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Original Article
Complications
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Does the Relationship of the Autonomic Symptoms Questionnaire COMPASS 31 with Cardiovascular Autonomic Tests Differ between Type 1 and Type 2 Diabetes Mellitus?
Ilenia D’Ippolito, Marika Menduni, Cinzia D’Amato, Aikaterini Andreadi, Davide Lauro, Vincenza Spallone
Received August 28, 2023  Accepted November 22, 2023  Published online February 26, 2024  
DOI: https://doi.org/10.4093/dmj.2023.0301    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The aim was to investigate if autonomic symptoms questionnaire Composite Autonomic Symptom Score (COMPASS) 31 has different association with cardiovascular autonomic neuropathy (CAN) and diagnostic performance between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).
Methods
Seventy-nine participants with T1DM and 140 with T2DM completed COMPASS 31 before cardiovascular reflex tests (CARTs) for CAN, and assessment of symptoms, signs, vibration, and thermal perception thresholds for diabetic polyneuropathy (DPN) diagnosis.
Results
COMPASS 31 total weighted score (TWS) was similar in the two groups, but significantly associated with confirmed CAN only in T1DM (P=0.0056) and not T2DM group (P=0.1768) and correlated with CARTs score more strongly in T1DM (rho=0.356, P=0.0016) than in T2DM group (rho=0.084, P=0.3218) (P=0.016). Only in T1DM and not T2DM group, the area under the receiver operating characteristic curve (AUC) reached a fair diagnostic accuracy (>0.7) for confirmed CAN (0.73±0.07 vs. 0.61±0.08) and DPN (0.75±0.06 vs. 0.68±0.05), although without a significant difference. COMPASS 31 TWS (cut-off 16.44) reached acceptable diagnostic performance in T1DM, with sensitivity for confirmed CAN 81.2% and sensitivity and specificity for DPN 76.3% and 78%, compared to T2DM group (all <70%). AUC for DPN of orthostatic intolerance domain was higher in T1DM compared to T2DM group (0.73±0.05 vs. 0.58±0.04, P=0.027).
Conclusion
COMPASS 31 is more weakly related to CAN in T2DM than in T1DM, with a fair diagnostic accuracy for confirmed CAN only in T1DM. This difference supports a multifactorial origin of symptoms and should be considered when using COMPASS 31.
Review
Complications
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Pharmacological and Nonpharmacological Treatments for Painful Diabetic Peripheral Neuropathy
Han Na Jang, Tae Jung Oh
Diabetes Metab J. 2023;47(6):743-756.   Published online September 6, 2023
DOI: https://doi.org/10.4093/dmj.2023.0018
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  • 6 Crossref
AbstractAbstract PDFPubReader   ePub   
Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%–25% of patients with diabetes experience neuropathic pain, referred to as “painful DPN.” Appropriate treatment of painful DPN is important because this pain contributes to a poor quality of life by causing sleep disturbance, anxiety, and depression. The basic principle for the management of painful DPN is to control hyperglycemia and other modifiable risk factors, but these may be insufficient for preventing or improving DPN. Because there is no promising diseasemodifying medication for DPN, the pain itself needs to be managed when treating painful DPN. Drugs for neuropathic pain, such as gabapentinoids, serotonin–norepinephrine reuptake inhibitors, tricyclic antidepressants, alpha-lipoic acid, sodium channel blockers, and topical capsaicin, are used for the management of painful DPN. The U.S. Food and Drug Administration (FDA) has approved pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch as drugs for the treatment of painful DPN. Recently, spinal cord stimulation using electrical stimulation is approved by the FDA for the treatment for painful DPN. This review describes the currently available pharmacological and nonpharmacological treatments for painful DPN.

