Tuomilehto J, Balkau B, Borch-Johnsen K, Pyorala K. Prevalence of the metabolic syndrome and its relation to all-cause and cardiovascular mortality in nondiabetic European men and women. Arch Intern Med 2004; 164(10): 1066-76.
[http://dx.doi.org/10.1001/archinte.164.10.1066] [PMID: 15159263]
[121]
Santomauro AT, Boden G, Silva ME, et al. Overnight lowering of free fatty acids with Acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects. Diabetes 1999; 48(9): 1836-41.
[http://dx.doi.org/10.2337/diabetes.48.9.1836] [PMID: 10480616]
[122]
Iqbal J, Al Qarni A, Hawwari A, Alghanem AF, Ahmed G. Metabolic syndrome, dyslipidemia and regulation of lipoprotein metabolism. Curr Diabetes Rev 2018; 14(5): 427-33.
[http://dx.doi.org/10.2174/1573399813666170705161039] [PMID: 28677496]
[123]
Bjornstad P, Eckel RH. Pathogenesis of lipid disorders in insulin resistance: A brief review. Curr Diab Rep 2018; 18(12): 127.
[http://dx.doi.org/10.1007/s11892-018-1101-6] [PMID: 30328521]
[124]
Krauss RM. Lipids and lipoproteins in patients with type 2 diabetes. Diabetes Care 2004; 27(6): 1496-504.
[http://dx.doi.org/10.2337/diacare.27.6.1496] [PMID: 15161808]
[125]
Mineo C, Deguchi H, Griffin JH, Shaul PW. Endothelial and antithrombotic actions of HDL. Circ Res 2006; 98(11): 1352-64.
[http://dx.doi.org/10.1161/01.RES.0000225982.01988.93] [PMID: 16763172]
[126]
Tall AR. An overview of reverse cholesterol transport. Eur Heart J 1998; 19 (Suppl. A): A31-5.
[127]
Qu L, Fang S, Lan Z, et al. Association between atherogenic index of plasma and new-onset stroke in individuals with different glucose metabolism status: Insights from CHARLS. Cardiovasc Diabetol 2024; 23(1): 215.
[http://dx.doi.org/10.1186/s12933-024-02314-y] [PMID: 38907337]
[128]
Rokicka D, Hudzik B, Wróbel M, et al. The prognostic impact of insulin resistance surrogates in patients with acute myocardial infarction with and without type 2 diabetes. Cardiovasc Diabetol 2024; 23(1): 147.
[http://dx.doi.org/10.1186/s12933-024-02240-z] [PMID: 38685054]
[129]
Dong W, Gong Y, Zhao J, Wang Y, Li B, Yang Y. A combined analysis of TyG index, SII index, and SIRI index: Positive association with CHD risk and coronary atherosclerosis severity in patients with NAFLD. Front Endocrinol (Lausanne) 2024; 14: 1281839.
[http://dx.doi.org/10.3389/fendo.2023.1281839] [PMID: 38260163]
[130]
Lembo G, Napoli R, Capaldo B, et al. Abnormal sympathetic overactivity evoked by insulin in the skeletal muscle of patients with essential hypertension. J Clin Invest 1992; 90(1): 24-9.
[http://dx.doi.org/10.1172/JCI115842] [PMID: 1634611]
[131]
Sowers JR. Hypertension, angiotensin II, and oxidative stress. N Engl J Med 2002; 346(25): 1999-2001.
[http://dx.doi.org/10.1056/NEJMe020054] [PMID: 12075063]
[132]
Lamounier-Zepter V, Ehrhart-Bornstein M, Bornstein SR. Insulin resistance in hypertension and cardiovascular disease. Best Pract Res Clin Endocrinol Metab 2006; 20(3): 355-67.
[http://dx.doi.org/10.1016/j.beem.2006.07.002] [PMID: 16980199]
[133]
Hall J, Brands MW, Henegar JR. Mechanisms of hypertension and kidney disease in obesity. Ann N Y Acad Sci 1999; 892(1): 91-107.
