Intima and media thickness of peripheral arteries measured by high-resolution ultrasound in Diabetes Mellitus patients with macrovascular or microvascular complications and their relationship with Homocysteine

Intima and media thickness of peripheral arteries measured by high-resolution ultrasound in Diabetes Mellitus patients with macrovascular or microvascular complications and their relationship with Homocysteine | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Intima and media thickness of peripheral arteries measured by high-resolution ultrasound in Diabetes Mellitus patients with macrovascular or microvascular complications and their relationship with Homocysteine Suqin Jin, Siyu Zhao, Xiaoyu Yue, Mei Zhang, Xianghua Zhuang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6806257/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Oct, 2025 Read the published version in BMC Endocrine Disorders → Version 1 posted 11 You are reading this latest preprint version Abstract Background Pathological changes of arterial vasculature plays a pivotal role in the development of macrovascular and microvascular complications of diabetes mellitus (DM). Compared to traditional carotid intima-media thickness (CIMT), separate measurement of arterial intima and media thickness by high-resolution ultrasound could reveal the vascular anatomical changes in such patients more precisely. Homocysteine (Hcy) is reported closely related to macrovascular and microvascular complications in DM patients. The purpose of this study was to explore intima and media thickness of carotid arteries, radial arteries and podalic arteries in DM patients with macrovascular or microvascular complications and to explore their diagnostic value for these patients as well as their relationship with Hcy. Methods A total of 123 DM patients and 102 healthy controls were enrolled in this study. Arterial ultrasound examination was performed using a 24-MHz probe (i24Lx8), and intima and media thickness of carotid arteries (CIT and CMT), radial arteries (RIT and RMT) and podalic arteries (PIT and PMT) were measured. Serum levels of fasting glucose, low-density lipoprotein cholesterol, Hcy, and clinical information were also collected. Results CIT, RIT and PIT were all substantially thicker in DM patients. CIT, CMT and CIMT were thicker in DM patients with macrovascular complications than those without macrovascular complications, as well as RMT and PMT. Additionally, there was a correlation between Hcy and CIT in DM patient (r = 0.254, P = 0.006). CIT was associated with traditional risk factors including age, systolic blood pressure and HCY. Conclusions Measurement of arterial intima and media thickness with high-resolution ultrasound might be a promising tool to reveal arterial pathological changes in DM patients and their subgroups. intima thickness media thickness diabetes mellitus complication homocysteine Figures Figure 1 Introduction Homocysteine (Hcy) is a metabolic intermediate produced by demethylation of methionine (Met). It has physiological significance for cell cycle progression and maintenance of intracellular homeostasis. 1 Elevated HCY can destroy vascular endothelial cells, induce thrombosis and promote the proliferation of vascular smooth muscle cells to form atherosclerosis, further leading to a variety of cardio-cerebrovascular diseases. 2 The level of serum Hcy in patients with diabetes mellitus (DM) is closely related to macrovascular and microvascular complications. It is reported that the level of Hcy in DM patients complicated with coronary heart disease was significantly higher than that in patients with no history of coronary artery disease; 3 and the level of Hcy in patients with cerebral infarction was also significantly higher than that in the control group. 4 A meta-analysis of a prospective study showed that if the level of Hcy was reduced by 25%, the risk of ischemic heart disease could be reduced by 11%, and the risk of stroke could be reduced by 19%. 5 The prevalence rate of peripheral vascular disease in diabetic patients with Hcy level ≥ 15µ/l was higher than that in patients with Hcy level ≤ 15µ/l (16% vs. 3.1%; P < 0.05; OR 5.33; 95% CI 1.18–21.5), 6 as well as prevalence of microvascular complications including nephropathy (93.3% vs. 12.8%; P < 0.05; OR 7.15; 95% CI 2.9–17.9). 6 The occurrence of diabetic retinopathy and microalbuminuria is also increased in patients with elevated Hcy level. 7 , 8 Carotid intima-media thickness (CIMT), a marker of subclinical atherosclerosis, can be used to predict cardiovascular risk, 9 – 12 as well as microvascular and macrovascular complications in DM patients. 10 It is the most widely used non-invasive imaging method to evaluate atherosclerosis and cardiovascular risk. 13 Some studies found that CIMT is associated with the progression of albuminuria 14 and chronic kidney disease in DM patients. 15 However, due to limited ultrasound resolution in clinical routine practice, carotid intima thickness and media thickness are not clearly distinguished, the influence of hyperglycemia status on vascular structure detected by ultrasound in DM patients is unclear. It is reported that angiogenic abnormality should occur in diabetes mellitus patients, involving several pathological conditions including atherosclerosis which happened predominantly in the intima layer. Atherosclerosis is caused by complex interactions of various factors, and diabetes further accelerates these interactions. 16 Endothelial dysfunction, inflammation, changes in mineral metabolism, advanced glycation end products and oxidative stress caused by diabetes may contribute to intimal hyperplasia and vascular calcification. 17 , 18 Therefore, measurement of arterial intima thickness in patients with diabetes may better reflect the condition of patients with diabetes. Besides, there are a few studies reporting the correlation between HCY level and CIMT. 19 , 20 However, the relationship between CIT and Hcy was not investigated. With the development of 24-MHz high-frequency high resolution (~ 60um) ultrasound probe, arterial intima thickness and media thickness could be measured separately, including carotid artery and peripheral artery, and its accuracy has been verified. 21 The purpose of this study was to investigate intima thickness, media thickness, intima-media thickness (IMT) in DM patients and their relationship with Hcy. Methods Study population A total of 123 adult DM patients admitted into the Second Hospital of Shandong University and Qilu Hospital of Shandong University were enrolled in this study. All patients met the 2011 American Diabetes Association criteria 22 and were aged 18–80 years and have completed the examination of diabetes-related vascular complications. The exclusion criteria were severe infection, hepatorenal insufficiency, Takayasu arteritis and other systemic diseases. Patients with carotid endarterectomy, stenting, extracranial-intracranial arterial bypass grafting or other possible causes of carotid disease were also excluded from this study. All DM patients were further categorized into with-macrovascular complication subgroup or without-macrovascular complication subgroup according to accompanying macrovascular or microvascular complications. Macrovascular complications include coronary heart disease, cerebrovascular disease and peripheral vascular disease. Coronary artery disease (CAD) was diagnosed according to clinical and electrocardiographic criteria. 9 Cerebrovascular disease (CVD) included clinically diagnosed cerebral infarction or a history of transient cerebral ischemia. 23 Peripheral vascular disease (PVD) was diagnosed by clinical symptoms of arterial lesions or a pathological systolic blood pressure index 30mg/24h within 3–6 months or estimated glomerular filtration rate (eGFR) < 60ml/min/1.73 m. 25 The diagnostic criteria of diabetic neuropathy included ①definite history of diabetes mellitus,②neuropathy occurring at or after the diagnosis of diabetes, ③clinical symptoms and signs in accordance with the manifestation of diabetic neuropathy, and ④ neuropathies caused by other causes should be excluded. Noticeably, patients with macrovascular and microvascular complications were allocated into macrovascular complication subgroup, and patients with no vascular complication or only microvascular complication were categorized into non-macrovascular complication subgroup. The control group included 102 age and gender matched volunteers, with no history of DM, nor physical or laboratory evidence for DM. The exclusion criteria were the same as in DM group. The study protocol was approved by the Ethics Committees of The Second Hospital of Shandong University and Shandong University Qilu Hospital and informed consents were obtained from all participants. Demographic characteristics Data on age, gender, body mass index (BMI), history of current or previous smoking, systolic blood pressure (SBP), diastolic blood pressure (DBP) and administration of antihypertensive drugs and statins were collected on enrollment. Serum levels of fasting blood glucose (GLU), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and homocysteine (Hcy) were tested in clinical laboratory department of the two hospitals. Carotid, radial and dorsalis pedis artery ultrasonography and image analysis All subjects underwent carotid, radial and dorsalis pedis arteries ultrasonography examination in the supine position as previously reported. 21 Briefly, a 24-MHz high-frequency linear transducer (PLI-2004BX) connected to the ultrasound system (Aplio i900, Canon-Toshiba ultrasound, Japanese Tochigi-Ken) was used to sequentially scan the bilateral carotid, radial and podalic arteries. The scanning range of the carotid artery is from the proximal end of the common carotid artery to the bifurcation of the common carotid artery. Longitudinal section of the bilateral radial arteries 1-2cm proximal to styloid process and the longitudinal section of the bilateral dorsalis pedis artery at the neck level of the ankle joint were also scanned. The ECG was recorded at the same time. The stilled images of carotid artery, radial artery and dorsalis pedis artery at the peak of R wave were analyzed with software embedded in the ultrasound machine. Intima thickness (IT) and media thickness (MT) for every artery was measured. IT was defined as the distance from the leading edge of the lumen-intima interface to the intima-media interface of the far wall, and MT as the distance from the intima-media interface to the leading edge of the media-adventitia interface of the far wall. IMT was the sum of IT and MT. Carotid intima thickness (CIT) and carotid media thickness (CMT) of the posterior wall of the bilateral common carotid arteries were measured at the sites 1.5cm, 2cm and 2.5cm proximal to carotid bifurcation. An averaged value of the 6 points of bilateral carotid arteries were defined as CIT and CMT. Measurements of radial and dorsalis pedis arteries were performed in the far wall of bilateral arteries in the long-axis views. The mean values of the bilateral radial IT (RIT) and radial MT (RMT) measurements in each participant were calculated as final RIT and RMT, respectively, as well as podalic IT (PIT) and podalic MT (PMT). 