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Diabetologia. 2018 Jan;61(1):231-241. doi: 10.1007/s00125-017-4470-5. Epub 2017 Nov 3.

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.

Author information

1
Division of Epidemiology & Biostatistics, School of Public Health, Faculty of Medicine, The University of Queensland, Herston Campus - Public Health Building, Herston Rd, Brisbane, 4006, Australia. i.ferreira@uq.edu.au.
2
Steno Diabetes Centre, Gentofte, Denmark.
3
Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, Glostrup, Denmark.
4
Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), Peter Debyelaan 25, 6229HX, Maastricht, the Netherlands.
5
CARIM School for Cardiovascular Diseases, MUMC+, Maastricht, the Netherlands.
6
Department of Medical Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
7
Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), Peter Debyelaan 25, 6229HX, Maastricht, the Netherlands. cda.stehouwer@mumc.nl.
8
CARIM School for Cardiovascular Diseases, MUMC+, Maastricht, the Netherlands. cda.stehouwer@mumc.nl.
9
Faculty of Health, University of Copenhagen, Copenhagen, Denmark.
10
HEALTH, Aarhus University, Aarhus, Denmark.

Abstract

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, HbA1c, 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.

KEYWORDS:

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

PMID:
29101422
DOI:
10.1007/s00125-017-4470-5
[Indexed for MEDLINE]

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