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1
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Pierre-Jerome C. The peripheral nervous system: peripheral neuropathies in the diabetic foot. MYOPATHIES AND TENDINOPATHIES OF THE DIABETIC FOOT 2025:451-482. [DOI: 10.1016/b978-0-443-13328-2.00022-2] [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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2
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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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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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Aung NL. A1C: Episode 3. Clin Diabetes 2024; 42:448-451. [PMID: 39015166 PMCID: PMC11247035 DOI: 10.2337/cd24-0038] [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: 07/18/2024]
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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: 50] [Impact Index Per Article: 50.0] [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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Gad H, Elgassim E, Mohammed I, Yaser Alhaddad A, Ahmed Hussein Zaky Aly H, Cabibihan JJ, Al-Ali A, Kumar Sadasivuni K, Petropoulos IN, Ponirakis G, Abuhelaiqa W, Jayyousi A, AlMohanadi D, Baagar K, Malik RA. Cardiovascular autonomic neuropathy is associated with increased glycemic variability driven by hyperglycemia rather than hypoglycemia in patients with diabetes. Diabetes Res Clin Pract 2023; 200:110670. [PMID: 37169307 DOI: 10.1016/j.diabres.2023.110670] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 03/27/2023] [Accepted: 04/11/2023] [Indexed: 05/13/2023]
Abstract
AIM Cardiac autonomic neuropathy (CAN) has been suggested to be associated with hypoglycemia and impaired hypoglycemia unawareness. We have assessed the relationship between CAN and extensive measures of glucose variability (GV) in patients with type 1 and type 2 diabetes. METHODS Participants with diabetes underwent continuous glucose monitoring (CGM) to obtain measures of GV and the extent of hyperglycemia and hypoglycemia and cardiovascular autonomic reflex testing. RESULTS Of the 40 participants (20 T1DM and 20 T2DM) (aged 40.70±13.73 years, diabetes duration 14.43±7.35 years, HbA1c 8.85±1.70%), 23 (57.5%) had CAN. Despite a lower coefficient of variation (CV) (31.26±11.87 vs. 40.33±11.03, P=0.018), they had a higher CONGA (8.42±2.58 vs. 6.68±1.88, P=0.024) with a lower median LBGI (1.60 (range: 0.20-3.50) vs. 4.90 (range: 3.20-7.40), P=0.010) and percentage median time spent in hypoglycemia (4 (range:4-13) vs. 1 (range:0-5), P=0.008), compared to those without CAN. The percentage GRADEEuglycemia (3.30±2.78 vs. 5.69±3.09, P=0.017) and GRADEHypoglycemia (0.3 (range: 0 - 3.80) vs. 1.8 (range: 0.9-6.5), P=0.036) were significantly lower, while the percentage median GRADEHyperglycemia (95.45 (range:93-98) vs. 91.6 (82.8-95.1), P=0.013) was significantly higher in participants with CAN compared to those without CAN. CONCLUSION CAN was associated with increased glycemic variability with less time in euglycemia attributed to a greater time in hyperglycemia but not hypoglycemia.
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Affiliation(s)
- Hoda Gad
- Department of Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Einas Elgassim
- Department of Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar
| | - Ibrahim Mohammed
- Department of Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar; Internal Medicine, Albany Medical Center Hospital, Albany, New York, USA
| | - Ahmad Yaser Alhaddad
- Department of Mechanical and Industrial Engineering, Qatar University, Doha, Qatar
| | | | - John-John Cabibihan
- Department of Mechanical and Industrial Engineering, Qatar University, Doha, Qatar
| | - Abdulaziz Al-Ali
- KINDI Center for computing research, Qatar University, Doha, Qatar
| | | | | | | | | | - Amin Jayyousi
- Hamad Medical Corporation, National Diabetes Center, Doha, Qatar
| | - Dabia AlMohanadi
- Hamad Medical Corporation, National Diabetes Center, Doha, Qatar
| | - Khaled Baagar
- Hamad Medical Corporation, National Diabetes Center, Doha, Qatar
| | - Rayaz A Malik
- Department of Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar; Institute of Cardiovascular Medicine, University of Manchester, Manchester, UK.
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7
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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: 82] [Impact Index Per Article: 41.0] [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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Aitkens L, Downey G. A case of dysautonomia after COVID-19 infection in a patient with poorly controlled type I diabetes. Clin Case Rep 2023; 11:e6889. [PMID: 36703776 PMCID: PMC9871405 DOI: 10.1002/ccr3.6889] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2022] [Revised: 12/19/2022] [Accepted: 01/03/2023] [Indexed: 01/25/2023] Open
Abstract
COVID-19 has been linked to dysautonomia in the current literature, as has uncontrolled diabetes. Here, we present a case report of severe dysautonomia following a COVID-19 infection in a patient with pre-existing poorly controlled type-1 diabetes. This patient exhibited symptoms consistent with both postural orthostatic tachycardia syndrome (POTS), as well as orthostatic hypotension. His symptoms became so severe that he was unable to come to a standing position without experiencing syncope. Extensive workup was completed to identify an alternative cause of his dysautonomia with inconclusive results. Dysautonomia can have devastating consequences in regard to physical, social, and psychological health. Counseling individuals with poorly controlled diabetes about the importance of maintaining tight blood glucose control and avoiding COVID-19 infection should be primary interventions when treating patients with this DM1. Early detection and management of diabetes mellitus, COVID-19, and of possible resultant dysautonomia through medical interventions, as well as lifestyle changes, are extremely important measures to avoid development of dangerous and potentially life-threatening consequences.
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Affiliation(s)
- Lorry Aitkens
- Department of Internal MedicineMedical College of Georgia at Augusta UniversityAugustaGeorgiaUSA
| | - George Downey
- Department of Internal MedicineMedical College of Georgia at Augusta UniversityAugustaGeorgiaUSA
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9
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Cardiac Autonomic Neuropathy in Type 1 and 2 Diabetes: Epidemiology, Pathophysiology, and Management. Clin Ther 2022; 44:1394-1416. [DOI: 10.1016/j.clinthera.2022.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 07/23/2022] [Accepted: 09/06/2022] [Indexed: 11/21/2022]
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Kostourou DT, Milonas D, Polychronopoulos G, Sofogianni A, Tziomalos K. The Role of Angiotensin Receptor Blockers in the Personalized Management of Diabetic Neuropathy. J Pers Med 2022; 12:1253. [PMID: 36013202 PMCID: PMC9410471 DOI: 10.3390/jpm12081253] [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: 06/27/2022] [Revised: 07/27/2022] [Accepted: 07/29/2022] [Indexed: 11/20/2022] Open
Abstract
Neuropathy is a frequent complication of diabetes mellitus (DM) and is associated with the increased risk ofamputation and vascular events. Tight glycemic control is an important component inthe prevention of diabetic neuropathy. However, accumulating data suggest that angiotensin receptor blockers (ARBs) might also be useful in this setting. We discuss the findings of both experimental and clinical studies that evaluated the effects of ARBs on indices of diabetic neuropathy. We also review the implicated mechanisms of the neuroprotective actions of these agents. Overall, it appears that ARBs might be a helpful tool for preventing and delaying the progression of diabetic neuropathy, but more data are needed to clarify their role in the management of this overlooked complication of DM.
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Affiliation(s)
| | | | | | | | - Konstantinos Tziomalos
- First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki 54636, Greece; (D.-T.K.); (D.M.); (G.P.); (A.S.)
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Safi M, Borup A, Stevns Hansen C, Rossing P, Thorsten Jensen M, Christoffersen C. Association between plasma apolipoprotein M and cardiac autonomic neuropathy in type 1 diabetes. Diabetes Res Clin Pract 2022; 189:109943. [PMID: 35690270 DOI: 10.1016/j.diabres.2022.109943] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Revised: 05/09/2022] [Accepted: 06/06/2022] [Indexed: 11/23/2022]
Abstract
AIM Diabetes may lead to severe complications e.g. cardiac autonomic neuropathy (CAN) characterized by an increased risk of cardiovascular mortality. CAN is diagnosed by a decreased heart rate viability (HRV). Sphingosine-1-Phosphate (S1P) carried by the HDL-associated apolipoprotein M (apoM) is linked to a reduction in the heart rate, and treatment with an S1P-agonist increases HRV. The present study aimed to investigate if plasma apoM was associated with an increased risk of CAN. METHODS The study includes 278 individuals with Type 1 Diabetes recruited from Steno Diabetes Center in Copenhagen from 2010 to 2012. RESULTS A change of 0.1 µM plasma apoM was associated with the diagnosis of CAN (Odds ratio: 1.11 (1.02; 1.21), p = 0.013). ApoM plasma levels were also positively associated with CAN when adjusted for age and gender (Odds ratio: 1.11 (1.02; 1.21), p = 0.013) as well as lipids, beta-blockers, blood pressure, and alcohol (Odds ratio: 1.14 (1.04; 1.26), p = 0.005) and Hbga1c and time with diabetes (Odds ratio: 1.13 (1.02; 1.25), p = 0.01). Plasma apoM was also associated with a significantly lower SDNN as well as high frequency power in all adjusted models. CONCLUSION Increased plasma apoM was associated with an increased risk of CAN as well as a significant reduction in HRV indices. This could represent changes in parasympathetic activity, but, further studies are needed to also explore additional molecular alterations behind such observations.
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Affiliation(s)
- Mostafa Safi
- Department of Clinical Biochemistry, Rigshospitalet, Denmark; Department of Biomedical Sciences, University of Copenhagen, Denmark
| | - Anna Borup
- Department of Clinical Biochemistry, Rigshospitalet, Denmark; Department of Biomedical Sciences, University of Copenhagen, Denmark
| | | | - Peter Rossing
- Steno Diabetes Center Copenhagen, Gentofte, Denmark; Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark
| | - Magnus Thorsten Jensen
- Institute of Clinical Medicine, Faculty of Health Sciences, University of Copenhagen, Denmark; Department of Cardiology, Copenhagen University Hospital Amager Hvidovre, Denmark
| | - Christina Christoffersen
- Department of Clinical Biochemistry, Rigshospitalet, Denmark; Department of Biomedical Sciences, University of Copenhagen, Denmark.
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Mizokami-Stout K, Bailey R, Ang L, Aleppo G, Levy CJ, Rickels MR, Shah VN, Polsky S, Nelson B, Carlson AL, Vendrame F, Pop-Busui R. Symptomatic diabetic autonomic neuropathy in type 1 diabetes (T1D): Findings from the T1D exchange. J Diabetes Complications 2022; 36:108148. [PMID: 35279403 DOI: 10.1016/j.jdiacomp.2022.108148] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 02/02/2022] [Accepted: 02/03/2022] [Indexed: 10/19/2022]
Abstract
AIMS We aimed to evaluate the contemporary prevalence of and risk factors for symptomatic diabetic autonomic neuropathy (DAN) in participants with type 1 diabetes (T1D) enrolled in the T1D Exchange Clinic Registry. METHODS DAN symptoms and severity were assessed with the Survey of Autonomic Symptoms (SAS) in adults with ≥5 years of T1D participating in the T1D Exchange from years 2010-2017. Associations of demographic, clinical, and laboratory factors with symptomatic DAN were assessed. RESULTS Of the 4919 eligible T1D participants, 965 (20%) individuals completed the SAS questionnaire [mean age 40 ± 17 years, median diabetes duration 20 years (IQR: 13,34), 64% female, 90% non-Hispanic White, and 82% with private insurance]. DAN symptoms were present in 166 (17%) of responders with 72% experiencing moderate severity symptoms or worse. Symptomatic DAN participants had higher hemoglobin A1c (p = 0.03), longer duration (p = 0.004), were more likely to be female (p = 0.03), and more likely to have lower income (p = 0.03) versus no DAN symptoms. Symptomatic DAN was associated with diabetic peripheral neuropathy (p < 0.0001), smoking (p = 0.002), cardiovascular disease (p = 0.02), depression (p < 0.001), and opioid use (p = 0.004). CONCLUSIONS DAN symptoms are common in T1D. Socioeconomic factors and psychological comorbidities may contribute to DAN symptoms and should be explored further.
