|
1
|
Addleman JS, Lackey NS, Tobin MA, Lara GA, Sinha S, Morse RM, Hajduczok AG, Gharbo RS, Gevirtz RN. Heart Rate Variability Applications in Medical Specialties: A Narrative Review. Appl Psychophysiol Biofeedback 2025:10.1007/s10484-025-09708-y. [PMID: 40293647 DOI: 10.1007/s10484-025-09708-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/30/2025]
Abstract
HRV is clinically considered to be a surrogate measure of the asymmetrical interplay of the sympathetic and parasympathetic nervous system. While HRV has become an increasingly measured variable through commercially-available wearable devices, HRV is not routinely monitored or utilized in healthcare settings at this time. The purpose of this narrative review is to discuss and evaluate the current research and potential future applications of HRV in several medical specialties, including critical care, cardiology, pulmonology, nephrology, gastroenterology, endocrinology, infectious disease, hematology and oncology, neurology and rehabilitation, sports medicine, surgery and anesthesiology, rheumatology and chronic pain, obstetrics and gynecology, pediatrics, and psychiatry/psychology. A narrative literature review was conducted with search terms including HRV and relevant terminology to the medical specialty in question. While HRV has demonstrated promise for some diagnoses as a non-invasive, easy to use, and cost-effective metric for early disease detection, prognosis and mortality prediction, disease monitoring, and biofeedback therapy, several issues plague the current literature. Substantial heterogeneity exists in the current HRV literature which limits its applicability in clinical practice. However, applications of HRV in psychiatry, critical care, and in specific chronic diseases demonstrate sufficient evidence to warrant clinical application regardless of the surmountable research issues. More data is needed to understand the exact impact of standardizing HRV monitoring and treatment protocols on patient outcomes in each of the clinical contexts discussed in this paper.
Collapse
Affiliation(s)
| | - Nicholas S Lackey
- Center for Applied Biobehavioral Sciences (CABS), Alliant International University, San Diego, CA, USA.
| | - Molly A Tobin
- Touro University CA College of Osteopathic Medicine, Vallejo, CA, USA
| | - Grace A Lara
- Touro University CA College of Osteopathic Medicine, Vallejo, CA, USA
| | - Sankalp Sinha
- Touro University CA College of Osteopathic Medicine, Vallejo, CA, USA
| | - Rebecca M Morse
- Touro University CA College of Osteopathic Medicine, Vallejo, CA, USA
| | - Alexander G Hajduczok
- Division of Cardiovascular Medicine, Department of Medicine, University of California, San Diego, CA, USA
| | - Raouf S Gharbo
- Virginia Commonwealth University School of Medicine Department of Physical Medicine and Rehabilitation, Richmond, VA, USA
| | - Richard N Gevirtz
- Center for Applied Biobehavioral Sciences (CABS), Alliant International University, San Diego, CA, USA
| |
Collapse
|
|
2
|
Reyes-Lagos JJ, Guzmán-Ramos K, Lomelí J, Pliego-Carrillo AC, Peña-Castillo MÁ, López-Sánchez P, Trujillo-Condes VE, Garay-Jiménez LI, Echeverría JC, Villegas-Zarco MF, Santiago-Fuentes LM. Diabetes alters cardiorespiratory dynamics: insights from short-term recurrence quantification analysis of pulse-respiration quotient. Front Physiol 2025; 16:1584922. [PMID: 40352153 PMCID: PMC12061984 DOI: 10.3389/fphys.2025.1584922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Accepted: 03/24/2025] [Indexed: 05/14/2025] Open
Abstract
Introduction The Pulse-Respiration Quotient (PRQ) is considered a powerful tool for assessing dynamic interactions between cardiac and respiratory rhythms. Type 2 diabetes mellitus (T2DM) disrupts autonomic control, potentially compromising the complexity and adaptability of cardiorespiratory dynamics. In this cross-sectional, exploratory study, we investigated whether T2DM alters cardiorespiratory dynamics by analyzing short-term PRQ signals using conventional linear indices and Recurrence Quantification Analysis (RQA). Methods Thirty-eight participants (20 T2DM and 18 controls) completed four standardized tasks-supine rest, orthostatic challenge, paced breathing, and the Valsalva maneuver-while electrocardiographic and respiratory signals were continuously recorded. From these signals, R-to-R peak interval (RRI) and breath-to-breath (BB) time series were derived, allowing us to compute the PRQ time series as the ratio of instantaneous heart rate to instantaneous breathing rate. Linear indices of PRQ and RQA metrics were then calculated for the PRQ signals, enabling comparisons between groups (T2DM vs. control) and across tasks. Additionally, entropy-based mutual information (MI) between RRI and BB was assessed as a quantitative measure of cardiorespiratory coupling. Results T2DM participants exhibited higher recurrence rates and prolonged recurrence time of the first type in the PRQ series, especially during paced breathing, suggesting a more rigid and less adaptive control mechanism. Although linear PRQ indices showed changes in some stage-dependent responses, they were less adept than RQA metrics at discerning subtle differences between groups. Furthermore, the complementary cardiorespiratory coupling assessment by MI revealed distinct compensatory patterns in T2DM during paced respiration and Valsalva. Conclusion These findings indicate potential dysautonomia or partial autonomic dysregulation in individuals with T2DM, as reflected by altered cardiorespiratory dynamics and reduced adaptability.
Collapse
Affiliation(s)
- José Javier Reyes-Lagos
- Facultad de Medicina, Universidad Autónoma del Estado de México, Toluca de Lerdo, Toluca, Mexico
| | - Kioko Guzmán-Ramos
- Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana Unidad Lerma, Lerma, Mexico
| | - Joel Lomelí
- Escuela Superior de Medicina, Instituto Politécnico Nacional, Miguel Hidalgo, Mexico City, Mexico
| | | | - Miguel Ángel Peña-Castillo
- Departamento de Ingeniería Eléctrica, Universidad Autónoma Metropolitana Unidad Iztapalapa, Iztapalapa, Mexico City, Mexico
| | - Pedro López-Sánchez
- Escuela Superior de Medicina, Instituto Politécnico Nacional, Miguel Hidalgo, Mexico City, Mexico
| | | | - Laura Ivoone Garay-Jiménez
- Unidad Profesional Interdisciplinaria en Ingeniería y Tecnologías Avanzadas, Instituto Politécnico Nacional, Mexico City, Mexico
| | - Juan Carlos Echeverría
- Departamento de Ingeniería Eléctrica, Universidad Autónoma Metropolitana Unidad Iztapalapa, Iztapalapa, Mexico City, Mexico
| | | | - Laura Mercedes Santiago-Fuentes
- Facultad de Medicina, Universidad Autónoma del Estado de México, Toluca de Lerdo, Toluca, Mexico
- Departamento de Ciencias de la Salud, Universidad Autónoma Metropolitana Unidad Iztapalapa, Iztapalapa, Mexico City, Mexico
| |
Collapse
|
|
3
|
Bekenova N, Aitkaliyev A, Vochshenkova T, Kassiyeva B, Benberin V. Cardiac Autonomic Neuropathy Is Not Associated with Apolipoprotein E Gene Isoforms in the Kazakh Population: A Case-Control Study. Diagnostics (Basel) 2024; 14:1978. [PMID: 39272762 PMCID: PMC11394646 DOI: 10.3390/diagnostics14171978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2024] [Revised: 08/30/2024] [Accepted: 09/01/2024] [Indexed: 09/15/2024] Open
Abstract
The absence of an early diagnosis of cardiac autonomic neuropathy might increase the risk of the disease, progressing to an irreversible stage. Therefore, this study aims to investigate the APOE gene isoforms in patients with cardiac autonomic neuropathy to identify early markers for predicting this disease in the Kazakh population. A total of 147 patients with cardiac neuropathy and 153 controls were examined in this case-control study. Patients were genotyped for two polymorphisms of the APOE gene using real-time PCR. Statistical calculations were performed using binary logistic regression. As a result of our study, we found that there was no statistically significant difference in the frequency of any APOE gene isoforms (APOE (ε2/ε2), APOE (ε2/ε3), APOE (ε2/ε4), APOE (ε3/ε3), or APOE (ε4/ε4)) between the patient group and the control group (p = 0.69, p = 0.64, p = 0.19, p = 0.22, p = 0.97, respectively). Thus, cardiac autonomic neuropathy is not associated with APOE gene isoforms in the Kazakh population.
