Introduction
Type 2 diabetes mellitus (T2DM) is a common clinical metabolic disease. The global diabetes prevalence in 20-79-year-olds in 2021 was estimated to be 10.5% (536.6 million people), with a predicted rise to 12.2% (783.2 million) by 2045 [1]. Diabetic neuropathy is the most common and troublesome complication of diabetes, affecting up to half of all patients with diabetes [2, 3], and it increases the risk of foot ulceration, amputation, cardiovascular dysfunction, myocardial infarction, and sudden death [2, 4]. Therefore, early recognition and appropriate management of neuropathy in patients with diabetes is important. However, the diagnosis of diabetic neuropathy at present is mainly based on clinical manifestations such as limb pain, numbness, paraesthesia, muscle weakness, and muscle atrophy, but half of the patients missed the diagnosis due to a lack of obvious symptoms [5, 6].
With the advancement of ultrasound technology and the improvement of resolution, high-frequency ultrasound (HFU) is safer and more targeted, allowing noninvasive examination of nerves in real-time. Several studies have shown that the peripheral nerve cross-sectional area (CSA) of diabetic peripheral neuropathy (DPN) patients is larger than that of the control group, which may help to detect neuropathy early and guide the diagnosis and treatment of DPN [7, 8]. Moreover, the increased CSA is positively correlated with the severity of diabetic neuropathy [9].
As the longest cranial nerve and an important part of the autonomic nerve, the vagus nerve has the widest distribution in the body and runs a superficial course in the neck, and its anatomical location and characteristic appearance is easily measured using HFU [10]. However, the HFU measurement of the vagus nerve in diabetes was very limited. The study showed that the CSA of the vagus nerve was significantly smaller in patients with diabetes compared with normal controls [11]. Autonomic neuropathies are commonly coexistent with DPN [12], both of which account for 90% of diabetic neuropathy [13]. Tahniyah et al. found that all patients with electrophysiologically diagnosed DPN had cardiac autonomic neuropathy [12]. The DCCT/EDIC study demonstrated that DPN and cardiovascular autonomic neuropathy had similar risk factors, such as older age, sustained albuminuria, longer duration, higher mean pulse rate, and b-blocker use [14].
Therefore, the present study investigated the characteristics of the cervical vagus nerve on HFU in patients with T2DM and DPN.
Material and methods
The study protocol was approved by the Ethics Committees of Nanjing Medical University Affiliated Wuxi People’s Hospital (ethical batch number: KY21068), and it was registered with the Chinese Clinical Trial Registry (ChiCTR2200065538). All participants provided written informed consent before study enrolment.
Participants
Healthy controls and patients with T2DM were from the physical examination centre and endocrinology department of Wuxi People’s Hospital, respectively. All patients met the 1999 World Health Organization diagnostic criteria for diabetes. According to the results of the nerve conduction study (NCS), the patients with T2DM were divided into those with non-diabetic peripheral neuropathy (NDPN group) and those with DPN (DPN group) based on abnormal nerve conduction velocity (NCV) (2 or more abnormal nerves) [15]. The exclusion criteria were: (1) pregnancy and lactation; (2) type 1 diabetes or other special types of diabetes; (3) acute complications of diabetes (diabetic ketoacidosis, non-ketotic hyperosmolar coma); (4) various nondiabetic neurological diseases, including vitamin B12 deficiency, cervical and lumbar spine diseases, cerebral infarction, chronic inflammatory demyelinating neuropathy, hereditary neuropathy, etc.; (5) a history of neurotoxic drugs (such as chemotherapy drugs); (6) heart failure, respiratory failure, severely impaired liver and kidney functions, acute metabolic disorders, and infectious fever; and (7) a history of neck injury or surgery, and scars that may influence the examination.
The inclusion criteria of healthy controls were as follows: age over 18 years, body mass index (BMI) between 18 and 28 kg/m2, fasting blood glucose (FBG) < 5.6 mmol/L, and no history of other diseases. The exclusion criteria were T2DM and the above exclusion criteria for patients with T2DM.