21 Statistical analysis SPSS version 23.0 (SPSS, Chicago, IL) was used for statistical analysis. Continuous data was expressed by mean ± SD. Categorical data was expressed as number (percentage). Kolmogorov-Smirnov was used to test the normal distribution of the data. Independent t-test was used to compare continuous data sets with normal distribution. Mann Whitney U test was used to compare the continuous data of non-normal distribution. Chi-square test was used to compare categorical data. Spearman correlation analysis was used to explore the correlation between plasma HCY and ultrasound parameters. Multivariate linear regression analysis was performed to analyze the relationship between ultrasound parameters and biochemical markers or traditional risk factors. A two tailed p <0.05 was considered statistically significant. Results Demographic characteristics and ultrasound parameters in DM patients and healthy controls Demographic characteristics and ultrasound parameters of DM and control groups were listed in Table 1 . BMI, SBP, DBP, TG and GLU were all significantly higher in DM group than control group, as well as administration of statins and antihypertensives ( P 0.05). CIT, CMT, CIMT, RIT and PIT were substantially thicker in DM patients. The relative differences for CIT, RIT and PIT were 33.7%, 34.9% and 39.5% respectively between DM patients and healthy controls, all of which were greater than media thickness and intima-media thickness. (Table 1 , Fig. 1 ). Table 1 Demographic, biochemical and ultrasonic data in DM patients and healthy controls DM (n = 123) Control (n = 102) p value Age (year) 57.57 ± 12.81 58.66 ± 7.61 0.431 Male (n, %) 73 (59.3%) 54 (52.9%) 0.348 BMI (kg/m2) 26.34 ± 4.02 23.98 ± 3.30 < 0.001 Smoking (n, %) 41 (33.3%) 25 (24.5%) 0.144 SBP (mmHg) 132.13 ± 15.66 127.20 ± 12.92 0.012 DBP (mmHg) 82.46 ± 9.37 75.51 ± 10.92 < 0.001 Statins (n, %) 29 (23.6%) 1 (1.0%) < 0.001 Antihypertensives (n, %) 54 (43.9%) 1 (1.0%) < 0.001 TC (mmol/L) 4.51 ± 1.22 4.63 ± 1.05 0.438 TG (mmol/L) 1.81 ± 1.69 1.34 ± 0.73 0.006 HDL-C (mmol/l) 1.06 ± 0.29 1.29 ± 0.30 < 0.001 LDL-C (mmol/L) 2.67 ± 0.97 2.83 ± 0.70 0.142 HCY (mmol/L) 11.84 ± 4.05 14.50 ± 8.45 0.005 GLU (mmol/L) 9.91 ± 3.73 5.12 ± 0.79 < 0.001 CIT (×10 − 2 mm) 31.40 ± 7.56 23.48 ± 4.82 < 0.001 CMT (×10 − 2 mm) 43.86 ± 12.18 40.87 ± 10.23 0.046 CIMT (×10 − 2 mm) 75.27 ± 16.27 64.35 ± 13.13 < 0.001 RIT (×10 − 2 mm) 14.83 ± 4.40 10.99 ± 2.28 < 0.001 RMT (×10 − 2 mm) 15.28 ± 4.89 15.20 ± 4.68 0.901 PIT (×10 − 2 mm) 14.15 ± 3.92 10.14 ± 2.21 < 0.001 PMT (×10 − 2 mm) 14.57 ± 5.24 15.83 ± 5.34 0.076 Data were expressed as mean ± SD or n (%). BMI = body mass index; CIMT = carotid intima-media thickness; CIT = carotid intima thickness; CMT = carotid media thickness; DBP = diastolic blood pressure; GLU = fasting glucose; HCY = homocysteine; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; PIT = podalic intima thickness; PMT = podalic media thickness; RIT = radial intima thickness; RMT = radial media thickness; SBP = systolic blood pressure; TC = total cholesterol; TG = triglyceride. Comparison of intima and media thickness of arteries between DM subgroups Among all the DM patients, 21 patients were with macrovascular complications, 14 were with microvascular complications, 77 were with macrovascular and microvascular complications, and 11 were without vascular complications. The number for macrovascular subgroup and non-macrovascular subgroup were 98 and 25, respectively. CIT, CMT, CIMT, RMT and PMT were all substantially thicker in DM patients with macrovascular complications than those without macrovascular complications, indicating media layer was more involved in the development of macrovascular complications. The relative difference in CMT between the two subgroups were the largest (28.4%) among all carotid, radial and podalic ultrasound parameters, while that of CIT being 20.6% and CIMT being 25.0%. By contrast, there was no difference between the two subgroups in terms of RIT and PIT. (Table 2 ). Table 2 Demographic, biochemical and ultrasonic data in diabetic macrovascular lesion subgroup and non-macrovascular lesion subgroup Macrovascular lesion (n = 98) Non-macrovascular lesion (n = 25) p value Age (year) 60.04 ± 10.76 47.88 ± 15.60 0.001 Male (n, %) 60 (61.2%) 13 (52.0%) 0.495 BMI (kg/m2) 26.58 ± 3.82 25.43 ± 4.65 0.206 Smoking (n, %) 35 (35.7%) 6 (24.0%) 0.344 SBP (mmHg) 134.63 ± 14.39 122.32 ± 16.85 < 0.001 DBP (mmHg) 83.21 ± 9.22 79.48 ± 9.59 0.075 Statins (n, %) 28 (28.6%) 1 (4.0%) 0.014 Antihypertensives (n, %) 51 (52.0%) 3 (12.0%) < 0.001 TC (mmol/L) 4.54 ± 1.27 4.39 ± 1.00 0.586 TG (mmol/L) 1.78 ± 1.36 1.95 ± 2.70 0.658 HDL-C (mmol/l) 1.06 ± 0.28 1.08 ± 0.34 0.676 LDL-C (mmol/L) 2.72 ± 1.03 2.43 ± 0.64 0.087 HCY (mmol/L) 12.19 ± 4.05 10.47 ± 3.84 0.070 GLU (mmol/L) 9.83 ± 3.70 10.23 ± 3.94 0.639 CIT (×10 − 2 mm) 32.53 ± 7.75 26.98 ± 4.70 0.001 CMT (×10 − 2 mm) 45.93 ± 11.59 35.77 ± 11.21 <0.001 CIMT (×10 − 2 mm) 78.46 ± 15.43 62.75 ± 13.36 <0.001 RIT (×10 − 2 mm) 14.92 ± 4.60 14.48 ± 3.60 0.659 RMT (×10 − 2 mm) 15.91 ± 5.06 12.78 ± 3.07 0.004 PIT (×10 − 2 mm) 14.28 ± 4.09 13.64 ± 3.18 0.468 PMT (×10 − 2 mm) 15.08 ± 5.57 12.60 ± 3.04 0.004 Data were expressed as mean ± SD or n (%). BMI = body mass index; CIMT = carotid intima-media thickness; CIT = carotid intima thickness; CMT = carotid media thickness; DBP = diastolic blood pressure; GLU = fasting glucose; HCY = homocysteine; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; PIT = podalic intima thickness; PMT = podalic media thickness; RIT = radial intima thickness; RMT = radial media thickness; SBP = systolic blood pressure; TC = total cholesterol; TG = triglyceride. Correlation between Hcy and arterial intima and media thickness in DM There is a positive correlation between CIMT and Hcy in this study, which is in agreement with previous reports. 19 , 20 , 26 In addition, Hcy was found correlated with CIT, CMT, RMT, and PMT (correlation efficiency was 0.254, 0.266, 0.292 and 0.236, respectively, P < 0.05 for all). (Table 3 ). Table 3 Spearman correlation analysis between peripheral arterial intima-media thickness and Hcy Variables CIT CMT CIMT RIT RMT PIT PMT Hcy level Spearman correlation 0.254 0.266 0.317 0.003 0.292 -0.018 0.236 p-Value 0.006 0.004 0.001 0.975 0.002 0.852 0.011 CIT = carotid intima thickness; CMT = carotid media thickness; CIMT = carotid intima-media thickness; HCY = homocysteine; PIT = podalic intima thickness; PMT = podalic media thickness; RIT = radial intima thickness; RMT = radial media thickness. Multivariate linear regression analysis of risk factors for CIT The multivariate linear regression analysis was performed to determine contributing factors for ultrasound parameters in DM. The results showed that age, SBP and Hcy were associated with CIT. (Tables 4 ). Table 4 Multivariate linear regression analysis of variables in DM patients Factor CIT CMT RIT RMT PIT PMT Age 0.002(0.001 to 0.003)* 0.005(0.003 to 0.008)** 0.001(0.000 to 0.002)* 0.001(0.000 to 0.002)* 0.001(0.000 to 0.002)** 0.001(0.000 to 0.002) Male -0.003(-0.039 to 0.032) 0.042(-0.009 to 0.093) -0.013(-0.036 to 0.010) -0.002(-0.024 to 0.021) 0.015(-0.003 to 0.033) 0.012(-0.014 to 0.037) smoking -0.006(-0.052 to 0.040) 0.049(-0.016 to 0.115) -0.001(-0.031 to 0.028) 0.004(-0.025 to 0.033) -0.015(-0.038 to 0.008) 0.020(-0.012 to 0.053) Alcohol 0.039(-0.007 to 0.086) -0.054(-0.120 to 0.013) 0.030(0.000 to 0.060)* 0.014(-0.016 to 0.044) 0.027(0.004 to 0.050)* 0.010(-0.023 to 0.044) BMI 0.003(-0.001 to 0.006) 0.004(-0.002 to 0.009) 0.001(-0.001 to 0.004) 0.002(0.000 to 0.005) 0.000(-0.002 to 0.002) 0.001(-0.002 to 0.003) SBP 0.002(0.000 to 0.003)* 0.002(0.000 to 0.004) 0.000(-0.001 to 0.001) 0.001(0.000 to 0.002) 0.000(-0.001 to 0.001) 0.000(-0.001 to 0.002) DBP -0.003(-0.006 to 0.001) 0.000(-0.004 to 0.004) 0.000(-0.002 to 0.001) 0.000(-0.001 to 0.002) 0.000(-0.001 to 0.002) 0.000(-0.002 to 0.001) Statins 0.008(-0.027 to 0.042) -0.018(-0.067 to 0.032) -0.007(-0.029 to 0.015) 0.000(-0.021 to 0.022) -0.013(-0.030 to 0.004) -0.002(-0.026 to 0.023) Antihype-rtensives -0.020(-0.053 to 0.013) -0.037(-0.085 to 0.010) -0.020(-0.041 to 0.001) 0.000(-0.021 to 0.021) 0.004(-0.012 to 0.021) 0.009(-0.015 to 0.032) Glu 0.001(-0.003 to 0.005) -0.004(-0.010 to 0.002) -0.002(-0.004 to 0.001) 0.000(-0.003 to 0.003) -0.002(-0.004 to 0.001) 0.000(-0.003 to 0.003) TG 0.001(-0.010 to 0.013) 0.006(-0.011 to 0.023) 0.000(-0.007 to 0.008) -0.001(-0.008 to 0.007) 0.003(-0.003 to 0.009) -0.002(-0.011 to 0.006) Hcy 0.005(0.001 to 0.009)* -0.001(-0.007 to 0.004) -0.001(-0.003 to 0.002) 0.000(-0.002 to 0.003) -0.003(-0.005 to -0.001)* 0.000(-0.003 to 0.003) Data were expressed as regression coefficients (95% confidence interval). *P < 0.05; **P < 0.01 BMI = body mass index; CIT = carotid intima thickness; CMT = carotid media thickness; DBP = Diastolic blood pressure; GLU = fasting glucose; HCY = homocysteine; HDL-C = high-density lipoprotein cholesterol; PIT = podalic intima thickness; PMT = podalic media thickness; RIT = radial intima thickness; RMT = radial media thickness; SBP = systolic blood pressure; TG = triglyceride. Discussion There were several important findings in this study. First, intima layer was predominantly thickened in DM patients. Second, arterial media thickness was more involved in DM patients with macrovascular complications. Third, HCY was correlated with intima and media thickness in DM patients. Fourth, CIT was associated with traditional risk factors including age, systolic blood pressure and HCY. There is a wealth of evidence showing the relationship between the thickened CIMT and DM. CIMT was also an independent predictor of stroke, especially in stroke patients caused by cerebral ischemia, and predictor of stroke recurrence in diabetic population. 27 However, whether intima or media layer was more involved remains unclear due to previous low-resolution ultrasound probe used in clinical routine practice, failing to distinguish the two layers separately. Some studies reported that there is a more active atherogenic process in DM patients, indicating intima layer might be more involved due to atherosclerosis. 