Clinical and Immunohistochemical Evaluation of Peripheral Neuropathy in Diabetic Patients

Clinical and Immunohistochemical Evaluation of Peripheral Neuropathy in Diabetic Patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical and Immunohistochemical Evaluation of Peripheral Neuropathy in Diabetic Patients Oyunbileg Bavuu, Sainbileg Sonomtseren, Bayarmaa Enkhbat This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8518662/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 20 You are reading this latest preprint version Abstract Background Diabetic peripheral neuropathy is a prevalent and severe complication of diabetes that significantly impacts a patient’s quality of life. Early diagnosis through clinical examination and intraepidermal nerve fiber density (IENFD) measurement is essential. However, limited healthcare access and specialists, and uncontrolled blood glucose levels increase the risk of lower limb amputation. This is the first study in Mongolia to evaluate epidermal nerve fibers for the assessment of DPN. Methods and Results Thirty diabetic patients (20–74 years) underwent foot examination and skin punch biopsies. The skin biopsies were analyzed by immunohistochemistry using protein gene product 9.5 (PGP 9.5) antibody to quantify the total IENF. Among participants, 94% had poor glycemic control, were diagnosed with 26.7% mild, 40% moderate, and 16.7% severe neuropathy. The average number of epidermal nerve fibers in 1 mm was 7.87 ± 4.72, reflecting an 86.7% reduction. DPN showed a strong correlation with both diabetes duration (V = 0.876, p < 0.0001) and HbA1C level (V = 0.760, p < 0.0001). The specificity and sensitivity of the immunohistochemistry method were 40% and 92%, respectively. Conclusion DPN severity is associated with diabetes duration and poor glycemic control. IENFD highlights a more objective measure of small nerve fiber reduction, and combining it with clinical assessment provides a comprehensive and accurate approach for diagnosing DPN. Early detection of DPN, strict glycemic control, and integration of IENFD into diagnostic protocols are urgently needed, particularly in developing countries such as Mongolia. Diabetes diabetic neuropathy epidermal nerve fiber immunohistochemistry skin biopsy Figures Figure 1 Figure 2 Figure 3 1. Background Diabetic peripheral neuropathy (DPN) is a prevalent and severe complication of diabetes mellitus, affecting nearly 50% of diabetic patients and leading to significant health issues and increased healthcare costs [ 1 , 2 ]. In Mongolia, the prevalence of diabetes has risen from 3.1% in 1999 to 10% in 2019 [ 3 ], with DPN affecting 71% of diabetic patients. Those with DPN had 3 times higher incidence of history of foot ulceration compared to patients without DPN [ 4 ]. The early symptoms of diabetic neuropathy, such as pain, loss of proprioception and sense of temperature, and alteration in sweating, are due to the degeneration of small somatic nerve fibers, which traditional physical, neurophysiological, and neuropathological tests may not detect [ 5 ]. Thus, emphasizing the need for more sensitive and specific diagnostics to detect DPN earlier stage. Intraepidermal nerve fiber density (IENFD) in skin biopsy, using pan-neuronal marker Protein Gene Product (PGP 9.5), became popular to diagnose small nerve fibers even before clinical symptoms [ 6 ]. In both animal and human studies, a decrease in PGP 9.5 IENFD has been demonstrated in cases of DPN. These findings have shown high sensitivity and specificity for detecting early nerve damage associated with DPN [ 7 – 10 ]. Currently, there’s no information on the early effects of diabetes on peripheral nerve fibers in Mongolia. In this study, we evaluated diabetic peripheral neuropathy using traditional functional tests and a modern diagnostic approach involving skin punch biopsy with the PGP 9.5 antibody. We aimed to emphasize the importance of early detection and the potential integration of this technique into diagnostic protocols to improve clinical outcomes for patients with diabetes in Mongolia. 2. Methods A cross-sectional study recruited 30 diabetic patients, aged between 20 and 74 years, from the Endocrinology Hospital in Ulaanbaatar, Mongolia. 2.1. Measurement of metabolic parameters All participants were measured for body composition, including current weight, height, waist circumference, and body fat. Weight and body fat mass were assessed using a digital body composition monitor (CITIZEN Body Fat Analyzer BM-100), and height and circumference were measured to the nearest 0.1 cm with light indoor clothing. Body Mass Index (BMI) was calculated as weight in kilograms (kg) divided by the square of height in meters and categorized based on the WHO BMI guidelines: 30 kg/m² as obese. Blood pressure (BP) was measured using an automated device (Omron HCR-7104) after participants relaxed for at least 30 min in a quiet room. All measurements were conducted by a trained assistant following standard protocols. 2.2. Diabetic peripheral neuropathy assessment The neuropathic symptoms, such as numbness, tingling, burning, and sharp pain in the feet or leg pain, were assessed by questionnaire. General inspections evaluated skin color and texture (dryness, thickness), nail abnormalities, foot deformities, callus formation, fissures, infection, ulceration, and history of amputation. Common forefoot deformities, such as claw and hammer toe, which increase plantar pressures and cause breakdown, were identified. Additionally, the evaluation included checking for Charcot arthropathy, a unilateral red, hot, swollen, flat foot with deformity, particularly affecting the midfoot. The clinical exam for diabetic neuropathy was designed to identify the loss of protective sensation, which includes five simple clinical tests. The pressure sensation test used 10 g monofilaments (SEMMES-WEINSTEIN) to screen for pressure sensation loss, associated with large-fiber nerve function. The monofilament applied a 10 g force to the 1st, 3rd, and 5th metatarsal heads and plantar surface of the distal hallux on each foot while the patient’s eyes were closed. The sensation was first demonstrated to the patient on the upper arm. During the test, the patient was asked to respond “yes” or “no” to indicate whether they felt monofilament and to identify the site, avoiding areas with calluses. A maximum score is 10; a score of 8 or less indicates neuropathy, and the absence of feeling indicates a complete lack of pressure sensation. The vibration sensation test was assessed bilaterally at the hallux using a 128 Hz tuning fork (RYDEL SEIFFER). With the patient lying supine, the fork was placed on the dorsal hallux, and the amplitude increased until the patient could detect the vibration. Normal values were specified as 6/8–8/8 for patients under 40 and 5/8–8/8 for patients over 40. Loss of sensation was characterized by scores below 6/8 for under 40, and below 5/8 for those over 40. The absence of feeling indicated the complete lack of vibration sensation. Pinprick sensation test used a single-use disposable pin “NEUROTIPS”, applied to the toenail on the dorsal surface of the hallux with pressure. An inability to perceive pinprick sensation on either hallux was considered abnormal. Patients were also assessed for their ability to distinguish between a sharp and a non-sharp end. The responses were categorized as follows: no neuropathy (clearly distinguishable), neuropathy (occasional difficulty), and complete absence (inability to distinguish). The thermal sensation test used a TIP-TERM pen-shaped device with a plastic end and a metal end to evaluate the presence of neuropathy. Patients were assessed for their ability to distinguish between cold and warm temperatures applied to the skin in the outlined areas. The responses were reported as follows: no neuropathy (clearly distinguishable), neuropathy (occasional difficulty), and complete absence (inability to distinguish between temperatures). The tactile sensation (light touch) test used cotton wool to lightly touch the skin and determine if patients felt the sensation symmetrically in all areas. The responses were reported as follows: no neuropathy (clearly distinguishable), neuropathy (occasional difficulty), and complete absence (inability to distinguish light touch). In addition, the ankle tendon reflex was assessed by the hammer with the patient kneeling or resting on the examination couch. Diabetic peripheral neuropathy was classified as follows: no neuropathy (no signs or symptoms), mild neuropathy (both signs and symptoms present), and severe neuropathy (severe signs and symptoms of diabetic polyneuropathy or absence of all peripheral sensations). 2.3. Diabetic peripheral artery disease assessment The vascular assessment was performed by palpating the posterior tibial and dorsalis pedis artery pulses, and categorizing them as present, weak, or absent. Additionally, the ankle-brachial index (ABI) was used to diagnose lower limb vascular insufficiency, which compares the systolic blood pressure in the ankle to the systolic blood pressure in the brachial. An ABI of 0.9 to 1.3 was considered normal, whereas values below 0.9 or above 1.3 were associated with claudication. 