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Current Diabetes Reviews

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ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

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General Review Article

Diabetic Complications: An Update on Pathobiology and Therapeutic Strategies

Author(s): Karthika Nellaiappan, Kumari Preeti, Dharmendra Kumar Khatri and Shashi Bala Singh*

Volume 18, Issue 1, 2022

Published on: 09 March, 2021

Article ID: e030821192146 Pages: 14

DOI: 10.2174/1573399817666210309104203

Price: $65

Abstract

Despite the advent of novel therapies which manage and control diabetes well, the increased risk of morbidity and mortality in diabetic subjects is associated with the devastating secondary complications it produces. Long-standing diabetes majorly drives cellular and molecular alterations, which eventually damage both small and large blood vessels. The complications are prevalent both in type I and type II diabetic subjects. The microvascular complications include diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, while the macrovascular complications include diabetic heart disease and stroke. The current therapeutic strategy alleviates the complications to some extent but does not cure or prevent them. Also, the recent clinical trial outcomes in this field are disappointing. Success in the drug discovery of diabetic complications may be achieved by a better understanding of the underlying pathophysiology and by recognising the crucial factors contributing to the development and progression of the disease. In this review, we discuss the well-studied cellular mechanisms leading to the development and progression of diabetic complications. In addition, we also highlight the various therapeutic paradigms currently in clinical practice.

Keywords: Diabetes, diabetic neuropathy, diabetic kidney disease, diabetic retinopathy, diabetic heart disease, pathophysiology, drug-discovery.

[1]
Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010; 87(1): 4-14.
[http://dx.doi.org/10.1016/j.diabres.2009.10.007] [PMID: 19896746]
[2]
Mathis D, Vence L, Benoist C. β-Cell death during progression to diabetes. Nature 2001; 414(6865): 792-8.
[http://dx.doi.org/10.1038/414792a] [PMID: 11742411]
[3]
Kempen JH, Friedman DS, Congdon NG, Group BODPS. The prevalence of diabetic retinopathy in the united states. Invest Ophthalmol Vis Sci 2002; 43(13): 4381-1.
[4]
Lim AKh. Diabetic nephropathy - complications and treatment. Int J Nephrol Renovasc Dis 2014; 7: 361-81.
[http://dx.doi.org/10.2147/IJNRD.S40172] [PMID: 25342915]
[5]
Gross JL, de Azevedo MJ, Silveiro SP, Canani LH, Caramori ML, Zelmanovitz T. Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care 2005; 28(1): 164-76.
[http://dx.doi.org/10.2337/diacare.28.1.164] [PMID: 15616252]
[6]
Singh R, Kishore L, Kaur N. Diabetic peripheral neuropathy: current perspective and future directions. Pharmacol Res 2014; 80: 21-35.
[http://dx.doi.org/10.1016/j.phrs.2013.12.005] [PMID: 24373831]
[7]
Jia G, Hill MA, Sowers JR. Diabetic cardiomyopathy: an update of mechanisms contributing to this clinical entity. Circ Res 2018; 122(4): 624-38.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.311586] [PMID: 29449364]
[8]
Molitch ME, Adler AI, Flyvbjerg A, et al. Diabetic kidney disease: a clinical update from Kidney Disease: Improving Global Outcomes. Kidney Int 2015; 87(1): 20-30.
[http://dx.doi.org/10.1038/ki.2014.128] [PMID: 24786708]
[9]
Simó R, Stitt AW, Gardner TW. Neurodegeneration in diabetic retinopathy: does it really matter? Diabetologia 2018; 61(9): 1902-12.
[http://dx.doi.org/10.1007/s00125-018-4692-1] [PMID: 30030554]
[10]
Chakravarthy H, Devanathan V. Molecular mechanisms mediating diabetic retinal neurodegeneration: potential research avenues and therapeutic targets. J Mol Neurosci 2018; 66(3): 445-61.
