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Køhler E, Dalgas U, Buhl CS, Brincks J. Content and effects of balance training in people with diabetic peripheral neuropathy - a systematic review and meta-analysis. Physiother Theory Pract 2025; 41:1083-1094. [PMID: 39162012 DOI: 10.1080/09593985.2024.2391823] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 08/01/2024] [Accepted: 08/08/2024] [Indexed: 08/21/2024]
Abstract
BACKGROUND Diabetic Peripheral Neuropathy (DPN) impairs balance due to sensory loss, proprioceptive deficits, muscle weakness, altered gait, and delayed reflexes. Targeted aerobic and balance training seem promising to mitigate these issues. However, the exact content of a recommended training regime is yet to be determined. OBJECTIVE To delineate and synthesise balance training content and efficacy for people with DPN. METHODS The literature search was conducted on PubMed and Embase in accordance with the PRISMA-checklist. Last search was performed on April 29, 2024. Inclusion criteria were established using the PICO-framework. Methodological quality was assessed using the TESTEX Scale. Meta-analyses were exclusively applied to studies featuring a passive control group. RESULTS A total of 2007 articles were identified. Twelve studies were included in the qualitative synthesis. Seven studies were included in the meta-analyses. Two studies were of high quality. Most studies reported the frequency, session time, duration, and setting of balance training, while none reported the intensity. The meta-analyses showed a standardized mean difference in favor of balance training compared to passive control for One-Legged Stance (openeyes) (0.89[0.5,1.28]), One-Legged Stance (closed eyes) (1.48[0.36, 2.60]), Postural sway (-0.71[-1.04, -0,37]), Timed Up and Go(-0.94[-1.78, -0.10]), and Berg Balance Scale (2.26[0.48, 4.05]), respectively. CONCLUSION Studies are few and generally of low methodological quality. The content of balance training interventions is minimally described, especially concerning the applied intensity. However, balance training does seem to improve balance outcomes in people with DPN, but given the methodological limitations, interpretation must be cautious.
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Affiliation(s)
- Esben Køhler
- Department of Public Health, Section of Sports Science, Aarhus University, Aarhus, Denmark
| | - Ulrik Dalgas
- Department of Public Health, Section of Sports Science, Aarhus University, Aarhus, Denmark
| | | | - John Brincks
- Research Centre for Health and Welfare Technology - Programme for Rehabilitation, VIA University College, Aarhus, Denmark
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Gogan A, Potre O, Avram VF, Andor M, Caruntu F, Timar B. Cardiac Autonomic Neuropathy in Diabetes Mellitus: Pathogenesis, Epidemiology, Diagnosis and Clinical Implications: A Narrative Review. J Clin Med 2025; 14:671. [PMID: 39941342 PMCID: PMC11818907 DOI: 10.3390/jcm14030671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2024] [Revised: 01/12/2025] [Accepted: 01/17/2025] [Indexed: 02/16/2025] Open
Abstract
Background: Cardiac autonomic neuropathy (CAN) is a serious but sometimes underdiagnosed complications of Diabetes Mellitus (DM). Because of the subtle onset and non-specific symptoms that can be mistaken for other conditions, CAN is frequently underdiagnosed despite the serious consequences that can appear. Its significance as an independent risk factor for cardiovascular events, including arrhythmias, sudden cardiac death, and silent myocardial ischemia, is being demonstrated by recent studies. The objective of this review article is to highlight the reasons why CAN is underdiagnosed and its association with decreased cardiovascular risk and promote clinical awareness. This review article summarizes the epidemiology, influence on the cardiovascular system and diagnostic methods of CAN, and the clinical implications of diabetic neuropathy. This review analyzes available data from papers relevant to the topic of diabetic neuropathy, cardiac autonomic neuropathy, and cardiovascular system implications. Conclusions: CAN is still underdiagnosed despite its clinical impact because routine screening is lacking, and healthcare providers are not aware of it. To improve outcomes for people with DM, it is necessary to introduce standardized diagnostic procedures into clinical practice and increase the knowledge about CAN.
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Affiliation(s)
- Alexandra Gogan
- Doctoral School of Medicine, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania;
- First Department of Internal Medicine, Medical Semiology II, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania; (M.A.); (F.C.)
- Cardiology Clinic, Institute of Cardiovascular Disease, 300310 Timisoara, Romania
| | - Ovidiu Potre
- First Department of Internal Medicine, Hematology, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania
- Multidisciplinary Research Centre for Malignant Hematological Disease (CCMHM), “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Vlad-Florian Avram
- Department of Diabetes, “Pius Brinzeu” Emergency Hospital, 300723 Timisoara, Romania; (V.-F.A.); (B.T.)
- Centre for Molecular Research in Nephrology and Vascular Disease, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania
- Second Department of Internal Medicine, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania
| | - Minodora Andor
- First Department of Internal Medicine, Medical Semiology II, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania; (M.A.); (F.C.)
- Multidisciplinary Heart Research Center, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania
- Cardiology Clinic of Timisoara Municipal Clinical Emergency Hospital, 300040 Timisoara, Romania
| | - Florina Caruntu
- First Department of Internal Medicine, Medical Semiology II, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania; (M.A.); (F.C.)
- Multidisciplinary Heart Research Center, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania
- Cardiology Clinic of Timisoara Municipal Clinical Emergency Hospital, 300040 Timisoara, Romania
| | - Bogdan Timar
- Department of Diabetes, “Pius Brinzeu” Emergency Hospital, 300723 Timisoara, Romania; (V.-F.A.); (B.T.)
- Centre for Molecular Research in Nephrology and Vascular Disease, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania
- Second Department of Internal Medicine, “Victor Babes” University of Medicine and Pharmacy, 3000041 Timisoara, Romania
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ElSayed NA, McCoy RG, Aleppo G, Balapattabi K, Beverly EA, Briggs Early K, Bruemmer D, Callaghan BC, Echouffo-Tcheugui JB, Ekhlaspour L, Frykberg RG, Garg R, Garg SJ, Giurini JM, Khunti K, Lal R, Lingvay I, Matfin G, Pandya N, Pekas EJ, Pilla SJ, Polsky S, Segal AR, Seley JJ, Stanton RC, Bannuru RR. 12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes-2025. Diabetes Care 2025; 48:S252-S265. [PMID: 39651973 PMCID: PMC11635040 DOI: 10.2337/dc25-s012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2024]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Yapislar H, Gurler EB. Management of Microcomplications of Diabetes Mellitus: Challenges, Current Trends, and Future Perspectives in Treatment. Biomedicines 2024; 12:1958. [PMID: 39335472 PMCID: PMC11429415 DOI: 10.3390/biomedicines12091958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 08/12/2024] [Accepted: 08/13/2024] [Indexed: 09/30/2024] Open
Abstract
Diabetes mellitus is a chronic metabolic disorder characterized by high blood sugar levels, which can lead to severe health issues if not managed effectively. Recent statistics indicate a significant global impact, with 463 million adults diagnosed worldwide and this projected to rise to 700 million by 2045. Type 1 diabetes is an autoimmune disorder where the immune system attacks pancreatic beta cells, reducing insulin production. Type 2 diabetes is primarily due to insulin resistance. Both types of diabetes are linked to severe microvascular and macrovascular complications if unmanaged. Microvascular complications, such as diabetic retinopathy, nephropathy, and neuropathy, result from damage to small blood vessels and can lead to organ and tissue dysfunction. Chronic hyperglycemia plays a central role in the onset of these complications, with prolonged high blood sugar levels causing extensive vascular damage. The emerging treatments and current research focus on various aspects, from insulin resistance to the intricate cellular damage induced by glucose toxicity. Understanding and intervening in these pathways are critical for developing effective treatments and managing diabetes long term. Furthermore, ongoing health initiatives, such as increasing awareness, encouraging early detection, and improving treatments, are in place to manage diabetes globally and mitigate its impact on health and society. These initiatives are a testament to the collective effort to combat this global health challenge.
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Affiliation(s)
- Hande Yapislar
- Department of Physiology, Faculty of Medicine, Acibadem University, 34752 Istanbul, Türkiye
| | - Esra Bihter Gurler
- Department of Basic Sciences, Faculty of Dentistry, Istanbul Galata University, 34430 Istanbul, Türkiye
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Ricciardi D, Galiero R, Todisco V, Tedeschi G, Loffredo G, Caturano A, Rinaldi L, Cirillo G, Sasso FC. Neurophysiological assessment of peripheral neuropathy through whole plantar nerve conduction in type 2 diabetes mellitus and healthy control subjects. METABOLISM AND TARGET ORGAN DAMAGE 2024; 4. [DOI: 10.20517/mtod.2024.20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
Aim: To neurophysiologically characterize the innervation of the sole and assess the diagnostic efficacy of whole plantar nerve (WPN) conduction study in type 2 diabetes mellitus (T2DM) patients and healthy control subjects.
Methods: This single-center prospective observational case-control study involved 51 individuals with T2DM and 34 healthy controls. All subjects underwent validated screening tests for peripheral neuropathy (PN), including proximal and distal sural nerve conduction study and WPN.
Results: The median amplitude of the compound nerve action potentials (CNAPs) and the sensory conduction velocity (SCV) recorded by WPN conduction were significantly lower in patients with T2DM as compared to healthy controls. Sural nerve conduction revealed that both proximal and distal sensory nerve action potentials amplitude and SCV were significantly lower in subjects with diabetes, as compared to healthy controls. As compared with sural nerve conduction, WPN shows a Sensitivity of 77% and a negative predictive value (NPV) of 77%.
Conclusions: WPN conduction study is helpful in characterizing the most distal nerve fibers in patients with T2DM and healthy controls. WPN may represent a useful tool in the diagnosis of length-dependent diabetic polyneuropathy.
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Moon JS, Kang S, Choi JH, Lee KA, Moon JH, Chon S, Kim DJ, Kim HJ, Seo JA, Kim MK, Lim JH, Song YJ, Yang YS, Kim JH, Lee YB, Noh J, Hur KY, Park JS, Rhee SY, Kim HJ, Kim HM, Ko JH, Kim NH, Kim CH, Ahn J, Oh TJ, Kim SK, Kim J, Han E, Jin SM, Bae J, Jeon E, Kim JM, Kang SM, Park JH, Yun JS, Cha BS, Moon MK, Lee BW. 2023 Clinical Practice Guidelines for Diabetes Management in Korea: Full Version Recommendation of the Korean Diabetes Association. Diabetes Metab J 2024; 48:546-708. [PMID: 39091005 PMCID: PMC11307112 DOI: 10.4093/dmj.2024.0249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Accepted: 06/20/2024] [Indexed: 08/04/2024] Open
Affiliation(s)
- Jun Sung Moon
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Shinae Kang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Jong Han Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
| | - Kyung Ae Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Hospital, Jeonbuk National University Medical School, Jeonju, Korea
| | - Joon Ho Moon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Suk Chon
- Department of Endocrinology and Metabolism, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Dae Jung Kim
- Department of Endocrinology and Metabolism, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea
| | - Hyun Jin Kim
- Department of Internal Medicine, Chungnam National University Hospital, Chungnam National University College of Medicine, Daejeon, Korea
| | - Ji A Seo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Ansan Hospital, Korea University College of Medicine, Ansan, Korea
| | - Mee Kyoung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jeong Hyun Lim
- Department of Food Service and Nutrition Care, Seoul National University Hospital, Seoul, Korea
| | - Yoon Ju Song
- Department of Food Science and Nutrition, The Catholic University of Korea, Bucheon, Korea
| | - Ye Seul Yang
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
| | - Jae Hyeon Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - You-Bin Lee
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Junghyun Noh
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Korea
| | - Kyu Yeon Hur
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jong Suk Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Youl Rhee
- Department of Endocrinology and Metabolism, College of Medicine, Kyung Hee University, Seoul, Korea
| | - Hae Jin Kim
- Department of Endocrinology and Metabolism, Ajou University Hospital, Ajou University School of Medicine, Suwon, Korea
| | - Hyun Min Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Jung Hae Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Nam Hoon Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea
| | - Chong Hwa Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Sejong General Hospital, Bucheon, Korea
| | - Jeeyun Ahn
- Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Tae Jung Oh
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Soo-Kyung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Jaehyun Kim
- Department of Pediatrics, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Eugene Han
- Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Sang-Man Jin
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jaehyun Bae
- Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Korea
| | - Eonju Jeon
- Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea
| | - Ji Min Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
| | - Seon Mee Kang
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea
| | - Jung Hwan Park
- Division of Endocrinology & Metabolism, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea
| | - Jae-Seung Yun
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Bong-Soo Cha
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Min Kyong Moon
- Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea
| | - Byung-Wan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Strand N, Anderson MA, Attanti S, Gill B, Wie C, Dawodu A, Pagan-Rosado R, Harbell MW, Maloney JA. Diabetic Neuropathy: Pathophysiology Review. Curr Pain Headache Rep 2024; 28:481-487. [PMID: 38558164 DOI: 10.1007/s11916-024-01243-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/16/2024] [Indexed: 04/04/2024]
Abstract
PURPOSE OF REVIEW Diabetic neuropathy is a debilitating complication of diabetes mellitus that affects millions of individuals worldwide. It is characterized by nerve damage resulting from prolonged exposure to high blood glucose levels. Diabetic neuropathy may cause a range of symptoms, including pain, numbness, muscle weakness, autonomic dysfunction, and foot ulcers, potentially causing significant impairment to the quality of life for those affected. This review article aims to provide a comprehensive overview of the pathophysiology of diabetic neuropathy. The etiology of diabetic neuropathy will be discussed, including risk factors, predisposing conditions, and an overview of the complex interplay between hyperglycemia, metabolic dysregulation, and nerve damage. Additionally, we will explore the molecular mechanisms and pathways of diabetic neuropathy, including the impact of hyperglycemia on nerve function, abnormalities in glucose metabolism, the role of advanced glycation end products (AGEs), and inflammatory and immune-mediated processes. We will provide an overview of the various nerve fibers affected by diabetic neuropathy and explore the common symptoms and complications associated with diabetic neuropathy in the pain medicine field. RECENT FINDINGS This review highlights advances in understanding the pathophysiology of diabetic neuropathy as well as reviews potential novel therapeutic strategies and promising areas for future research. In conclusion, this review article aims to shed light on the pathophysiology of diabetic neuropathy, its far-reaching consequences, and the evolving strategies for prevention and management. In understanding the mechanisms of diabetic neuropathy and the ongoing research in this area, healthcare professionals can better serve patients with diabetes, ultimately improving well-being and reducing complications.