[http://dx.doi.org/10.1111/j.1749-6632.1999.tb07788.x] [PMID: 10842655]
[134]
Wang F, Han L, Hu D. Fasting insulin, insulin resistance and risk of hypertension in the general population: A meta-analysis. Clin Chim Acta 2017; 464: 57-63.
[http://dx.doi.org/10.1016/j.cca.2016.11.009] [PMID: 27836689]
[135]
Calhoun DA. Use of aldosterone antagonists in resistant hypertension. Prog Cardiovasc Dis 2006; 48(6): 387-96.
[http://dx.doi.org/10.1016/j.pcad.2006.02.002] [PMID: 16714158]
[136]
Groenland EH, Bots ML, Asselbergs FW, et al. Apparent treatment resistant hypertension and the risk of recurrent cardiovascular events and mortality in patients with established vascular disease. Int J Cardiol 2021; 334: 135-41.
[http://dx.doi.org/10.1016/j.ijcard.2021.04.047] [PMID: 33932429]
[137]
Briones AM, Nguyen Dinh Cat A, Callera GE, et al. Adipocytes produce aldosterone through calcineurin-dependent signaling pathways: Implications in diabetes mellitus-associated obesity and vascular dysfunction. Hypertension 2012; 59(5): 1069-78.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.111.190223] [PMID: 22493070]
[138]
Rao A, Pandya V, Whaley-Connell A. Obesity and insulin resistance in resistant hypertension: Implications for the kidney. Adv Chronic Kidney Dis 2015; 22(3): 211-7.
[http://dx.doi.org/10.1053/j.ackd.2014.12.004] [PMID: 25908470]
[139]
Wada T, Ohshima S, Fujisawa E, Koya D, Tsuneki H, Sasaoka T. Aldosterone inhibits insulin-induced glucose uptake by degradation of insulin receptor substrate (IRS) 1 and IRS2 via a reactive oxygen species-mediated pathway in 3T3-L1 adipocytes. Endocrinology 2009; 150(4): 1662-9.
[http://dx.doi.org/10.1210/en.2008-1018] [PMID: 19095745]
[140]
Li P, Zhang XN, Pan CM, et al. Aldosterone perturbs adiponectin and PAI-1 expression and secretion in 3T3-L1 adipocytes. Horm Metab Res 2011; 43(7): 464-9.
[http://dx.doi.org/10.1055/s-0031-1277226] [PMID: 21667402]
[141]
Gilbert KC, Brown NJ. Aldosterone and inflammation. Curr Opin Endocrinol Diabetes Obes 2010; 17(3): 199-204.
[http://dx.doi.org/10.1097/MED.0b013e3283391989] [PMID: 20422780]
[142]
Papaetis GS. Incretin-based therapies in prediabetes: Current evidence and future perspectives. World J Diabetes 2014; 5(6): 817-34.
[http://dx.doi.org/10.4239/wjd.v5.i6.817] [PMID: 25512784]
[143]
Kanat M, Winnier D, Norton L, et al. The relationship between beta-cell function and glycated hemoglobin: Results from the veterans administration genetic epidemiology study. Diabetes Care 2011; 34(4): 1006-10.
[http://dx.doi.org/10.2337/dc10-1352] [PMID: 21346184]
[144]
Papaetis GS. Empagliflozin therapy and insulin resistance-associated disorders: Effects and promises beyond a diabetic state. Arch Med Sci Atheroscler Dis 2021; 6: e57-78.
[http://dx.doi.org/10.5114/amsad.2021.105314] [PMID: 34027215]
[145]
Pendergrass M, Bertoldo A, Bonadonna R, et al. Muscle glucose transport and phosphorylation in type 2 diabetic, obese nondiabetic, and genetically predisposed individuals. Am J Physiol Endocrinol Metab 2007; 292(1): E92-E100.
[http://dx.doi.org/10.1152/ajpendo.00617.2005] [PMID: 16896161]
[146]
Abdul-Ghani MA, Tripathy D, DeFronzo RA. Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose. Diabetes Care 2006; 29(5): 1130-9.