Collapse
Affiliation(s)
- Nazira Bekenova
- Department of Science, Medical Centre Hospital of President's Affairs Administration of the Republic of Kazakhstan, Astana 010000, Kazakhstan
| | - Alisher Aitkaliyev
- Department of Science, Medical Centre Hospital of President's Affairs Administration of the Republic of Kazakhstan, Astana 010000, Kazakhstan
| | - Tamara Vochshenkova
- Department of Science, Medical Centre Hospital of President's Affairs Administration of the Republic of Kazakhstan, Astana 010000, Kazakhstan
| | - Balzhan Kassiyeva
- Department of Science, Medical Centre Hospital of President's Affairs Administration of the Republic of Kazakhstan, Astana 010000, Kazakhstan
| | - Valeriy Benberin
- Department of Science, Medical Centre Hospital of President's Affairs Administration of the Republic of Kazakhstan, Astana 010000, Kazakhstan
- Institute of Innovative and Preventive Medicine, Astana 010000, Kazakhstan
| |
Collapse
|
|
4
|
Jarrett MS, Anderson T, Wideman L, Davis PG. Direct and indirect effects of adiposity on markers of autonomic nervous system activity in older adults. PLoS One 2024; 19:e0303117. [PMID: 38753844 PMCID: PMC11098483 DOI: 10.1371/journal.pone.0303117] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 04/12/2024] [Indexed: 05/18/2024] Open
Abstract
Several cardiovascular disease (CVD) risk factors (e.g., hypertension, poor glycemic control) can affect and be affected by autonomic nervous system (ANS) activity. Since excess adiposity can influence CVD development through its effect on hypertension and diabetes mellitus, it is important to determine how adiposity and altered ANS activity are related. The present study employed structural equation modeling to investigate the relation between adiposity and ANS activity both directly and indirectly through biological variables typically associated with glycemic impairment and cardiac stress in older adults. Utilizing the Atherosclerosis Risk in Communities (ARIC) dataset, 1,145 non-smoking adults (74±4.8 yrs, 62.8% female) free from known CVD, hypertension, and diabetes and not currently taking beta-blockers were evaluated for fasting blood glucose (FBG), insulin, and HbA1c concentrations, waist circumference (WC), blood pressure (BP), and markers of ANS activity. WC was recorded just above the iliac crest and was used to reflect central adiposity. Resting 2-minute electrocardiograph recordings, pulse wave velocity, and ankle-brachial index data were used to assess the root mean square of successive differences in RR intervals (RMSSD) and the pre-ejection period (PEP), markers of parasympathetic and sympathetic activity, respectively. FBG, insulin, and HbA1c inferred a latent variable termed glycemic impairment (GI), whereas heart rate and diastolic BP inferred a latent variable termed cardiac stress (CS). The structural equation model fit was acceptable [root mean square error of approximation = 0.050 (90% CI = .036, .066), comparative fit index = .970, Tucker Lewis Index = 0.929], with adiposity having both significant direct (β = 0.208, p = 0.018) and indirect (β = -.217, p = .041) effects on PEP through GI. Adiposity displayed no significant direct effect on RMSSD. CS displayed a significant pathway (β = -0.524, p = 0.035) on RMSSD, but the indirect effect of WC on RMSSD through CS did not reach statistical significance (β = -0.094, p = 0.137). These results suggest that adiposity's relation to ANS activity is multifaceted, as increased central adiposity had opposing direct and indirect effects on markers of sympathetic activity in this population of older adults.
Collapse
Affiliation(s)
- Michael S. Jarrett
- Department of Kinesiology, University of North Carolina at Greensboro, Greensboro, North Carolina, United States of America
- Department of Exercise Physiology, Winston Salem State University, Winston Salem, North Carolina, United States of America
| | - Travis Anderson
- Department of Kinesiology, University of North Carolina at Greensboro, Greensboro, North Carolina, United States of America
- United States Olympic and Paralympic Committee, Colorado Springs, Colorado, United States of America
| | - Laurie Wideman
- Department of Kinesiology, University of North Carolina at Greensboro, Greensboro, North Carolina, United States of America
| | - Paul G. Davis
- Department of Kinesiology, University of North Carolina at Greensboro, Greensboro, North Carolina, United States of America
| |
Collapse
|
|
5
|
Sharma C, Suliman A, Al Hamed S, Yasin J, AlKaabi J, Aburawi EH. Lipid profile, inflammatory biomarkers, endothelial dysfunction, and heart rate variability in adolescents with type 1 diabetes. A case-control study among UAE population. Heliyon 2024; 10:e29623. [PMID: 38694062 PMCID: PMC11058295 DOI: 10.1016/j.heliyon.2024.e29623] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 04/02/2024] [Accepted: 04/11/2024] [Indexed: 05/03/2024] Open
Abstract
Background Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by the chronic inflammation and cause of endothelial dysfunction (ED). Heart rate variability (HRV) is a marker of sympathetic and parasympathetic autonomic nervous system dysfunction. We investigated the association of lipid profile, inflammatory biomarkers, endothelial dysfunction, and heart rate variability in adolescents with T1DM among UAE population. Method In this case-control study we recruited 126 adolescents (13-22 years) from Abu Dhabi, UAE (United Arab Emirates). Demographic, anthropometric, blood and urine samples were collected after an overnight fasting. HRV measurements were determined per Task Force recommendations. Independent t-test or Mann-Whitney U test and Pearson's Chi-squared test were used to compare groups. Adjusted conditional logistic regression model was used to identify the determinants independently associated with T1DM. Results The mean ages in control (n = 47) and patient (n = 79) groups were 17.5 ± 4.6 and 18.6 ± 4.8 years, respectively. A family history of diabetes and waist and hip circumferences significantly differed between the groups (p = 0.030 and 0.010). The patients with T1DM exhibited significantly higher levels of atherogenic markers than control. Endothelial dysfunction biomarkers such as levels of sICAM-1 (p < 0.001), adiponectin (p < 0.001) and 25-hydroxyvitamin D (p < 0.001) were significantly different in the control group compared with those in the T1DM group. There was a significant difference in SDNN intervals, NN50, pNN50, and SD1/SD2 among the two groups. In adjusted analysis, total cholesterol (adjusted Odds Ratio (aOR): 2.78, 95 % CI:1.37-5.64; p = 0.005), LDL (2.66, 95%CI:1.19-5.92; p = 0.017), and triglycerides (5.51, 95%CI:1.57-19.41; p = 0.008) were significantly associated with developing T1DM. The HRV indicators were significantly associated with decrease odds of T1DM after controlling for SBP, BMI, and family history of DM. Conclusion In this study, adolescents with T1DM showed a significant association with lipid profile, ED, and HRV compared with controls. Thus, an early attention to diabetes control is required to reduce the risk of cardiac autonomic neuropathy leading to various cardiovascular diseases.
Collapse
Affiliation(s)
- Charu Sharma
- Department of Internal Medicine, United Arab Emirates
| | | | - Sania Al Hamed
- Department of Paediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, P. O. Box 15551, United Arab Emirates
| | - Javed Yasin
- Department of Internal Medicine, United Arab Emirates
| | - Juma AlKaabi
- Department of Internal Medicine, United Arab Emirates
| | - Elhadi Husein Aburawi
- Department of Paediatrics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, P. O. Box 15551, United Arab Emirates
| |
Collapse
|
|
6
|
Bekenova N, Sibagatova A, Aitkaliyev A, Vochshenkova T, Kassiyeva B, Benberin V. Genetic markers of cardiac autonomic neuropathy in the Kazakh population. BMC Cardiovasc Disord 2024; 24:242. [PMID: 38724937 PMCID: PMC11080244 DOI: 10.1186/s12872-024-03912-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Accepted: 04/30/2024] [Indexed: 05/13/2024] Open
Abstract
BACKGROUND Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that increases the risk of morbidity and mortality by disrupting cardiac innervation. Recent evidence suggests that CAN may manifest even before the onset of DM, with prediabetes and metabolic syndrome potentially serving as precursors. This study aims to identify genetic markers associated with CAN development in the Kazakh population by investigating the SNPs of specific genes. MATERIALS AND METHODS A case-control study involved 82 patients with CAN (cases) and 100 patients without CAN (controls). A total of 182 individuals of Kazakh nationality were enrolled from a hospital affiliated with the RSE "Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan". 7 SNPs of genes FTO, PPARG, SNCA, XRCC1, FLACC1/CASP8 were studied. Statistical analysis was performed using Chi-square methods, calculation of odds ratios (OR) with 95% confidence intervals (CI), and logistic regression in SPSS 26.0. RESULTS Among the SNCA gene polymorphisms, rs2737029 was significantly associated with CAN, almost doubling the risk of CAN (OR 2.03(1.09-3.77), p = 0.03). However, no statistically significant association with CAN was detected with the rs2736990 of the SNCA gene (OR 1.00 CI (0.63-1.59), p = 0.99). rs12149832 of the FTO gene increased the risk of CAN threefold (OR 3.22(1.04-9.95), p = 0.04), while rs1801282 of the PPARG gene and rs13016963 of the FLACC1 gene increased the risk twofold (OR 2.56(1.19-5.49), p = 0.02) and (OR 2.34(1.00-5.46), p = 0.05) respectively. rs1108775 and rs1799782 of the XRCC1 gene were associated with reduced chances of developing CAN both before and after adjustment (OR 0.24, CI (0.09-0.68), p = 0.007, and OR 0.43, CI (0.22-0.84), p = 0.02, respectively). CONCLUSION The study suggests that rs2737029 (SNCA gene), rs12149832 (FTO gene), rs1801282 (PPARG gene), and rs13016963 (FLACC1 gene) may be predisposing factors for CAN development. Additionally, SNPs rs1108775 and rs1799782 (XRCC1 gene) may confer resistance to CAN. Only one polymorphism rs2736990 of the SNCA gene was not associated with CAN.
Collapse
Affiliation(s)
- Nazira Bekenova
- Gerontology Center, Medical Centre Hospital of President's Affairs Administration of the Republic of Kazakhstan, Mangilik El 80, Astana City, 010000, Kazakhstan.
| | - Ainur Sibagatova
- Gerontology Center, Medical Centre Hospital of President's Affairs Administration of the Republic of Kazakhstan, Mangilik El 80, Astana City, 010000, Kazakhstan
| | - Alisher Aitkaliyev
- Gerontology Center, Medical Centre Hospital of President's Affairs Administration of the Republic of Kazakhstan, Mangilik El 80, Astana City, 010000, Kazakhstan
| | - Tamara Vochshenkova
- Gerontology Center, Medical Centre Hospital of President's Affairs Administration of the Republic of Kazakhstan, Mangilik El 80, Astana City, 010000, Kazakhstan
| | - Balzhan Kassiyeva
- Gerontology Center, Medical Centre Hospital of President's Affairs Administration of the Republic of Kazakhstan, Mangilik El 80, Astana City, 010000, Kazakhstan
| | - Valeriy Benberin
- Gerontology Center, Medical Centre Hospital of President's Affairs Administration of the Republic of Kazakhstan, Mangilik El 80, Astana City, 010000, Kazakhstan
| |
Collapse
|
|
7
|
Hajdu M, Garmpis K, Vértes V, Vorobcsuk-Varga N, Molnár GA, Hejjel L, Wittmann I, Faludi R. Determinants of the heart rate variability in type 1 diabetes mellitus. Front Endocrinol (Lausanne) 2023; 14:1247054. [PMID: 37854193 PMCID: PMC10579906 DOI: 10.3389/fendo.2023.1247054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Accepted: 09/04/2023] [Indexed: 10/20/2023] Open
Abstract
Background Evaluation of heart rate variability (HRV) detects the early subclinical alterations of the autonomic nervous system. Thus, impaired HRV is the earliest subclinical marker of cardiac autonomic neuropathy (CAN) in type 1 diabetes mellitus (T1DM). Objectives We aimed to explore the HRV parameters in asymptomatic T1DM patients and compare them with the results obtained in healthy subjects. Potential associations between HRV parameters and the established risk factors for CAN and cardiovascular diseases were also investigated. Methods Seventy T1DM patients (38 ± 12 years, 46 females) and 30 healthy subjects were enrolled into the study. For HRV analysis, beat-to-beat heart rate was recorded for 30 min. The less noisy 5-min segment of the recording was analyzed by Bittium Cardiac Navigator HRV analysis software. Time domain, frequency domain, and nonlinear indices were calculated. Results Regarding ratio of low to high frequency component (LF/HF), no differences were found between the two populations (p = 0.227). All the further, time domain, frequency domain, and nonlinear HRV indices were significantly lower in T1DM patients (each p < 0.001). In multiple linear models, disease duration remained the only independent predictor of LF/HF ratio (p = 0.019). HbA1c was found to be significant independent predictor of all further time domain (SDNN, p < 0.001; rMSSD, p < 0.001), frequency domain (VLF, p < 0.001; LF, p = 0.002; HF, p = 0.006; Total Power, p = 0.002), and nonlinear indices (SD1, p = 0.006; SD2, p = 0.007), alone, or in combination with other factors, such as age or body mass index. Conclusion Asymptomatic T1DM patients have significantly reduced overall HRV as compared with healthy subjects, indicating subclinical CAN. Quality of the glycemic control is important determinant of HRV among T1DM patients. This relationship is independent of other risk factors for CAN or cardiovascular diseases.
Collapse
Affiliation(s)
- Máté Hajdu
- Heart Institute, Medical School, University of Pécs, Pécs, Hungary
| | | | - Vivien Vértes
- Heart Institute, Medical School, University of Pécs, Pécs, Hungary
| | | | - Gergő Attila Molnár
- 2nd Department of Internal Medicine and Nephrological Center, Medical School, University of Pécs, Pécs, Hungary
| | - László Hejjel
- Heart Institute, Medical School, University of Pécs, Pécs, Hungary
| | - István Wittmann
- 2nd Department of Internal Medicine and Nephrological Center, Medical School, University of Pécs, Pécs, Hungary
| | - Réka Faludi
- Heart Institute, Medical School, University of Pécs, Pécs, Hungary
| |
Collapse
|
|
8
|
Bossenger NR, Lewis GN, Rice DA, Shepherd D. The autonomic and nociceptive response to acute experimental stress is impaired in people with knee osteoarthritis: A preliminary study. NEUROBIOLOGY OF PAIN (CAMBRIDGE, MASS.) 2023; 14:100144. [PMID: 38099282 PMCID: PMC10719531 DOI: 10.1016/j.ynpai.2023.100144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 09/19/2023] [Accepted: 09/19/2023] [Indexed: 12/17/2023]
Abstract
Objective Alterations in autonomic function are evident in some chronic pain conditions but have not been thoroughly examined in people with osteoarthritis (OA). The study aimed to examine resting autonomic nervous system (ANS) function in people with knee OA, and the response of the autonomic and nociceptive systems to acute stress. Methods A preliminary cross-sectional study was undertaken involving people with knee OA (n = 14), fibromyalgia (n = 13), and pain-free controls (n = 15). The sympathetic and parasympathetic components of the ANS were assessed through measures of pre-ejection period (PEP), skin conductance level (SCL), and high frequency heart rate variability (HF HRV). The nociceptive system was assessed through pain ratings associated with a tonic heat pain stimulus. In separate sessions, ANS and heat pain measures were assessed at rest and in response to nociceptive and mental arithmetic stressors. Results The knee OA group showed reduced HF HRV at rest and reduced modulation in response to stress. Resting PEP and SCL were normal in the knee OA group but PEP modulation was impaired in both chronic pain groups during nociceptive stress. The expected reduction in tonic heat pain ratings in response to stress was lacking in the knee OA and FM groups. Conclusion Preliminary evidence shows impaired parasympathetic nervous system function at rest and in response to nociceptive and mental stress in people with knee OA, with some evidence of altered sympathetic nervous system function. Impaired ANS function could contribute to ongoing pain experienced, and interventions that target ANS function could be beneficial.