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Affiliation(s)
- Natalie Strand
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Phoenix, AZ, USA.
| | | | | | - Benjamin Gill
- Department of Anesthesiology, University of Utah, Salt Lake City, UT, USA
| | - Christopher Wie
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Phoenix, AZ, USA
| | - Azizat Dawodu
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Phoenix, AZ, USA
| | | | - Monica W Harbell
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Phoenix, AZ, USA
| | - Jillian A Maloney
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Phoenix, AZ, USA
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Lee CG, Ciarleglio A, Edelstein SL, Crandall JP, Dabelea D, Goldberg RB, Kahn SE, Knowler WC, Ma MT, White NH, Herman WH. Prevalence of Distal Symmetrical Polyneuropathy by Diabetes Prevention Program Treatment Group, Diabetes Status, Duration of Diabetes, and Cumulative Glycemic Exposure. Diabetes Care 2024; 47:810-817. [PMID: 38502874 PMCID: PMC11043227 DOI: 10.2337/dc23-2009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 01/16/2024] [Indexed: 03/21/2024]
Abstract
OBJECTIVE To assess associations between distal symmetric polyneuropathy (DSPN) and Diabetes Prevention Program (DPP) treatment groups, diabetes status or duration, and cumulative glycemic exposure approximately 21 years after DPP randomization. RESEARCH DESIGN AND METHODS In the DPP, 3,234 adults ≥25 years old at high risk for diabetes were randomized to an intensive lifestyle (ILS), metformin, or placebo intervention to prevent diabetes. After the DPP ended, 2,779 joined the Diabetes Prevention Program Outcomes Study (DPPOS). Open-label metformin was continued, placebo was discontinued, ILS was provided in the form of semiannual group-based classes, and all participants were offered quarterly lifestyle classes. Symptoms and signs of DSPN were assessed in 1,792 participants at DPPOS year 17. Multivariable logistic regression models were used to evaluate DSPN associations with treatment group, diabetes status/duration, and cumulative glycemic exposure. RESULTS At 21 years after DPP randomization, 66% of subjects had diabetes. DSPN prevalence did not differ by initial DPP treatment assignment (ILS 21.5%, metformin 21.5%, and placebo 21.9%). There was a significant interaction between treatment assignment to ILS and age (P < 0.05) on DSPN. At DPPOS year 17, the odds ratio for DSPN in comparison with ILS with placebo was 17.4% (95% CI 3.0, 29.3) lower with increasing 5-year age intervals. DSPN prevalence was slightly lower for those at risk for diabetes (19.6%) versus those with diabetes (22.7%) and was associated with longer diabetes duration and time-weighted HbA1c (P values <0.001). CONCLUSIONS The likelihood of DSPN was similar across DPP treatment groups but higher for those with diabetes, longer diabetes duration, and higher cumulative glycemic exposure. ILS may have long-term benefits on DSPN for older adults.
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Affiliation(s)
- Christine G. Lee
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
| | - Adam Ciarleglio
- Biostatistics Center and Milken Institute School of Public Health, The George Washington University, Rockville, MD
| | - Sharon L. Edelstein
- Biostatistics Center and Milken Institute School of Public Health, The George Washington University, Rockville, MD
| | - Jill P. Crandall
- Division of Endocrinology and Fleischer Institute for Diabetes and Metabolism, Albert Einstein College of Medicine, Bronx, NY
| | - Dana Dabelea
- University of Colorado Anschutz Medical Campus, Aurora, CO
| | | | - Steven E. Kahn
- VA Puget Sound Health Care System and University of Washington, Seattle, WA
| | - William C. Knowler
- Biostatistics Center and Milken Institute School of Public Health, The George Washington University, Rockville, MD
| | - Maxwell T. Ma
- VA Puget Sound Health Care System and University of Washington, Seattle, WA
| | - Neil H. White
- Department of Pediatrics, Washington University School of Medicine in St. Louis, St Louis, MO
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Abstract
Diabetic neuropathy is a highly prevalent complication of diabetes. It consists of a broad range of neuropathic conditions, such as distal symmetric polyneuropathy and various forms of autonomic neuropathies involving the cardiovascular, gastrointestinal, and urogenital systems. Prevention or diagnosis in early stages of disease is crucial to prevent symptomatic onset and progression, particularly in the absence of current disease-modifying therapies. In this review, we describe the four main types of diabetic neuropathy. We review current understanding with respect to diagnosis and treatment while highlighting knowledge gaps and future directions.
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Affiliation(s)
- Brendan R Dillon
- Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA;
| | - Lynn Ang
- Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA; ,
| | - Rodica Pop-Busui
- Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA; ,
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Baicus C, Purcarea A, von Elm E, Delcea C, Furtunescu FL. Alpha-lipoic acid for diabetic peripheral neuropathy. Cochrane Database Syst Rev 2024; 1:CD012967. [PMID: 38205823 PMCID: PMC10782777 DOI: 10.1002/14651858.cd012967.pub2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/12/2024]
Abstract
BACKGROUND Diabetic peripheral neuropathy (DPN) is a frequent complication in people living with type 1 or type 2 diabetes. There is currently no effective treatment for DPN. Although alpha-lipoic acid (ALA, also known as thioctic acid) is widely used, there is no consensus about its benefits and harms. OBJECTIVES To assess the effects of alpha-lipoic acid as a disease-modifying agent in people with diabetic peripheral neuropathy. SEARCH METHODS On 11 September 2022, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and two clinical trials registers. We also searched the reference lists of the included studies and relevant review articles for additional references not identified by the electronic searches. SELECTION CRITERIA We included randomised clinical trials (RCTs) that compared ALA with placebo in adults (aged 18 years or older) and that applied the study interventions for at least six months. There were no language restrictions. DATA COLLECTION AND ANALYSIS We used standard methods expected by Cochrane. The primary outcome was change in neuropathy symptoms expressed as changes in the Total Symptom Score (TSS) at six months after randomisation. Secondary outcomes were change in neuropathy symptoms at six to 12 months and at 12 to 24 months, change in impairment, change in any validated quality of life total score, complications of DPN, and adverse events. We assessed the certainty of the evidence using GRADE. MAIN RESULTS Our analysis incorporated three trials involving 816 participants. Two studies included people with type 1 or type 2 diabetes, while one study included only people with type 2 diabetes. The duration of treatment was between six months and 48 months. We judged all studies at high risk of overall bias due to attrition. ALA compared with placebo probably has little or no effect on neuropathy symptoms measured by TSS (lower score is better) after six months (mean difference (MD) -0.16 points, 95% confidence interval (CI) -0.83 to 0.51; 1 study, 330 participants; moderate-certainty evidence). The CI of this effect estimate did not contain the minimal clinically important difference (MCID) of 0.97 points. ALA compared with placebo may have little or no effect on impairment measured by the Neuropathy Impairment Score-Lower Limbs (NIS-LL; lower score is better) after six months (MD -1.02 points, 95% CI -2.93 to 0.89; 1 study, 245 participants; low-certainty evidence). However, we cannot rule out a significant benefit, because the lower limit of the CI surpassed the MCID of 2 points. There is probably little or no difference between ALA and placebo in terms of adverse events leading to cessation of treatment within six months (risk ratio (RR) 1.48, 95% CI 0.50 to 4.35; 3 studies, 1090 participants; moderate-certainty evidence). No studies reported quality of life or complications associated with DPN. AUTHORS' CONCLUSIONS Our analysis suggests that ALA probably has little or no effect on neuropathy symptoms or adverse events at six months, and may have little or no effect on impairment at six months. All the studies were at high risk of attrition bias. Therefore, future RCTs should ensure complete follow-up and transparent reporting of any participants missing from the analyses.
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Affiliation(s)
- Cristian Baicus
- Internal Medicine, Colentina University Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Adrian Purcarea
- Department of Fundamental, Prophylactic and Clinical Sciences, Faculty of Medicine, Transilvania University, Brasov, Romania
- Internist.ro Clinic, Brasov, Romania
| | - Erik von Elm
- Cochrane Switzerland, Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland
| | - Caterina Delcea
- Internal Medicine, Colentina University Hospital, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | - Florentina L Furtunescu
- Public Health and Management, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
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Aziz N, Dash B, Wal P, Kumari P, Joshi P, Wal A. New Horizons in Diabetic Neuropathies: An Updated Review on their Pathology, Diagnosis, Mechanism, Screening Techniques, Pharmacological, and Future Approaches. Curr Diabetes Rev 2024; 20:e201023222416. [PMID: 37867268 DOI: 10.2174/0115733998242299231011181615] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Revised: 07/16/2023] [Accepted: 08/25/2023] [Indexed: 10/24/2023]
Abstract
BACKGROUND One of the largest problems for global public health is diabetes mellitus (DM) and its micro and macrovascular consequences. Although prevention, diagnosis, and treatment have generally improved, its incidence is predicted to keep rising over the coming years. Due to the intricacy of the molecular mechanisms, which include inflammation, oxidative stress, and angiogenesis, among others, discovering treatments to stop or slow the course of diabetic complications is still a current unmet need. METHODS The pathogenesis and development of diabetic neuropathies may be explained by a wide variety of molecular pathways, hexosamine pathways, such as MAPK pathway, PARP pathway, oxidative stress pathway polyol (sorbitol) pathway, cyclooxygenase pathway, and lipoxygenase pathway. Although diabetic neuropathies can be treated symptomatically, there are limited options for treating the underlying cause. RESULT Various pathways and screening models involved in diabetic neuropathies are discussed, along with their possible outcomes. Moreover, both medicinal and non-medical approaches to therapy are also explored. CONCLUSION This study highlights the probable involvement of several processes and pathways in the establishment of diabetic neuropathies and presents in-depth knowledge of new therapeutic approaches intended to stop, delay, or reverse different types of diabetic complications.
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Affiliation(s)
- Namra Aziz
- Pranveer Singh Institute of Technology (Pharmacy), Bhauti, Kanpur 209305, UP, India
| | - Biswajit Dash
- Department of Pharmaceutical Technology, School of Medical Sciences, ADAMAS University, Kolkata 700 126, West Bengal, India
| | - Pranay Wal
- Pranveer Singh Institute of Technology (Pharmacy), Bhauti, Kanpur 209305, UP, India
| | - Prachi Kumari
- Pranveer Singh Institute of Technology (Pharmacy), Bhauti, Kanpur 209305, UP, India
| | - Poonam Joshi
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun 248007, Uttarakhand, India
| | - Ankita Wal
- Pranveer Singh Institute of Technology (Pharmacy), Bhauti, Kanpur 209305, UP, India
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12
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Spallone V. Diabetic neuropathy: Current issues in diagnosis and prevention. CHRONIC COMPLICATIONS OF DIABETES MELLITUS 2024:117-163. [DOI: 10.1016/b978-0-323-88426-6.00016-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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13
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ElSayed NA, Aleppo G, Bannuru RR, Bruemmer D, Collins BS, Ekhlaspour L, Gibbons CH, Giurini JM, Hilliard ME, Johnson EL, Khunti K, Lingvay I, Matfin G, McCoy RG, Perry ML, Pilla SJ, Polsky S, Prahalad P, Pratley RE, Segal AR, Seley JJ, Silva PS, Stanton RC, Gabbay RA. 12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes-2024. Diabetes Care 2024; 47:S231-S243. [PMID: 38078577 PMCID: PMC10725803 DOI: 10.2337/dc24-s012] [Citation(s) in RCA: 62] [Impact Index Per Article: 62.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2023]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, an interprofessional expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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14
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Tewari J, Roy S, Rana A, Tewari A. Cost-Effective Offloading of Diabetic Foot Ulcer in a Resource-Crunch Setting: A Case Report. Cureus 2023; 15:e51173. [PMID: 38283420 PMCID: PMC10815781 DOI: 10.7759/cureus.51173] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/27/2023] [Indexed: 01/30/2024] Open
Abstract
Diabetic foot ulcers (DFUs) pose a significant threat to people with diabetes, particularly in regions with limited healthcare resources, such as India. This case report focuses on a cost-effective offloading strategy for managing a chronic non-healing heel ulcer in a 55-year-old female with uncontrolled type 2 diabetes mellitus. While the gold standard for DFU management often involves total contact casts, this method may not be practical for all patients. Our approach involved repurposing used gloves and surgical paper tape for offloading, resulting in quick healing of the ulcer within six weeks. Achieving euglycemic status and sufficient wound debridement were key components of the treatment. This case highlights the importance of resource-efficient strategies in DFU management, especially in settings where traditional methods face practical limitations. Future research is needed to validate the efficacy of such approaches and pave the way for more accessible and effective treatments for DFUs.
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Affiliation(s)
- Jay Tewari
- Internal Medicine, King George's Medical University, Lucknow, IND
| | - Shubhajeet Roy
- Faculty of Medicine, King George's Medical University, Lucknow, IND
| | - Anadika Rana
- Internal Medicine, King George's Medical University, Lucknow, IND
| | - Ajoy Tewari
- Diabetes and Endocrinology, Jai Clinic & Diabetes Care Center, Lucknow, IND
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15
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Tsilingiris D, Schimpfle L, von Rauchhaupt E, Sulaj A, Seebauer L, Bartl H, Herzig S, Szendroedi J, Kopf S, Kender Z. Dysmetabolism-related Early Sensory Deficits and Their Relationship With Peripheral Neuropathy Development. J Clin Endocrinol Metab 2023; 108:e979-e988. [PMID: 37139855 PMCID: PMC10505541 DOI: 10.1210/clinem/dgad248] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 04/03/2023] [Accepted: 05/02/2023] [Indexed: 05/05/2023]
Abstract
AIM To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development. METHODS A total of 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as "healthy" and those with EPSD based on a standardized QST protocol. A total of 196 were followed-up over a mean of 2.64 years for PN occurrence. RESULTS Among those without T2DM, apart from male sex, height, and higher fat and lower lean mass, only higher insulin resistance (IR; homeostatic model assessment for IR: odds ratio [OR], 1.70; P = .009; McAuley index OR, 0.62, P = .008), was independently associated with EPSD. In T2DM, metabolic syndrome (OR, 18.32; P < .001) and skin advanced glycation end-products (AGEs; OR, 5.66; P = .003) were independent predictors of EPSD. In longitudinal analysis, T2DM (hazard ratio [HR], 3.32 vs no diabetes mellitus; P < .001), EPSD (adjusted HR, 1.88 vs healthy; P = .049 adjusted for diabetes mellitus and sex), higher IR and AGEs predicted PN development. Among the 3 EPSD-associated sensory phenotypes, "sensory loss" was most strongly associated with PN development (adjusted HR, 4.35; P = .011). CONCLUSION We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, metabolic syndrome, and higher AGEs, which in turn are shown to influence PN development.