[http://dx.doi.org/10.2337/dc05-2179] [PMID: 16644654]
[147]
Coutinho M, Gerstein HC, Wang Y, Yusuf S. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care 1999; 22(2): 233-40.
[http://dx.doi.org/10.2337/diacare.22.2.233] [PMID: 10333939]
[148]
Decode Study Group, the European Diabetes Epidemiology Group.. Glucose tolerance and cardiovascular mortality: Comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med 2001; 161(3): 397-405.
[http://dx.doi.org/10.1001/archinte.161.3.397] [PMID: 11176766]
[149]
Qiao Q, Pyörälä K, Pyörälä M, et al. Two-hour glucose is a better risk predictor for incident coronary heart disease and cardiovascular mortality than fasting glucose. Eur Heart J 2002; 23(16): 1267-75.
[http://dx.doi.org/10.1053/euhj.2001.3113] [PMID: 12175663]
[150]
Rijkelijkhuizen JM, Nijpels G, Heine RJ, Bouter LM, Stehouwer CDA, Dekker JM. High risk of cardiovascular mortality in individuals with impaired fasting glucose is explained by conversion to diabetes: The Hoorn study. Diabetes Care 2007; 30(2): 332-6.
[http://dx.doi.org/10.2337/dc06-1238] [PMID: 17259503]
[151]
DeFronzo RA, Abdul-Ghani M. Assessment and treatment of cardiovascular risk in prediabetes: Impaired glucose tolerance and impaired fasting glucose. Am J Cardiol 2011; 108(3): 3B-24B.
[http://dx.doi.org/10.1016/j.amjcard.2011.03.013] [PMID: 21802577]
[152]
Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetes patients. Diabetes Care 2003; 26(3): 881-5.
[http://dx.doi.org/10.2337/diacare.26.3.881] [PMID: 12610053]
[153]
Saely CH, Drexel H, Sourij H, et al. Key role of postchallenge hyperglycemia for the presence and extent of coronary atherosclerosis: An angiographic study. Atherosclerosis 2008; 199(2): 317-22.
[http://dx.doi.org/10.1016/j.atherosclerosis.2007.11.020] [PMID: 18187138]
[154]
Ceriello A. Impaired glucose tolerance and cardiovascular disease: The possible role of post-prandial hyperglycemia. Am Heart J 2004; 147(5): 803-7.
[http://dx.doi.org/10.1016/j.ahj.2003.11.020] [PMID: 15131534]
[155]
Liang Y, Wang M, Wang C, Liu Y, Naruse K, Takahashi K. The mechanisms of the development of atherosclerosis in prediabetes. Int J Mol Sci 2021; 22(8): 4108.
[http://dx.doi.org/10.3390/ijms22084108] [PMID: 33921168]
[156]
Kawai T, Autieri MV, Scalia R. Adipose tissue inflammation and metabolic dysfunction in obesity. Am J Physiol Cell Physiol 2021; 320(3): C375-91.
[http://dx.doi.org/10.1152/ajpcell.00379.2020] [PMID: 33356944]
[157]
Catalano KJ, Stefanovski D, Bergman RN. Critical role of the mesenteric depot versus other intra-abdominal adipose depots in the development of insulin resistance in young rats. Diabetes 2010; 59(6): 1416-23.
[http://dx.doi.org/10.2337/db08-0675] [PMID: 20299478]
[158]
Papaetis GS, Orphanidou D, Panagiotou TN. Thiazolidinediones and type 2 diabetes: From cellular targets to cardiovascular benefit. Curr Drug Targets 2011; 12(10): 1498-512.
[http://dx.doi.org/10.2174/138945011796818243] [PMID: 21675944]
[159]
Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 2007; 117(1): 175-84.
[http://dx.doi.org/10.1172/JCI29881] [PMID: 17200717]
[160]
Lee Y, Wang MY, Kakuma T, et al. Liporegulation in diet-induced obesity. The antisteatotic role of hyperleptinemia. J Biol Chem 2001; 276(8): 5629-35.
