ABSTRACT
Background
Diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN) are common complications of type 2 diabetes mellitus (T2DM). Although nerve conduction studies (NCS) and sympathetic skin response (SSR) can detect DPN, the more sensitive method for early diagnosis remains unclear. Furthermore, whether DPN can be used as a predictor for diabetic nephropathy needs clarification.
Methods
We evaluated nerve conduction studies, sympathetic skin response, and the diabetic nephropathy indicator microalbuminuria (MAU) in 192 patients with type 2 diabetes mellitus and 50 healthy controls.
Results
Patients with type 2 diabetes mellitus showed a lower sensory nerve conduction velocity (SCV), sensory active nerve potential (SNAP), motor nerve conduction velocity (MCV), and compound motor action potential (CMAP) than the controls on NCS. Abnormal rates for nerve conduction studies and sympathetic skin response were 75.0% and 83.3%, respectively, in patients with type 2 diabetes mellitus. Interestingly, 54.2% of patients with normal nerve conduction studies had an abnormal sympathetic skin response. Moreover, we found a positive correlation between sympathetic skin response and microalbuminuria for the first time. The abnormal rate of microalbuminuria was 53.8%, lower than that of abnormal nerve conduction studies or sympathetic skin response patients.
Conclusion
Sympathetic skin response is a more sensitive method than nerve conduction studies for the early diagnosis of diabetic peripheral neuropathy. Abnormal sympathetic skin response might serve as an indicator for early diabetic nephropathy. Additionally, diabetic peripheral neuropathy may occur earlier than diabetic nephropathy in the development of type 2 diabetes mellitus.
Keywords: Diabetic nephropathy, Diabetic peripheral neuropathy, Microalbuminuria, Nerve conduction studies, Sympathetic skin response
INTRODUCTION
Diabetes mellitus (DM) is a prevalent global epidemic, affecting over 450 million individuals worldwide 1 . Peripheral neuropathy, with or without diabetes, is a common disorder affecting more than 8% of the general population 2 . Diabetic peripheral neuropathy (DPN) is the most frequent complication of diabetes, particularly in pre‐diabetes and type 2 diabetes mellitus (T2DM) 3 . Diabetic peripheral neuropathy is a sensory neuropathy that presents with positive sensory symptoms such as pain, tingling, and paresthesia in the feet, as well as negative symptoms such as numbness. In later stages, motor nerves may also be affected, leading to distal weakness in the toes, ankles, and legs 3 , 4 . Diabetic peripheral neuropathy is recognized as the leading cause of morbidity and disability among diabetic patients, with approximately half of all diabetic patients experiencing diabetic peripheral neuropathy at some point in their lives 3 , 5 .
Nerve conduction studies (NCS) are used widely to assess neuronal function in clinical settings 6 , 7 . Specifically, nerve conduction studies can measure sensory nerve conduction velocity (SCV) and sensory active nerve potential (SNAP), as well as motor nerve conduction velocity (MCV) and compound motor action potential (CMAP), making it a useful tool for evaluating the severity of diabetic peripheral neuropathy 8 , 9 . Another diagnostic test, the sympathetic skin response (SSR), measures the electrical activity of the skin after electrical stimulation and is also useful in assessing diabetic peripheral neuropathy 10 , 11 . However, it remains unclear which diagnostic test is more sensitive in detecting early diabetic peripheral neuropathy, even though limited studies have suggested that the sympathetic skin response may be more sensitive than nerve conduction studies in small populations 11 , 12 , 13 . Therefore, the purpose of this study is to determine if sympathetic skin response is more sensitive in detecting early diabetic peripheral neuropathy by analyzing a larger population.
Diabetes is associated with numerous severe complications 14 . Diabetic nephropathy (DN), another prevalent complication of diabetes, is a leading cause of death among patients with diabetes 15 , 16 , 17 . Diabetic nephropathy and diabetic peripheral neuropathy are two common microvascular complications of diabetes 18 . Previous research has indicated that diabetic nephropathy and diabetic peripheral neuropathy share common risk factors and pathogenic mechanisms 19 , 20 , implying a correlation between the two conditions. These findings suggest that the indicators of diabetic peripheral neuropathy could potentially serve as early warning signs for diabetic nephropathy. Therefore, the aim of this study was to investigate which diagnostic test (NCS or SSR) is more sensitive in detecting diabetic peripheral neuropathy, and to explore whether sympathetic skin response could serve as a novel warning indicator for early diabetic nephropathy.