28 It is also reported that atherosclerosis serves as a common pathology in macrovessels and microvessels in DM patients with diabetic panvascular disease (DPD). 29 However, there are other study showing that tunica media to internal lumen ratio of small artery was increased in non-insulin-dependent diabetes mellitus, suggesting media thickness was involved. 30 Moreover, vasculature changes of different arteries in DM patients were not reported in literature. In this study, we found CIT, RIT and PIT were substantially thicker in DM patients, all of which were greater than media thickness and intima-media thickness comparing to healthy population, indicating intima layer was more involved in DM patient and might be a novel vascular lesion for DM patients screening, irrespective of large-sized carotid or medium-sized radial and podalic artery. By comparing ultrasound parameters between DM patients with macrovascular complication subgroup and patients with non-macrovascular complication subgroup, it is noted that there was no difference between the two subgroups regarding RIT and PIT, the difference for CIT was statistically significant yet not remarkable, all the three parameters were thicker than control group irrespective of subgroup difference, indicating intima layers might be a novel vascular lesion for DM patients screening. By contrast, CMT, RMT and PMT were all substantially thicker in DM patients with macrovascular complications subgroup, suggesting media layer was more involved in the development of macrovascular complications and could be a promising differential tool for macrovascular complication prediction. The mechanisms of vascular injury induced by homocysteine include oxidative stress, DNA dysfunction, decreased availability of nitric oxide (NO), endothelial cytotoxicity, smooth muscle cell proliferation, enhanced platelet aggregation, impaired fibrinolytic system, increased leukocyte adhesion and induction of chronic inflammation. 7 These pathological changes are characterized by blood flow-mediated vasodilation damage, mainly due to the production of nitric oxide (NO) and the decrease of bioavailability. 31 Nitric oxide is the most effective endogenous vasodilator 32 and an atherosclerotic protective molecule. 33 The imbalance of its synthesis can lead to and enhance oxidative stress and atherosclerosis. In this study, Hcy was found correlated with CIT, CMT, RMT, and PMT, as well as CIMT, which was in accordance with previous study. Multivariate linear regression analysis also revealed that CIT was associate with age, SBP and Hcy. To our surprise, neither serum level of fasting glucose nor TG was not associate with CIT. This might be due to optimal hypoglycemic treatment in DM patients according to current guidelines, fasting glucose was no longer a best biomarker reflecting severity of DM status. Unfortunately, interpretation of HbA1c was not applicable due to limited sample size. It was also reported that postprandial hypertriglyceridemia despite normal TG levels may be an independent risk factor for early atherosclerosis in type 2 diabetes, 34 which should be analyzed in future study. There are several limitations in this study. First, the sample size for this study is relatively small, evading further analysis and more detailed subgroup classification. Second, this study is a cross-sectional study without follow up information, the predictive value for ultrasound parameters were not applicable. These deficiencies need a large-number multi-centered prospective studies to confirm the conclusions of this study. Conclusion Measurement of arterial intima and media thickness with high-resolution ultrasound might be a promising tool to reveal arterial pathological changes in DM patients and their subgroups. Declarations Author Contributions: Mingjun Xu had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Suqin Jin, Mei Zhang, Xianghua Zhuang, Mingjun Xu and Zhaohong Xie Acquisition, analysis, or interpretation of data: Siyu Zhao, Xiaoyu Yue, Xiaoyu Wan, Mingjun Xu，Suqin Jin, Drafting of the manuscript: Suqin Jin, Mingjun Xu, Siyu Zhao Critical revision of the manuscript for important intellectual content: Mei Zhang, Mingjun Xu and Zhaohong Xie Statistical analysis: Siyu Zhao, Mingjun Xu Study supervision: Suqin Jin, Mingjun Xu and Zhaohong Xie All authors have seen and approved the manuscript as submitted. Declarations of interest: None. Clinical Trial Number: Not applicable. Consent to Publish declaration: Not applicable. Funding: This work was supported by grants from the Natural Science Foundation of Shandong Province (ZR2020QH122), Jinan clinical medical science and technology innovation program (201907056) and National Natural Science Foundation of China (No. 82001834). Availability of data and materials: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate: The study protocol was approved by the Ethics Committees of The Second Hospital of Shandong University and Shandong University Qilu Hospital and informed consents were obtained from all participants. References Finkelstein JD, Martin JJ.Homocysteine. Int J Biochem Cell Biol. 2000;32(4):385-389. Lin T, Liu JC, Chang LY, et al.Association of C-reactive protein and homocysteine with subclinical coronary plaque subtype and stenosis using low-dose MDCT coronary angiography. Atherosclerosis. 2010; 212(2):501-506. Rudy A, Kowalska I, Straczkowski M, et al. Homocysteine concentrations and vascular complications in patients with type 2 diabetes. Diabetes Metab. 2005;31(2):112-117. Zhang T, Jiang Y, Zhang S, et al. 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Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus. Arteriosclerosis, thrombosis, and vascular biology. 2017;37(2): 191–204. Dai Z, Jiao Y, Fan Q, et al. Homocysteine, interleukin-1β, and fasting blood glucose levels as prognostic markers for diabetes mellitus complicated with cerebral infarction and correlated with carotid intima-media thickness. Exp Ther Med . 2020;19(2):1167-1174. Adachi H, Hirai Y, Fujiura Y, et al. Plasma homocysteine levels and atherosclerosis in Japan: epidemiological study by use of carotid ultrasonography. Stroke . 2002;33(9):2177-2181. Xu M, Jin S, Li F, et al. The Diagnostic Value of Radial and Carotid Intima Thickness Measured by High-Resolution Ultrasound for Ischemic Stroke. J Am Soc Echocardiogr . 2021;34(1):72-82. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care . 2011;34 Suppl 1(Suppl 1):S62-S69. Kosiborod M, Gomes MB, Nicolucci A, et al. Vascular complications in patients with type 2 diabetes: prevalence and associated factors in 38 countries (the DISCOVER study program). Cardiovasc Diabetol. 2018;17(1):150. Girard E, Nacher M, Bukasa-Kakamba J, et al. Vitamin D Deficiency in Patients with Diabetes in French Guiana: Epidemiology and Relation with Microvascular and Macrovascular Complications. Nutrients . 2021;13(12):4302. Tuttle KR, Bakris GL, Bilous RW, et al. Diabetic kidney disease: a report from an ADA Consensus Conference. Diabetes Care . 2014;37(10):2864-2883. Devasia AJ, Joy B, Tarey SD. Serum homocysteine as a risk factor for carotid intimal thickening in acute stroke: A cross sectional observational study. Ann Indian Acad Neurol . 2016;19(1):48-51. Vigili de Kreutzenberg S, Tiengo A, Avogaro A. Cerebrovascular disease in diabetes mellitus: the role of carotid intima-media thickness. Nutr Metab Cardiovasc Dis. 2009;19(9):667-673. Yahagi K, Kolodgie FD, Lutter C, et al. Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus. Arterioscler Thromb Vasc Biol. 2017;37(2):191-204. Li Y, Liu Y, Liu S, et al. Diabetic vascular diseases: molecular mechanisms and therapeutic strategies. Signal Transduct Target Ther. 2023 Apr 10;8(1):152. Rizzoni D, Rosei EA. Small artery remodeling in diabetes mellitus. Nutr Metab Cardiovasc Dis . 2009;19(8):587-592. Pushpakumar S, Kundu S, Sen U. Endothelial dysfunction: the link between homocysteine and hydrogen sulfide. Curr Med Chem . 2014;21(32):3662-3672. Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation . 2004;109(23 Suppl 1):III27-III32. Berenji Ardestani S, Eftedal I, Pedersen M, et al. Endothelial dysfunction in small arteries and early signs of atherosclerosis in ApoE knockout rats. Scientific reports . 2020;10(1):15296. Teno S, Uto Y, Nagashima H, et al. Association of postprandial hypertriglyceridemia and carotid intima-media thickness in patients with type 2 diabetes. Diabetes Care. 2000;23(9):1401-1406. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 22 Oct, 2025 Read the published version in BMC Endocrine Disorders → Version 1 posted Editorial decision: Revision requested 18 Aug, 2025 Reviews received at journal 05 Aug, 2025 Reviewers agreed at journal 23 Jul, 2025 Reviews received at journal 16 Jul, 2025 Reviewers agreed at journal 10 Jul, 2025 Reviewers agreed at journal 10 Jul, 2025 Reviewers invited by journal 03 Jul, 2025 Editor invited by journal 10 Jun, 2025 Editor assigned by journal 06 Jun, 2025 Submission checks completed at journal 06 Jun, 2025 First submitted to journal 02 Jun, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6806257","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":481217407,"identity":"e6467f92-8963-4faf-93af-5ad59ca70b4c","order_by":0,"name":"Suqin Jin","email":"","orcid":"","institution":"The Second Hospital of Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Suqin","middleName":"","lastName":"Jin","suffix":""},{"id":481217408,"identity":"090b19b2-97b6-450c-8ed8-ee5dcb13c36b","order_by":1,"name":"Siyu Zhao","email":"","orcid":"","institution":"The Second Hospital of Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Siyu","middleName":"","lastName":"Zhao","suffix":""},{"id":481217409,"identity":"3f9235ba-7177-449c-bbd0-0bf738501c97","order_by":2,"name":"Xiaoyu Yue","email":"","orcid":"","institution":"Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoyu","middleName":"","lastName":"Yue","suffix":""},{"id":481217410,"identity":"3d8fe7ce-eeaf-4962-b289-cad6c4b9a44f","order_by":3,"name":"Mei Zhang","email":"","orcid":"","institution":"Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Mei","middleName":"","lastName":"Zhang","suffix":""},{"id":481217411,"identity":"f293dc7b-cd6e-48db-84a6-ea87005b1b95","order_by":4,"name":"Xianghua Zhuang","email":"","orcid":"","institution":"The Second Hospital of Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Xianghua","middleName":"","lastName":"Zhuang","suffix":""},{"id":481217412,"identity":"b6f664e7-1096-421f-9992-b0978b94f8a1","order_by":5,"name":"Zhaohong