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Affiliation(s)
| | - Ryan Bailey
- Jaeb Center for Health Research, Tampa, FL, United States of America
| | - Lynn Ang
- University of Michigan, Ann Arbor, MI, United States of America
| | - Grazia Aleppo
- Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America
| | - Carol J Levy
- Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Michael R Rickels
- Rodebaugh Diabetes Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States of America
| | - Viral N Shah
- Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America
| | - Sarit Polsky
- Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America
| | - Bryce Nelson
- Children's Hospital of Richmond, Virginia Commonwealth University, Richmond, VA, United States of America
| | - Anders L Carlson
- International Diabetes Center, Minneapolis, MN, United States of America
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13
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Tang G, Pi L, Guo H, Hu Z, Zhou C, Hu Q, Peng H, Xiao Z, Zhang Z, Wang M, Peng T, Huang J, Liang S, Li G. Naringin Relieves Diabetic Cardiac Autonomic Neuropathy Mediated by P2Y14 Receptor in Superior Cervical Ganglion. Front Pharmacol 2022; 13:873090. [PMID: 35529431 PMCID: PMC9068893 DOI: 10.3389/fphar.2022.873090] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 03/23/2022] [Indexed: 12/30/2022] Open
Abstract
Diabetes mellitus (DM), an emerging chronic epidemic, contributes to mortality and morbidity around the world. Diabetic cardiac autonomic neuropathy (DCAN) is one of the most common complications associated with DM. Previous studies have shown that satellite glial cells (SGCs) in the superior cervical ganglia (SCG) play an indispensable role in DCAN progression. In addition, it has been shown that purinergic neurotransmitters, as well as metabotropic GPCRs, are involved in the pathophysiological process of DCAN. Furthermore, one traditional Chinese medicine, naringin may potently alleviate the effects of DCAN. Ferroptosis may be involved in DCAN progression. However, the role of naringin in DCAN as well as its detailed mechanism requires further investigation. In this research, we attempted to identify the effect and relevant mechanism of naringin in DCAN mitigation. We observed that compared with those of normal subjects, there were significantly elevated expression levels of P2Y14 and IL-1β in diabetic rats, both of which were remarkably diminished by treatment with either P2Y14 shRNA or naringin. In addition, abnormalities in blood pressure (BP), heart rate (HR), heart rate variability (HRV), sympathetic nerve discharge (SND), and cardiac structure in the diabetic model can also be partially returned to normal through the use of those treatments. Furthermore, a reduced expression of NRF2 and GPX4, as well as an elevated level of ROS, were detected in diabetic cases, which can also be improved with those treatments. Our results showed that naringin can effectively relieve DCAN mediated by the P2Y14 receptor of SGCs in the SCG. Moreover, the NRF2/GPX4 pathway involved in ferroptosis may become one of the principal mechanisms participating in DCAN progression, which can be modulated by P2Y14-targeted naringin and thus relieve DCAN. Hopefully, our research can supply one novel therapeutic target and provide a brilliant perspective for the treatment of DCAN.
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Affiliation(s)
- Gan Tang
- Queen Mary School, Medical School of Nanchang University, Nanchang, China
| | - Lingzhi Pi
- School of Basic Medicine, Medical School of Nanchang University, Nanchang, China
| | - Hongmin Guo
- Department of Physiology, Medical School of Nanchang University, Nanchang, China
| | - Zihui Hu
- Department of Physiology, Medical School of Nanchang University, Nanchang, China
| | - Congfa Zhou
- Department of Anatomy, Medical School of Nanchang University, Nanchang, China
| | - Qixing Hu
- Department of Physiology, Medical School of Nanchang University, Nanchang, China
| | - Hao Peng
- School of Basic Medicine, Medical School of Nanchang University, Nanchang, China
| | - Zehao Xiao
- Queen Mary School, Medical School of Nanchang University, Nanchang, China
| | - Zhihua Zhang
- Queen Mary School, Medical School of Nanchang University, Nanchang, China
| | - Miaomiao Wang
- Queen Mary School, Medical School of Nanchang University, Nanchang, China
| | - Taotao Peng
- School of Basic Medicine, Medical School of Nanchang University, Nanchang, China
| | - Jiaqi Huang
- Queen Mary School, Medical School of Nanchang University, Nanchang, China
| | - Shangdong Liang
- Department of Physiology, Medical School of Nanchang University, Nanchang, China
| | - Guilin Li
- Department of Physiology, Medical School of Nanchang University, Nanchang, China
- *Correspondence: Guilin Li,
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14
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Wang J, Xu Z, Lv K, Ye Y, Luo D, Wan L, Zhou F, Yu A, Wang S, Liu J, Gao L. The Predictive Value of Serum Calcium on Heart Rate Variability and Cardiac Function in Type 2 Diabetes Patients. Front Endocrinol (Lausanne) 2022; 13:864008. [PMID: 35498438 PMCID: PMC9047897 DOI: 10.3389/fendo.2022.864008] [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: 01/27/2022] [Accepted: 03/03/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Cardiovascular autonomic neuropathy (CAN) is common in patients with type 2 diabetes mellitus (T2DM), mainly presented as decreased heart rate variability (HRV) which often leads to cardiac death. However, HRV measurement is not convenient in most clinics. Therefore, identifying high-risk patients for CAN in diabetes with easier measurements is crucial for the early intervention and prevention of catastrophic consequences. METHODS In this cross-sectional study, 675 T2DM patients with normocalcemia were selected. Of these, they were divided into two groups: normal HRV group (n = 425, 100 ms≤ SDNN ≤180 ms) vs. declined HRV group (n = 250, SDNN <100 ms). All patients' clinical data were collected and the correlation of clinical variables with HRV were analyzed by correlation and logistic regression analysis. The area below the ROC curve was used to evaluate the predictive performance of serum calcium on HRV. RESULTS In this study, declines in HRV were present in 37.0% of T2DM patients. Significant differences in albumin-adjusted serum calcium levels (CaA) (8.86 ± 0.27 vs. 9.13 ± 0.39 mg/dl, p <0.001) and E/A (0.78 ± 0.22 vs. 0.83 ± 0.26, p = 0.029) were observed between declined HRV and normal HRV groups. Bivariate linear correlation analysis showed that CaA and E/A were positively correlated with HRV parameters including SDNN (p < 0.001), SDNN index (p < 0.001), and Triangle index (p < 0.05). The AUC in the ROC curve for the prediction of CaA on HRV was 0.730 (95% CI (0.750-0.815), p < 0.001). The cutoff value of CaA was 8.87 mg/dl (sensitivity 0.644, specificity 0.814). The T2DM patients with CaA <8.87 mg/dl had significantly lower HRV parameters (SDNN, SDNN index, rMSSD, and triangle index) than those with CaA ≥8.87 mg/dl (p < 0.01, respectively). Multivariate logistic regression analysis showed a significantly increased risk of declined HRV in subjects with CaA level <8.87 mg/dl [OR (95% CI), 0.049 (0.024-0.099), p < 0.001]. CONCLUSIONS Declined HRV is associated with a lower CaA level and worse cardiac function. The serum calcium level can be used for risk evaluation of declined HRV in T2DM patients even within the normocalcemic range.
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Affiliation(s)
- Junyi Wang
- Department of Endocrinology & Metabolism, Renmin Hospital of Wuhan University, Wuhan, China
| | - Zihui Xu
- Department of Endocrinology & Metabolism, Renmin Hospital of Wuhan University, Wuhan, China
| | - Kang Lv
- Shenzhen University, College of Big Data and Internet, Shenzhen, China
| | - Yingchun Ye
- Department of Endocrinology & Metabolism, Renmin Hospital of Wuhan University, Wuhan, China
| | - Deng Luo
- Department of Endocrinology & Metabolism, Renmin Hospital of Wuhan University, Wuhan, China
| | - Li Wan
- Department of Endocrinology & Metabolism, Renmin Hospital of Wuhan University, Wuhan, China
| | - Fen Zhou
- Department of Endocrinology & Metabolism, Renmin Hospital of Wuhan University, Wuhan, China
| | - Ailin Yu
- Department of Endocrinology & Metabolism, Renmin Hospital of Wuhan University, Wuhan, China
| | - Shuo Wang
- Department of Endocrinology & Metabolism, Renmin Hospital of Wuhan University, Wuhan, China
| | - Jingcheng Liu
- Department of Endocrinology & Metabolism, Renmin Hospital of Wuhan University, Wuhan, China
| | - Ling Gao
- Department of Endocrinology & Metabolism, Renmin Hospital of Wuhan University, Wuhan, China
- *Correspondence: Ling Gao,
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15
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Bönhof GJ, Herder C, Ziegler D. Diagnostic Tools, Biomarkers, and Treatments in Diabetic polyneuropathy and Cardiovascular Autonomic Neuropathy. Curr Diabetes Rev 2022; 18:e120421192781. [PMID: 33845748 DOI: 10.2174/1573399817666210412123740] [Citation(s) in RCA: 4] [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: 01/14/2021] [Revised: 02/24/2021] [Accepted: 03/02/2021] [Indexed: 11/22/2022]
Abstract
The various manifestations of diabetic neuropathy, including distal symmetric sensorimotor polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN), are among the most prevalent chronic complications of diabetes. Major clinical complications of diabetic neuropathies, such as neuropathic pain, chronic foot ulcers, and orthostatic hypotension, are associated with considerable morbidity, increased mortality, and diminished quality of life. Despite the substantial individual and socioeconomic burden, the strategies to diagnose and treat diabetic neuropathies remain insufficient. This review provides an overview of the current clinical aspects and recent advances in exploring local and systemic biomarkers of both DSPN and CAN assessed in human studies (such as biomarkers of inflammation and oxidative stress) for better understanding of the underlying pathophysiology and for improving early detection. Current therapeutic options for DSPN are (I) causal treatment, including lifestyle modification, optimal glycemic control, and multifactorial risk intervention, (II) pharmacotherapy derived from pathogenetic concepts, and (III) analgesic treatment against neuropathic pain. Recent advances in each category are discussed, including non-pharmacological approaches, such as electrical stimulation. Finally, the current therapeutic options for cardiovascular autonomic complications are provided. These insights should contribute to a broader understanding of the various manifestations of diabetic neuropathies from both the research and clinical perspectives.
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Affiliation(s)
- Gidon J Bönhof
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Department of Endocrinology, Medical Faculty and University Hospital, Heinrich Heine University, Düsseldorf, Germany
| | - Christian Herder
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Department of Endocrinology, Medical Faculty and University Hospital, Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany
| | - Dan Ziegler
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Department of Endocrinology, Medical Faculty and University Hospital, Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany
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16
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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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17
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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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18
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Huang L, Shen X, Huang L, Yan S, Wu P. Identification of independent risk factors for diabetic neuropathy progression in patients with type 2 diabetes mellitus. J Int Med Res 2021; 49:3000605211044366. [PMID: 34559575 PMCID: PMC8485273 DOI: 10.1177/03000605211044366] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Objective To identify independent risk factors for diabetic neuropathy (DN) in patients with type 2 diabetes mellitus (T2DM). Methods We retrospectively analyzed 376 patients with T2DM at the First Affiliated Hospital of Fujian Medical University, China between January 2013 and October 2016. Multivariate logistic regression was used to explore potential risk factors for progression of DN in patients with T2DM. Effect sizes were estimated using odds ratios (ORs) and 95% confidence intervals (CIs). Results The prevalence of DN in patients with T2DM was 43.1%. Multivariate logistic regression indicated that retinopathy (OR: 2.755, 95% CI: 1.599–4.746); diabetic nephropathy (OR: 2.196, 95% CI: 1.279–3.772); longer duration of T2DM (OR: 1.081, 95% CI: 1.045–1.120); use of insulin (OR: 1.091, 95% CI: 1.018–1.170); longer history of alcohol consumption (OR: 1.034, 95% CI: 1.010–1.059); and higher blood urea nitrogen (OR: 1.081, 95% CI: 1.009–1.159) were associated with increased risk of DN in patients with T2DM. Conclusions Retinopathy, diabetic nephropathy, longer duration of T2DM, use of insulin, longer history of alcohol consumption, and higher blood urea nitrogen were independent risk factors for DN. These findings should be verified in large-scale prospective studies.