METHODS
Participants
Following the China guideline for type 2 diabetes (2017), 192 patients with type 2 diabetes mellitus aged 28–90, excluding those with kidney disease, drug or heavy metal poisoning, tumor, acute peripheral neuropathy, hypothyroidism, vitamin B12 deficiency, connective tissue disease, severe cardiovascular disease, liver and kidney disease, limb swelling or injury, pacemakers or intolerance to electrical stimulation pain were recruited. The diagnostic criteria for type 2 diabetes mellitus were listed as follows: (1) the typical symptoms of diabetes (including polyuria, polydipsia, polyphagia, and weight loss) plus random plasma glucose ≥11.1 mmol/L; (2) no typical symptoms of diabetes plus fasting plasma glucose (FPG) ≥ 7.0 mmol/L; (3) no typical symptoms of diabetes plus oral glucose tolerance test (OGTT) 2 h plasma glucose (2hPG) ≥ 11.1 mmol/L. The control group consisted of 50 healthy subjects aged 37–80, and their baseline characteristics are shown in Table 1. Written informed consent was obtained from all participants, and the study was conducted in accordance with ethical standards.
Table 1.
Baseline characteristics of subjects
| Characteristics | Control | T2DM |
|---|---|---|
| Number (Men/Women) | 20/30 | 93/99 |
| Age (year) | 62.1 ± 11.6 | 63.9 ± 12.2 |
| Ethnic group | Han | Han |
| Duration of diabetes (year) | / | 9.7 ± 7.3 |
Nerve conduction studies were performed on the median nerve, ulnar nerve, medial plantar nerve, superficial peroneal nerve, and sural nerve of SCV and SNAP. Nerve conduction studies were also performed in the median nerve, ulnar nerve, posterior tibial nerve, and peroneal nerve of motor nerve conduction velocity and CMAP using Synergy Mobile (Oxford, UK) in a quiet room at 25°C. Diabetic peripheral neuropathy was defined when the nerve conduction velocity (NCV) or amplitude of at least two different nerves showed abnormal results, combined with at least two of the following criteria: (a) lower extremity neurological symptoms, (b) bilaterally ankle reflex weakening, (c) bilateral medial malleolus vibration feeling 21 .
Synergy Mobile (Oxford, UK) was used to identify the sympathetic skin response in a quiet room at 25°C using a disc electrode with a diameter of 10 mm on the palmar and dorsal sides of hands and feet. Diabetic peripheral neuropathy was defined when the latency or amplitude of at least one limb was abnormal, combined with clinical examinations for sensory, numbness, pain, burning sensations, and atrophy.
Microalbuminuria (MAU) was identified as an early indicator of kidney disease using the 24 h microalbuminuria method 22 , 23 . Urine samples were collected within 24 h and submitted for analysis 22 , 23 . Microalbuminuria was determined by pyrogallol red molybdate complex method, with the normal reference value of 24 h microalbuminuria being 0–150 mg 22 , 23 .
Statistical analysis
Statistical analyses were conducted using SPSS 22.0 (IBM, USA). Continuous variables were expressed as mean ± SD, and differences among groups were tested using the Tukey multiple comparison test in anova. The classification data were analyzed by Kendall's tau‐b test, and a value of P <0.05 was considered significant. For continuous variables, the results were expressed as mean ± SD. Tukey multiple comparison test in anova was used to test the differences among groups. The classification data were analyzed by Kendall's tau‐b test. SPSS 22.0 (IBM, USA) was used for statistical analysis. A value of P < 0.05 was significant.
RESULTS
Comparison of NCS between T2DM group and control group
For nerve conduction studies, sensory nerve conduction was evaluated and compared between the type 2 diabetes mellitus group and the control group. The results showed that the SNAP and SCV were 0 μV in some nerves of patients with type 2 diabetes mellitus, including median nerve (wrist‐digit III), ulnar nerve, medial plantar nerve, superficial peroneal nerve, and sural nerve (Table 2). The incidence of abnormal SNAP and SCV was higher in patients with type 2 diabetes mellitus compared with healthy controls (Table 2), indicating that type 2 diabetes mellitus can cause damage to sensory nerve conduction. Furthermore, the damage to the medial plantar nerve and superficial peroneal nerve was found to be more severe than that of the sural nerve (Table 3).