2.4. The intraepidermal nerve fiber assessment Skin punch tissue samples were obtained from the distal leg (10 cm above the lateral malleolus) using a 3 mm disposable punch under sterile technique, following local anesthesia with 2% lidocaine. The skin samples were fixed in a 10% formalin solution at 4°C, and then the tissues were embedded in paraffin, and the paraffin blocks were sectioned into 5-µm-thick slices. The specimens were blocked with 10% normal goat serum at room temperature (RT) for 30 minutes in a dark place, then incubated with the PGP 9.5 primary antibody overnight in a moist chamber at 4°C. Subsequently, the sections were incubated with anti-rabbit IgG secondary antibody for 30 min at RT. Detection was performed using the avidin-biotin-peroxidase method. Images were captured at x40 objective magnification along the entire length, and nerve fibers were counted in four non-consecutive sections; mean values were used for statistical analysis. Two independent blinded observers were quantified with no significant difference between observers. The quantitative evaluation of diabetic neuropathy was based on the number of intraepidermal nerve fibers (fibers/mm 2 ). Nerve fibers were counted and classified as follows: no neuropathy (more than 12), mild neuropathy (9–12 nerve fibers), moderate neuropathy (5–8 nerve fibers), and severe neuropathy (0–4 nerve fibers). 2.5. Statistical analysis All graphs, calculations, and statistical analyses were performed using GraphPad Prism software. Data were assessed for normality, with continuous data expressed as mean ± SD and categorical variables expressed as numbers with percentages. Student’s t-test was used to compare continuous variables, and the Chi-square test to compare categorical variables. An analysis of variance (ANOVA) was utilized for multiple group comparisons. Unconditional logistic regression models were used to calculate adjusted odds ratios [ 8 ] and their 95% confidence intervals (CIs). Statistical significance was accepted at a P value of less than 0.05. 3. Results 3.1 . Patients with T2DM exhibited higher cardiometabolic risk compared to T1DM The study included a total of 30 patients with diabetes (33.3% male, 66.7% female). The mean age of patients was 49.07 ± 4.09 (20–74) years, with 56.7% of participants over 50 years. Patients with T1DM were significantly younger than those with T2DM, although diabetes duration did not differ between the groups (mean 9.46 ± 5.74 years). Systolic blood pressure was significantly higher in the T2DM group (p = 0.001), whereas heart rate and diastolic blood pressure showed no significant differences between the groups. Patients with T2DM also had a higher body mass index (BMI), waist circumference (WC), and body fat mass (p < 0.001) compared with T1DM. No significant differences were observed in fasting blood glucose, HbA1C, and total cholesterol levels (Tables 1 and 2). Despite similar glycemic control and diabetes duration, patients with T2DM exhibited greater cardiovascular and microvascular risk factors, as well as obesity-related parameters, compared to T1DM. Table 1 Basic characteristics of diabetic patients Parameters Total T1DM (n = 9) T2DM (n = 21) P-value Age (years) 49.07 ± 14.90 31.67 ± 9.73 56.52 ± 9.45 < 0.001 Diabetes duration (years) 9.46 ± 5.74 10.89 ± 5.90 8.85 ± 5.71 0.397 Heart rate (bpm) 90.07 ± 14.51 95.11 ± 17.81 87.90 ± 12.73 0.293 Systolic BP (mm Hg) 146.2 ± 23.8 127.3 ± 4.85 154.3 ± 4.91 0.001 Diastolic BP (mm Hg) 90.8 ± 12.21 84.78 ± 3.32 93.38 ± 2.69 0.059 Body mass index (kg/m 2 ) 27.59 ± 5.37 21.75 ± 2.42 30.09 ± 4.19 < 0.001 Waist circumference (cm) 96 ± 16.39 76.78 ± 6.41 104.24 ± 11.64 < 0.001 Body fat mass (%) 33.81 ± 11.59 20.97 ± 8.25 39.31 ± 7.87 < 0.001 Total cholesterol (mmol/L) 8.01 ± 7.52 8.20 ± 8.22 7.93 ± 7.41 0.935 FBG (mmol/L) 13.88 ± 5.26 14.71 ± 7.66 13.52 ± 4.03 0.670 HbA1C (%) 9.81 ± 1.9 9.98 ± 1.77 9.73 ± 2.00 0.731 FBG : Fasting blood glucose, HbA1C : Glycated hemoglobin Table 2 Comparison of age, sex, and metabolic profiles between T1DM and T2DM groups Variables Total (n = 30) T1DM (n = 9) T2DM (n = 21) P-value N (%) N (%) N (%) Age group (years) 19–29 5 16.7 5 55.6 0 0 60 8 26.7 0 0 8 38.1 Sex Male 10 33.3 3 33.3 7 33.3 0.999 Female 20 66.7 6 66.7 14 66.7 Diabetic duration 0–1 years 2 6.7 0 0 2 9.5 0.459 1–5 years 7 23.3 2 22.2 5 23.8 5–10 years 10 33.3 2 22.2 8 38.1 > 10 years 11 36.7 5 55.6 6 28.6 Body fat mass Normal 11 36.7 8 88.9 3 14.3 < 0.001 High 19 63.3 1 11.1 18 85.7 BMI Normal 10 33.3 8 88.9 2 9.6 < 0.001 Overweight 8 26.7 1 11.1 7 33.3 Obesity 12 40 0 0 12 57.1 HbA1C (%) 7.5 28 94 9 100 19 90.4 BMI : Body Mass Index Among the participants, the majority (94%) demonstrated poor glycemic control (HbA1C > 7.5%), while only 3% had moderately controlled (HbA1C 6.5% − 7.5%), and 3% had good-controlled (HbA1C < 6.5%) glycemic levels. In contrast, all male participants (100%) and all patients with diabetes duration more than 5 years (n = 21) had poorly controlled blood glucose, suggesting an association between diabetes duration and glycemic control (Fig. 1A and 1B). However, no significant difference in glycemic control was observed between T1DM and T2DM. 3.2 . Foot examinations revealed a high prevalence of peripheral neuropathy in diabetic patients. Most participants experienced at least one symptom of DPN, with numbness and pain during walking, reported 83.3% and 60%, respectively. Table 3 showed other DPN symptoms, including dry skin (83.3%) and increased skin thickness (76.7%). Consistent with these findings, we observed loss of vibration (53.3%) and thermal sensation (76.7%), while the Achilles reflex was absent (66.7%) in diabetic patients (Table 4). Vascular assessment demonstrated absent or weak pedal pulses in up to one-third of patients. Furthermore, an abnormal ankle-brachial index (ABI) was found in 6.7% of participants, suggesting early or asymptomatic peripheral artery disease. Table 3 Clinical Characteristics of Diabetic Peripheral Neuropathy Signs and symptoms Total (n = 30) T1DM (n = 9) T2DM (n = 21) P-value N (%) N (%) N (%) Signs in foot Yes 25 83.3 9 100 16 76.2 0.286 No 5 16.7 0 0 5 23.8 Foot ulcer before Yes 9 30 4 44.4 5 23.8 0.389 No 21 70 5 55.6 16 76.2 Pain in walking Yes 18 60 6 66.7 12 57.1 0.704 No 12 40 3 33.3 9 42.9 Changes of skin color Yes 6 20 1 11.1 5 23.8 0.637 No 24 80 8 88.9 16 76.2 Dry skin Yes 25 83.3 6 66.7 19 90.5 0.143 No 5 16.7 3 33.3 2 9.5 Nail problems Yes 20 66.7 6 66.7 14 66.7 0.999 No 10 33.3 3 33.3 7 33.3 Foot deformation Yes 1 3.3 1 11.1 0 0 0.300 No 29 96.7 8 88.9 21 100 Calluses Yes 9 30 2 22.2 7 33.3 0.681 No 21 70 7 77.8 14 66.7 Skin thickness Yes 23 76.7 4 44.4 19 90.5 0.014 No 7 23.3 5 55.6 2 9.5 Cracked skin Yes 3 10 2 22.2 1 4.8 0.207 No 27 90 7 77.8 20 95.2 Foot infection Yes 2 6.7 1 11.1 1 4.8 0.517 No 28 93.3 8 88.9 20 95.2 Foot ulcer Yes 2 6.7 1 11.1 1 4.8 0.517 No 28 93.3 8 88.9 20 95.2 Amputaion Yes 1 3.3 1 11.1 0 0 0.300 No 29 96.7 8 88.9 21 100 Table 4 Assessment of Peripheral Neuropathy by Clinical Examination Neuropathy test Total (n = 30) T1DM (n = 9) T2DM (n = 21) P-value N (%) N (%) N (%) Pressure sensation Normal 22 73.3 7 77.8 15 71.4 0.999 Loss 8 26.7 2 22.2 6 28.6 Vibration sensation Normal 14 46.7 6 66.7 8 38.1 0.236 Loss 16 53.3 3 33.3 13 61.9 Pinprick sensation Normal 11 36.7 3 33.3 8 38.1 0.999 Loss 19 63.3 6 66.7 13 61.9 Thermal sensation Normal 7 23.3 1 11.1 6 28.6 0.393 Loss 23 76.7 8 88.9 15 71.4 Tactile sensation Normal 13 43.3 6 66.7 7 33.3 0.123 Loss 17 56.7 3 33.3 14 66.7 Achilles reflex Normal 8 26.6 3 33.3 5 23.8 0.651 Absence on both 20 66.7 5 55.6 15 71.4 Absence on one side 2 6.7 1 11.1 1 4.8 The prevalence of DPN among study participants was 83.3% as determined by food examination. According to the severity of neuropathy classification, 26,7% of patients had mild neuropathy, 40% moderate, and 16.6% severe neuropathy. However, there was no significant difference in the prevalence or severity between type 1 and type 2 diabetes mellitus (Fig. 2A). 3.3 . Reduction of intraepidermal nerve fiber density correlated with metabolic risk in diabetic patients. Diabetic peripheral neuropathy (DPN) was diagnosed based on intraepidermal nerve fiber density (IENFD) assessed per 1 mm 2 of skin. Mean IENFD was 7.87 ± 4.72 fibers/mm² overall, 6.44 ± 2.83 fibers/mm² in T1DM, and 8.48 ± 5.27 fibers/mm² in T2DM patients. A total of 26 individuals (86.7%) were diagnosed with DPN as defined by an IENFD of fewer than 12 nerve fibers per mm 2 (Fig. 3A). Among that, mild DPN was observed in 6 (20%), moderate DPN in 7 (23.3%), while severe DPN in 13 (43.4%) individuals. All T1DM patients exhibited DPN as diagnosed by skin punch biopsy, whereas 4 (19%) patients with T2DM detected no DPN (Fig. 2B). Figure 3B showed correlation of DPN with diabetes duration (V = 0.876, p < 0.0001) and HbA1C levels (V = 0.760, p < 0.0001). The sensitivity and specificity of IENFD (< 12 fibers/mm 2 ) were 92% and 40% respectively, with a positive predictive value (PPV) of 88.5%, a negative predictive value (NPV) of 50%, and an overall diagnostic accuracy of 83.3% (Fig. 3C). 