Collection of general data and biochemical indicators
The age, sex, weight, height, heart rate, systolic and diastolic blood pressure, smoking history, duration of diabetes, medication history, diabetes complications, and comorbidities of the participants were recorded. BMI was calculated as weight divided by the square of the height (kg/m2).
All subjects took a venous blood test in the morning after fasting for 8 hours. Glycosylated haemoglobin (HbA1c) was measured using a high-performance liquid chromatograph, triglyceride and total cholesterol were measured using the enzyme endpoint method, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were measured using the direct method, and FBG was measured using the hexokinase endpoint method. The detection instrument for the above indicators is the American Beckman Coulter AU5800 automatic biochemical analyser, and the kits were purchased from the American Beckman Coulter company. The detection method of fasting C-peptide (FCP) was electrochemiluminescence, and the detection instrument was a Roche cobas®8000 automatic biochemical immunoassay analyser; the kit was purchased from Roche.
The FBG and FCP were used to calculate homeostasis model assessment 2 estimates of insulin resistance (HOMA2-IR) and homeostasis model assessment 2 estimates of b-cell function (HOMA2-B) with the HOMA2 calculator (Website: http://www.dtu.ox.ac.uk/homa). Eight patients (DPN = 4, NDPN = 4) with values beyond the defined range of HOMA2 calculators were removed. Islet b-cell function was evaluated using the C-peptide index, which was calculated by the formula: FCP (ng/mL) × 100 / [FBG (mmol/L) × 18] [16].
Electrodiagnostic examinations
NCS was performed for all patients with T2DM using an electromyography/evoked potential instrument (Alpine bioMed ApS, Danish, represented by Shanghai Bendi Medical Equipment Co. Ltd.) on both lower and upper extremities. This test was done on the skin surface with a temperature of 32–34°C and in a room at 20–25℃. Each sensory NCS was performed for the median nerve, ulnar nerve, and superficial peroneal nerve. Motor NCS was performed for the median nerve, ulnar nerve, and common peroneal nerve. NCS was evaluated using 5 parameters: latency, amplitude, time limit, conduction distance, and conduction velocity in the patients.
Measurement instruments
All subjects completed the Survey of Autonomic Symptoms (SAS) and the 31-item Composite Autonomic Symptom Score (COMPASS 31) independently in a quiet environment to assess autonomic symptoms, and those who were unable to complete them independently due to the their educational level were questioned by the same physician.
SAS is an important scale for the assessment of early diabetic autonomic neuropathy, involving the following autonomic symptom domains: gastrointestinal, urinary, orthostatic, sudomotor, vasomotor, and sexual dysfunction [17]. This survey consists of 11 questions for women and 12 for men, and each item is rated by an impact score ranging from 1 (least severe) to 5 (most severe). Thus, the total number of symptoms reported was 0 to 11 for women and 0 to 12 for men, and the total score ranged from 0 to 55 points for women and 0 to 60 points for men.
COMPASS 31 is a simplified and validated version of the original COMPASS scale (164 items) that quantifies symptom severity in 6 domains of autonomic nerves, with a total of 31 questions [18]. It comprises 6 different domains including orthostatic intolerance (4 items), vasomotor dysfunction (3 items), secretomotor dysfunction (4 items), gastrointestinal dysfunction (12 items), bladder dysfunction (3 items), and pupillomotor dysfunction (5 items). The scores in each domain are weighted and summed to obtain an autonomic symptom score ranging from 0 to 100. The higher the scores, the more severe the autonomic symptoms.
