Microvascular degenerative complications are associated with increased aortic stiffness in type 2 diabetic patients

doi:10.1016/j.atherosclerosis.2008.12.027

Atherosclerosis

Volume 205, Issue 2, August 2009, Pages 472-476

https://doi.org/10.1016/j.atherosclerosis.2008.12.027 Get rights and content

Abstract

Objective

Diabetes is a risk factor for increased arterial stiffness; however, few studies had investigated its associated factors. The aim was to evaluate the correlates of increased arterial stiffness in type 2 diabetes, particularly the relationships with microvascular complications.

Methods

482 type 2 diabetic patients without peripheral arterial disease were evaluated in a cross-sectional study. Clinical (including tests of cardiovascular dysautonomy), laboratory, ECG, echocardiographic and 24 h ambulatory blood pressure monitoring data were obtained. Arterial stiffness was assessed by carotid–femoral (aortic) and carotid-radial (peripheral) pulse wave velocity (PWV) measurements. Statistics included multivariate linear and logistic regressions to investigate the independent correlates of increased arterial stiffness.

Results

No diabetes-related variable was associated with peripheral arterial stiffness. 148 patients (31%) had increased aortic PWV (>12 m/s). On multiple linear regression, retinopathy and nephropathy, besides age, heart rate, 24 h pulse pressure, diabetes duration, dyslipidemia and number of antihypertensive drugs in use, were independently associated with aortic PWV. On multivariate logistic regression increased aortic stiffness was associated with retinopathy (odds ratio: 3.83, 95% confidence interval [CI]: 2.24–6.56, p < 0.001) and peripheral neuropathy (odds ratio: 1.79, 95%CI: 1.06–3.02, p = 0.03) after adjusting for possible confounding variables. Other variables associated with increased aortic stiffness were older age, heart rate, diabetes duration, 24 h pulse pressure, dyslipidemia and physical inactivity.

Conclusions

In type 2 diabetic patients, increased central arterial stiffness is associated with the presence of microvascular complications independent of other established determinants of aortic stiffness.

Introduction

In recent years, there is a growing knowledge on the importance of arterial stiffness in the pathogenesis of cardiovascular diseases [1], [2]. Arterial stiffness depends on the structural and geometric properties of the arterial wall and on the distending pressure, and ageing and blood pressure (BP) are its main determinants [1], [2]. The measurement of aortic pulse wave velocity (PWV) is considered the gold-standard evaluation of arterial stiffness [1]. Furthermore, aortic stiffness has been demonstrated to predict cardiovascular morbidity and mortality above and beyond other traditional cardiovascular risk factors [3], [4], [5], [6].

Type 2 diabetic patients have increased arterial stiffness [7], [8], [9] and are at particularly augmented risk for cardiovascular morbidity and mortality. This high cardiovascular risk is not completely explained by clustering of traditional risk factors and increased arterial stiffness may be one pathophysiological mechanism linking diabetes to increased cardiovascular morbi-mortality [10]. Nevertheless, factors associated with increased arterial stiffness in diabetic patients have not been completely explored, particularly the relationships with microvascular complications. In this regard, previous studies have generally addressed specific microvascular complications, such as microalbuminuria [11], [12], renal failure [13], retinopathy [14], [15], cardiovascular dysautonomy [16] or neuropathy [17], without a comprehensive analysis of all microvascular complications. Furthermore, it was recently demonstrated [18] that the presence of diabetic retinopathy was a risk marker for cardiovascular mortality. Hence, we hypothesized that increased arterial stiffness may be the pathophysiological link between microvascular damage and macrovascular clinical events.

Therefore, we planned to investigate the multivariate correlates of increased arterial stiffness, assessed by aortic and peripheral PWV, in a cohort of patients with type 2 diabetes, with particular attention to the relationships between increased stiffness and the presence of microvascular complications.