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Affiliation(s)
- Linjing Huang
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.,Fujian Province Clinical Research Center for Metabolic Diseases, Fuzhou, Fujian, China.,Diabetes Research Institute of Fujian Province, Fuzhou, Fujian, China.,Metabolic Diseases Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Ximei Shen
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.,Fujian Province Clinical Research Center for Metabolic Diseases, Fuzhou, Fujian, China.,Diabetes Research Institute of Fujian Province, Fuzhou, Fujian, China.,Metabolic Diseases Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Lingning Huang
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.,Fujian Province Clinical Research Center for Metabolic Diseases, Fuzhou, Fujian, China.,Diabetes Research Institute of Fujian Province, Fuzhou, Fujian, China.,Metabolic Diseases Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Sunjie Yan
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.,Fujian Province Clinical Research Center for Metabolic Diseases, Fuzhou, Fujian, China.,Diabetes Research Institute of Fujian Province, Fuzhou, Fujian, China.,Metabolic Diseases Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Peiwen Wu
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.,Fujian Province Clinical Research Center for Metabolic Diseases, Fuzhou, Fujian, China.,Diabetes Research Institute of Fujian Province, Fuzhou, Fujian, China.,Metabolic Diseases Research Institute, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
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19
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Liu Y, Peng Y, Jin J, Chen Y, Chen C, Chen Z, Huang H, Xu L. Insulin resistance is independently associated with cardiovascular autonomic neuropathy in type 2 diabetes. J Diabetes Investig 2021; 12:1651-1662. [PMID: 33460512 PMCID: PMC8409868 DOI: 10.1111/jdi.13507] [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: 11/24/2020] [Revised: 12/26/2020] [Accepted: 01/13/2021] [Indexed: 12/24/2022] Open
Abstract
AIMS/INTRODUCTION Diabetic cardiovascular autonomic neuropathy (DCAN) seriously threatens the prognosis and quality of life of patients with type 2 diabetes mellitus, associated with increased mortality. The present study aimed to investigate the relevant risk factors of DCAN. MATERIALS AND METHODS The present study enrolled a total of 109 patients with type 2 diabetes mellitus. DCAN was defined as a score of at least 2 points in Ewing tests. The updated homeostasis model assessment of insulin resistance (HOMA2-IR) based on fasting C-peptide was calculated to reflect insulin resistance. Logistic regression analysis, interaction and stratified analyses were used to investigate the relationship between HOMA2-IR or other indicators and DCAN. Receiver operating characteristic analysis was carried out to estimate the discriminative value of the variables independently associated with DCAN and to determine the optimal cut-off point of these models to screen DCAN. RESULTS The HOMA2-IR levels were significantly higher in patients with DCAN, and tended to be worsened with the progression of the DCAN. Logistic regression analysis showed an independent association between HOMA2-IR (odds ratio 39.30, 95% confidence interval 7.17-215.47) and DCAN. HOMA2-IR (area under the curve 0.878, 95% confidence interval 0.810-0.946; cut-off value 1.735) individually predicted DCAN significantly higher than the other independent risk factors individually used, whereas models combining HOMA2-IR and other risk factors did not significantly boost the diagnostic power. CONCLUSIONS Insulin resistance is independently associated with DCAN. HOMA2-IR presents to be a highly accurate and parsimonious indicator for DCAN screening. Patients with HOMA2-IR >1.735 are at a high risk of DCAN; thus, priority diagnostic tests should be carried out for these patients for timely integrated intervention.
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Affiliation(s)
- Yingshan Liu
- Department of EndocrinologyShenzhen HospitalSouthern Medical UniversityShenzhenChina
- The Third School of Clinical MedicineSouthern Medical UniversityGuangzhouChina
| | - Yu Peng
- Department of NeurologyNanfang HospitalSouthern Medical UniversityGuangzhouChina
| | - Jing Jin
- Department of EndocrinologyShenzhen HospitalSouthern Medical UniversityShenzhenChina
- The Third School of Clinical MedicineSouthern Medical UniversityGuangzhouChina
| | - Yanshan Chen
- Department of EndocrinologyShenzhen HospitalSouthern Medical UniversityShenzhenChina
- The Third School of Clinical MedicineSouthern Medical UniversityGuangzhouChina
| | - Chuna Chen
- Department of EndocrinologyShenzhen HospitalSouthern Medical UniversityShenzhenChina
- The Third School of Clinical MedicineSouthern Medical UniversityGuangzhouChina
| | - Zhenguo Chen
- Department of EndocrinologyShenzhen HospitalSouthern Medical UniversityShenzhenChina
- The Third School of Clinical MedicineSouthern Medical UniversityGuangzhouChina
| | - Haishan Huang
- Department of EndocrinologyShenzhen HospitalSouthern Medical UniversityShenzhenChina
- The Third School of Clinical MedicineSouthern Medical UniversityGuangzhouChina
| | - Lingling Xu
- Department of EndocrinologyShenzhen HospitalSouthern Medical UniversityShenzhenChina
- The Third School of Clinical MedicineSouthern Medical UniversityGuangzhouChina
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20
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Lai Y, Huang C, Cheng B, Tsai N, Chiu W, Chang H, Chen J, Lu C. Feasibility of combining heart rate variability and electrochemical skin conductance as screening and severity evaluation of cardiovascular autonomic neuropathy in type 2 diabetes. J Diabetes Investig 2021; 12:1671-1679. [PMID: 33522129 PMCID: PMC8409849 DOI: 10.1111/jdi.13518] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 01/26/2021] [Accepted: 01/28/2021] [Indexed: 11/30/2022] Open
Abstract
AIMS/INTRODUCTION Clinical studies show that either heart rate variability (HRV) or electrochemical skin conductance (ESC) alone can serve as a simple and objective method for screening cardiovascular autonomic neuropathy (CAN). We tested the hypothesis that combining these two quantitative approaches can not only reinforce accuracy in CAN screening but also provide a better estimate of CAN severity in patients with type 2 diabetes (T2DM) who had already had CAN in outpatient clinics. MATERIALS AND METHODS Each patient received a complete battery of cardiovascular autonomic reflex tests (CARTs), with ESC measured by SUDOSCAN, time domain of HRV measured by standard deviation of all normal RR intervals (SDNN) and frequency domain of HRV (low frequency [LF], high frequency [HF], and LF/HF ratio), and peripheral blood studies for vascular risk factors. Severity of CAN was measured by CAN score. RESULTS The 90 T2DM patients included 50 males and 40 females. Those with more severe CAN had lower values in feet ESC (P = 0.023) and SDNN (P < 0.0001). Multiple linear regression analysis also showed that feet ESC and SDNN value (P = 0.003 and P < 0.0001) were significantly associated with CAN score. Combining SDNN and feet ESC also can increase the diagnostic accuracy of CAN with respective to sensitivity and specificity by using receiver operating characteristic analysis. CONCLUSIONS Combining the results of SDNN and feet ESC can not only assess, but also quantitatively reflect the progress or improvement of autonomic nerve function (including sympathetic and parasympathetic activity) in patients with T2DM.
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Affiliation(s)
- Yun‐Ru Lai
- Department of NeurologyKaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKaohsiungTaiwan
| | - Chih‐Cheng Huang
- Department of NeurologyKaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKaohsiungTaiwan
| | - Ben‐Chung Cheng
- Department of Internal MedicineKaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKaohsiungTaiwan
| | - Nai‐Wen Tsai
- Department of NeurologyKaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKaohsiungTaiwan
| | - Wen‐Chan Chiu
- Department of Internal MedicineKaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKaohsiungTaiwan
| | - Hsueh‐Wen Chang
- Department of Biological ScienceNational Sun Yat‐Sen UniversityKaohsiungTaiwan
| | - Jung‐Fu Chen
- Department of Internal MedicineKaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKaohsiungTaiwan
| | - Cheng‐Hsien Lu
- Department of NeurologyKaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKaohsiungTaiwan
- Department of Internal MedicineKaohsiung Chang Gung Memorial HospitalChang Gung University College of MedicineKaohsiungTaiwan
- Department of NeurologyXiamen Chang Gung Memorial HospitalXiamen, FujianChina
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21
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Cardiac Autonomic Neuropathy Is Not Reversed by Euglycemia Following Islet Transplantation. Transplantation 2021; 105:1125-1129. [PMID: 32590611 DOI: 10.1097/tp.0000000000003377] [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]
Abstract
BACKGROUND Cardiac autonomic neuropathy (CAN) is a significant cause of morbidity and mortality for people with type 1 (T1D) and type 2 (T2D) diabetes. Heart rate variability (HRV) has been shown to be a marker of CAN with 24-hour Holter monitoring being a robust modality to assess HRV. METHODS To investigate the impact of hypoglycemia on CAN and its potential reversibility with islet transplantation, we compared HRV assessment by 24-hour Holter monitor on a total of 109 subjects from 5 cohorts: (1) T1D with recurrent severe hypoglycemia and on waiting list for islet transplant, (2) T1D following islet cell transplantation (ICT), (3) T2D without hypoglycemia, (4) individuals with prediabetes, and (5) controls without diabetes. SD of the normal-normal interval, square root of the mean squared differences of successive normal-normal intervals (rMSSD) and total spectral power were analyzed. RESULTS There was no significant difference in HRV parameters between T1D subjects and T1D post ICT suggesting CAN is not reversible at a median of 4 years postislet transplant. There was a significant difference in controls and T1D in rMSSD and between controls and T2D in total power. The differential effect on rMSSD in T1D and T2D suggests potential greater impact of hypoglycemia on rMSSD. CONCLUSIONS Achieving euglycemia after ICT may not reverse CAN once established with no significant difference in HRV parameters at a median of 4 years postislet transplant. Differential effects of T1D as compared with T2D on CAN were identified.
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22
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Serdarova M, Dimova R, Chakarova N, Grozeva G, Todorova A, Tankova T. Relationship between cardiac autonomic neuropathy and cardio-metabolic risk profile in adults with type 1 diabetes. Diabetes Res Clin Pract 2021; 174:108721. [PMID: 33640411 DOI: 10.1016/j.diabres.2021.108721] [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: 06/01/2020] [Revised: 09/01/2020] [Accepted: 02/06/2021] [Indexed: 10/22/2022]
Abstract
AIM The present study aims to determine the prevalence and association of cardiac autonomic neuropathy (CAN) with some traditional cardio-metabolic risk factors in adults with type 1 diabetes (T1D). MATERIAL AND METHODS 235 adults with T1D, divided into three groups according to diabetes duration, were recruited in this cross-sectional study from May 2017 till December 2018. Anthropometric parameters and blood pressure were measured. Lipids, liver enzymes, uric acid, creatinine, HbA1c and high sensitive C-reactive protein (hsCRP) were measured at fasting. Albumin/creatinine ratio (ACR) was measured in a first spot urine sample. Body composition was evaluated using bio-impedance analysis, Inbody720 (Biospace, USA). Advanced glycation end products (AGEs) were assessed by autofluorescence method, AGE Reader (Diagnoptics, The Netherlands). CAN was assessed by ANX-3.0 monitoring technology (ANSAR Medical Technologies, Inc., Philadelphia, PA), applying standard clinical tests. 2005 IDF and 2009 JIS definitions were used to define Metabolic Syndrome (MetS). RESULTS The prevalence of CAN was 23% and increased with diabetes duration. Sympathetic activity was independently related to age, albumin/creatinine ratio (ACR) and total body fat mass, and parasympathetic activity - to age and ACR. Elevated hsCRP, AGEs and body fat, diabetic retinopathy and nephropathy, as well as hypertension, dyslipidemia and metabolic syndrome were found to increase the risk of CAN in T1D. CONCLUSION CAN appears to be a common complication of T1D, especially with longer duration, and is found to be related to diabetic microvascular disease and metabolic syndrome components.
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Affiliation(s)
- M Serdarova
- Department of Endocrinology, Medical University of Sofia, Bulgaria.
| | - R Dimova
- Department of Endocrinology, Medical University of Sofia, Bulgaria
| | - N Chakarova
- Department of Endocrinology, Medical University of Sofia, Bulgaria
| | - G Grozeva
- Department of Endocrinology, Medical University of Sofia, Bulgaria
| | - A Todorova
- Department of Endocrinology, Medical University of Sofia, Bulgaria
| | - T Tankova
- Department of Endocrinology, Medical University of Sofia, Bulgaria
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23
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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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24
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Akinci G, Savelieff MG, Gallagher G, Callaghan BC, Feldman EL. Diabetic neuropathy in children and youth: New and emerging risk factors. Pediatr Diabetes 2021; 22:132-147. [PMID: 33205601 PMCID: PMC11533219 DOI: 10.1111/pedi.13153] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 11/02/2020] [Accepted: 11/12/2020] [Indexed: 12/23/2022] Open
Abstract
Pediatric neuropathy attributed to metabolic dysfunction is a well-known complication in children and youth with type 1 diabetes. Moreover, the rise of obesity and in particular of type 2 diabetes may cause an uptick in pediatric neuropathy incidence. However, despite the anticipated increase in neuropathy incidence, pathogenic insights and strategies to prevent or manage neuropathy in the setting of diabetes and obesity in children and youth remain unknown. Data from adult studies and available youth cohort studies are providing an initial understanding of potential diagnostic, management, and preventative measures in early life. This review discusses the current state of knowledge emanating from these efforts, with particular emphasis on the prevalence, clinical presentation, diagnostic approaches and considerations, and risk factors of neuropathy in type 1 and type 2 diabetes in children and youth. Also highlighted are current management strategies and recommendations for neuropathy in children and youth with diabetes. This knowledge, along with continued and sustained emphasis on identifying and eliminating modifiable risk factors, completing randomized controlled trials to assess effectiveness of strategies like weight loss and exercise, and enhancing awareness to support early detection and prevention, are pertinent to addressing the rising incidence of neuropathy associated with diabetes and obesity in children and youth.