Xie","email":"","orcid":"","institution":"The Second Hospital of Shandong University","correspondingAuthor":false,"prefix":"","firstName":"Zhaohong","middleName":"","lastName":"Xie","suffix":""},{"id":481217413,"identity":"2e38ee5c-126e-4fce-8a4c-891d62436a5e","order_by":6,"name":"Mingjun Xu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuUlEQVRIiWNgGAWjYHCCxAcfftjw8PM3EK8l2XBmT5qM5IwDxGthk+ZhO2xj0JBApHqDawceSPDwnOcxYDjA+OFjDhFaJGcnJBhIWNzmMWduYJacuY0ILfzSCUA9PLd5LBsOsDHzEqOFDajlQALbOR4DIEmcFqAtiUDzD5CgBeiXZMbGnmQeyRkHm4nzi8HtnPTff37Y2fPzNx/88JEYLQwMPAlQBmMDUeqBgP0AsSpHwSgYBaNgpAIARuY1/ebq0RkAAAAASUVORK5CYII=","orcid":"","institution":"Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University","correspondingAuthor":true,"prefix":"","firstName":"Mingjun","middleName":"","lastName":"Xu","suffix":""}],"badges":[],"createdAt":"2025-06-03 02:53:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6806257/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6806257/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12902-025-02064-2","type":"published","date":"2025-10-22T16:17:15+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":86217372,"identity":"d0b9264b-7b69-42e2-9a33-3f780b9220af","added_by":"auto","created_at":"2025-07-08 06:20:58","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":383603,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMeasurements of the intima thickness and media thickness of the carotid, radial and podalic arteries in a diabetic patient and a healthy subject. (A)\u003c/strong\u003e Measurements of carotid intima thickness (CIT) and media thickness (CMT) in a diabetic patient; \u003cstrong\u003e(B)\u003c/strong\u003e Measurements of radial intima thickness (RIT) and media thickness (RMT) in a diabetic patient; \u003cstrong\u003e(C)\u003c/strong\u003e Measurements of podalicintima thickness (PIT) and media thickness (PMT) in a diabetic patient; \u003cstrong\u003e(D)\u003c/strong\u003e Measurements of CIT and CMT in a healthy subject; \u003cstrong\u003e(E)\u003c/strong\u003e Measurements of RIT and RMT in a healthy subject; \u003cstrong\u003e(F)\u003c/strong\u003e Measurements of PIT and PMT in a healthy subject.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6806257/v1/1eb0c5e3de1febe78f0e81de.png"},{"id":94490588,"identity":"e2af9a4e-a498-458e-8c0a-a3d05fea6170","added_by":"auto","created_at":"2025-10-27 17:12:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1568372,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6806257/v1/9fa4a9cf-73e9-498e-a11d-12783df5edb9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Intima and media thickness of peripheral arteries measured by high-resolution ultrasound in Diabetes Mellitus patients with macrovascular or microvascular complications and their relationship with Homocysteine","fulltext":[{"header":"Introduction","content":"\u003cp\u003eHomocysteine (Hcy) is a metabolic intermediate produced by demethylation of methionine (Met). It has physiological significance for cell cycle progression and maintenance of intracellular homeostasis.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Elevated HCY can destroy vascular endothelial cells, induce thrombosis and promote the proliferation of vascular smooth muscle cells to form atherosclerosis, further leading to a variety of cardio-cerebrovascular diseases.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e The level of serum Hcy in patients with diabetes mellitus (DM) is closely related to macrovascular and microvascular complications. It is reported that the level of Hcy in DM patients complicated with coronary heart disease was significantly higher than that in patients with no history of coronary artery disease;\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e and the level of Hcy in patients with cerebral infarction was also significantly higher than that in the control group.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e A meta-analysis of a prospective study showed that if the level of Hcy was reduced by 25%, the risk of ischemic heart disease could be reduced by 11%, and the risk of stroke could be reduced by 19%.\u003csup\u003e5\u003c/sup\u003e The prevalence rate of peripheral vascular disease in diabetic patients with Hcy level\u0026thinsp;\u0026ge;\u0026thinsp;15\u0026micro;/l was higher than that in patients with Hcy level\u0026thinsp;\u0026le;\u0026thinsp;15\u0026micro;/l (16% vs. 3.1%; P\u0026thinsp;\u0026lt;\u0026thinsp;0.05; OR 5.33; 95% CI 1.18\u0026ndash;21.5),\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e as well as prevalence of microvascular complications including nephropathy (93.3% vs. 12.8%; P\u0026thinsp;\u0026lt;\u0026thinsp;0.05; OR 7.15; 95% CI 2.9\u0026ndash;17.9). \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e The occurrence of diabetic retinopathy and microalbuminuria is also increased in patients with elevated Hcy level.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eCarotid intima-media thickness (CIMT), a marker of subclinical atherosclerosis, can be used to predict cardiovascular risk,\u003csup\u003e\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e as well as microvascular and macrovascular complications in DM patients.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e It is the most widely used non-invasive imaging method to evaluate atherosclerosis and cardiovascular risk.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e Some studies found that CIMT is associated with the progression of albuminuria\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e and chronic kidney disease in DM patients.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e However, due to limited ultrasound resolution in clinical routine practice, carotid intima thickness and media thickness are not clearly distinguished, the influence of hyperglycemia status on vascular structure detected by ultrasound in DM patients is unclear. It is reported that angiogenic abnormality should occur in diabetes mellitus patients, involving several pathological conditions including atherosclerosis which happened predominantly in the intima layer. Atherosclerosis is caused by complex interactions of various factors, and diabetes further accelerates these interactions.\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e Endothelial dysfunction, inflammation, changes in mineral metabolism, advanced glycation end products and oxidative stress caused by diabetes may contribute to intimal hyperplasia and vascular calcification.\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e Therefore, measurement of arterial intima thickness in patients with diabetes may better reflect the condition of patients with diabetes. Besides, there are a few studies reporting the correlation between HCY level and CIMT.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e However, the relationship between CIT and Hcy was not investigated. With the development of 24-MHz high-frequency high resolution (~\u0026thinsp;60um) ultrasound probe, arterial intima thickness and media thickness could be measured separately, including carotid artery and peripheral artery, and its accuracy has been verified.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe purpose of this study was to investigate intima thickness, media thickness, intima-media thickness (IMT) in DM patients and their relationship with Hcy.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy population\u003c/h2\u003e\u003cp\u003eA total of 123 adult DM patients admitted into the Second Hospital of Shandong University and Qilu Hospital of Shandong University were enrolled in this study. All patients met the 2011 American Diabetes Association criteria\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e and were aged 18\u0026ndash;80 years and have completed the examination of diabetes-related vascular complications. The exclusion criteria were severe infection, hepatorenal insufficiency, Takayasu arteritis and other systemic diseases. Patients with carotid endarterectomy, stenting, extracranial-intracranial arterial bypass grafting or other possible causes of carotid disease were also excluded from this study. All DM patients were further categorized into with-macrovascular complication subgroup or without-macrovascular complication subgroup according to accompanying macrovascular or microvascular complications. Macrovascular complications include coronary heart disease, cerebrovascular disease and peripheral vascular disease. Coronary artery disease (CAD) was diagnosed according to clinical and electrocardiographic criteria.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Cerebrovascular disease (CVD) included clinically diagnosed cerebral infarction or a history of transient cerebral ischemia.\u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e Peripheral vascular disease (PVD) was diagnosed by clinical symptoms of arterial lesions or a pathological systolic blood pressure index\u0026thinsp;\u0026lt;\u0026thinsp;0.9.\u003csup\u003e24\u003c/sup\u003e Microvascular complications include nephropathy, neuropathy and retinopathy. The diagnosis of nephropathy Include at least twice albuminuria \u0026gt;30mg/24h within 3\u0026ndash;6 months or estimated glomerular filtration rate (eGFR)\u0026thinsp;\u0026lt;\u0026thinsp;60ml/min/1.73 m.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e The diagnostic criteria of diabetic neuropathy included ①definite history of diabetes mellitus,②neuropathy occurring at or after the diagnosis of diabetes, ③clinical symptoms and signs in accordance with the manifestation of diabetic neuropathy, and ④ neuropathies caused by other causes should be excluded. Noticeably, patients with macrovascular and microvascular complications were allocated into macrovascular complication subgroup, and patients with no vascular complication or only microvascular complication were categorized into non-macrovascular complication subgroup. The control group included 102 age and gender matched volunteers, with no history of DM, nor physical or laboratory evidence for DM. The exclusion criteria were the same as in DM group. The study protocol was approved by the Ethics Committees of The Second Hospital of Shandong University and Shandong University Qilu Hospital and informed consents were obtained from all participants.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eDemographic characteristics\u003c/h3\u003e\n\u003cp\u003eData on age, gender, body mass index (BMI), history of current or previous smoking, systolic blood pressure (SBP), diastolic blood pressure (DBP) and administration of antihypertensive drugs and statins were collected on enrollment. Serum levels of fasting blood glucose (GLU), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and homocysteine (Hcy) were tested in clinical laboratory department of the two hospitals.