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 ePub: 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

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Nutrition, Metabolism and Cardiovascular Diseases.2026; 36(2): 104370. CrossRef
Effectiveness of Alpha Lipoic Acid in Type 2 Diabetes Mellitus patients with Cardiac Autonomic Neuropathy
Geetha. P, Bharathi. D, Deepa. N, Gopi. G, Shamshath Begum, Devi. T
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Protocol for the FibroCAN study: a randomised controlled trial of finerenone treatment for early-stage cardiovascular autonomic neuropathy in type 2 diabetes
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Aikaterini Eleftheriadou, Vincenza Spallone, Abd A. Tahrani, Uazman Alam
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Remodeling of the Intracardiac Ganglia During the Development of Cardiovascular Autonomic Dysfunction in Type 2 Diabetes: Molecular Mechanisms and Therapeutics
Anthony J. Evans, Yu-Long Li
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Chaitali A Chindhalore, Ganesh N Dakhale, Prathamesh H Kamble, Bharatsing D Rathod, Sunita Kumbhalkar, Mrunal S Phatak
Cureus.2023;[Epub] CrossRef
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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
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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
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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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Gastroesophageal reflux disease influences blood pressure components, lipid profile and cardiovascular diseases: Evidence from a Mendelian randomization study
Qiang Wu, Changjing He, Wanzhong Huang, Chaoqun Song, Xin Hao, Qing Zeng, Dazhi Lan, Qiang Su
Journal of Translational Internal Medicine.2024; 12(5): 510. CrossRef
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Endokrynologia.2023; 28(3): 270. CrossRef
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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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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
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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.

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Patterns of Nerve Conduction Abnormalities in Patients with Type 2 Diabetes Mellitus According to the Clinical Phenotype Determined by the Current Perception Threshold
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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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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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Yue Wang, Ping Liu, Chang Shang, Yahui Wang, Mengfei Yuan, Guozhen Zhao, Luying Sun
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Factors Affecting Arterial Stiffness and Brachial-Ankle Pulse Wave Velocity in Patients With Type 2 Diabetes
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Bo Hyun Kim, Jae Sik Jang, Yong Seop Kwon, June Hyung Kim, In Joo Kim, Chang Won Lee
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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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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.

Citations

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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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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.

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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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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 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.

Citations

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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

A Clinical Study on the Diabetic Foot Wound.: J Young Kim, Kyung Tai Lee, Ki Won Young, Seung Keun Hwang; Korean Diabetes J. 2007;31(1):89-95. Published online January 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.1.89

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PURPOSE: To make protocol on diabetic foot ulcer, with making use of this protocol, investigate hospitalized patients who have had diabetic foot wound and define pattern, characteristics and problems of diabetic foot in hospitalized patients MATERIALS AND METHODS: From Oct. 2002 to Sep. 2003, Seventy-two patients who had been admitted to our hospital due to treatment of diabetic foot wound studied with use of the protocol designed by the authors. RESULTS: The mean age of patients was 64.3 years and male patients were twice as many as female. The most common cause of hospitalization was infection of diabetic foot (77.7%). As a basic pathology of diabetic foot, the main pathology of diabetic foot was the neuropathy that is four times more than vasculopathy. The causations of wound were infection with no specific cause (40.0%). No statistical difference was found between timing of hospitalization and the results of treatment in vasculopathic group but in neuropathic ulcer group, the major procedure such as amputation, and the times of debridement in operation room and are more common in patients who were hospitalized after 3rd days of beginning of symptoms than within 3rd day. CONCLUSION: The education that the patient having a foot symptom have to visit the hospital as soon as possible on patients is important to prevent morbidity of diabetic foot wound, long hospitalization and amputation. The protocol that we are presenting can be modified for other study related to diabetic foot.

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Educational Needs Associated with the Level of Complication and Comparative Risk Perceptions in People with Type 2 Diabetes
Youngji Hwang, Dongsuk Lee, Yeon Sook Kim
Osong Public Health and Research Perspectives.2020; 11(4): 170. CrossRef
The Changes of Trends in the Diagnosis and Treatment of Diabetic Foot Ulcer over a 10-Year Period: Single Center Study
Choong Hee Kim, Jun Sung Moon, Seung Min Chung, Eun Jung Kong, Chul Hyun Park, Woo Sung Yoon, Tae Gon Kim, Woong Kim, Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee
Diabetes & Metabolism Journal.2018; 42(4): 308. CrossRef
Factors Contributing to Diabetic Foot Ulcer among Patients with Type 2 Diabetes Mellitus
Seo Jin Park, Taeyoung Yang, Jun Young Lee, Jinhee Kim
Korean Journal of Adult Nursing.2018; 30(1): 106. CrossRef
Prevalence and Current Status of Treatment of Diabetic Foot in South Korea
Jae-Ik Bae, Je Hwan Won, Jun Su Kim, Man Deuk Kim, Chang Jin Yoon, Yun Ku Cho
Journal of the Korean Society of Radiology.2016; 74(3): 169. CrossRef
Diabetic Foot
Kwang-Won Kim
Journal of the Korean Medical Association.2007; 50(5): 447. CrossRef

Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus.: Seung Hyun Ko, Hyuk Sang Kwon, Jung Min Lee, Sung Rae Kim, Jae Hyung Cho, Ki Dong Yoo, Yong Moon Park, Won Chul Lee, Ki Ho Song, Kun Ho Yoon, Bong Yun Cha, Ho Young Son, Yu Bai Ahn; Korean Diabetes J. 2006;30(3):226-235. Published online May 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.3.226

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Abstract PDF

BACKGROUND
Diabetic autonomic neuropathy has a significant negative impact on survival and quality of life in type 2 diabetic patients. Especially cardiovascular autonomic neuropathy (CAN) is clinically important, because of its correlation to cardiovascular death. Therefore, we investigated the prevalence of CAN in Korean type 2 diabetic patients. METHODS: 1798 type 2 diabetic patients, 727 males and 1071 females, visited Diabetes Clinic at St. Vincent Hospital, Korea, were included from January 2001 to December 2005. Clinical evaluation, laboratory test and assessment of diabetic complication were completed. Standard test for CAN were performed: 1) heart rate variability (HRV) during deep breathing (E/I ratio) 2) Valsalva maneuver 3) 30:15 ratio 4) blood pressure response to standing. CAN score was determined according to the results of the test as following: 0 = normal, 1 = abnormal. RESULTS: Mean age and diabetic duration of patients were 56.7 +/- 10.9, and 9.4 +/- 7.5 years. Normal and abnormal CAN were detected in 815 (45.3%) and 983 (54.7%) of the patients, respectively. Abnormal E/I, valsalva, and 30:15 ratio were found in 333 (18.5%), 717 (39.9%), and 546 (30.4%) patients, respectively. Age, diabetic duration, postprandial hyperglycemia, HbA1c, C-reactive protein, and microalbumuria levels were significantly different between normal and abnormal CAN groups. 49 (6.0%) patients of normal and 100 (10.2%) patients of abnormal CAN group showed previous attack of stroke (P = 0.004). In addition, diabetic foot was more frequent in patients with CAN (normal vs. abnormal, 14 (1.7%) vs. 73 (7.4%), P < 0.05). CONCLUSION: CAN is frequently found in Korean type 2 diabetic patients. It was associated with diabetic duration, uncontrolled diabetes, increased albumin excretion rate, presence of retinopathy, postprandial hyperglycemia.