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Affiliation(s)
- Gulcin Akinci
- Department of Neurology, University of Michigan Medicine, Ann Arbor, MI
| | | | - Gary Gallagher
- Department of Neurology, University of Michigan Medicine, Ann Arbor, MI
| | | | - Eva L. Feldman
- Department of Neurology, University of Michigan Medicine, Ann Arbor, MI
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25
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Mohiuddin MS, Himeno T, Yamada Y, Morishita Y, Kondo M, Tsunekawa S, Kato Y, Nakamura J, Kamiya H. Glucagon Prevents Cytotoxicity Induced by Methylglyoxal in a Rat Neuronal Cell Line Model. Biomolecules 2021; 11:biom11020287. [PMID: 33672050 PMCID: PMC7919475 DOI: 10.3390/biom11020287] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Revised: 02/11/2021] [Accepted: 02/12/2021] [Indexed: 12/14/2022] Open
Abstract
Although diabetic polyneuropathy (DPN) is a frequent diabetic complication, no effective therapeutic approach has been established. Glucagon is a crucial hormone for glucose homeostasis but has pleiotropic effects, including neuroprotective effects in the central nervous system. However, the importance of glucagon in the peripheral nervous system (PNS) has not been clarified. Here, we hypothesized that glucagon might have a neuroprotective function in the PNS. The immortalized rat dorsal root ganglion (DRG) neuronal cell line 50B11 was treated with methylglyoxal (MG) to mimic an in vitro DPN model. The cells were cultured with or without glucagon or MG. Neurotoxicity, survival, apoptosis, neurite projection, cyclic adenosine monophosphate (cAMP), and protein kinase A (PKA) were examined. Glucagon had no cytotoxicity and rescued the cells from neurotoxicity. Cell survival was increased by glucagon. The ratio of apoptotic cells, which was increased by MG, was reduced by glucagon. Neurite outgrowth was accelerated in glucagon-treated cells. Cyclic AMP and PKA accumulated in the cells after glucagon stimulation. In conclusion, glucagon protected the DRG neuronal cells from MG-induced cellular stress. The cAMP/PKA pathway may have significant roles in those protective effects of glucagon. Glucagon may be a potential target for the treatment of DPN.
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Eleftheriadou A, Williams S, Nevitt S, Brown E, Roylance R, Wilding JPH, Cuthbertson DJ, Alam U. The prevalence of cardiac autonomic neuropathy in prediabetes: a systematic review. Diabetologia 2021; 64:288-303. [PMID: 33164108 PMCID: PMC7801295 DOI: 10.1007/s00125-020-05316-z] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Accepted: 09/10/2020] [Indexed: 02/07/2023]
Abstract
AIMS/HYPOTHESIS Cardiac autonomic neuropathy (CAN) is independently associated with silent myocardial ischaemia, major cardiovascular events, myocardial dysfunction and cardiovascular mortality. Several studies have highlighted the increased prevalence of CAN in prediabetes (impaired glucose tolerance and/or impaired fasting glucose). Considering the exponential rise of prediabetes, we aimed to determine the prevalence of CAN through a systematic literature review. METHODS This systematic review was registered with PROSPERO (CRD42019125447). An electronic literature search was performed using MEDLINE, EMBASE, PubMed, Web of Science, Scopus and Cochrane databases. Published full text, English language articles that provide CAN prevalence data of studies in individuals with prediabetes and aged over 18 years were included. Prevalence data for normal glucose tolerance and diabetes were also extracted from the selected articles, if present. All articles were screened by two independent reviewers using a priori criteria. Methodological quality and risk of bias were evaluated using a critical appraisal tool. RESULTS Database searches found 4500 articles; subsequently, 199 full text articles were screened, 11 of which fulfilled the inclusion criteria (4431 total participants, 1730 people with prediabetes, 1999 people with normal glucose tolerance [NGT] and 702 people with predominantly type 2 diabetes). Six of the selected studies reported definite CAN prevalence data (9-39%). Only a single large population-based study by Ziegler et al (KORA S4 study, 1332 participants) determined definite CAN based on two or more positive autonomic function tests (AFTs), with a mean prevalence of 9% in all prediabetes groups (isolated impaired glucose tolerance 5.9%; isolated impaired fasting glucose 8.1%; impaired fasting glucose plus impaired glucose tolerance 11.4%), which was higher than NGT (4.5%). This study is most likely to provide a reliable population-specific estimate of CAN in prediabetes. There was a higher than expected prevalence of CAN in prediabetes (9-38%) when compared with normal glucose tolerance (0-18%) within the same studies (n = 8). There was a wide prevalence of possible CAN based on one positive AFT (n = 5). There was heterogeneity between the studies with variations in the definition of CAN, methodology and characteristics of the populations, which likely contributed to the diversity of prevalence estimates. The overall risk of bias was low. CONCLUSIONS/INTERPRETATION There is a higher than expected prevalence of CAN in prediabetes. Early detection of CAN in prediabetes through population screening needs careful consideration in view of the excess morbidity and mortality risk associated with this condition. Graphical abstract.
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Affiliation(s)
- Aikaterini Eleftheriadou
- Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
| | - Scott Williams
- Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
| | - Sarah Nevitt
- Department of Biostatistics, University of Liverpool, Liverpool, UK
| | - Emily Brown
- Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
| | - Rebecca Roylance
- Edge Hill University Library, Aintree University Hospital NHS Foundation Trust, Liverpool, UK
| | - John P H Wilding
- Obesity and Endocrinology Research, Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
| | - Daniel J Cuthbertson
- Obesity and Endocrinology Research, Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK
| | - Uazman Alam
- Division of Diabetes, Endocrinology and Gastroenterology, Institute of Human Development, University of Manchester, Manchester, UK.
- Pain Research Institute and Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool and Aintree University Hospital NHS Foundation Trust, Liverpool, UK.
- Department of Diabetes and Endocrinology, Liverpool University Hospital NHS Trust, Liverpool, UK.
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Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, Federici M, Filippatos G, Grobbee DE, Hansen TB, Huikuri HV, Johansson I, Jüni P, Lettino M, Marx N, Mellbin LG, Östgren CJ, Rocca B, Roffi M, Sattar N, Seferović PM, Sousa-Uva M, Valensi P, Wheeler DC. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 2021; 41:255-323. [PMID: 31497854 DOI: 10.1093/eurheartj/ehz486] [Citation(s) in RCA: 2534] [Impact Index Per Article: 633.5] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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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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Vágvölgyi A, Maróti Á, Szűcs M, Póczik C, Urbán-Pap D, Baczkó I, Nemes A, Csajbók É, Sepp K, Kempler P, Orosz A, Várkonyi T, Lengyel C. Peripheral and Autonomic Neuropathy Status of Young Patients With Type 1 Diabetes Mellitus at the Time of Transition From Pediatric Care to Adult-Oriented Diabetes Care. Front Endocrinol (Lausanne) 2021; 12:719953. [PMID: 34512550 PMCID: PMC8430208 DOI: 10.3389/fendo.2021.719953] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 08/06/2021] [Indexed: 11/16/2022] Open
Abstract
INTRODUCTION The prevalence of neuropathic lesions in young patients with type 1 diabetes mellitus (T1DM) at the time of transition from pediatric care to adult-oriented diabetes care is poorly studied. A comparative study with healthy volunteers to assess the possible neuropathic condition of this special population and to identify the potential early screening needs has not been performed yet. The results may provide important feedback to pediatric diabetes care and a remarkable baseline reference point for further follow up in adult diabetes care. PATIENTS AND METHODS Twenty-nine young patients with T1DM [age: 22.4 ± 2.9 years; HbA1c: 8.5 ± 2.1%, diabetes duration: 12.2 ± 5.8 years; (mean ± SD)] and 30 healthy volunteers (age: 21.5 ± 1.6 years; HbA1c: 5.3 ± 0.3%) were involved in the study. Autonomic function was assessed by standard cardiovascular reflex tests. Complex peripheral neuropathic testing was performed by Neurometer®, Neuropad®-test, Tiptherm®, Monofilament®, and Rydel-Seiffer tuning fork tests. RESULTS T1DM patients had significantly higher diastolic blood pressure than controls (80 ± 9 vs. 74 ± 8 mmHg, p < 0.01), but there was no significant difference in systolic blood pressure (127 ± 26 vs. 121 ± 13 mmHg). Cardiovascular reflex tests had not revealed any significant differences between the T1DM patients and controls. No significant differences with Neurometer®, Neuropad®-test, and Monofilament® were detected between the two groups. The vibrational sensing on the radius on both sides was significantly impaired in the T1DM group compared to the controls with Rydel-Seiffer tuning fork test (right: 7.5 ± 1.0 vs. 7.9 ± 0.3; left: 7.5 ± 0.9 vs. 7.9 ± 0.3, p < 0.05). The Tiptherm®-test also identified a significant impairment in T1DM patients (11 sensing failures vs. 1, p < 0.001). In addition, the neuropathic complaints were significantly more frequently present in the T1DM patient group than in the controls (9 vs. 0, p < 0.01). CONCLUSION In this young T1DM population, cardiovascular autonomic neuropathy and cardiac morphological alterations could not be found. However, Rydel-Seiffer tuning fork and Tiptherm®-tests revealed peripheral sensory neurological impairments in young T1DM patients at the time of their transition to adult diabetes care.
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Affiliation(s)
- Anna Vágvölgyi
- Department of Medicine, University of Szeged, Szeged, Hungary
| | - Ágnes Maróti
- Department of Pediatrics and Pediatric Health Center, University of Szeged, Szeged, Hungary
| | - Mónika Szűcs
- Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary
| | - Csongor Póczik
- Department of Medicine, University of Szeged, Szeged, Hungary
| | - Dóra Urbán-Pap
- Department of Medical Physics and Informatics, University of Szeged, Szeged, Hungary
| | - István Baczkó
- Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary
- Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, University of Szeged, Szeged, Hungary
| | - Attila Nemes
- Department of Medicine, University of Szeged, Szeged, Hungary
| | - Éva Csajbók
- Department of Medicine, University of Szeged, Szeged, Hungary
| | - Krisztián Sepp
- Department of Medicine, University of Szeged, Szeged, Hungary
| | - Péter Kempler
- Department of Oncology and Internal Medicine, Semmelweis University, Budapest, Hungary
| | - Andrea Orosz
- Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary
- *Correspondence: Andrea Orosz,
| | - Tamás Várkonyi
- Department of Medicine, University of Szeged, Szeged, Hungary
| | - Csaba Lengyel
- Department of Medicine, University of Szeged, Szeged, Hungary
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Cheshire WP, Freeman R, Gibbons CH, Cortelli P, Wenning GK, Hilz MJ, Spies JM, Lipp A, Sandroni P, Wada N, Mano A, Ah Kim H, Kimpinski K, Iodice V, Idiáquez J, Thaisetthawatkul P, Coon EA, Low PA, Singer W. Electrodiagnostic assessment of the autonomic nervous system: A consensus statement endorsed by the American Autonomic Society, American Academy of Neurology, and the International Federation of Clinical Neurophysiology. Clin Neurophysiol 2020; 132:666-682. [PMID: 33419664 DOI: 10.1016/j.clinph.2020.11.024] [Citation(s) in RCA: 89] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 11/02/2020] [Accepted: 11/28/2020] [Indexed: 12/17/2022]
Abstract
Evaluation of disorders of the autonomic nervous system is both an art and a science, calling upon the physician's most astute clinical skills as well as knowledge of autonomic neurology and physiology. Over the last three decades, the development of noninvasive clinical tests that assess the function of autonomic nerves, the validation and standardization of these tests, and the growth of a large body of literature characterizing test results in patients with autonomic disorders have equipped clinical practice further with a valuable set of objective tools to assist diagnosis and prognosis. This review, based on current evidence, outlines an international expert consensus set of recommendations to guide clinical electrodiagnostic autonomic testing. Grading and localization of autonomic deficits incorporates scores from sympathetic cardiovascular adrenergic, parasympathetic cardiovagal, and sudomotor testing, as no single test alone is sufficient to diagnose the degree or distribution of autonomic failure. The composite autonomic severity score (CASS) is a useful score of autonomic failure that is normalized for age and gender. Valid indications for autonomic testing include generalized autonomic failure, regional or selective system syndromes of autonomic impairment, peripheral autonomic neuropathy and ganglionopathy, small fiber neuropathy, orthostatic hypotension, orthostatic intolerance, syncope, neurodegenerative disorders, autonomic hyperactivity, and anhidrosis.
