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Markers of subclinical atherosclerosis and arterial stiffness in type 2 diabetes
Linköping University, Department of Medical and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences.
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Type 2 diabetes is a common disease with increased mortality and morbidity due to cardiovascular disease (CVD). This thesis is based on three studies that evaluated traditionally used and emerging risk markers to identify individuals with high-risk of developing CVD in middle-aged men and women with type 2 diabetes. One study was conducted to compare the equivalence between two different ultrasound techniques to measure intima-media thickness since IMT was used to evaluate subclinical atherosclerosis as a surrogate endpoint.

Methods: Data from the cohort study, cardiovascular risk in type 2 diabetes – a prospective study in primary care (CARDIPP) was used in paper I, III and IV. In paper I, baseline data from the first 247 subjects was analysed. Associations between traditionally measured lipids, apolipoproteins, glycaemic control and low-grade inflammation and IMT were analysed.

In paper III, the full baseline cohort, with data from 761 subjects from the CARDIPP study was cross-sectionally analysed regarding correlations between abdominal obesity measured as waist circumference (WC) and sagittal abdominal diameter (SAD), inflammatory markers and IMT and pulse wave velocity (PWV). In paper IV, the associations reported in paper I and III were prospectively investigated with data from the first year of follow-up four years after the baseline investigations in CARDIPP-revisited.

In paper II a study was performed on 24 young healthy subjects, both men and women. IMT was measured in the common carotid artery (CCA) and in the abdominal aorta (AA), by two skilled ultrasonographers, with 2 different ultrasound techniques in a randomised order.

Results: ApoB/apoA-I ratio (r=0.207, p=0.001), apoB (r=0.166, p=0.009) and non HDLcholesterol (nHDL-c) (0.129, p=0.046) correlated with IMT.

In CCA IMT was equivalent using B-mode- and M-mode respectively. However in AA, IMT was 11.5% thicker using B-mode.

Abdominal obesity were significantly correlated with; IL-6 and CRP (both p<0.001, WC and SAD respectively), IMT (WC p=0.012, SAD p=0.003) and PWV (p<0.001 WC and SAD respectively). Adjusting for age, sex, treatment with statins, systolic blood pressure (SBP), Body Mass Index (BMI), CRP and HbA1c, SAD (p=0.047) but not WC, remained associated with IMT.

There were significant correlations between apoB (r=0.144, p=0.03) and CRP (r=0.172, p=0.009) measured at baseline and IMT measured at follow-up. After adjustment for sex, age, treatment with statins and Hba1c, the associations remained statistically significant. HbA1c, total cholesterol or LDL-cholesterol did not correlate to IMT at follow-up. Baseline body mass index (BMI) (r=0.130, p=0.049), WC (r=0.147, p=0.027) and SAD (r=0.184, p=0.007) correlated to PWV at follow-up. Challenged with sex, SBP and HbA1c, the association between SAD, not WC nor BMI, and PWV remained statistically significant (p=0.036).

Conclusions: There was a significant association between apoB/apoA-I ratio and IMT. The association was independent of conventional lipids, CRP, glycaemic control and use of statins. Both SAD and WC were associated with inflammation, atherosclerosis and arterial stiffness. However, SAD was slightly more robustly associated to subclinical organ damage, compared with WC. Prospectively; apoB and CRP, but not LDL-cholesterol predicted increased subclinical atherosclerosis. Furthermore, SAD was more independent in predicting arterial stiffness over time, compared with WC, in middle-aged men and women with type 2 diabetes.

The two different ultrasound techniques, B-mode and M-mode, measured different IMT thickness in the aorta, emphasizing the importance of using similar technique when comparing the impact of absolute values of IMT on cardiovascular disease.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press , 2011. , 56 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1260
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-71404ISBN: 978-91-7393-075-8 (print)OAI: oai:DiVA.org:liu-71404DiVA: diva2:448221
Public defence
2011-11-04, Eken, Hälsouniversitetet, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2011-10-14 Created: 2011-10-14 Last updated: 2017-03-27Bibliographically approved
List of papers
1. Complications Carotid intima-media thickness and apolipoprotein B/apolipoprotein A-I ratio in middle-aged patients with Type 2 diabetes
Open this publication in new window or tab >>Complications Carotid intima-media thickness and apolipoprotein B/apolipoprotein A-I ratio in middle-aged patients with Type 2 diabetes
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2009 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 26, no 4, 384-390 p.Article in journal (Refereed) Published
Abstract [en]