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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 & Metabolism Journal.2017; 41(4): 275. CrossRef
Screening of Autonomic Neuropathy in Patients with Type 2 Diabetes
Bo Kyung Koo
Diabetes & Metabolism Journal.2014; 38(5): 346. CrossRef
Decision trees and multi-level ensemble classifiers for neurological diagnostics
Herbert F. Jelinek, Jemal H. Abawajy, Andrei V. Kelarev, Morshed U. Chowdhury, Andrew Stranieri
AIMS Medical Science.2014; 1(1): 1. CrossRef
Correlation between Predictors for Diabetic Gastroparesis and Gastric Emptying Scintigraphy
Kyung-Ju Lee, Kyoung-Ho Ryu, Jin-Ook Chung, Dong-Hyeok Cho, Dong-Jin Chung, Min-Young Chung
Chonnam Medical Journal.2009; 45(3): 175. CrossRef
Epidemiologic Characteristics of Diabetes Mellitus in Korea: Current Status of Diabetic Patients Using Korean Health Insurance Database
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Korean Diabetes Journal.2009; 33(5): 357. CrossRef
The Status of Diabetes Mellitus and Effects of Related Factors on Heart Rate Variability in a Community
Kyeong-Soon Chang, Kwan Lee, Hyun-Sul Lim
Korean Diabetes Journal.2009; 33(6): 537. CrossRef

The Effects of Alpha-Lipoic Acid on Epidermal Nerve Preservation in the Diabetic Neuropathy of OLETF Rats.: Ming Han Piao, Ji Hyun Park, Hong Sun Baek, Tae Sun Park; Korean Diabetes J. 2006;30(3):170-176. Published online May 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.3.170

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Abstract PDF: BACKGROUND
Alpha-Lipoic acid (ALA) administration has been reported to ameliorate some of symptoms of peripheral polyneuropathy in diabetic patients and to improve endoneurial nutritive neural blood flow and nerve conduction velocity in diabetic rats. But it is not clear whether ALA has the preservation effect on epidermal nerve fibers (ENFs) density. METHODS: We tested the efficacy of ALA in preserving current perception thresholds (CPTs) and ENFs (numbers/mm) in OLETF (Otsuka Long-Evans Tokushima Fatty) rats, an animal model of type 2 diabetes, which were fed with sucrose until diabetes mellitus developed. Thereafter, one group of OLETF rats was fed with ALA and the other was not for 40 weeks. Diabetic rats were administered with ALA (80 mg/kg of body weight/day) by oral feeding for 40 weeks. The effect of ALA treatment on ENFs preservation was assessed by protein gene product 9.5 immunostaining. Quantification of neuropathic symptoms on the dorsum of hind paws of rat was measured by CPT test every 4 weeks. RESULTS: Numbers of ENF significantly decreased in OLETF rats fed without ALA compared with OLETF rats fed with ALA (P < 0.01). The thresholds at 2000, 250 and 5 Hz in OLETF rats fed with ALA did not increased and OLETF rats without ALA significantly increased at 80 weeks (P < 0.01). CONCLUSION: These observations suggest that administrations of ALA may be useful for preserving ENFs and CPTs in OLETF rats dorsum of hind paws skin.

Case Report

A Case of Chronic Inflammatory Demyelinating Polyneuropathy in a Girl with Type 1 DM .: Yi Sun Jang, Hye Soo Kim, Jong Min Lee; Korean Diabetes J. 2006;30(2):130-135. Published online March 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.2.130

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Abstract PDF: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated disorder characterized by the symmetrical weakness in both proximal and distal muscles for at least 2 months, hyporeflexia or areflexia, nerve conduction abnormalities, and high CSF protein level. Diabetes mellitus, monoclonal gammopathy, hepatitis C infection, HIV infection, SLE, Sjogren syndrome and lymphoma have been associated with CIDP. The incidence of CIDP in diabetes is not known exactly, but occur more common among diabetic than nondiabetic patients. There is sometimes a difficulty in distinguishing between diabetic polyneuropathy and CIDP, but differential diagnosis is important because CIDP is treatable with immune-modulating therapy. We report a case of CIDP in 22-year-old girl with type 1 DM who presented with generalized motor weakness and walking disturbance which were treated with iv immunoglobulin

Randomized Controlled Trial

The Comparison of Efficacy with alpha-lipoic Acid Treatment Methods in Diabetic Polyneuropathy.: Hyejin Lee, Kyung Wan Min, Kyung Ah Han; Korean Diabetes J. 2006;30(2):112-121. Published online March 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.2.112

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Abstract PDF: BACKGROUND
Diabetic neuropathy represents a major health problem, as it is responsible for substantial morbidity, increased mortality, and impaired quality of life. Antioxidant treatment has been shown to prevent nerve dysfunction, providing a rationale for a potential therapeutic value in diabetic patients. The safety and efficacy of alpha-lipoic acid (ALA) given intravenously were proved in many studies, but the oral treatment remains to be established. Therefore we compare the efficacy and safety of ALA given intravenously followed by oral treatment and given only orally. METHODS: 45 outpatients were randomly assigned to sequential treatment with ALA intravenously for 2 weeks, followed by orally for 10 weeks (group 1, n = 21); ALA orally for 12 weeks (group 2, n = 24). The primary end point was change of the sum score of severity and duration of total symptom score (TSS). HbA1c and safety parameters were determined at baseline and after 12 weeks. RESULTS: The TSS was significantly decreased from baseline to 2 week and 12 week in both groups. But no significant differences between the two groups were noted at 2 week and 12 week. There were no significant changes in HbA1c and safety parameters between baseline and 12 week. The rate of adverse events were 47.6% in group 1 and 12.5% in group 2. CONCLUSION: We conclude that both methods of ALA treatment are effective to improve the symptoms of diabetic polyneuropathy, and the safety was probably superior in oral treatment method

Original Articles

Effect of 12-week Oral Treatment with alpha-lipoic acid on the Nerve Conduction in Symptomatic Diabetic Neuropathy.: Tae Seo Sohn, Jung Min Lee, Sang Ah Chang, Hyun Shik Son, Bong Youn Cha, Ho Young Son, Kwang Woo Lee, Sung Ku Kang; Korean Diabetes J. 2005;29(6):533-539. Published online November 1, 2005

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Abstract PDF: BACKGROUND
Diabetic peripheral neuropathy is multifactorial disorder arising from hyperglycemia and insulin deficiency. It has been suggested that oxidative stress resulting from enhanced free-radical formation and defects in antioxidant defence plays a major role among the putative pathogenic mechanisms of diabetic neuropathy. As alpha-lipoic acid, a natural antioxidant, has been suggested to improve symptoms of diabetic neuropathy, we assessed the efficacy of alpha-lipoic acid on neuropathic symptoms and peripheral nerve conduction in patients with type 2 diabetes mellitus with symptomatic polyneuropathy. METHODS: A cohort of 30 type 2 diabetic patients with symptomatic polyneuropathy received a daily dose of 600 mg alpha-lipoic acid, and was followed for 3 months. Neuropathic symptoms (pain, burning, paraesthesiae, and numbness) of the feet were scored at monthly interval and summarized as a Total Symptom Score (TSS). Nerve conduction study was done before and after 3 month treatment of alpha-lipoic acid. RESULTS: Treatment of alpha-lipoic acid given 600 mg per oral for 12 weeks improved the symptoms of diabetic polyneuropathy. Effects of alpha-lipoic acid on nerve conduction study were that in the motor nerve, the amplitudes of median nerve and tibial nerve and the conduction velocity of tibial nerve improved after 12 weeks treatment. In the sensory nerve, the conduction velocities of median nerve, ulnar nerve, and sural nerve improved after 12 weeks. CONCLUSION: alpha-Lipoic acid was effective in the treatment of diabetic peripheral polyneuropathy improving both clinical manifestations and nerve conduction. The improvement of clinical manifestations may be due to improved conduction velocity of sensory fibers.