Citations

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  • J-2156, a small molecule somatostatin type 4 receptor agonist, alleviated hindpaw hypersensitivity in the streptozotocin-induced rat model of painful diabetic neuropathy but with a 2-fold decrease in potency at an advanced stage in the model, mimicking mo
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    Kevin Woo
    Clinics in Geriatric Medicine.2024; 40(3): 501.     CrossRef
  • Diabetic Neuropathy: A Guide to Pain Management
    Emily X. Zhang, Cyrus Yazdi, Rahib K. Islam, Ahmed I. Anwar, Alana Alvares-Amado, Horace Townsend, Kaitlyn E. Allen, Elena Plakotaris, Jon D. Hirsch, Ross G. Rieger, Varsha Allampalli, Jamal Hasoon, Kazi N. Islam, Sahar Shekoohi, Alan D. Kaye, Christopher
    Current Pain and Headache Reports.2024;[Epub]     CrossRef
  • Expert opinion on screening, diagnosis and management of diabetic peripheral neuropathy: a multidisciplinary approach
    Aysegul Atmaca, Aysegul Ketenci, Ibrahim Sahin, Ihsan Sukru Sengun, Ramazan Ilyas Oner, Hacer Erdem Tilki, Mine Adas, Hatice Soyleli, Tevfik Demir
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Predicting the efficacy of rehabilitation in patients with type 2 diabetes and diabetic polyneuropathy
    T.H. Bakaliuk, N.R. Makarchuk, H.O. Stelmakh, V.I. Pankiv, I.I. Kamyshna
    INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2024; 20(3): 155.     CrossRef
  • Xiaoke Bitong capsule alleviates inflammatory impairment via inhibition of the TNF signaling pathway to against diabetic peripheral neuropathy
    Lulu Tian, Meiqi Yang, Shanjie Tu, Kaixin Chang, Huanyu Jiang, Yuwei Jiang, Lu Ding, Zhiwei Weng, Yueqiang Wang, Xiaolong Tan, Chunxiao Zong, Buyang Chen, Xiaobing Dou, Xiuge Wang, Xuchen Qi
    Phytomedicine.2024; : 155867.     CrossRef
Original Article
Complications
Effect of the Glucagon-Like Peptide-1 Receptor Agonists on Autonomic Function in Subjects with Diabetes: A Systematic Review and Meta-Analysis
Carla Greco, Daniele Santi, Giulia Brigante, Chiara Pacchioni, Manuela Simoni
Diabetes Metab J. 2022;46(6):901-911.   Published online April 12, 2022
DOI: https://doi.org/10.4093/dmj.2021.0314
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  • 6 Web of Science
  • 7 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
In addition to the metabolic effects in diabetes, glucagon-like peptide 1 receptor (GLP-1R) agonists lead to a small but substantial increase in heart rate (HR). However, the GLP-1R actions on the autonomic nervous system (ANS) in diabetes remain debated. Therefore, this meta-analysis evaluates the effect of GLP-1R agonist on measures of ANS function in diabetes.
Methods
According to the Cochrane Collaboration and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, we conducted a meta-analysis considering clinical trials in which the autonomic function was evaluated in diabetic subjects chronically treated with GLP-1R agonists. The outcomes were the change of ANS function measured by heart rate variability (HRV) and cardiac autonomic reflex tests (CARTs).
Results
In the studies enrolled, HR significantly increased after treatment (P<0.001), whereas low frequency/high frequency ratio did not differ (P=0.410); no changes in other measures of HRV were detected. Considering CARTs, only the 30:15 value derived from lying-to-standing test was significantly lower after treatment (P=0.002), but only two studies reported this measurement. No differences in other CARTs outcome were observed.
Conclusion
The meta-analysis confirms the HR increase but seems to exclude an alteration of the sympatho-vagal balance due to chronic treatment with GLP-1R agonists in diabetes, considering the available measures of ANS function.

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  • Liraglutide does not increase heart rate of diabetic patients during acute myocardial infarction
    Qianyi Li, Chunxuan Wu, Shiqun Sun, Lingchao Yang, Yanyan Li, Yixin Niu, Li Zhang, Wei Li, Ying Yu
    Journal of Diabetes.2024;[Epub]     CrossRef
  • A randomized, double‐blind trial assessing the efficacy and safety of two doses of dulaglutide in Japanese participants with type 2 diabetes (AWARD‐JPN)
    Tomoaki Morioka, Masakazu Takeuchi, Akichika Ozeki, Masanori Emoto
    Diabetes, Obesity and Metabolism.2024; 26(8): 3167.     CrossRef
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    Eun Roh, Kyung Mook Choi
    International Journal of Molecular Sciences.2023; 24(4): 3384.     CrossRef
  • Effects of new hypoglycemic drugs on cardiac remodeling: a systematic review and network meta-analysis
    Yi-lin Huang, Xiao-zhuo Xu, Jing Liu, Pin-yao Wang, Xue-li Wang, Hong-lin Feng, Cheng-jiang Liu, Xu Han
    BMC Cardiovascular Disorders.2023;[Epub]     CrossRef
  • Obesity and hypertension: Obesity medicine association (OMA) clinical practice statement (CPS) 2023
    Tiffany Lowe Clayton, Angela Fitch, Harold Edward Bays
    Obesity Pillars.2023; 8: 100083.     CrossRef
  • Incretins and microvascular complications of diabetes: neuropathy, nephropathy, retinopathy and microangiopathy
    Jonathan Goldney, Jack A. Sargeant, Melanie J. Davies
    Diabetologia.2023; 66(10): 1832.     CrossRef
  • Diabetes-Induced Cardiac Autonomic Neuropathy: Impact on Heart Function and Prognosis
    Susumu Z. Sudo, Tadeu L. Montagnoli, Bruna de S. Rocha, Aimeé D. Santos, Mauro P. L. de Sá, Gisele Zapata-Sudo
    Biomedicines.2022; 10(12): 3258.     CrossRef
Review
Complications
Peripheral Neuropathy Phenotyping in Rat Models of Type 2 Diabetes Mellitus: Evaluating Uptake of the Neurodiab Guidelines and Identifying Future Directions
Md Jakir Hossain, Michael D. Kendig, Meg E. Letton, Margaret J. Morris, Ria Arnold
Diabetes Metab J. 2022;46(2):198-221.   Published online March 24, 2022
DOI: https://doi.org/10.4093/dmj.2021.0347
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AbstractAbstract PDFPubReader   ePub   
Diabetic peripheral neuropathy (DPN) affects over half of type 2 diabetes mellitus (T2DM) patients, with an urgent need for effective pharmacotherapies. While many rat and mouse models of T2DM exist, the phenotyping of DPN has been challenging with inconsistencies across laboratories. To better characterize DPN in rodents, a consensus guideline was published in 2014 to accelerate the translation of preclinical findings. Here we review DPN phenotyping in rat models of T2DM against the ‘Neurodiab’ criteria to identify uptake of the guidelines and discuss how DPN phenotypes differ between models and according to diabetes duration and sex. A search of PubMed, Scopus and Web of Science databases identified 125 studies, categorised as either diet and/or chemically induced models or transgenic/spontaneous models of T2DM. The use of diet and chemically induced T2DM models has exceeded that of transgenic models in recent years, and the introduction of the Neurodiab guidelines has not appreciably increased the number of studies assessing all key DPN endpoints. Combined high-fat diet and low dose streptozotocin rat models are the most frequently used and well characterised. Overall, we recommend adherence to Neurodiab guidelines for creating better animal models of DPN to accelerate translation and drug development.