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Affiliation(s)
- William P Cheshire
- Department of Neurology, Mayo Clinic, 4500 San Pablo Rd., Jacksonville, Florida 32224, USA
| | - Roy Freeman
- Department of Neurology, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215-5400, USA
| | - Christopher H Gibbons
- Department of Neurology, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215-5400, USA
| | - Pietro Cortelli
- DIBINEM - University of Bologna, Bologna, Italy; IRCCS Istituto di Scienze Neurologiche, Bologna, Italy
| | - Gregor K Wenning
- Section of Clinical Neurobiology, Department of Neurology, Medical University of Innsbruck, Anichstraße 35, A-6020 Innsbruck, Austria
| | - Max J Hilz
- Department of Neurology, University of Erlangen-Nuremberg, Schwabachanlage 6, Erlangen 91054, Germany
| | - Judith M Spies
- Department of Neurology, Level 8 East, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050, Australia
| | - Axel Lipp
- Park-Klinik Weißensee, Schönstraße 80, Berlin 13086, Germany
| | - Paola Sandroni
- Department of Neurology, Mayo Clinic, 200 First St. SW, Rochester, Minnesota 55905, USA
| | - Naoki Wada
- Department of Renal and Urologic Surgery, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa 078-8510, Japan
| | - Akiko Mano
- Department of Cardiothoracic Surgery, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakae-Cho Itabashi-ku, Tokyo 173-0015, Japan
| | - Hyun Ah Kim
- Department of Neurology, Keimyung University Dongsan Hospital, 2800 Dalgubeol Daero, Dalseo-gu, Daegu, South Korea
| | - Kurt Kimpinski
- School of Kinesiology, Western University, London, Ontario, Canada; Department of Clinical Neurological Sciences, University Hospital, London Health Sciences Centre, London, Ontario, Canada; Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada
| | - Valeria Iodice
- Autonomic Unit, National Hospital for Neurology and Neurosurgery, Queen Square, Division of Clinical Neurology, Institute of Neurology, University College London, WC1N 3BG London, United Kingdom
| | - Juan Idiáquez
- Department of Neurologia, Facultad de Medicina, University of Valparaíso, 7 Norte 1122, Valparaíso, 2531094, Chile
| | - Pariwat Thaisetthawatkul
- Department of Neurological Sciences, 988435 University of Nebraska Medical Center, Omaha, Nebraska 68198-8435, USA
| | - Elizabeth A Coon
- Department of Neurology, Mayo Clinic, 200 First St. SW, Rochester, Minnesota 55905, USA
| | - Phillip A Low
- Department of Neurology, Mayo Clinic, 200 First St. SW, Rochester, Minnesota 55905, USA.
| | - Wolfgang Singer
- Department of Neurology, Mayo Clinic, 200 First St. SW, Rochester, Minnesota 55905, USA.
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Decreased glomerular filtration rate and increased albuminuria for identification of cardiovascular autonomic neuropathy in subjects with and without diabetes. Auton Neurosci 2020; 230:102757. [PMID: 33316751 DOI: 10.1016/j.autneu.2020.102757] [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: 05/11/2019] [Revised: 02/21/2020] [Accepted: 11/22/2020] [Indexed: 10/22/2022]
Abstract
OBJECTIVE The purpose of this study was to determine the relationship between chronic kidney disease (CKD) and cardiovascular autonomic neuropathy (CAN). RESEARCH DESIGN AND METHODS From October 2008 to May 2011, we enrolled 218 patients with diabetes and 62 nondiabetic subjects. Heart rate variability was represented as the maximal heart rate minus the minimal heart rate (HRmax-min) during a one-minute deep breathing test. Normal, impaired cardiovascular autonomic function and CAN were defined as s HRmax-min > 15 beats/min, HRmax-min of 10-15 beats/min and HRmax-min < 10 beats/min, respectively. CKD was diagnosed if the estimated glomerular filtration rate (eGFR) was <60/min/1.73 m2 or albuminuria. RESULTS In our sample, 19.4% of nondiabetic subjects and 49.5% of diabetic subjects had CKD. The prevalence of CAN was higher among patients with diabetes than among nondiabetic subjects (26.4 vs. 4.9%). A significant association was observed between eGFR and HRmax-min. CAN was independently associated with CKD with an adjusted odds ratio of 2.77 (95% CI, 1.15-6.68) in diabetic patients. A positive linear trend was observed for the odds of CAN with increasing CKD severity in diabetes. The areas under the curve (AUCs) for the predictive ability of eGFR for the risk of impaired cardiovascular autonomic function for nondiabetic group and CAN for the diabetic group were 0.734 and 0.703, respectively. Adding age, sex, body mass index, and albuminuria to the prediction model increased the AUCs to 0.852 and 0.791, respectively. CONCLUSION CKD is associated with the risk of CAN in both nondiabetic and diabetic subjects. eGFR and albuminuria improve the prediction of CAN.
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Porter JA, MacKenzie KE, Darlow BA, Pearson JF, Day AS. A questionnaire-based assessment of gastrointestinal symptoms in children with type 1 diabetes mellitus. Transl Pediatr 2020; 9:743-749. [PMID: 33457295 PMCID: PMC7804482 DOI: 10.21037/tp-20-139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Children commonly report gastrointestinal symptoms. Limited evidence suggests that children with type 1 diabetes mellitus (T1DM) report more gastrointestinal symptoms than healthy children without diabetes. The aim of this study was to ascertain the pattern and severity gastrointestinal symptoms reported by children with diabetes and healthy children without diabetes. METHODS After recruitment, children (less than 16 years of age) with type 1 diabetes and healthy control children reported their recent gastrointestinal symptoms using a short questionnaire. A five-point Likert scale was utilised to grade the severity of each symptom and an overall symptom score for each child was derived. RESULTS One hundred and fifty cases (88% of eligible population) and 94 controls completed the questionnaire. Both groups had similarly high rates of any gastrointestinal symptom [80% of controls vs. 85% cases, OR 1.5 (95% CI: 0.7-3.1)]. Children with diabetes had higher mean scores for abdominal pain (1.3 vs. 1.0, P=0.02) and reflux (0.4 vs. 0.20, P=0.02). Cases also had a higher overall mean score than controls (4.9 vs. 3.4, P=0.02). CONCLUSIONS Overall, gastrointestinal symptoms were reported at the same frequency by both groups of children. However, the children with diabetes had more severe symptoms, especially those of reflux and abdominal pain. The reasons for these differences remain to be elucidated.
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Affiliation(s)
- Jody A Porter
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand.,Department of Paediatrics, Christchurch Hospital, Christchurch, New Zealand
| | - Karen E MacKenzie
- Department of Paediatrics, Christchurch Hospital, Christchurch, New Zealand
| | - Brian A Darlow
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand
| | - John F Pearson
- Department of Population Health, University of Otago Christchurch, Christchurch, New Zealand
| | - Andrew S Day
- Department of Paediatrics, University of Otago Christchurch, Christchurch, New Zealand.,Department of Paediatrics, Christchurch Hospital, Christchurch, New Zealand
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Leptin mediate central obesity on the severity of cardiovascular autonomic neuropathy in well-controlled type 2 diabetes and prediabetes. J Transl Med 2020; 18:396. [PMID: 33076921 PMCID: PMC7574496 DOI: 10.1186/s12967-020-02559-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 10/03/2020] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Evidences support the view that central obesity is an independently cardiovascular risk. It is thought that leptin contributes to autonomic dysfunction and cardiovascular risks in type 1 and type 2 diabetes mellitus (T1DM and T2DM). This raises the possibility that leptin might mediate the relationship between central obesity and the severity of cardiovascular autonomic neuropathy (CAN) in patients with well-controlled T2DM and prediabetes. METHODS The complete cardiovascular reflex tests and biomarkers were assessed for each patient. The severity of CAN was assessed using composite autonomic scoring scale (CASS). A single-level three-variable mediation model was used to investigate the possible relationships among central obesity [as indicated by waist circumference (WC)], leptin level, and severity of CAN (as indicated by CASS value). RESULTS A total of 107 patients were included in this study: 90 with diabetes and 17 with prediabetes. The results demonstrate that increased WC is associated with increased severity of CAN (r = 0.242, P = 0.017). We further discovered that leptin level is positively correlated with WC (r = 0.504, P < 0.0001) and the CASS value (r = 0.36, P < 0.0001). Further mediation analysis shows that leptin level serves as mediators between higher WC and higher CASS. CONCLUSIONS Our results highlighted the relationship among leptin, central obesity, and severity of CAN. As the leptin level serves as mediator between central obesity and severity of CAN, a longitudinal study is needed to confirm that control of WC can decrease leptin levels and can be effective in reducing CAN progression.
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Agochukwu-Mmonu N, Pop-Busui R, Wessells H, Sarma AV. Autonomic neuropathy and urologic complications in diabetes. Auton Neurosci 2020; 229:102736. [PMID: 33197694 DOI: 10.1016/j.autneu.2020.102736] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2019] [Revised: 05/21/2020] [Accepted: 10/05/2020] [Indexed: 12/31/2022]
Abstract
Diabetic autonomic neuropathy affects the entire autonomic nervous system and can lead to dysfunction of the cardiovascular, gastrointestinal, and genitourinary organ systems. Genitourinary dysfunction associated with diabetic autonomic neuropathy includes diabetic bladder dysfunction, sexual dysfunction, and recurrent urinary tract infections. Urological complications in diabetes mellitus are very common; in fact, genitourinary complications are more common than diabetic neuropathy or nephropathy. While several studies have reported on genitourinary dysfunction in individuals with diabetes, UroEDIC, an ancillary study to the Diabetes Control and Complications Trial (DCCT) and its observational follow up, the Epidemiology of Diabetes Interventions and Complications study (EDIC), comprehensively characterized the association between urologic complications and cardiovascular autonomic neuropathy. UroEDIC demonstrated significant associations between autonomic neuropathy and urologic complications in type 1 diabetes, specifically erectile dysfunction, female sexual dysfunction, and lower urinary tract symptoms. In this narrative review, we review the current literature on urological complications in diabetes.
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Affiliation(s)
| | - Rodica Pop-Busui
- Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States of America
| | - Hunter Wessells
- Department of Urology, University of Washington School of Medicine, Seattle, WA, United States of America
| | - Aruna V Sarma
- Department of Urology, University of Michigan, Ann Arbor, MI, United States of America
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Zilliox LA, Russell JW. Is there cardiac autonomic neuropathy in prediabetes? Auton Neurosci 2020; 229:102722. [PMID: 33011523 DOI: 10.1016/j.autneu.2020.102722] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 06/09/2020] [Accepted: 08/24/2020] [Indexed: 02/09/2023]
Abstract
Although there is considerably more data showing an association between type 2 diabetes mellitus (T2DM) and autonomic neuropathy, accumulating evidence indicates that cardiovascular autonomic neuropathy (CAN) is common in persons with impaired glucose tolerance (IGT). Furthermore, CAN may occur early after a metabolic insult and obesity, especially among mean, and seems to play an important role in the early pathogenesis of CAN. Autonomic symptoms are common in subjects with IGT. In addition to defects in CAN, in subjects with IGT, there is impaired sudomotor function and abnormalities of endothelial peripheral vasoreactivity. At the present time, the only interventions that may be effective in preventing or reversing IGT associated autonomic neuropathy are lifestyle improvement. These include a tailored diet and exercise program. Other approaches that may be beneficial include modulation of oxidative stress and improvement of metabolic regulation in subjects with IGT. Interventions are most likely to be effective early in the course of disease and therefore it is extremely important to have early diagnosis of IGT and autonomic neuropathy.
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Affiliation(s)
- Lindsay A Zilliox
- Department of Neurology, University of Maryland and Maryland VA Healthcare System, Baltimore, MD, United States of America
| | - James W Russell
- Department of Neurology, University of Maryland and Maryland VA Healthcare System, Baltimore, MD, United States of America.