Evaluation of the Indicator Test(NeurocheckTM) in the Diagnosis of Peripheral Neuropathy among Type 2 Diabetic Patients.: Tae Seo Sohn, Hyun Shik Son, Jae Myung Yu, Bong Soo Cha, Kyung Wan Min, Sei Hyun Baik; Korean Diabetes J. 2005;29(3):247-253. Published online May 1, 2005

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Abstract PDF: BACKGROUND
Eighty-five percent of the lower-limb amputations that are done for patients with diabetes are preceded by foot ulceration, and this suggests that prevention and the appropriate management of foot lesions are of paramount importance. Ulceration is caused by several factors acting together, but they are particularly caused by neuropathy. Various aspects of the neurovascular function can be evaluated with specialized tests, but these tests have generally not been well standardized and they have limited clinical utility. A new indicator test(NeurocheckTM) that utilizes the water-induced color change of a cobaltII compound from blue to pink has been introduced. The aim of the present study was to evaluate this new indicator test in the diagnosis of peripheral neuropathy among type 2 diabetic patients. METHOD: This study included 124 diabetic patients(45 men and 79 women) who were recruited from 5 diabetic centers in Korea. The presence of diabetic neuropathy was diagnosed by nerve conduction study. The degree of the patient's symptom was checked as the total symptom score(TSS). Autonomic sudomotor neuropathy was assessed by means of the new indicator test(NeurocheckTM). The degree of color change in 10 minutes was assessed as a complete color change, an incomplete color change or no color change. RESULTS: Of the 124 diabetics patients we investigated, 109 patients were proven to have peripheral neuropathy by nerve conduction study. Autonomic sudomotor neuropathy by NeurocheckTM was diagnosed in 94 patients with peripheral neuropathy(86.2%) and in 6 patients(40%) without peripheral neuropathy. The overall measure of agreement between NeurocheckTM and the electrodiagnostic test was 0.3673(0.1547, 0.58). The sensitivity and specificity of NeurocheckTM was higher in women(91.2% and 63.6%, respectively) than in men(78.0% and 50.0%, respectively). The measure of agreement in women was 0.5093(0.2396, 0.9601) and in the men it was 0.1567(-0.1423, 0.4588). CONCLUSION: The new indicator test has a high sensitivity for the diagnosis of peripheral neuropathy among diabetic patients, especially in women. It is likely that the new indicator test is useful clinically as a screening and diagnostic tool for diabetic neuropathy. Since the specificity of the test is somewhat low, the patients with a high total symptom score and who are without sudomotor neuropathy may need further diagnostic evaluation on neuropathy

Prolonged QT Interval and the BMI, Systolic BP and HDL-Cholesterol in Type 2 Diabetic Patients.: Chunggu Cho, Hye Jung No, Hyo Jeong Oh, Bong Joon Yang, Ha Young Kim, Byoung Hyun Park; Korean Diabetes J. 2005;29(3):215-222. Published online May 1, 2005

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Abstract PDF: BACKGROUND
A prolonged QT interval is considered as an indicator of an increased risk of coronary heart disease, malignant ventricular arrhythmias and/or sudden death. QT interval prolongation has been reported to be a common finding in patients with obesity and diabetic autonomic neuropathy and it is well known that both leptin and insulin stimulate sympathetic activity. The waist to hip ratio and the plasma insulin levels were recently reported to be correlated with the QT intervals and the sympathovagal balance. The aim of the present study was to evaluate the association of the features of metabolic syndrome and the QT interval in type 2 diabetic patients. METHODS: We studied 114 type 2 diabetes(45 males and 69 females). The QT intervals were measured by a software program and then the QTc was calculated. The fasting glucose, total cholesterol, triglyceride and high-density lipoprotein(HDL)-cholesterol, HbAIC and Cpeptide were measured. All the patients received clinical tests for cardiovascular autonomic dysfunction by the Ewing's method. RESULTS: A significant difference was found in the mean QT interval between the patients with an autonomic score>=1 and the patients who were without cardiac autonomic neuropathy(autonomic score=0). On Pearson's simple regression analysis, the QT interval showed positive correlations with the BMI, fasting C-peptide, systolic blood pressure(sBP), and age. The QT interval also showed negative correlation with the HDL-cholesterol. The associations of the QTc with triglyceride, fasting glucose, and the autonomic score did not reach statistical significance. On the multiple regression analysis, the QT interval was independently correlated with BMI, systolic BP and HDL-cholesterol but not with the other variables that we tested(c-peptide, autonomic score, diastolic blood pressure, glycated hemoglobin, triglyceride and cholesterol). CONCLUSION: Our results suggest that a variety of features of metabolic syndrome are associated with QT interval prolongation in the type 2 diabetic patients

Case Report

A Case of Acute Multifocal Bacterial Nephritis Associated with Diabetic Autonomic Neuropathy.: Eun Kyung Park, Jae Hak Lee, Ji Sung Yoon, Ji O Mok, Yeo Joo Kim, Hyeong Kyu Park, Chul Hee Kim, Sang Jin Kim, Dong Won Byun, Kyo Il Suh, Myung Hi Yoo; Korean Diabetes J. 2003;27(4):379-384. Published online August 1, 2003

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Abstract PDF: Acute multifocal bacterial nephritis is a severe form of acute renal infection in which a heavy leukocytic infiltrate occurs throughout the kidney. It is also an early phase of renal corticomedullary abscess. Clinically, patients have evidence of a severe urinary tract infection secondary to a gram-negative organism and there are frequently signs of sepsis. About half of the reported patients have been diabetics. Urinary tract infections are more common in diabetic women than in non-diabetic women. A variety of factors may contribute. The most important predisposing factor may be bladder dysfunction as a result of diabetic neuropathy and cystopathy. Diabetic cystopathy begins as decreased bladder sensation and decreased reflex detrusor activity caused by neuropathy affecting sympathetic and parasympathetic afferent fibers. Impaired bladder sensation results in bladder distention and increased residual urine volume. Long-term effects may eventually be vesicoureteral reflux and recurrent upper urinary tract infection. However, until now no diabetic patient with acute multifocal bacterial nephritis has been reported in Korea. Acute multifocal bacterial nephritis can be diagnosed by clinical manifestations and on radiologic grounds, including abdominal computed tomography showing multiple, wedge shaped, poorly defined areas of decreased contrast enhancement in multiple renal lobes. Therefore, we report the first Korean case of acute multifocal bacterial nephritis associated with diabetic autonomic neuropathy and review the literatures.

Original Articles

Changes in Cutaneous Blood Flow in Type 2 Diabetics with or without Neuropathy and Retinopathy.: Chang Hoon Choi, Ju Young Lee, Sin Won Lee, Gui Hwa Jung, Jung Guk Kim, Sung Woo Ha, Bo Wan Kim; Korean Diabetes J. 2003;27(1):18-25. Published online February 1, 2003

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Abstract PDF: BACKGROUND
Although diabetic microangiopathy has its greatest clinical effects in the retina, kidneys and nerves there is much evidence that the process is generalized, and that these lesions involve most capillary beds. However, the potential relationship between the presence of diabetic neuropathy, and/or retinopathy, and skin blood flow has not been fully evaluated. Therefore we measured the cutaneous blood flow in diabetics, both with and without microangiopathy, to determine the relationship between microangiopathy and the cutaneous blood flow. METHODS: One hundred-and nineteen type 2 diabetic patients were classified into four categories, based on the presence of polyneuropathy or retinopathy. The skin blood flow was measured in the diabetic patients with or without neuropathy and retinopathy, before, during and after exposure to cold. Before, during and 1 min after the application of a cold-pack, skin blood flow measurements were performed using a laser Doppler techniques at the following right-sided locations: (1) the dorsum of the wrist and ankle, as nutritive microvasculatures, and (2) the pulp of tip of the index finger and big toe, as themoregulatory ones. RESULTS: During the 1-min cold applications, the percentage changes in the decrement of the skin blood flow, at the 4 skin sites, showed decreasing trends in the neuropathy group. However, the differences in the diabetics with neuropathy were not significantly greater than in those without neuropathy. The changes at the same sites in the group with retinopathy were similar to those with neuropathy. The percentage changes in the increment of the skin blood flow were measured at the 4 skin sites 1 min after exposure to cold, and also showed a blunted tendency in both the diabetic neuropathy and retinopathy groups. The percentage changes in the flow increment at the pulp of the big toe were greater in the diabetics without neuropathy or retinopathy, compared to those with these complications (p<0.05). CONCLUSION: These results suggest that changes in the cutaneous blood flow would be more predominant at the thermoregulatory vasculature sites in the type 2 diabetics with neuropathy or retinopathy, and seems to be related to diabetic microangiopathy.

