Carotid atherosclerosis, a chronic disease with increased carotid arterial wall thickness as well as stiffness and/or the development of carotid plaque, is associated with the occurrence of cerebrovascular events, including transient ischemia attack (TIA) and stroke. According to the World Health Organization (WHO), about 15 million of people worldwide suffer from stroke annually, and one-third of them may die and another one-third may be permanently disabled.
Type 2 diabetes mellitus (DM) is one of the major risk factors associated with carotid atherosclerosis [
Plaque, IMT, and arterial stiffness of the carotid artery are common characteristics for assessing carotid atherosclerosis. Carotid plaque narrows the lumen of the carotid artery or may rupture leading to the formation of thrombus, reducing or blocking the blood supply to the brain. Carotid plaque score has been used to quantify the severity of carotid atherosclerosis [
Thus, the present study aimed to investigate the cumulative effects of hypertension, dyslipidemia, and CKD on the characteristics of carotid atherosclerosis, including the presence of plaque, carotid plaque score, carotid IMT, and carotid arterial stiffness in Chinese patients with type 2 DM.
In the study, subjects with type 2 diabetes were recruited from a local Chinese nonprofit making organisation for patients with diabetes (Angel of Diabetics Organisation, Hong Kong). The organisation has over 3000 registered patients who have been clinically diagnosed with DM and have regular follow-ups in diabetes clinics. Posters were put up in the premises of the Angel of Diabetics Organisation for recruitment of the patients. In the present study, the inclusion criteria of the subjects were Chinese patients with type 2 DM and older than 18 years, while the exclusion criteria of subjects were previous radiotherapy of the neck, carotid endarterectomy, and carotid stenting. Other atherosclerosis risk factors of subjects, including smoking, hypertension, dyslipidemia, and CKD, were identified with a questionnaire and a blood test. However, there was only one smoker in the 107 recruited subjects and was subsequently excluded to avoid statistical bias. As a result, a total of 106 Chinese subjects with type 2 diabetes were included in the study. The mean age of the subjects was 58.1 ± 9.0 years (ranging from 35 to 78 years) and 63.2% of them were women
This study was approved by the Human Subject Ethics Subcommittee of the Hong Kong Polytechnic University. Written consent was obtained from the subjects before the commencement of the interview and ultrasound examination.
For each subject, the brachial blood pressure was measured with a sphygmomanometer (Tensoval, Hartmann, Germany) at the left upper arm in sitting posture after at least 10 minutes of rest. A total of 3 mL of overnight fasting blood sample was obtained and blood tests were performed by a certified medical laboratory (Bright Growth Medical Laboratory Limited, Hong Kong). The levels of blood glucose, hemoglobin A1c (HbA1c), total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride, and creatinine were determined by automated clinical chemistry analyzer using reagent cartridges recommended by the manufacturer (Dimension Xpand Plus, Siemens Healthcare, Germany). Estimated glomerular filtration rate (eGFR) was defined and calculated using the CKD-EPI (chronic kidney disease epidemiology collaboration) equation [
All ultrasound examinations were performed in a 22°C air-conditioned examination room using the Esaote MyLab Twice ultrasound unit in conjunction with a 4–13 MHz linear transducer (Esaote, Genoa, Italy). For each subject, the systolic and diastolic pressures were inputted into the ultrasound unit for evaluating carotid arterial stiffness.
Both the left and right carotid arteries were scanned and evaluated. All ultrasound examinations were performed by the same operator. The carotid arteries were assessed for the presence of carotid plaque, carotid plaque score, carotid IMT, and carotid arterial stiffness. Plaque was defined as focal thickening >50% of the adjacent intima-media layer [
Carotid IMT and carotid arterial stiffness were evaluated using the automated quantification programmes of the ultrasound unit: radiofrequency-based quality intima-media thickness (RF-QIMT) and radiofrequency-based quality arterial stiffness (RF-QAS), respectively (Figure
Measurements of the intima-media thickness and stiffness in the common carotid artery. (a) Longitudinal grey scale sonogram showing the measurement of the intima-media thickness of a common carotid artery (CCA) using radiofrequency-based quality intima-media thickness. (b) Longitudinal grey scale sonogram showing the measurement of the arterial stiffness of the same CCA using radiofrequency-based quality arterial stiffness. The arrows indicate the inferior end of the carotid bulb and the double-arrows lines show a distance of 1 cm.
In the evaluation of carotid arterial stiffness, five arterial stiffness parameters were investigated in the study: distensibility coefficient
Continuous data are expressed as means ± SD. The normality of distribution was checked using Shapiro-Wilk test. The adjusted comparisons between study groups were performed using ANCOVA or logistic regression. The association between atherosclerosis risk factors of subjects and carotid plaque score were determined using ordinal regression. Paired
In the 106 subjects with type 2 diabetes, the mean blood glucose and HbA1c level were 7.53 ± 1.65 mmol/L and 6.90 ± 0.96%, respectively. Among these 106 subjects, 17 subjects did not have any additional atherosclerosis risk factor (Group 1), 49 had one additional atherosclerosis risk factor (Group 2), and 40 had two or three additional atherosclerosis risk factors (Group 3). There were no significant differences of blood glucose and HbA1c level between the three groups (Table
Demographic and ultrasonographic characteristics in Chinese subjects with type 2 diabetes with different numbers of atherosclerosis risk factors.
