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Cho I, Lim S, Kwon M, Chung SM, Moon JS, Yoon JS, Won KC. Cardiovascular autonomic neuropathy and the risk of diabetic kidney disease. Front Endocrinol (Lausanne) 2024; 15:1462610. [PMID: 39329106 PMCID: PMC11424464 DOI: 10.3389/fendo.2024.1462610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Accepted: 08/27/2024] [Indexed: 09/28/2024] Open
Abstract
Background Cardiovascular autonomic neuropathy (CAN) is known to affect patients with diabetes mellitus (DM) and cause adverse renal outcomes. We aimed to analyze the association between CAN and diabetic kidney disease (DKD). Method We enrolled 254 DM patients (mean age, 56.7 ± 15.2 years; male: female ratio, 1.17:1) with 19 (7.5%) type 1 DM patients and 235 (92.5%) type 2 DM patients. All patients had undergone cardiovascular autonomic function tests between January 2019 and December 2021 in a tertiary hospital in Korea. Cardiovascular autonomic neuropathy was categorized as normal, early, or definite after measuring three heart rate variability parameters. Diabetic kidney disease refers to a persistently elevated urinary albumin-creatinine ratio (uACR ≥30 mg/g) or reduced estimated glomerular filtration rate (eGFR <60 mL/min/1.73 m2). Logistic and Cox regression analyses were performed. Results Patients with elevated uACR (n=107) and reduced eGFR (n=32) had a higher rate of definite CAN. After adjusting for covariates, definite CAN was associated with elevated uACR (OR=2.4, 95% CI 1.07-5.36) but not with reduced eGFR (OR=3.43, 95% CI 0.62-18.90). A total of 94 patients repeated uACR measurements within 2 years (mean follow-up, 586.3 ± 116.8 days). Both definite and early CAN were independent risk factors for elevated uACR (HR=8.61 and 8.35, respectively; both p<0.05). In addition, high-density lipoprotein cholesterol, ACE inhibitors/angiotensin receptor blockers and glucagon-like peptide-1 receptor agonists were independent protective factors for elevated uACR (HR=0.96, 0.25, and 0.07, respectively; all p<0.05). Conclusion Cardiovascular autonomic neuropathy is a potential indicator of DKD. Comprehensive management of DKD in the early stages of CAN may prevent microalbuminuria.
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Affiliation(s)
- Injeong Cho
- College of Medicine, Yeungnam University, Daegu, Republic of Korea
| | - Seohyun Lim
- College of Medicine, Yeungnam University, Daegu, Republic of Korea
| | - Minjae Kwon
- College of Medicine, Yeungnam University, Daegu, Republic of Korea
| | - Seung Min Chung
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea
| | - Jun Sung Moon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea
| | - Ji Sung Yoon
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea
| | - Kyu Chang Won
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea
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Sloan L, Cheng AYY, Escalada J, Haluzík M, Mauricio D. The role of basal insulins in the treatment of people with type 2 diabetes and chronic kidney disease: A narrative review. Diabetes Obes Metab 2024; 26:1157-1170. [PMID: 38225217 DOI: 10.1111/dom.15425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Revised: 12/05/2023] [Accepted: 12/05/2023] [Indexed: 01/17/2024]
Abstract
The majority of cases of chronic kidney disease (CKD) worldwide are driven by the presence of type 2 diabetes (T2D), resulting in an increase in CKD rates over the past few decades. The existence of CKD alongside diabetes is associated with increased burden of cardiovascular disease and increased risk of death. Optimal glycaemic control is essential to prevent progression of CKD, but achieving glycaemic targets in people with CKD and diabetes can be challenging because of increased risk of hypoglycaemia and limitations on glucose-lowering therapeutic options. This review considers the challenges in management of T2D in people with impaired kidney function and assesses evidence for use of basal insulin analogues in people with CKD.
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Affiliation(s)
- Lance Sloan
- Texas Institute for Kidney and Endocrine Disorders, Lufkin, Texas, USA
- University of Texas Medical Branch, Galveston, Texas, USA
| | - Alice Y Y Cheng
- Trillium Health Partners & Unity Health, University of Toronto, Toronto, Ontario, Canada
| | - Javier Escalada
- Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain
- Center for Biomedical Research in Physiopathology of Obesity and Nutrition (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain
- Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain
| | - Martin Haluzík
- Diabetes Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
| | - Didac Mauricio
- Center for Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), Instituto de Salud Carlos III, Barcelona, Spain
- Department of Endocrinology and Nutrition, CIBERDEM, Hospital de la Santa Creu i Sant Pau & Sant Pau Biomedical Research Institute (IIB Sant Pau), Barcelona, Spain
- Faculty of Medicine, University of Vic (UVIC/UCC), Vic, Spain
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Bjerre-Christensen T, Winther SA, Tofte N, Theilade S, Ahluwalia TS, Lajer M, Hansen TW, Rossing P, Hansen CS. Cardiovascular autonomic neuropathy and the impact on progression of diabetic kidney disease in type 1 diabetes. BMJ Open Diabetes Res Care 2021; 9:9/1/e002289. [PMID: 34645614 PMCID: PMC8515448 DOI: 10.1136/bmjdrc-2021-002289] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 09/26/2021] [Indexed: 01/22/2023] Open
Abstract
INTRODUCTION We investigated the association between cardiovascular autonomic neuropathy (CAN) and decline in kidney function in type 1 diabetes. RESEARCH DESIGN AND METHODS We included 329 persons with type 1 diabetes. CAN was assessed by cardiovascular reflex tests (CARTs): heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio) and to the Valsalva maneuvre. Two or more pathological CARTs defined CAN diagnosis. Outcomes were yearly change in albuminuria or yearly change in estimated glomerular filtration rate (eGFR). An endpoint of eGFR decline >30%, development of end-stage kidney disease (ESKD) or death was examined.Associations were assessed by linear and Cox regression. RESULTS Participants were aged 55.2 (9.4) years, 52% were male, with a diabetes duration of 40.1 (8.9) years, HbA1c of 7.9% (62.5 mmol/mol), eGFR 77.9 (27.7) mL/min/1.73 m2, urinary albumin excretion rate of 14.5 (7-58) mg/24 hours, and 31% were diagnosed with CAN.CAN was associated with a 7.8% higher albuminuria increase per year (95% CI: 0.50% to 15.63%, p=0.036) versus no CAN. The endpoint of ESKD, all-cause mortality and ≥30% decline in eGFR was associated with CAN (HR=2.497, p=0.0254). CONCLUSION CAN and sympathetic dysfunction were associated with increase in albuminuria in individuals with type 1 diabetes suggesting its role as a potential marker of diabetic kidney disease progression.
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Affiliation(s)
| | | | - Nete Tofte
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | | | - Tarunveer S Ahluwalia
- Department of Biology, Steno Diabetes Center Copenhagen, Gentofte, Denmark
- Department of Biology, University of Copenhagen, Copenhagen, Denmark
| | - Maria Lajer
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | | | - Peter Rossing
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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Choi MS, Jun JE, Park SW, Yoo JH, Ahn J, Kim G, Jin SM, Hur KY, Lee MK, Kim JH. Association of Urinary N-Acetyl-β-D-Glucosaminidase with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes Mellitus without Nephropathy. Diabetes Metab J 2021; 45:349-357. [PMID: 33517614 PMCID: PMC8164949 DOI: 10.4093/dmj.2019.0211] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2019] [Accepted: 02/26/2020] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Cardiovascular autonomic neuropathy (CAN) is a common microvascular complication of diabetes and related to albuminuria in diabetic nephropathy (DN). Urinary N-acetyl-β-D-glucosaminidase (uNAG) is a renal tubular injury marker which has been reported as an early marker of DN even in patients with normoalbuminuria. This study evaluated whether uNAG is associated with the presence and severity of CAN in patients with type 1 diabetes mellitus (T1DM) without nephropathy. METHODS This cross-sectional study comprised 247 subjects with T1DM without chronic kidney disease and albuminuria who had results for both uNAG and autonomic function tests within 3 months. The presence of CAN was assessed by age-dependent reference values for four autonomic function tests. Total CAN score was assessed as the sum of the partial points of five cardiovascular reflex tests and was used to estimate the severity of CAN. The correlations between uNAG and heart rate variability (HRV) parameters were analyzed. RESULTS The association between log-uNAG and presence of CAN was significant in a multivariate logistic regression model (adjusted odds ratio, 2.39; 95% confidence interval [CI], 1.08 to 5.28; P=0.031). Total CAN score was positively associated with loguNAG (β=0.261, P=0.026) in the multivariate linear regression model. Log-uNAG was inversely correlated with frequency-domain and time-domain indices of HRV. CONCLUSION This study verified the association of uNAG with presence and severity of CAN and changes in HRV in T1DM patients without nephropathy. The potential role of uNAG should be further assessed for high-risk patients for CAN in T1DM patients without nephropathy.
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Affiliation(s)
- Min Sun Choi
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ji Eun Jun
- Division of Endocrinology and Metabolism, Department of Medicine, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea
| | - Sung Woon Park
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jee Hee Yoo
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea
| | - Jiyeon Ahn
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Myongji Hospital, Hanyang University College of Medicine, Goyang, Korea
| | - Gyuri Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Sang-Man Jin
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyu Yeon Hur
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Moon-Kyu Lee
- Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School 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
- Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University, Seoul, Korea
- Corresponding author: Jae Hyeon Kim https://orcid.org/0000-0001-5001-963X Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea E-mail:
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Laursen JC, Rasmussen IKB, Zobel EH, Hasbak P, von Scholten BJ, Holmvang L, Ripa RS, Hansen CS, Frimodt-Moeller M, Kjaer A, Rossing P, Hansen TW. The Association Between Cardiovascular Autonomic Function and Changes in Kidney and Myocardial Function in Type 2 Diabetes and Healthy Controls. Front Endocrinol (Lausanne) 2021; 12:780679. [PMID: 34966359 PMCID: PMC8710600 DOI: 10.3389/fendo.2021.780679] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 11/15/2021] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND The mechanisms linking cardiovascular autonomic neuropathy, diabetic kidney disease and cardiovascular mortality in type 2 diabetes are widely unknown. We investigated the relationship between baseline cardiovascular autonomic function and changes in kidney and myocardial function over six years in patients with type 2 diabetes and healthy controls. METHODS Post-hoc analysis of a cohort study in 24 patients with type 2 diabetes and 18 healthy controls. Baseline determinants were cardiovascular autonomic reflex tests (heart rate response to: standing (30:15); deep breathing (E:I); and the Valsalva test) and time- and frequency-domain heart rate variability indices. Outcomes were changes in estimated glomerular filtration rate (eGFR), albuminuria, myocardial flow reserve (MFR) measured by cardiac 82Rb Positron emission tomography computed tomography (PET/CT), and coronary artery calcium score (CACS). RESULTS Mean age at inclusion was 61 ± 10 years and 36% were female. Mean follow up time was 6 ± 0 years. A lower response in heart rate to the Valsalva test (corresponding to weaker autonomic function) was associated with a larger decline in eGFR (p=0.04), but not significantly after adjustment for sex, baseline age, smoking status, systolic blood pressure, heart rate, HbA1c, body mass index and baseline eGFR (p=0.12). A higher baseline response in heart rate to standing (30:15) was associated with a larger decline in myocardial flow reserve in the unadjusted analysis (p=0.02) and after adjustment (p=0.02). A higher response in heart rate to the Valsalva maneuver was associated with a larger increase in CACS (p = 0.02), but the association became insignificant after adjustment (p = 0.16). CONCLUSION A lower response in heart rate to the Valsalva test was associated with a larger decline in kidney function, indicating that autonomic dysfunction may predict future loss of kidney function. However, we did not find any association between lower values in cardiovascular autonomic function at baseline and a worsening in albuminuria, myocardial function, or atherosclerotic burden.