Differences in Dynamic Plantar Pressure in Type 2 Diabetics with or without Peripheral Neuropathy.: Gui Hwa Jeong, Ju Young Lee, Shin Won Lee, Chang Hoon Choi, Soon Hee Lee, Jung Guk Kim, Sung Woo Ha, Bo Wan Kim; Korean Diabetes J. 2002;26(6):481-489. Published online December 1, 2002

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Abstract PDF: BACKGROUND
Foot ulcers, and lower-extremity amputations, are relatively common complications of diabetes mellitus and their clinical management is very important. High plantar pressure is known to be a major risk factor of foot ulceration in diabetic patients. The EMED-system is used for the assessment of pressure distribution for the identification of focal areas at high risk of ulceration that merit protection from preventive footwear. However, a potential relationship between diabetic neuropathy and the plantar pressure has not been fully evaluated. Changes in the plantar pressure were measured in diabetic patients, both with and without peripheral polyneuropathy, using the EMED - AT system to clarify if diabetic neuropathy increases the plantar pressure. METHODS: Ninety seven patients with type 2 diabetes were divided into two groups on the basis of their peripheral polyneuropathy. No patient had a past history of foot ulceration. The clinical characteristics of 2 groups were analyzed, and their plantar pressures was measured using the EMED - AT system. These results were analyzed, with the EMED software program, after their division into ten masks for a so-called "regional analysis". The pressure time (PTI) and force- time (FTI) integrals were analyzed for each mask on both feet. RESULTS: The diabetic neuropathy (DN) group showed significantly higher FTI levels in both masks 05 (area of the 1st metatarsal head) and masks 08 (area of the hallux) than the diabetic control (DC) group. The PTI was also higher in right the mask 08 of the DN group than in the DC group. CONCLUSION: These results suggest that peripheral neuropathy to be an important risk factor, and predictor of diabetic foot ulcers, due to the increasing plantar pressure in some areas of the foot. Measurement of the plantar pressure may be a useful method for the diagnosis and monitoring of foot disorders in diabetic patients with peripheral neuropathy.

Factors Determining Circadian Blood Pressure Rhythm in Normotensive Patients with Type 2 Diabetes.: Jae Hong Kim, Jin Ho Kim, Mi Jung Eun, Si Hyung Lee, Kyeong Cheol Shin, Kyu Chang Won, Ihn Ho Cho, Hyoung Woo Lee; Korean Diabetes J. 2002;26(5):416-430. Published online October 1, 2002

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Abstract PDF: BACKGROUND
Within healthy subjects, there exists the so-called 'dipper phenomenon', where the circadian blood pressure rhythm, that is the systolic and diastolic blood pressures values, are lower at night than during the day. The loss of nocturnal dipping in BP has prognostic value with regard to end-organ damage and vascular events in both hypertension and diabetic patients. A blunted nocturnal decrease in BP has been described in diabetic patients, and has been associated with autonomic neuropathy or nephropathy, but much controversy relating to this still exists. This study was designed to evaluate the factors that influence abnormal circadian blood pressure rhythm. METHODS: 24hr blood pressure monitoring was applied to 99 normotensive type 2 diabetes patients,comprising of 55 males and 44 females, with a mean age: 56 3 years, who visited our hospital between March 2000 and February 2002 for measurement of 24hr systolic and diastolic blood pressures. The control groups was 21 white coat hypertension type 2 diabetic patients, comprising of 15 males and 6 females, with a mean age of 53 4 years. The controls were subgrouped according to their standard cardiovascular autonomic function test(CAN) or nephropathy stage. All patients divided dipper, mean(day time night time) systolic BP/mean(day time-night time) diastolic BP above 10mmHg/5mmHg, and non-dipper groups. RESULTS: The prevalence of non-dipper phenomenon was much greater in the type 2 diabetes patients than in the control groups(p<0.05). There was a significant difference between the dipper and non-dipper groups in the 24hr total urine protein and CAN(p<0.05). In the type 2 diabetes patients, sub-grouped according to their nephropathy stage, there was a significant difference between the microalbuminuric and proteinuric groups relating to the prevalence of the non-dipper phenomenon (p<0.05). The circadian blood pressure, according to the nephropathy stage, the CAN in the normoalbuminuria group, the albumin excretion in the microalbuminuria group, CAN and 24hr total urine protein in the proteinuric group, may useful in determining abnormal circadian rhythm (p<0.05). There was no significant difference between the dipper and non-dipper groups with regard to neuropathy and retinopathy (p<0.05). CONCLUSION: In the early stage of diabetic nephropathy, autonomic dysfunction may have a relatively dominant influence on abnormal circadian blood pressure rhythm. Nephropathy was progressed in diabetic patients: therefore diabetic nephropathy may itself have an influence on abnormal circadian blood pressure rhythm.

Detection of Diabetic Autonomic Neuropathy by 24-Hour Heart Rate Variability Analysis in Type 2 Diabetes Mellitus Patients.: Young Hee Rho, Nan Hee Kim, Dong Lim Kim, Dong Hyun Shin, Sin Gon Kim, Kyung Mook Choi, Woo Hyuk Song, Sei Hyun Baik, Woo Keun Seo, Min Kyu Park, Dong Seop Choi; Korean Diabetes J. 2002;26(3):208-219. Published online June 1, 2002

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Abstract PDF: BACKGROUND
Diabetic autonomic neuropathy is a relatively common diabetic complication, associated with high long-term mortality. Ewing's test is known as the 'gold standard' for evaluating and diagnosing this disease, yet is not widely used due to the inconvenient procedures of the test. 24-hour Holter EKG monitoring, and the analytical product, heart rate variability, is being introduced as a relatively simple and reliable procedure for the evaluation of diabetic autonomic neuropathy. We explored whether such heart rate variability products derived from Holter monitoring, correlated with the presence, absence, or severity of diabetes mellitus, and whether it correlated well with conventional autonomic tests. METHODS: We compared 59 type 2 diabetic patients with 71 normal subjects. All underwent 24-hr Holter EKG monitoring and basic autonomic evaluations, such as the head-up tilting, hand grip, and deep breathing-heart rate variability tests. Those who had diabetes also underwent evaluation for basic blood chemistry, and complication studies, for things such as: 24-hour urine albumin excretion, fundoscopy and nerve conduction. RESULTS: Variables for heart rate variability were expressed as SDDN, rMSSD, LF, HF, and LF/HF, where SDDN is the Standard Deviation of all RR intervals, rMSSD the square root of the mean of the sum of the squares of differences between adjacent RR intervals, LF the power in the Low Frequency range and HF the power in the High Frequency range, with LF/HF being the ratio between LF and HF. Heart rate variability was significantly lower in terms of rMSSD, LF, HF, but not in terms of the LF/HF ratio, for the diabetic patients compared to the normal subjects. These three variables also correlated with the conventional autonomic tests of systolic blood pressure changes during standing up (negatively), and heart rate variability during deep breathing (positively). SDDN, rMSSD, LF, and HF also correlated negatively with the duration of diabetes. SDDN, LF and HF were significantly lower among patients who had complications such as: retinopathy, nephropathy or peripheral neuropathy, than in those who did not. CONCLUSION: Heart rate variability was lower in type 2 diabetic patients than the control subjects, which correlated well with the duration of diabetes mellitus, diabetic chronic complications and the conventional autonomic nervous function tests, so could be an useful adjunct or even a replacement, for conventional autonomic nervous system testing procedures. More research is needed in this field.

Effect of Nerve Growth Factor on Cultured Mouse Dorsal Root Ganglion Cells in Hyperglycemic Condition.: Byoung Hyun Park, Chung Gu Cho, Geun Young Jang, Ki Hun Kim, Seung Taeck Park; Korean Diabetes J. 2001;25(4):286-296. Published online August 1, 2001

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Abstract PDF: BACKGROUND
Multiple etiology of diabetic neuropathy has been proposed, including altered polyol metabolism, superoxide radical formation, protein glycation, vascular insufficiency, blunted nitric oxide production and neurotrophic factor (NTF) deficiency. Nerve growth factor (NGF) is a member and family of neurotrophic factors. NGF is produced in tissues innervated by its responsive neurons. In the peripheral nervous system, NGF messenger RNA (mRNA) is produced in target fields of small pain and temperature-mediating dorsal root ganglia (DRG) sensory neurons and sympathetic neurons. NGF has been shown to promote their survival, differentiation, and maintenance. However, the mechanism of neuronal damage in diabetes and the effect of NGF on diabetic neuropathy are not clear. METHODS: In order to clarify the effect of NGF, the changes of cell viability were evaluated by MTT assay on mouse cultured dorsal root ganglion cells which were grown with media containing concentrations of high glucose for inducing hyperglycemic condition. Furthermore, the neuroprotective effect of nerve growth factor (NGF) against hyperglycemia-induced dorsal root ganglion cell changes were also examined. RESULTS: 1. Cell viability of cultured mouse dorsal root ganglion cells treated with hyperglycemic media made with 15, 25 mM glucose was markedly decreased in a dose-dependent manner when compared with control medium (normoglycemic medium) containing concentration of 5.5 mM glucose (p<0.05). 2. Cultured dorsal root ganglion cells exposed to hyperglycemic medium made with 25 mM glucose for 72 hours showed morphological changes such as dissociations, loss of neurites and decrease of cell viability (p<0.05). 3. Pretreatment of 150 ng/mL NGF for 2 hours significantly increased the cell viability of cultured dorsal root ganglion cells which exposed to hyperglycemic medium (25 mM glucose for 72 hours). CONCLUSION: Findings from this study suggested that hyperglycemic condition induces the decrease of cell viability and morphological changes (loss of neurites, dissociation) on cultured dorsal root ganglion cells of mouse. Furthermore, selective neurotrophic factors such as NGF are very effective in preventing dysfunction and morphological changes of DRG cells induced by hyperglycemic condition.

