Biomarkers of inflammation and endothelial dysfunction as predictors of pulse pressure and incident hypertension in type 1 diabetes: a 20 year life-course study in an inception cohort.

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0006777 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0428 (Electronic) Linking ISSN: 0012186X NLM ISO Abbreviation: Diabetologia Subsets: MEDLINE

Original Publication: Berlin Springer Verlag

Biomarkers/*blood ; Diabetes Mellitus, Type 1/*blood ; Inflammation/*blood; Blood Pressure/physiology ; C-Reactive Protein/metabolism ; E-Selectin/blood ; Humans ; Hypertension/blood ; Hypertension/metabolism ; Intercellular Adhesion Molecule-1/blood ; Vascular Stiffness/drug effects

Aims/hypothesis: Vascular inflammation and endothelial dysfunction are thought to contribute to arterial stiffening and hypertension. This study aims to test this hypothesis with longitudinal data in the context of type 1 diabetes.
Methods: We investigated, in an inception cohort of 277 individuals with type 1 diabetes, the course, tracking and temporal inter-relationships of BP, specifically pulse pressure (a marker of arterial stiffening) and hypertension, and the following biomarkers of systemic and vascular inflammation/endothelial dysfunction: C-reactive protein (CRP), soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular cellular adhesion molecule-1 (sVCAM-1) and soluble E-selectin (sE-selectin). These biomarkers and other risk factors were measured at baseline and repeatedly up to 20 years after the onset of type 1 diabetes. Data were analysed with generalised estimating equations including adjustments for age, sex, smoking status, BMI, HbA 1c , serum creatinine, total cholesterol, urinary AER, insulin treatment dose and mean arterial pressure.
Results: Increases were noted in all biomarkers except sE-selectin, which decreased over time. Levels differed from baseline at 2-4 years and preceded the increase in pulse pressure, which occurred at 8-10 years after the onset of type 1 diabetes. Higher levels of sICAM-1 and sVCAM-1, but not CRP or sE-selectin, at baseline and throughout the 20 year follow-up, were significantly associated with higher (changes in) pulse pressure at subsequent time points. Higher levels of sVCAM-1 at baseline and during follow-up were also significantly associated with the prevalence (OR 3.60 [95% CI 1.36, 9.53] and OR 2.28 [1.03, 5.25], respectively) and incidence (OR 2.89 [1.08, 7.75] and OR 3.06 [1.01, 9.26], respectively) of hypertension. We also investigated the longitudinal associations between BP or hypertension as determinants of subsequent (changes in) levels of CRP, sICAM-1, sVCAM-1 and sE-selectin, but did not find evidence to support a reverse causality hypothesis.
Conclusions/interpretation: These findings support the involvement of vascular endothelial dysfunction and inflammation in the development of premature arterial stiffening and hypertension in type 1 diabetes.