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Affiliation(s)
- Jens Christian Laursen
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, The University of Copenhagen, Copenhagen, Denmark
- *Correspondence: Jens Christian Laursen,
| | - Ida Kirstine B. Rasmussen
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, The University of Copenhagen, Copenhagen, Denmark
| | - Emilie H. Zobel
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Novo Nordisk, Bagsvaerd, Denmark
| | - Philip Hasbak
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet, Copenhagen, Denmark
| | - Bernt Johan von Scholten
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Novo Nordisk, Bagsvaerd, Denmark
| | - Lene Holmvang
- Department of Cardiology, Rigshospitalet, Copenhagen, Denmark
| | - Rasmus S. Ripa
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet, Copenhagen, Denmark
| | | | | | - Andreas Kjaer
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, The University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet, Copenhagen, Denmark
| | - Peter Rossing
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, The University of Copenhagen, Copenhagen, Denmark
| | - Tine W. Hansen
- Complications Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, The University of Copenhagen, Copenhagen, Denmark
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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: 27] [Impact Index Per Article: 5.4] [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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Role of dipstick proteinuria for predicting cardiovascular events: a Japanese cardiovascular hospital database analysis. Heart Vessels 2020; 35:1256-1269. [PMID: 32248254 DOI: 10.1007/s00380-020-01596-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/25/2019] [Accepted: 03/27/2020] [Indexed: 12/21/2022]
Abstract
Initial screening for proteinuria by urine dipstick test (UDT) may be useful for predicting clinical outcomes. The Shinken Database includes all the new patients visiting the Cardiovascular Institute Hospital in Tokyo, Japan. Patients for whom UDT was performed at their initial visit between 2004 and 2010 (n = 7131) were divided into three groups according to the test results: negative, trace, and positive (1+ to 4+) proteinuria. During the mean follow-up period of 3.4 years, 233 (3.1%) deaths, 255 (3.6%) heart failure (HF) events, and 106 (1.5%) ischemic stroke (IS) events occurred. Prevalence of atherothrombotic risks increased with an increase in the amounts of proteinuria. The incidence of all-cause death, HF and IS events increased significantly from negative to trace to positive proteinuria groups (log rank test, P for trend < 0.001). Multivariate analysis revealed independent association between proteinuria and all-cause death [hazard ratio (HR): 1.50, 95% confidence interval (CI) 1.07-2.10], HF (HR: 1.55, 95% CI 1.14-2.12), and IS (HR: 2.08, 95% CI 1.26-3.45). Even trace proteinuria was independently associated with HF (HR: 1.64, 95% CI 1.07-2.53) and IS (HR: 2.17, 95% CI 1.14-4.11) and with all-cause death (HR: 1.56, 95% CI 0.99-2.47). In conclusions, dipstick proteinuria was independently associated with cardiovascular events and death, suggesting that the UDT is a useful tool for evaluating patients' risk for such adverse events.
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Pan Q, Li Q, Deng W, Zhao D, Qi L, Huang W, Ma L, Li H, Li Y, Lyu X, Wang A, Yao H, Guo L, Xing X. Prevalence and Diagnosis of Diabetic Cardiovascular Autonomic Neuropathy in Beijing, China: A Retrospective Multicenter Clinical Study. Front Neurosci 2019; 13:1144. [PMID: 31708736 PMCID: PMC6823192 DOI: 10.3389/fnins.2019.01144] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2018] [Accepted: 10/10/2019] [Indexed: 12/15/2022] Open
Abstract
Cardiovascular autonomic neuropathy (CAN) is a debilitating condition occurring among diabetic patients especially those with long duration of disease. Whereas incidences and treatment of CAN has been well described for Western populations, fewer studies have been conducted among the Chinese. This study, therefore, aimed to assess the prevalence of CAN among sampled Chinese diabetic patients. Accordingly, 2,048 participants with a history of type 1 diabetes mellitus (T1DM, 73) and type 2 diabetes mellitus (T2DM, 1975) were randomly sampled from 13 hospitals. Patients’ biodata were recorded, and autonomic nervous system function tests performed to aid in the preliminary diagnosis of CAN. The final CAN diagnosis was based on the Ewing’s test in which heart rate variation (HRV) values were evaluated through deep-breathing (DB), lying-to-standing (LS), and Valsalva (V) tests. Systolic blood pressure (SBP) variation values were also evaluated through LS. In the T1DM group, 61.6% patients were diagnosed with CAN and no differences were observed in the baseline and clinical data between this group and those without CAN (P > 0.05). In the T2DM group, 62.6% patients were diagnosed with CAN and statistically significant differences were found between the CAN and non- CAN group with regards to age, duration of diabetes, metformin treatment, retinopathy, and hypertension history (P < 0.05). The most common manifestations of CAN included weakness (28.6%), dizziness (23.4%), frequent urination (19.6%), upper body sweating (18.3%), and nocturia (15.9%). Additionally, duration of disease and age were independent risk factors for CAN in T1DM and T2DM, respectively. On diagnosis, a combination of the V test + LS test provided the highest sensitivity of detecting CAN among T1DM group (sensitivity = 97.6%, AUC = 0.887) while for T2DM category, DB test had the highest sensitivity (83.6%), and maximal AUC (0.856) was found with V test + DB test. The overall prevalence of diabetes with CAN in the study was up to 63%.
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Affiliation(s)
- Qi Pan
- Department of Endocrinology, National Center of Gerontology, Beijing Hospital, Beijing, China
| | - Quanmin Li
- The PLA Rocket Force Characteristic Medical Center, Beijing, China
| | - Wei Deng
- Department of Endocrinology, Beijing Jishuitan Hospital, Beijing, China
| | - Dong Zhao
- Center for Endocrine Metabolism and Immune Diseases, Luhe Hospital, Capital Medical University, Beijing, China
| | - Lin Qi
- Department of Endocrinology, Beijing Yanhua Hospital, Beijing, China
| | - Wei Huang
- Department of Endocrinology, Beijing Haidian Hospital, Beijing, China
| | - Li Ma
- South Section, Department of Endocrinology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hongmei Li
- Department of Endocrinology, Emergency General Hospital, Beijing, China
| | - Yufeng Li
- Department of Endocrinology, Beijing Pinggu Hospital, Beijing, China
| | - Xiaofeng Lyu
- Department of Endocrinology, Seventh Medical Center of PLA General Hospital, Beijing, China
| | - Aihong Wang
- PLA Strategic Support Force Characteristic Medical Center, Beijing, China
| | - Hebin Yao
- Department of Endocrinology, Sixth Medical Center of PLA General Hospital, Beijing, China
| | - Lixin Guo
- Department of Endocrinology, National Center of Gerontology, Beijing Hospital, Beijing, China
| | - Xiaoyan Xing
- Department of Endocrinology, China-Japan Friendship Hospital, Beijing, China
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Spallone V. Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet. Diabetes Metab J 2019; 43:3-30. [PMID: 30793549 PMCID: PMC6387879 DOI: 10.4093/dmj.2018.0259] [Citation(s) in RCA: 170] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 02/01/2019] [Indexed: 12/15/2022] Open
Abstract
The burden of diabetic cardiovascular autonomic neuropathy (CAN) is expected to increase due to the diabetes epidemic and its early and widespread appearance. CAN has a definite prognostic role for mortality and cardiovascular morbidity. Putative mechanisms for this are tachycardia, QT interval prolongation, orthostatic hypotension, reverse dipping, and impaired heart rate variability, while emerging mechanisms like inflammation support the pervasiveness of autonomic dysfunction. Efforts to overcome CAN under-diagnosis are on the table: by promoting screening for symptoms and signs; by simplifying cardiovascular reflex tests; and by selecting the candidates for screening. CAN assessment allows for treatment of its manifestations, cardiovascular risk stratification, and tailoring therapeutic targets. Risk factors for CAN are mainly glycaemic control in type 1 diabetes mellitus (T1DM) and, in addition, hypertension, dyslipidaemia, and obesity in type 2 diabetes mellitus (T2DM), while preliminary data regard glycaemic variability, vitamin B12 and D changes, oxidative stress, inflammation, and genetic biomarkers. Glycaemic control prevents CAN in T1DM, whereas multifactorial intervention might be effective in T2DM. Lifestyle intervention improves autonomic function mostly in pre-diabetes. While there is no conclusive evidence for a disease-modifying therapy, treatment of CAN manifestations is available. The modulation of autonomic function by SGLT2i represents a promising research field with possible clinical relevance.
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Affiliation(s)
- Vincenza Spallone
- Division of Endocrinology, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
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Abstract
PURPOSE OF REVIEW This review considers the relationship between abnormal blood pressure (BP) variability and autonomic dysfunction through an attempt to answer questions about its clinical relevance and pertinence to diabetes and cardiovascular autonomic neuropathy (CAN) and which therapeutic measures can lessen its cardiovascular impact. RECENT FINDINGS Office, ambulatory, and home BP monitoring identify posture-related, circadian, short-term, and long-term BP variabilities. Abnormal BP variability is a risk marker for organ damage, mortality, and cardiovascular events. Moreover, BP variability changes are common in diabetes and associated with CAN and possibly exacerbated by comorbidities like nephropathy, obstructive sleep apnoea syndrome, and chronic pain. The prognostic role of nondipping and reverse dipping is well documented in diabetes. Some findings suggest the possibility of restoring dipping with the dosage time of antihypertensive agents. Diabetes is a favorable scenario for altered BP variability, which might mediate the harmful effects of CAN. Preliminary data suggest the protective effect of targeting BP variability. However, further longitudinal outcome studies are needed. In the meantime, BP variability measures and practical expedients in antihypertensive treatment should be implemented in diabetes.
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Affiliation(s)
- Vincenza Spallone
- Endocrinology, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier, 1, 00133, Rome, Italy.
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11
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Matta M, Pavy-Le Traon A, Perez-Lloret S, Laporte C, Berdugo I, Nasr N, Hanaire H, Senard JM. Predictors of Cardiovascular Autonomic Neuropathy Onset and Progression in a Cohort of Type 1 Diabetic Patients. J Diabetes Res 2018; 2018:5601351. [PMID: 29693021 PMCID: PMC5859848 DOI: 10.1155/2018/5601351] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Revised: 01/16/2018] [Accepted: 01/29/2018] [Indexed: 12/12/2022] Open
Abstract
AIM The prevalence of cardiovascular autonomic neuropathy (CAN) in diabetes mellitus is well documented. However, the rate and predictors of both the development and progression of CAN have been less studied. Hereby, we assessed the rate and the major risk factors for CAN initiation and progression in a cohort of type 1 diabetic patients followed over a three-year period. METHODS 175 type 1 diabetic patients (mean age: 50 ± 11 years; female/male: 76/99) with positive bedside screening for CAN were included and underwent 2 standardized autonomic testings using 4 standardized tests (deep breathing, Valsalva maneuver, 30/15 ratio, and changes in blood pressure during standing), separated by 3 ± 1 years. CAN staging was achieved according to the Toronto Consensus Panel on Diabetic Autonomic Neuropathy into 4 categories: absent, possible, confirmed, or severe CAN. RESULTS Out of the 175 patients included, 31.4% were free of CAN, 34.2% had possible CAN, 24.6% had confirmed CAN, and 9.7% exhibited severe CAN at the first assessment. Among the 103 patients with nonsevere CAN at inclusion, forty-one (39.8%) had an increase of at least one category when reassessed and 62 (60.2%) remained stable. A bivariate analysis indicated that only BMI and exposure to selective serotonin reuptake inhibitors (SSRIs) were significantly different in both groups. A multivariate analysis indicated that lower BMI (OR: 0.15, CI 95%: 0.05-0.48, p = 0.003) and SSRI exposure (OR: 4.18, CI 95%: 1.03-16.97, p = 0.04) were the sole predictors of CAN deterioration. In the 55 patients negative for CAN at the first laboratory assessment, 12 became positive at the second assessment. CONCLUSION No clear predictive factor for CAN onset was identified. However, once present, CAN progression was related to low BMI and SSRI exposure.