4. Discussion The study provides comprehensive evidence regarding the prevalence and characteristics of diabetic peripheral neuropathy (DPN) in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Utilizing clinical foot examinations and intraepidermal nerve fiber density analysis, we found that many participants displayed clinical symptoms of DPN, and a substantial proportion confirmed the presence of neuropathy through reduced epidermal nerve fibers. In this study, patients with T2DM have significantly higher cardiovascular risk factors, including BMI, waist circumference, systolic blood pressure, and body fat mass, than those with T1DM, despite similar diabetes duration and glycemic control. These findings were consistent with previous studies that highlight patients with T2DM have increased metabolic syndrome and obesity-related complications, which further elevate their risk for neuropathy and cardiovascular disease [ 11 – 14 ]. Diabetic peripheral neuropathy is commonly diagnosed by clinical examination, which evaluates pain, vibration sense, and other sensory functions. However, the accuracy of these evaluations depends on both the examiner and the stage of the disease [ 15 ]. In our study, over 75% of patients reported symptoms such as numbness and pain, and sensory testing revealed loss of thermal, vibration, and pinprick sensations. These findings are similar to other large-scale studies, including MONICA/KORA study in Germany [ 16 , 17 ], which reported a high prevalence of sensory abnormalities in patients with poor glycemic control and long-standing diabetes [ 18 , 19 ]. Importantly, subclinical signs of peripheral artery disease were also observed in patients with diabetes, emphasizing the value of early detection and vascular screening in diabetic care [ 20 , 21 ]. Evaluating IENFD via skin biopsy provides a more objective method, especially for small fiber neuropathy that may not be identified by clinical examination. Moreover, skin biopsy allows for a detailed assessment of nerve damage, supporting a more effective treatment strategy [ 22 , 23 ]. In our study, IENFD confirmed reduced small nerve fiber density in the majority (86.7%) of participants, with most exhibiting moderate to severe stages, and all T1DM patients were diagnosed with DPN. These findings support previous reports that small fiber neuropathy may develop early in T1DM, even without overt metabolic features [ 24 , 25 ]. Callaghan et al. and Tesfaye et al. reported the role of chronic hyperglycemia in peripheral nerve degeneration [ 12 , 18 , 26 ]. Consistently, we observed a strong correlation between DPN and both diabetes duration (V = 0.876, p < 0.0001) and HbA1C levels (V = 0.760, p < 0.0001). Our finding suggests that age and duration of DM in practitioners may not be major determinants of neuropathic risk, but improved glucose monitoring can be critical for preventing the development of diabetes related neuropathic complications. The diagnostic performance of IENFD for clinically defined DPN demonstrated high sensitivity (92%), but low specificity (40%), with a diagnostic accuracy of 83.3%. These suggest that IENFD is a sensitive and objective biomarker for small fiber damage, particularly valuable for subclinical signs and early stages of neuropathy [ 6 , 27 , 28 ]. Previous studies conducted by Devigili et al. and Lauria et al. have demonstrated that skin biopsy is a reliable tool for diagnosing small fiber neuropathy, with a diagnostic yield exceeding 85% when combined with clinical assessment [ 6 , 29 ]. Moreover, Grazia Devigili and Valeria Tugnoli in 2008 [ 29 ], evaluated 486 individuals using multiple diagnostic methods, including clinical sensory tests, autonomic function tests, electromyography, and skin biopsies. Results showed that among 150 patients diagnosed with neuropathy (77 females and 73 males, aged 22 to 84, average age 60), 54.6% were diagnosed through sensory evaluations, 46.9% through nerve conduction studies, and 88% through skin biopsies. Combining with those studies and our results identified the assessment of epidermal nerve fiber density (IENFD) as the most accurate and reliable approach, particularly for early detection of DPN, despite its time-consuming and costly. 5. Study limitations This study includes multiple diagnostic methods, including validated questionnaires, foot examination, and histological analysis. However, we did not include electrophysiological tests such as nerve conduction studies, which may be more important for large fiber function. Skin punch biopsy is also not widely available and can only be performed in specialized centers with trained staff in Mongolia. Follow-up skin biopsies can be useful to monitor the progression of neuropathy and treatment results. In addition, the number of participants was relatively small, which may limit the statistical difference and generalizability of the findings to broader populations. Conclusion The prevalence of diabetic peripheral neuropathy (DPN) is alarmingly high among patients with diabetes mellitus. Diabetes duration and poor glycemic control were strongly associated with greater severity of DPN. Intraepidermal nerve fiber density (IENFD) highlights a more objective method for diagnosis; however, a combination of clinical assessment with IENFD analysis provides a comprehensive and accurate approach for diagnosing DPN in both clinical and research fields. Declarations 7.1. Ethics approval and consent to participate The study protocol was approved by the Biomedical Research Ethical Committee of the Mongolian National University of Medical Sciences (approval number: #13-09/1A), and was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants before participation. Exclusion criteria included non-diabetic individuals with neurological or other systemic disorders, and patients who declined to participate. 7.2. Consent for publication Not applicable 7.3. Availability of data and materials The data supporting the findings of this study are included in this article. Additional datasets generated and analyzed during the current study are available from the corresponding author on reasonable request. 7.4. Comp eting interest s All authors declare that there is no conflict of interest regarding the publication of this article. 7.5. Funding This study received no specific funding, grants, or other financial support during the preparation of this manuscript. 7.6. Authors’ contributions Dr. Oyunbileg performed most of the experiments and prepared the manuscript. Dr. Bayarmaa designed the experiments and reviewed and edited the manuscript, and Dr. Sainbileg reviewed and edited the manuscript. All authors discussed the results and approved the manuscript. 7.6. Acknowledgments We gratefully acknowledge the members and colleagues of the Department of Endocrinology in the School of Medicine, Mongolia; the Department of Forensic Medicine in the School of BioMedical Sciences, Mongolia; Yonsei University College of Medicine, Korea; and Jeonbuk National University, Korea, for their invaluable guidance and assistance. We also thank the doctors and staff of Endomed Endocrinology hospital for their support and for approving the performance of skin biopsies at their facility. References Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract. 2019;157:107843. Patterson CC, Karuranga S, Salpea P, Saeedi P, Dahlquist G, Soltesz G et al. 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Nat Rev Endocrinol. 2021;17(7):400–20. Selvarajah D, Kar D, Khunti K, Davies MJ, Scott AR, Walker J, et al. Diabetic peripheral neuropathy: advances in diagnosis and strategies for screening and early intervention. Lancet Diabetes Endocrinol. 2019;7(12):938–48. Gibbons CH, Griffin JW, Polydefkis M, Bonyhay I, Brown A, Hauer PE, et al. The utility of skin biopsy for prediction of progression in suspected small fiber neuropathy. Neurology. 2006;66(2):256–8. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the. use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. J Peripher Nerv Syst. 2010;15(2):79–92. Malik RA. Diabetic neuropathy: A focus on small fibres. Diabetes Metab Res Rev. 2020;36(Suppl 1):e3255. Devigili G, Cazzato D, Lauria G. Clinical diagnosis and management of small fiber neuropathy: an update on best practice. Expert Rev Neurother. 2020;20(9):967–80. Vas PR, Sharma S, Rayman G. Distal Sensorimotor Neuropathy: Improvements in Diagnosis. Rev Diabet Stud. 2015;12(1–2):29–47. Sommer C. Skin biopsy as a diagnostic tool. Curr Opin Neurol. 2008;21(5):563–8. Timar B, Popescu S, Timar R, Baderca F, Duica B, Vlad M, et al. The usefulness of quantifying intraepidermal nerve fibers density in the diagnostic of diabetic peripheral neuropathy: a cross-sectional study. Diabetol Metab Syndr. 2016;8:31. Devigili G, Tugnoli V, Penza P, Camozzi F, Lombardi R, Melli G, et al. The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. Brain. 2008;131(Pt 7):1912–25. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 17 Apr, 2026 Reviews received at journal 17 Apr, 2026 Reviews received at journal 08 Feb, 2026 Reviews received at journal 05 Feb, 2026 Reviews received at journal 02 Feb, 2026 Reviewers agreed at journal 02 Feb, 2026 Reviews received at journal 31 Jan, 2026 Reviewers agreed at journal 31 Jan, 2026 Reviewers agreed at journal 31 Jan, 2026 Reviewers agreed at journal 30 Jan, 2026 Reviews received at journal 30 Jan, 2026 Reviewers agreed at journal 30 Jan, 2026 Reviews received at journal 30 Jan, 2026 Reviewers agreed at journal 30 Jan, 2026 Reviewers agreed at journal 30 Jan, 2026 Reviewers invited by journal 30 Jan, 2026 Editor invited by journal 09 Jan, 2026 Editor assigned by journal 08 Jan, 2026 Submission checks completed at journal 08 Jan, 2026 First submitted to journal 05 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8518662","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":583682140,"identity":"1e402cd1-0fba-4fe0-ba5c-5a08fd7710cb","order_by":0,"name":"Oyunbileg Bavuu","email":"","orcid":"","institution":"Mongolian National University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Oyunbileg","middleName":"","lastName":"Bavuu","suffix":""},{"id":583682144,"identity":"9e2be5f6-1d2f-4176-bc12-b345179cdbcc","order_by":1,"name":"Sainbileg Sonomtseren","email":"","orcid":"","institution":"Mongolian National University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Sainbileg","middleName":"","lastName":"Sonomtseren","suffix":""},{"id":583682149,"identity":"3267bfea-66ae-42e7-b3ce-b9e786ac9280","order_by":2,"name":"Bayarmaa Enkhbat","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8klEQVRIiWNgGAWjYBACAwST+QAWQfxa2BJI1sJjgEUQCzBnP2P4uTLHTp6Bvefr5sK2bfYM7M3bJBhz7uDUYtmTYyx5dluyYQPP2W23Z7bdTmzgOVYmwbjtGW6HHcgxkGzcxszYIJG77TZv2+0EBokcM6CWw7i1nH9j/LNxW719g/ybZyAt9gzybwhouZFjBrTlcGKDBA8bSAvQOh78WixnPCuzbNx2PLmNJ83sNs+524lARrFFIh4t5vzJm282bqu27Wc//Ow2T9lte372wxtvfMSjhYGBAxILbDA+mJGARwMDA/sDvNKjYBSMglEwChgAtClUjkm7I34AAAAASUVORK5CYII=","orcid":"","institution":"Mongolian National University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Bayarmaa","middleName":"","lastName":"Enkhbat","suffix":""}],"badges":[],"createdAt":"2026-01-05 08:23:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8518662/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8518662/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101789165,"identity":"ddf15c11-784c-435f-b83e-bbcc03b3892c","added_by":"auto","created_at":"2026-02-03 15:56:22","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":483668,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of glycemic control between genders and diabetes duration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe bar graph illustrates (A) the percentage of participants with glycemic control. All male participants exhibited poor control, whereas female participants showed 14.3% good control (HbA1C level \u0026lt; 6.5%), 4.8% moderate control (HbA1C level 6.5% - 7.5%), and 81% poor control (HbA1C level \u0026gt; 7.5%).\u003c/p\u003e\n\u003cp\u003eA scatterplot shows (B) a positive correlation between longer diabetes duration with higher HbA1C levels. Correlation was assessed using Spearman correlation analysis; p \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8518662/v1/b9c74f2361f496af2b28e47f.png"},{"id":101789161,"identity":"ca2f771f-985f-4695-ab84-7f097eaef76c","added_by":"auto","created_at":"2026-02-03 15:56:22","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":223542,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparison of clinical examination and skin punch biopsy of DPN in T1DM and T2DM patients\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe results from clinical examination showed (A) that 11.1% of T1DM and 19% of T2DM patients were diagnosed with no DPN. In the skin punch biopsy (B), 100% of T1DM patients were diagnosed with DPN, which was categorized as mild, moderate, or severe. The results highlighted a significant discrepancy in DPN diagnosis between the two methods, particularly in T1DM patients.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8518662/v1/ee7a1cc69c8ae3cf686d38bc.png"},{"id":101789106,"identity":"0e91444b-862c-47e4-bd1e-1a8f2b9d833a","added_by":"auto","created_at":"2026-02-03 15:56:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":2024578,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eIENFD demonstrated greater diagnostic accuracy than clinical examination in the early stages of DPN.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e(A) Representative images of skin biopsy specimens from the distal leg of patients with mild (upper panel) and severe (lower panel) diabetic neuropathy. Sections were immunostained with antibodies against protein gene product 9.5 for bright-field microscopy (magnification x 40, scale bar 100 µm). Arrows indicate intraepidermal nerve fibers that are counted throughout the section. Patients with severe neuropathy show a complete loss of intraepidermal nerve fibers.\u003c/p\u003e\n\u003cp\u003e(B) Box plots that show the distribution of the diabetes duration and HbA1C levels across DPN stages based on IENFD. The boxes represent the interquartile range (IQR), with the horizontal line indicating the median. Whiskers extend to 1.5 times the IQR. Progressive loss of nerve fibers is associated with longer disease duration and high HbA1C levels, supporting a correlation between hyperglycemia and small nerve damage.\u003c/p\u003e\n\u003cp\u003e(C) Receiver operating characteristic (ROC) curve showing the diagnostic performance of IENF for DPN detection. The x-axis represents the false positive rate (1-specificity) and the y-axis represents sensitivity (true positive rate). Bar graph comparing the diagnostic performance of IENFD against conventional clinical examination for DPN. IENFD demonstrated superior sensitivity in the early stage of neuropathy. Error bars represent the 95% confidence intervals (95% CI) for each value.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8518662/v1/d7b3517aaa9b7830af7b62b3.png"},{"id":101880684,"identity":"d1db6c95-7506-4dad-bf11-d52be05ce2e0","added_by":"auto","created_at":"2026-02-04 15:05:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5340845,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8518662/v1/cc0dac6b-1f29-45e7-a068-6aa1badbbfd7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical and Immunohistochemical Evaluation of Peripheral Neuropathy in Diabetic Patients","fulltext":[{"header":"1. Background","content":"\u003cp\u003eDiabetic peripheral neuropathy (DPN) is a prevalent and severe complication of diabetes mellitus, affecting nearly 50% of diabetic patients and leading to significant health issues and increased healthcare costs [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In Mongolia, the prevalence of diabetes has risen from 3.1% in 1999 to 10% in 2019 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], with DPN affecting 71% of diabetic patients. Those with DPN had 3 times higher incidence of history of foot ulceration compared to patients without DPN [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe early symptoms of diabetic neuropathy, such as pain, loss of proprioception and sense of temperature, and alteration in sweating, are due to the degeneration of small somatic nerve fibers, which traditional physical, neurophysiological, and neuropathological tests may not detect [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Thus, emphasizing the need for more sensitive and specific diagnostics to detect DPN earlier stage. Intraepidermal nerve fiber density (IENFD) in skin biopsy, using pan-neuronal marker Protein Gene Product (PGP 9.5), became popular to diagnose small nerve fibers even before clinical symptoms [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In both animal and human studies, a decrease in PGP 9.5 IENFD has been demonstrated in cases of DPN. These findings have shown high sensitivity and specificity for detecting early nerve damage associated with DPN [\u003cspan additionalcitationids=\"CR8 CR9\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCurrently, there\u0026rsquo;s no information on the early effects of diabetes on peripheral nerve fibers in Mongolia. In this study, we evaluated diabetic peripheral neuropathy using traditional functional tests and a modern diagnostic approach involving skin punch biopsy with the PGP 9.5 antibody. We aimed to emphasize the importance of early detection and the potential integration of this technique into diagnostic protocols to improve clinical outcomes for patients with diabetes in Mongolia.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003eA cross-sectional study recruited 30 diabetic patients, aged between 20 and 74 years, from the Endocrinology Hospital in Ulaanbaatar, Mongolia.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Measurement of metabolic parameters\u003c/h2\u003e \u003cp\u003eAll participants were measured for body composition, including current weight, height, waist circumference, and body fat. Weight and body fat mass were assessed using a digital body composition monitor (CITIZEN Body Fat Analyzer BM-100), and height and circumference were measured to the nearest 0.1 cm with light indoor clothing. Body Mass Index (BMI) was calculated as weight in kilograms (kg) divided by the square of height in meters and categorized based on the WHO BMI guidelines: \u0026lt; 18.5 kg/m\u0026sup2; as underweight, 18.5 to 24.9 kg/m\u0026sup2; as normal weight, 25 to 29.9 kg/m\u0026sup2; as overweight, and \u0026gt;\u0026thinsp;30 kg/m\u0026sup2; as obese. Blood pressure (BP) was measured using an automated device (Omron HCR-7104) after participants relaxed for at least 30 min in a quiet room. All measurements were conducted by a trained assistant following standard protocols.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Diabetic peripheral neuropathy assessment\u003c/h2\u003e \u003cp\u003eThe neuropathic symptoms, such as numbness, tingling, burning, and sharp pain in the feet or leg pain, were assessed by questionnaire. General inspections evaluated skin color and texture (dryness, thickness), nail abnormalities, foot deformities, callus formation, fissures, infection, ulceration, and history of amputation. Common forefoot deformities, such as claw and hammer toe, which increase plantar pressures and cause breakdown, were identified. Additionally, the evaluation included checking for Charcot arthropathy, a unilateral red, hot, swollen, flat foot with deformity, particularly affecting the midfoot.\u003c/p\u003e \u003cp\u003eThe clinical exam for diabetic neuropathy was designed to identify the loss of protective sensation, which includes five simple clinical tests.\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe pressure sensation test used 10 g monofilaments (SEMMES-WEINSTEIN) to screen for pressure sensation loss, associated with large-fiber nerve function. The monofilament applied a 10 g force to the 1st, 3rd, and 5th metatarsal heads and plantar surface of the distal hallux on each foot while the patient\u0026rsquo;s eyes were closed. The sensation was first demonstrated to the patient on the upper arm. During the test, the patient was asked to respond \u0026ldquo;yes\u0026rdquo; or \u0026ldquo;no\u0026rdquo; to indicate whether they felt monofilament and to identify the site, avoiding areas with calluses. A maximum score is 10; a score of 8 or less indicates neuropathy, and the absence of feeling indicates a complete lack of pressure sensation.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe vibration sensation test was assessed bilaterally at the hallux using a 128 Hz tuning fork (RYDEL SEIFFER). With the patient lying supine, the fork was placed on the dorsal hallux, and the amplitude increased until the patient could detect the vibration. Normal values were specified as 6/8\u0026ndash;8/8 for patients under 40 and 5/8\u0026ndash;8/8 for patients over 40. Loss of sensation was characterized by scores below 6/8 for under 40, and below 5/8 for those over 40. The absence of feeling indicated the complete lack of vibration sensation.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003ePinprick sensation test used a single-use disposable pin \u0026ldquo;NEUROTIPS\u0026rdquo;, applied to the toenail on the dorsal surface of the hallux with pressure. An inability to perceive pinprick sensation on either hallux was considered abnormal. Patients were also assessed for their ability to distinguish between a sharp and a non-sharp end. The responses were categorized as follows: no neuropathy (clearly distinguishable), neuropathy (occasional difficulty), and complete absence (inability to distinguish).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe thermal sensation test used a TIP-TERM pen-shaped device with a plastic end and a metal end to evaluate the presence of neuropathy. Patients were assessed for their ability to distinguish between cold and warm temperatures applied to the skin in the outlined areas. The responses were reported as follows: no neuropathy (clearly distinguishable), neuropathy (occasional difficulty), and complete absence (inability to distinguish between temperatures).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eThe tactile sensation (light touch) test used cotton wool to lightly touch the skin and determine if patients felt the sensation symmetrically in all areas. The responses were reported as follows: no neuropathy (clearly distinguishable), neuropathy (occasional difficulty), and complete absence (inability to distinguish light touch).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cp\u003eIn addition, the ankle tendon reflex was assessed by the hammer with the patient kneeling or resting on the examination couch.\u003c/p\u003e \u003cp\u003eDiabetic peripheral neuropathy was classified as follows: no neuropathy (no signs or symptoms), mild neuropathy (both signs and symptoms present), and severe neuropathy (severe signs and symptoms of diabetic polyneuropathy or absence of all peripheral sensations).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Diabetic peripheral artery disease assessment\u003c/h2\u003e \u003cp\u003eThe vascular assessment was performed by palpating the posterior tibial and dorsalis pedis artery pulses, and categorizing them as present, weak, or absent. Additionally, the ankle-brachial index (ABI) was used to diagnose lower limb vascular insufficiency, which compares the systolic blood pressure in the ankle to the systolic blood pressure in the brachial. An ABI of 0.9 to 1.3 was considered normal, whereas values below 0.9 or above 1.3 were associated with claudication.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. The intraepidermal nerve fiber assessment\u003c/h2\u003e \u003cp\u003eSkin punch tissue samples were obtained from the distal leg (10 cm above the lateral malleolus) using a 3 mm disposable punch under sterile technique, following local anesthesia with 2% lidocaine. The skin samples were fixed in a 10% formalin solution at 4\u0026deg;C, and then the tissues were embedded in paraffin, and the paraffin blocks were sectioned into 5-\u0026micro;m-thick slices. The specimens were blocked with 10% normal goat serum at room temperature (RT) for 30 minutes in a dark place, then incubated with the PGP 9.5 primary antibody overnight in a moist chamber at 4\u0026deg;C. Subsequently, the sections were incubated with anti-rabbit IgG secondary antibody for 30 min at RT. Detection was performed using the avidin-biotin-peroxidase method. Images were captured at x40 objective magnification along the entire length, and nerve fibers were counted in four non-consecutive sections; mean values were used for statistical analysis. Two independent blinded observers were quantified with no significant difference between observers. The quantitative evaluation of diabetic neuropathy was based on the number of intraepidermal nerve fibers (fibers/mm\u003csup\u003e2\u003c/sup\u003e). Nerve fibers were counted and classified as follows: no neuropathy (more than 12), mild neuropathy (9\u0026ndash;12 nerve fibers), moderate neuropathy (5\u0026ndash;8 nerve fibers), and severe neuropathy (0\u0026ndash;4 nerve fibers).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5. Statistical analysis\u003c/h2\u003e \u003cp\u003eAll graphs, calculations, and statistical analyses were performed using GraphPad Prism software. Data were assessed for normality, with continuous data expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD and categorical variables expressed as numbers with percentages. Student\u0026rsquo;s t-test was used to compare continuous variables, and the Chi-square test to compare categorical variables. An analysis of variance (ANOVA) was utilized for multiple group comparisons. Unconditional logistic regression models were used to calculate adjusted odds ratios [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] and their 95% confidence intervals (CIs). Statistical significance was accepted at a P value of less than 0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec9\"\u003e\n \u003ch2\u003e\u003cstrong\u003e3.1\u003c/strong\u003e. \u003cstrong\u003ePatients with T2DM exhibited higher cardiometabolic risk compared to T1DM\u003c/strong\u003e\u003c/h2\u003e\n \u003cp\u003eThe study included a total of 30 patients with diabetes (33.3% male, 66.7% female). The mean age of patients was 49.07 ± 4.09 (20–74) years, with 56.7% of participants over 50 years. Patients with T1DM were significantly younger than those with T2DM, although diabetes duration did not differ between the groups (mean 9.46 ± 5.74 years). Systolic blood pressure was significantly higher in the T2DM group (p = 0.001), whereas heart rate and diastolic blood pressure showed no significant differences between the groups. Patients with T2DM also had a higher body mass index (BMI), waist circumference (WC), and body fat mass (p \u0026lt; 0.001) compared with T1DM. No significant differences were observed in fasting blood glucose, HbA1C, and total cholesterol levels (Tables\u0026nbsp;1 and 2). Despite similar glycemic control and diabetes duration, patients with T2DM exhibited greater cardiovascular and microvascular risk factors, as well as obesity-related parameters, compared to T1DM.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eBasic characteristics of diabetic patients\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"5\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eParameters\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eT1DM (n = 9)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eT2DM (n = 21)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e49.07 ± 14.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e31.67 ± 9.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e56.52 ± 9.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetes duration (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.46 ± 5.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10.89 ± 5.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.85 ± 5.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.397\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHeart rate (bpm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e90.07 ± 14.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e95.11 ± 17.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e87.90 ± 12.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.293\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSystolic BP (mm Hg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e146.2 ± 23.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e127.3 ± 4.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e154.3 ± 4.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiastolic BP (mm Hg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e90.8 ± 12.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e84.78 ± 3.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e93.38 ± 2.69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.059\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody mass index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27.59 ± 5.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21.75 ± 2.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30.09 ± 4.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWaist circumference (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e96 ± 16.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e76.78 ± 6.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e104.24 ± 11.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody fat mass (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33.81 ± 11.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20.97 ± 8.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e39.31 ± 7.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTotal cholesterol (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.01 ± 7.