\u003c/p\u003e\n\u003ch3\u003eCarotid, radial and dorsalis pedis artery ultrasonography and image analysis\u003c/h3\u003e\n\u003cp\u003eAll subjects underwent carotid, radial and dorsalis pedis arteries ultrasonography examination in the supine position as previously reported.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e Briefly, a 24-MHz high-frequency linear transducer (PLI-2004BX) connected to the ultrasound system (Aplio i900, Canon-Toshiba ultrasound, Japanese Tochigi-Ken) was used to sequentially scan the bilateral carotid, radial and podalic arteries. The scanning range of the carotid artery is from the proximal end of the common carotid artery to the bifurcation of the common carotid artery. Longitudinal section of the bilateral radial arteries 1-2cm proximal to styloid process and the longitudinal section of the bilateral dorsalis pedis artery at the neck level of the ankle joint were also scanned. The ECG was recorded at the same time.\u003c/p\u003e\u003cp\u003eThe stilled images of carotid artery, radial artery and dorsalis pedis artery at the peak of R wave were analyzed with software embedded in the ultrasound machine. Intima thickness (IT) and media thickness (MT) for every artery was measured. IT was defined as the distance from the leading edge of the lumen-intima interface to the intima-media interface of the far wall, and MT as the distance from the intima-media interface to the leading edge of the media-adventitia interface of the far wall. IMT was the sum of IT and MT. Carotid intima thickness (CIT) and carotid media thickness (CMT) of the posterior wall of the bilateral common carotid arteries were measured at the sites 1.5cm, 2cm and 2.5cm proximal to carotid bifurcation. An averaged value of the 6 points of bilateral carotid arteries were defined as CIT and CMT. Measurements of radial and dorsalis pedis arteries were performed in the far wall of bilateral arteries in the long-axis views. The mean values of the bilateral radial IT (RIT) and radial MT (RMT) measurements in each participant were calculated as final RIT and RMT, respectively, as well as podalic IT (PIT) and podalic MT (PMT).\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eSPSS version 23.0 (SPSS, Chicago, IL) was used for statistical analysis. Continuous data was expressed by mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD. Categorical data was expressed as number (percentage). Kolmogorov-Smirnov was used to test the normal distribution of the data. Independent t-test was used to compare continuous data sets with normal distribution. Mann Whitney U test was used to compare the continuous data of non-normal distribution. Chi-square test was used to compare categorical data. Spearman correlation analysis was used to explore the correlation between plasma HCY and ultrasound parameters. Multivariate linear regression analysis was performed to analyze the relationship between ultrasound parameters and biochemical markers or traditional risk factors. A two tailed \u003cem\u003ep\u003c/em\u003e\u0026lt;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eDemographic characteristics and ultrasound parameters in DM patients and healthy controls\u003c/h2\u003e\u003cp\u003eDemographic characteristics and ultrasound parameters of DM and control groups were listed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. BMI, SBP, DBP, TG and GLU were all significantly higher in DM group than control group, as well as administration of statins and antihypertensives (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 for all). There was no difference between the two groups in terms of gender, age, history of smoking, TC and LDL‑C (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). CIT, CMT, CIMT, RIT and PIT were substantially thicker in DM patients. The relative differences for CIT, RIT and PIT were 33.7%, 34.9% and 39.5% respectively between DM patients and healthy controls, all of which were greater than media thickness and intima-media thickness. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic, biochemical and ultrasonic data in DM patients and healthy controls\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDM (n\u0026thinsp;=\u0026thinsp;123)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eControl (n\u0026thinsp;=\u0026thinsp;102)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003ep value\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e57.57\u0026thinsp;\u0026plusmn;\u0026thinsp;12.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e58.66\u0026thinsp;\u0026plusmn;\u0026thinsp;7.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.431\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e73 (59.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54 (52.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.348\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI (kg/m2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26.34\u0026thinsp;\u0026plusmn;\u0026thinsp;4.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23.98\u0026thinsp;\u0026plusmn;\u0026thinsp;3.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25 (24.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.144\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSBP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e132.13\u0026thinsp;\u0026plusmn;\u0026thinsp;15.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e127.20\u0026thinsp;\u0026plusmn;\u0026thinsp;12.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.012\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDBP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e82.46\u0026thinsp;\u0026plusmn;\u0026thinsp;9.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e75.51\u0026thinsp;\u0026plusmn;\u0026thinsp;10.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStatins (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29 (23.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntihypertensives (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e54 (43.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTC (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.51\u0026thinsp;\u0026plusmn;\u0026thinsp;1.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.63\u0026thinsp;\u0026plusmn;\u0026thinsp;1.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.438\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTG (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.81\u0026thinsp;\u0026plusmn;\u0026thinsp;1.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.006\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHDL-C (mmol/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLDL-C (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.142\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHCY (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11.84\u0026thinsp;\u0026plusmn;\u0026thinsp;4.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.50\u0026thinsp;\u0026plusmn;\u0026thinsp;8.45\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.005\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGLU (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.91\u0026thinsp;\u0026plusmn;\u0026thinsp;3.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.12\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCIT (\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003emm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31.40\u0026thinsp;\u0026plusmn;\u0026thinsp;7.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23.48\u0026thinsp;\u0026plusmn;\u0026thinsp;4.82\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCMT (\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003emm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e43.86\u0026thinsp;\u0026plusmn;\u0026thinsp;12.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40.87\u0026thinsp;\u0026plusmn;\u0026thinsp;10.23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.046\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCIMT (\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003emm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e75.27\u0026thinsp;\u0026plusmn;\u0026thinsp;16.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64.35\u0026thinsp;\u0026plusmn;\u0026thinsp;13.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRIT (\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003emm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.83\u0026thinsp;\u0026plusmn;\u0026thinsp;4.40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.99\u0026thinsp;\u0026plusmn;\u0026thinsp;2.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRMT (\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003emm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15.28\u0026thinsp;\u0026plusmn;\u0026thinsp;4.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15.20\u0026thinsp;\u0026plusmn;\u0026thinsp;4.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.901\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePIT (\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003emm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.15\u0026thinsp;\u0026plusmn;\u0026thinsp;3.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.14\u0026thinsp;\u0026plusmn;\u0026thinsp;2.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePMT (\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003emm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.57\u0026thinsp;\u0026plusmn;\u0026thinsp;5.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15.83\u0026thinsp;\u0026plusmn;\u0026thinsp;5.34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.076\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eData were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or n (%).\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eBMI\u0026thinsp;=\u0026thinsp;body mass index; CIMT\u0026thinsp;=\u0026thinsp;carotid intima-media thickness; CIT\u0026thinsp;=\u0026thinsp;carotid intima thickness; CMT\u0026thinsp;=\u0026thinsp;carotid media thickness; DBP\u0026thinsp;=\u0026thinsp;diastolic blood pressure; GLU\u0026thinsp;=\u0026thinsp;fasting glucose; HCY\u0026thinsp;=\u0026thinsp;homocysteine; HDL-C\u0026thinsp;=\u0026thinsp;high-density lipoprotein cholesterol; LDL-C\u0026thinsp;=\u0026thinsp;low-density lipoprotein cholesterol; PIT\u0026thinsp;=\u0026thinsp;podalic intima thickness; PMT\u0026thinsp;=\u0026thinsp;podalic media thickness; RIT\u0026thinsp;=\u0026thinsp;radial intima thickness; RMT\u0026thinsp;=\u0026thinsp;radial media thickness; SBP\u0026thinsp;=\u0026thinsp;systolic blood pressure; TC\u0026thinsp;=\u0026thinsp;total cholesterol; TG\u0026thinsp;=\u0026thinsp;triglyceride.