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Affiliation(s)
- M. Matta
- Service de Diabétologie et maladies métaboliques, CHU de Toulouse, 1 avenue Jean Poulhès, 31059 Toulouse Cedex 9, France
| | - A. Pavy-Le Traon
- Service de Neurologie, Hôpital Pierre-Paul Riquet, Place du Docteur Baylac-TSA 40031, 31059 Toulouse Cedex 9, France
- Institut des Maladies Métaboliques et Cardiovasculaires, INSERM, Université de Toulouse, 1 avenue Jean Poulhès, BP 84225, 31432 Toulouse Cedex 4, France
| | - S. Perez-Lloret
- Institute of Cardiology Research, University of Buenos Aires, National Research Council (CONICET-ININCA), Buenos Aires, Argentina
| | - C. Laporte
- Service de Diabétologie et maladies métaboliques, CHU de Toulouse, 1 avenue Jean Poulhès, 31059 Toulouse Cedex 9, France
| | - I. Berdugo
- Service de Diabétologie et maladies métaboliques, CHU de Toulouse, 1 avenue Jean Poulhès, 31059 Toulouse Cedex 9, France
| | - N. Nasr
- Service de Neurologie, Hôpital Pierre-Paul Riquet, Place du Docteur Baylac-TSA 40031, 31059 Toulouse Cedex 9, France
- Institut des Maladies Métaboliques et Cardiovasculaires, INSERM, Université de Toulouse, 1 avenue Jean Poulhès, BP 84225, 31432 Toulouse Cedex 4, France
| | - H. Hanaire
- Service de Diabétologie et maladies métaboliques, CHU de Toulouse, 1 avenue Jean Poulhès, 31059 Toulouse Cedex 9, France
| | - J. M. Senard
- Institut des Maladies Métaboliques et Cardiovasculaires, INSERM, Université de Toulouse, 1 avenue Jean Poulhès, BP 84225, 31432 Toulouse Cedex 4, France
- Service de Pharmacologie Clinique, Faculté de Médecine, CHU de Toulouse, 37 allées Jules Guesde, 31000 Toulouse, France
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Liu Q, Han L, Chang F, Chen G, Li X, Xia L. The relationship between the autonomic nervous function and early renal dysfunction in elderly patients with mild-to-moderate essential hypertension. Clin Exp Hypertens 2017; 40:136-140. [PMID: 28786697 DOI: 10.1080/10641963.2017.1346110] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Qunwei Liu
- Department of Cardiology, Civil Aviation General Hospital, Beijing, PR China
| | - Limin Han
- Department of Cardiology, Civil Aviation General Hospital, Beijing, PR China
| | - Feng Chang
- Department of Cardiology, Civil Aviation General Hospital, Beijing, PR China
| | - Guoyan Chen
- Department of Cardiology, Civil Aviation General Hospital, Beijing, PR China
| | - Xinrui Li
- Department of Cardiology, Civil Aviation General Hospital, Beijing, PR China
| | - Lijiao Xia
- Clinical laboratory, Civil Aviation General Hospital, Beijing, PR China
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13
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Wheelock KM, Jaiswal M, Martin CL, Fufaa GD, Weil EJ, Lemley KV, Yee B, Feldman E, Brosius FC, Knowler WC, Nelson RG, Pop-Busui R. Cardiovascular autonomic neuropathy associates with nephropathy lesions in American Indians with type 2 diabetes. J Diabetes Complications 2016; 30:873-9. [PMID: 27041674 PMCID: PMC4912901 DOI: 10.1016/j.jdiacomp.2016.03.008] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2016] [Revised: 03/04/2016] [Accepted: 03/09/2016] [Indexed: 12/15/2022]
Abstract
AIMS Cardiovascular autonomic neuropathy (CAN) predicts clinical diabetic nephropathy (DN). We investigated the relationship between DN structural lesions and CAN. METHODS Sixty three Pima Indians with type 2 diabetes underwent kidney biopsies following a 6-year clinical trial testing the renoprotective efficacy of losartan vs. placebo. CAN was assessed a median 9.2years later. CAN variables included expiration/inspiration ratio (E/I), standard deviation of the normal R-R interval (sdNN), and low and high frequency signal power and their ratio (LF, HF, LF/HF); lower values reflect more severe neuropathy. Associations of CAN with renal structural variables were assessed by linear regression adjusted for age, sex, diabetes duration, blood pressure, HbA1c, glomerular filtration rate, and treatment assignment during the trial. RESULTS Global glomerular sclerosis was negatively associated with sdNN (partial r=-0.35, p=0.01) and LF (r=-0.32, p=0.02); glomerular basement membrane width was negatively associated with all measures of CAN except for LF/HF (r=-0.28 to -0.42, p<0.05); filtration surface density was positively associated with sdNN, LF, and HF (r=0.31 to 0.38, p<0.05); and cortical interstitial fractional volume was negatively associated with HF (r=-0.27, p=0.04). CONCLUSIONS CAN associates with DN lesions.
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Affiliation(s)
| | - Mamta Jaiswal
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI
| | - Catherine L Martin
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI
| | - Gudeta D Fufaa
- Phoenix Epidemiology and Clinical Research Branch, Phoenix, AZ
| | - E Jennifer Weil
- Phoenix Epidemiology and Clinical Research Branch, Phoenix, AZ
| | - Kevin V Lemley
- Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, CA
| | - Berne Yee
- Southwest Kidney Institute, Phoenix, AZ
| | - Eva Feldman
- Department of Neurology, University of Michigan Medical School, Ann Arbor, MI
| | - Frank C Brosius
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI
| | | | - Robert G Nelson
- Phoenix Epidemiology and Clinical Research Branch, Phoenix, AZ.
| | - Rodica Pop-Busui
- Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI
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Duvnjak L, Tomić M, Blaslov K, Vučković Rebrina S. Autonomic nervous system function assessed by conventional and spectral analysis might be useful in terms of predicting retinal deterioration in persons with type 1 diabetes mellitus. Diabetes Res Clin Pract 2016; 116:111-6. [PMID: 27321325 DOI: 10.1016/j.diabres.2016.04.042] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2016] [Revised: 04/01/2016] [Accepted: 04/21/2016] [Indexed: 01/29/2023]
Abstract
AIMS To determine whether cardiac autonomic dysfunction represents a risk factor for diabetic retinopathy (DR) development and progression in persons with type 1 diabetes mellitus (T1DM). METHODS The study comprised 154 normoalbuminuric persons with T1DM divided into two groups according to the DR presence: with and without DR. Cardiovascular autonomic functioning was measured at baseline using conventional and spectral analysis. Participants were re-examined for the DR presence 18months after. RESULTS The group with DR had longer disease duration compared to the group without DR (20 vrs 11.5years, p<0.001), heart rate coefficient of variation (HRV-CV) at rest and during deep breathing were lower in participants with DR (p=0.001 and 0.004), as well did spectral indices of HRV: low frequency (LF) band, high frequency (HF) band (p=0.003 and 0.022) while LF/HF ratio indicating sympathovagal balance was higher (p=0.037). No difference in glycaemic control or blood pressure value were observed. Twenty-one (13.36%) participants developed non proliferative DR or progressed to proliferative DR. Cox proportional regression showed that the 18months risk from retinal deterioration was reduced by 33.4% by each increase in the HRV-CV of 1%, 12.7% for the same HRV-CV increase during deep breathing while LF band of 1ms(2) results in 8.6% risk reduction. CONCLUSIONS This study provides evidence that DR should not be considered merely a metabolic control manifestation and that HRV-CV as well as spectral indices of HRV might serve as a practical tool to identify a subgroup of T1DM patients with higher risk of retinal deterioration.
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Affiliation(s)
- L Duvnjak
- Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases, University Hospital Merkur, Zagreb, Croatia; School of Medicine Zagreb, Croatia
| | - M Tomić
- Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases, University Hospital Merkur, Zagreb, Croatia
| | - K Blaslov
- Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases, University Hospital Merkur, Zagreb, Croatia.
| | - S Vučković Rebrina
- Vuk Vrhovac Clinic for Diabetes, Endocrinology and Metabolic Diseases, University Hospital Merkur, Zagreb, Croatia
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Orlov S, Cherney DZI, Pop-Busui R, Lovblom LE, Ficociello LH, Smiles AM, Warram JH, Krolewski AS, Perkins BA. Cardiac autonomic neuropathy and early progressive renal decline in patients with nonmacroalbuminuric type 1 diabetes. Clin J Am Soc Nephrol 2015; 10:1136-44. [PMID: 26092828 DOI: 10.2215/cjn.11441114] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2014] [Accepted: 03/16/2015] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND OBJECTIVES Cardiac autonomic neuropathy predicts future adverse renal outcomes in the general population. This study sought to determine its relationship with early progressive renal decline in type 1 diabetes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A subset of participants with normoalbuminuria (n=204) or microalbuminuria (n=166) from the First Joslin Kidney Study underwent assessment for cardiac autonomic neuropathy using heart rate variability during baseline visits performed from January 1991 to April 1992. Cardiac autonomic neuropathy was defined as an R-R variation (mean circular resultant) <20. Participants also had baseline and follow-up measurement of eGFR. Early progressive renal decline was evaluated according to two definitions: early GFR loss (slope of eGFR estimated by cystatin C <-3.3%/year) and incident advanced CKD (stage ≥3, defined by eGFR [calculated by Modification of Diet in Renal Disease method] <60 ml/min per 1.73 m(2)). Association with baseline cardiac autonomic neuropathy was assessed by adjusted logistic regression and Cox proportional hazards. RESULTS Among the 370 participants, 47 (13%) had baseline cardiac autonomic neuropathy, 51 (14%) had early GFR loss, and 68 (18%) had incident advanced CKD over a median 14-year follow-up. Early GFR loss occurred in 15 (32%) of the 47 patients with baseline autonomic neuropathy and in 32 (10%) of the 323 without baseline autonomic neuropathy (P<0.001). Baseline autonomic neuropathy was strongly associated with odds of early GFR loss (adjusted odds ratio, 4.09; 95% confidence interval, 1.65 to 10.12; P=0.002). Incident advanced CKD was observed in 22 (47%) of those with baseline autonomic neuropathy and 46 (14%) of those without baseline autonomic neuropathy (P<0.001). Autonomic neuropathy was independently associated with incident advanced CKD (adjusted hazard ratio, 2.76; 95% confidence interval, 1.44 to 5.30; P=0.002). CONCLUSIONS Cardiac autonomic neuropathy was a strong independent predictor of the long-term risk of early progressive renal decline in type 1 diabetes. Future research should explore the mechanisms by which autonomic neuropathy may be associated with renal function loss.
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Affiliation(s)
- Steven Orlov
- Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - David Z I Cherney
- Division of Nephrology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Rodica Pop-Busui
- Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan Health System, University of Michigan, Ann Arbor, Michigan; and
| | - Leif E Lovblom
- Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Linda H Ficociello
- Section on Genetics and Epidemiology, Research Division, Department of Medicine, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts
| | - Adam M Smiles
- Section on Genetics and Epidemiology, Research Division, Department of Medicine, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts
| | - James H Warram
- Section on Genetics and Epidemiology, Research Division, Department of Medicine, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts
| | - Andrzej S Krolewski
- Section on Genetics and Epidemiology, Research Division, Department of Medicine, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts
| | - Bruce A Perkins
- Division of Endocrinology and Metabolism, Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada;
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Cho YH, Craig ME, Davis EA, Cotterill AM, Couper JJ, Cameron FJ, Benitez-Aguirre PZ, Dalton RN, Dunger DB, Jones TW, Donaghue KC. Cardiac autonomic dysfunction is associated with high-risk albumin-to-creatinine ratio in young adolescents with type 1 diabetes in AdDIT (adolescent type 1 diabetes cardio-renal interventional trial). Diabetes Care 2015; 38:676-81. [PMID: 25573882 DOI: 10.2337/dc14-1848] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE This study examined the association between cardiac autonomic dysfunction and high albumin-to-creatinine ratio (ACR) in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS Adolescents recruited as part of a multicenter screening study (n = 445, 49% female, aged 10-17 years, mean duration 6.9 years; mean HbA1c 8.4%, 68 mmol/mol) underwent a 10-min continuous electrocardiogram recording for heart rate variability analysis. Time-domain heart rate variability measures included baseline heart rate, SD of the R-R interval (SDNN), and root mean squared difference of successive R-R intervals (RMSSD). Spectral analysis included sympathetic (low-frequency) and parasympathetic (high-frequency) components. Standardized ACR were calculated from six early morning urine collections using an established algorithm, reflecting age, sex, and duration, and stratified into ACR tertiles, where the upper tertile reflects higher nephropathy risk. RESULTS The upper-tertile ACR group had a faster heart rate (76 vs. 73 bpm; P < 0.01) and less heart rate variability (SDNN 68 vs. 76 ms, P = 0.02; RMSSD 63 vs. 71 ms, P = 0.04). HbA1c was 8.5% (69 mmol/mmol) in the upper tertile vs. 8.3% (67 mmol/mol) in the lower tertiles (P = 0.07). In multivariable analysis, upper-tertile ACR was associated with faster heart rate (β = 2.5, 95% CI 0.2-4.8, P = 0.03) and lower RMSSD (β = -9.5, 95% CI -18.2 to -0.8, P = 0.03), independent of age and HbA1c. CONCLUSIONS Adolescents at potentially higher risk for nephropathy show an adverse cardiac autonomic profile, indicating sympathetic overdrive, compared with the lower-risk group. Longitudinal follow-up of this cohort will further characterize the relationship between autonomic and renal dysfunction and the effect of interventions in this population.