Section snippets

Study patients and baseline procedures

It was a cross-sectional study within a cohort of 540 type 2 diabetic patients enrolled from August 2004 to December 2007 in the outpatient clinic of a tertiary-care university hospital. Criteria to consider diabetes as type 2 was the diagnosis after 30 years old and to have remained on oral anti-diabetic treatment without insulin use for at least 1 year after diagnosis. Exclusion criteria to enter the cohort have been reported elsewhere [19]. All patients gave written informed consent and

Baseline characteristics and bivariate comparisons between patients with and without increased arterial stiffness

Aortic PWV averaged 11.14 m/s (SD: 2.37, range: 6.33–21.90 m/s) and peripheral PWV 10.56 m/s (SD: 1.53, range: 6.17–16.00 m/s); both had normal distributions. One hundred forty-eight patients (31%) had increased aortic stiffness, whereas 75 patients (16%) had increased peripheral arterial stiffness. Patients with increased peripheral PWV were more frequently males (62% vs. 33%, p < 0.001), and had higher ambulatory 24 h SBP (134 ± 17 vs. 128 ± 15 mmHg, p = 0.006) and DBP (80 ± 11 vs. 73 ± 9 mmHg, p < 0.001) than

Discussion

This study has two main findings: first, it demonstrates that the presence of diabetic retinopathy, nephropathy (microalbuminuria appears to be its most important component) and peripheral neuropathy are associated with increased central aortic stiffness, independent of other established determinants of aortic stiffness, such as ageing, BP levels and other cardiovascular risk factors; whereas peripheral arterial stiffness is not associated with any diabetes-related variable. Second, it confirms

References (25)

O. Ogawa et al.
Arterial stiffness is associated with diabetic retinopathy in type 2 diabetes
Diab Res Clin Pract
(2005)
S. Laurent et al.
Expert consensus document on arterial stiffness: methodological issues and clinical applications
Eur Heart J
(2006)
S. Laurent et al.
Recent advances in arterial stiffness and wave reflection in human hypertension
Hypertension
(2007)
S. Laurent et al.
Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients
Hypertension
(2001)
K. Cruickshank et al.
Aortic pulse wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function?
Circulation
(2002)
F.U. Mattace-Raso et al.
Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam study
Circulation
(2006)
T. Willum-Hansen et al.
Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population
Circulation
(2006)
H. Taniwaki et al.
Correlation between the intima-media thickness of carotid artery and aortic pulse wave velocity in patients with type 2 diabetes Vessel wall properties in type 2 diabetes
Diab Care
(1999)
E. Kimoto et al.
Preferential stiffening of central over peripheral arteries in type 2 diabetes
Diabetes
(2003)
L. De Angelis et al.
Sex differences in age-related stiffening of aorta in subjects with type 2 diabetes
Hypertension
(2004)

C.D. Stehouwer et al.

Arterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular disease

Diabetologia

(2008)

A. Smith et al.

Aortic pulse wave velocity and albuminuria in patients with type 2 diabetes

J Am Soc Nephrol

(2005)

Cited by (65)