[http://dx.doi.org/10.1007/s12031-018-1188-x] [PMID: 30293228]
[11]
Kern TS. Contributions of inflammatory processes to the development of the early stages of diabetic retinopathy. Exp Diabetes Res 2007; 2007
[http://dx.doi.org/10.1155/2007/95103]
[12]
Wilkinson CP, Ferris FL III, Klein RE, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology 2003; 110(9): 1677-82.
[http://dx.doi.org/10.1016/S0161-6420(03)00475-5] [PMID: 13129861]
[13]
Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol 1974; 34(1): 29-34.
[http://dx.doi.org/10.1016/0002-9149(74)90089-7] [PMID: 4835750]
[14]
Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013; 128(16): e240-327.
[http://dx.doi.org/10.1161/CIR.0b013e31829e8776] [PMID: 23741058]
[15]
Rydén L, Grant PJ, Anker SD, et al. ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the easd: the task force on diabetes, pre-diabetes, and cardiovascular diseases of the european society of cardiology (ESC) and developed in collaboration with the european association for the study of diabetes (EASD). Eur Heart J 2013; 34(39): 3035-87.
[http://dx.doi.org/10.1093/eurheartj/eht108] [PMID: 23996285]
[16]
Felício JS, Koury CC, Carvalho CT, et al. Present insights on cardiomyopathy in diabetic patients. Curr Diabetes Rev 2016; 12(4): 384-95.
[http://dx.doi.org/10.2174/1573399812666150914120529] [PMID: 26364799]
[17]
Hadi HA, Suwaidi JA. Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manag 2007; 3(6): 853-76.
[PMID: 18200806]
[18]
Sandoo A, van Zanten JJCSV, Metsios GS, Carroll D, Kitas GD. The endothelium and its role in regulating vascular tone. Open Cardiovasc Med J 2010; 4: 302-12.
[http://dx.doi.org/10.2174/1874192401004010302] [PMID: 21339899]
[19]
Dewanjee S, Das S, Das AK, et al. Molecular mechanism of diabetic neuropathy and its pharmacotherapeutic targets. Eur J Pharmacol 2018; 833: 472-523.
[http://dx.doi.org/10.1016/j.ejphar.2018.06.034] [PMID: 29966615]
[20]
Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005; 54(6): 1615-25.
[http://dx.doi.org/10.2337/diabetes.54.6.1615] [PMID: 15919781]
[21]
Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414(6865): 813-20.
[http://dx.doi.org/10.1038/414813a] [PMID: 11742414]
[22]
Lutchmansingh FK, Hsu JW, Bennett FI, et al. Glutathione metabolism in type 2 diabetes and its relationship with microvascular complications and glycemia. PLoS One 2018; 13(6): e0198626.
[http://dx.doi.org/10.1371/journal.pone.0198626] [PMID: 29879181]
[23]
Singh VP, Bali A, Singh N, Jaggi AS. Advanced glycation end products and diabetic complications. Korean J Physiol Pharmacol 2014; 18(1): 1-14.
[http://dx.doi.org/10.4196/kjpp.2014.18.1.1] [PMID: 24634591]
[24]
Bucciarelli LG, Wendt T, Rong L, et al. RAGE is a multiligand receptor of the immunoglobulin superfamily: implications for homeostasis and chronic disease. Cell Mol Life Sci 2002; 59(7): 1117-28.
[http://dx.doi.org/10.1007/s00018-002-8491-x] [PMID: 12222959]
[25]
Tóbon-Velasco JC, Cuevas E, Torres-Ramos MA. Receptor for AGEs (RAGE) as mediator of NF-kB pathway activation in neuroinflammation and oxidative stress. CNS Neurol Disord Drug Targets 2014; 13(9): 1615-26.
[http://dx.doi.org/10.2174/1871527313666140806144831] [PMID: 25106630]
[26]
Aldini G, Vistoli G, Stefek M, et al. Molecular strategies to prevent, inhibit, and degrade advanced glycoxidation and advanced lipoxidation end products. Free Radic Res 2013; 47(1): 93-137.