Ultrasonographic studies
HFU tests were performed via nerve tracing with a high-resolution linear transducer (4–15 MHz, L12-5, Philips IU Elite, Netherlands). Participants were placed in a supine position with the head slightly extended and then rotated to the opposite side of the scan. In most cases, the vagus nerve was located in the carotid sheath, antero-laterally to the common carotid artery, and dorsally to the internal jugular vein [19]. The probe was placed at the thyroid gland level where the vagus nerve could clearly be differentiated [20]. Each nerve was studied in a position where it had a nearly elliptic cross-sectional shape, by the same sonographer, holding the transducer in an axial position. Then the long diameter a and the short diameter b (perpendicular to a) were measured separately, and the ellipse area formula was used to calculate the CSA of vagus nerve = a×b×π/4. The vagus nerve consists of several hypoechoic fascicles surrounded by hyperechoic epineurial tissue, giving the nerve a honeycomb appearance. The study finally observed and recorded whether the characteristic structure was visible in HFU. The image and data acquisition process were completed by the same experienced professional sonographer, who was blinded to the grouping of the subjects.
Statistical analysis
Sample size calculation: according to the preliminary test, the average CSA of the vagus nerve in 20 patients with T2DM was 1.45 mm2, and the average area of 20 healthy controls was 1.81 mm2, with a standard deviation of 0.5 mm2. In the PASS 15.0 sample size calculation software, the 2 independent samples t-test calculation module in the mean was selected, the test level a was taken as 0.05, and the test power was taken as 90% to calculate the sample size, and at least 42 subjects were required for each of the 2 groups.
SPSS 25.0 statistical software was used for data analysis. The Shapiro-Wilk test was used to test the normality of the measurement data, and those with normal distribution were expressed as the mean ± standard deviation; the independent samples t-test was used for comparison between the 2 groups. Those without normal distribution were expressed as the median (quartile), and the independent-sample Mann-Whitney U-test was used for comparison between the 2 groups. Enumeration data were expressed by frequency (proportion) [n (%)], and the c2 test was used. Binary logistic regression analysis identified the influencing factors of patients with DPN, and the receiver operating characteristic (ROC) curve was drawn to calculate the area under the curve (AUC) to analyse the possibility of evaluating the vagus nerve ultrasound measurement parameters as predictors of DPN. Pearson test was used for normally distributed data, and Spearman test was used for non-normally distributed data, to analyse the correlation between ultrasound measurement parameters and general clinical indicators, electromyography conduction velocity, SAS, and COMPASS 31 scales. p < 0.05 was regarded as a statistically significant difference.
Results
Comparison between the T2DM group and the healthy control group
A total of 87 patients with T2DM and 43 healthy controls were finally included in this study according to the calculation results of the aforementioned sample size. It is worth mentioning that after 43 NDPN patients were enrolled, 44 DPN patients were included as the intergroup control according to age and gender matching. The comparison of clinical indicators between the 2 groups are presented in Table 1. In patients with T2DM, age, weight, BMI, FBG, and triglyceride levels were higher than in controls. The comparison of vagus nerve ultrasound measurement indexes between the 2 groups is shown in Table 2. The honeycomb structure in patients with T2DM decreased (51.2% vs. 18.4%, p < 0.001, after adjustment for age, p < 0.001). Typical ultrasound images of the right vagus nerve in healthy controls and T2DM groups are shown in Figure 1. Healthy people (Fig. 1A) have a typical honeycomb structure, but no honeycomb structure was observed in patients with T2DM (Fig. 1B).