[http://dx.doi.org/10.1074/jbc.M008553200] [PMID: 11096093]
[161]
Faber DR, De Groot PG, Visseren FLJ. Role of adipose tissue in haemostasis, coagulation and fibrinolysis. Obes Rev 2009; 10(5): 554-63.
[http://dx.doi.org/10.1111/j.1467-789X.2009.00593.x] [PMID: 19460118]
[162]
Yamamoto K, Takeshita K, Kojima T, Takamatsu J, Saito H. Aging and plasminogen activator inhibitor-1 (PAI-1) regulation: Implication in the pathogenesis of thrombotic disorders in the elderly. Cardiovasc Res 2005; 66(2): 276-85.
[http://dx.doi.org/10.1016/j.cardiores.2004.11.013] [PMID: 15820196]
[163]
Samad F, Ruf W. Inflammation, obesity, and thrombosis. Blood 2013; 122(20): 3415-22.
[http://dx.doi.org/10.1182/blood-2013-05-427708] [PMID: 24092932]
[164]
Santilli F, Vazzana N, Liani R, Guagnano MT, Davì G. Platelet activation in obesity and metabolic syndrome. Obes Rev 2012; 13(1): 27-42.
[http://dx.doi.org/10.1111/j.1467-789X.2011.00930.x] [PMID: 21917110]
[165]
Tsai AG, Bessesen DH. Obesity. Ann Intern Med 2019; 170(5): ITC33-48.
[http://dx.doi.org/10.7326/AITC201903050] [PMID: 30831593]
[166]
Kitabchi AE, Temprosa M, Knowler WC, et al. Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the diabetes prevention program: Effects of lifestyle intervention and metformin. Diabetes 2005; 54(8): 2404-14.
[http://dx.doi.org/10.2337/diabetes.54.8.2404] [PMID: 16046308]
[167]
Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346(6): 393-403.
[http://dx.doi.org/10.1056/NEJMoa012512] [PMID: 11832527]
[168]
Delahanty LM, Trief PM, Cibula DA, Weinstock RS. Barriers to weight loss and physical activity, and coach approaches to addressing barriers, in a real-world adaptation of the DPP lifestyle intervention: A process analysis. Diabetes Educ 2019; 45(6): 596-606.
[http://dx.doi.org/10.1177/0145721719883615] [PMID: 31682536]
[169]
Arterburn DE, Telem DA, Kushner RF, Courcoulas AP. Benefits and risks of bariatric surgery in adults: A review. JAMA 2020; 324(9): 879-87.
[http://dx.doi.org/10.1001/jama.2020.12567] [PMID: 32870301]
[170]
Sarkhosh K, Switzer NJ, El-Hadi M, Birch DW, Shi X, Karmali S. The impact of bariatric surgery on obstructive sleep apnea: A systematic review. Obes Surg 2013; 23(3): 414-23.
[http://dx.doi.org/10.1007/s11695-012-0862-2] [PMID: 23299507]
[171]
Escobar-Morreale HF, Botella-Carretero JI, Álvarez-Blasco F, Sancho J, San Millán JL. The polycystic ovary syndrome associated with morbid obesity may resolve after weight loss induced by bariatric surgery. J Clin Endocrinol Metab 2005; 90(12): 6364-9.
[http://dx.doi.org/10.1210/jc.2005-1490] [PMID: 16189250]
[172]
Athanasiadis DI, Martin A, Kapsampelis P, Monfared S, Stefanidis D. Factors associated with weight regain post-bariatric surgery: A systematic review. Surg Endosc 2021; 35(8): 4069-84.
[http://dx.doi.org/10.1007/s00464-021-08329-w] [PMID: 33650001]
[173]
Liu F, Wang Y, Yu J. Role of inflammation and immune response in atherosclerosis: Mechanisms, modulations, and therapeutic targets. Hum Immunol 2023; 84(9): 439-49.
[http://dx.doi.org/10.1016/j.humimm.2023.06.002] [PMID: 37353446]
[174]
Larsson J, Auscher S, Shamoun A, et al. Insulin resistance is associated with high-risk coronary artery plaque composition in asymptomatic men between 65 and 75 years and no diabetes: A DANCAVAS cross-sectional sub-study. Atherosclerosis 2023; 385: 117328.