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Affiliation(s)
- Yoon Hi Cho
- Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, New South Wales, Australia Discipline of Paediatrics and Child Health, The University of Sydney, Sydney, New South Wales, Australia
| | - Maria E Craig
- Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, New South Wales, Australia Discipline of Paediatrics and Child Health, The University of Sydney, Sydney, New South Wales, Australia School of Women's and Children's Health, University of New South Wales, Sydney, New South Wales, Australia
| | - Elizabeth A Davis
- Department of Endocrinology and Diabetes, Princess Margaret Hospital for Children, Perth, Western Australia, Australia Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia
| | - Andrew M Cotterill
- Department of Paediatric Endocrinology, Mater Children's Hospital, Brisbane, Queensland, Australia
| | - Jennifer J Couper
- Endocrinology and Diabetes Centre, Women's and Children's Hospital, and Robinson Institute, University of Adelaide, Adelaide, South Australia, Australia
| | - Fergus J Cameron
- Department of Endocrinology and Diabetes, Royal Children's Hospital, Melbourne, Victoria, Australia Murdoch Children's Research Institute, Melbourne, Victoria, Australia The University of Melbourne, Melbourne, Victoria, Australia
| | - Paul Z Benitez-Aguirre
- Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, New South Wales, Australia Discipline of Paediatrics and Child Health, The University of Sydney, Sydney, New South Wales, Australia
| | - R Neil Dalton
- WellChild Laboratory, St Thomas' Hospital, London, U.K
| | - David B Dunger
- University Department of Paediatrics, Addenbrooke's Hospital, Cambridge, U.K
| | - Timothy W Jones
- Department of Endocrinology and Diabetes, Princess Margaret Hospital for Children, Perth, Western Australia, Australia Telethon Kids Institute, University of Western Australia, Perth, Western Australia, Australia
| | - Kim C Donaghue
- Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, New South Wales, Australia Discipline of Paediatrics and Child Health, The University of Sydney, Sydney, New South Wales, Australia
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Yun JS, Ahn YB, Song KH, Yoo KD, Kim HW, Park YM, Ko SH. The association between abnormal heart rate variability and new onset of chronic kidney disease in patients with type 2 diabetes: a ten-year follow-up study. Diabetes Res Clin Pract 2015; 108:31-7. [PMID: 25656759 DOI: 10.1016/j.diabres.2015.01.031] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2014] [Revised: 12/02/2014] [Accepted: 01/18/2015] [Indexed: 01/08/2023]
Abstract
AIMS We investigated the association between cardiovascular autonomic neuropathy (CAN) and the future development of chronic kidney disease (CKD) in patients with type 2 diabetes. METHODS From Jan 2003 to Dec 2004, 1117 patients with type 2 diabetes without CKD (estimated glomerular filtration rate [eGFR] ≥ 60 ml/min/1.73 m(2)), aged 25-75 years, were consecutively enrolled. A cardiovascular autonomic function test (AFT) was performed using heart rate variability parameters. The eGFR was measured at least more than once every year, and new onset CKD was defined as eGFR < 60 ml/min/1.73 m(2) using a Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. RESULTS Among the 755 (67.6%) patients who completed the follow-up evaluation for 9.6 years, 272 patients (36.0%) showed a CKD stage ≥3. The patients who developed CKD were older, had a longer duration of diabetes, had hypertension, received more insulin and ACE inhibitor/angiotensin receptor blocker (ARB) treatment, and exhibited lower baseline eGFR, HbA1c, and albuminuria levels. Compared to patients without CKD, more patients with CKD at follow-up had CAN at baseline. In a multivariate analysis, after adjustment for age, sex, diabetes duration, presence of hypertension, mean HbA1c, diabetic complications, use of insulin, ACE inhibitor/ARB, statin, and baseline eGFR, the development of CKD was significantly associated with the presence of CAN (HR 2.62, 95% CI 1.87-3.67, P<0.001). CONCLUSIONS In this prospective, longitudinal, observational cohort study, we demonstrated that diabetic CAN was an independent prognostic factor for the future development of CKD in type 2 diabetes.
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Affiliation(s)
- Jae-Seung Yun
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Yu-Bae Ahn
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki-Ho Song
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Ki-Dong Yoo
- Division of Cardiology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Republic of Korea
| | - Hyung-Wook Kim
- Division of Nephrology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Republic of Korea
| | - Yong-Moon Park
- Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA
| | - Seung-Hyun Ko
- Division of Endocrinology and Metabolism, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
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Affiliation(s)
- George Jerums
- Endocrine Centre, Austin Health, Level 2 Centaur Building Repatriation Campus, Heidelberg West, VIC 3081, Australia
| | - Richard J MacIsaac
- Department of Endocrinology & Diabetes, St Vincent's Hospital, 35 Victoria Parade, Fitzroy, Melbourne, VIC 3065, Australia
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Tahrani AA, Dubb K, Raymond NT, Begum S, Altaf QA, Sadiqi H, Piya MK, Stevens MJ. Cardiac autonomic neuropathy predicts renal function decline in patients with type 2 diabetes: a cohort study. Diabetologia 2014; 57:1249-56. [PMID: 24623102 DOI: 10.1007/s00125-014-3211-2] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2013] [Accepted: 02/21/2014] [Indexed: 12/15/2022]
Abstract
AIMS/HYPOTHESIS The aim of this work was to assess the impact of cardiac autonomic neuropathy (CAN) on the development and progression of chronic kidney disease (CKD) in patients with type 2 diabetes. METHODS We conducted a cohort study in adults with type 2 diabetes. Patients with end-stage renal disease were excluded. CKD was defined as the presence of albuminuria (albumin/creatinine ratio GFR > 3.4 mg/mmol) or an estimated (eGFR) < 60 ml min(-1) 1.73 m(-2). CKD progression was based on repeated eGFR measurements and/or the development of albuminuria. CAN was assessed using heart rate variability. RESULTS Two hundred and four patients were included in the analysis. At baseline, the prevalence of CKD and CAN was 40% and 42%, respectively. Patients with CAN had lower eGFR and higher prevalence of albuminuria and CKD. Spectral analysis variables were independently associated with eGFR, albuminuria and CKD at baseline. After a follow-up of 2.5 years, eGFR declined to a greater extent in patients with CAN than in those without CAN (-9.0 ± 17.8% vs -3.3 ± 10.3%, p = 0.009). After adjustment for baseline eGFR and baseline differences, CAN remained an independent predictor of eGFR decline over the follow-up period (β = -3.5, p = 0.03). Spectral analysis variables were also independent predictors of eGFR decline. CONCLUSIONS/INTERPRETATION CAN was independently associated with CKD, albuminuria and eGFR in patients with type 2 diabetes. In addition, CAN was an independent predictor of the decline in eGFR over the follow-up period. CAN could be used to identify patients with type 2 diabetes who are at increased risk of rapid decline in eGFR, so that preventative therapies might be intensified.
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Affiliation(s)
- Abd A Tahrani
- Centre of Endocrinology, Diabetes and Metabolism, Institute of Biomedical Research, The Medical School, University of Birmingham, Birmingham, B15 2TT, UK,
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Dimitropoulos G, Tahrani AA, Stevens MJ. Cardiac autonomic neuropathy in patients with diabetes mellitus. World J Diabetes 2014; 5:17-39. [PMID: 24567799 PMCID: PMC3932425 DOI: 10.4239/wjd.v5.i1.17] [Citation(s) in RCA: 188] [Impact Index Per Article: 17.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2013] [Revised: 12/02/2013] [Accepted: 12/12/2013] [Indexed: 02/05/2023] Open
Abstract
Cardiac autonomic neuropathy (CAN) is an often overlooked and common complication of diabetes mellitus. CAN is associated with increased cardiovascular morbidity and mortality. The pathogenesis of CAN is complex and involves a cascade of pathways activated by hyperglycaemia resulting in neuronal ischaemia and cellular death. In addition, autoimmune and genetic factors are involved in the development of CAN. CAN might be subclinical for several years until the patient develops resting tachycardia, exercise intolerance, postural hypotension, cardiac dysfunction and diabetic cardiomyopathy. During its sub-clinical phase, heart rate variability that is influenced by the balance between parasympathetic and sympathetic tones can help in detecting CAN before the disease is symptomatic. Newer imaging techniques (such as scintigraphy) have allowed earlier detection of CAN in the pre-clinical phase and allowed better assessment of the sympathetic nervous system. One of the main difficulties in CAN research is the lack of a universally accepted definition of CAN; however, the Toronto Consensus Panel on Diabetic Neuropathy has recently issued guidance for the diagnosis and staging of CAN, and also proposed screening for CAN in patients with diabetes mellitus. A major challenge, however, is the lack of specific treatment to slow the progression or prevent the development of CAN. Lifestyle changes, improved metabolic control might prevent or slow the progression of CAN. Reversal will require combination of these treatments with new targeted therapeutic approaches. The aim of this article is to review the latest evidence regarding the epidemiology, pathogenesis, manifestations, diagnosis and treatment for CAN.
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Tannus LRM, Drummond KRG, Clemente ELDS, da Matta MDFB, Gomes MB, on behalf of the Brazilian Type 1 Diabetes Study Group (BrazDiab1SG). Predictors of cardiovascular autonomic neuropathy in patients with type 1 diabetes. Front Endocrinol (Lausanne) 2014; 5:191. [PMID: 25505446 PMCID: PMC4243695 DOI: 10.3389/fendo.2014.00191] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Accepted: 10/18/2014] [Indexed: 12/12/2022] Open
Abstract
Cardiovascular disease (CVD) is the leading cause of mortality in patients with type 1 diabetes (T1D). The cardiovascular autonomic neuropathy (CAN), although considered as an independent risk factor for CVD, remains underdiagnosed. The aim of this paper was to determine the prevalence, predictors of CAN in patients with T1D and its association with other chronic complications of diabetes. Patients with T1D underwent a clinical-epidemiological survey, had blood and urinary samples collected, performed ophthalmoscopic and clinical neurological examination and cardiovascular reflex tests. One hundred and fifty one patients with T1D, 53.6% female, 45.7% Caucasian, mean age of 33.4 ± 13 years, diabetes duration of 16.3 ± 9.5 years, and glycated hemoglobin levels of 9.1 ± 2% were evaluated. The prevalence of CAN in the studied population was 30.5%. CAN was associated with age (p = 0.01), diabetes duration (p = 0.036), hypertension (p = 0.001), resting heart rate (HR) (p = 0.000), HbA1c (p = 0.048), urea (p = 0.000), creatinine (p = 0.008), glomerular filtration rate (p = 0.000), urinary albumin concentration (p = 0.000), LDL (p = 0.048), free T4 (p = 0.023), hemoglobin (p = 0.01) and presence of retinopathy (p = 0.000), nephropathy (p = 0.000) and diabetic neuropathy (p = 0.000), the following symptoms syncope (p = 0.000), post prandial nausea (p = 0.042), early satiety (p = 0.031), sexual dysfunction (p = 0.049), and gustatory sweating (p = 0.018). In logistic regression model, it was observed that only resting HR, diabetic neuropathy, and retinopathy were independent associated with CAN. In conclusion, CAN is a common chronic complication of T1D affecting about 30% of the studied population and is associated with the presence of other chronic complications. Indicators of CAN included age, diabetes duration, hypertension, resting HR, diabetic neuropathy and retinopathy, and symptoms suggestive of autonomic neuropathy. This study confirms the importance of systematic and early screening for CAN.
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Affiliation(s)
- Lucianne Righeti Monteiro Tannus
- Unit of Diabetes, Department of Medicine, State University Hospital of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil
- *Correspondence: Lucianne Righeti Monteiro Tannus, Diabetes Unit, Department of Medicine, State University Hospital of Rio de Janeiro (UERJ), Avenida 28 de Setembro, 77, 3rd floor, Vila Isabel, Rio de Janeiro 20551-030, Brazil e-mail:
| | - Karla Rezende Guerra Drummond
- Unit of Diabetes, Department of Medicine, State University Hospital of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil
| | - Eliete Leão da Silva Clemente
- Unit of Diabetes, Department of Medicine, State University Hospital of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil
| | | | - Marilia Brito Gomes
- Unit of Diabetes, Department of Medicine, State University Hospital of Rio de Janeiro (UERJ), Rio de Janeiro, Brazil
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Ersoy B, Sayit E, Can S, Urk V, Batok D, Polat M. Gastric emptying of solids and its relationship with microalbuminuria in children and adolescents with type 1 diabetes mellitus. J Diabetes 2013; 5:319-24. [PMID: 23534498 DOI: 10.1111/1753-0407.12051] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2012] [Revised: 03/21/2013] [Accepted: 03/25/2013] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND The aims of the present study were to determine the frequency of delayed gastric emptying in children and adolescents with type 1 diabetes mellitus (T1DM) and to investigate the relationship between gastric emptying rate and other contributing factors (e.g. serum HbA1c, duration of diabetes and microalbuminuria) in these patients. METHODS This was a clinical trial evaluating the rate of gastric emptying of solid meals in 33 children and adolescents with T1DM and in 26 healthy peers using a radionuclide method. Three consecutive overnight urine collections were used to calculate the albumin excretion rate. RESULTS There was no significant difference in the gastric half-emptying time (GE t½ ) between patients and controls (151.7 ± 154.5 vs 109.8 ± 60.5 min, respectively; P=0.885) or the frequency of delayed gastric emptying (36.4% vs 30.8%, respectively; P=0.433). There was a moderately positive correlation between GE t½ and the duration of diabetes (r=0.380; P=0.029). There was no correlation between GE t½ and microalbumin levels in T1DM patients. In these patients, the body mass index standard deviation scores were significantly lower than in patients with normal gastric emptying (-0.13 ± 0.87 vs 0.7 ± 1.23, respectively; P=0.044). CONCLUSION Progression of delayed gastric emptying is more likely to be related to a longer duration of diabetes than glycemic control in children and adolescents with T1DM. Patients with delayed gastric emptying are thinner compared with patients with a normal rate of gastric emptying; they may also be asymptomatic.