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  • SIRT3 alleviates painful diabetic neuropathy by mediating the FoxO3a‐PINK1‐Parkin signaling pathway to activate mitophagy
    Jing Yang, Zhuoying Yu, Ye Jiang, Zixian Zhang, Yue Tian, Jie Cai, Min Wei, Yanhan Lyu, Dongsheng Yang, Shixiong Shen, Guo‐Gang Xing, Min Li
    CNS Neuroscience & Therapeutics.2024;[Epub]     CrossRef
  • Long-term sensorimotor changes after a sciatic nerve block with bupivacaine and liposomal bupivacaine in a high-fat diet/low-dose streptozotocin rodent model of diabetes
    Susanna C. Byram, Krista M. Lotesto, Michael Volyanyuk, Jacob E. Exline, Elizabeth A. Sager, Eileen M. Foecking
    Frontiers in Anesthesiology.2024;[Epub]     CrossRef
  • The impact of gut microbial dysbiosis on the atrophy of the hippocampus and abnormal metabolism of N-acetyl aspartate in type 2 diabetic rats
    Zhenyang Zhu, Qingqing Chen, Gege Jiang, Yuan Liang, Jing Shen, Jianlin Wu
    Heliyon.2024; 10(12): e33152.     CrossRef
  • Compound Qiying Granules alleviates diabetic peripheral neuropathy by inhibiting endoplasmic reticulum stress and apoptosis
    Yan Hu, Chen Chen, Zhengting Liang, Tao Liu, Xiaoling Hu, Guanying Wang, Jinxia Hu, Xiaolin Xie, Zhiyan Liu
    Molecular Medicine.2023;[Epub]     CrossRef
  • HCV affects KATP channels through GnT-IVa-mediated N-glycosylation of GLUT2 on the surface of pancreatic β-cells leading to impaired insulin secretion
    Ben Niu, Lijing Ma, Lixuan Yao, Yating Zhang, Heng Su
    Endocrine.2023; 84(2): 427.     CrossRef
  • Multimodal Comparison of Diabetic Neuropathy in Aged Streptozotocin-Treated Sprague–Dawley and Zucker Diabetic Fatty Rats
    Annalisa Canta, Valentina A. Carozzi, Alessia Chiorazzi, Cristina Meregalli, Norberto Oggioni, Virginia Rodriguez-Menendez, Barbara Sala, Roberto Cosimo Melcangi, Silvia Giatti, Raffaella Lombardi, Roberto Bianchi, Paola Marmiroli, Guido Cavaletti
    Biomedicines.2022; 11(1): 20.     CrossRef
Original Articles
Complications
Article image
SUDOSCAN in Combination with the Michigan Neuropathy Screening Instrument Is an Effective Tool for Screening Diabetic Peripheral Neuropathy
Tae Jung Oh, Yoojung Song, Hak Chul Jang, Sung Hee Choi
Diabetes Metab J. 2022;46(2):319-326.   Published online September 16, 2021
DOI: https://doi.org/10.4093/dmj.2021.0014
  • 6,404 View
  • 331 Download
  • 12 Web of Science
  • 13 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Screening for diabetic peripheral neuropathy (DPN) is important to prevent severe foot complication, but the detection rate of DPN is unsatisfactory. We investigated whether SUDOSCAN combined with Michigan Neuropathy Screening Instrument (MNSI) could be an effective tool for screening for DPN in people with type 2 diabetes mellitus (T2DM) in clinical practice.
Methods
We analysed the data for 144 people with T2DM without other cause of neuropathy. The presence of DPN was confirmed according to the Toronto Consensus criteria. Electrochemical skin conductance (ESC) of the feet was assessed using SUDOSCAN. We compared the discrimination power of following methods, MNSI only vs. SUDOSCAN only vs. MNSI plus SUDOSCAN vs. MNSI plus 10-g monofilament test.
Results
Confirmed DPN was detected in 27.8% of the participants. The optimal cut-off value of feet ESC to distinguish DPN was 56 μS. We made the DPN screening scores using the corresponding odds ratios for MNSI-Questionnaire, MNSI-Physical Examination, SUDOSCAN, and 10-g monofilament test. For distinguishing the presence of DPN, the MNSI plus SUDOSCAN model showed higher areas under the receiver operating characteristic curve (AUC) than MNSI only model (0.717 vs. 0.638, P=0.011), and SUDOSCAN only model or MNSI plus 10-g monofilament test showed comparable AUC with MNSI only model.
Conclusion
The screening model for DPN that includes both MNSI and SUDOSCAN can detect DPN with acceptable discrimination power and it may be useful in Korean patients with T2DM.