[http://dx.doi.org/10.1016/j.atherosclerosis.2023.117328] [PMID: 38390826]
[175]
Berisha-Muharremi V, Majnaric-Trtica L, Mujaj B. Insulin resistance is an important index to assess glucose and insulin metabolism, but not a biological risk factor for high-risk coronary artery plaque composition. Atherosclerosis 2024; 392: 117484.
[http://dx.doi.org/10.1016/j.atherosclerosis.2024.117484] [PMID: 38433071]
[176]
Larsson J, Auscher S, Pararajasingam G, et al. Reply to: “Insulin resistance is an important index to assess glucose and insulin metabolism, but not a biological risk factor for high-risk coronary artery plaque composition”. Atherosclerosis 2024; 392: 117524.
[http://dx.doi.org/10.1016/j.atherosclerosis.2024.117524] [PMID: 38523001]
[177]
Julla JB, Girard D, Diedisheim M, et al. Blood Monocyte Phenotype Is A Marker of Cardiovascular Risk in Type 2 Diabetes. Circ Res 2024; 134(2): 189-202.
[http://dx.doi.org/10.1161/CIRCRESAHA.123.322757] [PMID: 38152893]
[178]
Ridker PM, Bhatt DL, Pradhan AD, Glynn RJ, MacFadyen JG, Nissen SE. Inflammation and cholesterol as predictors of cardiovascular events among patients receiving statin therapy: A collaborative analysis of three randomised trials. Lancet 2023; 401(10384): 1293-301.
[http://dx.doi.org/10.1016/S0140-6736(23)00215-5] [PMID: 36893777]
[179]
Evans JL, Youngren JF, Goldfine ID. Effective treatments for insulin resistance: Trim the fat and douse the fire. Trends Endocrinol Metab 2004; 15(9): 425-31.
[http://dx.doi.org/10.1016/j.tem.2004.09.005] [PMID: 15519889]
[180]
Stagakis I, Bertsias G, Karvounaris S, et al. Anti-tumor necrosis factor therapy improves insulin resistance, beta cell function and insulin signaling in active rheumatoid arthritis patients with high insulin resistance. Arthritis Res Ther 2012; 14(3): R141.
[http://dx.doi.org/10.1186/ar3874] [PMID: 22691241]
[181]
van den Oever IAM, Baniaamam M, Simsek S, et al. The effect of anti-TNF treatment on body composition and insulin resistance in patients with rheumatoid arthritis. Rheumatol Int 2021; 41(2): 319-28.
[http://dx.doi.org/10.1007/s00296-020-04666-6] [PMID: 32776224]
[182]
Hassan NF, Hassan AH, El-Ansary MR. Cytokine modulation by etanercept ameliorates metabolic syndrome and its related complications induced in rats administered a high-fat high-fructose diet. Sci Rep 2022; 12(1): 20227.
[http://dx.doi.org/10.1038/s41598-022-24593-9] [PMID: 36418417]
[183]
Bernstein LE, Berry J, Kim S, Canavan B, Grinspoon SK. Effects of etanercept in patients with the metabolic syndrome. Arch Intern Med 2006; 166(8): 902-8.
[http://dx.doi.org/10.1001/archinte.166.8.902] [PMID: 16636217]
[184]
Li Z, Lin C, Cai X, et al. Anti-inflammatory therapies were associated with reduced risk of myocardial infarction in patients with established cardiovascular disease or high cardiovascular risks: A systematic review and meta-analysis of randomized controlled trials. Atherosclerosis 2023; 379: 117181.
[http://dx.doi.org/10.1016/j.atherosclerosis.2023.06.972] [PMID: 37527612]
[185]
Tardif JC, Kouz S, Waters DD, et al. Efficacy and safety of low-dose colchicine after myocardial infarction. N Engl J Med 2019; 381(26): 2497-505.
