Top

Published in:

Open Access 02-02-2024 | Diabetes-associated Diseases | Review

A Narrative Review of Diabetic Macroangiopathy: From Molecular Mechanism to Therapeutic Approaches

Authors: Jiacheng Yin, Xiaoxu Fu, Yue Luo, Yuling Leng, Lianjun Ao, Chunguang Xie

Published in: Diabetes Therapy | Issue 3/2024

Abstract

Diabetic macroangiopathy, a prevalent and severe complication of diabetes mellitus, significantly contributes to the increased morbidity and mortality rates among affected individuals. This complex disorder involves multifaceted molecular mechanisms that lead to the dysfunction and damage of large blood vessels, including atherosclerosis (AS) and peripheral arterial disease. Understanding the intricate pathways underlying the development and progression of diabetic macroangiopathy is crucial for the development of effective therapeutic interventions. This review aims to shed light on the molecular mechanism implicated in the pathogenesis of diabetic macroangiopathy. We delve into the intricate interplay of chronic inflammation, oxidative stress, endothelial dysfunction, and dysregulated angiogenesis, all of which contribute to the vascular complications observed in this disorder. By exploring the molecular mechanism involved in the disease we provide insight into potential therapeutic targets and strategies. Moreover, we discuss the current therapeutic approaches used for treating diabetic macroangiopathy, including glycemic control, lipid-lowering agents, and vascular interventions.

Okonkwo UA, Dipietro LA. Diabetes and wound angiogenesis. Int J Mol Sci. 2017. https://doi.org/10.3390/IJMS18071419.CrossRefPubMedPubMedCentral

Li Y, Liu Y, Liu S, et al. Diabetic vascular diseases: molecular mechanisms and therapeutic strategies. Signal Transduct Target Ther. 2023. https://doi.org/10.1038/s41392-023-01400-z.CrossRefPubMedPubMedCentral

Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87:4–14. https://doi.org/10.1016/J.DIABRES.2009.10.007.CrossRefPubMed

Harding JL, Pavkov ME, Magliano DJ, Shaw JE, Gregg EW. Global trends in diabetes complications: a review of current evidence. Diabetologia. 2019;62:3–16. https://doi.org/10.1007/S00125-018-4711-2.CrossRefPubMed

Tomic D, Shaw JE, Magliano DJ. The burden and risks of emerging complications of diabetes mellitus. Nat Rev Endocrinol. 2022;18:525–39. https://doi.org/10.1038/s41574-022-00690-7.CrossRefPubMedPubMedCentral

Zimmet P, Alberti KGMM, Shaw J. Global and societal implications of the diabetes epidemic. Nature. 2001;414:782–7. https://doi.org/10.1038/414782a.ADSCrossRefPubMed

Fowler MJ. Microvascular and macrovascular complications of diabetes. Clin Diabetes. 2008;26:77–82. https://doi.org/10.2337/diaclin.26.2.77.CrossRef

Kong P, Xie X, Li F, Liu Y, Lu Y. Placenta mesenchymal stem cell accelerates wound healing by enhancing angiogenesis in diabetic Goto-Kakizaki (GK) rats. Biochem Biophys Res Commun. 2013;438:410–9. https://doi.org/10.1016/j.bbrc.2013.07.088.CrossRefPubMed

Okonkwo UA, Chen L, Ma D, et al. Compromised angiogenesis and vascular integrity in impaired diabetic wound healing. PLoS ONE. 2020. https://doi.org/10.1371/JOURNAL.PONE.0231962.CrossRefPubMedPubMedCentral

10.

Demidova-Rice TN, Hamblin MR, Herman IM. Acute and impaired wound healing: pathophysiology and current methods for drug delivery, part 1: normal and chronic wounds: biology, causes, and approaches to care. Adv Skin Wound Care. 2012;25:304–14. https://doi.org/10.1097/01.ASW.0000416006.55218.D0.CrossRefPubMedPubMedCentral

11.

Singh MR, Saraf S, Vyas A, Jain V, Singh D. Innovative approaches in wound healing: trajectory and advances. Artif Cells Nanomed Biotechnol. 2013;41:202–12. https://doi.org/10.3109/21691401.2012.716065.CrossRefPubMed

12.

Johnson KE, Wilgus TA. Vascular endothelial growth factor and angiogenesis in the regulation of cutaneous wound repair. Adv Wound Care. 2014;3:647. https://doi.org/10.1089/WOUND.2013.0517.CrossRef

13.

Wietecha MS, Król MJ, Michalczyk ER, Chen L, Gettins PG, Dipietro LA. Pigment epithelium-derived factor as a multifunctional regulator of wound healing. Am J Physiol Heart Circ Physiol. 2015;309:H812–26. https://doi.org/10.1152/AJPHEART.00153.2015.CrossRefPubMedPubMedCentral

14.

Chen L, Dipietro LA. Production and function of pigment epithelium-derived factor in isolated skin keratinocytes. Exp Dermatol. 2014;23:436–8. https://doi.org/10.1111/EXD.12411.CrossRefPubMedPubMedCentral

15.

Schalkwijk CG, Micali LR, Wouters K. Advanced glycation endproducts in diabetes-related macrovascular complications: focus on methylglyoxal. Trends Endocrinol Metab. 2023;34:49–60. https://doi.org/10.1016/J.TEM.2022.11.004.CrossRefPubMed

16.

Rungratanawanich W, Qu Y, Wang X, Essa MM, Song BJ. Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury. Exp Mol Med. 2021;53:168–88. https://doi.org/10.1038/s12276-021-00561-7.CrossRefPubMedPubMedCentral

17.

Orasanu G, Plutzky J. The pathologic continuum of diabetic vascular disease. J Am Coll Cardiol. 2009. https://doi.org/10.1016/j.jacc.2008.09.055.CrossRefPubMedPubMedCentral

18.

Schelbert HR. Coronary circulatory function abnormalities in insulin resistance. Insights from positron emission tomography. J Am Coll Cardiol. 2009;53:3–8.CrossRef

19.

Isomaa B, Almgren P, Tuom T. Cardiovascular morbidity and mortality. Diabetes Care. 2001;24:683–9.CrossRefPubMed

20.

Mota RI, Morgan SE, Bahnson EM. Diabetic vasculopathy: macro and microvascular injury. Curr Pathobiol Rep. 2020. https://doi.org/10.1007/S40139-020-00205-X.CrossRefPubMedPubMedCentral

21.

Paneni F, Beckman JA, Creager MA, Cosentino F. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part I. Eur Heart J. 2013;34:2436–43. https://doi.org/10.1093/EURHEARTJ/EHT149.CrossRefPubMedPubMedCentral

22.

Beckman JA, Paneni F, Cosentino F, Creager MA. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part II. Eur Heart J. 2013;34:2444–56. https://doi.org/10.1093/EURHEARTJ/EHT142.CrossRefPubMed

23.

Cooper ME, Bonnet F, Oldfield M, Jandeleit-Dahm K. Mechanisms of diabetic vasculopathy: an overview. Am J Hypertens. 2001;14:475–86. https://doi.org/10.1016/S0895-7061(00)01323-6.CrossRefPubMed

24.

Papachristoforou E, Lambadiari V, Maratou E, Makrilakis K. Association of glycemic indices (hyperglycemia, glucose variability, and hypoglycemia) with oxidative stress and diabetic complications. J Diabetes Res. 2020. https://doi.org/10.1155/2020/7489795.CrossRefPubMedPubMedCentral

25.