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eComparison of intima and media thickness of arteries between DM subgroups\u003c/h3\u003e\n\u003cp\u003eAmong all the DM patients, 21 patients were with macrovascular complications, 14 were with microvascular complications, 77 were with macrovascular and microvascular complications, and 11 were without vascular complications. The number for macrovascular subgroup and non-macrovascular subgroup were 98 and 25, respectively. CIT, CMT, CIMT, RMT and PMT were all substantially thicker in DM patients with macrovascular complications than those without macrovascular complications, indicating media layer was more involved in the development of macrovascular complications. The relative difference in CMT between the two subgroups were the largest (28.4%) among all carotid, radial and podalic ultrasound parameters, while that of CIT being 20.6% and CIMT being 25.0%. By contrast, there was no difference between the two subgroups in terms of RIT and PIT. (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic, biochemical and ultrasonic data in diabetic macrovascular lesion subgroup and non-macrovascular lesion subgroup\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMacrovascular lesion\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;98)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon-macrovascular lesion\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;25)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60.04\u0026thinsp;\u0026plusmn;\u0026thinsp;10.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47.88\u0026thinsp;\u0026plusmn;\u0026thinsp;15.60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60 (61.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (52.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.495\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI (kg/m2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26.58\u0026thinsp;\u0026plusmn;\u0026thinsp;3.82\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25.43\u0026thinsp;\u0026plusmn;\u0026thinsp;4.65\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.206\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35 (35.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (24.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.344\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSBP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e134.63\u0026thinsp;\u0026plusmn;\u0026thinsp;14.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e122.32\u0026thinsp;\u0026plusmn;\u0026thinsp;16.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDBP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e83.21\u0026thinsp;\u0026plusmn;\u0026thinsp;9.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e79.48\u0026thinsp;\u0026plusmn;\u0026thinsp;9.59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.075\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStatins (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28 (28.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (4.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.014\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntihypertensives (n, %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e51 (52.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (12.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTC (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.54\u0026thinsp;\u0026plusmn;\u0026thinsp;1.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.39\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.586\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTG (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.78\u0026thinsp;\u0026plusmn;\u0026thinsp;1.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.95\u0026thinsp;\u0026plusmn;\u0026thinsp;2.70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.658\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHDL-C (mmol/l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.676\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLDL-C (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.72\u0026thinsp;\u0026plusmn;\u0026thinsp;1.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.087\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHCY (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.19\u0026thinsp;\u0026plusmn;\u0026thinsp;4.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.47\u0026thinsp;\u0026plusmn;\u0026thinsp;3.84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.070\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGLU (mmol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.83\u0026thinsp;\u0026plusmn;\u0026thinsp;3.70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.23\u0026thinsp;\u0026plusmn;\u0026thinsp;3.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.639\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCIT (\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003emm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32.53\u0026thinsp;\u0026plusmn;\u0026thinsp;7.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26.98\u0026thinsp;\u0026plusmn;\u0026thinsp;4.70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCMT (\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003emm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e45.93\u0026thinsp;\u0026plusmn;\u0026thinsp;11.59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35.77\u0026thinsp;\u0026plusmn;\u0026thinsp;11.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCIMT (\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003emm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e78.46\u0026thinsp;\u0026plusmn;\u0026thinsp;15.43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62.75\u0026thinsp;\u0026plusmn;\u0026thinsp;13.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;0.001\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRIT (\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003emm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.92\u0026thinsp;\u0026plusmn;\u0026thinsp;4.60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.48\u0026thinsp;\u0026plusmn;\u0026thinsp;3.60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.659\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRMT (\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003emm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15.91\u0026thinsp;\u0026plusmn;\u0026thinsp;5.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12.78\u0026thinsp;\u0026plusmn;\u0026thinsp;3.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePIT (\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003emm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14.28\u0026thinsp;\u0026plusmn;\u0026thinsp;4.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13.64\u0026thinsp;\u0026plusmn;\u0026thinsp;3.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.468\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePMT (\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;2\u003c/sup\u003emm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15.08\u0026thinsp;\u0026plusmn;\u0026thinsp;5.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12.60\u0026thinsp;\u0026plusmn;\u0026thinsp;3.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.004\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eData were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or n (%).\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eBMI\u0026thinsp;=\u0026thinsp;body mass index; CIMT\u0026thinsp;=\u0026thinsp;carotid intima-media thickness; CIT\u0026thinsp;=\u0026thinsp;carotid intima thickness; CMT\u0026thinsp;=\u0026thinsp;carotid media thickness; DBP\u0026thinsp;=\u0026thinsp;diastolic blood pressure; GLU\u0026thinsp;=\u0026thinsp;fasting glucose; HCY\u0026thinsp;=\u0026thinsp;homocysteine; HDL-C\u0026thinsp;=\u0026thinsp;high-density lipoprotein cholesterol; LDL-C\u0026thinsp;=\u0026thinsp;low-density lipoprotein cholesterol; PIT\u0026thinsp;=\u0026thinsp;podalic intima thickness; PMT\u0026thinsp;=\u0026thinsp;podalic media thickness; RIT\u0026thinsp;=\u0026thinsp;radial intima thickness; RMT\u0026thinsp;=\u0026thinsp;radial media thickness; SBP\u0026thinsp;=\u0026thinsp;systolic blood pressure; TC\u0026thinsp;=\u0026thinsp;total cholesterol; TG\u0026thinsp;=\u0026thinsp;triglyceride.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch3\u003eCorrelation between Hcy and arterial intima and media thickness in DM\u003c/h3\u003e\n\u003cp\u003eThere is a positive correlation between CIMT and Hcy in this study, which is in agreement with previous reports.\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e,\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e In addition, Hcy was found correlated with CIT, CMT, RMT, and PMT (correlation efficiency was 0.254, 0.266, 0.292 and 0.236, respectively, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 for all). (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSpearman correlation analysis between peripheral arterial intima-media thickness and Hcy\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"10\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCIT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCMT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCIMT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eRIT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eRMT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePIT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003ePMT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eHcy level\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSpearman correlation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.254\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.266\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.317\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.292\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e-0.018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.236\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ep-Value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.975\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.852\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e0.011\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"1\" nameend=\"c10\" namest=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"10\"\u003eCIT\u0026thinsp;=\u0026thinsp;carotid intima thickness; CMT\u0026thinsp;=\u0026thinsp;carotid media thickness; CIMT\u0026thinsp;=\u0026thinsp;carotid intima-media thickness; HCY\u0026thinsp;=\u0026thinsp;homocysteine; PIT\u0026thinsp;=\u0026thinsp;podalic intima thickness; PMT\u0026thinsp;=\u0026thinsp;podalic media thickness; RIT\u0026thinsp;=\u0026thinsp;radial intima thickness; RMT\u0026thinsp;=\u0026thinsp;radial media thickness.