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Affiliation(s)
- Betul Ersoy
- Division of Pediatric Endocrinology and Metabolism, Celal Bayar University, School of Medicine, Manisa, Turkey.
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23
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Additive effects of cilnidipine and angiotensin II receptor blocker in preventing the progression of diabetic nephropathy in diabetic spontaneously hypertensive rats. Clin Exp Nephrol 2012; 17:41-50. [DOI: 10.1007/s10157-012-0677-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2012] [Accepted: 07/25/2012] [Indexed: 10/28/2022]
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24
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Dias LD, Casali KR, Leguisamo NM, Azambuja F, Souza MS, Okamoto M, Machado UF, Irigoyen MC, Schaan BD. Renal denervation in an animal model of diabetes and hypertension: impact on the autonomic nervous system and nephropathy. Cardiovasc Diabetol 2011; 10:33. [PMID: 21496329 PMCID: PMC3110548 DOI: 10.1186/1475-2840-10-33] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2011] [Accepted: 04/17/2011] [Indexed: 11/11/2022] Open
Abstract
Background The effects of renal denervation on cardiovascular reflexes and markers of nephropathy in diabetic-hypertensive rats have not yet been explored. Methods Aim: To evaluate the effects of renal denervation on nephropathy development mechanisms (blood pressure, cardiovascular autonomic changes, renal GLUT2) in diabetic-hypertensive rats. Forty-one male spontaneously hypertensive rats (SHR) ~250 g were injected with STZ or not; 30 days later, surgical renal denervation (RD) or sham procedure was performed; 15 days later, glycemia and albuminuria (ELISA) were evaluated. Catheters were implanted into the femoral artery to evaluate arterial pressure (AP) and heart rate variability (spectral analysis) one day later in conscious animals. Animals were killed, kidneys removed, and cortical renal GLUT2 quantified (Western blotting). Results Higher glycemia (p < 0.05) and lower mean AP were observed in diabetics vs. nondiabetics (p < 0.05). Heart rate was higher in renal-denervated hypertensive and lower in diabetic-hypertensive rats (384.8 ± 37, 431.3 ± 36, 316.2 ± 5, 363.8 ± 12 bpm in SHR, RD-SHR, STZ-SHR and RD-STZ-SHR, respectively). Heart rate variability was higher in renal-denervated diabetic-hypertensive rats (55.75 ± 25.21, 73.40 ± 53.30, 148.4 ± 93 in RD-SHR, STZ-SHR- and RD-STZ-SHR, respectively, p < 0.05), as well as the LF component of AP variability (1.62 ± 0.9, 2.12 ± 0.9, 7.38 ± 6.5 in RD-SHR, STZ-SHR and RD-STZ-SHR, respectively, p < 0.05). GLUT2 renal content was higher in all groups vs. SHR. Conclusions Renal denervation in diabetic-hypertensive rats improved previously reduced heart rate variability. The GLUT2 equally overexpressed by diabetes and renal denervation may represent a maximal derangement effect of each condition.
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Affiliation(s)
- Lucinara D Dias
- Instituto de Cardiologia do Rio Grande do Sul/Fundação Universitária de Cardiologia (IC/FUC), Porto Alegre, Brazil
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25
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Ayad F, Belhadj M, Pariés J, Attali JR, Valensi P. Association between cardiac autonomic neuropathy and hypertension and its potential influence on diabetic complications. Diabet Med 2010; 27:804-11. [PMID: 20636962 DOI: 10.1111/j.1464-5491.2010.03027.x] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
AIMS To examine the association between cardiac autonomic neuropathy and hypertension and the role of this association in diabetic complications. METHODS We included 310 patients, 138 with Type 1 and 172 with Type 2 diabetes, 62 of them with hypertension. Cardiac autonomic neuropathy was assessed by analysing heart rate variations during three standard tests (deep breathing, lying to standing and Valsalva) and looking for postural hypotension. RESULTS Cardiac autonomic neuropathy was present in 123 patients and 39 also had hypertension. The prevalence of a cardiac autonomic neuropathy/hypertension association was higher in Type 2 patients (P < 0.002). The prevalence of hypertension increased with the severity of cardiac autonomic neuropathy. In multiple logistic regression analysis, cardiac autonomic neuropathy was an independent risk factor for hypertension [odds ratio 2.86 (1.54-5.32); P < 0.001]. Only confirmed or severe cardiac autonomic neuropathy (two or more abnormal function tests, respectively) were independent risk factors for hypertension (P < 0.005 and < 0.0001). Cardiac autonomic neuropathy was found in most of the patients with macrovascular complications, retinopathy or nephropathy, but a large majority of the patients with these complications exhibited the cardiac autonomic neuropathy/hypertension profile. This profile was more prevalent among the patients with coronary or peripheral artery disease or antecedent stroke than among those free of these complications (P < 0.001). In logistic regression analyses, the cardiac autonomic neuropathy/hypertension profile associated significantly with macro- and microvascular complications. CONCLUSIONS These data are strongly in favour of the role of cardiac autonomic neuropathy in hypertension in diabetic patients. The association of the cardiac autonomic neuropathy/hypertension profile with vascular complications is consistent with a deleterious effect on vascular hemodynamics and structure, additional to the effects of hypertension.
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Affiliation(s)
- F Ayad
- Department of Internal Medicine, University Hospital, Oran, Algeria
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26
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Hatzitolios AI, Didangelos TP, Zantidis AT, Tziomalos K, Giannakoulas GA, Karamitsos DT. Diabetes mellitus and cerebrovascular disease: which are the actual data? J Diabetes Complications 2009; 23:283-296. [PMID: 18358748 DOI: 10.1016/j.jdiacomp.2008.01.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2007] [Revised: 12/26/2007] [Accepted: 01/18/2008] [Indexed: 12/15/2022]
Abstract
Cerebrovascular disease (CeVD) represents a major cause of morbidity and mortality worldwide. Diabetes mellitus (DM) represents an independent risk factor for CeVD. The aim of the present review is to describe the epidemiology of CeVD in patients with DM and to explain how DM and diabetic autonomic neuropathy can increase the risk of CeVD. The prevention and management of CeVD in the diabetic population are also analyzed.
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Affiliation(s)
- Apostolos I Hatzitolios
- First Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
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27
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Kim YK, Lee JE, Kim YG, Kim DJ, Oh HY, Yang CW, Kim KW, Huh W. Cardiac autonomic neuropathy as a predictor of deterioration of the renal function in normoalbuminuric, normotensive patients with type 2 diabetes mellitus. J Korean Med Sci 2009; 24 Suppl:S69-74. [PMID: 19194565 PMCID: PMC2633204 DOI: 10.3346/jkms.2009.24.s1.s69] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2008] [Accepted: 01/12/2009] [Indexed: 01/13/2023] Open
Abstract
Our study was performed to determine whether cardiac autonomic neuropathy can predict deterioration of the renal function in normoalbuminuric, normotensive people with type 2 diabetes mellitus (DM). One hundred and fifty-six normoalbuminuric, normotensive people with type 2 DM were included in our retrospective longitudinal study. We categorized normal patterns, early patterns, and definite or severe patterns according to the results of the cardiac autonomic function test. Of 156 patients included, 54 had normal patterns, 75 had early patterns, 25 had definite or severe patterns, and 2 had atypical patterns. During a median follow-up of nine years, glomerular filtration rates (GFR) remained stable in the normal and early pattern groups (mean changes, 4.50% and 0.77%, respectively) but declined in those with definite or severe patterns (mean change, -10.28%; p=0.047). An abnormal heart response to the deep breathing test of the cardiac autonomic function tests was an independent predictor of GFR decline. Our data suggest that cardiac autonomic neuropathy, especially with a definite or severe pattern, might be associated with a subsequent deterioration in renal function in normoalbuminuric, normotensive people with type 2 DM.
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Affiliation(s)
- Yong Kyun Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jung Eun Lee
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yoon Goo Kim
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dae Joong Kim
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ha-Young Oh
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chul Woo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kwang-Won Kim
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Wooseong Huh
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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28
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Weck M. Treatment of hypertension in patients with diabetes mellitus. Clin Res Cardiol 2007; 96:707-18. [PMID: 17593318 DOI: 10.1007/s00392-007-0535-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2006] [Accepted: 04/11/2007] [Indexed: 10/23/2022]
Abstract
Antihypertensive treatment in diabetes mellitus, especially in diabetics known to have cardiac autonomic neuropathy, may have to consider the status of the autonomic nervous system. In diabetic subjects with cardiac autonomic neuropathy, vagal activity during the night is often reduced. The reduction results in relative or absolute sympathetic activation, which could increase cardiovascular risk. Pathophysiological and clinical data suggests that antihypertensive treatment should reduce rather than induce sympathetic activity in this setting. Beta blocking agents, ACE inhibitors, calcium antagonists of verapamil or diltiazem type and selective imidazoline receptor agonists reduce sympathetic activity and, therefore, may have a beneficial effect in diabetic patients with disturbed sympathovagal balance.
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Affiliation(s)
- Matthias Weck
- Clinic Bavaria Kreischa, Department of Diabetes, Metabolism and Endocrinology, An der Wolfsschlucht 1-2, 01731 Kreischa, Germany.
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29
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Chen HS, Wu TE, Jap TS, Lee SH, Wang ML, Lu RA, Chen RL, Lin HD. Decrease heart rate variability but preserve postural blood pressure change in type 2 diabetes with microalbuminuria. J Chin Med Assoc 2006; 69:254-8. [PMID: 16863010 DOI: 10.1016/s1726-4901(09)70252-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
BACKGROUND This study compares the cardiovascular autonomic function in type 2 diabetes with and without microalbuminuria, in order to identify the possible links between early nephropathy and diabetic autonomic neuropathy (DAN). METHODS Cardiovascular reflex tests were performed to determine the cardiovascular autonomic function. Thirty cases of type 2 diabetes with microalbuminuria were studied for evidence of DAN to compare with a normoalbuminuric group of 56 diabetic patients. RESULTS There was an increased prevalence of autonomic dysfunction in patients with microalbuminuria (63.3% in the microalbuminuria group vs. 40.0% in the normoalbuminuric controls, p = 0.001). These patients had lower heart rate variability during single breathing tests (6.9 +/- 4.3 vs. 9.6 +/- 3.6 beats/minute, p = 0.005), during 6 consecutive breathings (5.8 +/- 3.6 vs. 8.2 +/- 3.3 beats/minute, p = 0.005), after standing up (12.2 +/- 4.6 vs. 15.0 +/- 5.2 beats/ minute, p = 0.012), and during the Valsalva maneuver (11.3 +/- 3.5 vs. 13.2 +/- 3.6 beats/minute, p = 0.022). The heart rate variability with these stresses was revealed to be less favorable in subjects with microalbuminuria. However, blood pressure (BP) changes from the sitting to standing position were not significantly different for systolic BP (11.5 +/- 10.7 vs. 10.7 +/- 7.8 mmHg, p = 0.741) and diastolic BP (5.2 +/- 4.4 vs. 5.9 +/- 4.0 mmHg, p = 0.451) between the 2 groups. CONCLUSION Type 2 diabetic patients with microalbuminuria have diminished heart rate variability in response to deep breathing, change of position and the Valsalva maneuver, but they preserve BP response to postural change. Therefore, microalbuminuria seems to be associated with early DAN, but not with advanced DAN.
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Affiliation(s)
- Harn-Shen Chen
- Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taiwan, ROC.
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Schaan BD, Irigoyen MC, Lacchini S, Moreira ED, Schmid H, Machado UF. Sympathetic modulation of the renal glucose transporter GLUT2 in diabetic rats. Auton Neurosci 2005; 117:54-61. [PMID: 15620570 DOI: 10.1016/j.autneu.2004.11.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2004] [Revised: 10/28/2004] [Accepted: 11/02/2004] [Indexed: 10/26/2022]
Abstract
We have previously shown that the abolition of renal sympathetic nervous activity (RSNA) can influence cortical GLUT1 expression in diabetic rats. However, no study has examined the effects of nervous activity on expression of GLUT2, the major glucose transporter in proximal renal tubules, which participates in renal glucose handling. The aim of this study was to determine whether sympathetic activity modulates renal GLUT2 content. We studied diabetic and nondiabetic rats with normal, low, or high RSNA. The low-RSNA experiment used four groups of Wistar male rats: Wistar sham-operated, Wistar renal-denervated, Diabetic sham-operated, and Diabetic renal-denervated. The high-RSNA experiment used four groups of Wistar-Kyoto male rats: WKY (control), WKY-Diabetic, SHR (spontaneously hypertensive rats), and SHR-Diabetic. Renal denervation was confirmed by a decrease in intrarenal norepinephrine levels and sympathetic hyperactivity, by measurement of RSNA. Western blotting was used to determine the renal cortical GLUT2 protein content, and 24-h urinary sodium and glucose levels were also evaluated. Compared with controls (Wistar and WKY), diabetes increased the GLUT2 protein content in normal-RSNA Diabetics (47%) and WKY-Diabetics (83%). The renal denervation-induced decrease in RSNA reduced the GLUT2 content in both normal and diabetic rats (-21% and -15%, respectively). Compared to WKY rats, SHR presented elevated RSNA and also showed an increase in renal GLUT2 content (17%). Diabetes caused a major increase in GLUT2 protein (52%) in the SHR. These results demonstrate a direct relationship between RSNA and GLUT2 levels; they also reveal an additive effect of sympathetic hyperactivity and diabetes on GLUT2 expression, suggesting a new mechanism for modulating protein expression in renal tissue.