Table 2.
Comparison of SNAP and SCV between control group and type 2 diabetes mellitus group
| Normal value | Control | T2DM | P value | |
|---|---|---|---|---|
| SNAP at median nerve (Digit I) (μV) | >17 | 23.0 ± 9.7 | 12.7 ± 7.8 | <0.0001 |
| SNAP at median nerve (Digit III) (μV) | >8 | 19.7 ± 8.7 | 10.3 ± 7.4 (6 not evoked) | <0.0001 |
| SNAP at ulnar nerve (μV) | >7 | 13.1 ± 5.0 | 8.35 ± 5.0 (3 not evoked) | <0.0001 |
| SNAP at medial plantar nerve (μV) | >0.5 | 1.7 ± 0.96 | 1.29 ± 0.9 (99 not evoked) | 0.0377 |
| SNAP at superficial peroneal nerve (μV) |
>0.7 (Male) >1.2 (Female) |
2.9 ± 1.6 | 2.3 ± 1.5 (113 not evoked) | 0.0851 |
| SNAP at sural nerve (μV) | >6 | 21.8 ± 9.5 | 14.1 ± 7.9 (28 not evoked) | <0.0001 |
| SCV at median nerve (Digit I) (ms) | >45 | 49.1 ± 5.58 | 40.8 ± 8.2 | <0.0001 |
| SCV at median nerve (Digit III) (ms) | >45 | 52.0 ± 5.5 | 42.6 ± 8.3 (6 missing value) | <0.0001 |
| SCV at ulnar nerve (ms) | >45 | 53.3 ± 5.8 | 47.0 ± 9.1 (3 missing value) | <0.0001 |
| SCV at medial plantar nerve (ms) | >36 | 43.4 ± 4.8 | 40.0 ± 4.9 (99 missing value) | 0.7147 |
| SCV at superficial peroneal nerve (ms) | >40 | 53.7 ± 10.1 | 50.6 ± 5.6 (113 missing value) | 0.0336 |
| SCV at sural nerve (ms) | >40 | 60.1 ± 7.3 | 50.8 ± 7.9 (28 missing value) | <0.0001 |
Table 3.
Rate of patients with abnormal SNAP and SCV at medial plantar nerve, superficial peroneal nerve, and sural nerve
| Cases | Rate (%) | |
|---|---|---|
| SNAP at medial plantar nerve | 124 | 64.6 |
| SNAP at superficial peroneal nerve | 144 | 75.0 |
| SNAP at sural nerve | 109 | 56.8 |
| SCV at medial plantar nerve | 144 | 75.0 |
| SCV at superficial peroneal nerve | 124 | 64.6 |
| SCV at sural nerve | 130 | 67.7 |
Motor nerve conduction was also evaluated, and the results showed that CMAP was not evoked and MCV was a missing value in some nerves of patients with type 2 diabetes mellitus, including the posterior tibial nerve and peroneal nerve (Table 4). Among patients with type 2 diabetes mellitus with CMAP present, the CMAP was lower than that of healthy controls, indicating that type 2 diabetes mellitus can also cause damage to motor nerve conduction (Table 4).
Table 4.