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Azmi S, Alam U, Burgess J, Malik RA. State-of-the-art pharmacotherapy for diabetic neuropathy. Expert Opin Pharmacother 2020; 22:55-68. [PMID: 32866410 DOI: 10.1080/14656566.2020.1812578] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION The global epidemic of diabetes has led to an epidemic of diabetes complications. Diabetic neuropathy is the most common microvascular complication, of which diabetic peripheral neuropathy (DPN) and autonomic neuropathy (AN) are the most prevalent, affecting ~50% of patients. DPN results in pain with a poor quality of life and a loss of sensation with an increased risk of foot ulceration. Autonomic neuropathy can cause significant morbidity in a minority and is associated with increased mortality. The cornerstone of treatment to prevent or limit the progression of DPN/AN is multifactorial risk factor modification including treatment of glycemia, lipids and blood pressure. Whilst, there are no FDA-approved disease-modifying therapies, there are a number of therapies to relieve symptoms in DPN and AN. AREAS COVERED The authors discuss current approved therapies for painful diabetic neuropathy and autonomic neuropathy. They also address the potential role of improving risk factors to limit the development and progression of diabetic neuropathy and new pathogenetic and pain-relieving treatments. EXPERT OPINION The FDA-approved Pregabalin and Duloxetine over 25 years ago and Tapentadol, 6 years ago for painful diabetic neuropathy. There are currently no FDA-approved disease-modifying treatments for diabetic neuropathy which has been attributed to inappropriate models of the disease with limited translational capacity and major limitations of trial designs and endpoints in clinical trials.
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Affiliation(s)
- Shazli Azmi
- Institute of Cardiovascular Science, University of Manchester and Manchester NHS Foundation Trust , Manchester, UK
| | - Uazman Alam
- Division of Diabetes, Endocrinology and Gastroenterology, Institute of Human Development, University of Manchester , Manchester, UK.,Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool , Liverpool, UK.,Department of Diabetes and Endocrinology, Liverpool University Hospital NHS Foundation Trust , Liverpool, UK
| | - Jamie Burgess
- Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool , Liverpool, UK
| | - Rayaz A Malik
- Department of Medicine, Weill Cornell Medicine-Qatar , Doha, Qatar
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Araki E, Goto A, Kondo T, Noda M, Noto H, Origasa H, Osawa H, Taguchi A, Tanizawa Y, Tobe K, Yoshioka N. Japanese Clinical Practice Guideline for Diabetes 2019. Diabetol Int 2020; 11:165-223. [PMID: 32802702 PMCID: PMC7387396 DOI: 10.1007/s13340-020-00439-5] [Citation(s) in RCA: 267] [Impact Index Per Article: 53.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Indexed: 01/09/2023]
Affiliation(s)
- Eiichi Araki
- Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Atsushi Goto
- Department of Health Data Science, Graduate School of Data Science, Yokohama City University, Yokohama, Japan
| | - Tatsuya Kondo
- Department of Diabetes, Metabolism and Endocrinology, Kumamoto University Hospital, Kumamoto, Japan
| | - Mitsuhiko Noda
- Department of Diabetes, Metabolism and Endocrinology, Ichikawa Hospital, International University of Health and Welfare, Ichikawa, Japan
| | - Hiroshi Noto
- Division of Endocrinology and Metabolism, St. Luke’s International Hospital, Tokyo, Japan
| | - Hideki Origasa
- Department of Biostatistics and Clinical Epidemiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
| | - Haruhiko Osawa
- Department of Diabetes and Molecular Genetics, Ehime University Graduate School of Medicine, Toon, Japan
| | - Akihiko Taguchi
- Department of Endocrinology, Metabolism, Hematological Science and Therapeutics, Graduate School of Medicine, Yamaguchi University, Ube, Japan
| | - Yukio Tanizawa
- Department of Endocrinology, Metabolism, Hematological Science and Therapeutics, Graduate School of Medicine, Yamaguchi University, Ube, Japan
| | - Kazuyuki Tobe
- First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
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Araki E, Goto A, Kondo T, Noda M, Noto H, Origasa H, Osawa H, Taguchi A, Tanizawa Y, Tobe K, Yoshioka N. Japanese Clinical Practice Guideline for Diabetes 2019. J Diabetes Investig 2020; 11:1020-1076. [PMID: 33021749 PMCID: PMC7378414 DOI: 10.1111/jdi.13306] [Citation(s) in RCA: 176] [Impact Index Per Article: 35.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2020] [Accepted: 05/24/2020] [Indexed: 01/09/2023] Open
Affiliation(s)
- Eiichi Araki
- Department of Metabolic MedicineFaculty of Life SciencesKumamoto UniversityKumamotoJapan
| | - Atsushi Goto
- Department of Health Data ScienceGraduate School of Data ScienceYokohama City UniversityYokohamaJapan
| | - Tatsuya Kondo
- Department of Diabetes, Metabolism and EndocrinologyKumamoto University HospitalKumamotoJapan
| | - Mitsuhiko Noda
- Department of Diabetes, Metabolism and EndocrinologyIchikawa HospitalInternational University of Health and WelfareIchikawaJapan
| | - Hiroshi Noto
- Division of Endocrinology and MetabolismSt. Luke's International HospitalTokyoJapan
| | - Hideki Origasa
- Department of Biostatistics and Clinical EpidemiologyGraduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
| | - Haruhiko Osawa
- Department of Diabetes and Molecular GeneticsEhime University Graduate School of MedicineToonJapan
| | - Akihiko Taguchi
- Department of Endocrinology, Metabolism, Hematological Science and TherapeuticsGraduate School of MedicineYamaguchi UniversityUbeJapan
| | - Yukio Tanizawa
- Department of Endocrinology, Metabolism, Hematological Science and TherapeuticsGraduate School of MedicineYamaguchi UniversityUbeJapan
| | - Kazuyuki Tobe
- First Department of Internal MedicineGraduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyamaJapan
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Matsumoto A, Kuwata H, Kimura S, Matsumoto H, Ochi K, Moro-Oka Y, Watanabe A, Yamada H, Ishii H, Miyazawa T, Chen S, Baba T, Yoshida H, Nakamura T, Inoue H, Ogawa Y, Tanaka M, Miyahara Y, Suganami T. Hollow fiber-combined glucose-responsive gel technology as an in vivo electronics-free insulin delivery system. Commun Biol 2020; 3:313. [PMID: 32555343 PMCID: PMC7299969 DOI: 10.1038/s42003-020-1026-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Accepted: 05/21/2020] [Indexed: 12/18/2022] Open
Abstract
Accumulating evidence demonstrates that not only sustained elevation of blood glucose levels but also the glucose fluctuation represents key determinants for diabetic complications and mortality. Current closed-loop insulin therapy option is limited to the use of electronics-based systems, although it poses some technical issues with high cost. Here we demonstrate an electronics-free, synthetic boronate gel-based insulin-diffusion-control device technology that can cope with glucose fluctuations and potentially address the electronics-derived issues. The gel was combined with hemodialysis hollow fibers and scaled suitable for rats, serving as a subcutaneously implantable, insulin-diffusion-active site in a manner dependent on the subcutaneous glucose. Continuous glucose monitoring tests revealed that our device not only normalizes average glucose level of rats, but also markedly ameliorates the fluctuations over timescale of a day without inducing hypoglycemia. With inherent stability, diffusion-dependent scalability, and week-long & acute glucose-responsiveness, our technology may offer a low-cost alternative to current electronics-based approaches.
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MESH Headings
- Animals
- Blood Glucose/metabolism
- Diabetes Mellitus, Experimental/blood
- Diabetes Mellitus, Experimental/drug therapy
- Diabetes Mellitus, Type 1/blood
- Diabetes Mellitus, Type 1/drug therapy
- Drug Liberation
- Electronics
- Equipment Design
- Gels/chemistry
- Insulin/administration & dosage
- Insulin/pharmacokinetics
- Insulin Infusion Systems
- Insulin, Regular, Human/administration & dosage
- Insulin, Regular, Human/genetics
- Kidneys, Artificial
- Male
- Models, Theoretical
- Rats, Sprague-Dawley
- Temperature
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Affiliation(s)
- Akira Matsumoto
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan.
- Kanagawa Institute of Industrial Science and Technology, Ebina, Japan.
| | - Hirohito Kuwata
- Department of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
- Department of Diabetes and Endocrine Medicine, Nara Medical University, Kashihara, Japan
| | - Shinichiro Kimura
- Department of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hiroko Matsumoto
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan
- Kanagawa Institute of Industrial Science and Technology, Ebina, Japan
| | - Kozue Ochi
- Department of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
| | - Yuki Moro-Oka
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan
| | - Akiko Watanabe
- Department of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
| | - Hironori Yamada
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hitoshi Ishii
- Department of Doctor-Patient Relationships, Nara Medical University, Kashihara, Japan
| | - Taiki Miyazawa
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan
| | - Siyuan Chen
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan
- Kanagawa Institute of Industrial Science and Technology, Ebina, Japan
| | - Toshiaki Baba
- Research and Development Center, Medical Technology Division for Planning, Development and Marketing, Nipro Corporation, Kusatsu, Japan
| | - Hiroshi Yoshida
- Research and Development Center, Medical Technology Division for Planning, Development and Marketing, Nipro Corporation, Kusatsu, Japan
| | - Taichi Nakamura
- CAE Department, Advanced Technical Department, Nikon Systems Inc., Tokyo, Japan
| | - Hiroshi Inoue
- Metabolism and Nutrition Research Unit, Institute for Frontier Science Initiative, Kanazawa University, Kanazawa, Japan
| | - Yoshihiro Ogawa
- Department of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Miyako Tanaka
- Department of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan
- Department of Immunometabolism, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Yuji Miyahara
- Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Tokyo, Japan
| | - Takayoshi Suganami
- Department of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
- Department of Immunometabolism, Nagoya University Graduate School of Medicine, Nagoya, Japan.
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Gregory GA, Guo J, Klatman EL, Ahmadov GA, Besançon S, Gomez ED, Fawwad A, Ramaiya K, Wijesuriya MA, Orchard TJ, Ogle GD. Costs and outcomes of "intermediate" vs "minimal" care for youth-onset type 1 diabetes in six countries. Pediatr Diabetes 2020; 21:628-636. [PMID: 31970828 DOI: 10.1111/pedi.12988] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 12/02/2019] [Accepted: 01/13/2020] [Indexed: 12/11/2022] Open
Abstract
OBJECTIVE Data are needed to demonstrate that providing an "intermediate" level of type 1 diabetes (T1D) care is cost-effective compared to "minimal" care in less-resourced countries. We studied these care scenarios in six countries. METHODS We modeled the complications/costs/mortality/healthy life years (HLYs) associated with "intermediate" care including two blood glucose tests/day (mean HbA1c 9.0% [75 mmol/mol]) in three lower-gross domestic product (GDP) countries (Mali, Tanzania, Pakistan), or three tests/day (mean HbA1c 8.5% [69 mmol/mol]) in three higher-GDP countries (Bolivia, Sri Lanka, Azerbaijan); and compared findings to "minimal" care (mean HbA1c 12.5% [113 mmol/mol]). A discrete time Markov illness-death model with age and calendar-year-dependent transition probabilities was developed, with inputs of 30 years of complications and Standardized Mortality Rate data from the youth cohort in the Pittsburgh Epidemiology of Diabetes Complications Study, background mortality, and costs determined from international and local prices. RESULTS Cumulative 30 years incidences of complications were much lower for "intermediate care" than "minimal care", for example, for renal failure incidence was 68.1% (HbA1c 12.5%) compared to 3.9% (9%) and 2.4% (8.5%). For Mali, Tanzania, Pakistan, Bolivia, Sri Lanka, and Azerbaijan, 30 years survival was 50.1%/52.7%/76.7%/72.5%/82.8%/89.2% for "intermediate" and 8.5%/10.1%/39.4%/25.8%/45.5%/62.1% for "minimal" care, respectively. The cost of a HLY gained as a % GDP/capita was 141.1%/110.0%/52.3%/41.8%/17.0%/15.6%, respectively. CONCLUSIONS Marked reductions in complications rates and mortality are achievable with "intermediate" T1D care achieving mean clinic HbA1c of 8.5% to 9% (69-75 mmol/mol). This is also "very cost-effective" in four of six countries according to the WHO "Fair Choices" approach which costs HLYs gained against GDP/capita.