Patel S, Srivastava S, Singh MR, Singh D. Mechanistic insight into diabetic wounds: pathogenesis, molecular targets and treatment strategies to pace wound healing. Biomed Pharmacother. 2019;112: 108615. https://doi.org/10.1016/J.BIOPHA.2019.108615.CrossRefPubMed

26.

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. N Engl J Med. 1993;329:977–86. https://doi.org/10.1056/NEJM199309303291401.CrossRef

27.

Aronson D, Rayfield EJ. How hyperglycemia promotes atherosclerosis: molecular mechanisms. Cardiovasc Diabetol. 2002. https://doi.org/10.1186/1475-2840-1-1.CrossRefPubMedPubMedCentral

28.

Flier JS, Underhill LH, Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med. 1988;318:1315–21. https://doi.org/10.1056/NEJM198805193182007.CrossRef

29.

Rahman S, Rahman T, Ismail AAS, Rashid ARA. Diabetes-associated macrovasculopathy: pathophysiology and pathogenesis. Diabetes Obes Metab. 2007;9:767–80. https://doi.org/10.1111/J.1463-1326.2006.00655.X.CrossRefPubMed

30.

Gao S, Zhang Y, Liang K, Bi R, Du Y. Mesenchymal stem cells (MSCs): a novel therapy for type 2 diabetes. Stem Cells Int. 2022. https://doi.org/10.1155/2022/8637493.CrossRefPubMedPubMedCentral

31.

Elshemy MM, Asem M, Allemailem KS, Uto K, Ebara M, Nabil A. Antioxidative capacity of liver- and adipose-derived mesenchymal stem cell-conditioned media and their applicability in treatment of type 2 diabetic rats. Oxid Med Cell Longev. 2021. https://doi.org/10.1155/2021/8833467.CrossRefPubMedPubMedCentral

32.

Cooper-DeHoff RM, Pacanowski MA, Pepine CJ. Cardiovascular therapies and associated glucose homeostasis. Implications across the dysglycemia continuum. J Am Coll Cardiol. 2009. https://doi.org/10.1016/j.jacc.2008.10.037.CrossRefPubMedPubMedCentral

33.

Watkins PJ. ABC of diabetes: cardiovascular disease, hypertension, and lipids. BMJ. 2003;326:874. https://doi.org/10.1136/BMJ.326.7394.874.CrossRefPubMedPubMedCentral

34.

Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem. 1997;272:20963–6. https://doi.org/10.1074/jbc.272.34.20963.CrossRefPubMed

35.

Moldogazieva NT, Mokhosoev IM, Mel’Nikova TI, Porozov YB, Terentiev AA. Oxidative stress and advanced lipoxidation and glycation end products (ALEs and AGEs) in aging and age-related diseases. Oxid Med Cell Longev. 2019. https://doi.org/10.1155/2019/3085756.CrossRefPubMedPubMedCentral

36.

Schwartz CJ, Valente AJ, Sprague EA, Kelley JL, Cayatte AJ, Rozek MM. Pathogenesis of the atherosclerotic lesion. Implications for diabetes mellitus. Diabetes Care. 1992;15:1156–67. https://doi.org/10.2337/DIACARE.15.9.1156.CrossRefPubMed

37.

Meeuwisse-Pasterkamp SH, van der Klauw MM, Wolffenbuttel BHR. Type 2 diabetes mellitus: prevention of macrovascular complications. Expert Rev Cardiovasc Ther. 2008;6:323–41. https://doi.org/10.1586/14779072.6.3.323.CrossRefPubMed

38.

Dzau VJ. Tissue angiotensin and pathobiology of vascular disease a unifying hypothesis. Hypertension. 2001;37:1047–52. https://doi.org/10.1161/01.HYP.37.4.1047.CrossRefPubMed

39.

Schmidt AM. Diabetes mellitus and cardiovascular disease. Arterioscler Thromb Vasc Biol. 2019;39:558–68. https://doi.org/10.1161/ATVBAHA.119.310961.CrossRefPubMed

40.

Bucala R, Makita Z, Koschinsky T, Cerami A, Vlassara H. Lipid advanced glycosylation: pathway for lipid oxidation in vivo. Proc Natl Acad Sci USA. 1993;90:6434–8. https://doi.org/10.1073/PNAS.90.14.6434.ADSCrossRefPubMedPubMedCentral

41.

Yamagishi S, Matsui T, Nakamura K. Kinetics, role and therapeutic implications of endogenous soluble form of receptor for advanced glycation end products (SRAGE) in diabetes. Curr Drug Targets. 2007;8:1138–43. https://doi.org/10.2174/138945007782151298.CrossRefPubMed

42.

Bonora E, Formentini G, Calcaterra F, et al. HOMA-estimated insulin resistance is an independent predictor of cardiovascular disease in type 2 diabetic subjects: prospective data from the verona diabetes complications study. Diabetes Care. 2002;25:1135–41. https://doi.org/10.2337/DIACARE.25.7.1135.CrossRefPubMed

43.

Båvenholm P, Proudler A, Tornvall P, et al. Insulin, intact and split proinsulin, and coronary artery disease in young men. Circulation. 1995;92:1422–9. https://doi.org/10.1161/01.CIR.92.6.1422.CrossRefPubMed

44.

D’souza, Anna Marie. The effects of leptin knockout and insulin suppression on glucose metabolism in rodents. T. University of British Columbia, 2017. Web. 24 Jan. 2024. Electronic Theses and Dissertations (ETDs) 2008+. https://doi.org/10.14288/1.0354409

45.

Patel TP, Rawal K, Bagchi AK, et al. Insulin resistance: an additional risk factor in the pathogenesis of cardiovascular disease in type 2 diabetes. Heart Fail Rev. 2016;21:11–23. https://doi.org/10.1007/s10741-015-9515-6.CrossRefPubMed

46.

Egan BM, Greene EL, Goodfriend TL. Insulin resistance and cardiovascular disease. Am J Hypertens. 2001;14:116S-125S. https://doi.org/10.1016/S0895-7061(01)02078-7/2/AJH.116S.F4.JPEG.CrossRefPubMed

47.

Meigs JB, D’Agostino RB, Wilson PWF, Cupples LA, Nathan DM, Singer DE. Risk variable clustering in the insulin resistance syndrome: the Framingham offspring study. Diabetes. 1997;46:1594–600. https://doi.org/10.2337/DIACARE.46.10.1594.CrossRefPubMed

48.

Fiorentino T, Prioletta A, Zuo P, Folli F. Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases. Curr Pharm Des. 2013;19:5695–703. https://doi.org/10.2174/1381612811319320005.CrossRefPubMed

49.

Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes. 1991;40:405–12. https://doi.org/10.2337/DIAB.40.4.405.CrossRefPubMed

50.

Tesfamariam B, Cohen RA. Free radicals mediate endothelial cell dysfunction caused by elevated glucose. Am J Physiol. 1992. https://doi.org/10.1152/AJPHEART.1992.263.2.H321.CrossRefPubMed

51.

Giugliano D, Ceriello A, Paolisso G. Oxidative stress and diabetic vascular complications. Diabetes Care. 1996;19:257–67. https://doi.org/10.2337/DIACARE.19.3.257.CrossRefPubMed

52.

Hamilton SJ, Watts GF. Endothelial dysfunction in diabetes: pathogenesis, significance, and treatment. Rev Diabet Stud. 2013;10:133. https://doi.org/10.1900/RDS.2013.10.133.CrossRefPubMedPubMedCentral

53.

