Skip to main content
Top
Published in: Internal and Emergency Medicine 3/2020

01-04-2020 | Arterial Occlusive Disease | IM - REVIEW

Biomarkers of vascular disease in diabetes: the adipose-immune system cross talk

Authors: Federico Biscetti, Elisabetta Nardella, Andrea Leonardo Cecchini, Andrea Flex, Raffaele Landolfi

Published in: Internal and Emergency Medicine | Issue 3/2020

Login to get access

Abstract

Experimental and clinical studies aimed at investigating the mechanism(s) underlying vascular complications of diabetes indicate that a great number of molecules are involved in the pathogenesis of these complications. Most of these molecules are inflammatory mediators or markers generated by immune or adipose tissue. Some of them, i.e. resistin and sortilin, have been shown to be involved in the cross talk between adipocytes and inflammatory cells. This interaction is an attractive area of research, particularly in type 2 diabetes and obesity. Other proteins, such as adiponectin and visfatin, appear to be more promising as possible vascular markers. In addition, some molecules involved in calcium/phosphorus metabolism, such as klotho and FGF23, have an involvement in the pathogenesis of diabetic vasculopathy, which appears to be dependent on the degree of vascular impairment. Inflammatory markers are a promising tool for treatment decisions while measuring plasma levels of adipokines, sortilin, Klotho and FGF23 in adequately sized longitudinal studies is expected to allow a more precise characterization of diabetic vascular disease and the optimal use of personalized treatment strategies.
Literature
1.
go back to reference Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L, Thompson A, Sattar N, White IR, Ray KK, Danesh J, Collaboration ERF (2010) Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375(9733):2215–2222. https://doi.org/10.1016/S0140-6736(10)60484-9 CrossRefPubMed Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L, Thompson A, Sattar N, White IR, Ray KK, Danesh J, Collaboration ERF (2010) Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet 375(9733):2215–2222. https://​doi.​org/​10.​1016/​S0140-6736(10)60484-9 CrossRefPubMed
2.
go back to reference Sasso FC, Chiodini P, Carbonara O, De Nicola L, Conte G, Salvatore T, Nasti R, Marfella R, Gallo C, Signoriello S, Torella R, Minutolo R, Group NITDS (2012) High cardiovascular risk in patients with Type 2 diabetic nephropathy: the predictive role of albuminuria and glomerular filtration rate. The NID-2 Prospective Cohort Study. Nephrol Dial Transplant 27(6):2269–2274. https://doi.org/10.1093/ndt/gfr644 CrossRefPubMed Sasso FC, Chiodini P, Carbonara O, De Nicola L, Conte G, Salvatore T, Nasti R, Marfella R, Gallo C, Signoriello S, Torella R, Minutolo R, Group NITDS (2012) High cardiovascular risk in patients with Type 2 diabetic nephropathy: the predictive role of albuminuria and glomerular filtration rate. The NID-2 Prospective Cohort Study. Nephrol Dial Transplant 27(6):2269–2274. https://​doi.​org/​10.​1093/​ndt/​gfr644 CrossRefPubMed
10.
go back to reference Biscetti F, Ferraro PM, Hiatt WR, Angelini F, Nardella E, Cecchini AL, Santoliquido A, Pitocco D, Landolfi R, Flex A (2019) Inflammatory cytokines associated with failure of lower extremity endovascular revascularization (LER): A Prospective Study of a Population with diabetes. Diabetes Care. https://doi.org/10.2337/dc19-0408 CrossRefPubMed Biscetti F, Ferraro PM, Hiatt WR, Angelini F, Nardella E, Cecchini AL, Santoliquido A, Pitocco D, Landolfi R, Flex A (2019) Inflammatory cytokines associated with failure of lower extremity endovascular revascularization (LER): A Prospective Study of a Population with diabetes. Diabetes Care. https://​doi.​org/​10.​2337/​dc19-0408 CrossRefPubMed