J Hypertens. 2004 Apr;22(4):705-11. (PMID: 15126911)
Hypertension. 2007 Mar;49(3):432-8. (PMID: 17242302)
JAMA. 1998 Jul 8;280(2):140-6. (PMID: 9669786)
J Hypertens. 2001 May;19(5):857-61. (PMID: 11393667)
Diabetologia. 1999 Mar;42(3):351-7. (PMID: 10096789)
J Hypertens. 2003 Oct;21(10):1841-6. (PMID: 14508189)
Diabet Med. 2006 May;23(5):557-64. (PMID: 16681565)
JAMA. 2003 Dec 10;290(22):2945-51. (PMID: 14665655)
Diabetes Care. 2003 Apr;26(4):1258-64. (PMID: 12663607)
PLoS Med. 2011 Jun;8(6):e1000440. (PMID: 21695075)
Circulation. 2004 Aug 31;110(9):1076-82. (PMID: 15326070)
Diabetes Care. 2003 Jul;26(7):2165-73. (PMID: 12832330)
Clin Sci (Lond). 2005 Aug;109(2):143-59. (PMID: 16033329)
Am J Hypertens. 1997 Dec;10(12 Pt 1):1335-41. (PMID: 9443768)
J Clin Epidemiol. 2015 Oct;68(10):1165-75. (PMID: 25920943)
Diabetes. 1998 Apr;47(4):660-7. (PMID: 9568701)
Diabetologia. 2008 Apr;51(4):527-39. (PMID: 18239908)
J Hypertens. 2002 May;20(5):871-7. (PMID: 12011647)
Am Heart J. 2010 Jun;159(6):1074-80. (PMID: 20569722)
Arterioscler Thromb Vasc Biol. 2005 May;25(5):1051-6. (PMID: 15731495)
Hypertension. 1998 Nov;32(5):862-8. (PMID: 9822445)
Circulation. 2003 Jun 10;107(22):2864-9. (PMID: 12796414)
Diabetes. 2005 May;54(5):1523-7. (PMID: 15855341)
Nutr Metab Cardiovasc Dis. 2006 Oct;16(7):500-8. (PMID: 16979884)
Curr Opin Nephrol Hypertens. 2006 Mar;15(2):152-8. (PMID: 16481882)
Stat Med. 2005 Oct 15;24(19):2911-35. (PMID: 16152135)
Arterioscler Thromb Vasc Biol. 1999 Jul;19(7):1595-9. (PMID: 10397675)
Clin Chem. 2000 Jul;46(7):934-8. (PMID: 10894836)
Arch Intern Med. 2006 Feb 13;166(3):345-9. (PMID: 16476876)
J Am Coll Cardiol. 2005 Nov 15;46(10):1869-74. (PMID: 16286174)
Am J Epidemiol. 1997 May 15;145(10):888-98. (PMID: 9149660)
Diabetes. 2009 Jul;58(7):1668-71. (PMID: 19411615)
Diabetes Care. 1993 Oct;16(10):1394-401. (PMID: 8269800)
Hypertension. 2002 Feb;39(2):197-202. (PMID: 11847183)
Circulation. 2009 Jan 20;119(2):243-50. (PMID: 19118251)
JAMA. 1994 Jan 26;271(4):275-9. (PMID: 8295285)
Coron Artery Dis. 2004 Sep;15(6):331-6. (PMID: 15346091)
Stat Med. 2009 Dec 20;28(29):3657-69. (PMID: 19757484)
Circulation. 2005 May 17;111(19):2446-53. (PMID: 15867184)
J Hypertens. 2003 Nov;21(11):2035-44. (PMID: 14597846)
BMJ. 2004 May 8;328(7448):1105. (PMID: 15096438)
Hypertension. 2009 Feb;53(2):150-7. (PMID: 19075099)
QJM. 2000 Apr;93(4):231-6. (PMID: 10787451)
Diabetes Care. 2011 Apr;34(4):886-91. (PMID: 21330642)
Circulation. 2003 Dec 16;108(24):2993-9. (PMID: 14638538)
Hypertension. 2001 Sep;38(3):399-403. (PMID: 11566912)
Am J Hypertens. 2005 Jul;18(7):935-42. (PMID: 16053990)
Clin Sci (Lond). 2007 Jun;112(7):375-84. (PMID: 17324119)
Eur Heart J. 2010 Aug;31(15):1865-71. (PMID: 20197424)
J Hypertens. 2009 Jan;27(1):102-8. (PMID: 19145777)
Curr Vasc Pharmacol. 2010 Jul;8(4):509-16. (PMID: 19538178)

Keywords: Arterial stiffness; CRP; Endothelial dysfunction; Hypertension; Inflammation; Longitudinal study; Pulse pressure; Type 1 diabetes; sE-selectin; sICAM-1; sVCAM-1

0 (Biomarkers)
0 (E-Selectin)
126547-89-5 (Intercellular Adhesion Molecule-1)
9007-41-4 (C-Reactive Protein)

Date Created: 20171105 Date Completed: 20180717 Latest Revision: 20190418

20240628

PMC6448953

10.1007/s00125-017-4470-5

29101422