Kawano M, Koshikawa T, Kanzaki T, Morisaki N, Saito Y, Yoshida S. Diabetes mellitus induces accelerated growth of aortic smooth muscle cells: association with overexpression of PDGF beta-receptors. Eur J Clin Invest. 1993;23:84–90. https://doi.org/10.1111/J.1365-2362.1993.TB00745.X.CrossRefPubMed

54.

Inaba T, Ishibashi S, Gotoda T, et al. Enhanced expression of platelet-derived growth factor-beta receptor by high glucose. Involvement of platelet-derived growth factor in diabetic angiopathy. Diabetes. 1996;45:507–12. https://doi.org/10.2337/DIAB.45.4.507.CrossRefPubMed

55.

Blankenberg FG, Wen P, Dai M, et al. Detection of early atherosclerosis with radiolabeled monocyte chemoattractant protein-1 in prediabeteic Zucker rats. Pediatr Radiol. 2001;31:827–35. https://doi.org/10.1007/S002470100000/METRICS.CrossRefPubMed

56.

Gilbert RE, Rumble JR, Cao Z, et al. Endothelin receptor antagonism ameliorates mast cell infiltration, vascular hypertrophy, and epidermal growth factor expression in experimental diabetes. Circ Res. 2000;86:158–65. https://doi.org/10.1161/01.RES.86.2.158.CrossRefPubMed

57.

Haybar H, Bandar B, Torfi E, Mohebbi A, Saki N. Cytokines and their role in cardiovascular diseases. Cytokine. 2023. https://doi.org/10.1016/J.CYTO.2023.156261.CrossRefPubMed

58.

Blake GJ, Ridker PM. Novel clinical markers of vascular wall inflammation. Circ Inflamm. 2001. https://doi.org/10.1161/hh2101.099270.CrossRef

59.

Lüscher TF, Creager MA, Beckman JA, Cosentino F. Diabetes and vascular disease. Pathophysiology, clinical consequences, and medical therapy: part II. Circulation. 2003;108:1655–61. https://doi.org/10.1161/01.CIR.0000089189.70578.E2.CrossRefPubMed

60.

Shah AD, Langenberg C, Rapsomaniki E, et al. Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million people. Lancet Diabetes Endocrinol. 2015;3:105–13. https://doi.org/10.1016/S2213-8587(14)70219-0.CrossRefPubMedPubMedCentral

61.

Kosiborod M, Gomes MB, Nicolucci A, et al. Vascular Complications in patients with type 2 diabetes: prevalence and associated factors in 38 countries (the DISCOVER Study Program). Cardiovasc Diabetol. 2018. https://doi.org/10.1186/S12933-018-0787-8.CrossRefPubMedPubMedCentral

62.

Sun B, Luo Z, Zhou J. Comprehensive elaboration of glycemic variability in diabetic macrovascular and microvascular complications. Cardiovasc Diabetol. 2021. https://doi.org/10.1186/s12933-020-01200-7.CrossRefPubMedPubMedCentral

63.

Zhou X, Yu L, Zhao Y, Ge J. Panvascular medicine: an emerging discipline focusing on atherosclerotic diseases. Eur Heart J. 2022;43:4528–31. https://doi.org/10.1093/EURHEARTJ/EHAC448.CrossRefPubMed

64.

Pepine CJ. Insulin as a cardiovascular therapeutic: improving glycemic control in patients with coronary artery disease. J Am Coll Cardiol. 2009. https://doi.org/10.1016/j.jacc.2008.04.074.CrossRefPubMedPubMedCentral

65.

Qazi MU, Malik S. Diabetes and cardiovascular disease: insights from the framingham heart study. Glob Heart. 2013;8:43–8. https://doi.org/10.1016/j.gheart.2012.12.008.CrossRefPubMed

66.

Jensen LO, Maeng M, Thayssen P, et al. Influence of diabetes mellitus on clinical outcomes following primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction. Am J Cardiol. 2012;109:629–35. https://doi.org/10.1016/J.AMJCARD.2011.10.018.CrossRefPubMed

67.

Ram E, Sternik L, Klempfner R, et al. Type 2 diabetes mellitus increases the mortality risk after acute coronary syndrome treated with coronary artery bypass surgery. Cardiovasc Diabetol. 2020;19:1–9. https://doi.org/10.1186/S12933-020-01069-6/FIGURES/4.CrossRef

68.

Einarson TR, Acs A, Ludwig C, Panton UH. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017. Cardiovasc Diabetol. 2018;17:83. https://doi.org/10.1186/s12933-018-0728-6.CrossRefPubMedPubMedCentral

69.

Scott EW, Chris EAE. The influence of diabetes mellitus in patients undergoing coronary artery bypass graft surgery: a prospective cohort study. 2023. https://pubmed.ncbi.nlm.nih.gov/18807674/. Accessed 7 Sep 2023.

70.

Jia G, Hill MA, Sowers JR. Diabetic cardiomyopathy. Circ Res. 2018;122:624–38. https://doi.org/10.1161/CIRCRESAHA.117.311586.CrossRefPubMedPubMedCentral

71.

Rydén L, Armstrong PW, Cleland JGF, et al. Efficacy and safety of high-dose lisinopril in chronic heart failure patients at high cardiovascular risk, including those with diabetes mellitus: results from the ATLAS trial. Eur Heart J. 2000;21:1967–78. https://doi.org/10.1053/EUHJ.2000.2311.CrossRefPubMed

72.

Paolillo S, Marsico F, Prastaro M, et al. Diabetic cardiomyopathy: definition, diagnosis, and therapeutic implications. Heart Fail Clin. 2019;15:341–7. https://doi.org/10.1016/J.HFC.2019.02.003.CrossRefPubMed

73.

Tarquini R, Pala L, Brancati S, et al. Clinical approach to diabetic cardiomyopathy: a review of human studies. Curr Med Chem. 2017;25:1510–24. https://doi.org/10.2174/0929867324666170705111356.CrossRef

74.

Marwick TH, Ritchie R, Shaw JE, Kaye D. Implications of underlying mechanisms for the recognition and management of diabetic cardiomyopathy. J Am Coll Cardiol. 2018;71:339–51. https://doi.org/10.1016/J.JACC.2017.11.019.CrossRefPubMed

75.

Tawakol A, Jaffer F. Imaging the intersection of oxidative stress, lipids, and inflammation: progress toward personalized care of atherosclerosis. J Am Coll Cardiol. 2018;71:336–8. https://doi.org/10.1016/J.JACC.2017.11.031.CrossRefPubMed

76.

Khalid M, Petroianu G, Adem A. Advanced glycation end products and diabetes mellitus: mechanisms and perspectives. Biomolecules. 2022. https://doi.org/10.3390/BIOM12040542.CrossRefPubMedPubMedCentral

77.

Adeshara KA, Bangar NS, Doshi PR, Diwan A, Tupe RS. Action of metformin therapy against advanced glycation, oxidative stress and inflammation in type 2 diabetes patients: 3 months follow-up study. Diabetes Metab Syndr Clin Res Rev. 2020;14:1449–58. https://doi.org/10.1016/j.dsx.2020.07.036.CrossRef

78.