Citations

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  • Association of sudomotor dysfunction with risk of diabetic retinopathy in patients with type 2 diabetes
    Ming Wang, Niuniu Chen, Yaxin Wang, Jiaying Ni, Jingyi Lu, Weijing Zhao, Yating Cui, Ronghui Du, Wei Zhu, Jian Zhou
    Endocrine.2024; 84(3): 951.     CrossRef
  • Vitamin D deficiency increases the risk of diabetic peripheral neuropathy in elderly type 2 diabetes mellitus patients by predominantly increasing large-fiber lesions
    Sijia Fei, Jingwen Fan, Jiaming Cao, Huan Chen, Xiaoxia Wang, Qi Pan
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    Okti Sri Purwanti, Nursalam Nursalam, Moses Glorino Rumambo Pandin
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    Raffaele Galiero, Alfredo Caturano, Erica Vetrano, Domenico Beccia, Chiara Brin, Maria Alfano, Jessica Di Salvo, Raffaella Epifani, Alessia Piacevole, Giuseppina Tagliaferri, Maria Rocco, Ilaria Iadicicco, Giovanni Docimo, Luca Rinaldi, Celestino Sardu, T
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    Jean-Pierre Riveline, Roberto Mallone, Clarisse Tiercelin, Fetta Yaker, Laure Alexandre-Heymann, Lysa Khelifaoui, Florence Travert, Claire Fertichon, Jean-Baptiste Julla, Tiphaine Vidal-Trecan, Louis Potier, Jean-Francois Gautier, Etienne Larger, Jean-Pas
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  • Electrochemical Skin Conductance by Sudoscan in Non-Dialysis Chronic Kidney Disease Patients
    Liang-Te Chiu, Yu-Li Lin, Chih-Hsien Wang, Chii-Min Hwu, Hung-Hsiang Liou, Bang-Gee Hsu
    Journal of Clinical Medicine.2023; 13(1): 187.     CrossRef
  • The Presence of Clonal Hematopoiesis Is Negatively Associated with Diabetic Peripheral Neuropathy in Type 2 Diabetes
    Tae Jung Oh, Han Song, Youngil Koh, Sung Hee Choi
    Endocrinology and Metabolism.2022; 37(2): 243.     CrossRef
  • Case report: Significant relief of linezolid-induced peripheral neuropathy in a pre-XDR-TB case after acupuncture treatment
    Yuping Mo, Zhu Zhu, Jie Tan, Zhilin Liang, Jiahui Wu, Xingcheng Chen, Ming Hu, Peize Zhang, Guofang Deng, Liang Fu
    Frontiers in Neurology.2022;[Epub]     CrossRef
  • Detection of sudomotor alterations evaluated by Sudoscan in patients with recently diagnosed type 2 diabetes
    Ana Cristina García-Ulloa, Paloma Almeda-Valdes, Teresa Enedina Cuatecontzi-Xochitiotzi, Jorge Alberto Ramírez-García, Michelle Díaz-Pineda, Fernanda Garnica-Carrillo, Alejandra González-Duarte, K M Venkat Narayan, Carlos Alberto Aguilar-Salinas, Sergio H
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Complications
Article image
Influence of Glucose Fluctuation on Peripheral Nerve Damage in Streptozotocin-Induced Diabetic Rats
Yu Ji Kim, Na Young Lee, Kyung Ae Lee, Tae Sun Park, Heung Yong Jin
Diabetes Metab J. 2022;46(1):117-128.   Published online September 9, 2021
DOI: https://doi.org/10.4093/dmj.2020.0275
  • 5,725 View
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  • 4 Web of Science
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
Background
It is unclear whether glycemic variability (GV) is a risk factor for diabetic peripheral neuropathy (DPN), and whether control of GV is beneficial for DPN. The purpose of this study was to investigate the effect of GV on peripheral nerve damage by inducing glucose fluctuation in streptozotocin-induced diabetic rats.
Methods
Rats were divided into four groups: normal (normal glucose group [NOR]), diabetes without treatment (sustained severe hyperglycemia group; diabetes mellitus [DM]), diabetes+once daily insulin glargine (stable hyperglycemia group; DM+LAN), and diabetes+once daily insulin glargine with twice daily insulin glulisine (unstable glucose fluctuation group; DM+Lantus [LAN]+Apidra [API]). We measured anti-oxidant enzyme levels and behavioral responses against tactile, thermal, and pressure stimuli in the plasma of rats. We also performed a quantitative comparison of cutaneous and sciatic nerves according to glucose fluctuation.
Results
At week 24, intraepidermal nerve fiber density was less reduced in the insulin-administered groups compared to the DM group (P<0.05); however, a significant difference was not observed between the DM+LAN and DM+LAN+API groups irrespective of glucose fluctuation (P>0.05; 16.2±1.6, 12.4±2.0, 14.3±0.9, and 13.9±0.6 for NOR, DM, DM+LAN, and DM+LAN+API, respectively). The DM group exhibited significantly decreased glutathione levels compared to the insulin-administered groups (2.64±0.10 μmol/mL, DM+LAN; 1.93±0.0 μmol/mL, DM+LAN+API vs. 1.25±0.04 μmol/mL, DM; P<0.05).
Conclusion
Our study suggests that glucose control itself is more important than glucose fluctuation in the prevention of peripheral nerve damage, and intra-day glucose fluctuation has a limited effect on the progression of peripheral neuropathy in rats with diabetes.