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Affiliation(s)
- Gabriel A Gregory
- Life for a Child Program, Diabetes NSW, Glebe, New South Wales, Australia.,Sydney Medical School, University of Sydney, Sydney, Australia
| | - Jingchuan Guo
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Emma L Klatman
- Life for a Child Program, Diabetes NSW, Glebe, New South Wales, Australia
| | - Gunduz A Ahmadov
- The Endocrine Center, Baku, Azerbaijan.,Azerbaijan Medical University, Baku, Azerbaijan
| | | | | | - Asher Fawwad
- Baqai Institute of Diabetology and Endocrinology, Baqai Medical University, Karachi, Pakistan
| | | | - Mahen A Wijesuriya
- Diabetes Association of Sri Lanka, National Diabetes Centre, Colombo, Sri Lanka
| | - Trevor J Orchard
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Graham D Ogle
- Life for a Child Program, Diabetes NSW, Glebe, New South Wales, Australia.,Sydney Medical School, University of Sydney, Sydney, Australia
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Braffett BH, Gubitosi-Klug RA, Albers JW, Feldman EL, Martin CL, White NH, Orchard TJ, Lopes-Virella M, Lachin JM, Pop-Busui R. Risk Factors for Diabetic Peripheral Neuropathy and Cardiovascular Autonomic Neuropathy in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study. Diabetes 2020; 69:1000-1010. [PMID: 32051148 PMCID: PMC7171957 DOI: 10.2337/db19-1046] [Citation(s) in RCA: 118] [Impact Index Per Article: 23.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 02/07/2020] [Indexed: 12/19/2022]
Abstract
The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study demonstrated that intensive glucose control reduced the risk of developing diabetic peripheral neuropathy (DPN) and cardiovascular autonomic neuropathy (CAN). We evaluated multiple risk factors and phenotypes associated with DPN and CAN in this large, well-characterized cohort of participants with type 1 diabetes, followed for >23 years. DPN was defined by symptoms, signs, and nerve conduction study abnormalities in ≥2 nerves; CAN was assessed using standardized cardiovascular reflex tests. Generalized estimating equation models assessed the association of DPN and CAN with individual risk factors measured repeatedly. During DCCT/EDIC, 33% of participants developed DPN and 44% CAN. Higher mean HbA1c was the most significant risk factor for DPN, followed by older age, longer duration, greater height, macroalbuminuria, higher mean pulse rate, β-blocker use, and sustained albuminuria. The most significant risk factor for CAN was older age, followed by higher mean HbA1c, sustained albuminuria, longer duration of type 1 diabetes, higher mean pulse rate, higher mean systolic blood pressure, β-blocker use, estimated glomerular filtration rate <60 mL/min/1.73 m2, higher most recent pulse rate, and cigarette smoking. These findings identify risk factors and phenotypes of participants with diabetic neuropathy that can be used in the design of new interventional trials and for personalized approaches to neuropathy prevention.
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Affiliation(s)
| | - Rose A Gubitosi-Klug
- Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, OH
| | | | - Eva L Feldman
- University of Michigan Medical School, Ann Arbor, MI
| | | | - Neil H White
- Washington University School of Medicine in St. Louis, St Louis, MO
| | - Trevor J Orchard
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA
| | - Maria Lopes-Virella
- Department of Medicine, Medical University of South Carolina, Charleston, SC
| | - John M Lachin
- Biostatistics Center, George Washington University, Rockville, MD
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Ang L, Dillon B, Mizokami-Stout K, Pop-Busui R. Cardiovascular autonomic neuropathy: A silent killer with long reach. Auton Neurosci 2020; 225:102646. [PMID: 32106052 DOI: 10.1016/j.autneu.2020.102646] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 01/30/2020] [Accepted: 02/11/2020] [Indexed: 02/07/2023]
Abstract
Cardiovascular autonomic neuropathy (CAN) is a common and deadly complication of diabetes mellitus, which is frequently overlooked in clinical practice due to its characteristic subtle presentation earlier in disease. Yet, timely detection of CAN may help implementation of tailored interventions to prevent its progression and mitigate the risk of associated complications, including cardiovascular disease (CVD), cardiac arrhythmias, myocardial dysfunction leading to congestive heart failure and all-cause mortality. This review highlights current CAN epidemiology trends, novel mechanisms linking CAN with other diabetes complications and current recommendations for diagnosis and management of the disease in the clinical setting.
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Affiliation(s)
- Lynn Ang
- Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, United States of America
| | - Brendan Dillon
- University of Michigan Medical School, Ann Arbor, MI, United States of America
| | - Kara Mizokami-Stout
- Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, United States of America
| | - Rodica Pop-Busui
- Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, United States of America.
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43
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Guía ESC 2019 sobre diabetes, prediabetes y enfermedad cardiovascular, en colaboración con la European Association for the Study of Diabetes (EASD). Rev Esp Cardiol 2020. [DOI: 10.1016/j.recesp.2019.11.024] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Gastoł J, Kapusta P, Polus A, Pitera E, Biela M, Wołkow P, Pawliński Ł, Kieć-Wilk B. Epigenetic mechanism in search for the pathomechanism of diabetic neuropathy development in diabetes mellitus type 1 (T1DM). Endocrine 2020; 68:235-240. [PMID: 31902112 DOI: 10.1007/s12020-019-02172-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2019] [Accepted: 12/23/2019] [Indexed: 11/30/2022]
Abstract
OBJECTIVE The aim of this study was to check the hypothesis concerning the crucial role of DNA methylation (one of the epigenetic mechanisms) within selected genes related to the destruction and regeneration of neural cells and its input in the pathogenesis of diabetic neuropathy, using a model of the DNA in peripheral blood cells. METHODS A cross-sectional, case-control study was conducted, consisting of 24 adult Type 1 Diabetes Melitus (T1DM) patients with autonomic neuropathy (CAN), 25 T1DM patients without neuropathy and 25 matched, healthy adults acting as a control (Ctrl). The Ewing's tests, using the ProSciCard apparatus (Mewicon CATEEM-Tec GmbH), was employed to assess the severity of the patients' symptoms of autonomic neuropathy. For DNA methylation analysis, DNA material of each sample DNA after bisulfite conversion was used for the hybridization of BeadChips (Infinium Methylation EPIC Kit, Illumina), and imaged on the Illumina HiScan. The changes in the expression of selected genes were examined using real-time PCR. Probes were labeled using fluorescein amidite, FAM (Thermo Fisher Scientific). Amplification was performed using the continuous fluorescence detection 7900 HT Fast Real-Time PCR system (Thermo Fisher Scientific). The expression ratio of the target mRNA was normalized to the level of 18s RNA and compared with the control. Statistical analysis was performed using Statistica version 13.1. The statistically significant results were recognized, with a value of p < 0.05. RESULTS Clinical analysis of the investigated groups revealed a significantly higher percentage of personal insulin pump users in the group without neuropathy. The glucose metabolic control, based on the HbA1c level analysis, was also significantly better in T1DM patients without CAN. The Bumphunter method for DNA methylation analysis showed statistically significant regions related to the genes involved in nerve regeneration ninjurin 2 (NINJ2) and functionality (BR serine/threonine kinase 2 BRSK2, claudin 4 CLDN4). When compared with T1DM patients without neuropathy, T1DM patients with neuropathy showed significantly increased methylation in the first NINJ2 axon, and a lower level of DNA methylation in the region of the first intron of BRSK2, as well as the CLDN4 5'UTR regions. The qRT-PCR results confirmed the decreased expression of NINJ2 and CLDN4 genes in patients with T1DM with CAN. CONCLUSIONS The different DNA methylation profiles, correlating with the expression of genes related to nervous tissue development and regeneration in patients with T1DM with autonomic neuropathy provide evidence for the role of epigenetic mechanisms promoting the development of CAN, a chronic complication of T1DM.
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Affiliation(s)
| | - Przemysław Kapusta
- Center for Medical Genomics- Omicron, Jagiellonian University Medical College, Kraków, Poland
| | - Anna Polus
- Department of Clinical Biochemistry, Jagiellonian University Medical College, Kraków, Poland
| | - Ewelina Pitera
- Center for Medical Genomics- Omicron, Jagiellonian University Medical College, Kraków, Poland
| | - Maria Biela
- Department of Clinical Biochemistry, Jagiellonian University Medical College, Kraków, Poland
| | - Paweł Wołkow
- Center for Medical Genomics- Omicron, Jagiellonian University Medical College, Kraków, Poland
| | | | - Beata Kieć-Wilk
- University Hospital in Krakow, Kraków, Poland.
- Department of Metabolic Diseases, Jagiellonian University Medical College, Kraków, Poland.
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Ardeleanu V, Toma A, Pafili K, Papanas N, Motofei I, Diaconu CC, Rizzo M, Pantea Stoian A. Current Pharmacological Treatment of Painful Diabetic Neuropathy: A Narrative Review. ACTA ACUST UNITED AC 2020; 56:medicina56010025. [PMID: 31936646 PMCID: PMC7022869 DOI: 10.3390/medicina56010025] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2019] [Revised: 01/03/2020] [Accepted: 01/06/2020] [Indexed: 02/07/2023]
Abstract
Background and Objectives: Distal symmetrical polyneuropathy (DSPN) is one of the most common chronic complications of diabetes mellitus. Although it is usually characterized by progressive sensory loss, some patients may develop chronic pain. Assessment of DSPN is not difficult, but the biggest challenge is making the correct diagnosis and choosing the right treatment. The treatment of DSPN has three primary objectives: glycemic control, pathogenic mechanisms, and pain management. The aim of this brief narrative review is to summarize the current pharmacological treatment of painful DSPN. It also summarizes knowledge on pathogenesis-oriented therapy, which is generally overlooked in many publications and guidelines. Materials and Methods: The present review reports the relevant information available on DSPN treatment. The search was performed on PubMed, Cochrane, Semantic Scholar, Medline, Scopus, and Cochrane Library databases, including among others the terms "distal symmetrical polyneuropathy", "neuropathic pain treatment", "diabetic neuropathy", "diabetes complications", "glycaemic control", "antidepressants", "opioids", and "anticonvulsants". Results: First-line drugs include antidepressants (selective serotonin reuptake inhibitors and tricyclic antidepressants) and pregabalin. Second- and third-line drugs include opioids and topical analgesics. While potentially effective in the treatment of neuropathic pain, opioids are not considered to be the first choice because of adverse reactions and addiction concerns. Conclusions: DSPN is a common complication in patients with diabetes, and severely affects the quality of life of these patients. Although multiple therapies are available, the guidelines and recommendations regarding the treatment of diabetic neuropathy have failed to offer a unitary consensus, which often hinders the therapeutic options in clinical practice.
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Affiliation(s)
- Valeriu Ardeleanu
- Department of Surgery, University “Dunarea de Jos”, 800008 Galati, Romania;
- Department of Surgery, University “Ovidius’’, 900470 Constanta, Romania
- Arestetic Clinic, 800098 Galati, Romania
| | - Alexandra Toma
- Department of Surgery, University “Dunarea de Jos”, 800008 Galati, Romania;
- Department of Surgery, Emergency County Clinical Hospital “Sf. Apostol Andrei”, 800578 Galati, Romania
- Correspondence: (A.T.); (A.P.S.)
| | - Kalliopi Pafili
- Second Department of Internal Medicine, Diabetes Centre-Diabetic Foot Clinic, Democritus University of Thrace, University Hospital of Alexandroupolis, 681 00 Alexandroupolis, Greece; (K.P.); (N.P.)
| | - Nikolaos Papanas
- Second Department of Internal Medicine, Diabetes Centre-Diabetic Foot Clinic, Democritus University of Thrace, University Hospital of Alexandroupolis, 681 00 Alexandroupolis, Greece; (K.P.); (N.P.)
| | - Ion Motofei
- Department of Surgery, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Camelia Cristina Diaconu
- Internal Medicine Department, Clinical Emergency Hospital of Bucharest, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Manfredi Rizzo
- Biomedical Department of Internal Medicine and Medical Specialties School of Medicine, University of Palermo, 90133 Palermo, Italy;
- Division of Endocrinology, Diabetes and Metabolism, University of South Carolina School of Medicine Columbia, Columbia, SC 29209, USA
| | - Anca Pantea Stoian
- Diabetes, Nutrition and Metabolic Diseases Department, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania
- Correspondence: (A.T.); (A.P.S.)