[http://dx.doi.org/10.3109/10715762.2013.792926]
[27]
Ali AA, Lewis SM, Badgley HL, Allaben WT, Leakey JE. Oral glucosamine increases expression of transforming growth factor β1 (TGFβ1) and connective tissue growth factor (CTGF) mRNA in rat cartilage and kidney: implications for human efficacy and toxicity. Arch Biochem Biophys 2011; 510(1): 11-8.
[http://dx.doi.org/10.1016/j.abb.2011.03.014] [PMID: 21466783]
[28]
Kolm-Litty V, Sauer U, Nerlich A, Lehmann R, Schleicher ED. High glucose-induced transforming growth factor beta1 production is mediated by the hexosamine pathway in porcine glomerular mesangial cells. J Clin Invest 1998; 101(1): 160-9.
[http://dx.doi.org/10.1172/JCI119875] [PMID: 9421478]
[29]
Schleicher ED, Weigert C. Role of the hexosamine biosynthetic pathway in diabetic nephropathy. Kidney Int Suppl 2000; 77: S13-8.
[http://dx.doi.org/10.1046/j.1523-1755.2000.07703.x] [PMID: 10997685]
[30]
Weigert C, Friess U, Brodbeck K, Häring HU, Schleicher ED. Glutamine:fructose-6-phosphate aminotransferase enzyme activity is necessary for the induction of TGF-β1 and fibronectin expression in mesangial cells. Diabetologia 2003; 46(6): 852-5.
[http://dx.doi.org/10.1007/s00125-003-1122-8] [PMID: 12802498]
[31]
Ma J, Hart GW. Protein O-GlcNAcylation in diabetes and diabetic complications. Expert Rev Proteomics 2013; 10(4): 365-80.
[http://dx.doi.org/10.1586/14789450.2013.820536] [PMID: 23992419]
[32]
Cherepanova N, Shrimal S, Gilmore R. N-linked glycosylation and homeostasis of the endoplasmic reticulum. Curr Opin Cell Biol 2016; 41: 57-65.
[http://dx.doi.org/10.1016/j.ceb.2016.03.021] [PMID: 27085638]
[33]
Mailleux F, Gélinas R, Beauloye C, Horman S, Bertrand L. O-Glc-NAcylation, enemy or ally during cardiac hypertrophy development? Biochim Biophys Acta BBA - Mol Basis Dis 1862; 1862(12): 2232-43.
[34]
Steinberg SF. Structural basis of protein kinase C isoform function. Physiol Rev 2008; 88(4): 1341-78.
[http://dx.doi.org/10.1152/physrev.00034.2007] [PMID: 18923184]
[35]
Rask-Madsen C, King GL. Vascular complications of diabetes: mechanisms of injury and protective factors. Cell Metab 2013; 17(1): 20-33.
[http://dx.doi.org/10.1016/j.cmet.2012.11.012] [PMID: 23312281]
[36]
Ohshiro Y, Ma RC, Yasuda Y, et al. Reduction of diabetes-induced oxidative stress, fibrotic cytokine expression, and renal dysfunction in protein kinase Cbeta-null mice. Diabetes 2006; 55(11): 3112-20.
[http://dx.doi.org/10.2337/db06-0895] [PMID: 17065350]
[37]
Wakasaki H, Koya D, Schoen FJ, et al. Targeted overexpression of protein kinase C β2 isoform in myocardium causes cardiomyopathy. Proc Natl Acad Sci USA 1997; 94(17): 9320-5.
[http://dx.doi.org/10.1073/pnas.94.17.9320] [PMID: 9256480]
[38]
Wang ZB, Zhang S, Li Y, et al. LY333531, a PKCβ inhibitor, attenuates glomerular endothelial cell apoptosis in the early stage of mouse diabetic nephropathy via down-regulating swiprosin-1. Acta Pharmacol Sin 2017; 38(7): 1009-23.