Lin KH, Ali A, Kuo CH, et al. Carboxyl terminus of HSP70-interacting protein attenuates advanced glycation end products-induced cardiac injuries by promoting NFκB proteasomal degradation. J Cell Physiol. 2022;237:1888–901. https://doi.org/10.1002/JCP.30660.CrossRefPubMed

79.

Su SC, Hung YJ, Huang CL, et al. Cilostazol inhibits hyperglucose-induced vascular smooth muscle cell dysfunction by modulating the RAGE/ERK/NF-ΚB signaling pathways. J Biomed Sci. 2019. https://doi.org/10.1186/S12929-019-0550-9.CrossRefPubMedPubMedCentral

80.

Twarda-clapa A, Olczak A, Białkowska AM, Koziołkiewicz M. Advanced glycation end-products (AGEs): formation, chemistry, classification, receptors, and diseases related to AGEs. Cells. 2022. https://doi.org/10.3390/CELLS11081312.CrossRefPubMedPubMedCentral

81.

Hussain S, Khan AW, Akhmedov A, et al. Hyperglycemia induces myocardial dysfunction via epigenetic regulation of JunD. Circ Res. 2020;127:1261–73. https://doi.org/10.1161/CIRCRESAHA.120.317132.CrossRefPubMed

82.

Paneni F, Osto E, Costantino S, et al. Deletion of the activated protein-1 transcription factor JunD induces oxidative stress and accelerates age-related endothelial dysfunction. Circulation. 2013;127:1229–40. https://doi.org/10.1161/CIRCULATIONAHA.112.000826.CrossRefPubMed

83.

Costantino S, Akhmedov A, Melina G, et al. Obesity-induced activation of JunD promotes myocardial lipid accumulation and metabolic cardiomyopathy. Eur Heart J. 2019;40:997–1008. https://doi.org/10.1093/eurheartj/ehy903.CrossRefPubMed

84.

Wang Y, Luo W, Han J, et al. MD2 activation by direct AGE interaction drives inflammatory diabetic cardiomyopathy. Nat Commun. 2020;11:1–16. https://doi.org/10.1038/s41467-020-15978-3.ADSCrossRef

85.

De Ferranti SD, De Boer IH, Fonseca V, et al. Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. Diabetes Care. 2014;37:2843–63. https://doi.org/10.2337/dc14-1720.CrossRefPubMedPubMedCentral

86.

Zhang T, Sell P, Braun U, Leitges M. PKD1 protein is involved in reactive oxygen species-mediated mitochondrial depolarization in cooperation with protein kinase Cδ (PKCδ). J Biol Chem. 2015;290:10472. https://doi.org/10.1074/JBC.M114.619148.CrossRefPubMedPubMedCentral

87.

Ishii H, Koya D, King GL. Protein kinase C activation and its role in the development of vascular complications in diabetes mellitus. J Mol Med. 1997;76:21–31. https://doi.org/10.1007/S001090050187.CrossRef

88.

Koya D, King GL. Protein kinase C activation and the development of diabetic complications. Diabetes. 1998;47:859–66. https://doi.org/10.2337/DIABETES.47.6.859.CrossRefPubMed

89.

Das Evcimen N, King GL. The role of protein kinase C activation and the vascular complications of diabetes. Pharmacol Res. 2007;55:498–510. https://doi.org/10.1016/j.phrs.2007.04.016.CrossRefPubMed

90.

Li G, Yang L, Feng L, et al. Front cover: syringaresinol protects against type 1 diabetic cardiomyopathy by alleviating inflammation responses, cardiac fibrosis, and oxidative stress. Mol Nutr Food Res. 2020;64:2070040. https://doi.org/10.1002/MNFR.202070040.CrossRef

91.

García-Díez E, López-Oliva ME, Caro-Vadillo A, et al. Supplementation with a cocoa-carob blend, alone or in combination with metformin, attenuates diabetic cardiomyopathy, cardiac oxidative stress and inflammation in Zucker diabetic rats. Antioxidants. 2022. https://doi.org/10.3390/ANTIOX11020432.CrossRefPubMedPubMedCentral

92.

Al-Lahham S, Roelofsen H, Rezaee F, et al. Propionic acid affects immune status and metabolism in adipose tissue from overweight subjects. Eur J Clin Invest. 2012;42:357–64. https://doi.org/10.1111/J.1365-2362.2011.02590.X.CrossRefPubMed

93.

DeFronzo RA, Ferrannini E, Groop L, et al. Type 2 diabetes mellitus. Nat Rev Dis Prim. 2015;1:1–22. https://doi.org/10.1038/nrdp.2015.19.CrossRef

94.

Agarwal G, Singh S. Arrhythmias in type 2 diabetes mellitus. Indian J Endocrinol Metab. 2017;21:715. https://doi.org/10.4103/IJEM.IJEM_448_16.CrossRefPubMedPubMedCentral

95.

Movahed M-R, Hashemzadeh M, Mazen Jamal M. Diabetes mellitus is a strong, independent risk for atrial fibrillation and flutter in addition to other cardiovascular disease. Int J Cardiol. 2005;105(3):315-8. https://doi.org/10.1016/j.ijcard.2005.02.050.

96.

Chen R, Ovbiagele B, Feng W. Diabetes and stroke: epidemiology, pathophysiology, pharmaceuticals and outcomes. Am J Med Sci. 2016;351:380. https://doi.org/10.1016/J.AMJMS.2016.01.011.CrossRefPubMedPubMedCentral

97.

Mosenzon O, Cheng AYY, Rabinstein AA, Sacco S. Diabetes and stroke: what are the connections? J Stroke. 2023;25:26. https://doi.org/10.5853/JOS.2022.02306.CrossRefPubMedPubMedCentral

98.

Banday MZ, Sameer AS, Nissar S. Pathophysiology of diabetes: an overview. Avicenna J Med. 2020;10:174. https://doi.org/10.4103/AJM.AJM_53_20.CrossRefPubMedPubMedCentral

99.

Li Y, Zeng KW, Wang XM. Cerebral microangiopathy of diabetes. Zhongguo Zhong Yao Za Zhi. 2017;42:2247–53. https://doi.org/10.19540/J.CNKI.CJCMM.2017.0104.CrossRefPubMed

100.

Singh M, Kapoor A, Bhatnagar A. Physiological and pathological roles of aldose reductase. Metabolites. 2021. https://doi.org/10.3390/METABO11100655.CrossRefPubMedPubMedCentral

101.

Wilson DK, Bohren KM, Gabbay KH, Quiocho FA. An unlikely sugar substrate site in the 1.65 Å structure of the human aldose reductase holoenzyme implicated in diabetic complications. Science. 1992;257:81–4. https://doi.org/10.1126/SCIENCE.1621098.ADSCrossRefPubMed

102.

Umegaki H, Hayashi T, Nomura H, et al. Cognitive dysfunction: an emerging concept of a new diabetic complication in the elderly. Geriatr Gerontol Int. 2013;13:28–34. https://doi.org/10.1111/J.1447-0594.2012.00922.X.CrossRefPubMed

103.

White MF. The IRS-signalling system in insulin and cytokine action. Philos Trans R Soc B Biol Sci. 1996;351:181–9. https://doi.org/10.1098/rstb.1996.0015.ADSCrossRef

104.

White MF. The insulin signalling system and the IRS proteins. Diabetologia. 1997. https://doi.org/10.1007/S001250051387.CrossRefPubMed

105.

Furtado LM, Poon V, Klip A. GLUT4 activation: thoughts on possible mechanisms. Acta Physiol Scand. 2003;178:287–96. https://doi.org/10.1046/j.1365-201X.2003.01160.x.CrossRef

106.