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Affiliation(s)
- Beatriz D'Agord Schaan
- Instituto de Cardiologia do RS/Fundação Universitária de Cardiologia, Porto Alegre, RS, CEP 90620-001, Brazil.
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Gottsäter A, Kangro M, Sundkvist G. Early parasympathetic neuropathy associated with elevated fasting plasma C-peptide concentrations and late parasympathetic neuropathy with hyperglycaemia and other microvascular complications. Diabet Med 2004; 21:1304-9. [PMID: 15569133 DOI: 10.1111/j.1464-5491.2004.01340.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
AIMS To examine the relationship between parasympathetic neuropathy, hyperinsulinaemia, glycaemic control (HbA(1c)), and future diabetic complications. METHODS We assessed parasympathetic nerve function [expiration/inspiration (E/I) ratio], glomerular filtration rate (GFR), glycaemic control (HbA(1c)), fasting plasma (f-p-) C-peptide in 82 Type 2 diabetic patients (age 61 +/- 1 years) 5 and 12-15 years after diagnosis. Diabetic retinopathy was assessed 15 years after diagnosis. RESULTS High HbA(1c) values in the first study were associated with retinopathy (with 8.6 +/- 2.0 vs. without retinopathy 6.2 +/- 1.9%; P < 0.0001) and disturbed parasympathetic nerve function (low E/I ratio; r(s) = -0.41; P = 0.0061) in the second study, as well as with deteriorations in GFR between the first and second study (r(s) = 0.62; P < 0.0001). Patients with parasympathetic neuropathy in the first study had significantly higher f-p-C-peptide concentrations than those without 3 years (1.20 +/- 0.43 vs. 0.86 +/- 0.40 nmol/l; P = 0.0015) and 5 years (1.20 +/- 0.44 vs. 0.82 +/- 0.33 nmol/l; P < 0.0001), but not 15 years after diagnosis. CONCLUSION High HbA(1c) values 5 years after diagnosis of Type 2 diabetes were associated with retinopathy, disturbed parasympathetic nerve function, and deterioration in GFR 7-10 years later. Parasympathetic neuropathy 5 years after diagnosis was associated with high C-peptide concentrations. Parasympathetic nerve function has to be considered when beta-cell function is evaluated. Hyperglycaemia is an important factor for the development of complications in Type 2 diabetes.
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Affiliation(s)
- A Gottsäter
- Department of Vascular Diseases, University of Lund, University Hospital MAS, Malmo, Sweden.
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Forsén A, Kangro M, Sterner G, Norrgren K, Thorsson O, Wollmer P, Sundkvist G. A 14-year prospective study of autonomic nerve function in Type 1 diabetic patients: association with nephropathy. Diabet Med 2004; 21:852-8. [PMID: 15270788 DOI: 10.1111/j.1464-5491.2004.01255.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
AIMS Prospective studies of autonomic nerve function are rare. We have followed the progression of autonomic dysfunction in relation to nephropathy over 14 years in Type 1 diabetic patients. METHODS Autonomic nerve function was assessed by heart-rate responses to deep breathing (E/I ratio) and tilting (acceleration and brake indices) and by the postural blood pressure reaction in 58 patients, 43 of whom were reassessed after 14 years. Nephropathy was evaluated by the degree of albuminuria (albuminuria > 20 micro g/min or > 0.03 g/24 h) and glomerular filtration rate ((51)Cr-EDTA plasma clearance). The acceleration index had deteriorated after 7 years (P = 0.0155), whereas the E/I ratio (P = 0.0070) and the diastolic postural blood pressure reaction (P = 0.0054) had deteriorated 14 years after the baseline examination (age-corrected values). All those with albuminuria at the third examination showed signs of autonomic neuropathy at baseline (10 of 10) compared with only nine of 22 without (P = 0.0016). Multiple regression analysis showed that the association between autonomic dysfunction and future albuminuria was due to the E/I ratio. In addition, individuals with an abnormal postural diastolic blood pressure fall (n = 7) at baseline showed a greater fall in glomerular filtration rate more than others 7-14 years later [29 (16.5) ml/min/1.72 m(2) vs. 11 (9) ml/min/1.72 m(2); P = 0.0074]. CONCLUSION Autonomic nerve function had deteriorated after 14 years. Autonomic neuropathy and abnormal postural diastolic blood pressure falls at baseline were associated with future renal complications.
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Affiliation(s)
- A Forsén
- Department of Endocrinology, Lund University, Malmo University Hospital, Malmo, Sweden
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Moran A, Palmas W, Field L, Bhattarai J, Schwartz JE, Weinstock RS, Shea S. Cardiovascular autonomic neuropathy is associated with microalbuminuria in older patients with type 2 diabetes. Diabetes Care 2004; 27:972-7. [PMID: 15047658 DOI: 10.2337/diacare.27.4.972] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Cardiovascular autonomic neuropathy is associated with microalbuminuria in young and middle-aged patients with type 2 diabetes. We examined this relationship and the potential mediating role of blood pressure in older patients. RESEARCH DESIGN AND METHODS At least two of three components of cardiovascular autonomic testing were completed by 132 patients (mean age 70 +/- 5.6 years). Relative rankings on each of the components were averaged to create a summary heart rate variability (HRV) measure. The urine microalbumin-to-creatinine ratio (milligrams albumin/grams creatinine) was calculated. Blood pressure was measured at rest and by 24-h ambulatory recording. RESULTS Urine microalbumin-to-creatinine ratio was higher in those with lower HRV (mean urine microalbumin-to-creatinine ratio 28, 56, and 191 mg/g from the highest to lowest tertile of HRV; P < 0.0001). Resting and ambulatory blood pressure levels were negatively correlated with HRV and positively correlated with urine microalbumin-to-creatinine ratio. In multivariate analysis adjusting for age, duration of diabetes, HbA(1c), and HDL cholesterol, HRV and blood pressure were both independently associated with urine microalbumin-to-creatinine ratio, with no evidence that either mediates the effect of the other. CONCLUSIONS Cardiovascular autonomic neuropathy and blood pressure are independently associated with microalbuminuria in older patients with type 2 diabetes.
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Affiliation(s)
- Andrew Moran
- Division of General Medicine, Department of Medicine, Columbia University College of Physicians & Surgeons, New York, New York 10032. USA
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Torbjörnsdotter TB, Jaremko GA, Berg UB. Nondipping and its relation to glomerulopathy and hyperfiltration in adolescents with type 1 diabetes. Diabetes Care 2004; 27:510-6. [PMID: 14747237 DOI: 10.2337/diacare.27.2.510] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To determine whether there is a relation between dipping/nondipping status and end-organ damage (measured as renal glomerulopathy) and long-term renal function in order to predict the development of nephropathy in normoalbuminuric patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Analysis of renal biopsy and ambulatory blood pressure measurements was done in relation to renal function tests performed during a 10-year period. Forty unselected patients (16 girls), with a mean age of 17.7 years and a mean duration of 10.7 years, were studied. The renal biopsies were examined by electron microscopy. Ambulatory blood pressure was monitored (Space Labs 90 207). Systolic nondippers were defined as a <7%, diastolic nondippers as a <14%, and mean arterial blood pressure (MAP) nondippers as a <12% fall in blood pressure during the night. Renal function was evaluated every other year by clearances of inulin (glomerular filtration rate [GFR]) and para-amino hippurate (effective renal plasma flow [ERPF]), and filtration fraction (GFR/ERPF) was calculated. Overnight urinary albumin excretion rate and long-term mean HbA(1c) were measured. RESULTS MAP (27% of the patients) and diastolic nondippers (12%) had a significantly thicker basement membrane; larger mesangial matrix volume fraction; and higher long-term GFR, nighttime heart rate, and mean HbA(1c) than dippers. CONCLUSIONS Nondipping status was related to more renal morphological changes and long-term hyperfiltration in normoalbuminuric adolescents and young adults, despite a short duration of type 1 diabetes. Nondipping status may be an early predictor of later nephropathy.
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Affiliation(s)
- Torun B Torbjörnsdotter
- Department of Pediatrics, Karolinska Institutet, Huddinge University Hospital, Stockholm, Sweden.
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Valensi P, Pariès J, Attali JR. Cardiac autonomic neuropathy in diabetic patients: influence of diabetes duration, obesity, and microangiopathic complications--the French multicenter study. Metabolism 2003; 52:815-20. [PMID: 12870154 DOI: 10.1016/s0026-0495(03)00095-7] [Citation(s) in RCA: 152] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
The current study sought to examine in a large series of diabetic patients the prevalence of symptoms of autonomic neuropathy and subclinical cardiac autonomic neuropathy (CAN) and their determinants, particularly the influence of diabetes duration, obesity, and microangiopathic complications. Three hundred ninety-six patients, 245 type 1 and 151 type 2, were recruited in 7 French departments of diabetology. CAN was detected by measuring heart rate variability during 3 standardized tests: deep-breathing, Valsalva, and lying-to-standing tests. At least 24.5% of the patients had one or more symptoms suggesting overt autonomic neuropathy. They were older than those free of dysautonomic symptom (P<.001). The deep-breathing test correlated negatively with body mass index (BMI) in type 2 diabetic patients (P<.0001). In the whole population, the deep-breathing and Valsalva tests correlated negatively with diabetes duration (P=.0004 and.019, respectively) and the log urinary albumin/creatinine ratio (P<.002 and.001, respectively). The prevalence of CAN (51%) was higher than the prevalence of other diabetic complications. The rate of moderate and severe CAN (defined by 2 or 3 abnormal CAN function tests) was higher in type 1 than in type 2 diabetic patients (P=.031). It correlated with diabetes duration (P=.026) and was higher in the patients with retinopathy than in those without (P=.035). Among type 2 diabetic patients, the prevalence of CAN was higher in the obese ones (P=.033); in a logistic regression taking age, diabetes duration, and obesity as independent variables, CAN was associated independently with obesity (P=.034). Mild or moderate CAN was found in 33.8% and 13.0% of the 80 patients with diabetes duration less than 18 months. We conclude that CAN is found early in the course of diabetes and should be considered as a prognostic marker of microangiopathic complications. Obesity could be involved in the impairment of CAN function in type 2 diabetics and body weight control could provide an approach to reducing neuropathic complications.
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Affiliation(s)
- P Valensi
- Department of Endocrinology-Diabetology-Nutrition, Paris-Nord University, Bondy, France
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Abstract
Autonomic neuropathy affects every system in the body including the eye, cardiovascular, respiratory, and gastrointestinal and neurovascular systems. The diagnosis confers an attenuated life expectancy, but much can be done to alleviate symptoms and to address the underlying disorder.
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Affiliation(s)
- Aaron I Vinik
- Strelitz Diabetes Research Institutes, Departments of Internal Medicine and Anatomy/Neurobiology, Eastern Virginia Medical School, Norfolk, Va., USA
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Gottsäter A, Rydén-Ahlgren A, Szelag B, Hedblad B, Persson J, Berglund G, Wroblewski M, Sundkvist G. Cardiovascular autonomic neuropathy associated with carotid atherosclerosis in Type 2 diabetic patients. Diabet Med 2003; 20:495-9. [PMID: 12786687 DOI: 10.1046/j.1464-5491.2003.00956.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
AIMS To clarify if cardiovascular autonomic neuropathy is associated with carotid artery atherosclerotic plaques in Type 2 diabetic patients. METHODS Cardiovascular autonomic nerve function was related to carotid artery ultrasound in 61 Type 2 diabetic patients 5-6 years after diagnosis of diabetes. RESULTS Cardiovascular autonomic neuropathy [abnormal age corrected expiration/inspiration (E/I) ratio or acceleration index (AI)] was found in 13/61 (21%) patients. Patients with cardiovascular autonomic neuropathy showed increased degree of stenosis in the common carotid artery (24.6 +/- 13.2% vs. 14.7 +/- 9.2%; P = 0.014) and a tendency towards a higher plaque score (4.0 +/- 1.7 vs. 3.2 +/- 1.6; P = 0.064). Controlled for age, AI correlated inversely with degree of stenosis (r = -0.39; P = 0.005), plaque score (r = -0.39; P = 0.005), and mean (r = -0.33; P = 0.018) and maximum (r = -0.39; P = 0.004) intima-media thickness in the common carotid artery. In contrast, E/I ratio correlated only slightly with mean intima-media thickness in the common carotid artery (r = -0.28; P = 0.049). CONCLUSIONS Cardiovascular autonomic neuropathy was associated with carotid atherosclerosis in Type 2 diabetic patients. Abnormal E/I ratios reflect efferent structural damage to parasympathetic nerves whereas abnormal AI reflects afferent autonomic dysfunction possibly due to impaired baroreceptor sensitivity secondary to carotid atherosclerosis.