[http://dx.doi.org/10.1038/aps.2016.172] [PMID: 28414198]
[39]
Ayala JE, Bracy DP, McGuinness OP, Wasserman DH. Considerations in the design of hyperinsulinemic-euglycemic clamps in the conscious mouse. Diabetes 2006; 55(2): 390-7.
[http://dx.doi.org/10.2337/diabetes.55.02.06.db05-0686] [PMID: 16443772]
[40]
Murphy MP, Echtay KS, Blaikie FH, et al. Superoxide activates uncoupling proteins by generating carbon-centered radicals and initiating lipid peroxidation: studies using a mitochondria-targeted spin trap derived from α-phenyl-N-tert-butylnitrone. J Biol Chem 2003; 278(49): 48534-45.
[http://dx.doi.org/10.1074/jbc.M308529200] [PMID: 12972420]
[41]
Vené R, Delfino L, Castellani P, et al. Redox remodeling allows and controls B-cell activation and differentiation. Antioxid Redox Signal 2010; 13(8): 1145-55.
[http://dx.doi.org/10.1089/ars.2009.3078] [PMID: 20367281]
[42]
Goldberg IJ, Trent CM, Schulze PC. Lipid metabolism and toxicity in the heart. Cell Metab 2012; 15(6): 805-12.
[http://dx.doi.org/10.1016/j.cmet.2012.04.006] [PMID: 22682221]
[43]
Saponaro C, Gaggini M, Carli F, Gastaldelli A. The subtle balance between lipolysis and lipogenesis: a critical point in metabolic homeostasis. Nutrients 2015; 7(11): 9453-74.
[http://dx.doi.org/10.3390/nu7115475] [PMID: 26580649]
[44]
van Herpen NA, Schrauwen-Hinderling VB. Lipid accumulation in non-adipose tissue and lipotoxicity. Physiol Behav 2008; 94(2): 231-41.
[http://dx.doi.org/10.1016/j.physbeh.2007.11.049] [PMID: 18222498]
[45]
Tangvarasittichai S. Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World J Diabetes 2015; 6(3): 456-80.
[http://dx.doi.org/10.4239/wjd.v6.i3.456] [PMID: 25897356]
[46]
Li LO, Klett EL, Coleman RA. Acyl-CoA synthesis, lipid metabolism and lipotoxicity. Biochim Biophys Acta 2010; 1801(3): 246-51.
[http://dx.doi.org/10.1016/j.bbalip.2009.09.024] [PMID: 19818872]
[47]
Krock BL, Skuli N, Simon MC. Hypoxia-induced angiogenesis: good and evil. Genes Cancer 2011; 2(12): 1117-33.
[http://dx.doi.org/10.1177/1947601911423654] [PMID: 22866203]
[48]
Kang SJ, Schmack I, Yang ES, Berglin L, Grossniklaus HE. Effect of high-fat diet on the development of corneal neovascularizaion and intraocular inflammation. Invest Ophthalmol Vis Sci 2006; 47(13): 1641-1.
[49]
Long AN, Dagogo-Jack S. Comorbidities of diabetes and hypertension: mechanisms and approach to target organ protection. J Clin Hypertens 2011; 13(4): 244-51.
[http://dx.doi.org/10.1111/j.1751-7176.2011.00434.x] [PMID: 21466619]
[50]
Velloso LA, Folli F, Sun XJ, White MF, Saad MJ, Kahn CR. Cross-talk between the insulin and angiotensin signaling systems. Proc Natl Acad Sci USA 1996; 93(22): 12490-5.
[http://dx.doi.org/10.1073/pnas.93.22.12490] [PMID: 8901609]
[51]
Chawla T, Sharma D, Singh A. Role of the renin angiotensin system in diabetic nephropathy. World J Diabetes 2010; 1(5): 141-5.