Furtado LM, Somwar R, Sweeney G, Niu W, Klip A. Activation of the glucose transporter GLUT4 by insulin. Biochem Cell Biol. 2002;80:569–78. https://doi.org/10.1139/O02-156.CrossRefPubMed

107.

Theofilis P, Sagris M, Oikonomou E, et al. Inflammatory mechanisms contributing to endothelial dysfunction. Biomedicines. 2021. https://doi.org/10.3390/BIOMEDICINES9070781.CrossRefPubMedPubMedCentral

108.

Mussbacher M, Salzmann M, Brostjan C, et al. Cell type specific roles of NF-κB linking inflamation and thrombosis. Front Immunol. 2019. https://doi.org/10.3389/fimmu.2019.00085.CrossRefPubMedPubMedCentral

109.

Botham KM, Wheeler-Jones CPD. Postprandial lipoproteins and the molecular regulation of vascular homeostasis. Prog Lipid Res. 2013;52:446–64. https://doi.org/10.1016/j.plipres.2013.06.001.CrossRefPubMed

110.

Madonna R, De Caterina R. Cellular and molecular mechanisms of vascular injury in diabetes - part I: pathways of vascular disease in diabetes. Vascul Pharmacol. 2011;54:68–74. https://doi.org/10.1016/j.vph.2011.03.005.CrossRefPubMed

111.

Mattson MP. Glutamate and neurotrophic factors in neuronal plasticity and disease. Ann N Y Acad Sci. 2008;1144:97–112. https://doi.org/10.1196/ANNALS.1418.005.ADSCrossRefPubMedPubMedCentral

112.

Taylor S, Srinivasan B, Wordinger RJ, Roque RS. Glutamate stimulates neurotrophin expression in cultured müller cells. Mol Brain Res. 2003;111:189–97. https://doi.org/10.1016/S0169-328X(03)00030-5.CrossRefPubMed

113.

Huysman F, Mathieu C. Diabetes and peripheral vascular disease. Acta Chir Belg. 2009;109:587–94. https://doi.org/10.1080/00015458.2009.11680493.CrossRefPubMed

114.

Aquino R, Johnnides C, Makaroun M, et al. Natural history of claudication: long-term serial follow-up study of 1244 claudicants. J Vasc Surg. 2001;34:962–70. https://doi.org/10.1067/MVA.2001.119749.CrossRefPubMed

115.

Golledge J, Leicht A, Crowther RG, Clancy P, Spinks WL, Quigley F. Association of obesity and metabolic syndrome with the severity and outcome of intermittent claudication. J Vasc Surg. 2007;45:40–6. https://doi.org/10.1016/j.jvs.2006.09.006.CrossRefPubMed

116.

Yokoyama H, Sone H, Honjo J, et al. Relationship between a low ankle brachial index and all-cause death and cardiovascular events in subjects with and without diabetes. J Atheroscler Thromb. 2014;21:574–81. https://doi.org/10.5551/JAT.22491.CrossRefPubMed

117.

Altoijry A, AlGhofili H, Alanazi SN, et al. Diabetic foot and peripheral arterial disease: single centre experience. Saudi Med J. 2021;42:49–55. https://doi.org/10.15537/SMJ.2021.1.25640.CrossRefPubMedPubMedCentral

118.

Al-Thani H, El-Menyar A, Koshy V, et al. Implications of foot ulceration in hemodialysis patients: a 5-year observational study. J Diabetes Res. 2014. https://doi.org/10.1155/2014/945075.CrossRefPubMedPubMedCentral

119.

Rains JL, Jain SK. Oxidative stress, insulin signaling, and diabetes. Free Radic Biol Med. 2011;50:567–75. https://doi.org/10.1016/J.FREERADBIOMED.2010.12.006.CrossRefPubMed

120.

Newsholme P, Keane KN, Carlessi R, Cruzat V. Oxidative stress pathways in pancreatic β-cells and insulin-sensitive cells and tissues: importance to cell metabolism, function, and dysfunction. Am J Physiol Cell Physiol. 2019;317:C420–33. https://doi.org/10.1152/ajpcell.00141.2019.CrossRefPubMed

121.

Gurzov EN, Tran M, Fernandez-Rojo MA, et al. Hepatic oxidative stress promotes insulin-STAT-5 signaling and obesity by inactivating protein tyrosine phosphatase N2. Cell Metab. 2014;20:85. https://doi.org/10.1016/J.CMET.2014.05.011.CrossRefPubMedPubMedCentral

122.

Malhotra JD, Kaufman RJ. Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? Antioxid Redox Signal. 2007;9:2277–93. https://doi.org/10.1089/ARS.2007.1782.CrossRefPubMed

123.

Malhotra JD, Kaufman RJ. The endoplasmic reticulum and the unfolded protein response. Semin Cell Dev Biol. 2007;18:716–31. https://doi.org/10.1016/j.semcdb.2007.09.003.CrossRefPubMedPubMedCentral

124.

Kotlarsky P, Bolotin A, Dorfman K, Knyazer B, Lifshitz T, Levy J. Link between retinopathy and nephropathy caused by complications of diabetes mellitus type 2. Int Ophthalmol. 2015;35:59–66. https://doi.org/10.1007/S10792-014-0018-6.CrossRefPubMed

125.

Jawa A, Kcomt J, Fonseca VA. Diabetic nephropathy and retinopathy. Med Clin N Am. 2004;88:1001–36. https://doi.org/10.1016/j.mcna.2004.04.012.CrossRefPubMed

126.

Fadini GP, Albiero M, Bonora BM, Avogaro A. Angiogenic abnormalities in diabetes mellitus: mechanistic and clinical aspects. J Clin Endocrinol Metab. 2019;104:5431–44. https://doi.org/10.1210/JC.2019-00980.CrossRefPubMed

127.

Simo R, Carrasco E, Garcia-Ramirez M, Hernandez C. Angiogenic and antiangiogenic factors in proliferative diabetic retinopathy. Curr Diabetes Rev. 2006;2:71–98. https://doi.org/10.2174/157339906775473671.CrossRefPubMed

128.

Liu ZL, Chen HH, Zheng LL, Sun LP, Shi L. Angiogenic signaling pathways and anti-angiogenic therapy for cancer. Signal Transduct Target Ther. 2023;8:1–39. https://doi.org/10.1038/s41392-023-01460-1.CrossRefPubMedPubMedCentral

129.

Caldwell RB, Bartoli M, Behzadian MA, et al. Vascular endothelial growth factor and diabetic retinopathy: pathophysiological mechanisms and treatment perspectives. Diabetes Metab Res Rev. 2003;19:442–55. https://doi.org/10.1002/dmrr.415.CrossRefPubMed

130.

Caputa G, Flachsmann LJ, Cameron AM. Macrophage metabolism: a wound-healing perspective. Immunol Cell Biol. 2019;97:268–78. https://doi.org/10.1111/IMCB.12237.CrossRefPubMed

131.

Wilson K. Wound healing: the role of macrophages. Nurs Crit Care. 1997;2:291–6.PubMed

132.

Wang B, Chandrasekera P, Pippin J. Leptin- and leptin receptor-deficient rodent models: relevance for human type 2 diabetes. Curr Diabetes Rev. 2014;10:131–45. https://doi.org/10.2174/1573399810666140508121012.CrossRefPubMedPubMedCentral

133.

