Association between renin and atherosclerotic burden in subjects with and without type 2 diabetes.
Activation of the renin-angiotensin-aldosterone-system (RAAS) has been proposed to contribute to development of vascular complications in type 2 diabetes (T2D). The aim of the present study was to determine if plasma renin levels are associated with the severity of vascular changes in subjects with and without T2D.



Renin was analyzed by the Proximity Extension Assay in subjects with (n = 985) and without (n = 515) T2D participating in the SUMMIT (SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools) study and in 205 carotid endarterectomy patients. Vascular changes were assessed by determining ankle-brachial pressure index (ABPI), carotid intima-media thickness (IMT), carotid plaque area, pulse wave velocity (PWV) and the reactivity hyperemia index (RHI).



Plasma renin was elevated in subjects with T2D and demonstrated risk factor-independent association with prevalent cardiovascular disease both in subjects with and without T2D. Renin levels increased with age, body mass index, HbA1c and correlated inversely with HDL. Subjects with T2D had more severe carotid disease, increased arterial stiffness, and impaired endothelial function. Risk factor-independent associations between renin and APBI, bulb IMT, carotid plaque area were observed in both T2D and non-T2D subjects. These associations were independent of treatment with RAAS inhibitors. Only weak associations existed between plasma renin and the expression of pro-inflammatory and fibrous components in plaques from 205 endarterectomy patients.



Our findings provide clinical evidence for associations between systemic RAAS activation and atherosclerotic burden and suggest that this association is of particular importance in T2D.
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Isabel
I
Gonçalves
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Andreas
A
Edsfeldt
Medical Research Institute, University of Dundee, Dundee, UK.
Helen M
HM
Colhoun
Diabetes and Vascular Medicine, NIHR Exeter Clinical Research Facility and University of Exeter Medical School, Exeter, UK.
Angela C
AC
Shore
Department of Surgical, Medical, Molecular Pathology, and Critical Area Medicine, Pisa, Italy.
Carlo
C
Palombo
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Andrea
A
Natali
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Gunilla Nordin
GN
Fredrikson
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Harry
H
Björkbacka
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Maria
M
Wigren
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Eva
E
Bengtsson
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Gerd
G
Östling
Diabetes and Vascular Medicine, NIHR Exeter Clinical Research Facility and University of Exeter Medical School, Exeter, UK.
Kunihiko
K
Aizawa
Diabetes and Vascular Medicine, NIHR Exeter Clinical Research Facility and University of Exeter Medical School, Exeter, UK.
Francesco
F
Casanova
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
Margaretha
M
Persson
Diabetes and Vascular Medicine, NIHR Exeter Clinical Research Facility and University of Exeter Medical School, Exeter, UK.
Kim
K
Gooding
Diabetes and Vascular Medicine, NIHR Exeter Clinical Research Facility and University of Exeter Medical School, Exeter, UK.
Phil
P
Gates
Medical Research Institute, University of Dundee, Dundee, UK.
Faisel
F
Khan
Medical Research Institute, University of Dundee, Dundee, UK.
Helen C
HC
Looker
Medical Research Institute, University of Dundee, Dundee, UK.
Fiona
F
Adams
Medical Research Institute, University of Dundee, Dundee, UK.
Jill
J
Belch
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Silvia
S
Pinnola
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Elena
E
Venturi
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Michaela
M
Kozakova
AstraZeneca, Cardiovascular and Metabolic Diseases, Mölndal, Sweden.
Li-Ming
LM
Gan
AstraZeneca, Cardiovascular and Metabolic Diseases, Mölndal, Sweden.
Volker
V
Schnecke
Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden. jan.nilsson@med.lu.se.
Jan
J
Nilsson
D000368:Aged; D055109:Ankle Brachial Index; D015415:Biomarkers / Q000097:blood; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002340:Carotid Artery Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D059168:Carotid Intima-Media Thickness; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D058226:Plaque, Atherosclerotic / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D011379:Prognosis; D012083:Renin / Q000097:blood*; D012189:Retrospective Studies; D012307:Risk Factors; D059289:Vascular Stiffness / Q000502:physiology*
D015415:Biomarkers; D012083:Renin
Arterial stiffness; Atherosclerosis; Endothelial dysfunction; Renin; Type 2 diabetes