[http://dx.doi.org/10.4239/wjd.v1.i5.141] [PMID: 21537441]
[52]
Lowe G, Woodward M, Hillis G, et al. Circulating inflammatory markers and the risk of vascular complications and mortality in people with type 2 diabetes and cardiovascular disease or risk factors: the ADVANCE study. Diabetes 2014; 63(3): 1115-23.
[http://dx.doi.org/10.2337/db12-1625] [PMID: 24222348]
[53]
Carstensen M, Herder C, Kivimäki M, et al. Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes: Whitehall II prospective cohort study. Diabetes 2010; 59(5): 1222-7.
[http://dx.doi.org/10.2337/db09-1199] [PMID: 20185814]
[54]
Herder C, Brunner EJ, Rathmann W, et al. Elevated levels of the anti-inflammatory interleukin-1 receptor antagonist precede the onset of type 2 diabetes: the Whitehall II study. Diabetes Care 2009; 32(3): 421-3.
[http://dx.doi.org/10.2337/dc08-1161] [PMID: 19073760]
[55]
Akash MSH, Shen Q, Rehman K. shuqing chen. interleukin-1 receptor antagonist: a new therapy for type 2 diabetes mellitus. J Pharm Sci 2012; 101(5): 1654-58.
[http://dx.doi.org/10.1002/jps.23057]
[56]
Ibfelt T, Fischer CP, Plomgaard P, van Hall G, Pedersen BK. The acute effects of low-dose TNF-α on glucose metabolism and β- cell function in humans. Mediators Inflamm 2014; 2014: 295478.
[http://dx.doi.org/10.1155/2014/295478] [PMID: 24692847]
[57]
Manieri E, Sabio G. Stress kinases in the modulation of metabolism and energy balance. J Mol Endocrinol 2015; 55(2): R11-22.
[http://dx.doi.org/10.1530/JME-15-0146] [PMID: 26363062]
[58]
Maedler K, Sergeev P, Ris F, et al. Glucose-induced β cell production of IL-1β contributes to glucotoxicity in human pancreatic islets. J Clin Invest 2002; 110(6): 851-60.
[http://dx.doi.org/10.1172/JCI200215318] [PMID: 12235117]
[59]
Bhattacharya D, Mukhopadhyay M, Bhattacharyya M, Karmakar P. Is autophagy associated with diabetes mellitus and its complications? A review. EXCLI J 2018; 17: 709-20.
[PMID: 30190661]
[60]
Scheele C, Nielsen AR, Walden TB, et al. Altered regulation of the PINK1 locus: a link between type 2 diabetes and neurodegeneration? FASEB J 2007; 21(13): 3653-65.
[http://dx.doi.org/10.1096/fj.07-8520com] [PMID: 17567565]
[61]
Chen ZF, Li YB, Han JY, et al. The double-edged effect of autophagy in pancreatic beta cells and diabetes. Autophagy 2011; 7(1): 12-6.
[http://dx.doi.org/10.4161/auto.7.1.13607] [PMID: 20935505]
[62]
Ding Y, Choi ME. Autophagy in diabetic nephropathy. J Endocrinol 2015; 224(1): R15-30.
[http://dx.doi.org/10.1530/JOE-14-0437] [PMID: 25349246]
[63]
Park HL, Kim JH, Park CK. Different contributions of autophagy to retinal ganglion cell death in the diabetic and glaucomatous retinas. Sci Rep 2018; 8(1): 13321.
[http://dx.doi.org/10.1038/s41598-018-30165-7] [PMID: 30190527]
[64]
Oshitari T, Hata N, Yamamoto S. Endoplasmic reticulum stress and diabetic retinopathy. Vasc Health Risk Manag 2008; 4(1): 115-22.
[http://dx.doi.org/10.2147/vhrm.2008.04.01.115] [PMID: 18629365]
[65]
Inceoglu B, Bettaieb A, Trindade da Silva CA, Lee KSS, Haj FG, Hammock BD. Endoplasmic reticulum stress in the peripheral nervous system is a significant driver of neuropathic pain. Proc Natl Acad Sci USA 2015; 112(29): 9082-7.