[http://dx.doi.org/10.1056/NEJMoa1912388] [PMID: 31733140]
[186]
Schwarz N, Fernando S, Chen YC, et al. Colchicine exerts anti‐atherosclerotic and plaque‐stabilizing effects targeting foam cell formation. FASEB J 2023; 37(4): e22846.
[http://dx.doi.org/10.1096/fj.202201469R] [PMID: 36856983]
[187]
Demidowich AP, Levine JA, Onyekaba GI, et al. Effects of colchicine in adults with metabolic syndrome: A pilot randomized controlled trial. Diabetes Obes Metab 2019; 21(7): 1642-51.
[http://dx.doi.org/10.1111/dom.13702] [PMID: 30869182]
[188]
Spence JD, Viscoli C, Kernan WN, et al. Efficacy of lower doses of pioglitazone after stroke or transient ischaemic attack in patients with insulin resistance. Diabetes Obes Metab 2022; 24(6): 1150-8.
[http://dx.doi.org/10.1111/dom.14687] [PMID: 35253334]
[189]
Papaetis GS. Pioglitazone, bladder cancer, and the presumption of innocence. Curr Drug Saf 2022; 17(4): 294-318.
[http://dx.doi.org/10.2174/1574886317666220304124756] [PMID: 35249505]
[190]
Papaetis G. Pioglitazone in diabetic kidney disease: Forgotten but not gone. Arch Med Sci Atheroscler Dis 2022; 7(1): 78-93.
[http://dx.doi.org/10.5114/amsad/151046] [PMID: 36158067]
[191]
Meiring S, Busch CBE, van Baar ACG, et al. Eliminating exogenous insulin therapy in patients with type 2 diabetes by duodenal ablation and GLP-1RA decreases risk scores for cardiovascular events. Cardiovasc Diabetol 2022; 21(1): 191.
[http://dx.doi.org/10.1186/s12933-022-01628-z] [PMID: 36138441]
[192]
Meiring S, Meessen ECE, van Baar ACG, et al. Duodenal mucosal resurfacing with a GLP-1 receptor agonist increases postprandial unconjugated bile acids in patients with insulin-dependent type 2 diabetes. Am J Physiol Endocrinol Metab 2022; 322(2): E132-40.
[http://dx.doi.org/10.1152/ajpendo.00337.2021] [PMID: 34957857]
[193]
Wolosowicz M, Prokopiuk S, Kaminski TW. Recent advances in the treatment of insulin resistance targeting molecular and metabolic pathways: Fighting a losing battle? Medicina (Kaunas) 2022; 58(4): 472.
[http://dx.doi.org/10.3390/medicina58040472] [PMID: 35454311]
[194]
Lee CJ, Sears CL, Maruthur N. Gut microbiome and its role in obesity and insulin resistance. Ann N Y Acad Sci 2020; 1461(1): 37-52.
[http://dx.doi.org/10.1111/nyas.14107] [PMID: 31087391]
[195]
Ballanti M, Antonetti L, Mavilio M, et al. Decreased circulating IPA levels identify subjects with metabolic comorbidities: A multi-omics study. Pharmacol Res 2024; 204: 107207.
[http://dx.doi.org/10.1016/j.phrs.2024.107207] [PMID: 38734193]
[196]
Lee SH, Park SY, Choi CS. Insulin Resistance: From Mechanisms to Therapeutic Strategies. Diabetes Metab J 2022; 46(1): 15-37.
[http://dx.doi.org/10.4093/dmj.2021.0280] [PMID: 34965646]
[197]
Mastrototaro L, Roden M. Insulin resistance and insulin sensitizing agents. Metabolism 2021; 125: 154892.
[http://dx.doi.org/10.1016/j.metabol.2021.154892] [PMID: 34563556]
[198]
Schreyer E, Obringer C, Messaddeq N, et al. PATAS, a first-in-class therapeutic peptide biologic, improves whole-body insulin resistance and associated comorbidities in vivo. Diabetes 2022; 71(9): 2034-47.
[http://dx.doi.org/10.2337/db22-0058] [PMID: 35822820]
[199]
Sangwung P, Petersen KF, Shulman GI, Knowles JW. Mitochondrial dysfunction, insulin resistance, and potential genetic implications. Endocrinology 2020; 161(4): bqaa017.