Diastolic Dysfunction of Left Ventricle by Cardiovascular Autonomic Neuropathy in Type 2 Diabetic Patients Without Cardiovascular Symptom.: Duk Kyu Kim, Mi Kyoung Park, Do Young Kang; Korean Diabetes J. 2001;25(3):230-239. Published online June 1, 2001

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Abstract PDF: BACKGROUND
We investigated the effect of cardiovascular autonomic neuropathy for left ventricular function in cardiovascular symptom-free type 2 diabetic patients without other major risk factors known to cause cardiac dysfunction, especially diastolic dysfunction. METHODS: Forty seven patients (M:F=20:27, 53+/-10 years) with type 2 DM were enrolled in this study. None of the subjects had the macrovascular diabetic complications, hypertension, hypertrophic cardiomyopathy, valvular heart disease, alcoholic heart disease, congenital heart disease and older age (> 65 years). The patients were tested for cardiovascular autonomic neuropathy using five non-invasive tests of autonomic function. The response to each test was graded as 0, 0.5, 1. A patient was classified as having definite cardiovascular autonomic neuropathy if total score was 2 or more. Using these criteria, 26 patients (Group A) were determined to have cardiovascular autonomic neuropathy. Others were 21 patients (Group B). Tc-99 m RBC gated blood pool scintigraphy was performed as routine standard protocol. RESULTS: The degree of age, sex, body mass index (BMI), duration of diabetes, level of insulin, C-peptide, fructosamine, fasting plasma glucose, total cholesterol (TC), triglyceride (TG), HDL, LDL, BUN, creatinine and incidence of retinopathy, microalbuminuria were not different between group A and B. Heart rate response to Valsalva maneuver, heart rate response to standing were different between Group A and B (p=0.008, p=0.001, respectively). Ejection fraction of left ventricle were normal (> 50%) in all of patients. Maximal filling rate, average filling rate, maximal ejection rate and average ejection rate were increased in patients with cardiac autonomic neuropathy (p=0.03, p=0.05, p=0.02, p=0.04, respectively). Total score of autonomic function was significantly correlated with maximal filling rate (r=0.38, p=0.01), with average filling rate (r=0.37, p=0.01) and with maximal ejection rate (r=0.37, p=0.01). Maximal filling rate was most correlated with resting pulse (r=0.58, p<0.01). CONCLUSION: Cardiovascular autonomic neuropathy as single factor may result in diastolic dysfunction of left ventricle in cardiovascular symptom-free type 2 diabetic patients without other major factor known to cause cardiac diastolic dysfunction.

Chronic Diabetic Complications in the Insulin- Treated Animal Model of Type 2 Diabetes Mellitus.: Jee Won Park, Sung Kyu Lee, Hyo Jung Kim, Hae Lim Noh, Chang Young Hah, Su Jin Lee, Yoon Sok Chung, Kwan Woo Lee, Hyun Man Kim, Eun Ju Paek; Korean Diabetes J. 2001;25(3):200-210. Published online June 1, 2001

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Abstract PDF: BACKGROUND
Non-Insulin Dependent Diabetes Mellitus (NIDDM) is a characterized by insulin resistance and impairment of beta cell function. OLETF male rat usually developed NIDDM and obesity at 20 weeks old spontaneously. It is a metabolically characterized by insulin resistance in onset of early disease. However, body weight and insulin secretory function was gradually reduced during the diabetes developed. These characteristics of disease is similar to Korean type 2 diabetic patients. NIDDM patients in Korea are thought to be different from traditional NIDDM in western countries. They are non obese type and also has reduced insulin secretory function compared to western countries. These patients are not easily managed on diet and/or oral hypoglycemic agent. Reduced C-peptide and insulin concentrations in these patients are similar to patients with IDDM. In these patients, insulin therapy is effective to control glucose level. Therefore, we investigated the effect of insulin and oral hypoglycemic therapy to glucose control and severity of chronic complications in OLETF male rats of 6weeks (42 weeks old) and 14 weeks (50 weeks old) treated groups. MATERIAL AND METHODS: The OLETF male rats which are 36 weeks old is diagnosed to NIDDM. A total of 20 rats were stratified into the three groups: control group (n=3), OHA's group; rats treated by OHA's (n=3) and insulin group; rats treated with insulin (n=4). We evaluated anthropometry, fasting glucose and 75 gram OGATT, nerve conduction studies, sclerotic degree of kidney and thickness of carotid arteries at 42 and 50 weeks old. RESULTS: In the 42 weeks old groups (6 weeks treated group), there was a significant difference in weight gain in group 3 but no differences were observed in kidney tissue pathology and thickness of carotid arteries. In the 50 weeks old groups (14 weeks treated group), there were also no changes in the kidneys and arteries, but weight gain and peak amplitude in NCV was significantly higher in insulin - treated group. CONCLUSIONS: OLETF male rats as NIDDM animal mocel, with late stage diabetic complications show weight loss and decreased insulin secretory capacity. Insulin treated group shows improved blood glucose control. Also it showed improved severity of diabetic neuropathy.

Effect of Nerve Growth Factor on Cultured Rat Schwann Cells in Hyperglycemic Condition.: Geun Young Hyung, Kyoung Hee Kim, Seung Hoon Baek, Geun Young Jang, Chung Gu Cho; Korean Diabetes J. 2000;24(1):10-18. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Nerve growth factor (NGF) is produced in tissues innervafed by its responsive neurons. In the peripheral nervous system, NGF messenger RNA (mRNA) is produced in target fields of small pain and temperature-mediating dorsal root ganglia (DRG) sensory neurons and sympathetic neurons. NGF receptors are expressed in these neurons, and NGF has been shown to promote their survival, differentiation, as well as maintenance. However, the mechanism of neuronal damage in diabetes and the effect of NGF on diabetic neuropathy are unclear. METHODS: in order to clarify the effect of hyperglycemia, the hyperglycemia-induced cytotoxic effects were evaluated by MTT assay on cultured rat Schwann cells, Schwann cells were grown with media containing concentrations of high glucose for inducing hyperglycemic condition. The neuroprotective effect of nerve growth factor (NGF) against hyperglycemia-induced Schwann cell changes were also examined. RESULT: 1. MMT50 value was at concentration of 25mM glucose after 72 hours, 2. Cell viability of cultured rat Schwann cells treated with hyperglycemic media made with 25~35mM glucose was markedly decreased in a dose-dependent manner when compared with control medium (normoglycemic medium) containing concentration of 5.5 mM glucose, While cell number did not show a dose- dependent decrease. 3. Cultured Schwann cells exposed to hyperglycemic medium made with 25mM glucose for 72 hours did nof show any morphological change as well as decrease of cell number. 4. Pretreatment of 10 ng/mL NGF for 2 hours increased remarkably the cell viability of cultured Schwann cells exposed to hyperglycemic medium(25mM glucose for 72 hours). CONCLUSIONS: The results from this study suggested that hyperglycemic condition induces the decrease of cell viability on cultured Schwann cells of rat. But it did not show the decrease of cell number and rnorphological change. The selective neurotrophic factors such as NGF are very effective in preventing dysfunction of cells induced by hyperglycemic condition.

