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Early blood pressure alterations are associated with pro-inflammatory markers in type 1 diabetes mellitus

Journal of Human Hypertension volume 31, pages 151–156 (2017)Cite this article

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Abstract

The aim of this study was to evaluate the relationship between early blood pressure (BP) changes (detected using ambulatory BP monitoring; ABPM) with different markers of inflammation and endothelial dysfunction in patients with type 1 diabetes mellitus (T1DM). The study design was observational cross-sectional in 85 T1DM patients, clinically normotensive and with normo-albuminuria. We analyzed the relationships between ABPM-measured BP alterations over 24 h with the inflammatory cytokines (interleukin-6 (IL-6), tumor necrosis factor-α and vascular endothelial growth factor (VEGF)) and the markers of endothelial damage (vascular adhesion molecule, intercellular adhesion molecule and plasminogen activator inhibitor-1 (PAI)). Despite being recorded as normotensive, 27 (31.8%) subjects presented with an average of pathological BP. VEGF levels were significantly elevated in the patients with an altered mean diurnal values compared with normotensives (112.33 (72.87–213.53) pg ml−1 vs 71.03 (37.71–107.92) pg ml−1; P=0.007). Further, VEGF levels correlated significantly with the parameters of diurnal BP and of 24 h values. IL-6 concentration was a risk factor in the patients with hypertension (OR=1.406; P=0.027). There were no modifications in the levels of markers of endothelial damage. Summarizing, there is an increase in pro-inflammatory cytokines, but not the endothelial adhesion molecules, in early stages of arterial hypertension in patients with T1DM.

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References

  1. Arauz-Pacheco C, Parrott MA, Raskin P . The treatment of hypertension in adult patients with diabetes. Diabetes Care 2002; 25: 134–147.

    Article  PubMed  Google Scholar 

  2. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 2003; 289: 2560–2572.

    Article  CAS  PubMed  Google Scholar 

  3. Mancia G, Fagard R, NarkiewiczK, Redón J, Zanchetti A, Böhm M et al. ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2013; 34: 2159–2219.

    Article  PubMed  Google Scholar 

  4. Vílchez-López FJ, Carral-Sanlaureano F, Coserria-Sánchez C, Nieto A, Jiménez S, Aguilar-Diosdado M . Alterations in arterial pressure in patients with Type 1 diabetes are associated with long-term poor metabolic control and a more atherogenic lipid profile. J Endocrinol Invest 2011; 34: 24–29.

    Article  Google Scholar 

  5. Bautista LE, Vera LM, Arenas IA, Gamarra G . Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-alpha) and essential hypertension. J Hum Hypertens 2005; 19: 149–154.

    Article  CAS  PubMed  Google Scholar 

  6. Abramson JL, Lewis C, Murrah NV, Anderson GT, Vaccarino V . Relation of C-reactive protein and tumor necrosis factor-alpha to ambulatory blood pressure variability in healthy adults. Am J Cardiol 2006; 98: 649–652.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. von Känel R, Jain S, Mills PJ, Nelesen RA, Adler KA, Hong S et al. Relation of nocturnal blood pressure dipping to cellular adhesion, inflammation and hemostasis. J Hypertens 2004; 22: 2087–2093.

    Article  PubMed  Google Scholar 

  8. Pickering TG, Shimbo D, Hass D . Ambulatory blood-pressure monitoring. N Engl J Med 2006; 354: 2368–2374.

    Article  CAS  PubMed  Google Scholar 

  9. Basu S, Larsson A, Vessby J, Vessby B, Berne C . Type 1 diabetes is associated with increased cyclooxygenase-and cytokine-mediated inflammation. Diabetes Care 2005; 28: 1371–1375.

    Article  CAS  PubMed  Google Scholar 

  10. Castaño L, Eisenbarth GS . Type-I diabetes: a chronic autoimmune disease of human, mouse, and rat. Annu Rev Immunol 1990; 8: 647–679.

    Article  PubMed  Google Scholar 

  11. Quintana-Lopez L, Blandino-Rosano M, Perez-Arana G, Cebada-Aleu A, Lechuga-Sancho A, Aguilar-Diosdado M et al. Nitric oxide is a mediator of antiproliferative effects induced by proinflammatory cytokines on pancreatic beta cells. Mediators Inflamm 2013; 2013: 905175.

    Article  PubMed Central  PubMed  Google Scholar 

  12. Roca-Rodríguez MM, López-Tinoco C, Fernández-Deudero A, Murri M, García-Palacios MV, García-Valero MA et al. Adipokines and metabolic syndrome risk factors in women with previous gestational diabetes mellitus. Diabetes Metab Res Rev 2012; 28: 542–548.