Citations

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  • Glucose Fluctuation Inhibits Nrf2 Signaling Pathway in Hippocampal Tissues and Exacerbates Cognitive Impairment in Streptozotocin-Induced Diabetic Rats
    Haiyan Chi, Yujing Sun, Peng Lin, Junyu Zhou, Jinbiao Zhang, Yachao Yang, Yun Qiao, Deshan Liu, Eusebio Chiefari
    Journal of Diabetes Research.2024; 2024: 1.     CrossRef
  • Artesunate Inhibits Apoptosis and Promotes Survival in Schwann Cells via the PI3K/AKT/mTOR Axis in Diabetic Peripheral Neuropathy
    Xin Zhang, Zhifang Liang, Ying Zhou, Fang Wang, Shan Wei, Bing Tan, Yujie Guo
    Biological and Pharmaceutical Bulletin.2023; 46(6): 764.     CrossRef
  • The Potential of Glucose Treatment to Reduce Reactive Oxygen Species Production and Apoptosis of Inflamed Neural Cells In Vitro
    Juin-Hong Cherng, Shu-Jen Chang, Hsin-Da Tsai, Chung-Fang Chun, Gang-Yi Fan, Kenneth Dean Reeves, King Hei Stanley Lam, Yung-Tsan Wu
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    Haiyan Chi, Min Song, Jinbiao Zhang, Junyu Zhou, Deshan Liu, Victor Manuel Mendoza-Nuñez
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Complications
Article image
Study on Risk Factors of Peripheral Neuropathy in Type 2 Diabetes Mellitus and Establishment of Prediction Model
Birong Wu, Zheyun Niu, Fan Hu
Diabetes Metab J. 2021;45(4):526-538.   Published online July 30, 2021
DOI: https://doi.org/10.4093/dmj.2020.0100
  • 7,934 View
  • 326 Download
  • 16 Web of Science
  • 21 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Diabetic peripheral neuropathy (DPN) is one of the most serious complications of type 2 diabetes mellitus (T2DM). DPN increases the risk of ulcers, foot infections, and noninvasive amputations, ultimately leading to long-term disability.
Methods
Seven hundred patients with T2DM were investigated from 2013 to 2017 in the Sanlin community by obtaining basic data from the electronic medical record system (EMRS). From September 2018 to July 2019, 681 patients (19 missing) were investigated using a questionnaire, physical examination, biochemical index test, and follow-up Toronto clinical scoring system (TCSS) test. Patients with a TCSS score ≥6 points were diagnosed with DPN. After removing missing values, 612 patients were divided into groups in a 3:1 ratio for external validation. Using different Lasso analyses (misclassification error, mean squared error, –2log-likelihood, and area under curve) and a logistic regression analysis of the training set, models A, B, C, and D were established. The receiver operating characteristic (ROC) curve, calibration plot, dynamic component analysis (DCA) measurements, net classification improvement (NRI) and integrated discrimination improvement (IDI) were used to validate discrimination and clinical practicality of the model.
Results
Through data analysis, model A (containing four factors), model B (containing five factors), model C (containing seven factors), and model D (containing seven factors) were built. After calibration, ROC curve, DCA, NRI and IDI, models C and D exhibited better accuracy and greater predictive power.
Conclusion
Four prediction models were established to assist with the early screening of DPN in patients with T2DM. The influencing factors in model C and D are more important factors for patients with T2DM diagnosed with DPN.

Citations

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  • Diabetes Mellitusu Olan Bireylerde Periferal Nöropati ve Hemşirelik Bakımı
    Semanur BİLGİÇ, Burcu BAYRAK KAHRAMAN
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    Zhengang Wei, Xiaohua Wang, Liqin Lu, Su Li, Wenyan Long, Lin Zhang, Shaolin Shen
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    Ana Vitoria Lima de Paula, Gabrielly Menin Dykstra, Rebeca Barbosa da Rocha, Alessandra Tanuri Magalhães, Baldomero Antônio Kato da Silva, Vinicius Saura Cardoso
    Journal of Diabetes and its Complications.2024; 38(8): 108802.     CrossRef
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    Zhihui Tu, Juan Du, Xiaoxu Ge, Wenfang Peng, Lisha Shen, Lili Xia, Xiaohong Jiang, Fan Hu, Shan Huang
    Diabetes Therapy.2024;[Epub]     CrossRef
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    Wei Chu, Lin-Lin Ma, Bin-Xian Li, Ming-Cheng Li
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    Thomas W. King, Blake J. Cochran, Kerry-Anne Rye
    Arteriosclerosis, Thrombosis, and Vascular Biology.2023; 43(8): 1362.     CrossRef
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    Xin Luo, Jijia Sun, Hong Pan, Dian Zhou, Ping Huang, Jingjing Tang, Rong Shi, Hong Ye, Ying Zhao, An Zhang, Yee Gary Ang
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Complications
Article image
Association of Urinary N-Acetyl-β-D-Glucosaminidase with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes Mellitus without Nephropathy
Min Sun Choi, Ji Eun Jun, Sung Woon Park, Jee Hee Yoo, Jiyeon Ahn, Gyuri Kim, Sang-Man Jin, Kyu Yeon Hur, Moon-Kyu Lee, Jae Hyeon Kim
Diabetes Metab J. 2021;45(3):349-357.   Published online February 2, 2021
DOI: https://doi.org/10.4093/dmj.2019.0211
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
Background
Cardiovascular autonomic neuropathy (CAN) is a common microvascular complication of diabetes and related to albuminuria in diabetic nephropathy (DN). Urinary N-acetyl-β-D-glucosaminidase (uNAG) is a renal tubular injury marker which has been reported as an early marker of DN even in patients with normoalbuminuria. This study evaluated whether uNAG is associated with the presence and severity of CAN in patients with type 1 diabetes mellitus (T1DM) without nephropathy.
Methods
This cross-sectional study comprised 247 subjects with T1DM without chronic kidney disease and albuminuria who had results for both uNAG and autonomic function tests within 3 months. The presence of CAN was assessed by age-dependent reference values for four autonomic function tests. Total CAN score was assessed as the sum of the partial points of five cardiovascular reflex tests and was used to estimatethe severity of CAN. The correlations between uNAG and heart rate variability (HRV) parameters were analyzed.
Results
The association between log-uNAG and presence of CAN was significant in a multivariate logistic regression model (adjusted odds ratio, 2.39; 95% confidence interval [CI], 1.08 to 5.28; P=0.031). Total CAN score was positively associated with loguNAG (β=0.261, P=0.026) in the multivariate linear regression model. Log-uNAG was inversely correlated with frequency-domain and time-domain indices of HRV.
Conclusion
This study verified the association of uNAG with presence and severity of CAN and changes in HRV in T1DM patients without nephropathy. The potential role of uNAG should be further assessed for high-risk patients for CAN in T1DM patients without nephropathy.