Belke DD, Severson DL. Diabetes in mice with monogenic obesity: the db/db mouse and its use in the study of cardiac consequences. Methods Mol Biol. 2012;933:47–57. https://doi.org/10.1007/978-1-62703-068-7_4.CrossRefPubMed

134.

Hofmann A, Peitzsch M, Brunssen C, et al. Elevated steroid hormone production in the db/db mouse model of obesity and type 2 diabetes. Horm Metab Res. 2017;49:43–9. https://doi.org/10.1055/S-0042-116157.CrossRefPubMed

135.

Suriano F, Vieira-Silva S, Falony G, et al. Novel insights into the genetically obese (ob/ob) and diabetic (db/db) mice: two sides of the same coin. Microbiome. 2021. https://doi.org/10.1186/S40168-021-01097-8.CrossRefPubMedPubMedCentral

136.

Khanna S, Biswas S, Shang Y, et al. Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice. PLoS ONE. 2023. https://doi.org/10.1371/journal.pone.0009539.CrossRefPubMedPubMedCentral

137.

Chen S, Saeed AFUH, Liu Q, et al. Macrophages in immunoregulation and therapeutics. Signal Transduct Target Ther. 2023. https://doi.org/10.1038/s41392-023-01452-1.CrossRefPubMedPubMedCentral

138.

Galiano RD, Tepper OM, Pelo CR, et al. Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells. Am J Pathol. 2004;164:1935–47. https://doi.org/10.1016/S0002-9440(10)63754-6.CrossRefPubMedPubMedCentral

139.

Sun LL, Li WD, Lei FR, Li XQ. The regulatory role of microRNAs in angiogenesis-related diseases. J Cell Mol Med. 2018;22:4568–87. https://doi.org/10.1111/JCMM.13700.CrossRefPubMedPubMedCentral

140.

Tiwari A, Mukherjee B, Dixit M. MicroRNA key to angiogenesis regulation: MiRNA biology and therapy. Curr Cancer Drug Targets. 2017;18:266–77. https://doi.org/10.2174/1568009617666170630142725.CrossRef

141.

Winkle M, El-Daly SM, Fabbri M, Calin GA. Noncoding RNA therapeutics — challenges and potential solutions. Nat Rev Drug Discov. 2021;20:629–51. https://doi.org/10.1038/s41573-021-00219-z.CrossRefPubMedPubMedCentral

142.

Lenkala D, LaCroix B, Gamazon ER, Geeleher P, Im HK, Huang RS. The impact of MicroRNA expression on cellular proliferation. Hum Genet. 2014;133:931–8. https://doi.org/10.1007/s00439-014-1434-4.CrossRefPubMedPubMedCentral

143.

Kim M, Zhang X. The profiling and role of MiRNAs in diabetes mellitus. J diabetes Clin Res. 2019;1:5. https://doi.org/10.33696/DIABETES.1.003.CrossRefPubMedPubMedCentral

144.

Gollavilli PN, Parma B, Siddiqui A, et al. The role of MiR-200b/c in balancing EMT and proliferation revealed by an activity reporter. Oncogene. 2021;40:2309–22. https://doi.org/10.1038/s41388-021-01708-6.CrossRefPubMedPubMedCentral

145.

Kottaisamy CPD, Raj DS, Prasanth Kumar V, Sankaran U. Experimental animal models for diabetes and its related complications—a review lab. Anim Res. 2021;37(1):14. https://doi.org/10.1186/S42826-021-00101-4.CrossRef

146.

Fang JY, Lin CH, Huang TH, Chuang SY. In vivo rodent models of type 2 diabetes and their usefulness for evaluating flavonoid bioactivity. Nutrients. 2019. https://doi.org/10.3390/NU11030530.CrossRefPubMedPubMedCentral

147.

Tiaka EK, Papanas N, Manolakis AC, Maltezos E. The role of hyperbaric oxygen in the treatment of diabetic foot ulcers. Angioology. 2011;63:302–14. https://doi.org/10.1177/0003319711416804.CrossRef

148.

Kaya A, Aydin F, Altay T, Karapinar L, Ozturk H, Karakuzu C. Can major amputation rates be decreased in diabetic foot ulcers with hyperbaric oxygen therapy? Int Orthop. 2009;33:441. https://doi.org/10.1007/S00264-008-0623-Y.CrossRefPubMed

149.

Abidia A, Laden G, Kuhan G, et al. The role of hyperbaric oxygen therapy in ischaemic diabetic lower extremity ulcers: a double-blind randomized-controlled trial. Eur J Vasc Endovasc Surg. 2003;25:513–8. https://doi.org/10.1053/EJVS.2002.1911.CrossRefPubMed

150.

Al-Waili NS, Butler GJ, Beale J, et al. Influences of hyperbaric oxygen on blood pressure, heart rate and blood glucose levels in patients with diabetes mellitus and hypertension. Arch Med Res. 2006;37:991–7. https://doi.org/10.1016/J.ARCMED.2006.05.009.CrossRefPubMed

151.

Stoekenbroek RM, Santema TB, Legemate DA, Ubbink DT, Van Den Brink A, Koelemay MJW. Hyperbaric oxygen for the treatment of diabetic foot ulcers: a systematic review. Eur J Vasc Endovasc Surg. 2014;47:647–55. https://doi.org/10.1016/J.EJVS.2014.03.005.CrossRefPubMed

152.

Kwon MJ, An S, Choi S, et al. Effective healing of diabetic skin wounds by using nonviral gene therapy based on minicircle vascular endothelial growth factor DNA and a cationic dendrimer. J Gene Med. 2012;14:272–8. https://doi.org/10.1002/JGM.2618.CrossRefPubMed

153.

Barrientos S, Brem H, Stojadinovic O, Tomic-Canic M. Clinical application of growth factors and cytokines in wound healing. Wound Repair Regen. 2014;22:569. https://doi.org/10.1111/WRR.12205.CrossRefPubMedPubMedCentral

154.

Steed DL. Clinical evaluation of recombinant human platelet-derived growth factor for the treatment of lower extremity ulcers. Plast Reconstr Surg. 2006. https://doi.org/10.1097/01.PRS.0000222526.21512.4C.CrossRefPubMed

155.

Smiell JM, Wieman TJ, Steed DL, Perry BH, Sampson AR, Schwab BH. Efficacy and safety of becaplermin (recombinant human platelet-derived growth factor-BB) in patients with nonhealing, lower extremity diabetic ulcers: a combined analysis of four randomized studies. Wound Repair Regen. 1999;7:335–46. https://doi.org/10.1046/J.1524-475X.1999.00335.X.CrossRefPubMed

156.

De Pascale MR, Sommese L, Casamassimi A, Napoli C. Platelet derivatives in regenerative medicine: an update. Transfus Med Rev. 2015;29:52–61. https://doi.org/10.1016/J.TMRV.2014.11.001.CrossRefPubMed

157.

Bagheri M, Jahromi BM, Mirkhani H, et al. Azelnidipine, a new calcium channel blocker, promotes skin wound healing in diabetic rats. J Surg Res. 2011. https://doi.org/10.1016/J.JSS.2011.02.039.CrossRefPubMed

158.

Babaei S, Bayat M, Nouruzian M, Bayat M. Pentoxifylline improves cutaneous wound healing in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2013;700:165–72. https://doi.org/10.1016/J.EJPHAR.2012.11.024.CrossRefPubMed

159.