24.
go back to reference Dinarello CA, Ikejima T, Warner SJ, Orencole SF, Lonnemann G, Cannon JG, Libby P (1987) Interleukin 1 induces interleukin 1. I. Induction of circulating interleukin 1 in rabbits in vivo and in human mononuclear cells in vitro. J Immunol 139(6):1902–1910PubMed Dinarello CA, Ikejima T, Warner SJ, Orencole SF, Lonnemann G, Cannon JG, Libby P (1987) Interleukin 1 induces interleukin 1. I. Induction of circulating interleukin 1 in rabbits in vivo and in human mononuclear cells in vitro. J Immunol 139(6):1902–1910PubMed
25.
27.
go back to reference Schlesinger N, Alten RE, Bardin T, Schumacher HR, Bloch M, Gimona A, Krammer G, Murphy V, Richard D, So AK (2012) Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions. Ann Rheum Dis 71(11):1839–1848. https://doi.org/10.1136/annrheumdis-2011-200908 CrossRefPubMed Schlesinger N, Alten RE, Bardin T, Schumacher HR, Bloch M, Gimona A, Krammer G, Murphy V, Richard D, So AK (2012) Canakinumab for acute gouty arthritis in patients with limited treatment options: results from two randomised, multicentre, active-controlled, double-blind trials and their initial extensions. Ann Rheum Dis 71(11):1839–1848. https://​doi.​org/​10.​1136/​annrheumdis-2011-200908 CrossRefPubMed
38.
go back to reference Biscetti F, Straface G, De Cristofaro R, Lancellotti S, Rizzo P, Arena V, Stigliano E, Pecorini G, Egashira K, De Angelis G, Ghirlanda G, Flex A (2010) High-mobility group box-1 protein promotes angiogenesis after peripheral ischemia in diabetic mice through a VEGF-dependent mechanism. Diabetes 59(6):1496–1505. https://doi.org/10.2337/db09-1507 CrossRefPubMedPubMedCentral Biscetti F, Straface G, De Cristofaro R, Lancellotti S, Rizzo P, Arena V, Stigliano E, Pecorini G, Egashira K, De Angelis G, Ghirlanda G, Flex A (2010) High-mobility group box-1 protein promotes angiogenesis after peripheral ischemia in diabetic mice through a VEGF-dependent mechanism. Diabetes 59(6):1496–1505. https://​doi.​org/​10.​2337/​db09-1507 CrossRefPubMedPubMedCentral
43.
go back to reference Vionnet N, Hani EH, Dupont S, Gallina S, Francke S, Dotte S, De Matos F, Durand E, Leprêtre F, Lecoeur C, Gallina P, Zekiri L, Dina C, Froguel P (2000) Genomewide search for type 2 diabetes-susceptibility genes in French whites: evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2-diabetes locus on chromosome 1q21-q24. Am J Hum Genet 67(6):1470–1480. https://doi.org/10.1086/316887 CrossRefPubMedPubMedCentral Vionnet N, Hani EH, Dupont S, Gallina S, Francke S, Dotte S, De Matos F, Durand E, Leprêtre F, Lecoeur C, Gallina P, Zekiri L, Dina C, Froguel P (2000) Genomewide search for type 2 diabetes-susceptibility genes in French whites: evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2-diabetes locus on chromosome 1q21-q24. Am J Hum Genet 67(6):1470–1480. https://​doi.​org/​10.​1086/​316887 CrossRefPubMedPubMedCentral
44.
go back to reference Pilz S, Horejsi R, Möller R, Almer G, Scharnagl H, Stojakovic T, Dimitrova R, Weihrauch G, Borkenstein M, Maerz W, Schauenstein K, Mangge H (2005) Early atherosclerosis in obese juveniles is associated with low serum levels of adiponectin. J Clin Endocrinol Metab 90(8):4792–4796. https://doi.org/10.1210/jc.2005-0167 CrossRefPubMed Pilz S, Horejsi R, Möller R, Almer G, Scharnagl H, Stojakovic T, Dimitrova R, Weihrauch G, Borkenstein M, Maerz W, Schauenstein K, Mangge H (2005) Early atherosclerosis in obese juveniles is associated with low serum levels of adiponectin. J Clin Endocrinol Metab 90(8):4792–4796. https://​doi.​org/​10.​1210/​jc.​2005-0167 CrossRefPubMed