[http://dx.doi.org/10.1210/endocr/bqaa017] [PMID: 32060542]
[200]
Ciccarelli G, Conte S, Cimmino G, Maiorano P, Morrione A, Giordano A. Mitochondrial Dysfunction: The hidden player in the pathogenesis of atherosclerosis? Int J Mol Sci 2023; 24(2): 1086.
[http://dx.doi.org/10.3390/ijms24021086] [PMID: 36674602]
[201]
Abdel Mageed SS, Doghish AS, Ismail A, et al. The role of miRNAs in insulin resistance and diabetic macrovascular complications – A review. Int J Biol Macromol 2023; 230: 123189.
[http://dx.doi.org/10.1016/j.ijbiomac.2023.123189] [PMID: 36623613]
[202]
Zhou D, Lu P, Mo X, et al. Ferroptosis and metabolic syndrome and complications: Association, mechanism, and translational applications. Front Endocrinol (Lausanne) 2024; 14: 1248934.
[http://dx.doi.org/10.3389/fendo.2023.1248934] [PMID: 38260171]
[203]
Sasaki N, Ueno Y, Ozono R, Nakano Y, Higashi Y. Insulin resistance in the adipose tissue predicts future vascular resistance: The Hiroshima Study on Glucose Metabolism and Cardiovascular Diseases. Atherosclerosis 2024; 393: 117547.
[http://dx.doi.org/10.1016/j.atherosclerosis.2024.117547] [PMID: 38703418]
[204]
Liu G. Association between the metabolic score for insulin resistance (METS-IR) and arterial stiffness among health check-up population in Japan: A retrospective cross-sectional study. Front Endocrinol (Lausanne) 2024; 14: 1308719.
[http://dx.doi.org/10.3389/fendo.2023.1308719] [PMID: 38229737]
[205]
Reaven GM. Why Syndrome X? From Harold Himsworth to the insulin resistance syndrome. Cell Metab 2005; 1(1): 9-14.
[http://dx.doi.org/10.1016/j.cmet.2004.12.001] [PMID: 16054040]
[206]
De Vriese AS, Verbeuren TJ, Van de Voorde J, Lameire NH, Vanhoutte PM. Endothelial dysfunction in diabetes. Br J Pharmacol 2000; 130(5): 963-74.
[http://dx.doi.org/10.1038/sj.bjp.0703393] [PMID: 10882379]
[207]
Papaetis GS. SGLT2 inhibitors, intrarenal hypoxia and the diabetic kidney: Insights into pathophysiological concepts and current evidence. Arch Med Sci Atheroscler Dis 2023; 8(1): 155-68.
[http://dx.doi.org/10.5114/amsad/176658] [PMID: 38283924]
[208]
Golden SH, Folsom AR, Coresh J, Sharrett AR, Szklo M, Brancati F. Risk factor groupings related to insulin resistance and their synergistic effects on subclinical atherosclerosis: The atherosclerosis risk in communities study. Diabetes 2002; 51(10): 3069-76.
[http://dx.doi.org/10.2337/diabetes.51.10.3069] [PMID: 12351449]
[209]
D’Agostino RB Sr, Grundy S, Sullivan LM, Wilson P. Validation of the Framingham coronary heart disease prediction scores: Results of a multiple ethnic groups investigation. JAMA 2001; 286(2): 180-7.
[http://dx.doi.org/10.1001/jama.286.2.180] [PMID: 11448281]
[210]
Di Pino A, DeFronzo RA. Insulin resistance and atherosclerosis: Implications for insulin-sensitizing agents. Endocr Rev 2019; 40(6): 1447-67.
[http://dx.doi.org/10.1210/er.2018-00141] [PMID: 31050706]
[211]
Onyango AN. Cellular stresses and stress responses in the pathogenesis of insulin resistance. Oxid Med Cell Longev 2018; 2018(1): 4321714.
[http://dx.doi.org/10.1155/2018/4321714] [PMID: 30116482]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy