Diabetes & Metabolism Journal

Brief Report

Complication
Morphologic Comparison of Peripheral Nerves in Adipocyte Tissue from db/db Diabetic versus Normal Mice: Kyung Ae Lee, Na Young Lee, Tae Sun Park, Heung Yong Jin; Diabetes Metab J. 2018;42(2):169-172. Published online March 21, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.2.169

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Abstract PDF PubReader: Present study investigated the morphologic changes of autonomic nerves in the adipose tissue in diabetic animal model. Male obese type 2 diabetic db/db mice and age matched non-diabetic db/m control mice were used. Epididymal adipose tissue from diabetic db/db mice with that from control heterozygous db/m mice was compared using confocal microscopy-based method to visualize intact whole adipose tissue. Immunohistochemistry with tyrosine hydroxylase for sympathetic (SP), choline acetyltransferase for parasympathetic (PSP), and protein gene product 9.5 (PGP 9.5) for whole autonomic nerves was performed. The quantity of immunostained portion of SP, PSP, and PGP 9.5 stained nerve fibers showed decreased trend in diabetic group; however, the ratio of SP/PSP of adipose tissue was higher in diabetic group compared with control group as follows (0.70±0.30 vs. 0.95±0.25, P<0.05; normal vs. diabetic, respectively). Both SP and PSP nerve fibers were observed in white adipose tissue and PSP nerve fibers were suggested as more decreased in diabetes based on our observation.

Original Articles

Clinical Diabetes & Therapeutics
Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea: Sol Jae Lee, Su Jin Jeong, Yu Chang Lee, Yong Hoon Lee, Jung Eun Lee, Chong Hwa Kim, Kyung Wan Min, Bong Yun Cha; Diabetes Metab J. 2017;41(4):275-283. Published online July 6, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.4.275

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Background

Diabetic cardiac autonomic neuropathy (CAN) is one of the important complications of diabetes. It is characterized by reduced heart rate variability (HRV).

Methods

In this randomized, double-blind, placebo-controlled, multicenter trial, 75 patients were randomly assigned to one of two groups. One group (n=41) received α-lipoic acid (ALA) at an oral dose of 600 mg/day for the first 12 weeks and then 1,200 mg/day for the next 12 weeks. The other group (n=34) received placebo treatment for 24 weeks. CAN was assessed by measuring HRVs in people with diabetes.

Results

Most of the baseline measures for HRVs were similar between the ALA and placebo groups. Although there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial, we found a positive tendency in some of the HRV parameters of the ALA group. The standard deviations of normal-to-normal RR intervals in the standing position increased by 1.87 ms in the ALA group but decreased by −3.97 ms in the placebo group (P=0.06). The power spectrum of the low frequency (LF) band in the standing position increased by 15.77 ms² in the ALA group, whereas it declined by −15.04 ms² in the placebo group (P=0.08). The high frequency/LF ratio in the upright position increased by 0.35 in the ALA group, whereas it declined by −0.42 in the placebo group (P=0.06). There were no differences between the two groups regarding rates of adverse events.

Conclusion

Although a slight improvement tendency was seen in HRV in the ALA group, there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial. However, the high oral dose of ALA was well-tolerated.

Citations

Citations to this article as recorded by

Cardiovascular autonomic neuropathy in diabetes: an update with a focus on management
Aikaterini Eleftheriadou, Vincenza Spallone, Abd A. Tahrani, Uazman Alam
Diabetologia.2024;[Epub] CrossRef
Effect of Ramipril on Cardiac Autonomic Neuropathy in Patients With Type II Diabetes Mellitus
Chaitali A Chindhalore, Ganesh N Dakhale, Prathamesh H Kamble, Bharatsing D Rathod, Sunita Kumbhalkar, Mrunal S Phatak
Cureus.2023;[Epub] CrossRef
Evaluating treatment options for cardiovascular autonomic neuropathy in patients with diabetes mellitus: a systematic review
Jasmine KaiLi Goh, Leroy Koh
Diabetology International.2023; 14(3): 224. CrossRef
The effects of alpha lipoic acid (ALA) supplementation on blood pressure in adults: a GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials
Mahdi Vajdi, Nooshin Noshadi, Shirin Hassanizadeh, Atefeh Bonyadian, Hooria Seyedhosseini-Ghaheh, Gholamreza Askari
Frontiers in Cardiovascular Medicine.2023;[Epub] CrossRef
Combination Therapy of Alpha-Lipoic Acid, Gliclazide and Ramipril Protects Against Development of Diabetic Cardiomyopathy via Inhibition of TGF-β/Smad Pathway
George J. Dugbartey, Quinsker L. Wonje, Karl K. Alornyo, Louis Robertson, Ismaila Adams, Vincent Boima, Samuel D. Mensah
Frontiers in Pharmacology.2022;[Epub] CrossRef
Diabetic Gastroenteropathy: Soothe the Symptoms or Unravel a Cure?
Sondre Meling, Davide Bertoli, Dag A. Sangnes, Christina Brock, Asbjørn Drewes, Niels Ejskjaer, Georg Dimcevski, Eirik Søfteland
Current Diabetes Reviews.2022;[Epub] CrossRef
Efficacy and safety of oral alpha-lipoic acid supplementation for type 2 diabetes management: a systematic review and dose–response meta-analysis of randomized trials
Aliyu Tijani Jibril, Ahmad Jayedi, Sakineh Shab-Bidar
Endocrine Connections.2022;[Epub] CrossRef
Cardiac Autonomic Neuropathy in Type 1 and 2 Diabetes: Epidemiology, Pathophysiology, and Management
Scott Williams, Siddig Abdel Raheim, Muhammad Ilyas Khan, Umme Rubab, Prathap Kanagala, Sizheng Steven Zhao, Anne Marshall, Emily Brown, Uazman Alam
Clinical Therapeutics.2022; 44(10): 1394. CrossRef
An updated systematic review and dose-response meta-analysis of the effects of α-lipoic acid supplementation on glycemic markers in adults
Mahsa Mahmoudi-Nezhad, Mahdi Vajdi, Mahdieh Abbasalizad Farhangi
Nutrition.2021; 82: 111041. CrossRef
Management of diabetic neuropathy
Simona Cernea, Itamar Raz
Metabolism.2021; 123: 154867. CrossRef
Effect of alpha-lipoic acid on arterial stiffness parameters in type 2 diabetes mellitus patients with cardiac autonomic neuropathy
Victoria A. Serhiyenko, Ludmila M. Serhiyenko, Volodymyr B. Sehin, Alexandr A. Serhiyenko
Endocrine Regulations.2021; 55(4): 224. CrossRef
The Role of Alpha-lipoic Acid Supplementation in the Prevention of Diabetes Complications: A Comprehensive Review of Clinical Trials
Sarah Jeffrey, Punitha Isaac Samraj, Behin Sundara Raj
Current Diabetes Reviews.2021;[Epub] CrossRef
Safety Evaluation of α-Lipoic Acid Supplementation: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Clinical Studies
Federica Fogacci, Manfredi Rizzo, Christoffer Krogager, Cormac Kennedy, Coralie M.G. Georges, Tamara Knežević, Evangelos Liberopoulos, Alexandre Vallée, Pablo Pérez-Martínez, Eliane F.E. Wenstedt, Agnė Šatrauskienė, Michal Vrablík, Arrigo F.G. Cicero
Antioxidants.2020; 9(10): 1011. CrossRef
Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet
Vincenza Spallone
Diabetes & Metabolism Journal.2019; 43(1): 3. CrossRef
Alpha-lipoic acid (ALA) supplementation effect on glycemic and inflammatory biomarkers: A Systematic Review and meta- analysis
Mehran Rahimlou, Maryam Asadi, Nasrin Banaei Jahromi, Anahita Mansoori
Clinical Nutrition ESPEN.2019; 32: 16. CrossRef
Alpha-lipoic acid and diabetic cardiac autonomic neuropathy
Victoria Serhiyenko, Ludmila Serhiyenko, Alexandr Serhiyenko
MOJ Public Health.2019; 8(1): 8. CrossRef
Response: Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea (Diabetes Metab J 2017;41:275-83)
Chong Hwa Kim, Sol Jae Lee, Bong Yun Cha
Diabetes & Metabolism Journal.2017; 41(5): 420. CrossRef
Letter: Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea (Diabetes Metab J2017;41:275-83)
Jeongmin Lee, Jae Hyoung Cho
Diabetes & Metabolism Journal.2017; 41(5): 417. CrossRef

Complications
Prevalence and Risk Factors of Gastroesophageal Reflux Disease in Patients with Type 2 Diabetes Mellitus: Jun Ouk Ha, Tae Hee Lee, Chang Won Lee, Ja Young Park, Seong Ho Choi, Hee Seung Park, Jae Seung Lee, Seung Heon Lee, Eun Hee Seo, Young Hwan Kim, Young Woo Kang; Diabetes Metab J. 2016;40(4):297-307. Published online June 8, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.4.297

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Background

Gastrointestinal symptoms are common in patients with type 2 diabetes mellitus (T2DM). The prevalence of gastroesophageal reflux disease (GERD) in Korea appears to be increasing. Some studies have shown that T2DM is a risk factor for symptomatic GERD. However, this possibility is still debated, and the pathogenesis of GERD in T2DM is not yet fully understood. The aim of this study was to analyze the prevalence and risk factors (including autonomic neuropathy) of GERD in patients with T2DM.

Methods

This cross-sectional case-control study enrolled T2DM patients (n=258) and healthy controls (n=184). All participants underwent physical examinations and laboratory tests. We evaluated medical records and long-term diabetes complications, including peripheral and autonomic neuropathy in patients with T2DM. Esophagogastroduodenoscopy was performed in all patients. The Los Angeles (LA) classification was used to grade GERD. GERD was defined as LA grade A (or higher) or minimal change with GERD symptoms. GERD symptoms were examined using a frequency scale. Data were expressed as mean±standard error. Independent t-tests or chi-square tests were used to make comparisons between groups.

Results

The prevalence of GERD (32.6% vs. 35.9%, P=0.266) and GERD symptoms (58.8% vs. 59.2%, P=0.503) was not significantly different between T2DM patients and controls. We found no significant differences between T2DM patients with GERD and T2DM patients without GERD with respect to diabetic complications, including autonomic neuropathy, peripheral neuropathy, duration of DM, and glucose control.

Conclusion

The prevalence of GERD in patients with T2DM showed no difference from that of controls. GERD was also not associated with peripheral and cardiovascular autonomic neuropathy, age, or duration of DM in patients with T2DM.

Citations

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Ураження органів травлення при цукровому діабеті
M.O. Borovets , О.М. Radchenko , Kh.A. Moskva , O.Yo. Komarytsya , A.M. Urbanovych
Endokrynologia.2023; 28(3): 270. CrossRef
Metabolic effects of bariatric surgery on patients with type 2 diabetes: a population-based study
Erman O. Akpinar, Ronald S.L. Liem, Simon W. Nienhuijs, Jan Willem M. Greve, Perla J. Marang-van de Mheen, L.M. de Brauw, S.M.M. de Castro, S.L. Damen, A. Demirkiran, M. Dunkelgrun, I.F. Faneyte, G. van ‘t Hof, I.M.C. Janssen, R.A. Klaassen, E.A.G.L. Laga
Surgery for Obesity and Related Diseases.2021; 17(7): 1349. CrossRef
The effect of proton pump inhibitors on glycaemic control in diabetic patients
Muhammad Ali Rajput, Fizzah Ali, Tabassum Zehra, Shahid Zafar, Gunesh Kumar
Journal of Taibah University Medical Sciences.2020; 15(3): 218. CrossRef
Prediabetes and gastrointestinal (GI) symptoms; a cross-sectional study
Akram Ghadiri-Anari, Somaye Gholami, Fariba Zolfaghari, Nasim Namiranian
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2019; 13(1): 844. CrossRef
Gastrointestinal Symptoms in Diabetes: Prevalence, Assessment, Pathogenesis, and Management
Yang T. Du, Christopher K. Rayner, Karen L. Jones, Nicholas J. Talley, Michael Horowitz
Diabetes Care.2018; 41(3): 627. CrossRef
Features of Endoscopic Changes in Gastroesophageal Reflux Disease in Patients with Type II Diabetes Mellitus
Ye. S. Sirchak, M. P. Stan, Yo. I. Pichkar, V. V. Vajs
Ukraïnsʹkij žurnal medicini, bìologìï ta sportu.2018; 3(5): 166. CrossRef
Prevalence and Correlates of Gastroesophageal Reflux Disease in Southern Iran: Pars Cohort Study
Zohre Khodamoradi, Abdullah Gandomkar, Hossein Poustchi, Alireza Salehi, Mohammad Hadi Imanieh, Arash Etemadi, Reza Malekzadeh
Middle East Journal of Digestive Diseases.2017; 9(3): 129. CrossRef
Letter: Prevalence and Risk Factors of Gastroesophageal Reflux Disease in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J2016;40:297-307)
Dongwon Yi
Diabetes & Metabolism Journal.2016; 40(5): 418. CrossRef
Response: Prevalence and Risk Factors of Gastroesophageal Reflux Disease in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J2016;40:297-307)
Jun Ouk Ha, Tae Hee Lee, Chang Won Lee
Diabetes & Metabolism Journal.2016; 40(5): 420. CrossRef

Review

Pathophysiology
Morphologic Changes in Autonomic Nerves in Diabetic Autonomic Neuropathy: Heung Yong Jin, Hong Sun Baek, Tae Sun Park; Diabetes Metab J. 2015;39(6):461-467. Published online December 11, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.6.461

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Diabetic neuropathy is one of the major complications of diabetes, and it increases morbidity and mortality in patients with both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Because the autonomic nervous system, for example, parasympathetic axons, has a diffuse and wide distribution, we do not know the morphological changes that occur in autonomic neural control and their exact mechanisms in diabetic patients with diabetic autonomic neuropathy (DAN). Although the prevalence of sympathetic and parasympathetic neuropathy is similar in T1DM versus T2DM patients, sympathetic nerve function correlates with parasympathetic neuropathy only in T1DM patients. The explanation for these discrepancies might be that parasympathetic nerve function was more severely affected among T2DM patients. As parasympathetic nerve damage seems to be more advanced than sympathetic nerve damage, it might be that parasympathetic neuropathy precedes sympathetic neuropathy in T2DM, which was Ewing's concept. This could be explained by the intrinsic morphologic difference. Therefore, the morphological changes in the sympathetic and parasympathetic nerves of involved organs in T1DM and T2DM patients who have DAN should be evaluated. In this review, evaluation methods for morphological changes in the epidermal nerves of skin, and the intrinsic nerves of the stomach will be discussed.

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Impaired Cardiovagal Activity as a Link Between Hyperglycemia and Arterial Stiffness in Adults With Type 2 Diabetes Mellitus Among an Eastern Indian Population: A Cross-sectional Study
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Canadian Journal of Diabetes.2024; 48(3): 147. CrossRef
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European Journal of Neurology.2022; 29(7): 2097. CrossRef
Pathogenesis of Distal Symmetrical Polyneuropathy in Diabetes
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Critical Reviews in Food Science and Nutrition.2019; 59(6): 830. CrossRef
Pulse pressure amplification and cardiac autonomic dysfunction in patients with type 2 diabetes mellitus
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Original Articles

Relationship between the Korean Version Survey of the Autonomic Symptoms Score and Cardiac Autonomic Neuropathy Parameters in Patients with Diabetic Peripheral Neuropathy: Sun Hee Kim, Kyung Ae Lee, Heung Yong Jin, Hong Sun Baek, Tae Sun Park; Diabetes Metab J. 2014;38(5):349-355. Published online October 17, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.5.349

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Background

The Survey of Autonomic Symptom (SAS) scale was reported as an easy instrument to assess the autonomic symptoms in patients with early diabetic neuropathy. In this study, we investigated the relationship between the SAS scale and the parameters of cardiac autonomic neuropathy (CAN) in Korean patients with diabetic peripheral neuropathy (DPN).

Methods

The SAS scale was tested in 30 healthy controls and 73 patients with DPN at Chonbuk National University Hospital, in Korea. The SAS score was compared to the parameters of the CAN test and the total symptom score (TSS) for DPN in patients with DPN.

Results

The SAS symptom score and total impact score were increased in patients with DPN compared to the control group (P=0.01), particularly in sudomotor dysfunction (P=0.01), and vasomotor dysfunction (P=0.01). The SAS score was increased in patients with CAN compared to patients without CAN (P<0.05). Among the diverse CAN parameters, the valsalva ratio and postural hypotension were associated with the SAS score (P<0.05). However, there was no association between the SAS scale and TSS for DPN, and TSS for DPN did not differ between patients with and without CAN.

Conclusion

SAS is a simple instrument that can be used to assess autonomic symptoms in patients with diabetes and can be used as a screening tool for autonomic neuropathy, particularly for CAN.

Citations

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Autonomic neuropathic symptoms in patients with diabetes: practical tools for screening in daily routine
Ana Raquel Souza de Azevedo Vieira, Lara Benigno Porto-Dantas, Flaviene Alves do Prado Romani, Patrícia Souza Carvalho, Rodica Pop-Busui, Hermelinda Cordeiro Pedrosa
Diabetology & Metabolic Syndrome.2023;[Epub] CrossRef
Symptomatic diabetic autonomic neuropathy in type 1 diabetes (T1D): Findings from the T1D exchange
Kara Mizokami-Stout, Ryan Bailey, Lynn Ang, Grazia Aleppo, Carol J. Levy, Michael R. Rickels, Viral N. Shah, Sarit Polsky, Bryce Nelson, Anders L. Carlson, Francesco Vendrame, Rodica Pop-Busui
Journal of Diabetes and its Complications.2022; 36(5): 108148. CrossRef
Clinical Assessment Scales in Autonomic Nervous System Disorders
Eun Bin Cho, Ki-Jong Park
Journal of the Korean Neurological Association.2021; 39(2 Suppl): 60. CrossRef
Peripheral Nerve Conduction And Sympathetic Skin Response Are Reliable Methods to Detect Diabetic Cardiac Autonomic Neuropathy
Xiaopu Lin, Chuna Chen, Yingshan Liu, Yu Peng, Zhenguo Chen, Haishan Huang, Lingling Xu
Frontiers in Endocrinology.2021;[Epub] CrossRef
Predictive model to identify the risk of losing protective sensibility of the foot in patients with diabetes mellitus
Esther Chicharro‐Luna, Francisco José Pomares‐Gómez, Ana Belen Ortega‐Ávila, Ana Marchena‐Rodríguez, José Francisco Javier Blanquer‐Gregori, Emmanuel Navarro‐Flores
International Wound Journal.2020; 17(1): 220. CrossRef
The hemodynamic and pain impact of peripheral nerve block versus spinal anesthesia in diabetic patients undergoing diabetic foot surgery
Hou Yee Lai, Li Lian Foo, Siu Min Lim, Chen Fei Yong, Pui San Loh, Sook Hui Chaw, Mohd Shahnaz Hasan, Chew Yin Wang
Clinical Autonomic Research.2020; 30(1): 53. CrossRef
Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet
Vincenza Spallone
Diabetes & Metabolism Journal.2019; 43(1): 3. CrossRef
Validation of the Composite Autonomic Symptom Score 31 (COMPASS 31) for the assessment of symptoms of autonomic neuropathy in people with diabetes
C. Greco, F. Di Gennaro, C. D'Amato, R. Morganti, D. Corradini, A. Sun, S. Longo, D. Lauro, G. Pierangeli, P. Cortelli, V. Spallone
Diabetic Medicine.2017; 34(6): 834. CrossRef
Cardiovascular Autonomic Dysfunction Predicts Diabetic Foot Ulcers in Patients With Type 2 Diabetes Without Diabetic Polyneuropathy
Jae-Seung Yun, Seon-Ah Cha, Tae-Seok Lim, Eun-Young Lee, Ki-Ho Song, Yu-Bae Ahn, Ki-Dong Yoo, Joon-Sung Kim, Yong-Moon Park, Seung-Hyun Ko
Medicine.2016; 95(12): e3128. CrossRef
Retinal Neurodegeneration Associated With Peripheral Nerve Conduction and Autonomic Nerve Function in Diabetic Patients
Kiyoung Kim, Seung-Young Yu, Hyung Woo Kwak, Eung Suk Kim
American Journal of Ophthalmology.2016; 170: 15. CrossRef
Screening of Autonomic Neuropathy in Patients with Type 2 Diabetes
Bo Kyung Koo
Diabetes & Metabolism Journal.2014; 38(5): 346. CrossRef

Assessment of Diabetic Polyneuropathy and Autonomic Neuropathy Using Current Perception Threshold in Korean Patients with Diabetes Mellitus: Bo Kyung Koo, Jung Hun Ohn, Soo-Heon Kwak, Min Kyong Moon; Diabetes Metab J. 2014;38(4):285-293. Published online August 20, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.4.285

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Background

The current perception threshold (CPT) could be quantified by stimulating Aβ and C fibers at 2,000 and 5 Hz, respectively. C fibers play a role in the autonomic nervous system and are involved in temperature and pain sensation. We evaluated the usefulness of CPT for diagnosing distal polyneuropathy (DPN) and cardiovascular autonomic neuropathy (CAN) in diabetic patients.

Methods

The CPT was measured in the index finger (C7 level) and in the third toe (L5 level) in diabetic patients aged 30 to 69 years. We assessed DPN according to the neuropathy total symptom score-6 (NTSS-6) and 10-g monofilament pressure sensation. Subjects with a NTSS-6 >6 or with abnormal 10-g monofilament sensation were defined to have DPN. CAN was evaluated by spectral analysis of heart rate variability and by Ewing's traditional tests.

Results

The subjects with DPN had significantly higher CPT at all of the frequencies than the subjects without DPN (P<0.05). Abnormal 10-g monofilament sensation and NTSS-6 >6 could be most precisely predicted by CPT at 2,000 and 5 Hz, respectively. However, only 6.5% and 19.6% of subjects with DPN had an abnormal CPT at 2,000 Hz at the C7 and L5 levels. Although CPT at 5 Hz showed a negative correlation with the power of low and high frequency in the spectral analysis (P<0.05), only 16.7% of subjects with CAN exhibited an abnormal CPT at the same frequency.

Conclusion

Although the CPT is significantly associated with neuropathic symptoms or signs corresponding to the nerve fiber stimulated, it provides little additional information compared with conventional evaluations.

Citations

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New Perspective in Diabetic Neuropathy: From the Periphery to the Brain, a Call for Early Detection, and Precision Medicine
Heng Yang, Gordon Sloan, Yingchun Ye, Shuo Wang, Bihan Duan, Solomon Tesfaye, Ling Gao
Frontiers in Endocrinology.2020;[Epub] CrossRef
Patterns of Nerve Conduction Abnormalities in Patients with Type 2 Diabetes Mellitus According to the Clinical Phenotype Determined by the Current Perception Threshold
Joong Hyun Park, Jong Chul Won
Diabetes & Metabolism Journal.2018; 42(6): 519. CrossRef
Association between Pain Sensitivity, Central Sensitization, and Functional Disability in Adolescents With Joint Hypermobility
Elizabeth A. Bettini, Ki Moore, Yunfei Wang, Pamela S. Hinds, Julia C. Finkel
Journal of Pediatric Nursing.2018; 42: 34. CrossRef
The impact of neuropathic pain and other comorbidities on the quality of life in patients with diabetes
Vesna Dermanovic Dobrota, Pero Hrabac, Dinko Skegro, Ranko Smiljanic, Savko Dobrota, Ingrid Prkacin, Neva Brkljacic, Kristijan Peros, Martina Tomic, Vesna Lukinovic-Skudar, Vanja Basic Kes
Health and Quality of Life Outcomes.2014;[Epub] CrossRef

Ruboxistaurin for the Treatment of Diabetic Peripheral Neuropathy: A Systematic Review of Randomized Clinical Trials: Dipika Bansal, Yogesh Badhan, Kapil Gudala, Fabrizio Schifano; Diabetes Metab J. 2013;37(5):375-384. Published online October 17, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.5.375

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Background

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus. Protein kinase C (PKC) inhibitor's has been thought to be a potential disease modifying drug's in DPN as it slows or reverse neuropathy's progression. To assesses the efficacy and safety of ruboxistaurin on the progression of symptoms, signs, or functional disability in DPN.

Methods

A systematic review of the literature databases like PubMed, ProQuest, EBSCO, EMBASE, and Cochrane Central was performed up to August 2012. We included randomized controlled trials (RCTs) comparing PKC inhibitor ruboxistaurin (RBX) with control and lasting at least 6 months. Our primary outcome measure was change in neurological examination, measured by neurological total symptom score (NTSS) and vibration detection threshold (VDT). Secondary outcome measures were total quality of life (QoL), skin microvascular blood flow and others.

Results

Six RCTs were included in review. Change in neurological function assessed by NTSS was reported in six studies, out of which significant difference between the RBX and placebo group seen in four studies favouring treatment group while remaining two studies reported no significant difference. VDT was assessed in only one study in which no significant difference seen between RBX and placebo group. Two studies reported significant improvement in QoL data. Safety data was reported in only two studies in which none of side effect was related to RBX.

Conclusion

RBX had effects on DPN in some studies, but the evidence is not enough for meta-analysis and firm conclusion.

Citations

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Journal of Diabetes Science and Technology.2024; 18(1): 159. CrossRef
Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy
Yaowei Lv, Xiangyun Yao, Xiao Li, Yuanming Ouyang, Cunyi Fan, Yun Qian
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Relationships between Brachial-Ankle Pulse Wave Velocity and Peripheral Neuropathy in Type 2 Diabetes: Byung Kil Ha, Bong Gun Kim, Dong Hyun Kim, Soon Il Lee, Soon Myung Jung, Ja Young Park, Chang Won Lee, Sang Soo Kim, Bo Hyun Kim, In Ju Kim; Diabetes Metab J. 2012;36(6):443-451. Published online December 12, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.6.443

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Background

Brachial-ankle pulse wave velocity (baPWV) is known to be a good surrogate marker of clinical atherosclerosis. Atherosclerosis is a major predictor for developing neuropathy. The goal of this study was to determine the relationship between baPWV and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes.

Methods

A retrospective cross-sectional study was conducted involving 692 patients with type 2 diabetes. The correlation between increased baPWV and DPN, neurological symptoms, and neurological assessment was analyzed. DPN was examined using the total symptom score (TSS), ankle reflexes, the vibration test, and the 10-g monofilament test. DPN was defined as TSS ≥2 and an abnormal neurological assessment. Data were expressed as means±standard deviation for normally distributed data and as median (interquartile range) for non-normally distributed data. Independent t-tests or chi-square tests were used to make comparisons between groups, and a multiple logistic regression test was used to evaluate independent predictors of DPN. The Mantel-Haenszel chi-square test was used to adjust for age.

Results

Patients with DPN had higher baPWV and systolic blood pressure, and were more likely to be older and female, when compared to the control group. According to univariate analysis of risk factors for DPN, the odds ratio of the baPWV ≥1,600 cm/sec was 1.611 (95% confidence interval [CI], 1.072 to 2.422; P=0.021) and the odds ratio in female was 1.816 (95% CI, 1.195 to 2.760; P=0.005).

Conclusion

Increased baPWV was significantly correlated with peripheral neuropathy in patients with type 2 diabetes.

Citations

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Association of arterial stiffness and neuropathy in diabetes: a systematic review and meta-analysis
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Tae Hoon Lim, Seung Min Chung, Dong Sung Lee, Se Ra Choi, Jun Sung Moon, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee
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High Brachial Ankle Pulse Wave Velocity as a Marker for Predicting Coronary Artery Stenosis in Patients with Type 2 Diabetes
Bo Hyun Kim, Jae Sik Jang, Yong Seop Kwon, June Hyung Kim, In Joo Kim, Chang Won Lee
Endocrinology and Metabolism.2018; 33(1): 88. CrossRef
Nerve conduction velocity is negatively associated with intima-media thickness and brachial-ankle pulse wave velocity in men with type 2 diabetes mellitus
Sayuri Tanaka, Ippei Kanazawa, Toshitsugu Sugimoto, Rayaz A. Malik
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Anastasios Tentolouris, Ioanna Eleftheriadou, Pinelopi Grigoropoulou, Alexander Kokkinos, Gerasimos Siasos, Ioannis Ntanasis-Stathopoulos, Nikolaos Tentolouris
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Influence of Visceral Adiposity on Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus: Eun-Hee Jang, Na-Young Kim, Yong-Moon Park, Mee-Kyoung Kim, Ki Hyun Baek, Ki-Ho Song, Kwang Woo Lee, Hyuk-Sang Kwon; Diabetes Metab J. 2012;36(4):285-292. Published online August 20, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.4.285

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Abstract PDF PubReader

Background

The aim of this study was to investigate the influences of visceral adiposity on cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus.

Methods

Two hundred eleven patients with type 2 diabetes participated in this study. Anthropometric and metabolic parameters were measured, and the visceral fat area was assessed using computed tomography. CAN was diagnosed using a cardiovascular reflex test. We analyzed the correlation between the visceral fat area and each parameter in this test.

Results

The mean age, body mass index (BMI), and duration of diabetes of the study population were 60±14 years (mean±standard deviation), 25.1±4.2 kg/m², and 12.3±8.9 years, respectively. The visceral fat area showed positive correlations with age, BMI, waist circumference, and subcutaneous fat area. There was no statistically significant difference in the cardiovascular reflex test outcome between genders. Univariate linear regression analysis showed that an increased visceral fat area diminished good heart rate response to a Valsalva maneuver (R²=4.9%, P=0.013 in an unadjusted model), but only in women. This statistical association was preserved after adjusting for age and BMI (R²=9.8%, P=0.0072).

Conclusion

The results of this study suggest that visceral adiposity contributes to an autonomic imbalance to some degree, as demonstrated by the impaired cardiovascular reflex test among women with type 2 diabetes.

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Hideyo Tsutsui, Kyoko Nomura, Masataka Kusunoki, Tetsuya Ishiguro, Takayoshi Ohkubo, Yoshiharu Oshida
Diabetology International.2016; 7(3): 289. CrossRef
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Cardiovascular Diabetology.2014;[Epub] CrossRef

Clinical Significance of the Presence of Autonomic and Vestibular Dysfunction in Diabetic Patients with Peripheral Neuropathy: Soo Kyoung Kim, Kyeong Ju Lee, Jong Ryeal Hahm, Sang Min Lee, Tae Sik Jung, Jung Hwa Jung, Sungsu Kim, Deok Ryong Kim, Seong-Ki Ahn, Won-Hee Choi, Soon Il Chung; Diabetes Metab J. 2012;36(1):64-69. Published online February 17, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.1.64

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Background

We investigated the prevalence of diabetic autonomic neuropathy (DAN) and vestibular dysfunction (VD) in diabetic patients with peripheral neuropathy.

Methods

Thirty-five diabetic patients with peripheral neuropathy were enrolled from August 2008 to July 2009. All subjects underwent autonomic function tests. Nineteen of the patients (54.3%) underwent videonystagmography.

Results

Diabetic autonomic neuropathy was observed in 28 patients (80%). A mild degree of autonomic failure was observed in 18 patients (64.3%), and a moderate degree of autonomic failure was observed in ten patients (35.7%). Factors related to DAN included diabetic nephropathy (P=0.032), degree of chronic kidney disease (P=0.003), and duration of diabetes (P=0.044). Vestibular dysfunction was observed in 11 of 19 patients (57.9%). There was no significant association between DAN and VD.

Conclusion

Diabetic autonomic neuropathy was observed in 28 diabetic patients (80%) with peripheral neuropathy. Vestibular dysfunction was observed in nearly 60% of diabetic patients with peripheral neuropathy who complained of dizziness but showed no significant association with DAN. Diabetic patients who complained of dizziness need to examine both autonomic function and vestibular function.

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Review

Diabetic Peripheral Neuropathy in Type 2 Diabetes Mellitus in Korea: Seung-Hyun Ko, Bong-Yun Cha; Diabetes Metab J. 2012;36(1):6-12. Published online February 17, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.1.6

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Abstract PDF PubReader

Diabetic peripheral neuropathy (DPN), a common and troublesome complication in patients with type 2 diabetes mellitus (T2DM), contributes to a higher risk of diabetic foot ulcer and lower limb amputation. These situations can negatively impact the quality of life of affected individuals. Despite its high prevalence and clinical importance, most diabetes mellitus patients not only do not recognize the presence of diabetic neuropathy, but also do not report their symptoms to physicians or other health care providers. Therefore, DPN is usually under diagnosed and undertreated. For early detection and appropriate intervention for DPN, a careful history, physical with neurologic examination, and prompt treatment are needed in T2DM patients.

Citations

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Original Articles

The Association between Serum GGT Concentration and Diabetic Peripheral Polyneuropathy in Type 2 Diabetic Patients: Ho Chan Cho; Korean Diabetes J. 2010;34(2):111-118. Published online April 30, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.2.111

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Abstract PDF PubReader

Background

Diabetic peripheral polyneuropathy (DPP) is one of the common complications of diabetes mellitus (DM) and can lead to foot ulcers or amputation. The pathophysiology of DPP includes several factors such as metabolic, vascular, autoimmune, oxidative stress and neurohormonal growth-factor deficiency and recent studies have suggested the use of serum gamma-glutamyl transferase (GGT) as an early marker of oxidative stress. Therefore, we investigated whether serum GGT may be useful in predicting DPP.

Methods

We assessed 90 patients with type 2 DM who were evaluated for the presence of DPP using clnical neurologic examinations including nerve conduction velocity studies. We evaluated the association between serum GGT and the presence of DPP.

Results

The prevalence of DPP was 40% (36 cases) according to clinical neurological examinations. The serum GGT concentration was significantly elevated in type 2 diabetic patients with DPP compared to patients without DPP (P < 0.01). There were other factors significantly associated with DPP including smoking (P = 0.019), retinopathy (P = 0.014), blood pressure (P < 0.05), aspartate aminotransferase (P = 0.022), C-reactive protein (P = 0.036) and urine microalbumin/creatinine ratio (P = 0.004). Serum GGT was independently related with DPP according to multiple logistic analysis (P < 0.01).

Conclusion

This study shows that increased levels of serum GGT may have important clinical implications in the presence of DPP in patients with type 2 diabetes.

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The association of liver enzymes with diabetes mellitus risk in different obesity subgroups: A population-based study
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The Effect of Alpha-Lipoic Acid on the Protection of Epidermal Nerve Fibers and Microcapillaries in the Streptozotocin-Induced Diabetic Rats.: Ming Han Piao, Heung Yong Jin, Sun Kyung Song, Seun Mi Kang, So Young Kim, Ji Hyun Park, Hong Sun Baek, Tae Sun Park; Korean Diabetes J. 2007;31(6):488-497. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.488