Comparisons between Several Neurologic Tests of Large Myelinated Nerves in Type 2 Diabetic Patients with Peripheral Polyneuropathy.: Bo Wan Kim, Dong Hee Kim, Jung Guk Kim; Korean Diabetes J. 1999;23(4):562-574. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Neuropathy is the most common complication of diabetes mellitus but the prevalence is variable because there are many neurologic tests and criteria for diagnosis of neuropathy. Subjective symptoms of patients alone are not accurate for diagnosis of neuropathy, so objective sensory tests must be added. There have been few studies about correlation between each neurologic tests; furthermore there have been no studies on comparisons between each neurologic test in Korean diabetic patients. METHODS: From September 1997 to June 1998, 142 type 2 diabetic patients visited Kyungpook National University Hospital and included in this study. Every patient had nerve conduction study and vibration threshold test, pressure threshold test of 1 point and 2 point touch stimuli by pressure specified sensory device. Some of these patients had 10g monofilament test. From receiver operating characteristics curve, sensitivities of each test were calculated and compared with each test. RESULTS: 1. From receiver operating characteristics curve, when specificities of each test reached 90%, sensitivity of vibration perception threshold test of left great toe was 69.2 %, one point discrimination touch threshold test of left great toe was 50 %, and two point test was 31.6 %. Sensitivity of 10 g monofilament test was 57% and specificity was 85%. 2. Comparisons between each component of nerve conduction study and other neurologic test showed conduction velocity and amplitude were highly correlated with vibration perception threshold test, but F wave latency was highly correlated with one point discrimination threshold test. CONCLUSION: We though vibration perception threshold, lOg monofilament and quantitative sensory tests is adequate, simple and convenient tests in order to diagnose peripheral polyneuropathy. Of all these tests, vibration perception threshold was most useful as well as a sensitive test for screening and diagnosis of peripheral polyneuropathy in nan-insulin dependent diabetic patients.

Simple Diagnostic Method of Diabetic Distal Polyneuropathy in Type 2 Diabetics.: Chi Hak Kim, Kyung Il Lee, Sang Gil Han, Jeong Ho Heo, Kwang Jae Lee; Korean Diabetes J. 1998;22(4):561-567. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Early diagnosis of diabetic distal polyneuropathy, a common chronic complication of diabetes mellitus, is important in the management of diabetes mellitus. Michigan Diabetic Neuropathy Score(MDNS) is a good method for diagnosis of this complication but requires many check lists witb nerve conduction study, which may be troublesome in outpatients. This study was performed to investigate simple and convenient diagnostic means which can be substituted with MDNS. METHODS: 41 patients with type 2 diabetes mellitus were assessed with MDNS which include toe 128 Hz tuning fork test, 10 g filament test, pin wheel test and nerve conduction velocity(NCV). Additionally, l28 Hz tuning fork test, l0 g filament test, pin wheel test on fingers and Tacticon and vibration perception test with Bio-thesiometer on toes and fingers were performed. RESULTS: Toe and finger 128 Hz tuning fork, Tacticon and Bio-thesiometer tests were highly concordant with MDNS(kappa>0.40). Also combined tests such as toe and finger 128Hz tuning fork- Tacticon test and Tacticon-Bio-thesiometer test were highly concordant with MDNS(kappa > 0.40) and more sensitive than single tests. CONCLUSION: The results indicate that finger 128 Hz tuning fork - Tacticon combined test is good, simple and convenient in the diagnosis of diabetic distal polyneurapathy.

The Relation of QTc dispersion and Cardiovascular Autonomic Neuropathy in Patients with Type 2 Diabetes Mellitus.: Ji Sung Yoon, Kyu Chang Won, Hyoung Woo Lee; Korean Diabetes J. 1998;22(3):410-418. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The diabetic patients with cardiovascular autonomic neuropathy(CAN) have disturbance of repolarization due to sympathetic imbalance resulting in arrhythmogenesis, and finally leading to sudden death. QTc dispersion may provide regional variation in myocardial recovery time. Thus the hypothesis of this study was that QTc dispersion may be a useful tool in the assessment of arrhythmogenic potential in diabetic patients with CAN depending upon a severity of CAN. METHODS: Ninty-five patients with type 2 diabetes mellitus and 20 normal control subjects were studied. QTc interval and QTc dispersion was calculated from 12 lead ECG leads. QT dispersion was defined as difference between maximum and minimum QT interval and was corrected for heart rate using Bazzets formula. Cardiovascular autonomic neuropathy test(including resting heart rate, Valsalva maneuver, deep breathing, lying to standing, orthostatic hypotension) were assessed in all subjects. RESULTS: Among 95 diabetic patients, 43 patients (37%) had CAN. QTc interval and QT(QTc) dispersion were significantly greater in patients with CAN (p <0.05). There was no correlation between QTc interval and QTc dispersion. There was a statistically significant(r=0.48, p<0.001) correlation between systolic blood pressure response to standing and QTc dispersion. CONCLUSION: These results suggest that QTc dispersion may be an additional non-invasive diagnostic tool in the assessment of arrhythmogenic potential in diabetic patients with cardiovascular autonomic neuropathy.

Plasma Paraoxonase Activities in Type 2 Diabetes Mellitus.: Gyoung Mu Her, Hak Yeon Bae, Byoung Rai Lee; Korean Diabetes J. 1998;22(3):403-409. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Human serum paraoxonase is physically associated with HDL and has been implicated in the detoxification of organophosphate and possibly in the prevention of LDL lipid peroxidation. The activities of paraoxonase and levels of HDL cholesterol were measured in the serum of individuals with type 2 diabetes mellitus in order to evaluate whether a correlation exists between these cnzyme activities and the diabetes mellitus and dliabetic complications. METHODS: Plasma samples were obtain from 60 individuals with type 2 diabetes mellitus(32 women and 28 men; mean age=55.8 yrs) and 30 individuals with healthy control(16 women and 14 men; mean age=-54.1 yrs). Paraoxonase activities were measured spectrophotometrically in 0.1IM Tris-HC1 buffer(pH= 7.4) at 25C with paraoxon as substrate(5.5mM) at 405nm. RESULTS: No significant differences of plasma paraoxonase activity between healthy control and type 2 diabetes mellitus were observed. The significant difference of plasma paraoxonase activity between healthy control and type 2 diabetes mellitus with diabetic complications such as diabetic neuropathy, diabetic retinopathy and diabetic nephropathy were observed. The difference of plasma paraoxonase activity between individuals with type 2 diabetes mellitus without diabetic complication and type 2 diabetes mellitus with diabetic complications was significant. The correlation between paraoxonase activity and HDL-cholesterol, plasma lipoproteins, HbAlc and duration of diabetes were not observed. CONCLUSION: These experimental results suggested that the plasma paraoxonase activity wasnt decreased in individuals with type 2 diabetes mellitus without diabetic complication and the decrement of plasma paraoxonase activity was might be associated with diabetic chronic complications.

Association Between QTc Dispersion and Cardiovascular Autonomic Dysfuction in Non-insulin Dependent Dabetes Mellitus.: Jung Guk Kim, Hun Sik Park, Jick Hwa Nam, Byoung Ho Sin, Seong Mo Koo, Sung Woo Ha, Bo Wan Kim; Korean Diabetes J. 1998;22(2):173-181. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Diabetic patients with autonomic dysfunction have worse prognosis, including an increased incidence, of sudden death, than those without autonomic dysfunction. This event may be due to sympathetic imbalance causing disturbances of ventricular repolarization. QT dispersion have recently been demonstrated to reflect dispersion of ventricular refractoriness and is a marker of arrhythmogenic potential. METHODS: Sixty diabetic patients and 31 normal subjects were studied. All patients had clinical test for cardiovascular autonomic dysfunction by Ewings method and defined as normal, early involved, definitely involved, severely involved and atypical group for 5 validated tests. Resting standard 12-lead electrocardiograms were recorded for measurement of QT dispersion, defined as the difference of longest QT interval and shortest QT interval, and corrected for heart rate using Bazetts formula. RESULTS: Twenty-seven dIiabetic patient were abnormal in cardiovascular autonomic function tests. In these patients corrected QT dispersion (QTc) were significantly longer compared to that 33 patients without autonomic dysfunction(47.4+14.7 vs 22.6+ 8.1msec p<0.001). And also there was significant difference of QTc dispersion between normal subject and diabetic patients with autonomic neuropathy group(20.5+9.2 vs 47.4+14.7msec p<0.001). But there was no difference between normal control and diabetic patients without autonomic neuropathy group. And QTc dispersion was not related to the presence ot nephropathy, retinopathy or peripheral polyneuropathy. We also found that there was no relationship between the severity of autonomic neuropathy and degree of Q7c dispersion. CONCLUSION: We concluded that QTc dispersion may be a good method for evaluation of cardiovascular autonomic neuropathy and increased QTc dispersion may be one of the markers of arrhythmia in diabetic patients with autonomic neuropathy.