Hamed S, Ullmann Y, Masoud M, Hellou E, Khamaysi Z, Teot L. Topical erythropoietin promotes wound repair in diabetic rats. J Invest Dermatol. 2010;130:287–94. https://doi.org/10.1038/JID.2009.219.CrossRefPubMed

160.

Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group (1998). Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. New Engl J Med. 1998;339(19):1349–57. https://doi.org/10.1056/NEJM199811053391902.

161.

Scott JR, Tamura RN, Muangman P, Isik FF, Xie C, Gibran NS. Topical substance P increases inflammatory cell density in genetically diabetic murine wounds. Wound Repair Regen. 2008;16:529–33. https://doi.org/10.1111/J.1524-475X.2008.00400.X.CrossRefPubMed

162.

Hou Z, Nie C, Si Z, Ma Y. Deferoxamine enhances neovascularization and accelerates wound healing in diabetic rats via the accumulation of hypoxia-inducible factor-1α. Diabetes Res Clin Pract. 2013;101:62–71. https://doi.org/10.1016/J.DIABRES.2013.04.012.CrossRefPubMed

163.

Romana-Souza B, Nascimento AP, Monte-Alto-Costa A. Propranolol improves cutaneous wound healing in streptozotocin-induced diabetic rats. Eur J Pharmacol. 2009;611:77–84. https://doi.org/10.1016/J.EJPHAR.2009.03.053.CrossRefPubMed

164.

Kaur P, Sharma AK, Nag D, et al. Novel nano-insulin formulation modulates cytokine secretion and remodeling to accelerate diabetic wound healing. Nanomed Nanotechnol Biol Med. 2019;15:47–57. https://doi.org/10.1016/J.NANO.2018.08.013.CrossRef

165.

Lee CH, Chang SH, Chen WJ, et al. Augmentation of diabetic wound healing and enhancement of collagen content using nanofibrous glucophage-loaded collagen/PLGA scaffold membranes. J Colloid Interface Sci. 2015;439:88–97. https://doi.org/10.1016/J.JCIS.2014.10.028.ADSCrossRefPubMed

166.

Wang X, Sng MK, Foo S, et al. Early controlled release of peroxisome proliferator-activated receptor β/δ agonist gw501516 improves diabetic wound healing through redox modulation of wound microenvironment. J Control Release. 2015;197:138–47. https://doi.org/10.1016/J.JCONREL.2014.11.001.CrossRefPubMed

167.

Young GH, Lin JT, Cheng YF, et al. Modulation of adenine phosphoribosyltransferase-mediated salvage pathway to accelerate diabetic wound healing. FASEB J. 2021;35:e21296–e21296. https://doi.org/10.1096/FJ.202001736RR.CrossRefPubMed

168.

Whittam AJ, Maan ZN, Duscher D, et al. Small molecule inhibition of dipeptidyl peptidase-4 enhances bone marrow progenitor cell function and angiogenesis in diabetic wounds. Transl Res. 2019;205:51–63. https://doi.org/10.1016/J.TRSL.2018.10.006.CrossRefPubMed

169.

Hozzein WN, Badr G, Badr BM, et al. Bee venom improves diabetic wound healing by protecting functional macrophages from apoptosis and enhancing Nrf2, Ang-1 and Tie-2 signaling. Mol Immunol. 2018;103:322–35. https://doi.org/10.1016/J.MOLIMM.2018.10.016.CrossRefPubMed

170.

Kawai K, Kageyama A, Tsumano T, et al. Effects of adiponectin on growth and differentiation of human keratinocytes—implication of impaired wound healing in diabetes. Biochem Biophys Res Commun. 2008;374:269–73. https://doi.org/10.1016/J.BBRC.2008.07.045.CrossRefPubMed

171.

Moura LIF, Dias AMA, Leal EC, Carvalho L, De Sousa HC, Carvalho E. Chitosan-based dressings loaded with neurotensin–an efficient strategy to improve early diabetic wound healing. Acta Biomater. 2014;10:843–57. https://doi.org/10.1016/J.ACTBIO.2013.09.040.CrossRefPubMed

172.

Gooyit M, Peng Z, Wolter WR, et al. A chemical biological strategy to facilitate diabetic wound healing. ACS Chem Biol. 2014;9:105–10. https://doi.org/10.1021/CB4005468.CrossRefPubMed

173.

Galeano M, Polito F, Bitto A, et al. Systemic administration of high-molecular weight hyaluronan stimulates wound healing in genetically diabetic mice. Biochim Biophys Acta. 2011;1812:752–9. https://doi.org/10.1016/J.BBADIS.2011.03.012.CrossRefPubMed

174.

Chong HC, Chan JSK, Goh CQ, et al. Angiopoietin-like 4 stimulates STAT3-mediated INOS expression and enhances angiogenesis to accelerate wound healing in diabetic mice. Mol Ther. 2014;22:1593–604. https://doi.org/10.1038/MT.2014.102.CrossRefPubMedPubMedCentral

175.

Brown RL, Breeden MP, Greenhalgh DG. PDGF and TGF-alpha act synergistically to improve wound healing in the genetically diabetic mouse. J Surg Res. 1994;56:562–70. https://doi.org/10.1006/JSRE.1994.1090.CrossRefPubMed

176.

Reynolds K, Goldberg RB. Thiazolidinediones: beyond glycemic control. Treat Endocrinol. 2006;5:25–36. https://doi.org/10.2165/00024677-200605010-00004.CrossRefPubMed

177.

Hughes K, Aw TC, Kuperan P, Choo M. Central obesity, insulin resistance, syndrome X, lipoprotein(a), and cardiovascular risk in Indians, Malays, and Chinese in Singapore. J Epidemiol Community Health. 1997;51:394–9. https://doi.org/10.1136/JECH.51.4.394.CrossRefPubMedPubMedCentral

178.

McFarlane SI, Kumar A, Sowers JR. Mechanisms by which angiotensin-converting enzyme inhibitors prevent diabetes and cardiovascular disease. Am J Cardiol. 2003;91:30–7. https://doi.org/10.1016/S0002-9149(03)00432-6.CrossRef

179.

Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349–57. https://doi.org/10.1056/NEJM199811053391902.CrossRef

180.

Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels cholesterol and recurrent events trial investigators. N Engl J Med. 1996;335:1001–9. https://doi.org/10.1056/NEJM199610033351401.CrossRefPubMed

181.

Pyörälä K, Pedersen TR, Kjekshus J, Faergeman O, Olsson AG, Thorgeirsson G. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease. A subgroup analysis of the Scandinavian simvastatin survival study (4S). Diabetes Care. 1997;20:614–20. https://doi.org/10.2337/DIACARE.20.4.614.CrossRefPubMed

182.

Steiner G, Hamsten A, Hosking J, et al. Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the diabetes atherosclerosis intervention study, a randomised study. Lancet. 2001;357:905–10. https://doi.org/10.1016/S0140-6736(00)04209-4.CrossRef

183.

Elkeles RS, Diamond JR, Poulter C, et al. Cardiovascular outcomes in type 2 diabetes: a double-blind placebo-controlled study of bezafibrate: the St Mary’s, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) study. Diabetes Care. 1998;21:641–8. https://doi.org/10.2337/DIACARE.21.4.641.CrossRefPubMed

184.

Forzano I, Wilson S, Lombardi A, et al. SGLT2 inhibitors: an evidence-based update on cardiovascular implications. Expert Opin Investig Drugs. 2023;32:839–47. https://doi.org/10.1080/13543784.2023.2263354.CrossRefPubMed

185.