Collapse
Affiliation(s)
- Neil R Bossenger
- Health and Rehabilitation Research Institute, Auckland University of Technology, Auckland, New Zealand
| | - Gwyn N Lewis
- Health and Rehabilitation Research Institute, Auckland University of Technology, Auckland, New Zealand
| | - David A Rice
- Health and Rehabilitation Research Institute, Auckland University of Technology, Auckland, New Zealand
- Waitematā Pain Service, Te Whatu Ora Waitematā, Auckland, New Zealand
| | - Daniel Shepherd
- Department of Psychology, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland, New Zealand
| |
Collapse
|
|
9
|
Urbina EM, Isom S, Dabelea D, D’Agostino R, Daniels SR, Dolan LM, Imperatore G, Lustigova E, Marcovina S, Mottl A, Pihoker C, Shah AS. Association of Elevated Arterial Stiffness With Cardiac Target Organ Damage and Cardiac Autonomic Neuropathy in Young Adults With Diabetes: The SEARCH for Diabetes in Youth Study. Diabetes Care 2023; 46:786-793. [PMID: 36730642 PMCID: PMC10090911 DOI: 10.2337/dc22-1703] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 01/09/2023] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Adults with diabetes are at risk for cardiovascular (CV) events, possibly due to increased arterial stiffness (AS) and cardiac autonomic neuropathy (CAN). We sought to determine whether 1) AS is associated with cardiac target organ damage in young adults with youth-onset diabetes, 2) whether CAN is associated with AS, as one possible etiology for increased AS in this cohort, and 3) whether these relationships differ by type of diabetes. RESEARCH DESIGN AND METHODS Participants from the SEARCH for Diabetes in Youth Study (type 1 diabetes [T1D], n = 222; type 2 diabetes [T2D], n = 177; mean age 23 years) had clinical, echocardiographic, AS, and CAN assessed. Linear regression was performed to determine whether AS was associated with cardiac changes and CAN and whether relationships differed by diabetes type. RESULTS AS was significantly associated with cardiac structure (left ventricular mass index, P < 0.0001), systolic function (ejection fraction, P = 0.03) and diastolic function (transmitral peak early [E]/atrial [A] wave velocities ratio, P = 0.008; early [e']/atrial [a'] waves, P = 0.02) after adjustments for CV risk factors. The association between AS and CAN was not significant when other important covariates were added. These relationships were mostly similar in both T1D and T2D. CONCLUSIONS AS is associated with cardiac changes in young adults with diabetes. CAN-induced AS does not appear to be an etiology for cardiac abnormalities in this cohort.
Collapse
Affiliation(s)
- Elaine M. Urbina
- Department of Pediatrics, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, OH
| | - Scott Isom
- Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC
| | - Dana Dabelea
- Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, University of Colorado Anschutz Medical Campus (CU-Anschutz), Aurora, CO
| | - Ralph D’Agostino
- Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC
| | - Stephen R. Daniels
- Department of Pediatrics, University of Colorado Anschutz Medical Campus (CU-Anschutz), Aurora, CO
| | - Lawrence M. Dolan
- Department of Pediatrics, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, OH
| | - Giuseppina Imperatore
- Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA
| | - Eva Lustigova
- Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, CA
| | | | - Amy Mottl
- Division of Nephrology and Hypertension, University of North Carolina School of Medicine, Chapel Hill, NC
| | | | - Amy S. Shah
- Department of Pediatrics, Cincinnati Children’s Hospital Medical Center and University of Cincinnati, Cincinnati, OH
| |
Collapse
|
|
10
|
Pikov V. Bioelectronic medicine for restoring autonomic balance in autoimmune diseases. GUT MICROBIOTA AND INTEGRATIVE WELLNESS 2023; 1:182. [PMID: 37155473 PMCID: PMC10125261 DOI: 10.54844/gmiw.2022.0182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/10/2023]
Abstract
The aim of this mini-review is to introduce most prevalent autoimmune diseases, emphasize the importance of sympatho-parasympathetic imbalance in these autoimmune diseases, demonstrate how such imbalance can be effectively treated using the bioelectronic medicine, and describe potential mechanisms of bioelectronic medicine effects on the autoimmune activity at the cellular and molecular levels.
Collapse
|
|
11
|
Nattero-Chávez L, Insenser M, Quintero Tobar A, Fernández-Durán E, Dorado Avendaño B, Fiers T, Kaufman JM, Luque-Ramírez M, Escobar-Morreale HF. Sex differences and sex steroids influence on the presentation and severity of cardiovascular autonomic neuropathy of patients with type 1 diabetes. Cardiovasc Diabetol 2023; 22:32. [PMID: 36793089 PMCID: PMC10127589 DOI: 10.1186/s12933-023-01766-y] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2022] [Accepted: 02/05/2023] [Indexed: 02/17/2023] Open
Abstract
BACKGROUND Sex differences characterize cardiovascular outcomes in patients with type 1 diabetes. Cardioautonomic neuropathy is a common complication of type 1 diabetes that associates increased morbi-mortality. Data regarding the interplay between sex and cardiovascular autonomic neuropathy are scarce and controversial in these patients. We aimed to address sex-related differences in the prevalence of seemingly asymptomatic cardioautonomic neuropathy in type 1 diabetes, and their associations with sex steroids. METHODS We conducted a cross-sectional study including 322 consecutively recruited patients with type 1 diabetes. Cardioautonomic neuropathy was diagnosed using Ewing's score and power spectral heart rate data. We assessed sex hormones by liquid chromatography/tandem mass spectrometry. RESULTS When considering all subjects as a whole, asymptomatic cardioautonomic neuropathy prevalence was not significantly different between women and men. When age was taken into account, the prevalence of cardioautonomic neuropathy was similar among young men and those > 50 years. However, in women > 50 years, the prevalence of cardioautonomic neuropathy doubled that of young women [45.8% (32.6; 59.7) vs. 20.4% (13.7; 29.2), respectively]. The OR of having cardioautonomic neuropathy was 3.3 higher in women > 50 years than in their younger counterparts. Furthermore, women presented more severe cardioautonomic neuropathy than men. These differences were even more marked when women were classified according their menopausal status instead of age. Peri- and menopausal women had an OR 3.5 (1.7; 7.2) of having CAN compared with their reproductive-aged counterparts [CAN prevalence: 51% (37; 65) vs. 23% (16; 32), respectively]. A binary logistic regression model (R2: 0.161; P = 0.001) displayed age > 50 years as a significant determinant of cardioautonomic neuropathy only in women. Androgens were positively associated with heart rate variability in men, and negatively in women. Accordingly, cardioautonomic neuropathy was associated with increased testosterone/estradiol ratio in women but to decreased testosterone concentrations in men. CONCLUSIONS Menopause in women with type 1 diabetes is accompanied by an increase in the prevalence of asymptomatic cardioautonomic neuropathy. This age-related excess risk of cardioautonomic neuropathy is not observed in men. Men and women with type 1 diabetes have opposite associations between circulating androgens and indexes of cardioautonomic function. Trial registration ClinicalTrials.gov Identifier: NCT04950634.