Comparison of CMAP and MCV between control group and type 2 diabetes mellitus group
| Normal value | Control | T2DM | P value | |
|---|---|---|---|---|
| CMAP at median nerve (mV) | ≥7 | 10.4 ± 2.4 | 9.1 ± 4.1 | 0.0284 |
| CMAP at ulnar nerve (mV) | ≥7 | 10.0 ± 2.1 | 8.9 ± 1.8 | 0.0001 |
| CMAP at posterior tibial nerve (mV) | ≥4 | 15.2 ± 4.2 | 11.1 ± 5.1 (2 not evoked) | <0.0001 |
| CMAP at peroneal nerve (mV) |
≥3.6 (Male) ≥3 (Female) |
5.8 ± 1.5 | 4.2 ± 1.9 (6 not evoked) | 0.0002 |
| MCV at median nerve (ms) | >50 | 64.2 ± 5.9 | 56.0 ± 7.1 | <0.0001 |
| MCV at ulnar nerve (ms) | >50 | 59.9 ± 6.9 | 52.5 ± 6.1 | <0.0001 |
| MCV at posterior tibial nerve (ms) | >40 | 48.0 ± 5.0 | 42.4 ± 5.9 (2 missing value) | <0.0001 |
| MCV at peroneal nerve (ms) | >40 | 47.8 ± 4.2 | 42.6 ± 5.3 (6 missing value) | <0.0001 |
Furthermore, the sensitivity of nerve conduction studies in detecting diabetic peripheral neuropathy (DPN) was evaluated, and the results showed that 75.0% of patients with type 2 diabetes mellitus had abnormal nerve conduction studies.
Comparison of SSR between T2DM group and control group
The sympathetic skin response was evaluated and compared between the type 2 diabetes mellitus group and the control group. The results showed that the sympathetic skin response was a missing value (latency) or 0 mV (amplitude) in some patients with type 2 diabetes mellitus, including 47 for the hand and 74 for the foot (Table 5). Among patients with type 2 diabetes mellitus with sympathetic skin response present, the amplitude of sympathetic skin response was consistent with that of healthy controls, while latency of sympathetic skin response was significantly higher than that of healthy controls (Table 5), indicating that type 2 diabetes mellitus can cause damage to sympathetic skin response and latency of sympathetic skin response should be the appropriate indicator for diabetic peripheral neuropathy. Furthermore, the sensitivity of sympathetic skin response in detecting diabetic peripheral neuropathy was evaluated, and the results showed that 83.3% of patients with type 2 diabetes mellitus had abnormal sympathetic skin response, suggesting that sympathetic skin response is more sensitive to early diagnosis of diabetic peripheral neuropathy than nerve conduction studies.
Table 5.
Comparison of sympathetic skin response between control group and type 2 diabetes mellitus group
| Normal value | Control | T2DM | P value | |
|---|---|---|---|---|
| Latency in upper left limb (ms) | 1.3–1.5 |
1.3 ± 0.2 |
1.52 ± 0.25 (47 missing value) | <0.0001 |
| Amplitude in upper left limb (mV) | 0.484–1.128 | 4.0 ± 2.5 | 3.35 ± 2.83 (47 not evoked) | 0.0504 |
| Latency in upper right limb (ms) | 1.3–1.5 | 1.30 ± 0.14 | 1.50 ± 0.22 (47 missing value) | <0.0001 |
| Amplitude in upper right limb (mV) | 0.484–1.128 | 4.26 ± 2.89 | 3.22 ± 2.72 (47 not evoked) | 0.0950 |
| Latency in lower left limb (ms) | 1.9–2.2 | 1.91 ± 0.23 | 2.28 ± 0.45 (74 missing value) | <0.0001 |
| Amplitude in lower left limb (mV) | 0.364–0.916 | 2.25 ± 1.65 | 1.93 ± 1.76 (74 not evoked) | 0.5004 |
| Latency in lower right limb (ms) | 1.9–2.2 | 1.9 ± 0.25 | 2.25 ± 0.45 (73 missing value) | <0.0001 |
| Amplitude in lower right limb (mV) | 0.364–0.916 | 2.2 ± 1.9 | 1.88 ± 1.61 (73 not evoked) | 0.3420 |
Correlation between SSR and MAU in patients with T2DM
Microalbuminuria is a critical diagnostic indicator of diabetic neuropathy (DN) 24 , 25 . The correlation between sympathetic skin response and microalbuminuria in patients with type 2 diabetes mellitus was evaluated. The results showed that sympathetic skin response was positively correlated with microalbuminuria (Table 6), indicating that sympathetic skin response may also be an indicator of early diabetic nephropathy. Additionally, the abnormal rate of microalbuminuria was found to be lower than that of nerve conduction studies or sympathetic skin response, suggesting that diabetic peripheral neuropathy may occur earlier than diabetic nephropathy during the progression of type 2 diabetes mellitus.
Table 6.