QTc Interval and QT Dispersion Prolongation in NIDDM Patients with Diabetic Autonomic Neuropathy.: Yong Kyun Cho, Seung Won Lee, Won Tae Seo, Yoon Sang Choi, Jin Ho Kang, Man Ho Lee, Sang Jong Lee; Korean Diabetes J. 1998;22(1):93-102. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It has been reported that QTc interval and QT dispersion prolongation on 12 lead EKG reflects predictability and diagnosis of cardiovascular complications induced by autonomic nervous system abnormalities. We have investigated in NIDDM patients whether severity of cadiovascular autonomic neuropathy(CAN) evaluated by conventional standard cardiovascular autonomic function test is correlated with prolongation of QT, QTc interval and QT dispersion. In addition, whether these prolonagtion can reflect CAN and if any other clinical variables related to pralongatian exist. METHODS: Eighty patients(39 male, 41 female) treated with oral hypoglycemic agents or insulin after diagnosis of NIDDM in our hospital were included in the study. These patients were devided into three groups (Group I, 13 subjects: No CAN, Group II, 20 subjects: Borderline CAN, Group III, 47 subjects: Definite CAN) according to the score of standard catdiovascular autonomic function test(Deep breathing test, Lying to standing test, Heart ration on Valsalva manuever, Postural BP drop test). The measured QT, QTc interval and QT disp rsion of eaeh diabetic group and control group were analyzed. RESULTS: l. Statistically significant prolongation of QT,QTc, QT dispersion was observed in NIDDM tients as compared with those of control group(p=0.015, 0,021, 0.001). 2. Severity of autonomic neuropathy has shown positive correlation with only prolongation of QT dispersion(p<0.05) in three diabetic subgroups. 3. Statistically significant difference was not ob::rved in HbAlc and BMI between each patients groups of NIDDM(p>0.05) but both HbAlc and BMI showed weak positive correlation with prologation of QT dispersion(r=0.262, r=0.267 repectively). CONCLUSION: QTc interval and QT dispersion are considered easily accessible factors to predict and evaluate the degree of cardiovascular autonomic function abnormalities in NIDDM patients, yet further long term follow up and study in large group should be carried out to decide if these factor can predict and reflect severity of cardiovascular abnormalities such as ventricular arrhythmia, and sudden cardiac death. In additian, prolonged QT dispersion has shown weak positive correlation with both HbAlc and BMI and some other influential factors are suggested to play a role in autonomic neuropathy in NIDDM patients.

Relationship between Peripheral Neuropathy and Cardiovascular Autonomic Neuropathy in Non-Insulin Dependent Diabetics.: Sung Woo Ha, Hyun Jeong Lee, Jeung Hun Han, Sang Won Jung, Jick Hwa Nam, Byoung Ho Sin, Seong Mo Koo, Jung Guk Kim, Sam Kwon, Bo Wan Kim; Korean Diabetes J. 1997;21(4):476-483. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Autonomic neuropathy was detected in some diabetics with symmetric peripheral neuropathy, a common complication of diabetes mellitus that may be associated with considerable morbidity. There has been known to be similarity of pathogenic mechanism in two neuropathies. Then we examined nerve conduction velocity and cardiovascular autonomic function tests. We studied relationship between peripheral and cardiovascular autonomic neuropathy in non-insulin dependent diabetics. METHODS: We studied 166 patients with or witbout peripheral neuropathy who had been diagnosed as non-insulin dependent diabetes mellitus. We examined nerve conduction tests to assess diabetic peripheral neuropathy and classified them into 4 groups aecording to neuropathic symptoms and results of nerve conduction tests. We examined five cardiovascular autonomic function tests by Ewing's methods. RESULTS: 1. The duration of diabetes mellitus was significantly longer in the group of cliabetics with neuropathic symptoms and abnormal findings in the nerve conduction velocity tests than the other groups. The level of blood glucose was significantly higher in the group of diabetics with neuropathic symptoms and findings than the other groups. 2. In the 5 cardiovascular autonomic function tests, heart rate response to deep breathing and Valsalva maneuver had significant differences between the diabetic group with peripheral neuropathy and the other groups. 3. The frequency and severity of autonomic neuropathy were higher in the group with peripheral neuro-pathic symptoms and findings than the other groups without neuropathic syrnptoms and findings. There was an overall significant relationship between sensorirnotor neural function and autonomic function. 4. There was no association between peripheral neuropathy and nephropathy although peripheral neuropathy was related with retinopathy. CONCLUSION: Diabetic peripheral neuropathy accompanies autonomic neuropathy. Then, this result suggests that there is the relationship between peripheral and cardiovascular autonomic neuropathy.

Analgesic Effects of DA-5018, a New Capsaicin Derivative, in Hyperalgesia of Experimental Diabetic Neuropathy.: Eun Ju Bae, Soon How Kim, Moon Ho Son, Hee Kee Kim, Myeong Soo Shin, Hyun Ji Kim, Won Bae Kim; Korean Diabetes J. 1997;21(1):91-101. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Painful peripheral neuropathy is one of the most common complications of diabetes and not responsive to conventional analgesics. Capsaicin cream has been used to treat the pain associated with diabetic neuropathy, rheumatoid arthritis, osteoarthritis and postherpetic neuralgia. But its common side effect, burning sensation, limits the use of it. DA-5018 is a newly synthesized capsaicin derivative which shows more potent systemic and topical analgesia than capsaicin in various animal models of acute and chronic pain, but has little skin irritaion. This study was designed to evaluate the effect of DA-5018 administered systemically or topically on hyperalgesia in streptozotocin-induced diabetic and galactosaemic rats. METHODS: One group of SD rats was treated with streptozotocin(60mg/kg, I.v.) and the pain thresholds were determined weekly by Randall-Selitto paw pressure test. And the other group of SD rats was maintained on 50%-galactose diet until 4~5 weeks and the pain thresholds were determined as well, Drugs were administered subcutaneously once a day for 7 days or topically to the paw for 5 hours a day for 10 days at a time when the hyperalgesia was already present. The increase of pain thresholds by drug was regarded as an indication of analgesia. RESULTS: Streptozotocin-diabetic rats displayed a reduction of pain threshold. Similarly, galactosefeeding resulted in significant reduction of pain threshold. It is concluded that hyperalgesia is a constant feature of sensory dysfunction in experimental models of diabetic and nutritional neuropathy. DA-5018(0.2, 0.5mg/kg, s.c.) produced significant antinociception with efficacy similar to that of capsaicin(10mg/kg, s.c.) in streptozotocin-induced hyperalgesia and furthermore, no tolerance developed for 7 days. And this analgesic effect was superior to desipramine(10mg/kg, s.c.). But ketoprofen(10mg/kg, s.c.) produced no analgesia. Topically, 0.3% DA-5018 cream was as effective as Zostrix-HP(capsaicin 0.075%) both in streptozotocin-diabetic and galactosefed rats while Kenofen gel(ketoprofen 3%) was ineffective to reduce pain. CONCLUSION: These results demonstrate the potent analgesic efficacy of DA-5018 in diabetic pain models and suggest that topical DA-5018 cream may relieves pain caused by diabetic neuropathy offering an alternative for patients not responsive to other treatments or unable to tolerate capsaicin.