[http://dx.doi.org/10.1073/pnas.1510137112] [PMID: 26150506]
[66]
Xiong F-Y, Tang S-T, Su H, et al. Melatonin ameliorates myocardial apoptosis by suppressing endoplasmic reticulum stress in rats with long-term diabetic cardiomyopathy. Mol Med Rep 2018; 17(1): 374-81.
[PMID: 29115422]
[67]
Nathan DM, Genuth S, Lachin J, Cleary P, Crofford O. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329(14): 977-86.
[68]
Francis G, Martinez, Liu W, et al. Intranasal insulin ameliorates experimental diabetic neuropathy. Diabetes 1817; 58(4): 934-45.
[69]
Robertson RP, Davis C, Larsen J, Stratta R, Sutherland DE. Pancreas and islet transplantation in type 1 diabetes. Diabetes Care 2006; 29(4): 935-5.
[http://dx.doi.org/10.2337/diacare.29.04.06.dc06-9908] [PMID: 16567844]
[70]
Hsu WH, Hsiao PJ, Lin PC, Chen SC, Lee MY, Shin SJ. Effect of metformin on kidney function in patients with type 2 diabetes mellitus and moderate chronic kidney disease. Oncotarget 2017; 9(4): 5416-23.
[http://dx.doi.org/10.18632/oncotarget.23387] [PMID: 29435189]
[71]
Wile DJ, Toth C. Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy. Diabetes Care 2010; 33(1): 156-61.
[http://dx.doi.org/10.2337/dc09-0606] [PMID: 19846797]
[72]
Inzucchi SE, Wanner C, Hehnke U, et al. Retinopathy outcomes with empagliflozin versus placebo in the empa-reg outcome trial. Diabetes Care 2019; 42(4): e53-5.
[http://dx.doi.org/10.2337/dc18-1355] [PMID: 30705060]
[73]
Savelieff MG, Callaghan BC, Feldman EL. The emerging role of dyslipidemia in diabetic microvascular complications. Curr Opin Endocrinol Diabetes Obes 2020; 27(2): 115-23.
[http://dx.doi.org/10.1097/MED.0000000000000533] [PMID: 32073426]
[74]
Forbes JM, Cooper ME. Mechanisms of diabetic complications. Physiol Rev 2013; 93(1): 137-88.
[http://dx.doi.org/10.1152/physrev.00045.2011] [PMID: 23303908]
[75]
Mansi IA, Frei CR, Halm EA, Mortensen EM. Association of statins with diabetes mellitus and diabetic complications: role of confounders during follow-up. J Investig Med 2017; 65(1): 32-42.
[http://dx.doi.org/10.1136/jim-2016-000218] [PMID: 27574296]
[76]
Al-Rasheed NM, Al-Rasheed NM, Hasan IH, et al. Simvastatin ameliorates diabetic cardiomyopathy by attenuating oxidative stress and inflammation in rats. Oxid Med Cell Longev 2017; 2017: 1092015.
[http://dx.doi.org/10.1155/2017/1092015]
[77]
Al-Rasheed NM, Al-Rasheed NM, Bassiouni YA, et al. Simvastatin ameliorates diabetic nephropathy by attenuating oxidative stress and apoptosis in a rat model of streptozotocin-induced type 1 diabetes. Biomed Pharmacother 2018; 105(May): 290-8.
[http://dx.doi.org/10.1016/j.biopha.2018.05.130] [PMID: 29860221]
[78]
Carrillo-Ibarra S, Miranda-Díaz AG, Sifuentes-Franco S, et al. Effect of statins on oxidative DNA damage in diabetic polyneuropathy. J Circ Biomark 2018; 7(1)
[http://dx.doi.org/10.1177/1849454418804099]
[79]
Balendiran GK, Rajkumar B. Fibrates inhibit aldose reductase activity in the forward and reverse reactions. Biochem Pharmacol 2005; 70(11): 1653-63.