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  • Determination of Diabetes-associated Cardiovascular Autonomic Neuropathy Risk Factors among Insulin and Non-insulin Dependent Diabetics
    Ibrahim Abdulsada, Zain Alabdeen Obaid, Farah Almerza, Mays Alwaeli, Anmar Al-Elayawi, Taha Al-Dayyeni, Harir Al-Tuhafy
    The Journal of Medical Research.2023; 9(6): 141.     CrossRef
  • Association between carotid atherosclerosis and presence of intracranial atherosclerosis using three-dimensional high-resolution vessel wall magnetic resonance imaging in asymptomatic patients with type 2 diabetes
    Ji Eun Jun, You-Cheol Hwang, Kyu Jeong Ahn, Ho Yeon Chung, Geon-Ho Jahng, Soonchan Park, In-Kyung Jeong, Chang-Woo Ryu
    Diabetes Research and Clinical Practice.2022; 191: 110067.     CrossRef
Brief Report
Complications
Article image
Status of Diabetic Neuropathy in Korea: A National Health Insurance Service-National Sample Cohort Analysis (2006 to 2015)
Seong-Su Moon, Chong Hwa Kim, Seon Mee Kang, Eun Sook Kim, Tae Jung Oh, Jae-Seung Yun, Ho Chan Cho, Dae Jung Kim, Tae Sun Park
Diabetes Metab J. 2021;45(1):115-119.   Published online December 18, 2020
DOI: https://doi.org/10.4093/dmj.2020.0120
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
This report presents the status of diabetic neuropathy (DN) in Korea as determined using a National Health Insurance ServiceNational Sample Cohort (NHIS-NSC). Annual prevalences of DN were estimated by age and gender using descriptive statistics. Pharmacological treatments for DN were also analyzed. The annual prevalence of DN increased from 24.9% in 2006 to 26.6% in 2007, and thereafter, gradually subsided to 20.8% in 2015. In most cases, pharmacological treatments involved a single drug, which accounted for 91.6% of total prescriptions in 2015. The most commonly used drugs (in decreasing order) were thioctic acid, an anti-convulsive agent, or a tricyclic antidepressant. In conclusion, the prevalence of DN decreased over the 10-year study period. Thioctic acid monotherapy was usually prescribed for DN. To reduce the socio-economic burden of DN, more attention should be paid to the diagnosis of this condition and to the appropriate management of patients.

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  • Diabetic Neuropathy: A Guide to Pain Management
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    Min Kyung Hyun, Jang Won Lee, Seung-Hyun Ko
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    Han Na Jang, Tae Jung Oh
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    Seon Mee Kang
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    Seong-Su Moon, Chong Hwa Kim, Seon Mee Kang, Eun Sook Kim, Tae Jung Oh, Jae-Seung Yun, Ho Chan Cho, Dae Jung Kim, Tae Sun Park
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  • Status of Diabetic Neuropathy in Korea: A National Health Insurance Service-National Sample Cohort Analysis (2006 to 2015) (Diabetes Metab J 2021;45:115-9)
    Tímea Csákvári, Diána Elmer, Lilla Horváth, Imre Boncz
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Review
Complications
Article image
Lost in Translation? Measuring Diabetic Neuropathy in Humans and Animals
Heung Yong Jin, Seong-Su Moon, Nigel A. Calcutt
Diabetes Metab J. 2021;45(1):27-42.   Published online December 15, 2020
DOI: https://doi.org/10.4093/dmj.2020.0216
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Graphical AbstractGraphical Abstract AbstractAbstract PDFPubReader   ePub   
The worldwide diabetes epidemic is estimated to currently afflict almost 500 million persons. Long-term diabetes damages multiple organ systems with the blood vessels, eyes, kidneys and nervous systems being particularly vulnerable. These complications of diabetes reduce lifespan, impede quality of life and impose a huge social and economic burden on both the individual and society. Peripheral neuropathy is a debilitating complication that will impact over half of all persons with diabetes. There is no treatment for diabetic neuropathy and a disturbingly long history of therapeutic approaches showing promise in preclinical studies but failing to translate to the clinic. These failures have prompted re-examination of both the animal models and clinical trial design. This review focuses on the functional and structural parameters used as indices of peripheral neuropathy in preclinical and clinical studies and the extent to which they share a common pathogenesis and presentation. Nerve conduction studies in large myelinated fibers have long been the mainstay of preclinical efficacy screening programs and clinical trials, supplemented by quantitative sensory tests. However, a more refined approach is emerging that incorporates measures of small fiber density in the skin and cornea alongside these traditional assays at both preclinical and clinical phases.