Parameters | Total | Groups with different number of atherosclerosis risk factor |
|
||
---|---|---|---|---|---|
Group 1 |
Group 2 |
Group 3 | |||
Age, years |
|
|
|
|
— |
Gender (female/male), |
67/39 | 11/6 | 27/22 | 29/11 | — |
Presence of plaque, |
47 | 4 | 19 | 24 | 0.017* |
Plaque score | — | — | — | — | 0.005* |
Hypertension, |
60 | — | 27 | 33 | — |
Dyslipidemia, |
65 | — | 28 | 37 | — |
CKD, |
5 | — | 0 | 5 | — |
Coronary heart disease, |
1 | 0 | 0 | 1 | — |
Stroke, |
3 | 0 | 1 | 2 | — |
Blood glucose, mmol/L |
|
|
|
|
0.921 |
HbA1c, % |
|
|
|
|
0.981 |
Total cholesterol, mmol/L |
|
|
|
|
0.080 |
HDL, mmol/L |
|
|
|
|
0.814 |
LDL, mmol/L |
|
|
|
|
0.124 |
Triglyceride, mmol/L |
|
|
|
|
0.203 |
eGFR, mL/min per 1.73 m2 |
|
|
|
|
0.022* |
IMT, |
|
|
|
|
0.624 |
DC, 1/KPa |
|
|
|
|
0.441 |
CC, mm2/KPa |
|
|
|
|
0.343 |
|
|
|
|
|
0.866 |
|
|
|
|
|
0.633 |
PWV, m/s |
|
|
|
|
0.434 |
As shown in Table
Similarly, ordinal logistic regression analysis with the adjustment of age and gender showed carotid plaque score was significantly higher in groups with more atherosclerosis risk factors (Table
The effect of atherosclerosis risk factors on carotid plaque score in subjects with type 2 diabetes (
Parameters | Number of total |
Plaque score | |||
---|---|---|---|---|---|
Odds ratio | 95% CI |
|
|||
Lower | Upper | ||||
Gender (No. of female) | 67 | 1.22 | 0.55 | 2.71 | 0.634 |
Age (>60 years) | 50 | 2.75 | 1.26 | 6.00 | 0.011* |
Hypertension | 60 | 2.48 | 1.11 | 5.58 | 0.027* |
Dyslipidemia | 65 | 2.41 | 1.05 | 5.51 | 0.037* |
CKD | 5 | 7.80 | 1.46 | 41.72 | 0.016* |
In contrast, with the adjustment of age and gender of the subjects (ANCOVA), no significant differences of carotid IMT and carotid arterial stiffness were found in groups with different numbers of atherosclerosis risk factors.
In this study, it was found that the carotid artery with plaque did not have increased carotid IMT and carotid arterial stiffness. In the 106 subjects, 47 had carotid plaque while the other 59 subjects did not. After the adjustment of age and gender of subjects (ANCOVA), there were no significant differences of carotid IMT and carotid arterial stiffness in subjects with or without plaque (Table
Carotid IMT and carotid arterial stiffness in subjects with type 2 diabetes.
Parameters | Subjects with type 2 diabetes | |||||
---|---|---|---|---|---|---|
The subjects with plaque |
The subjects without plaque |
|
The left |
The right |
|
|
IMT, |
|
|
0.171 |
|
|
<0.001* |
DC, 1/KPa |
|
|
0.758 |
|
|
0.031* |
CC, mm2/KPa |
|
|
0.426 |
|
|
0.111 |
|
|
|
0.369 |
|
|
0.132 |
|
|
|
0.203 |
|
|
0.153 |
PWV, m/s |
|
|
0.209 |
|
|
0.265 |
The results of the study suggested that the left carotid artery in subjects with type 2 diabetes was more vulnerable to atherosclerosis when compared with the right carotid artery. In the 106 subjects, there were greater carotid IMT and smaller DC (stiffer) in the left carotid artery than in the right carotid artery (Table
DM, mainly type 2 DM, is an increasing health problem worldwide. It is estimated that global diabetes adults will achieve 552 million in 2030 [
DM is a common cause of atherosclerosis [
However, results showed that carotid IMT and carotid arterial stiffness did not significantly increase in the groups with more additional atherosclerosis risk factors (Table
The present study found that there were different atherosclerosis burdens between the left and right carotid artery in Chinese subjects with type 2 diabetes; the left carotid artery was more susceptible to carotid atherosclerosis. The result was consistent with Luo’s study in which the left carotid arterial wall was thicker than the right in the elderly as well as in the subjects with atherosclerotic diseases [
A limitation of this study is the small size of subjects, and thus the additive effects of atherosclerosis risk factors on carotid atherosclerosis in Chinese patients with type 2 diabetes may be not fully evaluated. Future investigations with larger sample size remain to be conducted. Because of limited number of subjects with smoking, this study did not assess the additive effect of smoking on carotid atherosclerosis in Chinese type 2 diabetics. Actually, smoking is a well-established risk factor of atherosclerosis and was shown to accentuate atherosclerosis in type 2 diabetics [
This study provides an understanding of the effects of additional atherosclerosis risk factors to carotid atherosclerosis in Chinese patients with type 2 DM. In these patients, the presence of hypertension, dyslipidemia, and CKD had cumulative effects on the burden of carotid plaque. As a result, prompt diagnoses and treatments of hypertension, dyslipidemia, and CKD are necessary for patients with diabetes, and more concern of carotid atherosclerosis should be given to the patients with more additional atherosclerosis risk factors.
All authors declare no conflict of interests for the data, results, and conclusions described in this study.
This research was funded by the research Grants from the Hong Kong Polytechnic University (G-U700 and RU2R).