45.
go back to reference Sasso FC, Pafundi PC, Marfella R, Calabrò P, Piscione F, Furbatto F, Esposito G, Galiero R, Gragnano F, Rinaldi L, Salvatore T, D'Amico M, Adinolfi LE, Sardu C (2019) Adiponectin and insulin resistance are related to restenosis and overall new PCI in subjects with normal glucose tolerance: the prospective AIRE Study. Cardiovasc Diabetol 18(1):24. https://doi.org/10.1186/s12933-019-0826-0 CrossRefPubMedPubMedCentral Sasso FC, Pafundi PC, Marfella R, Calabrò P, Piscione F, Furbatto F, Esposito G, Galiero R, Gragnano F, Rinaldi L, Salvatore T, D'Amico M, Adinolfi LE, Sardu C (2019) Adiponectin and insulin resistance are related to restenosis and overall new PCI in subjects with normal glucose tolerance: the prospective AIRE Study. Cardiovasc Diabetol 18(1):24. https://​doi.​org/​10.​1186/​s12933-019-0826-0 CrossRefPubMedPubMedCentral
46.
go back to reference Ezenwaka CE, Kalloo R (2005) Caribbean female patients with type 2 diabetes mellitus have lower serum levels of adiponectin than nondiabetic subjects. Neth J Med 63(2):64–69PubMed Ezenwaka CE, Kalloo R (2005) Caribbean female patients with type 2 diabetes mellitus have lower serum levels of adiponectin than nondiabetic subjects. Neth J Med 63(2):64–69PubMed
48.
go back to reference Hung WC, Wang CP, Lu LF, Yu TH, Chiu CA, Chung FM, Chen HJ, Houng JY, Shin SJ, Lee YJ (2010) Circulating adiponectin level is associated with major adverse cardiovascular events in type 2 diabetic patients with coronary artery disease. Endocr J 57(9):793–802CrossRef Hung WC, Wang CP, Lu LF, Yu TH, Chiu CA, Chung FM, Chen HJ, Houng JY, Shin SJ, Lee YJ (2010) Circulating adiponectin level is associated with major adverse cardiovascular events in type 2 diabetic patients with coronary artery disease. Endocr J 57(9):793–802CrossRef
49.
go back to reference Xiang K, Wang Y, Zheng T, Jia W, Li J, Chen L, Shen K, Wu S, Lin X, Zhang G, Wang C, Wang S, Lu H, Fang Q, Shi Y, Zhang R, Xu J, Weng Q (2004) Genome-wide search for type 2 diabetes/impaired glucose homeostasis susceptibility genes in the Chinese: significant linkage to chromosome 6q21-q23 and chromosome 1q21-q24. Diabetes 53(1):228–234CrossRef Xiang K, Wang Y, Zheng T, Jia W, Li J, Chen L, Shen K, Wu S, Lin X, Zhang G, Wang C, Wang S, Lu H, Fang Q, Shi Y, Zhang R, Xu J, Weng Q (2004) Genome-wide search for type 2 diabetes/impaired glucose homeostasis susceptibility genes in the Chinese: significant linkage to chromosome 6q21-q23 and chromosome 1q21-q24. Diabetes 53(1):228–234CrossRef
51.
go back to reference Yamawaki H (2011) Vascular effects of novel adipocytokines: focus on vascular contractility and inflammatory responses. Biol Pharm Bull 34(3):307–310CrossRef Yamawaki H (2011) Vascular effects of novel adipocytokines: focus on vascular contractility and inflammatory responses. Biol Pharm Bull 34(3):307–310CrossRef
60.
go back to reference Mazaherioun M, Hosseinzadeh-Attar MJ, Janani L, Vasheghani Farahani A, Rezvan N, Karbaschian Z, Hossein-Nezhad A (2012) Elevated serum visfatin levels in patients with acute myocardial infarction. Arch Iran Med 15(11):688–692PubMed Mazaherioun M, Hosseinzadeh-Attar MJ, Janani L, Vasheghani Farahani A, Rezvan N, Karbaschian Z, Hossein-Nezhad A (2012) Elevated serum visfatin levels in patients with acute myocardial infarction. Arch Iran Med 15(11):688–692PubMed
66.