Collapse
Affiliation(s)
- Lía Nattero-Chávez
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Carretera de Colmenar, Km 9.1, 28034, Madrid, Spain.,Diabetes, Obesity and Human Reproduction Research Group, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
| | - María Insenser
- Diabetes, Obesity and Human Reproduction Research Group, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
| | - Alejandra Quintero Tobar
- Diabetes, Obesity and Human Reproduction Research Group, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
| | - Elena Fernández-Durán
- Diabetes, Obesity and Human Reproduction Research Group, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain
| | - Beatriz Dorado Avendaño
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Carretera de Colmenar, Km 9.1, 28034, Madrid, Spain
| | - Tom Fiers
- Laboratory for Hormonology and Department of Endocrinology, Ghent University Hospital, 9000, Ghent, Belgium
| | - Jean-Marc Kaufman
- Laboratory for Hormonology and Department of Endocrinology, Ghent University Hospital, 9000, Ghent, Belgium
| | - Manuel Luque-Ramírez
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Carretera de Colmenar, Km 9.1, 28034, Madrid, Spain. .,Diabetes, Obesity and Human Reproduction Research Group, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, Madrid, Spain. .,University of Alcalá, Madrid, Spain.
| | - Héctor F Escobar-Morreale
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Carretera de Colmenar, Km 9.1, 28034, Madrid, Spain.,Laboratory for Hormonology and Department of Endocrinology, Ghent University Hospital, 9000, Ghent, Belgium.,University of Alcalá, Madrid, Spain
| |
Collapse
|
|
12
|
Elshenawy DSA, Ramadan NM, Abdo VB, Ashour RH. Sacubitril/valsartan combination enhanced cardiac glycophagy and prevented the progression of murine diabetic cardiomyopathy. Biomed Pharmacother 2022; 153:113382. [PMID: 36076522 DOI: 10.1016/j.biopha.2022.113382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 06/26/2022] [Accepted: 07/06/2022] [Indexed: 01/18/2023] Open
|
|
13
|
Shah AS, Isom S, D’Agostino R, Dolan LM, Dabelea D, Imperatore G, Mottl A, Lustigova E, Pihoker C, Marcovina S, Urbina EM. Longitudinal Changes in Arterial Stiffness and Heart Rate Variability in Youth-Onset Type 1 Versus Type 2 Diabetes: The SEARCH for Diabetes in Youth Study. Diabetes Care 2022; 45:1647-1656. [PMID: 35667385 PMCID: PMC9274217 DOI: 10.2337/dc21-2426] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2021] [Accepted: 03/02/2022] [Indexed: 02/03/2023]
Abstract
OBJECTIVE We compared arterial stiffness and heart rate variability (HRV) over time by diabetes type and determined the risk factors associated with worsening arterial stiffness and HRV in young adults with youth-onset diabetes. RESEARCH DESIGN AND METHODS Arterial stiffness (pulse wave velocity, augmentation index) and six indices of heart rate variability were measured twice, 4.5 years apart, among participants with either youth-onset type 1 or type 2 diabetes in the SEARCH for Diabetes in Youth study. Multivariable linear regression models were used to assess risk factors associated with arterial stiffness and HRV at follow-up. RESULTS Of 1,159 participants studied, 949 had type 1 diabetes (mean age 17.1 ± 4.7 years, 60.3% non-Hispanic White, 55% female) and 210 had type 2 diabetes (mean age 22.1 ± 3.5 years, 23.8% non-Hispanic White, 71% female) at initial assessment when diabetes duration was 7.9 years (both groups). Participants with type 2 versus type 1 diabetes had greater arterial stiffness and more abnormalities in HRV at initial and follow-up assessment and a greater change over time (all P < 0.05). Risk factors associated with worse arterial stiffness and HRV at follow-up in both types of diabetes included higher blood pressure, hemoglobin A1c, waist circumference, and triglycerides over time and longer diabetes duration. CONCLUSIONS Arterial stiffness and HRV worsened over time with greater changes among participants with type 2 versus type 1 diabetes and among those with features of the metabolic syndrome. The risk factor profile documents potentially modifiable pathways to prevent or limit cardiovascular complications in young adults with youth-onset diabetes.
Collapse
Affiliation(s)
- Amy S. Shah
- Department of Pediatrics, Cincinnati Children’s Hospital Medical Center and The University of Cincinnati, Cincinnati, OH
| | - Scott Isom
- Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC
| | - Ralph D’Agostino
- Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC
| | - Lawrence M. Dolan
- Department of Pediatrics, Cincinnati Children’s Hospital Medical Center and The University of Cincinnati, Cincinnati, OH
| | - Dana Dabelea
- Lifecourse Epidemiology of Adiposity and Diabetes Center, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Giuseppina Imperatore
- Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA
| | - Amy Mottl
- Division of Nephrology and Hypertension, University of North Carolina School of Medicine, Chapel Hill, NC
| | - Eva Lustigova
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA
| | | | | | - Elaine M. Urbina
- Department of Pediatrics, Cincinnati Children’s Hospital Medical Center and The University of Cincinnati, Cincinnati, OH
| |
Collapse
|
|
14
|
Castiglioni P, Faini A, Nys A, De Busser R, Scherrenberg M, Baldussu E, Parati G, Dendale P. Heart Rate Variability for the Early Detection of Cardiac Autonomic Dysfunction in Type 1 Diabetes. Front Physiol 2022; 13:937701. [PMID: 35846022 PMCID: PMC9281578 DOI: 10.3389/fphys.2022.937701] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 06/10/2022] [Indexed: 11/24/2022] Open
Abstract
Type 1 diabetes mellitus (T1DM) has an important impact on morbidity and mortality because it may start early in life. Therefore, the early detection of cardiovascular autonomic neuropathy (DCAN) in T1DM patients is important to intervene quickly and prevent further deterioration. Traditional autonomic function tests detect abnormalities in severely symptomatic patients but they are difficult to be standardized, require the patient’s active participation and their sensitivity to the early disease is limited. In comparison, heart rate variability (HRV) is easier to be measured and standardized. Therefore, we aim to find the HRV indexes that better identify DCAN at an early stage in T1DM patients, and evaluate if HRV is a valid alternative to traditional tests. For this aim, we administered the SCOPA-AUT questionnaire on symptoms of autonomic dysfunction as well as deep breathing, Valsalva, handgrip, head-up tilt (HUT), and cold-pressor tests, to 52 T1DM patients and 27 controls. We calculated HRV indexes during supine rest (SUP) and HUT, assessing differences between groups and postures by a linear mixed-effect model for repeated measures. Receiver Operating Characteristic (ROC) analysis quantified how each HRV index and autonomic test distinguishes between patients and controls. We found that the SCOPA-AUT score was slightly but significantly (p < 0.05) greater in patients, indicating an early DCAN. T1DM patients preserved the HRV response to changing posture but in SUP they showed significantly lower standard deviation and vagal indexes of HRV than controls. The area under the ROC curve of these HRV indexes was not lower than 0.68. By contrast, traditional autonomic tests did not differ between groups. Therefore, early DCAN initially causes an impairment of the cardiac vagal control manifest in conditions of elevated vagal tone, as in SUP. Compensatory adjustments of the sympathetic control might explain the unaltered response to traditional autonomic tests. In conclusion, vagal HRV indexes in SUP help to identify early DCAN better than traditional tests, potentially allowing rapid interventions.