Correlation between sympathetic skin response and microalbuminuria in patients with type 2 diabetes mellitus
| SSR | MAU | |
|---|---|---|
|
Kendall's tau‐B | ||
| SSR | ||
| R | 1.000 | 0.137 |
| Sig. | 0.048 | |
| N | 192 | 192 |
| MAU | ||
| R | 0.137 | 1.000 |
| Sig. | 0.048 | |
| N | 192 | 192 |
N, number of subjects; R, correlation coefficient; Sig, significance.
DISCUSSION
Diabetic peripheral neuropathy is a common complication of diabetes, especially in pre‐diabetes and type 2 diabetes mellitus 3 . However, early diagnosis of diabetic peripheral neuropathy is difficult due to its insidious onset 26 . Early diagnosis is critical to ameliorate diabetic peripheral neuropathy in patients with type 2 diabetes mellitus, as there is currently no effective drug or treatment for diabetic peripheral neuropathy 3 , 5 . Diabetic peripheral neuropathy is a disorder of both sensory and motor nerves 6 , 7 . Nerve conduction studies is a widely used method for assessing neuronal function in clinical settings and is a basic quantitative measurement method for the diagnosis of diabetic peripheral neuropathy 8 , 9 , 27 . Studies have shown that in patients with type 2 diabetes mellitus with abnormal SNAP and SCV, these values are significantly lower than those of the control group, as in previous studies 28 , 29 , 30 . Thus, SNAP and SCV should be promising indicators of diabetic peripheral neuropathy.
The sural nerve is highly affected in diabetic peripheral neuropathy, and nerve conduction studies of the sural nerve is considered the standard for the diagnosis of diabetic peripheral neuropathy. However, our study indicates that the incidence of abnormal SNAP and SCV in the medial plantar nerve and superficial peroneal nerve is higher than that in the sural nerve 31 , 32 , 33 . Studies on polyneuropathy and peripheral neuropathy in non‐diabetic patients have revealed that nerve conduction studies of the medial plantar nerve and superficial peroneal nerve is more sensitive than that of the sural nerve. Therefore, nerve conduction studies of the medial plantar nerve and superficial peroneal nerve may improve the diagnostic rate of diabetic peripheral neuropathy 34 , 35 , 36 . Additionally, injury of medial plantar nerve and superficial peroneal nerve caused by type 2 diabetes mellitus may be more severe than that of the sural nerve, possibly due to their location in the lower limbs and the increased weight they bear.
Although nerve conduction studies are a widely used method for the diagnosis of diabetic peripheral neuropathy, they cannot detect autonomic symptoms of the skin 10 , 11 . Sympathetic skin response is used to measure the electrical activity of the skin after electrical stimulation and is used widely in the assessment of diabetic peripheral neuropathy 11 , 13 , 37 , 38 . Several studies have suggested that sympathetic skin response is more sensitive than nerve conduction studies in detecting diabetic peripheral neuropathy in 50, 18, and 20 patients with type 2 diabetes mellitus, respectively 11 , 12 , 13 . Our study further confirms this finding in 192 patients with type 2 diabetes mellitus. In addition, the above studies have not confirmed whether sympathetic skin response is more sensitive than nerve conduction studies in detecting early diabetic peripheral neuropathy 11 , 12 , 13 . Therefore, the present study indicates that sympathetic skin response is more sensitive than nerve conduction studies in detecting early diabetic peripheral neuropathy in a large population for the first time.
The abnormal sympathetic skin response rate in patients with type 2 diabetes mellitus is 83.3%, and 26 of 48 patients with normal nerve conduction studies had abnormal sympathetic skin response. Thus, the combination of nerve conduction studies and sympathetic skin response can improve the sensitivity of nerve testing in the diagnosis of diabetic peripheral neuropathy 15 , 39 , 40 . Besides, a higher percentage of absent sympathetic skin response cases in the lower extremities were observed in this study, suggesting that diabetic peripheral neuropathy initiates in the lower extremities.