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    Raffaele Galiero, Alfredo Caturano, Erica Vetrano, Domenico Beccia, Chiara Brin, Maria Alfano, Jessica Di Salvo, Raffaella Epifani, Alessia Piacevole, Giuseppina Tagliaferri, Maria Rocco, Ilaria Iadicicco, Giovanni Docimo, Luca Rinaldi, Celestino Sardu, T
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    Jeffrey L. Chen, Andrew W. Hesseltine, Sara E. Nashi, Shawn M. Sills, Tory L. McJunkin, Sandeep Patil, Manish Bharara, David L. Caraway, Elizabeth S. Brooks
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    Min Shi, Xiangcheng Zhang, Ridong Zhang, Hong Zhang, Dalong Zhu, Xiao Han
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    Otto Jesus Hernandez Fustes
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    Heung Yong Jin, Seong-Su Moon, Nigel A. Calcutt
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    Amos Sunday Onikanni, Bashir Lawal, Augustine O Olusola, Janet O Olugbodi, Saidu Sani, Basiru Olaitan Ajiboye, Omotayo B Ilesanmi, Mohammed Alqarni, Gomaa Mostafa-Hedeab, Ahmad J Obaidullah, Gaber El-Saber Batiha, Alexander TH Wu
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Original Articles
Complications
Article image
Association between Sleep Quality and Painless Diabetic Peripheral Neuropathy Assessed by Current Perception Threshold in Type 2 Diabetes Mellitus
Dughyun Choi, Bo-Yeon Kim, Chan-Hee Jung, Chul-Hee Kim, Ji-Oh Mok
Diabetes Metab J. 2021;45(3):358-367.   Published online August 6, 2020
DOI: https://doi.org/10.4093/dmj.2019.0219
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Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

It is known that the painful sensation of diabetic peripheral neuropathy (DPN) results in sleep problems in type 2 diabetes mellitus (T2DM). However, it is not known that the painless DPN also is associated with poor sleep quality in T2DM. The purpose of the current study was to investigate the association between painless DPN and poor sleep quality in T2DM.

Methods

A total of 146 patients of T2DM who do not have any painful symptoms of DPN were recruited into the study. Among the patients, painless DPN was diagnosed by using the current perception threshold test. Sleep quality was assessed using the Pittsburgh Sleep Quality Index questionnaire.

Results

The percentage of painless DPN was significantly higher in the poor sleep quality group than the good sleep quality group (70.0% vs. 35.5%, P<0.001). In the subscale results, stimulus values at 2,000 Hz, hypoesthesia and hyperesthesia were more common in the poor sleep quality group than in the good sleep quality group (45.7% vs. 25.0%, P=0.009; 34.3% vs. 18.4%, P=0.029; 40.0% vs. 19.7%, P=0.007, respectively). The association of painless DPN and poor sleep quality remained significant after adjustment for significant covariates (odds ratio, 3.825; 95% confidence interval, 1.674 to 8.742; P<0.001).

Conclusion

The current study showed that painless DPN was associated with poor sleep quality. Future studies are required to clarify the pathophysiologic causal relationship between painless DPN and sleep quality.

Citations

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  • Deteriorated sleep quality and associate factors in patients with type 2 diabetes mellitus complicated with diabetic peripheral neuropathy
    Lin Fu, Liping Zhong, Xin Liao, Lingrui Wang, Youyi Wang, Xiuquan Shi, Yanna Zhou
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  • Sleep impairment: Is it an overlooked burden in painful diabetic peripheral neuropathy? A single-centre, cross-sectional study from south India
    Adlin Lawrence, Himsikhar Khataniar, Sinimol Joseph, Thenmozhi Nagarajan, Soumya Umesh, John Michael Raj A
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    Nishant Raizada, S. V. Madhu
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Drug/Regimen
γ-Linolenic Acid versus α-Lipoic Acid for Treating Painful Diabetic Neuropathy in Adults: A 12-Week, Double-Placebo, Randomized, Noninferiority Trial
Jong Chul Won, Hyuk-Sang Kwon, Seong-Su Moon, Sung Wan Chun, Chong Hwa Kim, Ie Byung Park, In Joo Kim, Jihyun Lee, Bong Yun Cha, Tae Sun Park
Diabetes Metab J. 2020;44(4):542-554.   Published online November 4, 2019
DOI: https://doi.org/10.4093/dmj.2019.0099
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

This study was a multicenter, parallel-group, double-blind, double-dummy, randomized, noninferiority trial to evaluate the efficacy and safety of γ-linolenic acid (GLA) relative to α-lipoic acid (ALA) over a 12-week treatment period in type 2 diabetes mellitus (T2DM) patients with painful diabetic peripheral neuropathy (DPN).

Methods

This study included 100 T2DM patients between 20 and 75 years of age who had painful DPN and received either GLA (320 mg/day) and placebo or ALA (600 mg/day) and placebo for 12 weeks. The primary outcome measures were mean changes in pain intensities as measured by the visual analogue scale (VAS) and the total symptom scores (TSS).

Results

Of the 100 subjects who initially participated in the study, 73 completed the 12-week treatment period. Per-protocol analyses revealed significant decreases in the mean VAS and TSS scores compared to baseline in both groups, but there were no significant differences between the groups. The treatment difference for the VAS (95% confidence interval [CI]) between the two groups was −0.65 (−1.526 to 0.213) and the upper bound of the 95% CI did not exceed the predefined noninferiority margin (δ1=0.51). For the TSS, the treatment difference was −0.05 (−1.211 to 1.101) but the upper bound of the 95% CI crossed the noninferiority margin (δ2=0.054). There were no serious adverse events associated with the treatments.

Conclusion

GLA treatment in patients with painful DPN was noninferior to ALA in terms of reducing pain intensity measured by the VAS over 12 weeks.

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    Yaowei Lv, Xiangyun Yao, Xiao Li, Yuanming Ouyang, Cunyi Fan, Yun Qian
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    Umut DALMIŞ, Emine Merve EKİCİ
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    Dan Ziegler
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Others
Increased Nociceptive Responses in Streptozotocin-Induced Diabetic Rats and the Related Expression of Spinal NR2B Subunit of N-Methyl-D-Aspartate Receptors
Che Aishah Nazariah Ismail, Rapeah Suppian, Che Badariah Abd Aziz, Khalilah Haris, Idris Long
Diabetes Metab J. 2019;43(2):222-235.   Published online November 19, 2018
DOI: https://doi.org/10.4093/dmj.2018.0020
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AbstractAbstract PDFPubReader   
Background

This study investigated the role of NR2B in a modulated pain process in the painful diabetic neuropathy (PDN) rat using various pain stimuli.