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eMultivariate linear regression analysis of risk factors for CIT\u003c/h2\u003e\u003cp\u003eThe multivariate linear regression analysis was performed to determine contributing factors for ultrasound parameters in DM. The results showed that age, SBP and Hcy were associated with CIT. (Tables\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultivariate linear regression analysis of variables in DM patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFactor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCIT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCMT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eRIT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRMT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePIT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003ePMT\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.002(0.001 to 0.003)*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.005(0.003 to 0.008)**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.001(0.000 to 0.002)*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.001(0.000 to 0.002)*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.001(0.000 to 0.002)**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.001(0.000 to 0.002)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.003(-0.039 to 0.032)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.042(-0.009 to 0.093)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.013(-0.036 to 0.010)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-0.002(-0.024 to 0.021)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.015(-0.003 to 0.033)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.012(-0.014 to 0.037)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003esmoking\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.006(-0.052 to 0.040)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.049(-0.016 to 0.115)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.001(-0.031 to 0.028)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.004(-0.025 to 0.033)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.015(-0.038 to 0.008)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.020(-0.012 to 0.053)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlcohol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.039(-0.007 to 0.086)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.054(-0.120 to 0.013)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.030(0.000 to 0.060)*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.014(-0.016 to 0.044)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.027(0.004 to 0.050)*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.010(-0.023 to 0.044)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.003(-0.001 to 0.006)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.004(-0.002 to 0.009)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.001(-0.001 to 0.004)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.002(0.000 to 0.005)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.000(-0.002 to 0.002)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.001(-0.002 to 0.003)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSBP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.002(0.000 to 0.003)*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.002(0.000 to 0.004)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.000(-0.001 to 0.001)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.001(0.000 to 0.002)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.000(-0.001 to 0.001)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.000(-0.001 to 0.002)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDBP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.003(-0.006 to 0.001)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.000(-0.004 to 0.004)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.000(-0.002 to 0.001)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000(-0.001 to 0.002)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.000(-0.001 to 0.002)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.000(-0.002 to 0.001)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStatins\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.008(-0.027 to 0.042)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.018(-0.067 to 0.032)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.007(-0.029 to 0.015)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000(-0.021 to 0.022)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.013(-0.030 to 0.004)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-0.002(-0.026 to 0.023)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAntihype-rtensives\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.020(-0.053 to 0.013)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.037(-0.085 to 0.010)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.020(-0.041 to 0.001)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000(-0.021 to 0.021)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.004(-0.012 to 0.021)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.009(-0.015 to 0.032)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlu\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.001(-0.003 to 0.005)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.004(-0.010 to 0.002)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.002(-0.004 to 0.001)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000(-0.003 to 0.003)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.002(-0.004 to 0.001)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.000(-0.003 to 0.003)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.001(-0.010 to 0.013)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.006(-0.011 to 0.023)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.000(-0.007 to 0.008)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-0.001(-0.008 to 0.007)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.003(-0.003 to 0.009)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-0.002(-0.011 to 0.006)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHcy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.005(0.001 to 0.009)*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-0.001(-0.007 to 0.004)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.001(-0.003 to 0.002)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000(-0.002 to 0.003)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.003(-0.005 to -0.001)*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.000(-0.003 to 0.003)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eData were expressed as regression coefficients (95% confidence interval). *P\u0026thinsp;\u0026lt;\u0026thinsp;0.05; **P\u0026thinsp;\u0026lt;\u0026thinsp;0.01\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eBMI\u0026thinsp;=\u0026thinsp;body mass index; CIT\u0026thinsp;=\u0026thinsp;carotid intima thickness; CMT\u0026thinsp;=\u0026thinsp;carotid media thickness; DBP\u0026thinsp;=\u0026thinsp;Diastolic blood pressure; GLU\u0026thinsp;=\u0026thinsp;fasting glucose; HCY\u0026thinsp;=\u0026thinsp;homocysteine; HDL-C\u0026thinsp;=\u0026thinsp;high-density lipoprotein cholesterol; PIT\u0026thinsp;=\u0026thinsp;podalic intima thickness; PMT\u0026thinsp;=\u0026thinsp;podalic media thickness; RIT\u0026thinsp;=\u0026thinsp;radial intima thickness; RMT\u0026thinsp;=\u0026thinsp;radial media thickness; SBP\u0026thinsp;=\u0026thinsp;systolic blood pressure; TG\u0026thinsp;=\u0026thinsp;triglyceride.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThere were several important findings in this study. First, intima layer was predominantly thickened in DM patients. Second, arterial media thickness was more involved in DM patients with macrovascular complications. Third, HCY was correlated with intima and media thickness in DM patients. Fourth, CIT was associated with traditional risk factors including age, systolic blood pressure and HCY.\u003c/p\u003e\u003cp\u003eThere is a wealth of evidence showing the relationship between the thickened CIMT and DM. CIMT was also an independent predictor of stroke, especially in stroke patients caused by cerebral ischemia, and predictor of stroke recurrence in diabetic population.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e However, whether intima or media layer was more involved remains unclear due to previous low-resolution ultrasound probe used in clinical routine practice, failing to distinguish the two layers separately. Some studies reported that there is a more active atherogenic process in DM patients, indicating intima layer might be more involved due to atherosclerosis.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e It is also reported that atherosclerosis serves as a common pathology in macrovessels and microvessels in DM patients with diabetic panvascular disease (DPD).\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e However, there are other study showing that tunica media to internal lumen ratio of small artery was increased in non-insulin-dependent diabetes mellitus, suggesting media thickness was involved.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e Moreover, vasculature changes of different arteries in DM patients were not reported in literature. In this study, we found CIT, RIT and PIT were substantially thicker in DM patients, all of which were greater than media thickness and intima-media thickness comparing to healthy population, indicating intima layer was more involved in DM patient and might be a novel vascular lesion for DM patients screening, irrespective of large-sized carotid or medium-sized radial and podalic artery.\u003c/p\u003e\u003cp\u003eBy comparing ultrasound parameters between DM patients with macrovascular complication subgroup and patients with non-macrovascular complication subgroup, it is noted that there was no difference between the two subgroups regarding RIT and PIT, the difference for CIT was statistically significant yet not remarkable, all the three parameters were thicker than control group irrespective of subgroup difference, indicating intima layers might be a novel vascular lesion for DM patients screening. By contrast, CMT, RMT and PMT were all substantially thicker in DM patients with macrovascular complications subgroup, suggesting media layer was more involved in the development of macrovascular complications and could be a promising differential tool for macrovascular complication prediction.