Diabetic nephropathy is another common complication of diabetes and one of the main causes of death in patients with diabetes 41 . Previous studies have suggested that diabetic peripheral neuropathy and diabetic nephropathy may develop in parallel, but whether they appear in succession has not been confirmed 24 , 25 . However, the role of the sympathetic skin response in the early detection of diabetic nephropathy has not been reported. Microalbuminuria is a basic diagnostic indicator of diabetic nephropathy. Our study indicates for the first time that sympathetic skin response is positively correlated with microalbuminuria, suggesting that sympathetic skin response may be used for the early diagnosis of diabetic peripheral neuropathy and diabetic nephropathy in type 2 diabetes mellitus patients without microalbuminuria. This raises the possibility that sympathetic skin response may be a warning indicator of early diabetic nephropathy, as peripheral nerve conduction velocity and amplitude in patients with type 2 diabetes mellitus were associated with diabetic microvascular complications 18 , 42 , 43 .
Overall, the novelty of this study is to reveal that sympathetic skin response is more sensitive than nerve conduction studies in the early detection of diabetic peripheral neuropathy, an abnormal sympathetic skin response may be an indicator of early diabetic nephropathy and diabetic peripheral neuropathy may occur earlier than diabetic nephropathy in the progression of type 2 diabetes mellitus for the first time.
CONCLUSION
The study suggests that sympathetic skin response is more sensitive than nerve conduction studies in the early diagnosis of diabetic peripheral neuropathy, and the combination of nerve conduction studies and sympathetic skin response can improve the sensitivity of nerve testing for the diagnosis of diabetic peripheral neuropathy. Furthermore, the study also suggests that abnormal sympathetic skin response may be an indicator of early diabetic nephropathy, indicating a possible relationship between diabetic peripheral neuropathy and diabetic nephropathy in the progression of type 2 diabetes mellitus. Additionally, the study suggests that diabetic peripheral neuropathy may occur earlier than diabetic nephropathy in the progression of type 2 diabetes mellitus.
DISCLOSURE
The authors declare no conflict of interest.
Approval of the research protocol: All procedures in the study were in accordance with the ethical committee of The Second Affiliated Hospital of Guangzhou Medical University (2019‐hs‐44) and the 1964 Declaration of Helsinki and its subsequent amendments or similar ethical standards.
Informed consent: Written informed consent was obtained from all participants.
Approval date of registry and the registration no. of the study/trial: The approval data of this study is Jan 15, 2020, and the Registration No. of the current study is 2019‐hs‐44.
Animal studies: N/A.
ACKNOWLEDGMENTS
This study was supported by The National Natural Science Foundation of China (No. 81701240), The Natural Science Foundation of Guangdong Province (No. 2016A030310283), and Guangzhou Science, Technology and Innovation Commission (No. 201704020043).
DATA AVAILABILITY STATEMENT
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
REFERENCES
- 1. Cho NH, Shaw JE, Karuranga S, et al. IDF diabetes atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 2018; 138: 271–281. [DOI] [PubMed] [Google Scholar]
- 2. Gregg EW, Sorlie P, Paulose‐Ram R, et al. Prevalence of lower‐extremity disease in the US adult population >=40 years of age with and without diabetes: 1999‐2000 national health and nutrition examination survey. Diabetes Care 2004; 27: 1591–1597. [DOI] [PubMed] [Google Scholar]
- 3. Feldman EL, Nave KA, Jensen TS, et al. New horizons in diabetic neuropathy: Mechanisms, bioenergetics, and pain. Neuron 2017; 93: 1296–1313. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Barrell K, Smith AG. Peripheral neuropathy. Med Clin North Am 2019; 103: 383–397. [DOI] [PubMed] [Google Scholar]