|
|
Control (n = 43) |
T2DM (n = 87) |
p-value |
|
Age [years] |
45 (34,48) |
50 (40,57) |
0.001 |
|
Gender [men/women] |
17/26 |
48/39 |
0.093 |
|
Height [cm] |
164.9 ± 7.9 |
165.5 ± 8.0 |
0.716 |
|
Weight [kg] |
62.9 ± 10.5 |
70.7 ± 12.3 |
< 0.001 |
|
BMI [kg/m2] |
23.06 ± 2.76 |
25.73 ± 3.45 |
< 0.001 |
|
Smoking history |
19 (44.2) |
31 (35.6) |
0.346 |
|
FBG [mmol/L] |
4.82 (4.55,5.17) |
7.72 (6.32,9.87) |
< 0.001 |
|
Triglycerides [mmol/L] |
1.02 (0.71,1.41) |
1.78 (1.13,2.56) |
< 0.001 |
|
Total cholesterol [mmol/L] |
4.55 (4.38,4.92) |
4.70 (3.86,5.84) |
0.902 |
|
High-density lipoprotein [mmol/L] |
1.38 ± 0.30 |
0.96 ± 0.21 |
< 0.001 |
|
Low-density lipoprotein [mmol/L] |
2.77 (2.35,3.09) |
2.67 (2.02,3.47) |
0.670 |
|
|
Control (n = 43) |
T2DM (n = 87) |
p-value |
p-valuea |
|
Left long diameter [mm] |
1.60 ± 0.23 |
1.59 ± 0.32 |
0.919 |
0.646 |
|
Right long diameter [mm] |
1.68 ± 0.30 |
1.72 ± 0.33 |
0.510 |
0.549 |
|
Left short diameter [mm] |
1.20 ± 0.20 |
1.20 ± 0.24 |
0.997 |
0.940 |
|
right short diameter [mm] |
1.29 ± 0.21 |
1.31 ± 0.24 |
0.723 |
0.960 |
|
Left CSA [mm2] |
1.50 ± 0.32 |
1.53 ± 0.51 |
0.747 |
0.993 |
|
Right CSA [mm2] |
1.73 ± 0.51 |
1.80 ± 0.58 |
0.515 |
0.730 |
|
Honeycomb structure(n/%) |
22 / 51.2 |
16 / 18.4 |
< 0.001 |
< 0.001 |
Comparison of the DPN group and the NDPN group
According to the NCS examination results, among the 87 patients with T2DM, 43 were not combined with DPN (NDPN group), and 44 were combined with DPN (DPN group). The comparison of clinical indicators between the 2 groups is shown in Table 3. The duration of diabetes in the DPN group was longer than that in the NDPN group (p = 0.002). The comparison of vagus nerve ultrasound measurement indexes between the NDPN group and the DPN group is shown in Table 4. The right long diameter (1.63 ± 0.28 vs. 1.81 ± 0.34, p = 0.008), short diameter (1.22 ± 0.23 vs. 1.39 ± 0.22, p = 0.001), and CSA (1.60 ± 0.52 vs. 2.00 ± 0.57, p = 0.001) of the DPN group were larger than those of the NDPN group. Typical ultrasound images of the right vagus nerve in patients with NDPN and DPN are shown in Figure 1. The vagus nerve cross-sectional area was smaller in NDPN patients (Fig. 1B) than in DPN patients (Fig. 1C), and no honeycomb structure was observed.
|
|
NDPN (n = 43) |
DPN (n = 44) |
p-value |
|
Age [years] |
47 (39,54) |
52 (43,57) |
0.090 |
|
Gender [men/women] |
23/20 |
25/19 |
0.755 |
|
Height [cm] |
164.2 ± 8.0 |
166.7 ± 7.9 |
0.149 |
|
Weight [kg] |
71.2 ± 12.3 |
70.3 ± 12.5 |
0.719 |
|
BMI [kg/m2] |
26.34 ± 3.72 |
25.13 ± 3.08 |
0.103 |
|
DM duration [year] |
1.0 (0.0,4.8) |
6.7 (1.0,15.3) |
0.002 |
|
Smoking history [n/%] |
16 (37.2) |
15 (34.1) |
0.761 |
|
Hypertension [n/%] |
15 (34.9) |
22 (50.0) |
0.154 |
|
Diabetic retinopathy [n/%] |
15 (34.9) |
23 (52.3) |
0.102 |
|
Diabetic nephropathy [n/%] |
17 (39.5) |
19 (43.2) |
0.730 |
|
Atherosclerosis [n/%] |
23 (53.5) |
24 (54.5) |
0.922 |
|
Insulin therapy [n/%] |
17 (39.5) |
25 (56.8) |
0.107 |
|
Metformin treatment [n/%] |