    Article  PubMed  Google Scholar 

  13. López-Tinoco C, Roca M, Fernández-Deudero A, García-Valero A, Bugatto F, Aguilar-Diosdado M et al. Cytokine profile, metabolic syndrome and cardiovascular disease risk in women with late-onset gestational diabetes mellitus. Cytokine 2012; 58: 14–19.

    Article  PubMed  Google Scholar 

  14. López-Tinoco C, Roca M, García-Valero A, Murri M, Tinahones FJ, Segundo C et al. Oxidative stress and antioxidant status in patients with late-onset gestational diabetes mellitus. Acta Diabetol 2013; 50: 201–208.

    Article  PubMed  Google Scholar 

  15. Lindmark S, Buren J, Eriksson JW . Insulin resistance, endocrine function and adipokines in type 2 diabetes patients at different glycaemic levels: potential impact for glucotoxicity in vivo. Clin Endocrinol (Oxf) 2006; 65: 301–309.

    Article  CAS  Google Scholar 

  16. Stentz FB, Umpierrez GE, Cuervo R, Kitabchi AE . Proinflammatory cytokines, markers of cardiovascular risks, oxidative stress, and lipid peroxidation in patients with hyperglycemic crises. Diabetes 2004; 53: 2079–2086.

    Article  CAS  PubMed  Google Scholar 

  17. Goldberg RB . Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications. J Clin Endocrinol Metab 2009; 94: 3171–3182.

    Article  CAS  PubMed  Google Scholar 

  18. Hartge MM, Unger T, Kintscher U . The endothelium and vascular inflammation in diabetes. Diabetes Vasc Dis Res 2007; 4: 84–88.

    Article  Google Scholar 

  19. Wärnberg J, Marcos A . Low-grade inflammation and the metabolic syndrome in children and adolescents. Curr Opin Lipidol 2008; 19: 11–15.

    Article  PubMed  Google Scholar 

  20. American Diabetes Association. Standards of medical care in diabetes-2003. Diabetes Care 2003; 26 (suppl1): S94–S98.

    Google Scholar 

  21. O'Brien E, Pickering T, Asmar R, Myers M, Parati G, Staessen J et al. Working Group on Blood Pressure Monitoring of the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults. Blood Press Monit 2002; 7: 3–17.

    Article  PubMed  Google Scholar 

  22. Sturrock ND, George E, Pound N, Stevenson J, Peck GM, Sowter H . Non-dipping circadian blood pressure and renal impairment are associated with increased mortality in diabetes mellitus. Diabet Med 2000; 17: 360–364.

    Article  CAS  PubMed  Google Scholar 

  23. Longo D, Dorigatti F, Palatini P . Masked hypertension in adults. Blood Press Monit 2005; 10 (6): 307–310.

    Article  PubMed  Google Scholar 

  24. American Diabetes Association. Standards in medical care in diabetes Possition Statement. Diabetes Care 2008; 31 (Suppl 1): S12–S54.

    Article  Google Scholar 

  25. Darcan S, Goksen D, Mir S, Serdaroglu E, Buyukinan M, Coker M et al. Alterations of blood pressure in type 1 diabetic children and adolescent. Pediatr Nephrol 2006; 21: 672–676.

    Article  PubMed  Google Scholar 

  26. Zorena K, Raczyńska D, Wiśniewski P, Malinowska E, Myśliwiec M, Raczyńska K et al. Relationship between serum transforming growth factor β 1 concentrations and the duration of type 1 diabetes mellitus in children and adolescents. Mediators Inflamm 2013; 2013: 849457.

    PubMed  PubMed Central  Google Scholar 

  27. Velarde MS, Del R, Carrizo T, Díaz EI, Fonio MC, Bazán MC et al. Inflammation markers and endothelial dysfunction in children with type 1 diabetes. Medicina (B Aires) 2010; 70: 44–48.

    CAS  Google Scholar 

  28. El Amine M, Sohawon S, Lagneau L, Gaham N, Noordally S . Plasma levels of ICAM-1 and circulating endothelial cells are elevated in unstable types 1 and 2 diabetes. Endocr Regul 2010; 44: 17–24.

    Article  CAS  PubMed  Google Scholar 

  29. Rodríguez L . Diabetes, hemoglobina glicosilada y disfunción endotelial. Nefrología 2000; 20, (suppl 1): 31.

    Google Scholar 

  30. Schram MT, Chaturvedi N, Schalkwijk CG, Fuller JH, Stehouwer CD, EURODIAB Prospective Complications Study Group. Markers of inflammation are cross-sectionally associated with microvascular complications and cardiovascular disease in type 1 diabetes—the EURODIAB Prospective Complications Study. Diabetologia 2005; 48: 370–378.