Methods

Thirty-two Sprague-Dawley male rats were randomly allocated into four groups (n=8): control, diabetes mellitus (DM) rats and diabetic rats treated with ifenprodil at a lower dose (0.5 µg/day) (I 0.5) or higher dose (1.0 µg/day) (I 1.0). DM was induced by a single injection of streptozotocin at 60 mg/kg on day 0 of experimentation. Diabetic status was assessed on day 3 of the experimentation. The responses on both tactile and thermal stimuli were assessed on day 0 (baseline), day 14 (pre-intervention), and day 22 (post-intervention). Ifenprodil was given intrathecally for 7 days from day 15 until day 21. On day 23, 5% formalin was injected into the rats' hind paw and the nociceptive responses were recorded for 1 hour. The rats were sacrificed 72 hours post-formalin injection and an analysis of the spinal NR2B expression was performed.

Results

DM rats showed a significant reduction in pain threshold in response to the tactile and thermal stimuli and higher nociceptive response during the formalin test accompanied by the higher expression of phosphorylated spinal NR2B in both sides of the spinal cord. Ifenprodil treatment for both doses showed anti-allodynic and anti-nociceptive effects with lower expression of phosphorylated and total spinal NR2B.

Conclusion

We suggest that the pain process in the streptozotocin-induced diabetic rat that has been modulated is associated with the higher phosphorylation of the spinal NR2B expression in the development of PDN, which is similar to other models of neuropathic rats.

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    Qi Wang, Yifei Ye, Linghui Yang, Lifan Xiao, Jin Liu, Wensheng Zhang, Guizhi Du
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Review
Complications
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 Metab J. 2019;43(1):3-30.   Published online November 2, 2018
DOI: https://doi.org/10.4093/dmj.2018.0259
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AbstractAbstract PDFPubReader   

The burden of diabetic cardiovascular autonomic neuropathy (CAN) is expected to increase due to the diabetes epidemic and its early and widespread appearance. CAN has a definite prognostic role for mortality and cardiovascular morbidity. Putative mechanisms for this are tachycardia, QT interval prolongation, orthostatic hypotension, reverse dipping, and impaired heart rate variability, while emerging mechanisms like inflammation support the pervasiveness of autonomic dysfunction. Efforts to overcome CAN under-diagnosis are on the table: by promoting screening for symptoms and signs; by simplifying cardiovascular reflex tests; and by selecting the candidates for screening. CAN assessment allows for treatment of its manifestations, cardiovascular risk stratification, and tailoring therapeutic targets. Risk factors for CAN are mainly glycaemic control in type 1 diabetes mellitus (T1DM) and, in addition, hypertension, dyslipidaemia, and obesity in type 2 diabetes mellitus (T2DM), while preliminary data regard glycaemic variability, vitamin B12 and D changes, oxidative stress, inflammation, and genetic biomarkers. Glycaemic control prevents CAN in T1DM, whereas multifactorial intervention might be effective in T2DM. Lifestyle intervention improves autonomic function mostly in pre-diabetes. While there is no conclusive evidence for a disease-modifying therapy, treatment of CAN manifestations is available. The modulation of autonomic function by SGLT2i represents a promising research field with possible clinical relevance.

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Original Article
Complications
Patterns of Nerve Conduction Abnormalities in Patients with Type 2 Diabetes Mellitus According to the Clinical Phenotype Determined by the Current Perception Threshold
Joong Hyun Park, Jong Chul Won
Diabetes Metab J. 2018;42(6):519-528.   Published online October 24, 2018
DOI: https://doi.org/10.4093/dmj.2018.0068
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AbstractAbstract PDFPubReader   
Background

Clinical manifestations of diabetic peripheral neuropathy (DPN) vary along the course of nerve damage. Nerve conduction studies (NCS) have been suggested as a way to confirm diagnoses of DPN, but the results have limited utility for evaluating clinical phenotypes. The current perception threshold (CPT) is a complementary method for diagnosing DPN and assessing DPN symptoms. We compared NCS variables according to clinical phenotypes determined by CPT measurements.

Methods

We retrospectively enrolled patients with type 2 diabetes mellitus who underwent both NCS and CPT tests using a neurometer. CPT grades were used to determine the clinical phenotypes of DPN: normoesthesia (0 to 1.66), hyperesthesia (1.67 to 6.62), and hypoesthesia/anesthesia (6.63 to 12.0). The Michigan Neuropathy Screening Instrument (MNSI) was used to determine a subjective symptom score. DPN was diagnosed based on both patient symptoms (MNSI score ≥3) and abnormal NCS results.

Results

A total of 202 patients (117 men and 85 women) were included in the final analysis. The average age was 62.6 years, and 71 patients (35.1%) were diagnosed with DPN. The CPT variables correlated with MNSI scores and NCS variables in patients with diabetes. Linear regression analyses indicated that hypoesthesia was associated with significantly lower summed velocities and sural amplitudes and velocities, and higher summed latencies, than normoesthesia. Sural amplitude was significantly lower in patients with hyperesthesia than in patients with normoesthesia.

Conclusion

NCS variables differed among patients with diabetes according to clinical phenotypes based on CPT and decreased sural nerve velocities was associated with hyperesthesia.

Citations

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