go back to reference Biscetti F, Straface G, Pitocco D, Angelini F, Tinelli G, Landolfi R, Flex A (2016) Fibroblast growth factor 23 serum level in type 2 diabetic Italian subjects with peripheral arterial disease and critical limb ischemia. Eur Rev Med Pharmacol Sci 20(19):4048–4054PubMed Biscetti F, Straface G, Pitocco D, Angelini F, Tinelli G, Landolfi R, Flex A (2016) Fibroblast growth factor 23 serum level in type 2 diabetic Italian subjects with peripheral arterial disease and critical limb ischemia. Eur Rev Med Pharmacol Sci 20(19):4048–4054PubMed
77.
go back to reference Martín-Núñez E, Donate-Correa J, López-Castillo Á, Delgado-Molinos A, Ferri C, Rodríguez-Ramos S, Cerro P, Pérez-Delgado N, Castro V, Hernández-Carballo C, Mora-Fernández C, Navarro-González JF (2017) Soluble levels and endogenous vascular gene expression of. Clin Sci (Lond) 131(21):2601–2609. https://doi.org/10.1042/CS20171242 CrossRef Martín-Núñez E, Donate-Correa J, López-Castillo Á, Delgado-Molinos A, Ferri C, Rodríguez-Ramos S, Cerro P, Pérez-Delgado N, Castro V, Hernández-Carballo C, Mora-Fernández C, Navarro-González JF (2017) Soluble levels and endogenous vascular gene expression of. Clin Sci (Lond) 131(21):2601–2609. https://​doi.​org/​10.​1042/​CS20171242 CrossRef
82.
go back to reference Sluijter JPG, Davidson SM, Boulanger CM, Buzás EI, de Kleijn DPV, Engel FB, Giricz Z, Hausenloy DJ, Kishore R, Lecour S, Leor J, Madonna R, Perrino C, Prunier F, Sahoo S, Schiffelers RM, Schulz R, Van Laake LW, Ytrehus K, Ferdinandy P (2018) Extracellular vesicles in diagnostics and therapy of the ischaemic heart: Position Paper from the Working Group on Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc Res 114(1):19–34. https://doi.org/10.1093/cvr/cvx211 CrossRefPubMed Sluijter JPG, Davidson SM, Boulanger CM, Buzás EI, de Kleijn DPV, Engel FB, Giricz Z, Hausenloy DJ, Kishore R, Lecour S, Leor J, Madonna R, Perrino C, Prunier F, Sahoo S, Schiffelers RM, Schulz R, Van Laake LW, Ytrehus K, Ferdinandy P (2018) Extracellular vesicles in diagnostics and therapy of the ischaemic heart: Position Paper from the Working Group on Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc Res 114(1):19–34. https://​doi.​org/​10.​1093/​cvr/​cvx211 CrossRefPubMed
86.
93.
go back to reference Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, Skene AM, Tan MH, Lefèbvre PJ, Murray GD, Standl E, Wilcox RG, Wilhelmsen L, Betteridge J, Birkeland K, Golay A, Heine RJ, Korányi L, Laakso M, Mokán M, Norkus A, Pirags V, Podar T, Scheen A, Scherbaum W, Schernthaner G, Schmitz O, Skrha J, Smith U, Taton J, Investigators P (2005) Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 366(9493):1279–1289. https://doi.org/10.1016/S0140-6736(05)67528-9 CrossRefPubMed Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK, Skene AM, Tan MH, Lefèbvre PJ, Murray GD, Standl E, Wilcox RG, Wilhelmsen L, Betteridge J, Birkeland K, Golay A, Heine RJ, Korányi L, Laakso M, Mokán M, Norkus A, Pirags V, Podar T, Scheen A, Scherbaum W, Schernthaner G, Schmitz O, Skrha J, Smith U, Taton J, Investigators P (2005) Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 366(9493):1279–1289. https://​doi.​org/​10.​1016/​S0140-6736(05)67528-9 CrossRefPubMed
Metadata
Title
Biomarkers of vascular disease in diabetes: the adipose-immune system cross talk
Authors
Federico Biscetti
Elisabetta Nardella
Andrea Leonardo Cecchini
Andrea Flex
Raffaele Landolfi
Publication date
01-04-2020
Publisher
Springer International Publishing
Published in
Internal and Emergency Medicine / Issue 3/2020
Print ISSN: 1828-0447
Electronic ISSN: 1970-9366
DOI
https://doi.org/10.1007/s11739-019-02270-6

Other articles of this Issue 3/2020

Internal and Emergency Medicine 3/2020 Go to the issue