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Abstract PDF: BACKGROUND
Diabetic neuropathy is associated with risk factors for macrovascular diseases and other microvascular complications. Alpha-lipoic acid (ALA) administration has been reported to improve metabolic abnormalities and ameliorate peripheral polyneuropathy in diabetic patients. In addition, ALA improves endoneurial nutritive neural blood flow and nerve conduction velocity in diabetic rats. But it is not clear whether ALA has a preservation effect on microvasculature in addition to the effect on intraepidermal nerve fibers (IENFs). We investigated the effect of ALA on intraepidermal nerve fiber density (numbers/mm) and cutaneous capillary length in streptozotocin-induced diabetic rats. METHODS: The rats were randomly divided into 3 groups: diabetes without diet control, diabetes with diet control, and diabetes with ALA treatment. Diabetes was induced by a single intraperitoneal injection of streptozotocin (60 mg/kg) and the effect of ALA treatment was assessed by IENF immunostained with protein gene product 9.5 and by quantification of total cutaneous capillary length with mouse anti-rat reca-1 immunostaining. RESULTS: The value of IENF density significantly increased in ALA treatment group compared with other groups (P < 0.05). Quantification of microvascularity was also significantly increased in ALA treatment group compared with other groups (P < 0.05). CONCLUSION: The results of this study suggest that ALA administration in diabetic rats may be beneficial in the prevention of peripheral neuropathy associated with improvement of microvascularity. And the symptomatic amelioration after ALA treatment may be attributed to this morphological improvement.

The Association of Aldose Reductase Gene Polymorphisms with Neuropathy in Patients with Type 2 Diabetes.: In Kyong Jeong, Kyong Soo Park, Min Kyong Moon, Jae Hyeon Kim, Chan Soo Shin, Seong Yeon Kim, Hong Kyu Lee; Korean Diabetes J. 2007;31(3):274-283. Published online May 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.3.274

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Abstract PDF

BACKGROUND
Previous studies have suggested that polymorphisms in and around the aldose reductase (AR) gene are associated with the development of diabetic microvascular disease. This study explored the hypothesis that the polymorphisms of the (A-C)n dinucleotide repeat sequence, located at 2.1 kilobase (kb) upstream of the transcription start site of AR gene, modulate the risk of diabetic neuropathy (DN). METHODS: 66 patients with DN, 30 without microvascular complications (MC) after 20 years of diabetes, and 87 normal healthy controls were studied. To test highly polymorphic microsatellite marker 2.1 kb upstream of the initiation site of the AR gene, we performed polymerase chain reaction using the primer labeled with fluorescent dye and GeneScan by ABI prism 377 automated DNA sequencer and ABI Genotyper software 2.0. RESULTS: Seven alleles (Z-6, Z-4, Z-2, Z, Z+2, Z+4 and Z+6) were identified. Z-2 allele was more frequently observed in patients with DN (77.3%) than in those without MC (43.3%, P = 0.007). The subgroup of patients who developed DN within 5 years after the diagnosis of diabetes also had higher frequency of Z-2 allele (91.7%) compared to those without MC (43.3%, P = 0.028). On the contrary, Z+6 allele tended to be more frequent in patients without MC (10.0%) than in those with DN (0%, P = 0.063). CONCLUSION: These results support the hypothesis that environmental-genetic interactions may modulate the risk of neuropathy in patients with diabetes. Particularly, the Z-2 allele, in the presence of diabetes, may be associated with the development of DN.

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The Association between Serum GGT Concentration and Diabetic Peripheral Polyneuropathy in Type 2 Diabetic Patients
Ho Chan Cho
Korean Diabetes Journal.2010; 34(2): 111. CrossRef

Erythropoietin Levels According to the Presence of Peripheral Neuropathy in Diabetic Patients with Anemia.: Heung Yong Jin, Su Jin Jeung, Chong Hwa Kim, Ji Hyun Park, Hong Sun Baek, Tae Sun Park; Korean Diabetes J. 2007;31(2):151-156. Published online March 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.2.151

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Abstract PDF

BACKGROUND
Peripheral neuropathy is a common complication of diabetes mellitus, contributing the greatest morbidity and mortality and impairing the quality of life. Recently the receptor of erythropoietin (Epo) was proven to be expressed in neuronal cell and recombinant human Epo (rhEpo) has been shown to have neuroprotective and neurotrophic potential in peripheral neuropathy. But there is no report about baseline Epo level in blood before rhEpo treatment with diabetic peripheral neuropathy. METHODS: From Jan. 2000 to Sep. 2006, diabetic patients were reviewed about Epo level in blood, anemia, and peripheral neuropathy in Chonbuk National University Hospital. And we compared the mean value of baseline Epo level in diabetic patients with anemia according to the peripheral neuropathy. RESULTS: The mean value of Epo of patients with peripheral neuropathy was lower than that of patients without peripheral neuropathy (16.3 +/- 7.1 vs 26.1 +/- 29.7 mU/mL, P < 0.05). There was no significance in the correlation between hemoglobin and Epo level in diabetic patients with anemia irrespective of presence of peripheral neuropathy (r = -0.02, P = 0.81). CONCLUSION: We suggest that decreased Epo level in blood is possible to be an additional cause in the development of peripheral neuropathy. However, simultaneously another possibility that neuropathy causes reduced Epo level should be considered, so further studies are warranted in this field.

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The Association between Serum GGT Concentration and Diabetic Peripheral Polyneuropathy in Type 2 Diabetic Patients
Ho Chan Cho
Korean Diabetes Journal.2010; 34(2): 111. CrossRef

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