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Affiliation(s)
- Dimitrios Tsilingiris
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
| | - Lukas Schimpfle
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Ekaterina von Rauchhaupt
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
| | - Alba Sulaj
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
| | - Lukas Seebauer
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
| | - Hannelore Bartl
- Department of General, Visceral and Transplant Surgery, University of Heidelberg, 69120 Heidelberg, Germany
| | - Stephan Herzig
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
- Joint Heidelberg-IDC Translational Diabetes Program, Helmholtz Center Munich, 85764 Neuherberg, Germany
- Helmholtz Center Munich, Institute for Diabetes and Cancer, 85764 Munich-Neuherberg, Germany
| | - Julia Szendroedi
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
- Joint Heidelberg-IDC Translational Diabetes Program, Helmholtz Center Munich, 85764 Neuherberg, Germany
| | - Stefan Kopf
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
| | - Zoltan Kender
- Department for Endocrinology, Diabetology, Metabolic Diseases and Clinical Chemistry, University Hospital Heidelberg, 69120 Heidelberg, Germany
- German Center for Diabetes Research (DZD), 85764 Munich-Neuherberg, Germany
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16
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Chang KC, Pai YW, Lin CH, Lee IT, Chang MH. The association between hyperlipidemia, lipid-lowering drugs and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus. PLoS One 2023; 18:e0287373. [PMID: 37319238 PMCID: PMC10270586 DOI: 10.1371/journal.pone.0287373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Accepted: 06/04/2023] [Indexed: 06/17/2023] Open
Abstract
AIMS Previous studies showed conflicting relationship between hyperlipidemia, lipid-lowering therapy and diabetic peripheral neuropathy (DPN). As most of these works emerges from the Western and Australian countries, our study aims to investigate whether hyperlipidemia or lipid-lowering therapy (LLT) is associated with DPN in Taiwanese patients with type 2 diabetes (T2D). METHODS A cross-sectional, hospital-based observation study in adults with T2D was conducted from January to October 2013. DPN was screened using the Michigan Neuropathy Screening Instrument. Data were obtained at the time of enrollment, including medication usage, anthropometric measurements and laboratory examinations. RESULTS 2,448 participants were enrolled, 524 (21.4%) of whom had DPN. Patients with DPN had significantly lower plasma total cholesterol (185.6 ± 38.6 vs 193.4 ± 42.3 mg/dL) and low-density lipoprotein cholesterol levels (114.6 ± 32.7 vs 119 ± 30.8 mg/dL). Multivariate analysis demonstrated that neither hyperlipidemia (adjusted OR (aOR), 0.81; 95% confidence interval (CI), 0.49-1.34) nor LLT (aOR, 1.10; 95% CI, 0.58-2.09) was associated with DPN. Subgroup analysis revealed that neither total cholesterol (aOR, 0.72; 95% CI, 0.2-2.62), low-density lipoprotein cholesterol levels (aOR, 0.75; 95% CI, 0.2-2.79), statin (aOR, 1.09; 95% CI, 0.59-2.03) nor fibrate (aOR, 1.73; 95% CI, 0.33-1.61) was associated with DPN. CONCLUSION Our results suggest that neither hyperlipidemia nor lipid-lowering medication was associated with DPN in adults with T2D. DPN is a multifactorial disease, and our findings indicate that lipid metabolism may play a minor role in its pathogenesis.
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Affiliation(s)
- Kuo-Cheng Chang
- Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Yen-Wei Pai
- Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Ching-Heng Lin
- Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan
| | - I-Te Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
- Department of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Ming-Hong Chang
- Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
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17
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Ismail CAN. Issues and challenges in diabetic neuropathy management: A narrative review. World J Diabetes 2023; 14:741-757. [PMID: 37383599 PMCID: PMC10294062 DOI: 10.4239/wjd.v14.i6.741] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 02/24/2023] [Accepted: 04/11/2023] [Indexed: 06/14/2023] Open
Abstract
Diabetic neuropathy (DN) is a devastating disorder with an increasing prevalence globally. This epidemic can pose a critical burden on individuals and com-munities, subsequently affecting the productivity and economic output of a country. With more people living a sedentary lifestyle, the incidence of DN is escalating worldwide. Many researchers have relentlessly worked on ways to combat this devastating disease. Their efforts have given rise to a number of commercially available therapies that can alleviate the symptoms of DN. Unfortunately, most of these therapies are only partially effective. Worse still, some are associated with unfavorable side effects. This narrative review aims to highlight current issues and challenges in the management of DN, especially from the perspective of molecular mechanisms that lead to its progression, with the hope of providing future direction in the management of DN. To improve the approaches to diabetic management, the suggested resolutions in the literature are also discussed in this review. This review will provide an in-depth understanding of the causative mechanisms of DN, apart from the insights to improve the quality and strategic approaches to DN management.
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Affiliation(s)
- Che Aishah Nazariah Ismail
- Department of Physiology, School of Medical Sciences, University Sains Malaysia Health Campus, Kubang Kerian 16150, Kelantan, Malaysia
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18
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Beros A, Sluyter J, Scragg RKR. Association of arterial stiffness and neuropathy in diabetes: a systematic review and meta-analysis. BMJ Open Diabetes Res Care 2023; 11:e003140. [PMID: 36746528 PMCID: PMC9906264 DOI: 10.1136/bmjdrc-2022-003140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2022] [Accepted: 01/08/2023] [Indexed: 02/08/2023] Open
Abstract
Evidence is still emerging on the relationships of arterial stiffness with cardiac autonomic neuropathy (CAN) and peripheral neuropathy (PN). To our knowledge no systematic reviews or meta-analyses of these associations have been published. The purpose of our review was to assess the association of arterial stiffness with each type of neuropathy. Medline and Embase were systematically searched for observational studies of arterial stiffness and neuropathy.The systematic review of 60 studies (25 for CAN and 37 for PN), 59 including people with diabetes, showed arterial stiffness overall was higher in people with neuropathy than people without neuropathy. Forty-three studies were included in the meta-analysis. For CAN (19 studies), arterial stiffness was increased in people with neuropathy compared with without, as measured by pulse wave velocity (PWV) (mean difference: 1.32 m/s, 95% CI 0.82 to 1.81, p<0.00001), pulse pressure (PP) (mean difference: 6.25 mmHg, 95% CI 4.51 to 7.99, p<0.00001) or augmentation index (mean difference: 5.52%, 95% CI 3.46 to 7.58, p<0.0001). For PN (26 studies), arterial stiffness was increased in people with neuropathy compared with those without, as measured by PWV (mean difference: 1.22 m/s, 95% CI 0.87 to 1.58, p<0.00001) or PP (mean difference: 4.59 mmHg, 95% CI 2.96 to 6.22, p<0.00001). Only two cohort studies were located so the temporality of the association between arterial stiffness and neuropathy remains unclear. Increased arterial stiffness is associated with CAN and PN.PROSPERO registration number: CRD42019129563.
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Affiliation(s)
- Angela Beros
- School of Population Health, University of Auckland, The University of Auckland Faculty of Medical and Health Sciences, Auckland, New Zealand
| | - John Sluyter
- School of Population Health, University of Auckland, The University of Auckland Faculty of Medical and Health Sciences, Auckland, New Zealand
| | - Robert Keith Rhodes Scragg
- School of Population Health, University of Auckland, The University of Auckland Faculty of Medical and Health Sciences, Auckland, New Zealand
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19
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Qi H, Kan K, Sticht C, Bennewitz K, Li S, Qian X, Poschet G, Kroll J. Acrolein-inducing ferroptosis contributes to impaired peripheral neurogenesis in zebrafish. Front Neurosci 2023; 16:1044213. [PMID: 36711148 PMCID: PMC9877442 DOI: 10.3389/fnins.2022.1044213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Accepted: 12/22/2022] [Indexed: 01/15/2023] Open
Abstract
Introduction Diabetes mellitus (DM) is associated with physiological disorders such as delayed wound healing, diabetic retinopathy, diabetic nephropathy, and diabetic peripheral neuropathy (DPN). Over 50% of diabetic patients will develop DPN, characterized by motor dysfunction and impaired sensory nerve function. In a previous study, we have uncovered acrolein (ACR) as an upstream initiator which induced impaired glucose homeostasis and microvascular alterations in zebrafish. Whether ACR has specific effects on peripheral neurogenesis and mediates DPN, is still waiting for clarification. Methods To evaluate the function of ACR in peripheral nerve development, in vivo experiments were performed in Tg(hb9:GFP) zebrafish. In addition, a series of rescue experiments, metabolomics assessment, and bioinformatics analysis was performed aimed at identifying the molecular mechanisms behind ACR's function and impaired neurogenesis. Results Impaired motor neuron development was confirmed in wild-type embryos treated with external ACR. ACR treated embryos displayed ferroptosis and reduction of several amino acids and increased glutathione (GSH). Furthermore, ferroptosis inducer caused similarly suppressed neurogenesis in zebrafish embryos, while anti-ACR treatment or ferroptosis inhibitor could successfully reverse the detrimental phenotypes of ACR on neurogenesis in zebrafish. Discussion Our data indicate that ACR could directly activate ferroptosis and impairs peripheral neurogenesis. The data strongly suggest ACR and activated ferroptosis as inducers and promising therapeutic targets for future DPN studies.
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Affiliation(s)
- Haozhe Qi
- Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany,Department of Vascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Kejia Kan
- Department of Vascular Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China,Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Carsten Sticht
- The Next-Generation Sequencing (NGS) Core Facility, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Katrin Bennewitz
- Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Shu Li
- Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Xin Qian
- Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Gernot Poschet
- Metabolomics Core Technology Platform, Centre for Organismal Studies, Heidelberg University, Heidelberg, Germany
| | - Jens Kroll
- Department of Vascular Biology and Tumor Angiogenesis, European Center for Angioscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany,*Correspondence: Jens Kroll,
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20
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Sabaghan M, Ataee S, Ataee M, Tebyanian M, Afrashteh S, Daneshi N. Diabetic peripheral neuropathy screening and the related risk factors to its prevalence in people with type 2 diabetes. Int J Diabetes Dev Ctries 2023. [DOI: 10.1007/s13410-022-01165-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
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21
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ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Gibbons CH, Giurini JM, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Seley JJ, Stanton RC, Sun JK, Gabbay RA, on behalf of the American Diabetes Association. 12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes-2023. Diabetes Care 2023; 46:S203-S215. [PMID: 36507636 PMCID: PMC9810462 DOI: 10.2337/dc23-s012] [Citation(s) in RCA: 88] [Impact Index Per Article: 44.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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22
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Ang L, Mizokami-Stout K, Eid SA, Elafros M, Callaghan B, Feldman EL, Pop-Busui R. The conundrum of diabetic neuropathies-Past, present, and future. J Diabetes Complications 2022; 36:108334. [PMID: 36306721 PMCID: PMC10202025 DOI: 10.1016/j.jdiacomp.2022.108334] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2022] [Revised: 10/01/2022] [Accepted: 10/01/2022] [Indexed: 10/31/2022]
Abstract
Diabetic neuropathy (DN) remains arguably the most prevalent chronic complication in people with both type 1 and type 2 diabetes, including in youth, despite changes in the current standards of clinical care. Additionally, emerging evidence demonstrates that neuropathy affects a large proportion of people with undiagnosed diabetes and/or prediabetes, as well as those with obesity. Here we summarize the latest epidemiology of DN, recent findings regarding the pathophysiology of the disease, as well as current outcome measures for screening and diagnosis, in research and clinical settings. The authors discuss novel perspectives on the impact of social determinants of health in DN development and management, and the latest evidence on effective therapies, including pharmacological and nonpharmacological therapies for neuropathic pain. Throughout the publication, we identify knowledge gaps and the need for future funding to address these gaps, as well as needs to advocate for a personalized care approach to reduce the burden of DN and optimize quality of life for all affected individuals.
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Affiliation(s)
- Lynn Ang
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, United States of America
| | - Kara Mizokami-Stout
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, United States of America; Ann Arbor Veteran Affairs Hospital, Ann Arbor, MI, United States of America
| | - Stephanie A Eid
- Department of Neurology, University of Michigan, Ann Arbor, MI, United States of America
| | - Melissa Elafros
- Department of Neurology, University of Michigan, Ann Arbor, MI, United States of America
| | - Brian Callaghan
- Department of Neurology, University of Michigan, Ann Arbor, MI, United States of America
| | - Eva L Feldman
- Department of Neurology, University of Michigan, Ann Arbor, MI, United States of America
| | - Rodica Pop-Busui
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, United States of America.
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23
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Blonde L, Umpierrez GE, Reddy SS, McGill JB, Berga SL, Bush M, Chandrasekaran S, DeFronzo RA, Einhorn D, Galindo RJ, Gardner TW, Garg R, Garvey WT, Hirsch IB, Hurley DL, Izuora K, Kosiborod M, Olson D, Patel SB, Pop-Busui R, Sadhu AR, Samson SL, Stec C, Tamborlane WV, Tuttle KR, Twining C, Vella A, Vellanki P, Weber SL. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. Endocr Pract 2022; 28:923-1049. [PMID: 35963508 PMCID: PMC10200071 DOI: 10.1016/j.eprac.2022.08.002] [Citation(s) in RCA: 234] [Impact Index Per Article: 78.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2022] [Revised: 08/01/2022] [Accepted: 08/02/2022] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers. METHODS The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development. RESULTS This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: (1) screening, diagnosis, glycemic targets, and glycemic monitoring; (2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; (3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; (4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes. CONCLUSIONS This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.
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Affiliation(s)
| | | | - S Sethu Reddy
- Central Michigan University, Mount Pleasant, Michigan
| | | | | | | | | | | | - Daniel Einhorn
- Scripps Whittier Diabetes Institute, La Jolla, California
| | | | | | - Rajesh Garg
- Lundquist Institute/Harbor-UCLA Medical Center, Torrance, California
| | | | | | | | | | | | - Darin Olson
- Colorado Mountain Medical, LLC, Avon, Colorado
| | | | | | - Archana R Sadhu
- Houston Methodist; Weill Cornell Medicine; Texas A&M College of Medicine; Houston, Texas
| | | | - Carla Stec
- American Association of Clinical Endocrinology, Jacksonville, Florida
| | | | - Katherine R Tuttle
- University of Washington and Providence Health Care, Seattle and Spokane, Washington
| | | | | | | | - Sandra L Weber
- University of South Carolina School of Medicine-Greenville, Prisma Health System, Greenville, South Carolina
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Ponirakis G, Al-Janahi I, Elgassim E, Gad H, Petropoulos IN, Khan A, Ali H, Siddique MA, Gul W, Ferdousi M, Kalteniece A, Mohamed FF, Ahmed LH, Dakroury Y, El Shewehy AM, Al-Mohamedi A, AlMarri F, Homssi M, Qazi M, Hadid NH, Al-Khayat F, Mahfoud ZR, Azmi S, Alam U, Zirie MA, Al-Ansari Y, Jayyousi A, Rigby AS, Kilpatrick ES, Atkin SL, Malik RA. Progressive loss of corneal nerve fibers is associated with physical inactivity and glucose lowering medication associated with weight gain in type 2 diabetes. J Diabetes Investig 2022; 13:1703-1710. [PMID: 35652859 PMCID: PMC9533053 DOI: 10.1111/jdi.13864] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 04/03/2022] [Accepted: 05/31/2022] [Indexed: 11/30/2022] Open
Abstract
Aims/Introduction Limited studies have identified risk factors linked to the progression of diabetic peripheral neuropathy (DPN) in type 2 diabetes. This study examined the association of risk factors with change in neuropathy measures over 2 years. Materials and Methods Participants with type 2 diabetes (n = 78) and controls (n = 26) underwent assessment of clinical and metabolic parameters and neuropathy using corneal confocal microscopy (CCM), vibration perception threshold (VPT), and the DN4 questionnaire at baseline and 2 year follow‐up. Results Participants with type 2 diabetes had a lower corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) (P ≤ 0.0001) and a higher VPT (P ≤ 0.01) compared with controls. Over 2 years, despite a modest reduction in HbA1c (P ≤ 0.001), body weight (P ≤ 0.05), and LDL (P ≤ 0.05) the prevalence of DPN (P = 0.28) and painful DPN (P = 0.21) did not change, but there was a significant further reduction in CNBD (P ≤ 0.0001) and CNFL (P ≤ 0.05). CNFD, CNBD, and CNFL decreased significantly in physically inactive subjects (P < 0.05–0.0001), whilst there was no change in CNFD (P = 0.07) or CNFL (P = 0.85) in physically active subjects. Furthermore, there was no change in CNFD (P = 0.82), CNBD (P = 0.08), or CNFL (P = 0.66) in patients treated with glucose lowering medication associated with weight loss, whilst CNBD (P = 0.001) decreased in patients on glucose lowering medication associated with weight gain. Conclusions In participants with type 2 diabetes, despite a modest improvement in HbA1c, body weight, and LDL there was a progressive loss of corneal nerve fibers; except in those who were physically active or on glucose lowering medication associated with weight loss.
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Affiliation(s)
- Georgios Ponirakis
- Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha, Qatar
| | - Ibrahim Al-Janahi
- National Diabetes Center, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Einas Elgassim
- Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha, Qatar
| | - Hoda Gad
- Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha, Qatar
| | | | - Adnan Khan
- Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha, Qatar
| | - Hamda Ali
- National Diabetes Center, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Mashhood A Siddique
- National Diabetes Center, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Wajiha Gul
- National Diabetes Center, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Maryam Ferdousi
- Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Alise Kalteniece
- Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK
| | - Fatima Fs Mohamed
- Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha, Qatar
| | - Lina Hm Ahmed
- Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha, Qatar
| | - Youssra Dakroury
- Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha, Qatar
| | - Abeer Mm El Shewehy
- Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha, Qatar
| | | | - Fatema AlMarri
- Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha, Qatar
| | - Moayad Homssi
- Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha, Qatar
| | - Murtaza Qazi
- Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha, Qatar
| | - Nebras H Hadid
- Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha, Qatar
| | - Fatima Al-Khayat
- Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha, Qatar
| | - Ziyad R Mahfoud
- Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha, Qatar
| | - Shazli Azmi
- Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.,Centre for Diabetes, Endocrinology and Metabolism, Manchester University NHS Foundation Trust, Manchester, UK
| | - Uazman Alam
- Department of Cardiovascular & Metabolic Medicine and the Pain Research Institute, Institute of Life Course and Medical Sciences, University of Liverpool, and Liverpool University Hospital NHS Foundation Trust, Liverpool, UK
| | - Mahmoud A Zirie
- National Diabetes Center, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Yousuf Al-Ansari
- National Diabetes Center, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Amin Jayyousi
- National Diabetes Center, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Alan S Rigby
- Centre for Diabetes, Endocrinology and Metabolism, Manchester University NHS Foundation Trust, Manchester, UK.,Hull York Medical School, University of Hull, Kingston Upon Hull, UK
| | - Eric S Kilpatrick
- Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.,Centre for Diabetes, Endocrinology and Metabolism, Manchester University NHS Foundation Trust, Manchester, UK.,Hull York Medical School, University of Hull, Kingston Upon Hull, UK
| | - Stephen L Atkin
- Royal College of Surgeons in Ireland Bahrain, Adliya, Kingdom of Bahrain
| | - Rayaz A Malik
- Department of Medicine, Weill Cornell Medicine-Qatar, Qatar Foundation, Doha, Qatar.,Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.,Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK
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25
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Carvajal-Moreno L, Coheña-Jiménez M, García-Ventura I, Pabón-Carrasco M, Pérez-Belloso AJ. Prevention of Peripheral Distal Polyneuropathy in Patients with Diabetes: A Systematic Review. J Clin Med 2022; 11:1723. [PMID: 35330052 PMCID: PMC8948704 DOI: 10.3390/jcm11061723] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 03/14/2022] [Accepted: 03/18/2022] [Indexed: 11/22/2022] Open
Abstract
Background: Diabetic peripheral neuropathy (DPN) is the most frequent chronic complication and is that which generates the highest disability and mortality in diabetes mellitus (DM). As it is currently the only microvascular complication of DM without a specific treatment, prevention is essential. The aim of this study was to determine the most effective preventive strategy to avoid or delay the appearance and/or development of DPN in patients with DM. Methods: A systematic search was carried out in the main health science databases (PubMed, Scopus, CINAHL, PEDro and The Cochrane Library) from 1 January 2010 to 31 August 2020. The study selection was conducted by two independent reviewers and data extraction was performed by the author. The eligibility criteria included randomized clinical trials (RCTs) and cohort studies from RCTs. Results: Eleven studies were selected that included 23,595 participants with DM. The interventions evaluated were intensive or standard glycemic control, the use of drugs to achieve glycemic control, and the promotion of a healthy lifestyle and exercise. Intensive glucose control achieved a significant reduction in the development of DPN in TIDM patients, and lifestyle modifications and exercise achieved it moderately in TIIDM patients. Conclusions: The main preventive strategy for DPN is intensive glycemic control with a target HbA1c < 6% in patients with TIDM and standard control of 7.0−7.9 in patients with TIIDM, incorporating lifestyle modifications.
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Affiliation(s)
- Lidia Carvajal-Moreno
- Department of Podiatry, University of Seville, 41009 Seville, Spain; (L.C.-M.); (I.G.-V.); (A.J.P.-B.)
| | - Manuel Coheña-Jiménez
- Department of Podiatry, University of Seville, 41009 Seville, Spain; (L.C.-M.); (I.G.-V.); (A.J.P.-B.)
| | - Irene García-Ventura
- Department of Podiatry, University of Seville, 41009 Seville, Spain; (L.C.-M.); (I.G.-V.); (A.J.P.-B.)
| | - Manuel Pabón-Carrasco
- Spanish Red Cross Nursing School, University of Seville, Avda. de la Cruz Roja, nº 1 Dpdo., 41009 Seville, Spain;
| | - Ana Juana Pérez-Belloso
- Department of Podiatry, University of Seville, 41009 Seville, Spain; (L.C.-M.); (I.G.-V.); (A.J.P.-B.)
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26
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Mondelli M, Aretini A, Ginanneschi F. Electrophysiological Study of the Tibial Nerve Across the Tarsal Tunnel in Distal Symmetric Diabetic Polyneuropathy. Am J Phys Med Rehabil 2022; 101:152-159. [PMID: 33901043 DOI: 10.1097/phm.0000000000001769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE The aim of the study was to demonstrate abnormalities of motor conduction of the tibial nerve across the tarsal tunnel in type 2 diabetes. DESIGN One hundred twenty-four consecutive patients (mean age = 66.6 yrs, 62.1% male) with distal symmetric diabetic polyneuropathy clinically diagnosed were prospectively enrolled. Nerve conduction studies of deep peroneal, tibial, superficial peroneal, medial plantar, and sural nerves and standard needle electromyography in the lower limbs were performed. Demographic, anthropometric, and clinical findings were collected. RESULTS Motor conduction velocity of the tibial nerve across tarsal tunnel was slowed in 60.5% of patients; another 4% showed conduction block across tarsal tunnel without reduction of motor conduction velocity. Overall percentage of abnormalities across tarsal tunnel (64.5%) exceeds that of the sensory conduction velocities of proximal sural and superficial peroneal nerves. Abnormal tibial motor conduction velocity across tarsal tunnel represents the most common abnormality among all motor nerve conduction study parameters and significantly correlates with hemoglobin level, diabetic neuropathic index score, and diabetic complications frequency. CONCLUSIONS Tibial conduction abnormalities across tarsal tunnel are the most sensitive motor parameter in distal symmetric diabetic polyneuropathy, second only to conduction abnormalities of sensory/mixed distal nerves of the feet. The use of nerve conduction studies across tarsal tunnel of the tibial nerve may be useful in the electrophysiological protocol to confirm the diagnosis of distal symmetric diabetic polyneuropathy.
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Affiliation(s)
- Mauro Mondelli
- From the EMG Service, Local Health Unit Toscana Sud Est, Siena, Italy (MM, AA); and Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy (FG)
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27
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Raghav A, Singh M, Jeong GB, Giri R, Agarwal S, Kala S. New horizons of biomaterials in treatment of nerve damage in diabetes mellitus: A translational prospective review. Front Endocrinol (Lausanne) 2022; 13:1036220. [PMID: 36387914 PMCID: PMC9647066 DOI: 10.3389/fendo.2022.1036220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Accepted: 09/28/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Peripheral nerve injury is a serious concern that leads to loss of neuronal communication that impairs the quality of life and, in adverse conditions, causes permanent disability. The limited availability of autografts with associated demerits shifts the paradigm of researchers to use biomaterials as an alternative treatment approach to recover nerve damage. PURPOSE The purpose of this study is to explore the role of biomaterials in translational treatment approaches in diabetic neuropathy. STUDY DESIGN The present study is a prospective review study. METHODS Published literature on the role of biomaterials in therapeutics was searched for. RESULTS Biomaterials can be implemented with desired characteristics to overcome the problem of nerve regeneration. Biomaterials can be further exploited in the treatment of nerve damage especially associated with PDN. These can be modified, customized, and engineered as scaffolds with the potential of mimicking the extracellular matrix of nerve tissue along with axonal regeneration. Due to their beneficial biological deeds, they can expedite tissue repair and serve as carriers of cellular and pharmacological treatments. Therefore, the emerging research area of biomaterials-mediated treatment of nerve damage provides opportunities to explore them as translational biomedical treatment approaches. CONCLUSIONS Pre-clinical and clinical trials in this direction are needed to establish the effective role of several biomaterials in the treatment of other human diseases.
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Affiliation(s)
- Alok Raghav
- Multidisciplinary Research Unit, Department of Health Research, Ganesh Shankar Vidyarthi Memorial (GSVM) Medical College, Kanpur, India
- *Correspondence: Alok Raghav,
| | - Manish Singh
- Multidisciplinary Research Unit, Department of Health Research, Ganesh Shankar Vidyarthi Memorial (GSVM) Medical College, Kanpur, India
- Department of Neurosurgery, Ganesh Shankar Vidyarthi Memorial (GSVM) Medical College, Kanpur, India
| | - Goo-Bo Jeong
- Department of Anatomy and Cell Biology, College of Medicine, Gachon University, Incheon, South Korea
| | - Richa Giri
- Multidisciplinary Research Unit, Department of Health Research, Ganesh Shankar Vidyarthi Memorial (GSVM) Medical College, Kanpur, India
- Kamlapat Singhania (KPS) Institute of Medicine, Ganesh Shankar Vidyarthi Memorial (GSVM) Medical College, Kanpur, India
| | - Saurabh Agarwal
- Multidisciplinary Research Unit, Department of Health Research, Ganesh Shankar Vidyarthi Memorial (GSVM) Medical College, Kanpur, India
- Kamlapat Singhania (KPS) Institute of Medicine, Ganesh Shankar Vidyarthi Memorial (GSVM) Medical College, Kanpur, India
| | - Sanjay Kala
- Department of Surgery, Ganesh Shankar Vidyarthi Memorial (GSVM) Medical College, Kanpur, India
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28
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Pop‐Busui R, Backlund JC, Bebu I, Braffett BH, Lorenzi G, White NH, Lachin JM, Soliman EZ. Utility of using electrocardiogram measures of heart rate variability as a measure of cardiovascular autonomic neuropathy in type 1 diabetes patients. J Diabetes Investig 2022; 13:125-133. [PMID: 34309223 PMCID: PMC8756321 DOI: 10.1111/jdi.13635] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 07/16/2021] [Accepted: 07/21/2021] [Indexed: 01/02/2023] Open
Abstract
AIMS/INTRODUCTION Cardiovascular autonomic neuropathy (CAN) is a predictor of cardiovascular disease and mortality. Cardiovascular reflex tests (CARTs) are the gold standard for the diagnosis of CAN, but might not be feasible in large research cohorts or in clinical care. We investigated whether measures of heart rate variability obtained from standard electrocardiogram (ECG) recordings provide a reliable measure of CAN. MATERIALS AND METHODS Standardized CARTs (R-R response to paced breathing, Valsalva, postural changes) and digitized 12-lead resting ECGs were obtained concomitantly in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications participants (n = 311). Standard deviation of normally conducted R-R intervals (SDNN) and the root mean square of successive differences between normal-to-normal R-R intervals (rMSSD) were measured from ECG. Sensitivity, specificity, probability of correct classification and Kappa statistics evaluated the agreement between ECG-derived CAN and CARTs-defined CAN. RESULTS Participants with CARTs-defined CAN had significantly lower SDNN and rMSSD compared with those without CAN (P < 0.001). The optimal cut-off points of ECG-derived CAN were <17.13 and <24.94 ms for SDNN and rMSSD, respectively. SDNN plays a dominant role in defining CAN, with an area under the curve of 0.73, indicating fair test performance. The Kappa statistic for SDNN was 0.41 (95% confidence interval 0.30-0.51) for the optimal cut-off point, showing fair agreement with CARTs-defined CAN. Combining SDNN and rMSSD optimal cut-off points does not provide additional predictive power for CAN. CONCLUSIONS These analyses are the first to show the agreement between indices of heart rate variability derived from ECGs and the gold standard CARTs, thus supporting potential use as a measure of CAN in clinical research and clinical care.
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Affiliation(s)
- Rodica Pop‐Busui
- Department of Internal MedicineDivision of Metabolism, Endocrinology and DiabetesUniversity of MichiganAnn ArborMichiganUSA
| | - Jye‐Yu C Backlund
- Biostatistics CenterThe George Washington UniversityRockvilleMarylandUSA
| | - Ionut Bebu
- Biostatistics CenterThe George Washington UniversityRockvilleMarylandUSA
| | - Barbara H Braffett
- Biostatistics CenterThe George Washington UniversityRockvilleMarylandUSA
| | - Gayle Lorenzi
- University of California San DiegoLa JollaCaliforniaUSA
| | | | - John M Lachin
- Biostatistics CenterThe George Washington UniversityRockvilleMarylandUSA
| | - Elsayed Z Soliman
- Epidemiological Cardiology Research Center (EPICARE)Department of Epidemiology and PreventionWake Forest School of MedicineWinston‐SalemNorth CarolinaUSA
- Department of MedicineSection on CardiologyWake Forest School of MedicineWinston‐SalemNorth CarolinaUSA
- Institute of Global Health and Human EcologySchool of Science and EngineeringAmerican University in CairoCairoEgypt
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Abstract
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc22-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc22-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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30
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Detection of diabetic polyneuropathy in a family medicine clinic by using monofilament. VOJNOSANIT PREGL 2022. [DOI: 10.2298/vsp200226053l] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Background/Aim. Diabetic polyneuropathy (DPN) is the most common microvascular complication of diabetes mellitus (DM), which may be present at the time of disease detection. Screening for DPN is performed for the patients with type 2 diabetes at the time of diagnosis and for type 1 diabetes 5 years after diagnosis. The primary aim of this study was to determine the prevalence of DNP among family medicine patients with DM aged 18 to 70 years using nylon monofilament. Methods. The cross-sectional study estimated the prevalence of DPN among primary care patients with DM in Banja Luka, Republic of Srpska, Bosnia and Herzegovina. Semmes-Weinstein nylon 10 g monofilament was used to detect DPN. Age, gender, duration of DM, type of therapy, symptoms, glycosylated hemoglobin (HbA1c), and risk factors (hypertension, smoking, dyslipidemia, obesity, physical inactivity) were analyzed. Data collection took place from June 1st, 2017 to May 31st, 2018. Results. The study included 228 patients, 132 (57.9%) men and 96 (42.1%) women. There was a statistically significant difference in the presence of all symptoms of DPN (tingling, burning, light burning, and stinging) among patients with different duration of DM (p < 0.01). Multivariate logistic regression revealed that patients who had hypertension [odds ratio (OR) = 26.2; 95% confidence interval (CI): 4.070?168.488; p = 0.001], used oral anti-diabetic therapy (OR = 12.3; 95% CI: 1.300?116.309; p = 0.029), had tingling (OR = 5.2; 95% CI: 1.431?18.571; p = 0.012) and a longer duration of diabetes (OR = 4.27; 95% CI: 1.983?9.175; p = 0.000) were more likely to have DPN. Conclusion. The prevalence of DPN in family medicine patients with DM using nylon monofilament was 24.2%. Determinants of DNP were the presence of symptoms of tingling, duration of diabetes, hypertension, and the use of oral antidiabetic therapy alone.
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31
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McIllhatton A, Lanting S, Lambkin D, Leigh L, Casey S, Chuter V. Reliability of recommended non-invasive chairside screening tests for diabetes-related peripheral neuropathy: a systematic review with meta-analyses. BMJ Open Diabetes Res Care 2021; 9:e002528. [PMID: 34952841 PMCID: PMC8710873 DOI: 10.1136/bmjdrc-2021-002528] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 11/14/2021] [Indexed: 01/08/2023] Open
Abstract
The objective is to determine, by systematic review, the reliability of testing methods for diagnosis of diabetes-related peripheral neuropathy (DPN) as recommended by the most recent guidelines from the International Diabetes Foundation, International Working Group on the Diabetic Foot and American Diabetes Association. Electronic searches of Cochrane Library, EBSCO Megafile Ultimate and EMBASE were performed to May 2021. Articles were included if they reported on the reliability of recommended chairside tests in diabetes cohorts. Quality appraisal was performed using a Quality Appraisal of Reliability Studies checklist and where possible, meta-analyses, with reliability reported as estimated Cohen's kappa (95% CI). Seventeen studies were eligible for inclusion. Pooled analysis found acceptable inter-rater reliability of vibration perception threshold (VPT) (κ=0.61 (0.50 to 0.73)) and ankle reflex testing (κ=0.60 (0.55 to 0.64)), but weak inter-rater reliability for pinprick (κ=0.45 (0.22 to 0.69)) and 128 Hz tuning fork (κ=0.42 (0.15 to 0.70)), though intra-rater reliability of the 128 Hz tuning fork was moderate (κ=0.54 (0.37 to 0.73)). Inter-rater reliability of the four-site monofilament was acceptable (κ=0.61 (0.45 to 0.77)). These results support the clinical use of VPT, ankle reflexes and four-site monofilament for screening and ongoing monitoring of DPN as recommended by the latest guidelines. The reliability of temperature perception, pinprick, proprioception, three-site monofilament and Ipswich touch test when performed in people with diabetes remains unclear.
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Affiliation(s)
- Ally McIllhatton
- Discipline of Podiatry, The University of Newcastle Faculty of Health and Medicine, Ourimbah, New South Wales, Australia
| | - Sean Lanting
- Discipline of Podiatry, The University of Newcastle Faculty of Health and Medicine, Ourimbah, New South Wales, Australia
| | - David Lambkin
- Hunter Medical Research Institute, The University of Newcastle, New Lambton, New South Wales, Australia
| | - Lucy Leigh
- Hunter Medical Research Institute, The University of Newcastle, New Lambton, New South Wales, Australia
| | - Sarah Casey
- Discipline of Podiatry, The University of Newcastle Faculty of Health and Medicine, Ourimbah, New South Wales, Australia
| | - Vivienne Chuter
- Discipline of Podiatry, The University of Newcastle Faculty of Health and Medicine, Ourimbah, New South Wales, Australia
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Cho NR, Yu Y, Oh CK, Ko DS, Myung K, Lee Y, Na HS, Kim YH. Neuropeptide Y: a potential theranostic biomarker for diabetic peripheral neuropathy in patients with type-2 diabetes. Ther Adv Chronic Dis 2021; 12:20406223211041936. [PMID: 34729143 PMCID: PMC8438932 DOI: 10.1177/20406223211041936] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2021] [Accepted: 08/03/2021] [Indexed: 01/08/2023] Open
Abstract
Background: Diabetic peripheral neuropathy (DPN), the most common microvascular complication of type-2 diabetes mellitus (T2DM), results in nontraumatic lower-limb amputations. When DPN is not detected early, disease progression is irreversible. Thus, biomarkers for diagnosing DPN are needed. Methods: We analyzed three data sets of T2DM DPN: two for mouse models (GSE70852 and GSE34889) and one for a human model (GSE24290). We found common differentially expressed genes (DEGs) in the two mouse data sets and validated them in the human data set. To identify the phenotypic function of the DEGs, we overexpressed them in zebrafish embryos. Clinical information and serum samples of T2DM patients with and without DPN were obtained from the Korea Biobank Network. To assess the plausibility of DEGs as biomarkers of DPN, we performed an enzyme-linked immunosorbent assay. Results: Among the DEGs, only NPY and SLPI were validated in the human data set. As npy is conserved in zebrafish, its mRNA was injected into zebrafish embryos, and it was observed that the branches of the central nervous system became thicker and the number of dendritic branches increased. Baseline characteristics between T2DM patients with and without DPN did not differ, except for the sex ratio. The mean serum NPY level was higher in T2DM patients with DPN than in those without DPN (p = 0.0328), whereas serum SLPI levels did not differ (p = 0.9651). Conclusion: In the pathogenesis of DPN, NPY may play a protective role in the peripheral nervous system and may be useful as a biomarker for detecting T2DM DPN.
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Affiliation(s)
- Noo Ree Cho
- Department of Anesthesiology and Pain Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea
| | - Yeuni Yu
- Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
| | - Chang-Kyu Oh
- Center for Genomic Integrity, Institute for Basic Science (IBS), Ulsan, Republic of Korea
| | - Dai Sik Ko
- Division of Vascular Surgery, Department of Surgery, Gachon University Gil Medical Center, Incheon, Republic of Korea
| | - Kyungjae Myung
- Department of Anatomy, School of Medicine, Inje University, Busan, Republic of Korea
| | - Yoonsung Lee
- Department of Anatomy, School of Medicine, Inje University, Busan, Republic of Korea
| | - Hee Sam Na
- Department of Oral Microbiology, School of Dentistry, Pusan National University, Yangsan 50612, Republic of Korea
| | - Yun Hak Kim
- Departments of Anatomy and Biomedical Informatics, School of Medicine, Pusan National University, Yangsan 50612, Republic of Korea. Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea
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33
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Ponirakis G, Abdul‐Ghani MA, Jayyousi A, Zirie MA, Al‐Mohannadi S, Almuhannadi H, Petropoulos IN, Khan A, Gad H, Migahid O, Megahed A, Qazi M, AlMarri F, Al‐Khayat F, Mahfoud Z, DeFronzo R, Malik RA. Insulin resistance limits corneal nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control. J Diabetes Investig 2021; 12:2002-2009. [PMID: 34002953 PMCID: PMC8565403 DOI: 10.1111/jdi.13582] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2020] [Revised: 03/22/2021] [Accepted: 04/15/2021] [Indexed: 01/04/2023] Open
Abstract
AIMS/INTRODUCTION This study aimed to investigate whether insulin resistance (IR) in individuals with type 2 diabetes undergoing intensive glycemic control determines the extent of improvement in neuropathy. MATERIALS AND METHODS This was an exploratory substudy of an open-label, randomized controlled trial of individuals with poorly controlled type 2 diabetes treated with exenatide and pioglitazone or insulin to achieve a glycated hemoglobin <7.0% (<53 mmol/mol). Baseline IR was defined using homeostasis model assessment of IR, and change in neuropathy was assessed using corneal confocal microscopy. RESULTS A total of 38 individuals with type 2 diabetes aged 50.2 ± 8.5 years with (n = 25, 66%) and without (n = 13, 34%) IR were studied. There was a significant decrease in glycated hemoglobin (P < 0.0001), diastolic blood pressure (P < 0.0001), total cholesterol (P < 0.01) and low-density lipoprotein (P = 0.05), and an increase in bodyweight (P < 0.0001) with treatment. Individuals with homeostasis model assessment of IR <1.9 showed a significant increase in corneal nerve fiber density (P ≤ 0.01), length (P ≤ 0.01) and branch density (P ≤ 0.01), whereas individuals with homeostasis model assessment of IR ≥1.9 showed no change. IR was negatively associated with change in corneal nerve fiber density after adjusting for change in bodyweight (P < 0.05). CONCLUSIONS Nerve regeneration might be limited in individuals with type 2 diabetes and IR undergoing treatment with pioglitazone plus exenatide or insulin to improve glycemic control.
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Affiliation(s)
- Georgios Ponirakis
- Weill Cornell Medicine in QatarQatar FoundationEducation City, DohaQatar
- Faculty of Science and EngineeringManchester Metropolitan UniversityManchesterUK
| | - Muhammad A Abdul‐Ghani
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
- Division of DiabetesUniversity of Texas Health Science CenterSan AntonioTexasUSA
| | - Amin Jayyousi
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
| | - Mahmoud A Zirie
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
| | - Salma Al‐Mohannadi
- Weill Cornell Medicine in QatarQatar FoundationEducation City, DohaQatar
| | - Hamad Almuhannadi
- Weill Cornell Medicine in QatarQatar FoundationEducation City, DohaQatar
| | | | - Adnan Khan
- Weill Cornell Medicine in QatarQatar FoundationEducation City, DohaQatar
| | - Hoda Gad
- Weill Cornell Medicine in QatarQatar FoundationEducation City, DohaQatar
| | - Osama Migahid
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
- Division of DiabetesUniversity of Texas Health Science CenterSan AntonioTexasUSA
| | - Ayman Megahed
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
| | - Murtaza Qazi
- Weill Cornell Medicine in QatarQatar FoundationEducation City, DohaQatar
| | - Fatema AlMarri
- Weill Cornell Medicine in QatarQatar FoundationEducation City, DohaQatar
| | - Fatima Al‐Khayat
- Weill Cornell Medicine in QatarQatar FoundationEducation City, DohaQatar
| | - Ziyad Mahfoud
- Weill Cornell Medicine in QatarQatar FoundationEducation City, DohaQatar
| | - Ralph DeFronzo
- Division of DiabetesUniversity of Texas Health Science CenterSan AntonioTexasUSA
| | - Rayaz A Malik
- Weill Cornell Medicine in QatarQatar FoundationEducation City, DohaQatar
- Faculty of Science and EngineeringManchester Metropolitan UniversityManchesterUK
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
- Institute of Cardiovascular ScienceUniversity of ManchesterManchesterUK
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Abstract
Diabetic neuropathy is a neurodegenerative disorder that may alter both the somatic and autonomic peripheral nervous systems in the context of diabetes mellitus (DM). It is a prevalent and burdensome chronic complication of DM, that requires timely management. Optimized glycemic control (mainly for type 1 DM), multifactorial intervention (mainly for type 2 DM), with lifestyle intervention/physical exercise, and weight loss represent the basis of management for diabetic distal symmetrical polyneuropathy, and should be implemented early in the disease course. Despite better understanding of the pathogenetic mechanisms of diabetic peripheral neuropathy, there is still a stringent need for more pathogenetic-based agents that would significantly modify the natural history of the disease. The paper reviews the available drugs and current recommendations for the management of distal symmetrical polyneuropathy, including pain management, and for diabetic autonomic neuropathy. Evaluation of drug combinations that would perhaps be more efficient in slowing the progression of the disease or even reversing it, and that would provide a better pain management is still needed.
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Affiliation(s)
- Simona Cernea
- Department M3/Internal Medicine I, "George Emil Palade" University of Medicine, Pharmacy, Science, and Technology of Târgu Mureş, Târgu Mureş, Romania; Diabetes, Nutrition and Metabolic Diseases Outpatient Unit, Emergency County Clinical Hospital, Târgu Mureş, Romania.
| | - Itamar Raz
- Diabetes Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel
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Greco C, Nascimbeni F, Carubbi F, Andreone P, Simoni M, Santi D. Association of Nonalcoholic Fatty Liver Disease (NAFLD) with Peripheral Diabetic Polyneuropathy: A Systematic Review and Meta-Analysis. J Clin Med 2021; 10:4466. [PMID: 34640482 PMCID: PMC8509344 DOI: 10.3390/jcm10194466] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 09/16/2021] [Accepted: 09/24/2021] [Indexed: 12/29/2022] Open
Abstract
AIMS The relationship between nonalcoholic fatty liver disease (NAFLD) and diabetic polyneuropathy (DPN) has been demonstrated in many studies, although results were conflicting. This meta-analysis aims to summarize available data and to estimate the DPN risk among NAFLD patients. MATERIALS AND METHODS We performed a comprehensive literature review until 4 June 2021. Clinical trials analyzing the association between NAFLD and DPN were included. RESULTS Thirteen studies (9614 participants) were included. DPN prevalence was significantly higher in patients with NALFD, compared to patients without NAFLD (OR (95%CI) 2.48 (1.42-4.34), p = 0.001; I2 96%). This finding was confirmed in type 2 diabetes (OR (95%CI) 2.51 (1.33-4.74), p = 0.005; I2 97%), but not in type 1 diabetes (OR (95%CI) 2.44 (0.85-6.99), p = 0.100; I2 77%). Also, body mass index and diabetes duration were higher in NAFLD subjects compared to those without NAFLD (p < 0.001), considering both type 2 and type 1 diabetes. CONCLUSION Despite a high heterogeneity among studies, a significantly increased DPN prevalence among type 2 diabetes subjects with NAFLD was observed. This result was not found in type 1 diabetes, probably due to the longer duration of disease. Physicians should pay more attention to the early detection of DPN, especially in patients with NAFLD.
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Affiliation(s)
- Carla Greco
- Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 42121 Modena, Italy; (M.S.); (D.S.)
- Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Ospedale Civile di Baggiovara, 41125 Modena, Italy
| | - Fabio Nascimbeni
- Division of Internal Medicine and Metabolism, Department of Internal Medicine, Azienda Ospedaliero-Universitaria of Modena, Ospedale Civile di Baggiovara, 41125 Modena, Italy; (F.N.); (F.C.); (P.A.)
| | - Francesca Carubbi
- Division of Internal Medicine and Metabolism, Department of Internal Medicine, Azienda Ospedaliero-Universitaria of Modena, Ospedale Civile di Baggiovara, 41125 Modena, Italy; (F.N.); (F.C.); (P.A.)
- Unit of Internal and Metabolic Medicine, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 42121 Modena, Italy
| | - Pietro Andreone
- Division of Internal Medicine and Metabolism, Department of Internal Medicine, Azienda Ospedaliero-Universitaria of Modena, Ospedale Civile di Baggiovara, 41125 Modena, Italy; (F.N.); (F.C.); (P.A.)
- Unit of Internal and Metabolic Medicine, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 42121 Modena, Italy
| | - Manuela Simoni
- Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 42121 Modena, Italy; (M.S.); (D.S.)
- Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Ospedale Civile di Baggiovara, 41125 Modena, Italy
| | - Daniele Santi
- Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 42121 Modena, Italy; (M.S.); (D.S.)
- Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Ospedale Civile di Baggiovara, 41125 Modena, Italy
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Ponirakis G, Abdul‐Ghani MA, Jayyousi A, Zirie MA, Qazi M, Almuhannadi H, Petropoulos IN, Khan A, Gad H, Migahid O, Megahed A, Al‐Mohannadi S, AlMarri F, Al‐Khayat F, Mahfoud Z, Al Hamad H, Ramadan M, DeFronzo R, Malik RA. Painful diabetic neuropathy is associated with increased nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control. J Diabetes Investig 2021; 12:1642-1650. [PMID: 33714226 PMCID: PMC8409832 DOI: 10.1111/jdi.13544] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Revised: 02/24/2021] [Accepted: 03/09/2021] [Indexed: 12/13/2022] Open
Abstract
AIMS/INTRODUCTION Painful diabetic peripheral neuropathy (pDPN) is associated with small nerve fiber degeneration and regeneration. This study investigated whether the presence of pDPN might influence nerve regeneration in patients with type 2 diabetes undergoing intensive glycemic control. MATERIALS AND METHODS This exploratory substudy of an open-label randomized controlled trial undertook the Douleur Neuropathique en 4 questionnaire and assessment of electrochemical skin conductance, vibration perception threshold and corneal nerve morphology using corneal confocal microscopy in participants with and without pDPN treated with exenatide and pioglitazone or basal-bolus insulin at baseline and 1-year follow up, and 18 controls at baseline only. RESULTS Participants with type 2 diabetes, with (n = 13) and without (n = 28) pDPN had comparable corneal nerve fiber measures, electrochemical skin conductance and vibration perception threshold at baseline, and pDPN was not associated with the severity of DPN. There was a significant glycated hemoglobin reduction (P < 0.0001) and weight gain (P < 0.005), irrespective of therapy. Participants with pDPN showed a significant increase in corneal nerve fiber density (P < 0.05), length (P < 0.0001) and branch density (P < 0.005), and a decrease in the Douleur Neuropathique en 4 score (P < 0.01), but no change in electrochemical skin conductance or vibration perception threshold. Participants without pDPN showed a significant increase in corneal nerve branch density (P < 0.01) and no change in any other neuropathy measures. A change in the severity of painful symptoms was not associated with corneal nerve regeneration and medication for pain. CONCLUSIONS This study showed that intensive glycemic control is associated with greater corneal nerve regeneration and an improvement in the severity of pain in patients with painful diabetic neuropathy.
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Affiliation(s)
- Georgios Ponirakis
- Weill Cornell Medicine‐QatarQatar FoundationEducation CityDohaQatar
- Faculty of Science and EngineeringManchester Metropolitan UniversityManchesterUK
| | - Muhammad A Abdul‐Ghani
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
- Division of DiabetesUniversity of Texas Health Science CenterSan AntonioTexasUSA
| | - Amin Jayyousi
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
| | - Mahmoud A Zirie
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
| | - Murtaza Qazi
- Weill Cornell Medicine‐QatarQatar FoundationEducation CityDohaQatar
| | | | | | - Adnan Khan
- Weill Cornell Medicine‐QatarQatar FoundationEducation CityDohaQatar
| | - Hoda Gad
- Weill Cornell Medicine‐QatarQatar FoundationEducation CityDohaQatar
| | - Osama Migahid
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
- Division of DiabetesUniversity of Texas Health Science CenterSan AntonioTexasUSA
| | - Ayman Megahed
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
| | | | - Fatema AlMarri
- Weill Cornell Medicine‐QatarQatar FoundationEducation CityDohaQatar
| | - Fatima Al‐Khayat
- Weill Cornell Medicine‐QatarQatar FoundationEducation CityDohaQatar
| | - Ziyad Mahfoud
- Weill Cornell Medicine‐QatarQatar FoundationEducation CityDohaQatar
| | | | | | - Ralph DeFronzo
- Division of DiabetesUniversity of Texas Health Science CenterSan AntonioTexasUSA
| | - Rayaz A Malik
- Weill Cornell Medicine‐QatarQatar FoundationEducation CityDohaQatar
- Faculty of Science and EngineeringManchester Metropolitan UniversityManchesterUK
- National Diabetes CenterHamad General HospitalHamad Medical CorporationDohaQatar
- Institute of Cardiovascular ScienceUniversity of ManchesterManchesterUK
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Bashir M, Elhadd T, Dabbous Z, Gul W, Salameh O, Siddiqui M, Al-Muhannadi H, Petropoulos I, Khan A, Ponirakis G, Malik RA. Optimal glycaemic and blood pressure but not lipid targets are related to a lower prevalence of diabetic microvascular complications. Diabetes Metab Syndr 2021; 15:102241. [PMID: 34390975 DOI: 10.1016/j.dsx.2021.102241] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 06/27/2021] [Accepted: 08/01/2021] [Indexed: 11/18/2022]
Abstract
BACKGROUND Diabetic microvascular complications are a major cause of morbidity and are related to glycaemic control and cardiovascular risk factors. AIMS We sought to determine the association of microvascular complications in relation to control of glycemia, blood pressure and lipids in T2DM patients attending secondary care in Qatar. METHODS This is a cross-sectional study undertaken in patients with T2DM attending Qatar's National Diabetes Centres. Patients underwent assessment of glycemia, blood pressure and lipids and prevalence of diabetic peripheral neuropathy (DPN), retinopathy and microalbuminuria. RESULTS We included 1114 subjects aged 52.1 ± 11.3 years with a duration of diabetes 10.0 ± 7.6 years and had a prevalence of 25.8% for DPN, 34.3% for painful DPN, 36.8% for microalbuminuria and 25.1% for retinopathy. Patients who achieved an HbA1c ≤ 7.0% compared to >7% had a significantly lower prevalence of DPN (P < 0.01), painful DPN (P < 0.01), retinopathy (P < 0.01) and microalbuminuria (P < 0.007). Patients who achieved a systolic BP ≤ 140 mmHg compared to >140 mmHg had a significantly lower prevalence of DPN (P < 0.001), painful DPN (P < 0.001), retinopathy (P < 0.001) and microalbuminuria (P < 0.001). Patients who achieved an LDL ≤2.6 mmol/l compared to >2.6 mmol/l had a significantly higher prevalence of DPN (P < 0.03), but no difference in other outcomes. There was no difference in microvascular complications between those who achieved a HDL-C ≥ 1.02 mmol/l, and among those who achieved triglycerides ≤1.7 mmol/l. CONCLUSIONS Optimal control of glycemia and blood pressure, but not lipids is associated with a lower prevalence of diabetic microvascular complications.
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Affiliation(s)
- Mohammad Bashir
- National Diabetes & Endocrine Centre, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Tarik Elhadd
- National Diabetes & Endocrine Centre, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar; National Diabetes & Endocrine Centre, Al-Wakra Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Zeinab Dabbous
- National Diabetes & Endocrine Centre, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Wajiha Gul
- National Diabetes & Endocrine Centre, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Obada Salameh
- National Diabetes & Endocrine Centre, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Mashhood Siddiqui
- National Diabetes & Endocrine Centre, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Hamad Al-Muhannadi
- Weill Cornell Medicine-Qatar, Qatar Foundation, Education City, Doha, Qatar
| | | | - Adnan Khan
- Weill Cornell Medicine-Qatar, Qatar Foundation, Education City, Doha, Qatar
| | - Georgios Ponirakis
- Weill Cornell Medicine-Qatar, Qatar Foundation, Education City, Doha, Qatar
| | - Rayaz A Malik
- Weill Cornell Medicine-Qatar, Qatar Foundation, Education City, Doha, Qatar; Institute of Cardiovascular Science, University of Manchester, Manchester, UK.
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Shi L, Wei H, Zhang T, Li Z, Chi X, Liu D, Chang D, Zhang Y, Wang X, Zhao Q. A potent weighted risk model for evaluating the occurrence and severity of diabetic foot ulcers. Diabetol Metab Syndr 2021; 13:92. [PMID: 34465375 PMCID: PMC8407043 DOI: 10.1186/s13098-021-00711-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 08/18/2021] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Diabetic foot ulcer (DFU) is a serious chronic complication of diabetes. This study aimed to establish weighted risk models for determining DFU occurrence and severity in diabetic patients. METHODS This was a multi-center hospital-based cross-sectional study. A total of 1488 diabetic patients with or without an ulcer from three tertiary hospitals were included in the study. Random forest method was used to develop weighted risk models for assessing DFU risk and severity. Receiver operating characteristic curves were used to validate the models and calculate the optimal cut-off values of the important risk factors. RESULTS We developed potent weighted risk models for evaluating DFU occurrence and severity. The top eight important risk factors for DFU onset were plasma fibrinogen, neutrophil percentage and hemoglobin levels in whole blood, stroke, estimated glomerular filtration rate, age, duration of diabetes, and serum albumin levels. The top 10 important risk factors for DFU severity were serum albumin, neutrophil percentage and hemoglobin levels in whole blood, plasma fibrinogen, hemoglobin A1c, estimated glomerular filtration rate, hypertension, serum uric acid, diabetic retinopathy, and sex. Furthermore, the area under curve values in the models using plasma fibrinogen as a single risk factor for determining DFU risk and severity were 0.86 (sensitivity 0.74, specificity 0.87) and 0.73 (sensitivity 0.76, specificity 0.58), respectively. The optimal cut-off values of plasma fibrinogen for determining DFU risk and severity were 3.88 g/L and 4.74 g/L, respectively. CONCLUSIONS We have established potent weighted risk models for DFU onset and severity, based on which precise prevention strategies can be formulated. Modification of important risk factors may help reduce the incidence and progression of DFUs in diabetic patients.
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Affiliation(s)
- Lu Shi
- Department of Geratology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Huiyi Wei
- Yan'an University, Yan'an, 716000, Shaanxi, China
| | - Tianxiao Zhang
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, Shaanxi, China
| | - Zhiying Li
- Department of Geratology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Xiaoxian Chi
- Department of Geratology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Dandan Liu
- Department of Geratology, Ninth Hospital of Xi'an, Xi'an, 710061, Shaanxi, China
| | - Dandan Chang
- Department of Geratology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
- Department of Endocrinology, The First Affiliated Hospital of Xi'an Medical College, Xi'an, 710077, Shaanxi, China
| | - Yueying Zhang
- Department of Geratology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Xiaodan Wang
- Department of Geratology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China
| | - Qingbin Zhao
- Department of Geratology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
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Sloan G, Selvarajah D, Tesfaye S. Pathogenesis, diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy. Nat Rev Endocrinol 2021; 17:400-420. [PMID: 34050323 DOI: 10.1038/s41574-021-00496-z] [Citation(s) in RCA: 231] [Impact Index Per Article: 57.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/15/2021] [Indexed: 02/08/2023]
Abstract
Diabetic sensorimotor peripheral neuropathy (DSPN) is a serious complication of diabetes mellitus and is associated with increased mortality, lower-limb amputations and distressing painful neuropathic symptoms (painful DSPN). Our understanding of the pathophysiology of the disease has largely been derived from animal models, which have identified key potential mechanisms. However, effective therapies in preclinical models have not translated into clinical trials and we have no universally accepted disease-modifying treatments. Moreover, the condition is generally diagnosed late when irreversible nerve damage has already taken place. Innovative point-of-care devices have great potential to enable the early diagnosis of DSPN when the condition might be more amenable to treatment. The management of painful DSPN remains less than optimal; however, studies suggest that a mechanism-based approach might offer an enhanced benefit in certain pain phenotypes. The management of patients with DSPN involves the control of individualized cardiometabolic targets, a multidisciplinary approach aimed at the prevention and management of foot complications, and the timely diagnosis and management of neuropathic pain. Here, we discuss the latest advances in the mechanisms of DSPN and painful DSPN, originating both from the periphery and the central nervous system, as well as the emerging diagnostics and treatments.