Collapse
Affiliation(s)
| | - Andrea Faini
- Istituto Auxologico Italiano, IRCCS, Milan, Italy
| | - Anika Nys
- UHasselt, Faculty of Medicine and Life Sciences, Diepenbeek, Belgium
| | - Renee De Busser
- KU Leuven, Faculty of Medicine and Life Sciences, Leuven, Belgium
| | - Martijn Scherrenberg
- UHasselt, Faculty of Medicine and Life Sciences, Diepenbeek, Belgium
- Heart Centre Hasselt, Jessa Hospital, Hasselt, Belgium
- Faculty of Medicine and Health Sciences, Antwerp University, Belgium
| | - Esmee Baldussu
- Maastricht UMC+, Maastricht, Netherlands
- KU Leuven, Faculty of Medicine and Life Sciences, Leuven, Belgium
| | - Gianfranco Parati
- Istituto Auxologico Italiano, IRCCS, Milan, Italy
- Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
| | - Paul Dendale
- UHasselt, Faculty of Medicine and Life Sciences, Diepenbeek, Belgium
- KU Leuven, Faculty of Medicine and Life Sciences, Leuven, Belgium
| |
Collapse
|
|
15
|
Factors Associated with Reduced Heart Rate Variability in the General Japanese Population: The Iwaki Cross-Sectional Research Study. Healthcare (Basel) 2022; 10:healthcare10050793. [PMID: 35627930 PMCID: PMC9141757 DOI: 10.3390/healthcare10050793] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 04/20/2022] [Accepted: 04/22/2022] [Indexed: 12/20/2022] Open
Abstract
Although many studies have reported factors associated with reduced heart rate variability (HRV) in Western populations, evidence is limited among Asian populations. Therefore, we investigated the factors associated with reduced HRV values in a general Japanese population by measuring HRV among the participants of the Iwaki Health Promotion Project who underwent medical examination in 2019. We performed 90-s HRV measurements in 1065 participants. Of these, we evaluated the coefficient of variation in R–R intervals (CVRR) and standard deviation in R–R intervals (SDNN). Blood was collected under a fasting condition, and investigations of glucose metabolism, lipid metabolism, renal function, liver function, advanced glycation end products, and blood pressure were performed. A multivariate regression analysis of the association between CVRR or SDNN and blood test parameters and blood pressure in 987 participants with adequately completed HRV assessments showed that reduced CVRR or SDNN was associated with higher levels of glycated hemoglobin (HbA1c), glycoalbumin, blood glucose, triglycerides, creatinine, plasma pentosidine, and diastolic blood pressure. In the general Japanese population, higher levels of HbA1c, glycoalbumin, blood glucose, triglycerides, creatinine, plasma pentosidine, and diastolic blood pressure are associated with reduced CVRR or SDNN, which are typical HRV parameters.
Collapse
|
|
16
|
Franceschi R, Mozzillo E, Di Candia F, Rosanio FM, Leonardi L, Liguori A, Micheli F, Cauvin V, Franzese A, Piona CA, Marcovecchio ML. A systematic review of the prevalence, risk factors and screening tools for autonomic and diabetic peripheral neuropathy in children, adolescents and young adults with type 1 diabetes. Acta Diabetol 2022; 59:293-308. [PMID: 35089443 DOI: 10.1007/s00592-022-01850-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Accepted: 01/09/2022] [Indexed: 01/09/2023]
Abstract
AIMS We aimed to estimate the prevalence of Diabetic peripheral neuropathy (DPN) and Cardiac autonomic neuropathy (CAN) in youth with type 1 diabetes; identify key risk factors; identify the most useful tests for the diagnostic evaluation of DPN and CAN; identify key treatment options for DPN and CAN. METHODS A systematic search was performed including studies published in the last 15 years. PICO framework was used in the selection process and evidence was assessed using the GRADE system. RESULTS A total of 758 studies were identified and a final number of 49 studies were included in this systematic review. According to moderate-high level quality studies, the prevalence of probable DPN, ranged between 13.5 and 62%; subclinical DPN between 22 and 88%; confirmed DPN between 2.6 and 11%. The Michigan Neuropathy Screening Instrument was the tool with higher sensitivity and specificity for detecting DPN, which needs to be confirmed by nerve conduction velocity. The prevalence of CAN was 4-39%. Specific treatment options for DPN or CAN in patients younger than 25 years are not available. Key risk factors for DPN and CAN are hyperglycemia/HbA1c, age, diabetes duration, the presence of other microvascular complications, waist/height ratio, lipid profile and blood pressure. For CAN, additional risk factors were cigarette smoking, BMI and total daily insulin. CONCLUSIONS Prevalence of neuropathy in youth with type 1 diabetes varies depending on different screening methods and characteristics of the study populations. However, the assessed studies confirmed a relatively high prevalence of subclinical neuropathy, reiterating the importance of early identification of risk factors to prevent this complication.
Collapse
Affiliation(s)
- Roberto Franceschi
- Pediatric Diabetology Unit, Pediatric Department, S. Chiara General Hospital, Largo Medaglie d'Oro, 9, 38122, Trento, Italy.
| | - Enza Mozzillo
- Department of Translational Medical Science, Section of Pediatrics, Regional Center of Pediatric Diabetes, Federico II University of Naples, Naples, Italy
| | - Francesca Di Candia
- Department of Translational Medical Science, Section of Pediatrics, Regional Center of Pediatric Diabetes, Federico II University of Naples, Naples, Italy
| | - Francesco Maria Rosanio
- Department of Translational Medical Science, Section of Pediatrics, Regional Center of Pediatric Diabetes, Federico II University of Naples, Naples, Italy
| | - Letizia Leonardi
- Pediatric Diabetology Unit, Pediatric Department, S. Chiara General Hospital, Largo Medaglie d'Oro, 9, 38122, Trento, Italy
| | - Alice Liguori
- Pediatric Diabetology Unit, Pediatric Department, S. Chiara General Hospital, Largo Medaglie d'Oro, 9, 38122, Trento, Italy
| | - Francesca Micheli
- Pediatric Diabetology Unit, Pediatric Department, S. Chiara General Hospital, Largo Medaglie d'Oro, 9, 38122, Trento, Italy
| | - Vittoria Cauvin
- Pediatric Diabetology Unit, Pediatric Department, S. Chiara General Hospital, Largo Medaglie d'Oro, 9, 38122, Trento, Italy
| | - Adriana Franzese
- Department of Translational Medical Science, Section of Pediatrics, Regional Center of Pediatric Diabetes, Federico II University of Naples, Naples, Italy
| | - Claudia Anita Piona
- Section of Pediatric Diabetes and Metabolism, Department of Surgery, Dentistry, Gynecology and Pediatrics, University and Azienda Ospedaliera, Universitaria Integrata of Verona, Verona, Italy
| | - M Loredana Marcovecchio
- Department of Paediatrics, University of Cambridge and Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| |
Collapse
|
|
17
|
Al Kury LT, Chacar S, Alefishat E, Khraibi AA, Nader M. Structural and Electrical Remodeling of the Sinoatrial Node in Diabetes: New Dimensions and Perspectives. Front Endocrinol (Lausanne) 2022; 13:946313. [PMID: 35872997 PMCID: PMC9302195 DOI: 10.3389/fendo.2022.946313] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 06/14/2022] [Indexed: 11/14/2022] Open
Abstract
The sinoatrial node (SAN) is composed of highly specialized cells that mandate the spontaneous beating of the heart through self-generation of an action potential (AP). Despite this automaticity, the SAN is under the modulation of the autonomic nervous system (ANS). In diabetes mellitus (DM), heart rate variability (HRV) manifests as a hallmark of diabetic cardiomyopathy. This is paralleled by an impaired regulation of the ANS, and by a pathological remodeling of the pacemaker structure and function. The direct effect of diabetes on the molecular signatures underscoring this pathology remains ill-defined. The recent focus on the electrical currents of the SAN in diabetes revealed a repressed firing rate of the AP and an elongation of its tracing, along with conduction abnormalities and contractile failure. These changes are blamed on the decreased expression of ion transporters and cell-cell communication ports at the SAN (i.e., HCN4, calcium and potassium channels, connexins 40, 45, and 46) which further promotes arrhythmias. Molecular analysis crystallized the RGS4 (regulator of potassium currents), mitochondrial thioredoxin-2 (reactive oxygen species; ROS scavenger), and the calcium-dependent calmodulin kinase II (CaMKII) as metabolic culprits of relaying the pathological remodeling of the SAN cells (SANCs) structure and function. A special attention is given to the oxidation of CaMKII and the generation of ROS that induce cell damage and apoptosis of diabetic SANCs. Consequently, the diabetic SAN contains a reduced number of cells with significant infiltration of fibrotic tissues that further delay the conduction of the AP between the SANCs. Failure of a genuine generation of AP and conduction of their derivative waves to the neighboring atrial myocardium may also occur as a result of the anti-diabetic regiment (both acute and/or chronic treatments). All together, these changes pose a challenge in the field of cardiology and call for further investigations to understand the etiology of the structural/functional remodeling of the SANCs in diabetes. Such an understanding may lead to more adequate therapies that can optimize glycemic control and improve health-related outcomes in patients with diabetes.