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.20 ± 8.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7.93 ± 7.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.935\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFBG (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13.88 ± 5.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14.71 ± 7.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13.52 ± 4.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.670\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHbA1C (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.81 ± 1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.98 ± 1.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.73 ± 2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.731\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e\u003cem\u003eFBG\u003c/em\u003e: Fasting blood glucose, \u003cem\u003eHbA1C\u003c/em\u003e: Glycated hemoglobin\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eComparison of age, sex, and metabolic profiles between T1DM and T2DM groups\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"8\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eTotal (n = 30)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eT1DM (n = 9)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eT2DM (n = 21)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge group (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19–29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"5\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30–39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40–49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50–59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt; 60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDiabetic duration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0–1 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"4\"\u003e\n \u003cp\u003e0.459\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1–5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5–10 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt; 10 years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e28.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody fat mass\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e36.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"3\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverweight\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eObesity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHbA1C (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt; 6.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"3\"\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.5–7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt; 7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cem\u003eBMI\u003c/em\u003e: Body Mass Index\u003c/p\u003e\n \u003cp\u003eAmong the participants, the majority (94%) demonstrated poor glycemic control (HbA1C \u0026gt; 7.5%), while only 3% had moderately controlled (HbA1C 6.5% − 7.5%), and 3% had good-controlled (HbA1C \u0026lt; 6.5%) glycemic levels. In contrast, all male participants (100%) and all patients with diabetes duration more than 5 years (n = 21) had poorly controlled blood glucose, suggesting an association between diabetes duration and glycemic control (Fig.\u0026nbsp;1A and 1B). However, no significant difference in glycemic control was observed between T1DM and T2DM.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\"\u003e\n \u003ch2\u003e\u003cstrong\u003e3.2\u003c/strong\u003e. \u003cstrong\u003eFoot examinations revealed a high prevalence of peripheral neuropathy in diabetic patients.\u003c/strong\u003e\u003c/h2\u003e\n \u003cp\u003eMost participants experienced at least one symptom of DPN, with numbness and pain during walking, reported 83.3% and 60%, respectively. Table\u0026nbsp;3 showed other DPN symptoms, including dry skin (83.3%) and increased skin thickness (76.7%). Consistent with these findings, we observed loss of vibration (53.3%) and thermal sensation (76.7%), while the Achilles reflex was absent (66.7%) in diabetic patients (Table\u0026nbsp;4). Vascular assessment demonstrated absent or weak pedal pulses in up to one-third of patients. Furthermore, an abnormal ankle-brachial index (ABI) was found in 6.7% of participants, suggesting early or asymptomatic peripheral artery disease.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 3\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eClinical Characteristics of Diabetic Peripheral Neuropathy\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"8\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSigns and symptoms\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eTotal (n = 30)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eT1DM (n = 9)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eT2DM (n = 21)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSigns in foot\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.286\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFoot ulcer before\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.389\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePain in walking\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.704\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChanges of skin color\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.637\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDry skin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e83.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.143\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNail problems\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFoot deformation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.300\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCalluses\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.681\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSkin thickness\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e44.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCracked skin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.207\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e77.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFoot infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.517\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e93.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFoot ulcer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.517\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e93.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAmputaion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.300\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e96.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e88.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e100\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 4\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eAssessment of Peripheral Neuropathy by Clinical Examination\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"8\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eNeuropathy test\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eTotal (n = 30)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eT1DM (n = 9)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eT2DM (n = 21)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(%)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e(%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePressure sensation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e73.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e77.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e71.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLoss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eVibration sensation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e46.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.236\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLoss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e53.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e61.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePinprick sensation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e36.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.999\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLoss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e63.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e61.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eThermal sensation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.393\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLoss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e76.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e88.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e71.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTactile sensation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e43.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"2\"\u003e\n \u003cp\u003e0.123\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLoss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e56.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAchilles reflex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e33.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" rowspan=\"3\"\u003e\n \u003cp\u003e0.651\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAbsence on both\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e55.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e71.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAbsence on one side\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e11.