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Affiliation(s)
- Gordon Sloan
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Dinesh Selvarajah
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
- Department of Oncology and Human Metabolism, University of Sheffield, Sheffield, UK
| | - Solomon Tesfaye
- Diabetes Research Unit, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK.
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40
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Galiero R, Ricciardi D, Pafundi PC, Todisco V, Tedeschi G, Cirillo G, Sasso FC. Whole plantar nerve conduction study: A new tool for early diagnosis of peripheral diabetic neuropathy. Diabetes Res Clin Pract 2021; 176:108856. [PMID: 33965449 DOI: 10.1016/j.diabres.2021.108856] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 04/23/2021] [Accepted: 05/01/2021] [Indexed: 12/17/2022]
Abstract
AIMS Peripheral neuropathy (PN) affects two-thirds of type 2 diabetes patients (T2DM). According to diabetic PN length-dependent pattern, neurophysiological evaluation of foot-sole nerves might increase NCS diagnostic sensitivity, hence allowing early diagnosis of PN. Thus, we aim to assess the ability of whole plantar nerve (WPN) conduction in diabetic PN early diagnosis. METHODS This is a single center prospective observational cohort study on 70 T2DM patients referred to Internal Medicine Unit of A.O.U. "Luigi Vanvitelli" between October 2019/October 2020. Primary endpoint was WPN efficacy assessment in PN early detection. As secondary, we evaluated (i) a potential cut-off of SNAPs amplitude by WPN and (ii) WPN diagnostic accuracy vs. gold-standard distal sural nerve conduction. RESULTS ROC curve analysis allowed to establish two potential cut-offs for people aged ≤60 years (AUROC: 0.83, 95%CI: 0.69-0.96, p < 0.001) and ≤60 years (AUROC: 0.76, 95%CI: 0.59-0.93, p = 0.017). In depth, we fixed a cut-off of WPN-SNAP amplitude of 4.55 μV and 2.65 μV, respectively, with subsequent 48 patients classified as PN-T2DM. CONCLUSIONS Our data support WPN conduction study reliability in characterizing the most distal sensory nerve fibers at lower limbs. Thus, WPN may represent an extremely useful diagnostic tool for diabetic PN early detection.
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Affiliation(s)
- Raffaele Galiero
- Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Luigi Miraglia 2, I-80138 Naples, Italy.
| | - Dario Ricciardi
- Division of Neurology and Neurophysiopathology, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Luigi Miraglia 2, I-80138 Naples, Italy
| | - Pia Clara Pafundi
- Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Luigi Miraglia 2, I-80138 Naples, Italy.
| | - Vincenzo Todisco
- Division of Neurology and Neurophysiopathology, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Luigi Miraglia 2, I-80138 Naples, Italy
| | - Gioacchino Tedeschi
- Division of Neurology and Neurophysiopathology, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Luigi Miraglia 2, I-80138 Naples, Italy.
| | - Giovanni Cirillo
- Division of Neurology and Neurophysiopathology, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Luigi Miraglia 2, I-80138 Naples, Italy; Division of Human Anatomy - Neuronal Networks Morphology Lab, University of Campania "Luigi Vanvitelli", Naples, Italy.
| | - Ferdinando Carlo Sasso
- Division of Internal Medicine, Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Piazza Luigi Miraglia 2, I-80138 Naples, Italy.
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Lin YK, Gao B, Liu L, Ang L, Mizokami-Stout K, Pop-Busui R, Zhang L. The Prevalence of Diabetic Microvascular Complications in China and the USA. Curr Diab Rep 2021; 21:16. [PMID: 33835284 DOI: 10.1007/s11892-021-01387-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/25/2021] [Indexed: 01/19/2023]
Abstract
PURPOSE OF REVIEW Diabetes can lead to development of devastating microvascular complications, such as nephropathy, retinopathy, and peripheral sensory and autonomic neuropathy. While China and the USA both face the threat of this major public health challenge, the literature is limited in describing similarities and differences in the prevalence, and risk factors for the development, of diabetic microvascular complications between these two countries. RECENT FINDINGS The current review discusses the following: (1) the most recent evidence on prevalence of diabetic microvascular complications in China and the USA (including downtrends of diabetes retinopathy and neuropathy in the USA); (2) differences in patient risk factors of these complications; (3) challenges and current knowledge gaps (such as lacking national epidemiological data of diabetic complications in China); and (4) potential future clinical and research opportunities (including needs in diabetes evaluation and management in remote areas and standardization of methods in evaluating diabetic complications across countries). Diabetic microvascular complications remain to be health threats in both China and the USA. Further investigations are needed for comprehensive understanding and effect prevention and management of these complications.
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Affiliation(s)
- Yu Kuei Lin
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
- Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Brehm Tower 5119, 1000 Wall Street, Ann Arbor, MI, USA.
| | - Bixia Gao
- Department of Medicine, Peking University First Hospital, Beijing, China
| | - Lili Liu
- Department of Medicine, Peking University First Hospital, Beijing, China
| | - Lynn Ang
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | | | - Rodica Pop-Busui
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA
| | - Luxia Zhang
- Renal Division, Department of Medicine, Peking University First Hospital, 8 Xishiku Street, Xicheng District, Beijing, 100034, China.
- Key Laboratory of Renal Disease, National Health Commission of the People's Republic of China, Beijing, China.
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.
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42
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Abstract
It is increasingly recognized that diabetic neuropathy is associated with early diabetes, prediabetes, and the metabolic syndrome. Early detection and diagnosis are important to slow progression and prevent complications. Although strict glucose control is an effective treatment in type 1 diabetes, it is less effective in type 2 diabetes. There is a growing body of literature that lifestyle interventions may be able to prevent or slow progression of neuropathy in type 2 diabetes. In addition to the typical distal symmetric polyneuropathy, there are many types of "atypical" diabetic neuropathies that are important to recognize.
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Affiliation(s)
- Lindsay A Zilliox
- Department of Neurology, University of Maryland School of Medicine & Maryland VA Healthcare System, 3S-130, 110 South Paca Street, Baltimore, MD 21201-1595, USA.
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43
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Abstract
The American Diabetes Association (ADA) "Standards of Medical Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee (https://doi.org/10.2337/dc21-SPPC), are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations, please refer to the Standards of Care Introduction (https://doi.org/10.2337/dc21-SINT). Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.
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Ponirakis G, Elhadd T, Chinnaiyan S, Hamza AH, Sheik S, Kalathingal MA, Anodiyil MS, Dabbous Z, Siddique MA, Almuhannadi H, Petropoulos IN, Khan A, Ae Ashawesh K, Dukhan KM, Mahfoud ZR, Zirie MA, Jayyousi A, Murgatroyd C, Slevin M, Malik RA. Prevalence and risk factors for diabetic neuropathy and painful diabetic neuropathy in primary and secondary healthcare in Qatar. J Diabetes Investig 2020; 12:592-600. [PMID: 32799429 PMCID: PMC8015833 DOI: 10.1111/jdi.13388] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Revised: 08/06/2020] [Accepted: 08/10/2020] [Indexed: 02/07/2023] Open
Abstract
Aims/Introduction This study determined the prevalence and risk factors for diabetic peripheral neuropathy (DPN) and painful DPN (pDPN) in patients with type 2 diabetes in primary healthcare (PHC) and secondary healthcare (SHC) in Qatar. Materials and Methods This was a cross‐sectional multicenter study. Adults with type 2 diabetes were randomly enrolled from four PHC centers and two diabetes centers in SHC in Qatar. Participants underwent assessment of clinical and metabolic parameters, DPN and pDPN. Results A total of 1,386 individuals with type 2 diabetes (297 from PHC and 1,089 from SHC) were recruited. The prevalence of DPN (14.8% vs 23.9%, P = 0.001) and pDPN (18.1% vs 37.5%, P < 0.0001) was significantly lower in PHC compared with SHC, whereas those with DPN at high risk for diabetic foot ulceration (31.8% vs 40.0%, P = 0.3) was comparable. The prevalence of undiagnosed DPN (79.5% vs 82.3%, P = 0.66) was comparably high, but undiagnosed pDPN (24.1% vs 71.5%, P < 0.0001) was lower in PHC compared with SHC. The odds of DPN and pDPN increased with age and diabetes duration, and DPN increased with poor glycemic control, hyperlipidemia and hypertension, whereas pDPN increased with obesity and reduced physical activity. Conclusions The prevalence of DPN and pDPN in type 2 diabetes is lower in PHC compared with SHC, and is attributed to overall better control of risk factors and referral bias due to patients with poorly managed complications being referred to SHC. However, approximately 80% of patients had not been previously diagnosed with DPN in PHC and SHC. Furthermore, we identified a number of modifiable risk factors for PDN and pDPN.
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Affiliation(s)
- Georgios Ponirakis
- Weill Cornell Medicine-Qatar, Qatar Foundation, Education City, Doha, Qatar.,Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK
| | - Tarik Elhadd
- National Diabetes Center, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.,National Diabetes Center, Al-Wakra Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Subitha Chinnaiyan
- National Diabetes Center, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Abdul H Hamza
- Umm Ghuwailina Primary Health Care, Umm Ghuwailina, Qatar
| | | | | | | | - Zeinab Dabbous
- National Diabetes Center, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Mashhood A Siddique
- National Diabetes Center, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Hamad Almuhannadi
- Weill Cornell Medicine-Qatar, Qatar Foundation, Education City, Doha, Qatar
| | | | - Adnan Khan
- Weill Cornell Medicine-Qatar, Qatar Foundation, Education City, Doha, Qatar
| | - Khaled Ae Ashawesh
- National Diabetes Center, Al-Wakra Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Khaled M Dukhan
- National Diabetes Center, Al-Wakra Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Ziyad R Mahfoud
- Weill Cornell Medicine-Qatar, Qatar Foundation, Education City, Doha, Qatar
| | - Mahmoud A Zirie
- National Diabetes Center, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | - Amin Jayyousi
- National Diabetes Center, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar
| | | | - Mark Slevin
- Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK
| | - Rayaz A Malik
- Weill Cornell Medicine-Qatar, Qatar Foundation, Education City, Doha, Qatar.,Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK.,National Diabetes Center, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar.,Institute of Cardiovascular Science, University of Manchester, Manchester, UK
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45
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Solomon WL, Hector SBE, Raghubeer S, Erasmus RT, Kengne AP, Matsha TE. Genome-Wide DNA Methylation and LncRNA-Associated DNA Methylation in Metformin-Treated and -Untreated Diabetes. EPIGENOMES 2020; 4:epigenomes4030019. [PMID: 34968291 PMCID: PMC8594715 DOI: 10.3390/epigenomes4030019] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 08/03/2020] [Accepted: 08/14/2020] [Indexed: 02/06/2023] Open
Abstract
Metformin, which is used as a first line treatment for type 2 diabetes mellitus (T2DM), has been shown to affect epigenetic patterns. In this study, we investigated the DNA methylation and potential lncRNA modifications in metformin-treated and newly diagnosed adults with T2DM. Genome-wide DNA methylation and lncRNA analysis were performed from the peripheral blood of 12 screen-detected and 12 metformin-treated T2DM individuals followed by gene ontology (GO) and KEGG pathway analysis. Differentially methylated regions (DMRs) observed showed 22 hypermethylated and 11 hypomethylated DMRs between individuals on metformin compared to screen-detected subjects. Amongst the hypomethylated DMR regions were the SLC gene family, specifically, SLC25A35 and SLC28A1. Fifty-seven lncRNA-associated DNA methylation regions included the mitochondrial ATP synthase-coupling factor 6 (ATP5J). Functional gene mapping and pathway analysis identified regions in the axon initial segment (AIS), node of Ranvier, cell periphery, cleavage furrow, cell surface furrow, and stress fiber. In conclusion, our study has identified a number of DMRs and lncRNA-associated DNA methylation regions in metformin-treated T2DM that are potential targets for therapeutic monitoring in patients with diabetes.
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Affiliation(s)
- Wendy L. Solomon
- SAMRC/CPUT/Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Science, Cape Peninsula University of Technology, P.O. Box 1906, Bellville, Cape Town 7530, South Africa; (W.L.S.); (S.B.E.H.); (S.R.)
| | - Stanton B. E. Hector
- SAMRC/CPUT/Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Science, Cape Peninsula University of Technology, P.O. Box 1906, Bellville, Cape Town 7530, South Africa; (W.L.S.); (S.B.E.H.); (S.R.)
| | - Shanel Raghubeer
- SAMRC/CPUT/Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Science, Cape Peninsula University of Technology, P.O. Box 1906, Bellville, Cape Town 7530, South Africa; (W.L.S.); (S.B.E.H.); (S.R.)
| | - Rajiv T. Erasmus
- Division of Chemical Pathology, Faculty of Health Sciences, National Health Laboratory Service (NHLS) and University of Stellenbosch, Cape Town 7505, South Africa;
| | - Andre P. Kengne
- Non-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town 7505, South Africa;
- Department of Medicine, University of Cape Town, Cape Town 7700, South Africa
| | - Tandi E. Matsha
- SAMRC/CPUT/Cardiometabolic Health Research Unit, Department of Biomedical Sciences, Faculty of Health and Wellness Science, Cape Peninsula University of Technology, P.O. Box 1906, Bellville, Cape Town 7530, South Africa; (W.L.S.); (S.B.E.H.); (S.R.)