Fitchett D, Inzucchi SE, Cannon CP, et al. Empagliflozin reduced mortality and hospitalization for heart failure across the spectrum of cardiovascular risk in the EMPA-REG OUTCOME trial. Circulation. 2019;139:1384–95. https://doi.org/10.1161/CIRCULATIONAHA.118.037778.CrossRefPubMed

186.

Giugliano D, Longo M, Signoriello S, et al. The effect of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors on cardiorenal outcomes: a network meta-analysis of 23 CVOTs. Cardiovasc Diabetol. 2022. https://doi.org/10.1186/S12933-022-01474-Z.CrossRefPubMedPubMedCentral

187.

Demuth HU, McIntosh CHS, Pederson RA. Type 2 diabetes—therapy with dipeptidyl peptidase IV inhibitors. Biochim Biophys Acta. 2005;1751:33–44. https://doi.org/10.1016/J.BBAPAP.2005.05.010.CrossRefPubMed

188.

Craddy P, Palin HJ, Johnson KI. Comparative effectiveness of dipeptidylpeptidase-4 inhibitors in type 2 diabetes: a systematic review and mixed treatment comparison. Diabetes Ther. 2014;5:1–41. https://doi.org/10.1007/S13300-014-0061-3.CrossRefPubMedPubMedCentral

189.

Dou J, Ma J, Liu J, Wang C, et al. Efficacy and safety of saxagliptin in combination with metformin as initial therapy in chinese patients with type 2 diabetes: results from the START study, a multicentre, randomized, double-blind, active-controlled, phase 3 trial. Diabetes Obes Metab. 2018;20:590–8. https://doi.org/10.1111/DOM.13117.CrossRefPubMed

190.

Behary P, Tharakan G, Alexiadou K, et al. Combined GLP-1, oxyntomodulin, and peptide YY improves body weight and glycemia in obesity and prediabetes/type 2 diabetes: a randomized, single-blinded. Placebo-Controlled Study Diabetes Care. 2019;42:1446–53. https://doi.org/10.2337/DC19-0449.CrossRefPubMed

191.

Yeh TL, Tsai MC, Tsai WH, Tu YK, Chien KL. Effect of glucagon-like peptide-1 receptor agonists on glycemic control, and weight reduction in adults: a multivariate meta-analysis. PLoS ONE. 2023. https://doi.org/10.1371/JOURNAL.PONE.0278685.CrossRefPubMedPubMedCentral

192.

Müller TD, Finan B, Bloom SR, et al. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019;30:72–130. https://doi.org/10.1016/J.MOLMET.2019.09.010.CrossRefPubMedPubMedCentral

193.

Nauck MA, Meier JJ. Are all GLP-1 agonists equal in the treatment of type 2 diabetes? Eur J Endocrinol. 2019;181:R211–34. https://doi.org/10.1530/EJE-19-0566.CrossRefPubMed

Title: A Narrative Review of Diabetic Macroangiopathy: From Molecular Mechanism to Therapeutic Approaches
Authors: Jiacheng Yin
Xiaoxu Fu
Yue Luo
Yuling Leng
Lianjun Ao
Chunguang Xie
Publication date: 02-02-2024
Publisher: Springer Healthcare
Keywords: Diabetes-associated Diseases
Diabetes and Cardiac Diseases
Angiology
Diabetes
Type 1 Diabetes
Type 2 Diabetes
Diabetes Therapy
Diabetes and Cardiac Diseases
Endocrinology
Arterial Occlusive Disease
Peripheral Arterial Disease
Peripheral Arterial Disease
Insulins
Insulins
Published in: Diabetes Therapy / Issue 3/2024
Print ISSN: 1869-6953
Electronic ISSN: 1869-6961
DOI: https://doi.org/10.1007/s13300-024-01532-7

Treat Obesity to Treat Type 2 Diabetes Mellitus

Open Access
Obesity
Review

Impact of Participant Characteristics on Clinical Outcomes with iGlarLixi in Type 2 Diabetes: Post Hoc Analysis of SPARTA Japan

Open Access
Insulins
Original Research

Association Between Adherence, A1C Improvement, and Type of Continuous Glucose Monitoring System in People with Type 1 Diabetes or Type 2 Diabetes Treated with Intensive Insulin Therapy

Open Access
Type 1 Diabetes
Original Research

Insulin Degludec in People with Type 2 Diabetes in China: A Non-interventional, Retrospective Chart Review Study (CN-TREAT)

Open Access
Insulins
Original Research

Real-World Use of Oral Semaglutide in Adults with Type 2 Diabetes: The PIONEER REAL Switzerland Multicentre, Prospective, Observational Study

Open Access
Semaglutide
Original Research

Risk of Dementia in Patients with Diabetes Using Sodium-Glucose Transporter 2 Inhibitors (SGLT2i): A Systematic Review, Meta-Analysis, and Meta-Regression

Open Access
Dementia
Original Research

Keynote webinar | Spotlight on menopause

Menopause
Video Series

Menopause can have a significant impact on the body, with effects ranging beyond the endocrine and reproductive systems. Learn about the broader systemic effects of menopause, so you can help patients in your clinics through the transition.

Prof. Martha Hickey

Dr. Claudia Barth

Dr. Samar El Khoudary

Developed by: Springer Medicine

Watch now

Keynote webinar | Spotlight on adolescent vaping

Live
Webinar | 29-01-2025 | 18:00 (CET)

Growing numbers of young people are using e-cigarettes, despite warnings of respiratory effects and addiction. How can doctors tackle the epidemic, and what health effects should you prepare to manage in your clinics?

Watch it live: Wednesday 29th January, 18:00-19:30 CET

Prof. Ann McNeill

Dr. Debbie Robson

Benji Horwell

Developed by: Springer Medicine

Join the webinar

Keynote webinar | Spotlight on modern management of frailty

Frailty in Geriatric Patients
On-demand webinar

Frailty has a significant impact on health and wellbeing, especially in older adults. Our experts explain the factors that contribute to the development of frailty and how you can manage the condition and reduce the risk of disability, dependency, and mortality in your patients.

Prof. Alfonso Cruz-Jentoft

Prof. Barbara C. van Munster

Prof. Mirko Petrovic

Developed by: Springer Medicine

Watch now

A quick guide to ECGs

Electrocardiography
Training Course

Improve your ECG interpretation skills with this comprehensive, rapid, interactive course. Expert advice provides detailed feedback as you work through 50 ECGs covering the most common cardiac presentations to ensure your practice stays up to date.

PD Dr. Carsten W. Israel

Developed by: Springer Medizin

Start the cases

At a glance: The STEP trials

Obesity
Clinical Trial Summary

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Image Credits

Cholesterol plaque in artery and human heart 3D illustration/© Rasi Bhadramani / Getty Images / iStock, Group of women outdoors/© Jade Maas/ peopleimages.com / Stock.adobe.com (symbolic image with models), Person in orange t-shirt using an e-cigarette/© licsiren / Getty Images / iStock (symbolic image with model), Frailty concept image/© ImagineStock / stock.adobe.com (symbolic image with models), Case-Based Insights teaser image/© Eva Künzel, Person walking/© _KUBE_ / Stock.adobe.com

Keynote webinar | Spotlight on adolescent vaping

Springer Medicine

Abstract

Please log in to get access to this content