- 5. Ward RE, Caserotti P, Cauley JA, et al. Mobility‐related consequences of reduced lower‐extremity peripheral nerve function with age: A systematic review. Aging Dis 2016; 7: 466–478. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. London ZN, Mundwiler A, Oral H, et al. Nerve conduction studies are safe in patients with central venous catheters. Muscle Nerve 2017; 56: 321–323. [DOI] [PubMed] [Google Scholar]
- 7. Tavee J. Nerve conduction studies: Basic concepts. Handb Clin Neurol 2019; 160: 217–224. [DOI] [PubMed] [Google Scholar]
- 8. Kiziltan ME, Gunduz A, Kiziltan G, et al. Peripheral neuropathy in patients with diabetic foot ulcers: Clinical and nerve conduction study. J Neurol Sci 2007; 258: 75–79. [DOI] [PubMed] [Google Scholar]
- 9. Braddom RL, Hollis JB, Castell DO. Diabetic peripheral neuropathy: A correlation of nerve conduction studies and clinical findings. Arch Phys Med Rehabil 1977; 58: 308–313. [PubMed] [Google Scholar]
- 10. Niakan E, Harati Y. Sympathetic skin response in diabetic peripheral neuropathy. Muscle Nerve 1988; 11: 261–264. [DOI] [PubMed] [Google Scholar]
- 11. Al‐Moallem MA, Zaidan RM, Alkali NH. The sympathetic skin response in diabetic neuropathy and its relationship to autonomic symptoms. Saudi Med J 2008; 29: 568–572. [PubMed] [Google Scholar]
- 12. Robles NR, Solis M, Albarran L, et al. Sympathetic skin response in hemodialysis patients: Correlation with nerve conduction studies and adequacy of dialysis. Nephron 1999; 82: 12–16. [DOI] [PubMed] [Google Scholar]
- 13. Nazhel B, Yetkin I, Irkec C, et al. Sympathetic skin response in diabetic neuropathy. Electromyogr Clin Neurophysiol 2002; 42: 181–185. [PubMed] [Google Scholar]
- 14. Unnikrishnan R, Anjana RM, Mohan V. Diabetes mellitus and its complications in India. Nat Rev Endocrinol 2016; 12: 357–370. [DOI] [PubMed] [Google Scholar]
- 15. Flyvbjerg A. The role of the complement system in diabetic nephropathy. Nat Rev Nephrol 2017; 13: 311–318. [DOI] [PubMed] [Google Scholar]
- 16. Zhang XX, Kong J, Yun K. Prevalence of diabetic nephropathy among patients with type 2 diabetes mellitus in China: A meta‐analysis of observational studies. J Diabetes Res 2020; 2020: 2315607. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. Thipsawat S. Early detection of diabetic nephropathy in patient with type 2 diabetes mellitus: A review of the literature. Diab Vasc Dis Res 2021; 18: 14791641211058856. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Papatheodorou K, Papanas N, Banach M, et al. Complications of diabetes 2016. J Diabetes Res 2016; 2016: 6989453. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Hur J, O'Brien PD, Nair V, et al. Transcriptional networks of murine diabetic peripheral neuropathy and nephropathy: Common and distinct gene expression patterns. Diabetologia 2016; 59: 1297–1306. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Dyck PJ, Davies JL, Wilson DM, et al. Risk factors for severity of diabetic polyneuropathy: Intensive longitudinal assessment of the Rochester diabetic neuropathy study cohort. Diabetes Care 1999; 22: 1479–1486. [DOI] [PubMed] [Google Scholar]
- 21. Roikjer J, Morch CD, Ejskjaer N. Diabetic peripheral neuropathy: Diagnosis and treatment. Curr Drug Saf 2021; 16: 2–16. [DOI] [PubMed] [Google Scholar]
- 22. De Silva L, Weir MR. Renin inhibition and microalbuminuria development: Meaningful predictor of kidney disease progression. Curr Opin Nephrol Hypertens 2010; 19: 437–443. [DOI] [PubMed] [Google Scholar]
- 23. Thakur V, Chattopadhyay M. Early urinary markers for diabetic and other kidney diseases. Curr Drug Targets 2018; 19: 825–831. [DOI] [PubMed] [Google Scholar]
- 24. Papadopoulou‐Marketou N, Kanaka‐Gantenbein C, Marketos N, et al. Biomarkers of diabetic nephropathy: A 2017 update. Crit Rev Clin Lab Sci 2017; 54: 326–342. [DOI] [PubMed] [Google Scholar]