Cardio-ankle vascular index is associated with diabetic retinopathy in younger than 70 years patients with type 2 diabetes mellitus
2019, Diabetes Research and Clinical Practice
Citation Excerpt :
This relationship was weaker and not significant in older patients. Our finding supports the results of previous studies [21,22] investigating the association between DR and arterial stiffness assessed by the carotid-femoral PWV (cfPWV) [23]. However, due to the time-consuming of this method which is partly operator dependent, cfPWV measurement has not become part of the daily routine in clinical work up of T2DM patients.
This study aimed to investigate the relationship between cardio-ankle vascular index (CAVI) and diabetic retinopathy (DR) in Caucasian patients with type 2 Diabetes Mellitus (T2DM).
This was a cross-sectional study of 299 T2DM patients admitted to Endocrine Unit of Foggia. DR was diagnosed using the International Clinical Disease Severity Scale of American Academy of Ophthalmology. The VaSera VS-1500N was used to measure CAVI. Because age is the most powerful determinant of arterial stiffness and affects the progression of DR, we divided the whole sample into two subgroups: above (older) and below (younger) 70 years.
The mean age of patients was 60.4 ± 12.6 years and the mean CAVI value was 8.6 ± 1.7. In the whole population DR was diagnosed in 74 (24.7%) patients. CAVI value was clearly higher in patients with DR (9.5 ± 1.6) than in those without (8.7 ± 1.7) (P = 0.001) although this difference was not any more significant when adjusted by age and gender (P = 0.067). In the multivariate model taking into account several possible confounders, the correlation between DR and CAVI remained significant only in younger subjects. In the same subgroup we found a significant association between the stages of DR and CAVI (p = 0.019 adjusted by age and gender).
This study shows that CAVI is significantly higher in younger patients with DR than in those without, with a relationship between the stages of DR and CAVI in the same subgroup. Physicians should pay attention to sub-clinical macroangiopathy in younger T2DM patients who have DR.
Retinal vessel reactivity is not attenuated in patients with type 2 diabetes compared with matched controls and is associated with peripheral endothelial function in controls
2019, Journal of Diabetes and its Complications
Attenuated retinal vasoreactivity in patients with type 2 diabetes preceding diabetic retinopathy development has been proposed to reflect local endothelial dysfunction.
Whether retinal vessel reactivity is associated with peripheral endothelial dysfunction and large artery stiffness in patients with type 2 diabetes remains to be elucidated.
Twenty patients with type 2 diabetes without retinopathy and 20 sex- and age matched controls (diabetes duration: 9.9 years (range 6.0;12.4), 40% male, age: 66.5 ± 7.3 (diabetes) and 65.2 ± 7.6 years (controls)) were included. Endothelial function was assessed using EndoPAT. Arterial stiffness was assessed by carotid-femoral pulse wave velocity using the SphygmoCor. Retinal blood supply regulation was examined by retinal arteriolar diameter change during 1) isometric exercise (hand-weight lifting), 2) exposure to flickering lights, and 3) a combined stimulus of 1) + 2) using the Dynamic Vessel Analyzer.
No significant differences were observed in retinal vessel reactivity in T2DM patients compared to controls. Endothelial function was associated with mean arteriolar diameter change during only the combination intervention, (Beta = 0.033 [0.0013;0.064], p = 0.042) in the overall population of patients and controls. When groups were analyzed separately, the associations was statistically significant only in controls. However, formal test for interaction was not statistically significant, p = 0.40. No association was observed between pulse wave velocity and retinal arteriolar %-diameter change in patients or controls.
Peripheral endothelial function was associated with retinal arteriolar diameter change in the combined sample. The association seemed to be driven primarily by the controls. Our findings indicate that peripheral endothelial function is reflective of endothelial function in the retina mainly in subjects without T2DM, whereas an association in T2DM without retinopathy was not observed. Further studies are needed in T2DM patients with more advanced retinopathy.
Usefulness of the vibration perception thresholds measurement as a diagnostic method for diabetic peripheral neuropathy: Results from the Rio de Janeiro type 2 diabetes cohort study
2018, Journal of Diabetes and its Complications
To investigate the associated factors with the vibration threshold perception (VPT) in patients with type 2 diabetes and to assess whether it is useful for detection of diabetic peripheral neuropathy (DPN).