AIMS: To explore the association between carotid intima-media thickness (IMT) and the apolipoprotein B (apoB)/apolipoprotein A-I (apoA-I) ratio compared with conventional lipids in middle-aged patients with Type 2 diabetes. METHODS: We analysed data from 247 patients with Type 2 diabetes, aged 55-66 years, in the Cardiovascular Risk factors in Patients with Diabetes-a Prospective study in Primary care (CARDIPP-1) study. Primary care nurses measured blood pressure and anthropometric characteristics. Blood samples were taken for laboratory analyses. The carotid IMT was determined by ultrasonography at the University Hospital in Linköping and at the County Hospital Ryhov, Jönköping, Sweden. RESULTS: The ApoB/apoA-I ratio (r = 0.207, P = 0.001), apoB (r = 0.166, P = 0.009) and non-high-density lipoprotein cholesterol (non-HDL-c) (r = 0.129, P = 0.046) correlated with IMT. Conventional lipids, high-sensitivity C-reactive protein (hsCRP), glycated haemoglobin (HbA(1c)) and systolic blood pressure were not significantly correlated to IMT. A stepwise logistic regression analysis was conducted with IMT as the dependent variable and the apoB/apoA-I ratio, HbA(1c), hsCRP, low-density lipoprotein cholesterol (LDL-c), total cholesterol, non-HDL-c and treatment with statins as independent variables. Following adjustment for age and gender, only the apoB/apoA-I ratio remained significantly associated with IMT (odds ratio 4.3, 95% confidence intervals 1.7-10.8, P = 0.002). CONCLUSIONS: We conclude that there was a significant association between the apoB/apoA-I ratio and IMT in middle-aged patients with Type 2 diabetes. The association was independent of conventional lipids, hsCRP, glycaemic control and use of statins.

Keyword
apolipoproteins, cardiovascular disease, lipid metabolism, type 2 diabetes
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-21140 (URN)10.1111/j.1464-5491.2009.02693.x (DOI)
Available from: 2009-09-29 Created: 2009-09-29 Last updated: 2017-12-13
2. Is there an underestimation of intima-media thickness based on M-mode ultrasound technique in the abdominal aorta?
Open this publication in new window or tab >>Is there an underestimation of intima-media thickness based on M-mode ultrasound technique in the abdominal aorta?
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2012 (English)In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 32, no 1, 1-4 p.Article in journal (Refereed) Published
Abstract [en]

Measuring intima-media thickness (IMT) in the common carotid artery (CCA) is a valuable resource for the evaluation of subclinical atherosclerosis. The main objective of this study was to explore whether a B-mode ultrasound technique, Philips ATL, and an M-mode ultrasound technique, Wall Track System (WTS), show interchangeable results when measured in CCA and the abdominal aorta (AA). A total of 24 healthy, young subjects were examined. IMT and lumen diameter (LD) of the AA and the CCA were measured twice by two skilled ultrasonographers with two different ultrasound equipment B-mode: (Philips, ATL and M-mode: WTS).The intra-observer variability of IMT in CCA and AA using B-mode showed a coefficient of variation 8% and 9%, and with M-mode 11% and 15%, respectively. Interobserver variability of IMT in CCA and AA using B-mode was 6% and 12%, and with M-mode 11% and 18%, respectively. CCA IMT was 0·53 ± 0·07 and 0·53 ± 0·09 mm using B-mode and M-mode, respectively. However, in AA, IMT was 0·61 ± 0·5 and 0·54 ± 0·10 mm using B-mode and M-mode, respectively. Thus, AA IMT was 11·5% thicker using B-mode (P<0·01). We received adequate IMT readings from the carotid artery as well as the AA using two commonly used B-mode and M-mode techniques. B-mode technique seems to show less variability, especially in the AA. More importantly, the two techniques measured different IMT thickness in the aorta, emphasizing the importance of using similar technique when comparing the impact of absolute values of IMT on cardiovascular disease.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2012
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-71400 (URN)10.1111/j.1475-097X.2011.01045.x (DOI)000297928900001 ()
Note