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eThe prevalence of DPN among study participants was 83.3% as determined by food examination. According to the severity of neuropathy classification, 26,7% of patients had mild neuropathy, 40% moderate, and 16.6% severe neuropathy. However, there was no significant difference in the prevalence or severity between type 1 and type 2 diabetes mellitus (Fig.\u0026nbsp;2A).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\"\u003e\n \u003ch2\u003e\u003cstrong\u003e3.3\u003c/strong\u003e. \u003cstrong\u003eReduction of intraepidermal nerve fiber density correlated with metabolic risk in diabetic patients.\u003c/strong\u003e\u003c/h2\u003e\n \u003cp\u003eDiabetic peripheral neuropathy (DPN) was diagnosed based on intraepidermal nerve fiber density (IENFD) assessed per 1 mm\u003csup\u003e2\u003c/sup\u003e of skin. Mean IENFD was 7.87 ± 4.72 fibers/mm² overall, 6.44 ± 2.83 fibers/mm² in T1DM, and 8.48 ± 5.27 fibers/mm² in T2DM patients. A total of 26 individuals (86.7%) were diagnosed with DPN as defined by an IENFD of fewer than 12 nerve fibers per mm\u003csup\u003e2\u003c/sup\u003e (Fig.\u0026nbsp;3A). Among that, mild DPN was observed in 6 (20%), moderate DPN in 7 (23.3%), while severe DPN in 13 (43.4%) individuals. All T1DM patients exhibited DPN as diagnosed by skin punch biopsy, whereas 4 (19%) patients with T2DM detected no DPN (Fig.\u0026nbsp;2B). Figure\u0026nbsp;3B showed correlation of DPN with diabetes duration (V = 0.876, p \u0026lt; 0.0001) and HbA1C levels (V = 0.760, p \u0026lt; 0.0001).\u003c/p\u003e\n \u003cp\u003eThe sensitivity and specificity of IENFD (\u0026lt; 12 fibers/mm\u003csup\u003e2\u003c/sup\u003e) were 92% and 40% respectively, with a positive predictive value (PPV) of 88.5%, a negative predictive value (NPV) of 50%, and an overall diagnostic accuracy of 83.3% (Fig.\u0026nbsp;3C).\u003c/p\u003e\n\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThe study provides comprehensive evidence regarding the prevalence and characteristics of diabetic peripheral neuropathy (DPN) in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Utilizing clinical foot examinations and intraepidermal nerve fiber density analysis, we found that many participants displayed clinical symptoms of DPN, and a substantial proportion confirmed the presence of neuropathy through reduced epidermal nerve fibers.\u003c/p\u003e \u003cp\u003eIn this study, patients with T2DM have significantly higher cardiovascular risk factors, including BMI, waist circumference, systolic blood pressure, and body fat mass, than those with T1DM, despite similar diabetes duration and glycemic control. These findings were consistent with previous studies that highlight patients with T2DM have increased metabolic syndrome and obesity-related complications, which further elevate their risk for neuropathy and cardiovascular disease [\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDiabetic peripheral neuropathy is commonly diagnosed by clinical examination, which evaluates pain, vibration sense, and other sensory functions. However, the accuracy of these evaluations depends on both the examiner and the stage of the disease [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In our study, over 75% of patients reported symptoms such as numbness and pain, and sensory testing revealed loss of thermal, vibration, and pinprick sensations. These findings are similar to other large-scale studies, including MONICA/KORA study in Germany [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e], which reported a high prevalence of sensory abnormalities in patients with poor glycemic control and long-standing diabetes [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Importantly, subclinical signs of peripheral artery disease were also observed in patients with diabetes, emphasizing the value of early detection and vascular screening in diabetic care [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEvaluating IENFD via skin biopsy provides a more objective method, especially for small fiber neuropathy that may not be identified by clinical examination. Moreover, skin biopsy allows for a detailed assessment of nerve damage, supporting a more effective treatment strategy [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In our study, IENFD confirmed reduced small nerve fiber density in the majority (86.7%) of participants, with most exhibiting moderate to severe stages, and all T1DM patients were diagnosed with DPN. These findings support previous reports that small fiber neuropathy may develop early in T1DM, even without overt metabolic features [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Callaghan et al. and Tesfaye et al. reported the role of chronic hyperglycemia in peripheral nerve degeneration [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Consistently, we observed a strong correlation between DPN and both diabetes duration (V\u0026thinsp;=\u0026thinsp;0.876, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and HbA1C levels (V\u0026thinsp;=\u0026thinsp;0.760, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). Our finding suggests that age and duration of DM in practitioners may not be major determinants of neuropathic risk, but improved glucose monitoring can be critical for preventing the development of diabetes related neuropathic complications. The diagnostic performance of IENFD for clinically defined DPN demonstrated high sensitivity (92%), but low specificity (40%), with a diagnostic accuracy of 83.3%. These suggest that IENFD is a sensitive and objective biomarker for small fiber damage, particularly valuable for subclinical signs and early stages of neuropathy [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Previous studies conducted by Devigili et al. and Lauria et al. have demonstrated that skin biopsy is a reliable tool for diagnosing small fiber neuropathy, with a diagnostic yield exceeding 85% when combined with clinical assessment [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Moreover, Grazia Devigili and Valeria Tugnoli in 2008 [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], evaluated 486 individuals using multiple diagnostic methods, including clinical sensory tests, autonomic function tests, electromyography, and skin biopsies. Results showed that among 150 patients diagnosed with neuropathy (77 females and 73 males, aged 22 to 84, average age 60), 54.6% were diagnosed through sensory evaluations, 46.9% through nerve conduction studies, and 88% through skin biopsies. Combining with those studies and our results identified the assessment of epidermal nerve fiber density (IENFD) as the most accurate and reliable approach, particularly for early detection of DPN, despite its time-consuming and costly.\u003c/p\u003e"},{"header":"5. Study limitations","content":"\u003cp\u003eThis study includes multiple diagnostic methods, including validated questionnaires, foot examination, and histological analysis. However, we did not include electrophysiological tests such as nerve conduction studies, which may be more important for large fiber function. Skin punch biopsy is also not widely available and can only be performed in specialized centers with trained staff in Mongolia. Follow-up skin biopsies can be useful to monitor the progression of neuropathy and treatment results. In addition, the number of participants was relatively small, which may limit the statistical difference and generalizability of the findings to broader populations.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe prevalence of diabetic peripheral neuropathy (DPN) is alarmingly high among patients with diabetes mellitus. Diabetes duration and poor glycemic control were strongly associated with greater severity of DPN. Intraepidermal nerve fiber density (IENFD) highlights a more objective method for diagnosis; however, a combination of clinical assessment with IENFD analysis provides a comprehensive and accurate approach for diagnosing DPN in both clinical and research fields.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e7.1. Ethics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by\u0026nbsp;the Biomedical Research Ethical Committee of the Mongolian National University of Medical Sciences (approval number: #13-09/1A),\u0026nbsp;and was conducted in accordance with the Declaration of Helsinki. Written informed consent was obtained from all\u0026nbsp;participants before participation. Exclusion criteria included non-diabetic individuals with neurological or other systemic disorders, and patients who declined to participate.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e7.2. Consent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e7.3. Availability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this study are included in this article. Additional datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e7.4. Comp\u003c/strong\u003e\u003cstrong\u003eeting interest\u003c/strong\u003e\u003cstrong\u003es\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that there is no conflict of interest regarding the publication of this article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e7.5. Funding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study received no specific funding, grants, or other financial support during the preparation of this manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e7.6. Authors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDr. Oyunbileg performed most of the experiments and prepared the manuscript. Dr. Bayarmaa designed the experiments and reviewed and edited the manuscript, and Dr. Sainbileg reviewed and edited the manuscript. All authors discussed the results and approved the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e7.6. Acknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe gratefully acknowledge the members and colleagues of the Department of Endocrinology in the School of Medicine, Mongolia; the Department of Forensic Medicine in the School of BioMedical Sciences, Mongolia; Yonsei University College of Medicine, Korea; and Jeonbuk National University, Korea, for their invaluable guidance and assistance. We also thank the doctors and staff of Endomed Endocrinology hospital for their support and for approving the performance of skin biopsies at their facility.