Collapse
Affiliation(s)
- Lina T. Al Kury
- Department of Health Sciences, College of Natural and Health Sciences, Zayed University, Abu Dhabi, United Arab Emirates
- *Correspondence: Lina T. Al Kury, ; Moni Nader,
| | - Stephanie Chacar
- Department of Physiology and Immunology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
| | - Eman Alefishat
- Department of Pharmacology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
- Department of Biopharmaceutics and Clinical Pharmacy, School of Pharmacy, The University of Jordan, Amman, Jordan
- Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
| | - Ali A. Khraibi
- Department of Physiology and Immunology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
- Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
| | - Moni Nader
- Department of Physiology and Immunology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
- Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates
- *Correspondence: Lina T. Al Kury, ; Moni Nader,
| |
Collapse
|
|
18
|
Faulkner MS, Smart MJ. Sleep quality and heart rate variability in adolescents with type 1 or type 2 diabetes. J Diabetes Complications 2021; 35:108049. [PMID: 34600825 PMCID: PMC8608749 DOI: 10.1016/j.jdiacomp.2021.108049] [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: 04/08/2021] [Revised: 09/07/2021] [Accepted: 09/14/2021] [Indexed: 11/18/2022]
Abstract
INTRODUCTION Decreased sleep quality and lower heart rate variability (HRV) have both independently been associated with diabetes and may contribute to risks for cardiovascular disease. Although poor sleep quality has been associated with lower HRV in adults with type 2 diabetes (T2D), studies of sleep quality in adolescents with (T2D) or studies examining the possible association of poor sleep quality with lower HRV in adolescents with T2D or T1D are not available. AIM Thus, we conducted a secondary analysis of data from an existing study to determine if there were associations between sleep quality and HRV in adolescents with T1D or T2D. METHODS Adolescents with T1D (n = 101) or T2D (n = 37) completed 24-h HRV Holter monitoring and analysis and a self-reported global measure of sleep quality. RESULTS Poor sleep quality was significantly associated with lower HRV, a known predictor for CV risk. Those with T2D had lower measures of HRV. CONCLUSIONS The evaluation of sleep quality and early signs of cardiovascular autonomic changes should be considered in routine assessments of adolescents with diabetes. Future research is warranted to examine more robust measures of sleep and HRV in adolescents with diabetes.
Collapse
Affiliation(s)
| | - Michael J Smart
- Georgia State University, P.O. Box 4019, Atlanta, GA 30302-4019, USA.
| |
Collapse
|
|
19
|
Piona C, Ventrici C, Marcovecchio L, Chiarelli F, Maffeis C, Bonfanti R, Rabbone I. Long-term complications of type 1 diabetes: what do we know and what do we need to understand? Minerva Pediatr (Torino) 2021; 73:504-522. [PMID: 34530587 DOI: 10.23736/s2724-5276.21.06545-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Long-term complications of type 1 diabetes (T1D) include microvascular complications and macrovascular disease. Despite the important advances in the treatment of T1D of the last decades, these complications still represent the leading cause of morbidity and mortality in patients with T1D. Extensive evidence indicates that structural and functional alterations of the kidney, retina, nerves and large arteries occur already in the first years after the onset of diabetes. We performed a comprehensive review of the available evidence on screening, diagnosis, prevention and treatment of vascular complications of T1D. In particular, we focused on three major challenges related to long-term complications of T1D: 1) finding of new biomarkers and diagnostic methods able to identify early signs of complications; 2) identifying specific risk factors for the development of these complications; 3) identifying and implementing new therapeutic strategies able to prevent the development and progression of vascular complications.
Collapse
Affiliation(s)
- Claudia Piona
- Paediatric Diabetes and Metabolic Disorders Unit, Regional Center for Paediatric Diabetes, University City Hospital of Verona, Italy
| | - Claudia Ventrici
- Paediatric Unit, Hospital of Polistena, Polistena, Reggio Calabria, Italy
| | | | | | - Claudio Maffeis
- Paediatric Diabetes and Metabolic Disorders Unit, Regional Center for Paediatric Diabetes, University City Hospital of Verona, Italy
| | - Riccardo Bonfanti
- Diabetes Research Institute, Department of Pediatrics, IRCCS San Raffaele Scientific Institute, Milano, Italy
| | - Ivana Rabbone
- Division of Paediatrics, Department of Health Sciences, University of Piemonte Orientale, Novara, Italy -
| |
Collapse
|
|
20
|
Eckstein ML, Moser O, Tripolt NJ, Pferschy PN, Obermayer AAM, Kojzar H, Mueller A, Abbas F, Sourij C, Sourij H. Rapid glucose rise reduces heart rate variability in adults with type 1 diabetes: A prospective secondary outcome analysis. Diabetes Obes Metab 2021; 23:1681-1684. [PMID: 33283963 PMCID: PMC8247286 DOI: 10.1111/dom.14287] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2020] [Revised: 11/10/2020] [Accepted: 11/28/2020] [Indexed: 01/24/2023]
Abstract
To investigate differences in heart rate variability (HRV) during oral glucose tolerance tests (OGTTs) in response to the rate of change in glucose and to different glycaemic ranges in individuals with type 1 diabetes. This was a single-centre, prospective, secondary outcome analysis in 17 individuals with type 1 diabetes (glycated haemoglobin 53 ± 6.3 mmol/L), who underwent two OGTTs (after 12 and 36 hours of fasting) investigating differences in HRV in response to rapid glucose increases/decreases and different glycaemic ranges during OGTT. Based on the rate of change in glucose level, the variables heart rate (P < 0.001), square root of the mean standard difference of successive R-R intervals (P = 0.002), percentage of pairs of R-R intervals with >50 ms difference (P < 0.001) and corrected QT interval (P = 0.04) were significantly altered, with HRV particularly reduced during episodes of rapid glucose rises. Glycaemic ranges during OGTT had no impact on HRV (P < 0.05). Individuals with type 1 diabetes showed no changes in HRV in response to different glycaemic ranges. HRV was dependent on the rate of change in glucose, especially rapid increases in glucose level.