VPTs were measured with Vibration Sensory Analyzer (VSA-3000) in 426 diabetic patients. The diagnosis of DPN was based on Neuropathy Symptom Score and Neuropathy Disability Score (NDS). ROC curve analysis and multiple linear and logistic regressions were performed to investigate the associations between VPT and DPN.
Values of VPT were progressively higher according to NDS stages. Age, height, diabetes duration, and mean cumulative HbA_1c exposure (partial correlation coefficients: 0.34; 0.27; 0.10; and 0.13; respectively) were the variables independently associated with VPT. Area under ROC curve of VPT for detection of DPN was 0.71 (95% CI: 0.66–0.75) and >8.9 μm was its best cut-off value. VPT, age, female sex, height, diabetes duration and mean HbA_1c levels were the independent correlates of the presence of DPN. An increased VPT triplicate the likelihood of having DPN (OR: 3.24; 95% CI: 2.05–5.11).
VPT, measured by an automatic device, shares common correlates with DPN and is strongly associated with its presence. VPT testing may be useful as a screening tool for DPN assessment.
The effects of metformin on maternal haemodynamics in gestational diabetes mellitus: A pilot study
2018, Diabetes Research and Clinical Practice
Gestational diabetes mellitus (GDM) is a major clinical challenge and is likely to remain so as the incidence of GDM continues to increase.
To assess longitudinal changes in maternal haemodynamics amongst women diagnosed with GDM requiring either metformin or dietary intervention in comparison to low-risk healthy controls.
Fifty-six pregnant women attending their first appointment at the GDM clinic and 60 low-risk healthy pregnant controls attending their routine antenatal clinics were recruited and assigned to three groups: GDM Metformin (GDM-M), GDM Diet (GDM-D) and Control. Non-invasive assessment of maternal haemodynamics, using recognised measures of arterial stiffness and central blood pressure (Arteriograph®), were undertaken under controlled conditions within four gestational windows: antenatal; AN1 (26–28 weeks), AN2 (32–34 weeks) and AN3 (37–40 weeks), and postnatal (PN) (6–8 weeks after delivery). Data were analysed using a linear mixed model incorporating gestational age and other relevant predictors, including age, blood pressure (BP), baseline bodyweight and pulse as fixed effects, and patient as a random effect.
Fitted linear mixed models showed evidence of a two-way interaction effect between groups (GDM-D, GDM-M and Control) and stages of gestation (AN1, AN2, AN3 and PN) for maternal haemodynamic parameters: brachial artery augmentation index (AIx) (p = 0.004), aortic AIx (p = 0.008), and central systolic BP (p = 0.001). However, differences in respect of aortic pulse wave velocity (p = 0.001) and heart rate (p < 0.001) were only significant for gestational stage. At AN2, we did not observe any evidence that the mean brachial Aix in the GDM-M was different from the control group (p = 0.158).
AIx and central systolic BP measures of arterial stiffness are adversely affected by GDM in comparison to controls during pregnancy. The possible beneficial effects of metformin therapy seen at 32 to 34 weeks of gestation require further exploration.
Mechanical Regulation of Retinal Vascular Inflammation and Degeneration in Diabetes
2024, Diabetes
Atomic Force Microscopy-Based Measurements of Retinal Microvessel Stiffness in Mice with Endothelial-Specific Deletion of CCN1
2023, Methods in Molecular Biology

View all citing articles on Scopus

View full text

Microvascular degenerative complications are associated with increased aortic stiffness in type 2 diabetic patients

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Study patients and baseline procedures

Baseline characteristics and bivariate comparisons between patients with and without increased arterial stiffness

Discussion

Diab Res Clin Pract

Expert consensus document on arterial stiffness: methodological issues and clinical applications

Eur Heart J

Recent advances in arterial stiffness and wave reflection in human hypertension

Hypertension

Aortic stiffness is an independent predictor of all-cause and cardiovascular mortality in hypertensive patients

Hypertension

Aortic pulse wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function?

Circulation

Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam study

Circulation

Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population

Circulation

Correlation between the intima-media thickness of carotid artery and aortic pulse wave velocity in patients with type 2 diabetes Vessel wall properties in type 2 diabetes

Diab Care

Preferential stiffening of central over peripheral arteries in type 2 diabetes

Diabetes

Sex differences in age-related stiffening of aorta in subjects with type 2 diabetes

Hypertension

Arterial stiffness in diabetes and the metabolic syndrome: a pathway to cardiovascular disease

Diabetologia

Aortic pulse wave velocity and albuminuria in patients with type 2 diabetes

J Am Soc Nephrol