- Correspondence: ; Tel.: +27-21-959-6366; Fax: +27-21-959-6760
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Wei W, Li L, Deng L, Wang ZJ, Dong JJ, Lyu XY, Jia T, Wang L, Wang HX, Mao H, Zhao S. Autologous Bone Marrow Mononuclear Cell Transplantation Therapy Improved Symptoms in Patients with Refractory Diabetic Sensorimotor Polyneuropathy via the Mechanisms of Paracrine and Immunomodulation: A Controlled Study. Cell Transplant 2020; 29:963689720949258. [PMID: 32787571 PMCID: PMC7563922 DOI: 10.1177/0963689720949258] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
We recently reported that transplantation of autologous bone marrow mononuclear
cells (BM-MNCs) may be an effective and promising therapy to treat refractory
diabetic sensorimotor polyneuropathy (DSPN) in patients with type 2 diabetes
mellitus (T2DM). This study was designed to investigate the potential mechanisms
of BM-MNCs therapy, which recruited 60 patients with DSPN, 30 T2DM patients
without complications, and 30 healthy control participants. All clinical
parameters, the levels of inflammatory markers, and growth factors in the three
groups were compared. Patients in DSPN group had higher level of tumor necrosis
factor-α (TNF-α) (DSPN vs control, 412.90 ± 64.58 vs 374.81 ± 63.18 pg/mL,
P < 0.01) and lower level of vascular endothelial growth
factor (VEGF) (DSPN vs control, 140.93 ± 24.78 vs 157.39 ± 25.11 pg/mL,
P < 0.01) than those in control group. DSPN group had
the highest level of soluble intercellular adhesion molecule-1 (sICAM-1) among
three groups (DSPN and DM vs control, 1477.56 ± 228.00 and 1342.17 ± 237.54 vs
1308.00 ± 200.94 ng/mL, P < 0.05). The level of nerve growth
factor in the DSPN group was slightly lower than that in the DM group (DSPN vs
DM, 3509.11 ± 438.39 vs 3734.87 ± 647.50 pg/mL, P < 0.05).
All patients with DSPN received one intramuscular injection of BM-MNCs and
clinical follow-ups after the therapy for 2 days, 1, 4, 12, 24, and 48 weeks.
Neuropathic symptoms of foot pain, numbness, and weakness were significantly
improved within 4 weeks after BM-MNCs injection. Patients with DSPN were divided
into the responder (n = 35) and nonresponder groups
(n = 19) based on the improvement of nerve conduction
velocity at 12 weeks post-transplantation. Compared with nonresponders,
responders were younger (57.3 ± 5.2 vs 62.0 ± 4.8, P <
0.01), had a shorter history of diabetes (7.1 ± 2.7 vs 11.2 ± 5.4 years,
P < 0.01), and had higher numbers of mobilized
CD34+ cells (17.61 ± 2.64 vs 14.79 ± 1.62 ×105/L,
P < 0.01) and BM-MNCs (12.05 ± 2.16 vs 9.84 ± 1.53
×108/L, P < 0.01). The levels of TNF-α and
sICAM-1 decreased just after BM-MNCs injection in both groups and slowly
reverted to baseline levels. The duration of the downtrend of TNF-α and sICAM-1
in the responder group lasted longer than that in the nonresponder group. Serum
level of VEGF in the responder group increased immediately after BM-MNC therapy
and reached the highest point after the injection for 12 weeks. On the other
hand, VEGF levels in the nonresponder group only increased slightly. Binary
logistic regression was performed to evaluate the corresponding prognostic
factors for BM-MNCs treatment. The number of applied CD34+ cells and
the duration of diabetes were the independent predictors of responding to
BM-MNCs therapy. No adverse event associated with the treatment was observed
during follow-up observations. These results indicated that BM-MNCs
transplantation is an effective and promising therapeutic strategy to treat
refractory DSPN. The immune regulation and paracrine function of BM-MNCs may
contribute to the improvement of DSPN.
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Affiliation(s)
- Wei Wei
- Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, 12403Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Li Li
- Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, 12403Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Lin Deng
- Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, 12403Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhong-Jing Wang
- Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, 12403Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Jing-Jian Dong
- Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, 12403Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiao-Yu Lyu
- Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, 12403Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Ting Jia
- Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, 12403Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Li Wang
- Department of Hematology, The Central Hospital of Wuhan, Tongji Medical College, 12403Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Hong-Xiang Wang
- Department of Hematology, The Central Hospital of Wuhan, Tongji Medical College, 12403Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Hong Mao
- Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, 12403Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Shi Zhao
- Department of Endocrinology, The Central Hospital of Wuhan, Tongji Medical College, 12403Huazhong University of Science and Technology, Wuhan, Hubei, China.,Regenerative Medical Center of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, 12403Huazhong University of Science and Technology, Wuhan, Hubei, China
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47
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Zang S, Shi L, Zhao J, Yang M, Liu J, Ding H. Prealbumin to fibrinogen ratio is closely associated with diabetic peripheral neuropathy. Endocr Connect 2020; 9:858-863. [PMID: 32880377 PMCID: PMC7487192 DOI: 10.1530/ec-20-0316] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Accepted: 08/06/2020] [Indexed: 12/22/2022]
Abstract
The aim of our study was to explore the diagnostic value of prealbumin to fibrinogen ratio (PFR) for predicting prognosis with the optimal cut-off value in diabetic peripheral neuropathy (DPN) patients. A total of 568 type 2 diabetes mellitus (T2DM) patients were enrolled in this study. The values including Toronto clinical neuropathy score (TCNS), nerve conduction velocity (NCV), vibration perception threshold (VPT), blood cells count, biochemical parameters, fibrinogen and PFR were recorded. The patients were divided into tertiles based on admission PFR value. First, clinical parameters were compared among the groups. Secondly, a logistic regression and ROC analysis were performed as the statistical model. The percentage of DPN, TCNS and VPT were significantly higher in the lowest PFR tertile than in the middle PFR tertile and the highest PFR tertile (P < 0.01-0.001). NCV was significantly lower in lowest PFR tertile than in the middle PFR tertile and the highest PFR tertile (P < 0.01-0.001). The Spearman correlation analysis showed that PFR was negatively correlated with TCNS and VPT (P < 0.001), while PFR was positively correlated with median motor NCV (P < 0.001), peroneal motor NCV (P < 0.001), median sensory NCV (P < 0.001), and peroneal sensory NCV (P < 0.001). After adjusting these potentially related factors, PFR was independently related to DPN (P = 0.007). The area under ROC curve was 0.627. This study finds the first evidence to suggest PFR may be the key component associated with DPN in T2DM, while PFR might underlie the pathophysiologic features of DPN.
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Affiliation(s)
- Shufei Zang
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
| | - Lei Shi
- Department of Neurology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
| | - Jinying Zhao
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
| | - Min Yang
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
| | - Jun Liu
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
| | - Heyuan Ding
- Department of Endocrinology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, China
- Correspondence should be addressed to H Ding:
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48
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Understanding Diabetic Neuropathy: Focus on Oxidative Stress. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2020; 2020:9524635. [PMID: 32832011 PMCID: PMC7422494 DOI: 10.1155/2020/9524635] [Citation(s) in RCA: 68] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/14/2020] [Accepted: 07/22/2020] [Indexed: 02/06/2023]
Abstract
Diabetic neuropathy is one of the clinical syndromes characterized by pain and substantial morbidity primarily due to a lesion of the somatosensory nervous system. The burden of diabetic neuropathy is related not only to the complexity of diabetes but also to the poor outcomes and difficult treatment options. There is no specific treatment for diabetic neuropathy other than glycemic control and diligent foot care. Although various metabolic pathways are impaired in diabetic neuropathy, enhanced cellular oxidative stress is proposed as a common initiator. A mechanism-based treatment of diabetic neuropathy is challenging; a better understanding of the pathophysiology of diabetic neuropathy will help to develop strategies for the new and correct diagnostic procedures and personalized interventions. Thus, we review the current knowledge of the pathophysiology in diabetic neuropathy. We focus on discussing how the defects in metabolic and vascular pathways converge to enhance oxidative stress and how they produce the onset and progression of nerve injury present in diabetic neuropathy. We discuss if the mechanisms underlying neuropathy are similarly operated in type I and type II diabetes and the progression of antioxidants in treating diabetic neuropathy.
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49
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Feng J, Wang H, Jing Z, Wang Y, Cheng Y, Wang W, Sun W. Role of Magnesium in Type 2 Diabetes Mellitus. Biol Trace Elem Res 2020; 196:74-85. [PMID: 31713111 DOI: 10.1007/s12011-019-01922-0] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2019] [Accepted: 09/26/2019] [Indexed: 12/11/2022]
Abstract
Magnesium (in its ionized and biologically active form, Mg2+) is an essential trace element that participates in numerous physiologic processes. Abnormal Mg2+ homeostasis can lead to many metabolic disorders, including diabetes mellitus (DM) and its complications. Mg2+ participates in energy generation and is required for DNA and RNA synthesis, reproduction, and protein synthesis. Additionally, Mg2+ acts as a calcium antagonist and protects vascular endothelial cells from oxidative stress. Imbalances in Mg2+ status, more frequently hypomagnesemia, inhibit glucose transporter type 4 translocation, increase insulin resistance, affect lipid metabolism, induce oxidative stress, and impair the antioxidant system of endothelial cells, In these ways, hypomagnesemia contributes to the initiation and progression of DM and its macrovascular and microvascular complications. In this review, we summarize recent advances in knowledge of the mechanisms whereby Mg2+ regulates insulin secretion and sensitivity. In addition, we discuss the future prospects for research regarding the mechanisms whereby Mg2+ status impacts DM and its complications.
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Affiliation(s)
- Jianan Feng
- Department of Nephrology, The First Hospital of Jilin University, 71 Xinmin Street, Jilin Province, Changchun, 130021, China
| | - Heyuan Wang
- Department of Endocrinology, The First Hospital of Jilin University, Changchun, 130021, Jilin, China
| | - Zhe Jing
- Department of Nephrology, The First Hospital of Jilin University, 71 Xinmin Street, Jilin Province, Changchun, 130021, China
- Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun, 130021, Jilin, China
| | - Yue Wang
- Department of Nephrology, The First Hospital of Jilin University, 71 Xinmin Street, Jilin Province, Changchun, 130021, China
| | - Yanli Cheng
- Department of Nephrology, The First Hospital of Jilin University, 71 Xinmin Street, Jilin Province, Changchun, 130021, China
| | - Wanning Wang
- Department of Nephrology, The First Hospital of Jilin University, 71 Xinmin Street, Jilin Province, Changchun, 130021, China
| | - Weixia Sun
- Department of Nephrology, The First Hospital of Jilin University, 71 Xinmin Street, Jilin Province, Changchun, 130021, China.
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50
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Mather KJ, Bebu I, Baker C, Cohen RM, Crandall JP, DeSouza C, Green JB, Kirkman MS, Krause-Steinrauf H, Larkin M, Pettus J, Seaquist ER, Soliman EZ, Schroeder EB, Wexler DJ, Pop-Busui R. Prevalence of microvascular and macrovascular disease in the Glycemia Reduction Approaches in Diabetes - A Comparative Effectiveness (GRADE) Study cohort. Diabetes Res Clin Pract 2020; 165:108235. [PMID: 32450102 PMCID: PMC7416515 DOI: 10.1016/j.diabres.2020.108235] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 04/08/2020] [Accepted: 05/18/2020] [Indexed: 12/18/2022]
Abstract
AIMS The Glycemia Reduction Approaches in Diabetes - A Comparative Effectiveness (GRADE) trial is a randomized clinical trial comparing glycemic effects of four diabetes medications added to metformin in type 2 diabetes (T2D). Microvascular and macrovascular diseases are secondary outcomes. We evaluated the prevalence and risk factor relationships for microvascular and macrovascular complications in the GRADE cohort at study entry. METHODS Complication prevalence and risk factors were analyzed based on data from screening in all consenting participants meeting GRADE eligibility. Logistic regression and Z-statistics were used to assess risk factor relationships with complications. RESULTS We enrolled 5047 T2D participants [mean age 57 years; 36% female; mean known T2D duration 4 years (all < 10 years); mean HbA1c 8.0% (∼64 mmol/mol) at screening]. Urinary albumin/creatinine ratio (ACR) ≥ 30 mg/gram was present in 15.9% participants; peripheral neuropathy (by Michigan Neuropathy Screening Instrument) in 21.5%; cardiovascular autonomic neuropathy by electrocardiography-derived indices in 9.7%; self-reported retinopathy in 1.0%. Myocardial infarction ascertained by self-report or electrocardiogram was present in 7.3%, and self-reported history of stroke in 2.0%. CONCLUSIONS In the GRADE cohort with < 10 years of T2D and a mean HbA1c of 8.0%, diabetes complications were present in a substantial fraction of participants, more so than might otherwise have been expected.
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Affiliation(s)
- Kieren J Mather
- Division of Endocrinology & Metabolism, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Ionut Bebu
- The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD, United States.
| | - Chelsea Baker
- Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, United States
| | - Robert M Cohen
- Division of Endocrinology, Diabetes & Metabolism, Department of Medicine, University of Cincinnati College of Medicine & Endocrine Section, Cincinnati VA Medical Center, Cincinnati OH, United States
| | - Jill P Crandall
- Division of Endocrinology and Fleischer Institute for Diabetes & Metabolism, Albert Einstein College of Medicine, Bronx, NY, United States
| | - Cyrus DeSouza
- Division of Diabetes, Endocrinology & Metabolism, University of Nebraska College of Medicine, Omaha, NE, United States
| | - Jennifer B Green
- Division of Endocrinology, Department of Medicine, Duke University Medical Center, Durham, NC, United States
| | - M Sue Kirkman
- Division of Endocrinology & Metabolism, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, United States
| | - Heidi Krause-Steinrauf
- The Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD, United States
| | - Mary Larkin
- Massachusetts General Hospital Diabetes Center and Harvard Medical School, Boston, MA, United States
| | - Jeremy Pettus
- Division of Endocrinology & Metabolism, Department of Medicine, University of California, San Diego, CA, United States
| | - Elizabeth R Seaquist
- Division of Diabetes and Endocrinology, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, United States
| | - Elsayed Z Soliman
- Epidemiological Cardiology Research Center, Department of Epidemiology and Prevention and Department of Internal Medicine-Cardiology Section, Wake Forest School of Medicine, Winston Salem, NC, United States
| | - Emily B Schroeder
- Institute for Health Research, Kaiser Permanente Colorado, Aurora, CO, United States
| | - Deborah J Wexler
- Massachusetts General Hospital Diabetes Center and Harvard Medical School, Boston, MA, United States
| | - Rodica Pop-Busui
- Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States
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