[http://dx.doi.org/10.1016/j.bcp.2005.06.029] [PMID: 16226225]
[80]
Ansquer JC, Foucher C, Aubonnet P, Le Malicot K. Fibrates and microvascular complications in diabetes-insight from the FIELD study. Curr Pharm Des 2009; 15(5): 537-52.
[http://dx.doi.org/10.2174/138161209787315701] [PMID: 19199980]
[81]
Rajamani K, Colman PG, Li LP, et al. Effect of fenofibrate on amputation events in people with type 2 diabetes mellitus (FIELD study): a prespecified analysis of a randomised controlled trial. Lancet 2009; 373(9677): 1780-8.
[http://dx.doi.org/10.1016/S0140-6736(09)60698-X] [PMID: 19465233]
[82]
Hu W, Song X, Yu H, Sun J, Zhao Y. Therapeutic potentials of extracellular vesicles for the treatment of diabetes and diabetic complications. Int J Mol Sci 2020; 21(14): 1-24.
[http://dx.doi.org/10.3390/ijms21145163] [PMID: 32708290]
[83]
Lovshin JA, Lytvyn Y, Lovblom LE, et al. Retinopathy and RAAS activation: Results from the canadian study of longevity in type 1 diabetes.Diabetes Care. American Diabetes Association Inc. 2019; pp. 273-80.
[84]
Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med 1993; 329(20): 1456-62.
[http://dx.doi.org/10.1056/NEJM199311113292004] [PMID: 8413456]
[85]
Hsueh WA, Wyne K. Renin-Angiotensin-aldosterone system in diabetes and hypertension. J Clin Hypertens (Greenwich) 2011; 13(4): 224-37.
[http://dx.doi.org/10.1111/j.1751-7176.2011.00449.x] [PMID: 21466617]
[86]
Leoncini G, Viazzi F, De Cosmo S, Russo G, Fioretto P, Pontremoli R. Blood pressure reduction and RAAS inhibition in diabetic kidney disease: therapeutic potentials and limitations. J Nephrol 2020; 33(5): 949-63.
[http://dx.doi.org/10.1007/s40620-020-00803-3] [PMID: 32681470]
[87]
Silva LB, dos Santos Neto AP, Maia SMAS, dos Santos Guimarães C, Quidute IL. The role of TNF-α as a proinflammatory cytokine in pathological processes. Open Dent J 2019; 13(1)https://opendentistryjournal.com/VOLUME/13/PAGE/332/FULLTEXT/
[88]
Lichtenstein GR. Comprehensive review: antitumor necrosis factor agents in inflammatory bowel disease and factors implicated in treatment response. Therap Adv Gastroenterol 2013; 6(4): 269-93.
[http://dx.doi.org/10.1177/1756283X13479826] [PMID: 23814608]
[89]
Dinarello CA, Simon A, van der Meer JWM. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov 2012; 11(8): 633-52.
[http://dx.doi.org/10.1038/nrd3800] [PMID: 22850787]
[90]
Peiró C, Lorenzo Ó, Carraro R, Sánchez-Ferrer CF. IL-1β Inhibition in Cardiovascular Complications Associated to Diabetes Mellitus. Front Pharmacol 2017; 8https://www.frontiersin.org/articles/10.3389/fphar.2017.00363/full
[91]
Sadik CD, Luster AD. Lipid-cytokine-chemokine cascades orchestrate leukocyte recruitment in inflammation. J Leukoc Biol 2012; 91(2): 207-15.
[http://dx.doi.org/10.1189/jlb.0811402] [PMID: 22058421]
[92]
Suzuki H, Kayama Y, Sakamoto M, et al. Arachidonate 12/15-lipoxygenase-induced inflammation and oxidative stress are involved in the development of diabetic cardiomyopathy. Diabetes 2015; 64(2): 618-30.