funding agencies|Swedish Research Council||Swedish Heart-Lung foundation||

Available from: 2011-10-14 Created: 2011-10-14 Last updated: 2017-12-08Bibliographically approved
3. Abdominal Obesity and low grade Systemic Inflammation as Markers for Subclinical Organ Damage in type 2 diabetes
Open this publication in new window or tab >>Abdominal Obesity and low grade Systemic Inflammation as Markers for Subclinical Organ Damage in type 2 diabetes
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2014 (English)In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 40, no 1, 76-81 p.Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to explore associations between abdominal obesity, inflammatory markers, and subclinical organ damage in 740 patients with type 2 diabetes. Waist circumference (WC) and sagittal abdominal diameter (SAD) was measured. Blood samples were analyzed for; C-reactive protein (CRP), interleukin (IL) -1β and IL-6. Carotid intimamedia thickness (IMT) was evaluated by ultrasonography. Aortic pulse wave velocity (PWV) was measured with applanation tonometry.

Abdominal obesity were significantly correlated with; IL-6, CRP (both p= <0.001, WC and SAD, respectively), IMT (WC p=0.012, SAD p=0.003) and PWV (p<0.001, for WC and SAD, respectively). In multiple linear regressions with IMT as dependent variable and age, sex, statins, systolic blood pressure (SBP), Body Mass Index (BMI), CRP and HbA1c, as independent variables, SAD (p=0.047) but not WC, remained associated with IMT. In stepwise linear regression, entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV.

We conclude that SAD and WC are feasible measures of obesity that provides information on inflammation, atherosclerosis and arterial stiffness in type 2 diabetes. However, SAD was slightly more robustly associated to subclinical organ damage, compared with WC.

Place, publisher, year, edition, pages
Elsevier, 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-71401 (URN)10.1016/j.diabet.2013.10.006 (DOI)000332356500010 ()24290615 (PubMedID)
Available from: 2011-10-14 Created: 2011-10-14 Last updated: 2017-12-08Bibliographically approved
4. Sagittal Abdominal Diameter is a more Independent Measure compared with Waist Circumference to predict Arterial Stiffness in subjects with Type 2 Diabetes
Open this publication in new window or tab >>Sagittal Abdominal Diameter is a more Independent Measure compared with Waist Circumference to predict Arterial Stiffness in subjects with Type 2 Diabetes
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Aim: The aim of this study was to prospectively explore how laboratory and anthropometric risk factors predicted subclinical organ damage in 255 patients, with type 2 diabetes, after four years.

Methods: Baseline investigations were performed in 2006 and were repeated at follow-up in 2010. Carotid intima-media thickness (IMT) was evaluated by ultrasonography and aortic pulse wave velocity (PWV) was measured with applanation tonometry over the carotid and femoral arteries at baseline and at follow-up in a cohort of subjects with type 2 diabetes aged 55-65 years old.

Results: There were significant correlations between apolipoprotein B (apoB) (r= 0.144, p=0.03), C - reactive protein (CRP) (r=0.172, p=0.009) at baseline and IMT measured at follow-up. After adjustment for sex, age, treatment with statins and Hba1c, the associations remained statistically significant. HbA1c, total cholesterol or LDL-cholesterol did not correlate to IMT at follow-up. Baseline body mass index (BMI) (r=0.130, p=0.049), waist circumference (WC) (r=0.147, p=0.027) and sagittal Abdominal Diameter (SAD) (r=0.184, p=0.007) correlated to PWV at follow-up. Challenged with sex, SBP and HbA1c, the association between SAD, not WC nor BMI, and PWV remained statistically significant (p=0.036). In a stepwise linear regression, entering both SAD and WC, the association between SAD and PWV was stronger than the association between WC and PWV.

Conclusion: We conclude that apoB and CRP, but not LDL-cholesterol predicted subclinical atherosclerosis. Furthermore, SAD was more independent in predicting arterial stiffness over time, compared with WC, in middle-aged men and women with type 2 diabetes.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-71402 (URN)
Available from: 2011-10-14 Created: 2011-10-14 Last updated: 2017-03-27Bibliographically approved

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