27 (62.8) |
30 (68.2) |
0.597 |
|
Glycated haemoglobin (%) |
9.88 ± 2.10 |
9.87 ± 1.93 |
0.986 |
|
FBG [mmol/L] |
7.72 (6.67,9.04) |
7.70 (5.94,11.05) |
0.410 |
|
FCP [ng/mL] |
1.97 ± 1.11 |
1.81 ± 0.91 |
0.467 |
|
HOMA2-IR |
1.83 ± 0.91 |
1.78 ± 0.80 |
0.776 |
|
HOMA2-b |
55.60 (38.60,70.00) |
45.95 (27.28,66.53) |
0.171 |
|
C-peptide index |
1.49 (0.78,1.80) |
1.11 (0.74,1.55) |
0.112 |
|
Triglycerides [mmol/L] |
1.65 (1.11,2.32) |
1.92 (1.34,2.67) |
0.188 |
|
Total cholesterol [mmol/L] |
4.80 ± 1.20 |
4.94 ± 1.44 |
0.635 |
|
High-density lipoprotein [mmol/L] |
0.97 (0.85,1.06) |
0.91 (0.77,1.12) |
0.393 |
|
Low-density lipoprotein [mmol/L] |
2.76 ± 0.91 |
2.79 ± 1.11 |
0.903 |
|
|
NDPN (n = 43) |
DPN (n = 44) |
p-value |
p-valuea |
|
Left long diameter [mm] |
1.53 ± 0.34 |
1.65 ± 0.29 |
0.076 |
0.140 |
|
Right long diameter [mm] |
1.63 ± 0.28 |
1.81 ± 0.34 |
0.008 |
0.043 |
|
Left short diameter [mm] |
1.15 ± 0.23 |
1.24 ± 0.24 |
0.094 |
0.195 |
|
Right short diameter[mm] |
1.22 ± 0.23 |
1.39 ± 0.22 |
0.001 |
0.008 |
|
Left CSA [mm2] |
1.42 ± 0.53 |
1.62 ± 0.48 |
0.070 |
0.163 |
|
Right CSA [mm2] |
1.60 ± 0.52 |
2.00 ± 0.57 |
0.001 |
0.009 |
|
Honeycomb structure [n/%] |
7 / 16.3 |
9 / 20.5 |
0.615 |
0.794 |
Regression analysis
Taking DPN or not as the dependent variable and the duration of diabetes, the long diameter, short diameter, and CSA of the right vagus nerve as independent variables, a stepwise binary logistic regression analysis was performed. The results showed that among the parameters measured by HFU, the CSA of the right vagus nerve (OR = 3.924, p = 0.002) was an independent risk factor for DPN. The possibility of right vagus nerve CSA as a predictor of DPN was assessed by ROC curve analysis (Fig. 2A). The results showed that AUC = 0.712 (95% CI: 0.602–0.822, p = 0.001), the best cut-off value was 1.71 mm2, the sensitivity was 72.7%, and the specificity was 69.8%.
Correlation analysis of vagus nerve ultrasound measurement parameters and other variables
The correlation analysis between the CSA of the right vagus nerve and clinical indicators in patients with T2DM showed that the right CSA was positively correlated with diabetes duration (r = 0.317, p = 0.003), and negatively correlated with C-peptide index (r = –0.236, p = 0.029). There was no correlation in the CSA with other clinical indicators including age, gender, height, weight, BMI, heart rate, systolic blood pressure, diastolic blood pressure, HbA1c, FBG, FCP, HOMA2-IR, HOMA2-b, and lipid levels.
Electromyography conduction velocity reflects the function of peripheral nerves. The correlation analysis between the CSA of the right vagus nerve in patients with T2DM and the conduction velocity of the right related nerve in electromyography is shown in Figure 2B-F. The CSA of the right vagus nerve was negatively correlated with the conduction velocities of the ulnar, median, and common peroneal nerves. Among them, the correlation with median nerve motor conduction velocity was the largest (r = –0.425, p < 0.001).