[http://dx.doi.org/10.2337/db13-1896] [PMID: 25187369]
[93]
Funk CD, FitzGerald GA. COX-2 inhibitors and cardiovascular risk. J Cardiovasc Pharmacol 2007; 50(5): 470-9.
[http://dx.doi.org/10.1097/FJC.0b013e318157f72d] [PMID: 18030055]
[94]
Chong ZZ, Maiese K. Mammalian target of rapamycin signaling in diabetic cardiovascular disease. Cardiovasc Diabetol 2012; 11: 45.
[http://dx.doi.org/10.1186/1475-2840-11-45] [PMID: 22545721]
[95]
Fervenza FC, Fitzpatrick PM, Mertz J, et al. Acute rapamycin nephrotoxicity in native kidneys of patients with chronic glomerulopathies. Nephrol Dial Transplant 2004; 19(5): 1288-92.
[http://dx.doi.org/10.1093/ndt/gfh079] [PMID: 15102967]
[96]
Liu WJ, Gan Y, Huang WF, et al. Lysosome restoration to activate podocyte autophagy: a new therapeutic strategy for diabetic kidney disease. Cell Death Dis 2019; 10(11): 806.
[http://dx.doi.org/10.1038/s41419-019-2002-6] [PMID: 31649253]
[97]
Chung JH, Manganiello V, Dyck JRB. Resveratrol as a calorie restriction mimetic: therapeutic implications. Trends Cell Biol 2012; 22(10): 546-54.
[http://dx.doi.org/10.1016/j.tcb.2012.07.004] [PMID: 22885100]
[98]
Price NL, Gomes AP, Ling AJY, et al. SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function. Cell Metab 2012; 15(5): 675-90.
[http://dx.doi.org/10.1016/j.cmet.2012.04.003] [PMID: 22560220]
[99]
Wang L, Chopp M, Szalad A, et al. Exosomes derived from schwann cells ameliorate peripheral neuropathy in type 2 diabetic mice. Diabetes 2020; 69(4): 749-59.
[http://dx.doi.org/10.2337/db19-0432] [PMID: 31915154]
[100]
Lopez-Verrilli MA, Picou F, Court FA. Schwann cell-derived exosomes enhance axonal regeneration in the peripheral nervous system. Glia 2013; 61(11): 1795-806.
[http://dx.doi.org/10.1002/glia.22558] [PMID: 24038411]
[101]
Fan B, Li C, Szalad A, et al. Mesenchymal stromal cell-derived exosomes ameliorate peripheral neuropathy in a mouse model of diabetes. Diabetologia 2020; 63(2): 431-43.
[http://dx.doi.org/10.1007/s00125-019-05043-0] [PMID: 31740984]
[102]
Safwat A, Sabry D, Ragiae A, Amer E, Mahmoud RH, Shamardan RM. Adipose mesenchymal stem cells-derived exosomes attenuate retina degeneration of streptozotocin-induced diabetes in rabbits. J Circ Biomark 2018; 7: 1849454418807827.
[http://dx.doi.org/10.1177/1849454418807827] [PMID: 30397416]
[103]
McClelland AD, Kantharidis P. microRNA in the development of diabetic complications. Clin Sci Lond Engl 1979; 126(2): 95-110.
[104]
Zhang X, Gong X, Han S, Zhang Y. MiR-29b protects dorsal root ganglia neurons from diabetic rat. Cell Biochem Biophys 2014; 70(2): 1105-11.
[http://dx.doi.org/10.1007/s12013-014-0029-y] [PMID: 24819309]
[105]
Lee HW, Khan SQ, Khaliqdina S, et al. Absence of miR-146a in Podocytes Increases Risk of Diabetic Glomerulopathy via Up-regulation of ErbB4 and Notch-1. J Biol Chem 2017; 292(2): 732-47.
[http://dx.doi.org/10.1074/jbc.M116.753822] [PMID: 27913625]

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