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Affiliation(s)
- A Gottsäter
- Department of Vascular Diseases, University of Lund, University Hospital, Malmö, Sweden.
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D'Agord Schaan B, Lacchini S, Bertoluci MC, Irigoyen MC, Machado UF, Schmid H. Impact of renal denervation on renal content of GLUT1, albuminuria and urinary TGF-beta1 in streptozotocin-induced diabetic rats. Auton Neurosci 2003; 104:88-94. [PMID: 12648610 DOI: 10.1016/s1566-0702(02)00295-3] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
In long-term diabetes mellitus, the progression of nephropathy has been related to the occurrence of autonomic neuropathy. This study was designed to evaluate the effects of bilateral denervation of the kidneys of streptozotocin-diabetic rats, an experimental model that presents diabetic nephropathy with increased abundance of cortical GLUT1 in the kidney and increased urinary excretion of albumin and transforming growth factor-beta1 (TGF-beta1). Twenty-four-hour urinary TGF-beta1 (ELISA), urinary albumin (electroimmunoassay) and GLUT1 protein levels (Western blotting) in the renal cortex and medulla were evaluated in diabetic (n=13) and control (n=13) rats 45 days after streptozotocin injection, submitted or not to surgical renal denervation. Evaluations were performed 15 days after the surgery. The effects of renal denervation were confirmed by intra-renal decrease of norepinephrine levels. Mean arterial pressure did not differ between diabetic and control rats, whether they underwent renal denervation or not. Renal denervation increased cortical (6905+/-287, 3506+/-193, 4144+/-246 and 5204+/-516 AU in renal-denervated controls, controls, renal-denervated diabetics and diabetics, respectively) and medullar GLUT1 protein in control rats, but reverted the cortical GLUT1 protein rise determined by diabetes. Although kidney denervation in diabetic rats induced a decrease in cortical GLUT1 abundance toward normal levels, these levels did not reach those of normal animals. However, renal denervation did not determine any changes in urinary albumin and urinary TGF-beta1 in both diabetic (127.3+/-12 microg/24 h and 111.8+/-24 ng mg(-1) creatinine, respectively) and control rats (45.9+/-3 microg/24 h and 13.4+/-4 ng mg(-1) creatinine, respectively). In conclusion, early-phase renal denervation in streptozotocin-diabetic rats produces a normalisation of previously elevated cortical GLUT1 protein content, but is not enough for reverting the increased urinary TGF-beta1 and albuminuria of diabetes.
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Affiliation(s)
- Beatriz D'Agord Schaan
- Instituto de Cardiologia do Rio Grande do Sul/FUC, Unidade de Pesquisa, Av Princesa Isabel, 395 Santana, 90.620-001, Porto Alegre RS, Brazil.
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Karavanaki K, Baum JD. Coexistence of impaired indices of autonomic neuropathy and diabetic nephropathy in a cohort of children with type 1 diabetes mellitus. J Pediatr Endocrinol Metab 2003; 16:79-90. [PMID: 12585344 DOI: 10.1515/jpem.2003.16.1.79] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
One hundred and twenty-nine (87%) out of a county population of 150 eligible children with type 1 diabetes mellitus (DM) and 144 age- and sex-matched control children participated in a longitudinal, epidemiological study of the evolution of diabetic microvascular disease. The mean (SD) age of the children with DM was 12.4 (+/- 3.4) years with a mean DM duration of 4.5 (+/- 3.2) years and a mean HbA1c of 11.1 (+/- 2.2)%. Two sets of measurements were made over a period of 18 months. Pupillary adaptation in darkness (PD), as an index of sympathetic dysfunction, was assessed using a portable Polaroid pupillometer. Urinary albumin excretion, as an index of incipient nephropathy, was assessed in children with DM from a fraction of all voidings during two separate 48-h periods and was expressed as urinary albumin/creatinine ratio (A/C). Heart rate variation (HRV), as an index of cardiovascular autonomic dysfunction, was assessed using a heart rate monitor and computer. Blood pressure (BP) was measured using a random zero sphygmomanometer. Reduced PD was found in 14/129 (13.8%) children with DM and in 5.8% of the controls. The diabetic children with reduced PD had longer DM duration, higher HbA1c, raised diastolic BP and higher urinary A/C than those with normal PD. Fifty percent of these children also had increased A/C and impaired HRV, in addition to impaired PD. Another group of 25/129 (19.4%) children with DM presented intermittently raised mean urinary A/C, while five children presented persistently raised A/C in both 48-h urine collections. The characteristics which differentiated the microalbuminuric group from the normoalbuminuric one were older age, longer DM duration, poorer glycemic control, reduced PD, impaired HRV and raised diastolic BP. It seems that diabetic nephropathy (DN) and autonomic neuropathy (DAN) exist in concert in childhood DM. Diabetic children with impaired indices of DN and DAN are older, pubertal and have longer DM duration and higher HbA1c values than the rest of the diabetic population.
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Affiliation(s)
- K Karavanaki
- 2nd Paediatric Department, Aghia Sophia Children's Hospital, Athens, Greece
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40
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Poulsen PL. Blood pressure and cardiac autonomic function in relation to risk factors and treatment perspectives in Type 1 diabetes. J Renin Angiotensin Aldosterone Syst 2002; 3:222-42. [PMID: 12584666 DOI: 10.3317/jraas.2002.044] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Abstract
The cumulative incidence of diabetic nephropathy in Type 1 diabetes mellitus is in the order of 25 30%. The recognition that elevated blood pressure (BP) is a major factor in the progression of these patients to end-stage renal failure has led to the widespread use of antihypertensive therapy in order to preserve glomerular filtration rate and ultimately to reduce mortality. The routine measurement of microalbuminuria allows early identification of the subgroup of patients at increased risk of developing clinical nephropathy. Microalbuminuric Type 1 diabetic patients show a number of characteristic pathological abnormalities. In addition to elevated BP and abnormal circadian rhythm, there are also associated abnormalities of vagal function, lipid profile and endothelial function, as well as an increased prevalence of retinopathy. The first section of this two-part review focusses on the early changes associated with renal involvement in Type 1 diabetes. It addresses the associations between urinary albumin excretion, glycaemic control, smoking, BP, circadian BP variation, QT interval abnormalities and autonomic function in three groups of patients; those with normoalbuminuria, those progressing towards microalbuminuria and those with established low-grade microalbuminuria.
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Kempler P, Tesfaye S, Chaturvedi N, Stevens LK, Webb DJ, Eaton S, Kerényi Z, Tamás G, Ward JD, Fuller JH. Autonomic neuropathy is associated with increased cardiovascular risk factors: the EURODIAB IDDM Complications Study. Diabet Med 2002; 19:900-9. [PMID: 12421426 DOI: 10.1046/j.1464-5491.2002.00821.x] [Citation(s) in RCA: 113] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
AIMS To assess the prevalence of and risk factors for autonomic neuropathy in the EURODIAB IDDM Complications Study. METHODS The study involved the examination of randomly selected Type I (insulin-dependent) diabetic patients from 31 centres in 16 European countries. Neuropathic symptoms and two tests of autonomic function (changes in heart rate and blood pressure from lying to standing) were assessed and data from 3007 patients were available for the present analysis. Autonomic neuropathy was defined as an abnormality of at least one of the tests. RESULTS The prevalence of autonomic neuropathy was 36% with no sex differences. The frequency of one and two abnormal reflex tests was 30% and 6%, respectively. The R-R ratio was abnormal in 24% of patients while 18% had orthostatic hypotension defined as a fall in systolic blood pressure > 20 mmHg on standing. Significant correlations were observed between autonomic neuropathy and age (P < 0.01), duration of diabetes (P < 0.0001), HbA1c (P < 0.0001), diastolic blood pressure (P < 0.05), lower HDL-cholesterol (P < 0.01), the presence of retinopathy (P < 0.0001) and albuminuria (P < 0.0001). New associations have been identified from the study: the strong relationship of autonomic neuropathy to cigarette smoking (P < 0.01), total cholesterol/HDL-cholesterol ratio (P < 0.05) and fasting triglyceride (P < 0.0001). As a key finding, autonomic neuropathy was related to the presence of cardiovascular disease (P < 0.0001). All analyses were adjusted for age, duration of diabetes and HbA1c. However, data have been only partly confirmed by logistic regression analyses. Frequency of dizziness on standing up was 18%, while only 4% of patients had nocturnal diarrhoea and 5% had problems with bladder control. CONCLUSION Cardiovascular reflex tests, even in the form of the two tests applied, rather than a questionnaire, seem to be appropriate for the diagnosis of autonomic neuropathy. The study has identified previously known and new potential risk factors for the development of autonomic neuropathy, which may be important for the development of risk reduction strategies. Our results may support the role of vascular factors in the pathogenesis of autonomic neuropathy.
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Affiliation(s)
- P Kempler
- Department of Medicine, Semmelweis University, Budapest, Hungary, Royal Hallamshire Hospital, Sheffield, London, UK
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Hoeldtke RD, Bryner KD, McNeill DR, Hobbs GR, Riggs JE, Warehime SS, Christie I, Ganser G, Van Dyke K. Nitrosative stress, uric Acid, and peripheral nerve function in early type 1 diabetes. Diabetes 2002; 51:2817-25. [PMID: 12196476 DOI: 10.2337/diabetes.51.9.2817] [Citation(s) in RCA: 76] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
The present study was performed to determine whether nitric oxide overproduction is associated with deterioration in peripheral nerve function in type 1 diabetes. We measured peripheral nerve function and biochemical indicators of nitrosative stress annually for 3 years in 37 patients with type 1 diabetes. Plasma nitrite and nitrate (collectively NO(x)) were 34.0 +/- 4.9 micro mol/l in the control subjects and 52.4 +/- 5.1, 50.0 +/- 5.1, and 49.0 +/- 5.2 in the diabetic patients at the first, second, and third evaluations, respectively (P < 0.01). Nitrotyrosine (NTY) was 13.3 +/- 2.0 micro mol/l in the control subjects and 26.8 +/- 4.4, 26.1 +/- 4.3, and 32.7 +/- 4.3 in the diabetic patients (P < 0.01). Uric acid was suppressed by 20% in the diabetic patients (P < 0.001). Composite motor nerve conduction velocity for the median, ulnar, and peroneal nerves was decreased in patients with high versus low NTY (mean Z score -0.522 +/- 0.25 versus 0.273 +/- 0.22; P < 0.025). Patients with high NO(x) had decreased sweating, and those with suppressed uric acid had decreased autonomic function. In conclusion, nitrosative stress in early diabetes is associated with suppressed uric acid and deterioration in peripheral nerve function.
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Affiliation(s)
- Robert D Hoeldtke
- Department of Medicine, West Virginia University (WVU), Morgantown, West Virginia 26506-9159, USA
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Duvnjak L, Vucković S, Car N, Metelko Z. Relationship between autonomic function, 24-h blood pressure, and albuminuria in normotensive, normoalbuminuric patients with Type 1 diabetes. J Diabetes Complications 2001; 15:314-9. [PMID: 11711325 DOI: 10.1016/s1056-8727(01)00164-7] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
We performed a battery of cardiovascular reflex tests, 24-h ambulatory blood pressure (AMBP) and 24-h urinary albumin excretion (UAE) in 116 normoalbuminuric and normotensive patients with Type 1 diabetes. Tests of heart rate variation (HRV) included the coefficient of variation (CV) and the low-frequency (LF), mid-frequency (MF), and high-frequency (HF) bands of spectral analysis at rest, HRV during deep breathing (CV, mean circular resultant--MCR), Valsalva ratio, and maximum/minimum 30:15 ratio. Autonomic neuropathy, characterized as an abnormality of more than two tests, was found in 33 patients. Patients with neuropathy compared to those without neuropathy showed significantly higher mean day and night diastolic blood pressure (dBP), mean systolic night blood pressure (sBP), and mean day and night heart rate (HR). Mean night dBP was inversely related to MF, HF, and HRV during deep breathing; mean day dBP and mean night sBP to HF; mean night HR to CV at rest, MF, HF, HRV during deep breathing, 30:15 ratio; mean day HR to HF, HRV during deep breathing, Valsalva, and 30:15 ratio. Mean 24-h UAE was not significantly different in neuropathic than in nonneuropathic patients. UAE was inversely related to CV at rest and HF. In the stepwise multiple regression analysis, reduced MF, HF, HRV during deep breathing, and high levels of UAE and HbA1c were associated with high night dBP. Autonomic neuropathy is already present in normotensive Type 1 diabetic patients at the normoalbuminuric stage and related to BP and albuminuria.