\u003c/p\u003e\u003cp\u003eThe mechanisms of vascular injury induced by homocysteine include oxidative stress, DNA dysfunction, decreased availability of nitric oxide (NO), endothelial cytotoxicity, smooth muscle cell proliferation, enhanced platelet aggregation, impaired fibrinolytic system, increased leukocyte adhesion and induction of chronic inflammation. \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e These pathological changes are characterized by blood flow-mediated vasodilation damage, mainly due to the production of nitric oxide (NO) and the decrease of bioavailability.\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e Nitric oxide is the most effective endogenous vasodilator\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e and an atherosclerotic protective molecule.\u003csup\u003e\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e The imbalance of its synthesis can lead to and enhance oxidative stress and atherosclerosis. In this study, Hcy was found correlated with CIT, CMT, RMT, and PMT, as well as CIMT, which was in accordance with previous study. Multivariate linear regression analysis also revealed that CIT was associate with age, SBP and Hcy. To our surprise, neither serum level of fasting glucose nor TG was not associate with CIT. This might be due to optimal hypoglycemic treatment in DM patients according to current guidelines, fasting glucose was no longer a best biomarker reflecting severity of DM status. Unfortunately, interpretation of HbA1c was not applicable due to limited sample size. It was also reported that postprandial hypertriglyceridemia despite normal TG levels may be an independent risk factor for early atherosclerosis in type 2 diabetes,\u003csup\u003e\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e which should be analyzed in future study.\u003c/p\u003e\u003cp\u003eThere are several limitations in this study. First, the sample size for this study is relatively small, evading further analysis and more detailed subgroup classification. Second, this study is a cross-sectional study without follow up information, the predictive value for ultrasound parameters were not applicable. These deficiencies need a large-number multi-centered prospective studies to confirm the conclusions of this study.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eMeasurement of arterial intima and media thickness with high-resolution ultrasound might be a promising tool to reveal arterial pathological changes in DM patients and their subgroups.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e Mingjun Xu had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConcept and design:\u0026nbsp;\u003c/strong\u003eSuqin Jin, Mei Zhang, Xianghua Zhuang, Mingjun Xu and Zhaohong Xie\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcquisition, analysis, or interpretation of data:\u003c/strong\u003e Siyu Zhao, Xiaoyu Yue, Xiaoyu Wan, Mingjun Xu，Suqin Jin,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDrafting of the manuscript:\u0026nbsp;\u003c/strong\u003eSuqin Jin, Mingjun Xu, Siyu Zhao\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCritical revision of the manuscript for important intellectual content:\u003c/strong\u003e Mei Zhang, Mingjun Xu and Zhaohong Xie\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis:\u0026nbsp;\u003c/strong\u003eSiyu Zhao, Mingjun Xu\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy supervision:\u0026nbsp;\u003c/strong\u003eSuqin Jin, Mingjun Xu and Zhaohong Xie\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors have seen and approved the manuscript as submitted.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations of interest:\u0026nbsp;\u003c/strong\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish declaration:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis work was supported by grants from the Natural Science Foundation of Shandong Province (ZR2020QH122), Jinan clinical medical science and technology innovation program (201907056) and National Natural Science Foundation of China (No. 82001834).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThe study protocol was approved by the Ethics Committees of The Second Hospital of Shandong University and Shandong University Qilu Hospital and informed consents were obtained from all participants.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eFinkelstein JD, Martin JJ.Homocysteine. \u003cem\u003eInt J Biochem Cell Biol. \u003c/em\u003e2000;32(4):385-389.\u003c/li\u003e\n\u003cli\u003eLin T, Liu JC, Chang LY, et al.Association of C-reactive protein and homocysteine with subclinical coronary plaque subtype and stenosis using low-dose MDCT coronary angiography.\u003cem\u003e \u003c/em\u003e\u003cem\u003eAtherosclerosis. \u003c/em\u003e2010; 212(2):501-506.\u003c/li\u003e\n\u003cli\u003eRudy A, Kowalska I, Straczkowski M, et al. 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Small artery remodeling in diabetes mellitus. \u003cem\u003eNutr Metab Cardiovasc Dis\u003c/em\u003e. 2009;19(8):587-592.\u003c/li\u003e\n\u003cli\u003ePushpakumar S, Kundu S, Sen U. Endothelial dysfunction: the link between homocysteine and hydrogen sulfide.\u003cem\u003e \u003c/em\u003e\u003cem\u003eCurr Med Chem\u003c/em\u003e. 2014;21(32):3662-3672.\u003c/li\u003e\n\u003cli\u003eDavignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. \u003cem\u003eCirculation\u003c/em\u003e. 2004;109(23 Suppl 1):III27-III32.\u003c/li\u003e\n\u003cli\u003eBerenji Ardestani S, Eftedal I, Pedersen M, et al. Endothelial dysfunction in small arteries and early signs of atherosclerosis in ApoE knockout rats. \u003cem\u003eScientific reports\u003c/em\u003e. 2020;10(1):15296. \u003c/li\u003e\n\u003cli\u003eTeno S, Uto Y, Nagashima H, et al. Association of postprandial hypertriglyceridemia and carotid intima-media thickness in patients with type 2 diabetes. \u003cem\u003eDiabetes Care.\u003c/em\u003e 2000;23(9):1401-1406. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"intima thickness, media thickness, diabetes mellitus, complication, homocysteine","lastPublishedDoi":"10.21203/rs.3.rs-6806257/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6806257/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003ePathological changes of arterial vasculature plays a pivotal role in the development of macrovascular and microvascular complications of diabetes mellitus (DM). Compared to traditional carotid intima-media thickness (CIMT), separate measurement of arterial intima and media thickness by high-resolution ultrasound could reveal the vascular anatomical changes in such patients more precisely. Homocysteine (Hcy) is reported closely related to macrovascular and microvascular complications in DM patients. The purpose of this study was to explore intima and media thickness of carotid arteries, radial arteries and podalic arteries in DM patients with macrovascular or microvascular complications and to explore their diagnostic value for these patients as well as their relationship with Hcy.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA total of 123 DM patients and 102 healthy controls were enrolled in this study. Arterial ultrasound examination was performed using a 24-MHz probe (i24Lx8), and intima and media thickness of carotid arteries (CIT and CMT), radial arteries (RIT and RMT) and podalic arteries (PIT and PMT) were measured. Serum levels of fasting glucose, low-density lipoprotein cholesterol, Hcy, and clinical information were also collected.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eCIT, RIT and PIT were all substantially thicker in DM patients. CIT, CMT and CIMT were thicker in DM patients with macrovascular complications than those without macrovascular complications, as well as RMT and PMT. Additionally, there was a correlation between Hcy and CIT in DM patient (r\u0026thinsp;=\u0026thinsp;0.254, P\u0026thinsp;=\u0026thinsp;0.006). CIT was associated with traditional risk factors including age, systolic blood pressure and HCY.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eMeasurement of arterial intima and media thickness with high-resolution ultrasound might be a promising tool to reveal arterial pathological changes in DM patients and their subgroups.\u003c/p\u003e","manuscriptTitle":"Intima and media thickness of peripheral arteries measured by high-resolution ultrasound in Diabetes Mellitus patients with macrovascular or microvascular complications and their relationship with Homocysteine","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-08 06:20:53","doi":"10.21203/rs.3.rs-6806257/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-18T04:39:54+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-05T17:43:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"289049010132547770100786774243423058227","date":"2025-07-23T14:54:28+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-16T22:32:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"160243356122420208989361751128354941660","date":"2025-07-10T20:55:07+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"282915069659581905527374686533080283600","date":"2025-07-10T09:21:45+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-03T12:55:48+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-06-10T08:05:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-06-06T15:29:30+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-06-06T15:29:04+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Endocrine Disorders","date":"2025-06-03T02:41:12+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"373ade76-83f4-432c-a86d-b695c8dc6994","owner":[],"postedDate":"July 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-27T16:34:43+00:00","versionOfRecord":{"articleIdentity":"rs-6806257","link":"https://doi.org/10.1186/s12902-025-02064-2","journal":{"identity":"bmc-endocrine-disorders","isVorOnly":false,"title":"BMC Endocrine Disorders"},"publishedOn":"2025-10-22 16:17:15","publishedOnDateReadable":"October 22nd, 2025"},"versionCreatedAt":"2025-07-08 06:20:53","video":"","vorDoi":"10.1186/s12902-025-02064-2","vorDoiUrl":"https://doi.org/10.1186/s12902-025-02064-2","workflowStages":[]},"version":"v1","identity":"rs-6806257","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6806257","identity":"rs-6806257","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}