The correlations between vagus nerve ultrasound measurement parameters with SAS and COMPASS 31 scales are shown in Table 5. There was no correlation between the long diameter, short diameter, and CSA of the vagus nerve with the number of symptoms, the total score of SAS, and COMPASS 31.
|
|
SAS |
COMPASS 31 |
||||
|
Total score |
Number of symptoms |
Total score |
||||
|
r |
p-value |
r |
p-value |
r |
p-value |
|
|
Left long diameter [mm] |
-0.050 |
0.576 |
0.035 |
0.694 |
0.025 |
0.782 |
|
Right long diameter [mm] |
0.062 |
0.490 |
0.087 |
0.329 |
0.059 |
0.511 |
|
Left short diameter [mm] |
0.000 |
0.999 |
0.026 |
0.768 |
0.029 |
0.744 |
|
right short diameter [mm] |
0.074 |
0.407 |
0.08 |
0.372 |
0.000 |
0.999 |
Discussion
The present study found impairment of the honeycomb structure of the cervical vagus nerve in patients with T2DM using HFU assessment. Moreover, we think that our study investigated the characteristics of cervical vagus nerve with HFU in patients with DPN for the first time. The results showed that the right vagus nerve CSA was negatively correlated with the conduction velocity of the peripheral nerves and may become a predictive factor of DPN.
In previous ultrasound studies of the vagus nerve, the parameters commonly used are the CSA and the 2 vertical diameters on the cross-section [19]. Our study firstly observed the absence of honeycomb structure in the vagus nerve of patients with T2DM, which was in accordance with the changes of peripheral nerves in these patients [21]. The honeycomb structure usually reflects the inner membrane of the nerve fibre bundle. The destruction of the honeycomb structure in patients with T2DM in our study may be due to the hyperglycaemia in these patients. The hyperglycaemic state affects membrane structures, resulting in reduced blood supply to the nerves, lack of oxygen, and swelling, disintegration, and demyelination of nerve cells [22].
Tawfik et al. found that the CSA of the vagus nerve in patients with diabetes was smaller than that of controls [11], which was not observed in the present study. One reason may be the different measurement positions of the vagus nerve: Tawfik et al. captured the nerve at the level of thyroid cartilage while we chose the thyroid gland level because of the least statistical heterogeneity at the thyroid gland level [20]. Therefore, the CSA of normal controls was lower than that in the study of Tawfik et al., which has been reported in previous studies [20, 23]. On the other hand, the study of Tawfik et al. recruited 7 patients with type 1 diabetes, which may also affect the results.
Although the change of vagus nerve CSA in patients with DPN has never been reported (as we are aware), the changes in vagus nerve CSA in patients with DPN in our study were consistent with previous studies on peripheral nerves: the CSAs of the ulnar nerve, median nerve, common peroneal nerve, tibial nerve, and sural nerves were significantly larger in the DPN group and significantly correlated with electrophysiological findings [7, 8, 24–26]. Therefore, our study demonstrated that in patients with DPN, the structural damage of peripherals and vagus nerves is synchronized. The possible explanation is that the conversion of glucose to sorbitol mediated by aldose reductase increases, which leads to an increase in nerve water content [27], which is manifested as a thickening of nerves under ultrasound. However, the aetiology and pathogenesis of diabetic neuropathy have not been fully elucidated.
In the present study, the right vagus nerve CSA mainly correlated with the duration of diabetes and C-peptide index. Long duration of diabetes has been demonstrated as a risk factor of DPN and autonomic neuropathy [14]. The C-peptide index reflected the b-cell function [16]. DPN is more popular in patients with insulin deficiency than in patients with insulin resistance [28] due to the increased glycaemic variability [29] and the high risk of hypoglycaemia [30]. Previous studies have also demonstrated that the vagus nerve plays an important role in the insulin secretion of b-cells [31, 32], and impairment of the vagus nerve may decrease b-cell function in patients with diabetic neuropathy.