\u0026nbsp;\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSaeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract. 2019;157:107843.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePatterson CC, Karuranga S, Salpea P, Saeedi P, Dahlquist G, Soltesz G et al. Worldwide estimates of incidence, prevalence and mortality of type 1 diabetes in children and adolescents: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107842.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDayan A, Erkhembayar R, Luvsandavaajav O, Mukhtar Y, Enkhtuvshin B, Tumenbayar B. Prevalence of Type 2 Diabetes in Mongolia: Results from Population-Based Survey Compared with 1999 Study. Diabetes Metab Syndr Obes. 2023;16:1833\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSainbileg S, Altaisaikhan K, Tsagaankhuu G. Prevalence of Diabetic neuropathy, risk factors, diagnosis and treatment. Mongolia: Mongolian National University of Medical Sciences; 2011.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLauria G, Cornblath DR, Johansson O, McArthur JC, Mellgren SI, Nolano M, et al. EFNS guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy. Eur J Neurol. 2005;12(10):747\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLauria G, Hsieh ST, Johansson O, Kennedy WR, Leger JM, Mellgren SI, et al. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on the use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. Eur J Neurol. 2010;17(7):903\u0026ndash;12. e44-9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWalk D, Wendelschafer-Crabb G, Davey C, Kennedy WR. 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Diabetes Care. 2017;40(4):569\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTesfaye S, Boulton AJ, Dyck PJ, Freeman R, Horowitz M, Kempler P, et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010;33(10):2285\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeldman EL, Callaghan BC, Pop-Busui R, Zochodne DW, Wright DE, Bennett DL, et al. Diabetic neuropathy. Nat Rev Dis Primers. 2019;5(1):41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSloan G, Selvarajah D, Tesfaye S. Pathogenesis, diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy. Nat Rev Endocrinol. 2021;17(7):400\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSelvarajah D, Kar D, Khunti K, Davies MJ, Scott AR, Walker J, et al. Diabetic peripheral neuropathy: advances in diagnosis and strategies for screening and early intervention. Lancet Diabetes Endocrinol. 2019;7(12):938\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGibbons CH, Griffin JW, Polydefkis M, Bonyhay I, Brown A, Hauer PE, et al. The utility of skin biopsy for prediction of progression in suspected small fiber neuropathy. Neurology. 2006;66(2):256\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEuropean Federation of Neurological Societies/Peripheral Nerve Society Guideline on the. use of skin biopsy in the diagnosis of small fiber neuropathy. Report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society. J Peripher Nerv Syst. 2010;15(2):79\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalik RA. Diabetic neuropathy: A focus on small fibres. Diabetes Metab Res Rev. 2020;36(Suppl 1):e3255.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDevigili G, Cazzato D, Lauria G. Clinical diagnosis and management of small fiber neuropathy: an update on best practice. Expert Rev Neurother. 2020;20(9):967\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVas PR, Sharma S, Rayman G. Distal Sensorimotor Neuropathy: Improvements in Diagnosis. Rev Diabet Stud. 2015;12(1\u0026ndash;2):29\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSommer C. Skin biopsy as a diagnostic tool. Curr Opin Neurol. 2008;21(5):563\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTimar B, Popescu S, Timar R, Baderca F, Duica B, Vlad M, et al. The usefulness of quantifying intraepidermal nerve fibers density in the diagnostic of diabetic peripheral neuropathy: a cross-sectional study. Diabetol Metab Syndr. 2016;8:31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDevigili G, Tugnoli V, Penza P, Camozzi F, Lombardi R, Melli G, et al. The diagnostic criteria for small fibre neuropathy: from symptoms to neuropathology. Brain. 2008;131(Pt 7):1912\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Diabetes, diabetic neuropathy, epidermal nerve fiber, immunohistochemistry, skin biopsy","lastPublishedDoi":"10.21203/rs.3.rs-8518662/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8518662/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eDiabetic peripheral neuropathy is a prevalent and severe complication of diabetes that significantly impacts a patient\u0026rsquo;s quality of life. Early diagnosis through clinical examination and intraepidermal nerve fiber density (IENFD) measurement is essential. However, limited healthcare access and specialists, and uncontrolled blood glucose levels increase the risk of lower limb amputation. This is the first study in Mongolia to evaluate epidermal nerve fibers for the assessment of DPN.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods and Results\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThirty diabetic patients (20\u0026ndash;74 years) underwent foot examination and skin punch biopsies. The skin biopsies were analyzed by immunohistochemistry using protein gene product 9.5 (PGP 9.5) antibody to quantify the total IENF. Among participants, 94% had poor glycemic control, were diagnosed with 26.7% mild, 40% moderate, and 16.7% severe neuropathy. The average number of epidermal nerve fibers in 1 mm was 7.87\u0026thinsp;\u0026plusmn;\u0026thinsp;4.72, reflecting an 86.7% reduction. DPN showed a strong correlation with both diabetes duration (V\u0026thinsp;=\u0026thinsp;0.876, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and HbA1C level (V\u0026thinsp;=\u0026thinsp;0.760, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). The specificity and sensitivity of the immunohistochemistry method were 40% and 92%, respectively.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e \u003cp\u003eDPN severity is associated with diabetes duration and poor glycemic control. IENFD highlights a more objective measure of small nerve fiber reduction, and combining it with clinical assessment provides a comprehensive and accurate approach for diagnosing DPN. Early detection of DPN, strict glycemic control, and integration of IENFD into diagnostic protocols are urgently needed, particularly in developing countries such as Mongolia.\u003c/p\u003e","manuscriptTitle":"Clinical and Immunohistochemical Evaluation of Peripheral Neuropathy in Diabetic Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-03 15:55:19","doi":"10.21203/rs.3.rs-8518662/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-04-17T08:53:08+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-17T06:42:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-08T05:30:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-05T17:49:09+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-02T15:29:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"157377556053629788624668766245820872695","date":"2026-02-02T13:45:24+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-01T04:16:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"276036715443186146580688721551216533645","date":"2026-02-01T04:08:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"313992506730539923616171518163305692349","date":"2026-01-31T09:19:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"332648209158373725912427929502455386965","date":"2026-01-30T13:26:24+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-30T12:03:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"254925865722250561665538357570220365301","date":"2026-01-30T11:28:01+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-30T11:23:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"173480412329656144065204295549910179388","date":"2026-01-30T11:01:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"308414846987642040925323223933615512449","date":"2026-01-30T07:53:31+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-30T07:04:01+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-09T06:45:49+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-08T07:28:14+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-08T07:27:37+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Endocrine Disorders","date":"2026-01-05T07:57:05+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"635204b0-bb4e-445d-b8c5-78c8cfeb22b5","owner":[],"postedDate":"February 3rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-04-17T09:10:57+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-03 15:55:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8518662","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8518662","identity":"rs-8518662","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}