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Affiliation(s)
- L Duvnjak
- University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Vuk Vrhovac, Dugi dol 4a, Zagreb, Croatia.
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Mojiminiyi OA, Abdella N, George S. Evaluation of serum cystatin C and chromogranin A as markers of nephropathy in patients with type 2 diabetes mellitus. Scand J Clin Lab Invest 2000; 60:483-9. [PMID: 11129064 DOI: 10.1080/003655100448464] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Nephropathy is a significant cause of morbidity and mortality in patients with diabetes mellitus (DM). The condition is characterized by persistent albuminuria and years of progressive renal structural changes associated with decline in the glomerular filtration rate (GFR). This study evaluates whether serum concentrations of the endogenous markers of GFR, cystatin C and chromogranin A could be used as indicators of nephropathy in 77 patients with Type 2 DM. On the basis of early morning urine microalbumin:creatinine ratio, patients were divided into patients without diabetic nephropathy (DN) who were normoalbuminuric (n = 27) and patients with DN who were microalbuminuric (n = 8) or macroalbuminuric (n = 42). Patients with reduced GFR or elevated serum cystatin C did not show the expected increase in serum chromogranin A. Twenty-six percent of the patients with normoalbuminuria and 6% of those with DN had serum chromogranin A below the detection limit of the assay (< 2 U/L). In patients with DN, serum chromogranin A showed significant correlation with serum cystatin C, but not with serum creatinine and creatinine clearance. Serum cystatin C and creatinine showed poor correlation with duration of DM and HbA1c. Serum cystatin C and creatinine were significantly higher in patients with DN than in normoalbuminuric patients. Serum cystatin C showed significant correlation with serum creatinine (rs = 0.45, p = 0.002), but not with creatinine clearance (rs = 0.23, p = 0.17) in patients with DN. Four of nine patients with creatinine clearance between 50 and 80 mL/min had increased (> or = 1.4 mg/L) serum cystatin C compared with only two patients with increased serum creatinine concentration. Twenty of 50 (40%) patients with DN had elevated serum cystatin C compared with 6 of 50 (12%) with elevated serum creatinine. If microalbuminuria is regarded as the "gold-standard" test, serum cystatin C has a sensitivity of 40% and specificity of 100% for the detection of DN. However, further studies are required to confirm the usefulness of serum cystatin C estimation as a screening test and as an early indicator and predictor of the development of DN.
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Affiliation(s)
- O A Mojiminiyi
- Department of Pathology, Faculty of Medicine, Kuwait University, Safat.
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Viswanathan V, Prasad D, Chamukuttan S, Ramachandran A. High prevalence and early onset of cardiac autonomic neuropathy among South Indian type 2 diabetic patients with nephropathy. Diabetes Res Clin Pract 2000; 48:211-6. [PMID: 10802160 DOI: 10.1016/s0168-8227(00)00127-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
OBJECTIVE This study was conducted to assess the adverse effects of diabetic nephropathy on cardiovascular autonomic neuropathy (CAN) in South Indian Type 2 diabetic patients. METHODS Comparison was made between Type 2 diabetic patients with nephropathy (group 1, n=25), Type 2 diabetic patients without nephropathy (group 2, n=25) and non-diabetic, non-hypertensive control subjects (n=20). All had a detailed clinical and biochemical work-up and cardiac assessment by ECG. Cardiac dysautonomia was assessed by a battery of five non-invasive autonomic function tests (ANF) as recommended by Ewing and Clarke [D.J. Ewing, B.F. Clarke, Diagnosis and Management of autonomic neuropathy. Br. Med. J. 285 (1982) 916-918]. RESULTS Group 1 patients showed a higher percentage of abnormal CAN function and a more severe form of CAN compared with patients in group 2. Group 1 patients showed early development of the abnormalities. They also had a higher prevalence of peripheral neuropathy compared with the patients without nephropathy. CONCLUSIONS The present study showed that the presence of nephropathy was associated with the risk of cardiac autonomic neuropathy in Type 2 diabetic patients and it probably had an earlier onset also in them.
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Affiliation(s)
- V Viswanathan
- Diabetes Research Centre, No. 4 Main Road, Royapuram, Madras, India.
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Stella P, Ellis D, Maser RE, Orchard TJ. Cardiovascular autonomic neuropathy (expiration and inspiration ratio) in type 1 diabetes. Incidence and predictors. J Diabetes Complications 2000; 14:1-6. [PMID: 10925059 DOI: 10.1016/s1056-8727(00)00054-4] [Citation(s) in RCA: 61] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
The pathogenesis of diabetic neuropathy is poorly understood. In this prospective study, we investigated the incidence rate and potential predictors for cardiovascular autonomic neuropathy (CAN) in a cohort of childhood-onset type 1 diabetic patients. Subjects from the Epidemiology of Diabetes Complications Study were examined at baseline and then biennially. CAN was diagnosed by abnormal (</=1. 1) expiration/inspiration ratio during deep breathing. During the 4. 7-year mean follow-up period, CAN developed in 104 patients from the 373 subjects who were free of CAN at baseline and provided follow-up data, an incidence-density of 5.9 cases/100 person-years. Cox proportional hazard modeling showed age (relative risk [RR]=2.15, p=0.0001), HbA1 (RR=1.50, p=0.0002) and nephropathy (albumin excretion >200 ug/min) (RR=2.46, p=0.0001) to be significant independent predictors. Hypertension was, however, predictive if nephropathy was not included in the model. We conclude that beyond age and poor glycemic control, nephropathy is a significant risk factor for CAN and this association may explain some of the increased mortality seen in CAN.
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Affiliation(s)
- P Stella
- Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, DLR Building, 3512 Fifth Avenue, Pittsburgh, PA 15213, USA
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Torffvit O. Diabetic nephropathy: what causes to treat? SCANDINAVIAN JOURNAL OF UROLOGY AND NEPHROLOGY 1999; 33:324-7. [PMID: 10572997 DOI: 10.1080/003655999750017419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/16/2022]
Abstract
In summary, diabetic nephropathy is characterized by a multifactorial disease process. The present survey points to several factors that are treatable by available drugs. We must now consider prophylactic treatment of patients with poor metabolic control not only to lower blood glucose levels, but also to protect against the harmful effects of glucose. ACE inhibitors and several other available drugs have such effects.
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Affiliation(s)
- O Torffvit
- Department of Internal Medicine, University Hospital, Lund, Sweden.
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48
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Wirta OR, Pasternack AI, Mustonen JT, Laippala PJ, Reinikainen PM. Urinary albumin excretion rate is independently related to autonomic neuropathy in type 2 diabetes mellitus. J Intern Med 1999; 245:329-35. [PMID: 10356594 DOI: 10.1046/j.1365-2796.1999.00499.x] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To evaluate if urinary albumin excretion rate (UAER) is independently related to subclinical autonomic neuropathy in type 2 diabetes. DESIGN A controlled cross-sectional study. SETTING Primary health care centre. SUBJECTS Consecutive recently diagnosed (< 1 year) type 2 diabetic patients (group A, n = 150) and patients with long-standing (median 11 years) type 2 diabetes (group B, n = 146) chosen at random. A nondiabetic control group (group C, n = 150) matched for age and gender to group A. MAIN OUTCOME MEASURES Neuropathy by cardiovascular reflex tests and UAER by nephelometry. METHODS Univariate statistics in group A + B (t-test chi 2- or McNemars test) with Valsalva and breathing ratios as categorical grouping variables and the independent variables gender, smoking, systolic and diastolic blood pressure, fasting serum cholesterol, HDL cholesterol, triglycerides, haemoglobin A1c, glucagon stimulated C-peptide, fasting and postload 1 and 2 h blood glucose and serum insulin, UAER, coronary heart disease and congestive heart failure. Logistic regression analyses in group A + B with Valsalva and breathing ratios as dependent categorical variables and age, systolic blood pressure, congestive heart failure, coronary heart disease, fasting blood glucose, serum triglycerides and UAER as independent variables. RESULTS Compared to nondiabetic subjects the diabetic patients of both groups were at increased risk of neuropathy as judged by the Valsalva ratio (P < 0.01). In known diabetic patients with a UAER > or = 30 mg 24-1 h neuropathy was more common than amongst their normoalbuminuric counterparts (Valsalva test P = 0.007, breathing test P = 0.02). In logistic regression analysis UAER independently explained abnormal Valsalva (P = 0.015) and breathing tests (P = 0.04) in the group A + B. CONCLUSIONS UAER is independently related to subclinical autonomic neuropathy in type 2 diabetes.
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Affiliation(s)
- O R Wirta
- Department of Medicine, Tampere University Hospital, Finland.
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de Kanter M, Lilja B, Elmståhl S, Eriksson KF, Sundkvist G. A prospective study of orthostatic blood pressure in diabetic patients. Clin Auton Res 1998; 8:189-93. [PMID: 9791738 DOI: 10.1007/bf02267780] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
Abstract
To clarify whether orthostatic blood pressure is affected by the type of diabetes, cardiac autonomic neuropathy, and the duration of diabetes, orthostatic blood pressure (passive 90 degrees tilt) was evaluated in 102 patients with insulin dependent diabetes mellitus (IDDM), 51 patients with non-insulin dependent diabetes mellitus (NIDDM), and in 238 control subjects in a first study followed up after 8 to 17 years. The heart rate reaction during deep breathing (E/I ratio) and to tilt (acceleration and brake indices) assessed cardiac autonomic function. In the first study, the lowest systolic blood pressure (LSBP) and the lowest diastolic blood pressure (LDBP) after tilt were significantly lower in IDDM patients compared with NIDDM patients (p < 0.001 for LSBP and p < 0.05 for LDBP) and controls (p < 0.001). LDBP was, however, also significantly lower (p < 0.05) in NIDDM patients than in controls. Hence, although most severe in IDDM, LDBP was disturbed in both types of diabetes. In IDDM, a low E/I ratio was associated with disturbed orthostatic blood pressure. At follow-up examinations, orthostatic blood pressure deteriorated in NIDDM but not in IDDM patients. In conclusion, LSBP and LDBP were impaired in IDDM patients compared with NIDDM and control subjects; however, LDBP was also impaired in NIDDM patients compared with controls. When the duration of diabetes increased, orthostatic blood pressure deteriorated in NIDDM but not in IDDM patients.
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Affiliation(s)
- M de Kanter
- Department of Endocrinology, Lund University, Malmö University Hospital, Sweden
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Howorka K, Pumprla J, Schabmann A. Optimal parameters of short-term heart rate spectrogram for routine evaluation of diabetic cardiovascular autonomic neuropathy. JOURNAL OF THE AUTONOMIC NERVOUS SYSTEM 1998; 69:164-72. [PMID: 9696273 DOI: 10.1016/s0165-1838(98)00015-0] [Citation(s) in RCA: 54] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Our aim was to select those parameters of heart rate variability (HRV) within its short-term power spectral analysis (PSA), which have a capability similar to that of the standard Ewing battery of cardiovascular function tests in determining different degrees of cardiovascular autonomic neuropathy (CAN) in diabetes and to compare the usefulness of both methods for diagnostic purposes in the everyday routine. Commonly used standard battery of cardiovascular autonomic function tests evaluated as total Ewing score as well as short-term PSA of HRV were used in 119 diabetic patients (age: 52.7 +/- 9.8, diabetes duration: 22.2 +/- 12.7 years). From this cohort, patients were selected according to the total Ewing score by matching for age, gender, BMI and diabetes type for 3 groups, each of 17 patients, with no CAN (total Ewing score 0-0.5), with early involvement (score 1.0-2.5) and with definite or severe CAN (score 3.0-5.0). Short-term PSA of HRV performed in three positions (supine1-standing-supine2) included frequency-domain and time-domain parameters of HRV. Cumulative spectral power of total frequency band (0.06-0.50 Hz) and spectral power of low-frequency band (0.06-0.15 Hz) during both supine positions proved to be the most selective and discriminating among all patient groups in inter-group comparison and in analysis of discriminance. The correlation between the total Ewing score and the cumulative spectral power of total frequency band was r = -0.87 (P < 0.001). About 83.2% of cases classified by short-term PSA of HRV using the variables selected by analysis of discriminance was congruent with the classification by the total Ewing score alone. Time expenditure for the performance of each examination was 31 +/- 10 min for Ewing test battery vs. 14 +/- 2 min for short-term PSA of HRV (P < 0.001). In summary, the latter method showed similar diagnostic value concerning the CAN as the classical Ewing standard battery of cardiovascular function tests, although its application proved to be shorter, less stressful and more independent from patient cooperation. Cumulative spectral power of total frequency band (LFHF cumpower) can be used for overall description of the degree of cardiac denervation in diabetes while using short-term PSA of HRV.
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Affiliation(s)
- K Howorka
- Department of Biomedical Engineering and Physics, University of Vienna, Austria.
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