    Article  CAS  PubMed  Google Scholar 

  31. Soedamah-Muthu SS, Chaturvedi N, Schalkwijk CG, Stehouwer CD, Ebeling P, Fuller JH . The EURODIAB Prospective Complications Study group. Soluble vascular cell adhesion molecule-1 and soluble E-selectin are associated with micro- and macro-vascular complications in type 1 diabetic patients. J Diabetes Complications 2006; 20: 188–195.

    Article  PubMed  Google Scholar 

  32. Targher G, Bertolini L, Zoppini G, Zenari L, Falezza G . Increased plasma markers of inflammation and endothelial dysfunction and their association with microvascular complications in type 1 diabetic patients without clinically manifest macroangiopathy. Diabetes Med 2005; 22: 999–1004.

    Article  CAS  Google Scholar 

  33. Astrup AS, Tarnow L, Pietraszek L, Schalkwijk CG, Stehouwer CD, Parving HH et al. Markers of endothelial dysfunction and inflammation in type 1 diabetic patients with or without diabetic nephropathy followed for 10 years: association with mortalit and decline of glomerular filtration rate. Diabetes Care 2008; 31: 1170–1176.

    Article  CAS  PubMed  Google Scholar 

  34. Bild D, Teutsch SM . The control of hypertension in persons with diabetes: a public health approach. Public Health Rep 1987; 102: 522–529.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329: 977–986.

    Article  Google Scholar 

  36. Zorena K, Myśliwska J, Myśliwiec M, Rybarczyk-Kapturska K, Malinowska E, Wiśniewski P et al. Association between vascular endothelial growth factor and hypertension in children and adolescents type I diabetes mellitus. J Hum Hypertens 2010; 24: 755–762.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Sahakyan K, Klein BE, Myers CE, Tsai MY, Klein R . Novel risk factors in long-term hypertension incidence in type 1 diabetes mellitus. Am Heart J 2010; 159 (6): 1074–1080.

    Article  PubMed Central  PubMed  Google Scholar 

  38. Ishikawa J, Hoshide S, Eguchi K, Ishikawa S, Pickering TG, Shimada K et al. Increased low-grade inflammation and plasminogen-activator inhibitor-1 level in nondippers with sleep apnea syndrome. J Hypertens 2008; 26 (6): 1181–1187.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Devaraj S, Cheung AT . Evidence of increased inflammation and microcirculatory abnormalities in patients with type 1 diabetes and their role in microvascular complications. Diabetes 2007; 56: 2790–2796.

    Article  CAS  PubMed  Google Scholar 

  40. Espósito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M et al. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 2002; 106: 2067–2072.

    Article  PubMed  Google Scholar 

  41. Lundman P, Eriksson MJ, Silveira A, Hansson LO, Pernow J, Ericsson CG et al. Relation of hypertriglyceridemia to plasma concentration of biochemical markers of inflammation and endothelial activation (C-reactive protein, interleukin-6, soluble adhesion molecules, von Willebrand factor, and endothelin-1). Am J Cardiol 2003; 91: 1128–1131.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was financed, in part, by a grant from the Spanish Diabetes Society. Editorial assistance was by Dr Peter R Turner.

Author information

Author notes

  1. I Mateo-Gavira and F J Vílchez-López: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Endocrinology, Puerta del Mar Hospital, Cadiz, Spain

    I Mateo-Gavira & F J Vílchez-López

  2. Department of Preventive Medicine and Public Health, Puerta del Mar Hospital, Cádiz, Spain

    M V García-Palacios

  3. Department of Endocrinology, Puerto Real Hospital, Cádiz, Spain

    F Carral-San Laureano

  4. Department of Investigation, Puerta del Mar Hospital, Cádiz, Spain

    F M Visiedo-García

  5. Department of Endocrinology and Investigation Unit, Puerta del Mar Hospital, Cádiz, Spain

    M Aguilar-Diosdado

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  1. I Mateo-Gavira
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Correspondence to M Aguilar-Diosdado.

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The authors declare no conflict of interest.

Additional information

This work was presented as an abstract at the 16th European Congress of Endocrinology (Poland); 3–7 May 2014 (published in Endocrine Abstracts 2014; vol. 35).

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Mateo-Gavira, I., Vílchez-López, F., García-Palacios, M. et al. Early blood pressure alterations are associated with pro-inflammatory markers in type 1 diabetes mellitus. J Hum Hypertens 31, 151–156 (2017). https://doi.org/10.1038/jhh.2016.56

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