- 25. Van JA, Scholey JW, Konvalinka A. Insights into diabetic kidney disease using urinary proteomics and bioinformatics. J Am Soc Nephrol 2017; 28: 1050–1061. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26. Javed S, Hayat T, Menon L, et al. Diabetic peripheral neuropathy in people with type 2 diabetes: Too little too late. Diabetic Med 2019; 37: 573–579. [DOI] [PubMed] [Google Scholar]
- 27. Wang F, Zhang J, Yu J, et al. Diagnostic accuracy of monofilament tests for detecting diabetic peripheral neuropathy: A systematic review and meta‐analysis. J Diabetes Res 2017; 2017: 8787261. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28. Brown JJ, Pribesh SL, Baskette KG, et al. A comparison of screening tools for the early detection of peripheral neuropathy in adults with and without type 2 diabetes. J Diabetes Res 2017; 2017: 1467213. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29. Vinik AI, Bril V, Litchy WJ, et al. Sural sensory action potential identifies diabetic peripheral neuropathy responders to therapy. Muscle Nerve 2005; 32: 619–625. [DOI] [PubMed] [Google Scholar]
- 30. Morimoto J, Suzuki Y, Tada A, et al. Time‐course changes in nerve conduction velocity (NCV) in type 2 diabetes. J Diabetes Complications 2012; 26: 237–240. [DOI] [PubMed] [Google Scholar]
- 31. Kushnir M, Klein C, Kimiagar Y, et al. Medial dorsal superficial peroneal nerve studies in patients with polyneuropathy and normal sural responses. Muscle Nerve 2005; 31: 386–389. [DOI] [PubMed] [Google Scholar]
- 32. Lo YL, Xu LQ, Leoh TH, et al. Superficial peroneal sensory and sural nerve conduction studies in peripheral neuropathy. J Clin Neurosci 2006; 13: 547–549. [DOI] [PubMed] [Google Scholar]
- 33. Sylantiev C, Schwartz R, Chapman J, et al. Medial plantar nerve testing facilitates identification of polyneuropathy. Muscle Nerve 2008; 38: 1595–1598. [DOI] [PubMed] [Google Scholar]
- 34. Sanada LS, Tavares MR, Sato KL, et al. Association of chronic diabetes and hypertension in sural nerve morphometry: An experimental study. Diabetol Metab Syndr 2015; 7: 9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35. Semprini R, Martorana A, Ragonese M, et al. Observational clinical and nerve conduction study on effects of a nutraceutical combination on painful diabetic distal symmetric sensory‐motor neuropathy in patients with diabetes type 1 and type 2. Minerva Med 2018; 109: 358–362. [DOI] [PubMed] [Google Scholar]
- 36. Kakrani AL, Gokhale VS, Vohra KV, et al. Clinical and nerve conduction study correlation in patients of diabetic neuropathy. J Assoc Physicians India 2014; 62: 24–27. [PubMed] [Google Scholar]
- 37. Huang YN, Jia ZR, Shi X, et al. Value of sympathetic skin response test in the early diagnosis of diabetic neuropathy. Chin Med J (Engl) 2004; 117: 1317–1320. [PubMed] [Google Scholar]
- 38. Braune HJ, Horter C. Sympathetic skin response in diabetic neuropathy: A prospective clinical and neurophysiological trial on 100 patients. J Neurol Sci 1996; 138: 120–124. [DOI] [PubMed] [Google Scholar]
- 39. Papadopoulou‐Marketou N, Chrousos GP, Kanaka‐Gantenbein C. Diabetic nephropathy in type 1 diabetes: A review of early natural history, pathogenesis, and diagnosis. Diabetes Metab Res Rev 2017; 33: e2841. [DOI] [PubMed] [Google Scholar]
- 40. Papadopoulou‐Marketou N, Paschou SA, Marketos N, et al. Diabetic nephropathy in type 1 diabetes. Minerva Med 2018; 109: 218–228. [DOI] [PubMed] [Google Scholar]
- 41. Dyck PJ, Kratz KM, Karnes JL, et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population‐based cohort: The Rochester diabetic neuropathy study. Neurology 1993; 43: 817–824. [DOI] [PubMed] [Google Scholar]
- 42. Xue‐lian Z, Wei W, Ren‐bin W, et al. Clinical association analysis between diabetic peripheral neuropathy and diabetic nephropathy. Chinese J Med 2018; 06: 606–609. [Google Scholar]
- 43. Charles M, Soedamah‐Muthu SS, Tesfaye S, et al. Low peripheral nerve conduction velocities and amplitudes are strongly related to diabetic microvascular complications in type 1 diabetes: The EURODIAB prospective complications study. Diabetes Care 2010; 33: 2648–2653. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.