The present study showed that the right vagus nerve CSA was positively correlated with the diagnosis of DPN, while the left side was not meaningful. This may be related to the asymmetry of the vagus nerve innervating the abdominal organs. The right vagus nerve mainly sends branches to the small intestine and the colon, while the left side dominantly innervates the stomach, the liver, and the upper part of the duodenum [33]. Several studies have also compared bilateral vagus nerves and found that the right CSA is larger than the left CSA of vagus [11, 34, 35]. As the results of the ROC analysis, the sensitivity and specificity of the cut-off value of 1.71 mm2 for the right vagus nerve CSA were 72.7% and 69.8%, respectively, which was similar to the studies using several peripheral nerves [7], but testing just one vagus nerve is more convenient and easier than testing multiple peripheral nerves. On the other hand, whether the combination of vagus and peripheral nerve assessment using HFU will further increase the specificity and sensitivity of the diagnosis of DPN deserves further investigation.
Consistent with previous studies, there were no significant differences in vagus nerve CSA between patients with and without autonomic symptoms [11, 36]. In addition, CSA was not correlated with the number of autonomic symptoms or the SAS impact score. The result was similar to that of a study of Parkinson’s patients using the SCOPA-AUT questionnaire to assess autonomic symptoms [37]. Changes in vagus nerve ultrasound characteristics may occur earlier than the onset of autonomic symptoms. The relationship between vagus nerve CSA and the assessment of early stages of autonomic neuropathy, such as heart rate variability, should be further investigated. A limitation of our study was the availability of objective measures of autonomic function. The assessment of autonomic symptoms using the SAS and COMPASS 31 may not reflect early autonomic neuropathy, and the relationship between the vagus nerve CSA and autonomic neuropathy in the present study was incomplete. The present study also lacked data on the vagus nerve tested at other levels, such as the carotid sinus and thyroid cartilage. The effectiveness of vagus nerve assessment at different levels in predicting DPN needs to be further evaluated.
Conclusions
HFU represents a convenient and noninvasive examination. This new technique leads to the expansion of neuroimaging in patients with diabetes, which can help us further understand the damage of nerves caused by diabetes in vivo. HFU shows a loss of honeycomb structure of the vagus nerve in T2DM patients and an increase of vagus nerve CSA in DPN patients. Although the damage to peripherals and vagus nerves seems similar in patients with DPN, symptoms of autonomic neuropathy appear later than those of peripheral neuropathy. Therefore, cervical vagus nerve HFU may be a useful tool to assist in the diagnosis of DPN and early screening of autonomic neuropathy.
Acknowledgements
We thank the staff from the Electromyogram Room of the Department of Neurology, the Affiliated Wuxi People’s Hospital of Nanjing Medical University, for their help.
Authorship confirmation/Contribution statement
L.X.: Conceptualization (equal); Funding acquisition (lead); Methodology (equal); Supervision (lead). X.J.: Conceptualization (equal); Investigation (equal). F.X.: Data curation (equal); Formal analysis (equal); Investigation (equal); Methodology (equal); Visualization (equal); Writing — original draft (equal). Q.W.: Data curation (equal); Investigation (equal); Visualization (equal); Writing — original draft (equal). Y.H.: Formal analysis(equal); Project administration (lead); Writing — review & editing (lead). L.L., Q.J., Y.H. and S.Y.: Writing — review & editing (supporting).
Conflict of interests
There are no conflicts of interest to declare.
Funding statement
This work was funded by the General project of Wuxi science and Technology Bureau, China (N20202006) and the scientific research project of Wuxi Municipal Health Commission (M202011).
Ethics statement
This study protocol was reviewed and approved by the Ethics Committee of Wuxi People’s Hospital (ethical batch number: KY21068). The patients/participants provided written informed consent to participate in this study. Written informed consent was obtained from the individual to publish any potentially identifiable images or data contained in this article.
Data sharing
Data supporting the findings of this study are available from the corresponding author (LX) upon reasonable request.