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Šimonienė D, Platūkiene A, Prakapienė E, Radzevičienė L, Veličkiene D. Insulin Resistance in Type 1 Diabetes Mellitus and Its Association with Patient's Micro- and Macrovascular Complications, Sex Hormones, and Other Clinical Data. Diabetes Ther 2020; 11:161-174. [PMID: 31792784 PMCID: PMC6965600 DOI: 10.1007/s13300-019-00729-5] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2019] [Indexed: 02/07/2023] Open
Abstract
INTRODUCTION The main objective of this research was to evaluate the association of insulin resistance (IR) with micro- and macrovascular complications, sex hormones, and other clinical data. METHODS Cross-sectional study of patients older than 18 years old with type 1 diabetes mellitus (T1DM) was performed. Participants filled in questionnaires about T1D, disease duration, smoking, glycemic control, chronic diabetes complications, and hypertension status. Data about chronic diabetic complications (neuropathy, retinopathy, and nephropathy) were collected from medical records. History of major cardiovascular events such as angina, myocardial infarction, and stroke were collected from medical records also. Laboratory tests including creatinine, cholesterol levels, testosterone (T), sex hormone-binding globulin (SHBG), estradiol levels, and albumin in 24-h urine sample were performed. IR was calculated using the following formula: estimated glucose disposal rate (eGDR) = 24.31 - [12.22 × waist-to-hip ratio (WHR)] - [3.29 × hypertension status (defined as 0 = no, 1 = yes)] - [0.57 × glycated hemoglobin (HbA1c)]. The data was considered statistically significant at p < 0.05. RESULTS A total of 200 people (mean age 39.9 ± 12.1 years) with T1D were included in the study. Patients with T1D were analyzed according to eGDR levels stratified by tertiles. The cutoff value of eGDR which reflects IR was less than 6.4 mg kg-1 min-1. When eGDR was less than 6.4 mg kg-1 min-1, diabetes microvascular complications occurred significantly more often (p < 0.001); the cutoff of eGDR for cardiovascular disease (CVD) events was less than 2.34 mg kg-1 min-1. Lower eGDR, longer diabetes duration, and lower HbA1c significantly increased CVD outcomes risk. eGDR was also significantly lower in smokers (7.3 ± 2.5 vs. non-smokers 8.2 ± 2.6, p = 0.011), the obese (lean 8.25 ± 2.47 vs. obese 5.36 ± 2.74, p < 0.000), older patients (less than 50 years 8.0 ± 2.5 vs. more than 50 years 6.2 ± 2.8, p = 0.001), men (men 6.4 ± 2.4 vs. women 8.7 ± 2.2, p < 0.001), patients with long-standing diabetes (< 10 years 7.3 ± 2.6 vs. > 10 years 8.7 ± 2.3, p < 0.001), and chronic diabetes complications (diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, p < 0.001), and patients with CVD (with CVD 5.5 ± 2.4 vs. no CVD 8.0 ± 2.4, p < 0.001). Patients with T1D and a family history of T2D were not susceptible to weight gain during intensive insulin treatment. Metabolic syndrome (MS) phenotype prevalence, including and dyslipidemia rate, were higher in the obese group than in normal weight, but a clear difference was not seen (p = 0.07). Positive linear correlation between men's T and eGDR level was observed (r = 0.33, p = 0.04), i.e., men with higher testosterone level had better insulin sensitivity. Other parameters (like T in women, estrogens, SHBG) did not show any significant association with eGDR. CONCLUSIONS According to stratified eGDR, IR was found for one-third of the current T1D population. Insulin resistant patients more frequently had microvascular complications and CVD events. Lower eGDR, longer diabetes duration, and lower HbA1c significantly increased CVD outcomes risk. IR was related to smoking, obesity, gender, age, and diabetes duration. Moreover, men's testosterone had a positive correlation with IR in T1D. Finally, patients with T1D and a positive family history of T2D were not susceptible to weight gain, while MS metabolic phenotype prevalence tended to be higher in obese than in lean patients with T1D, with a tendency to significant difference.
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Affiliation(s)
- Diana Šimonienė
- Department of Endocrinology, Lithuanian University of Health Sciences (LUHS), Kaunas, Lithuania.
| | | | - Edita Prakapienė
- Department of Endocrinology, Lithuanian University of Health Sciences (LUHS), Kaunas, Lithuania
| | - Lina Radzevičienė
- Department of Endocrinology, Lithuanian University of Health Sciences (LUHS), Kaunas, Lithuania
- LUHS, Institute of Endocrinology, Kaunas, Lithuania
| | - Džilda Veličkiene
- Department of Endocrinology, Lithuanian University of Health Sciences (LUHS), Kaunas, Lithuania
- LUHS, Institute of Endocrinology, Kaunas, Lithuania
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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/dc20-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/dc20-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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Christensen MMB, Hommel EE, Jørgensen ME, Fleischer J, Hansen CS. Glycemic Variability and Diabetic Neuropathy in Young Adults With Type 1 Diabetes. Front Endocrinol (Lausanne) 2020; 11:644. [PMID: 33071962 PMCID: PMC7538646 DOI: 10.3389/fendo.2020.00644] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 08/07/2020] [Indexed: 12/11/2022] Open
Abstract
Background: Glycemic variability (GV) may attribute to the pathogenesis of diabetic neuropathy. The aim of this cross-sectional study was to investigate the association between GV and distal symmetric polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) in a Danish population of young adults with type 1 diabetes. Methods: Young adults between 18 and 24 years with type 1 diabetes were included in this cross-sectional study. CAN was assessed by cardiovascular autonomic reflex tests (CARTs) and heart rate variability (HRV). DSPN was assessed by light pressure, pain and vibration perception, electrochemical skin conductance, sural nerve conduction velocity (SNCV), and amplitude potential (SNAP). GV were obtained by continuous glucose monitoring including coefficient of variation (CV), SD, continuous overall net glycemic action (CONGA), and mean amplitude of glucose excursions (MAGE). Results: The study comprised 133 young adults (43.6% males), mean age of 22 years (SD 1.6). Unadjusted, higher CV was associated with a decreased risk of sural nerve conduction (P = 0.03), abnormal SNAP (P = 0.04) and incidents of definite CAN (P = 0.04). Likewise, higher CONGA was associated with increasing incidents of subclinical DSPN (P = 0.03), abnormal SNAP (P = 0.01), and SNCV (P = 0.02). However, both associations were not statistically significant in the fully adjusted model. Higher MAGE was associated with slightly increasing measures of HRV (P = 0.03) but only when fully adjusted. When correcting for multiple tests significance was lost. A significant association was found between HbA1c and measures of both DSPN (P < 0.02) and HRV (P < 0.03) in fully adjusted models. Conclusions: No significant associations between GV and diabetic neuropathy were found after adjusting for risk factors and multiple tests. This suggests that GV may not be a risk factor for diabetic neuropathy in young adults with type 1 diabetes. However, long-term effects of GV excursions may still play a role in the pathogenic mechanisms leading to neuropathy in later life.
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Affiliation(s)
- Marie Mathilde Bjerg Christensen
- Department of Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark
- *Correspondence: Marie Mathilde Bjerg Christensen
| | | | - Marit Eika Jørgensen
- Department of Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark
- Department of Population Health and Morbidity, Health in Greenland, University of Southern Denmark, Odense, Denmark
- Institute of Nursing and Health Science, University of Greenland, Nuuk, Greenland
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Riguetto CM, Takano CR, Admoni SN, Parisi MCR, Giannella MLC, Pavin EJ, Moura Neto A. Identification and performance of multiple clinical and laboratorial risk factors for diagnosis of cardiac autonomic neuropathy in type 1 diabetes patients. J Diabetes Metab Disord 2019; 18:565-573. [PMID: 31890683 DOI: 10.1007/s40200-019-00467-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Accepted: 11/05/2019] [Indexed: 01/05/2023]
Abstract
Purpose The incidence of cardiac autonomic neuropathy (CAN) in patients with type 1 diabetes (T1D) is frequently underestimated. Individuals with T1D and CAN have an increased mortality risk, mainly from cardiovascular causes. The objectives of the present study were to assess the clinical and laboratory characteristics associated with CAN in patients with T1D and verify the ability of multiple clinical factors to help identify patients with this condition. Methods 102 patients with T1D were evaluated for CAN using standardized cardiovascular reflex testing. Clinical characteristics were used to compute a numerical score for CAN diagnosis and a ROC curve elaborated for assessment of the best cutoff to predict CAN. This score was then applied to the second sample of 120 patients. The sensitivity, specificity, and positive and negative predictive values were calculated. Results Prevalence of CAN was around 35% in the first sample of patients and just below 20% in the second sample. Hypertension, total cholesterol, triglycerides, postprandial sweating, diastolic blood pressure, abnormal right and left 10 g monofilament, retinopathy, and nephropathy were considered independent predictors of CAN. The CAN-score cut-off was 16.88. This yielded a sensitivity of 50%, specificity 73.8%, positive predictive value 22.9%, and negative predictive value 90.5%. Conclusion The use of a subset of clinical and laboratory characteristics can be more accessible than the cardiac reflex tests and more accurate than a single isolated characteristic.
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Affiliation(s)
- Cinthia Minatel Riguetto
- 1Endocrinology Division, Internal Medicine Department, Faculty of Medical Sciences, University of Campinas, Rua Tessália Vieira de Camargo, 126 Campinas, São Paulo, 13084-971 Brazil
| | - Caroline Rigoleto Takano
- 1Endocrinology Division, Internal Medicine Department, Faculty of Medical Sciences, University of Campinas, Rua Tessália Vieira de Camargo, 126 Campinas, São Paulo, 13084-971 Brazil
| | - Sharon Nina Admoni
- 2Serviço de Endocrinologia e Metabologia do Hospital da Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo Brazil
| | - Maria Candida Ribeiro Parisi
- 1Endocrinology Division, Internal Medicine Department, Faculty of Medical Sciences, University of Campinas, Rua Tessália Vieira de Camargo, 126 Campinas, São Paulo, 13084-971 Brazil
| | - Maria Lucia Correa Giannella
- 2Serviço de Endocrinologia e Metabologia do Hospital da Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo Brazil
| | - Elizabeth João Pavin
- 1Endocrinology Division, Internal Medicine Department, Faculty of Medical Sciences, University of Campinas, Rua Tessália Vieira de Camargo, 126 Campinas, São Paulo, 13084-971 Brazil
| | - Arnaldo Moura Neto
- 1Endocrinology Division, Internal Medicine Department, Faculty of Medical Sciences, University of Campinas, Rua Tessália Vieira de Camargo, 126 Campinas, São Paulo, 13084-971 Brazil
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Kim HY, Jung HW, Lee YA, Shin CH, Yang SW. Cardiac autonomic neuropathy in nonobese young adults with type 1 diabetes. Ann Pediatr Endocrinol Metab 2019; 24:180-186. [PMID: 31607111 PMCID: PMC6790876 DOI: 10.6065/apem.2019.24.3.180] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 01/16/2019] [Indexed: 12/30/2022] Open
Abstract
PURPOSE The aim of this study was to evaluate the prevalence and risk factors for cardiac autonomic neuropathy (CAN) in nonobese nonobese young type 1 diabetes mellitus (T1DM) patients without micro- or macrovascular complications. METHODS CAN was assessed in 95 patients with T1DM, aged 18-29 years, using standard cardiovascular reflex tests - heart rate response to deep breathing, standing, and the Valsalva maneuver and blood pressure response to standing. Furthermore, power spectral analyses of overall heart rate variability (HRV), standard deviation of NN intervals (SDNN), and total power (TP) were tested with DiCAN. CAN was defined as abnormal results for at least 1 of the 4 cardiovascular reflex tests. RESULTS The prevalence of CAN was 12.6%. The frequency of one and 2 abnormal reflex tests was 10.5% and 2.1%, respectively. No significant differences were observed in age, sex, mean hemoglobin A1c (HbA1c) level, and duration of diabetes with respect to presence of CAN. Patients with CAN exhibited lower overall HRV parameters (SDNN and TP) compared with those without CAN even though there was no statistical significance. In multivariable analyses, higher mean HbA1c level was significantly associated with lower overall HRV (β=-44.42, P=0.002 for SDNN and β=-2.82, P<0.001 for TP). CONCLUSION CAN can be detected in 12.6% of young adult T1DM patients even without other micro- or macrovascular complications. Glycemic control is the main determinant to maintain overall HRV and prevent CAN.
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Affiliation(s)
- Hwa Young Kim
- Department of Pediatrics, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea
| | - Hae Woon Jung
- Department of Pediatrics, Kyung Hee University Medical Center, Seoul, Korea
| | - Young Ah Lee
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea,Address for correspondence: Young Ah Lee, MD, PhD Division of Endocrinology and Metabolism, Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-2072-2308 Fax: +82-2-743-3455 E-mail:
| | - Choong Ho Shin
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
| | - Sei Won Yang
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
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