Relationship between Cardiovascular Autonomic Neuropathy and Diabetic Retinopathy in Patients with Non-Insulin Dependent Diabetes Mellitus.: Jae Chun Lee, Sang Yob Nam, Ji Sung Yoon, Jin Chul Park, Kyu Chang Won, Ihn Ho Cho, Hyoung Woo Lee, Hyun Woo Lee; Korean Diabetes J. 1997;21(1):82-90. Published online January 1, 2001

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Abstract PDF: BACKGROUND
The presence of cardiovascular autonomic neuropathy may play a permissive role in the development and progression of diabetic retinopathy. But, there is little information regarding the degree of association between the progression of diabetic retinopathy and cardiovascular autonomic neuropathy in patients with non-insulin dependent diabetes mellitus. Thus, this study defined the relationship between the progression of diabetic retinopathy and cardiovascular autonomic neuropathy in patients with non-insulin dependent diabetes mellitus. METHODS: Seventy-nine patients with non-insulin dependent diabetes mellitus were separated into 2 groups based on the presence of cardiovascular autonomic neuropathy. Age, body mass index, duration of illness, plasma creatinine, BUN, fasting plasma glueose, glycated hemoglobin, lipid profile and 24hr urine total protein were not statistically different among the two groups. According to indirect ophthalmoscopy, patients were also classified as having proliferative, non-proliferative or no retinopathy. RESULTS: The results showed a striking relntionship between cardiovascular autonomic neuropathy and proliferative diabetic retinopathy(p<0.01). Corrected QT interval was more prolonged in non-insulin dependent diabetes mellitus patients with cnrdiovascular autonomic neuropathy than patients without cardiovascular autonomic neuropathy(p<0.05). In non-insulin dependent diabetes mellitus patients with cardiovascular autonomic neuropathy, there was no relationship between the prolongation of corrected QT interval and proliferative diabetic retinopathy, and there was no significant relationship between each of 5 components of cardiovascular autonomic neuropathy test and proliferative diiabetic retinopathy. CONCLUSION: These results suggest that the presence of cardiovascular autonomic neuropathy is strongly associated with proliferative retinopathy in patients with non-insulin dependent diabetes mellitus. But, long-term prospective studies on large cohorts of patients must be done to evaluate if cardiovascular autonomic neuropathy would be a risk factor or a risk indicator of an etiologic process underlying the development of proliferative retinopathy.

Venous Oxygenation in the Feet of Diabetics with Neuropathic foot Ulceration.: Chung Gu Cho; Korean Diabetes J. 1997;21(1):74-81. Published online January 1, 2001

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Abstract PDF: BACKGROUND
Diabetic patients with non-infected neuropathic foot lesions frequently have prominent pedal arteries and distended dorsal foot veins, both in the ulcerated and in the non-ulcerated foot. Such patients also have increased blood flow in the lower limbs as suggested by plethysmographic and ultrasound studies. Accordingly, the aim of this study was to evaluate the venous oxygenation, as determined by partial pressure of oxygen(PO), in the feet of diabetics with and without foot ulceration and neuropathy in order to confirm the arteriovenous(A-V) shunting in the diabetic neuropathic foot may be important in the pathogenesis of ulceration. METHODS: Venous PO was measured in the feet and hands of four subject groups: 8 diabetics with neuropathy and foot ulceration(group 1); 10 diabetics with neuropathy but no ulceration(group 2); 10 diabetics with no evidence of neuropathy(group 3); and 9 non-diabetic controls(group 4). After an initial 30-min period of stabilization, veins on the dorsum of each foot and on the back of the hand were cannulated using a Butterly infusion set, 0.8mm gauge. Blood was withdrawn from each site into a heparinized glass syringe for immediate analysis of PO using a blood gas analyser. RESULTS: The mean venous PO2 in the feet of diabetic subjects with neuropathy and foot ulceration (group 1: 60.7+6.3mmHg)was significantly higher than in controls(group 4: 44.3+6.0mmHg) or the other two diabetic groups(group 2: 52.3+9.0mmHg, group 3: 46.1+5.5mmHg). Venous PO2 in the feet of the diabetic subjects with ulcers was also significantly higher than in their hands(45.4+5.8mmHg) or in the hands of the other groups(group 2:.46.6+6.3mmHg, group 3: 44.5+4.9mmHg, group 4: 44.9+5.1mmHg). CONCLUSION: These results provide further evidence of abnormal blood flow in the diabetic neuropathic foot and are compatible with arteriovenous shunting.

The Effect of Ginkgo Biloba Extract on Diabetic Peripheral Neuropathy - A 12 week, randomized, placebo-controlled, double-blind trial -.: Kyung Mook Choi, Dong Rim Kim, Nan Hee Kim, Sei Hyun Baik, Dong Seop Choi; Korean Diabetes J. 2000;24(3):375-384. Published online January 1, 2001

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Abstract PDF: BACKGROUND
In the pathogenesis of diabetic neuropathy, metabolic derangement and ischemic damage have been considered as the major possible mechanisms. Ginkgo biloba extract was known to improve microcirculation by its vasodilator and antiplatelet effects, and used for peripheral and cerebral circulatory disorder. It also acts as free radical scavenger and inhibits oxidative damage. Thus, in this study we evaluate the effects of Ginkgo biloba extract on symptoms and nerve conduction study in patients with diabetic peripheral neuropathy. METHODS: In this study, over 3 months period, we recruited a total of 33 type 2 diabetic patients with peripheral neuropathy. Nineteen patients were randomly assigned to receive placebo, and fourteen patients to receive Ginkgo biloba extract (40 mg tid) for a duration of 12 weeks. We measured fasting blood glucose, postprandial 2 hour blood glucose levels, glycosylated hemoglobin and the lipid profiles. Clinical evaluation included neuropathy symptom score and nerve conduction study, and it was performed before and after the treatment. RESULTS: During the treatment, fasting blood glucose, postprandial 2 hour blood glucose, glycosylated hemoglobin and the lipid profiles were not significantly changed. Furthermore, no significant changes of neuropathy symptom score were observed during the treatment period. However, in Ginkgo biloba extract treatment group, motor nerve conduction velocities of median and ulnar nerve were improved significantly when compared to the placebo group. CONCLUSION: With the 12 weeks Ginkgo biloba extract treatment, we observed some improvement of nerve conduction velocity without any serious side effect.

Peripheral Polyneruopathy and Hypoinsulinemia in Patients with Type 2 Diabetes.: Y S Jung, K Y Lee, S K Lee, H K Kim, H Y Park, M H Kang; Korean Diabetes J. 2000;24(2):256-266. Published online January 1, 2001

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Abstract PDF: BACKGROUND
There is little information on the risk factors for diabetic polyneuro-pathy other than glycemic control and duration of diabetes. The relation between diabetic polyneuropathy and hypoinsulinemia is controversial. This study is to determine whether hypoinsulinemia is an additional factor influencing the development of polyneuropathy in patients with type 2 diabetes. METHODS: We performed an oral glucose tolerance test with C-peptide measure-ment in 1'P2 patients with type 2 diabetes. Peripheral polyneuropathy was diagnosed when the patients had both typical symptoms of polyneuropathy and abnormal physical findings or NCV. We analysed the relation between metabolic variables including fasting and postprandial C-peptide levels and diabetic polyneuropathy. RESULTS: In addition to retinopathy and nephropathy, duration of diabetes, low C-peptide level (fasting and postprandial), insulin use, and high HDL-cholesterol level were associated with diabetic polyneuropathy. Multivariate logistic regression model revealed that an independent assoclation of diabetes duration and postprandial 2-hour C-peptide concentration with polyneuropathy. When we stratified the patients into the two groups according to the median duration of diabetes (8 years), the association of low postprandial C-peptide concentration with polyneuro-pathy was significant only in the shorter duration group(< 8 years). However, significant association of HbA(1c) level was shown in the longar duration group. CONCLUSION: Decreased insulin secretory function of the pancreas as well as increased duration of diabetes was indepandently associated with diabetic polyneuropathy in patients with type 2 diabetes. Hypoinsulinemia might be an additional risk factor for the development of diabetic polyneuropathy in type 2 diabetic patients, particularly with short duration, To confirm these relationship further longitudinal study in a large cohort is necessary.

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