Collapse
Affiliation(s)
- Max L. Eckstein
- Cardiovascular Diabetology Research Group, Division of Endocrinology and Diabetology, Department of Internal MedicineMedical University of GrazGrazAustria
- Division of Exercise Physiology and Metabolism, Department of Sport ScienceUniversity of BayreuthBayreuthGermany
| | - Othmar Moser
- Cardiovascular Diabetology Research Group, Division of Endocrinology and Diabetology, Department of Internal MedicineMedical University of GrazGrazAustria
- Division of Exercise Physiology and Metabolism, Department of Sport ScienceUniversity of BayreuthBayreuthGermany
| | - Norbert J. Tripolt
- Cardiovascular Diabetology Research Group, Division of Endocrinology and Diabetology, Department of Internal MedicineMedical University of GrazGrazAustria
| | - Peter N. Pferschy
- Cardiovascular Diabetology Research Group, Division of Endocrinology and Diabetology, Department of Internal MedicineMedical University of GrazGrazAustria
| | - Anna A. M. Obermayer
- Cardiovascular Diabetology Research Group, Division of Endocrinology and Diabetology, Department of Internal MedicineMedical University of GrazGrazAustria
| | - Harald Kojzar
- Cardiovascular Diabetology Research Group, Division of Endocrinology and Diabetology, Department of Internal MedicineMedical University of GrazGrazAustria
| | - Alexander Mueller
- Cardiovascular Diabetology Research Group, Division of Endocrinology and Diabetology, Department of Internal MedicineMedical University of GrazGrazAustria
- Exercise Physiology, Training & Training Therapy Research Group, Institute of Sports ScienceUniversity of GrazGrazAustria
| | - Farah Abbas
- Cardiovascular Diabetology Research Group, Division of Endocrinology and Diabetology, Department of Internal MedicineMedical University of GrazGrazAustria
| | - Caren Sourij
- Division of Cardiology, Department of Internal MedicineMedical University of GrazGrazAustria
| | - Harald Sourij
- Cardiovascular Diabetology Research Group, Division of Endocrinology and Diabetology, Department of Internal MedicineMedical University of GrazGrazAustria
- Center for Biomarker Research in Medicine, CBmedGrazAustria
| |
Collapse
|
|
21
|
Schleier Y, Moreno-Loaiza O, López Alarcón MM, Lopes Martins EG, Braga BC, Ramos IP, Galina A, Medei EH. NOD Mice Recapitulate the Cardiac Disturbances Observed in Type 1 Diabetes. J Cardiovasc Transl Res 2021; 14:271-282. [PMID: 32468298 DOI: 10.1007/s12265-020-10039-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 05/20/2020] [Indexed: 10/24/2022]
Abstract
This work aimed at testing the hypothesis that NOD/ShiLtJ mice (NOD) recapitulate the cardiac disturbances observed on type 1 diabetes (T1D). NOD mice were studied 4 weeks after the onset of hyperglycemia, and NOR/Lt mice matched as control. Cardiac function was evaluated by echocardiography and electrocardiography (ECG). Action potentials (AP) and Ca2+ transients were evaluated at whole heart level. Heart mitochondrial function was evaluated by high-resolution respirometry and H2O2 release. NOD mice presented a reduction in hearth weight. Mitochondrial oxygen fluxes and H2O2 release were similar between NOD and NOR mice. ECG revealed a QJ interval prolongation in NOD mice. Furthermore, AP duration at 30% of repolarization was increased, and it depicted slower Ca2+ transient kinetics. NOD mice presented greater number/severity of ventricular arrhythmias both in vivo and in vitro. In conclusion, NOD mice evoked cardiac electrical and calcium handling disturbances similar to the observed in T1D. Graphical Abstract .
Collapse
Affiliation(s)
- Ygor Schleier
- Laboratory of Cardioimmunology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Oscar Moreno-Loaiza
- Laboratory of Cardioimmunology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Maria Micaela López Alarcón
- Laboratory of Cardioimmunology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Eduarda Gabrielle Lopes Martins
- Laboratory of Cardioimmunology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
- Laboratory of Bioenergetics and Mitochondrial Physiology, Institute of Medical Biochemistry Leopoldo de Meis, Center for Health Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Bruno Cabral Braga
- Laboratory of Cardioimmunology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Isalira Peroba Ramos
- National Center for Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Antonio Galina
- Laboratory of Bioenergetics and Mitochondrial Physiology, Institute of Medical Biochemistry Leopoldo de Meis, Center for Health Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Emiliano Horacio Medei
- Laboratory of Cardioimmunology, Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
- National Center for Structural Biology and Bioimaging, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
- Carlos Chagas Filho Biophysics Institute - UFRJ, Avenida Carlos Chagas Filho, 373-CCS-Bloco G, Rio de Janeiro, RJ, 21941-902, Brazil.
| |
Collapse
|
|
22
|
Akinci G, Savelieff MG, Gallagher G, Callaghan BC, Feldman EL. Diabetic neuropathy in children and youth: New and emerging risk factors. Pediatr Diabetes 2021; 22:132-147. [PMID: 33205601 PMCID: PMC11533219 DOI: 10.1111/pedi.13153] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Revised: 11/02/2020] [Accepted: 11/12/2020] [Indexed: 12/23/2022] Open
Abstract
Pediatric neuropathy attributed to metabolic dysfunction is a well-known complication in children and youth with type 1 diabetes. Moreover, the rise of obesity and in particular of type 2 diabetes may cause an uptick in pediatric neuropathy incidence. However, despite the anticipated increase in neuropathy incidence, pathogenic insights and strategies to prevent or manage neuropathy in the setting of diabetes and obesity in children and youth remain unknown. Data from adult studies and available youth cohort studies are providing an initial understanding of potential diagnostic, management, and preventative measures in early life. This review discusses the current state of knowledge emanating from these efforts, with particular emphasis on the prevalence, clinical presentation, diagnostic approaches and considerations, and risk factors of neuropathy in type 1 and type 2 diabetes in children and youth. Also highlighted are current management strategies and recommendations for neuropathy in children and youth with diabetes. This knowledge, along with continued and sustained emphasis on identifying and eliminating modifiable risk factors, completing randomized controlled trials to assess effectiveness of strategies like weight loss and exercise, and enhancing awareness to support early detection and prevention, are pertinent to addressing the rising incidence of neuropathy associated with diabetes and obesity in children and youth.
Collapse
Affiliation(s)
- Gulcin Akinci
- Department of Neurology, University of Michigan Medicine, Ann Arbor, MI
| | | | - Gary Gallagher
- Department of Neurology, University of Michigan Medicine, Ann Arbor, MI
| | | | - Eva L. Feldman
- Department of Neurology, University of Michigan Medicine, Ann Arbor, MI
| |
Collapse
|
|
23
|
Liese AD, Couch SC, The NS, Crandell JL, Lawrence JM, Crume TL, Mayer-Davis EJ, Zhong VW, Urbina EM. Association between diet quality indices and arterial stiffness in youth with type 1 diabetes: SEARCH for Diabetes in Youth Nutrition Ancillary Study. J Diabetes Complications 2020; 34:107709. [PMID: 32888787 PMCID: PMC7673264 DOI: 10.1016/j.jdiacomp.2020.107709] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2020] [Revised: 07/22/2020] [Accepted: 08/12/2020] [Indexed: 02/07/2023]
Abstract
AIMS We studied the association of three distinct diet quality indices and two measures of arterial stiffness in youth and young adults (YYA) aged 10 to 30 with T1D. METHODS Cross-sectional (n = 1421) and longitudinal (n = 520) analyses were conducted in T1D YYA participating in the SEARCH for Diabetes in Youth Study. The diet quality indices included the Dietary Approaches to Stop Hypertension (DASH) index, the Healthy Eating Index 2015 (HEI-2015), and a modified Mediterranean Diet Quality Index (mKIDMED). Arterial stiffness was measured with pulse wave velocity (PWV) and augmentation index (AIx) obtained using a SphygmoCor-Vx device and tonometer. RESULTS Average diet quality was moderate to poor, with mean scores of 41 (DASH, range 0-80), 55 (HEI-2015, range 0-100), 3.7 (mKIDMED, range - 3-12). None of the diet quality scores was associated with the central PWV or Aix, independent of demographic, clinical and lifestyle factors, body mass index and HbA1c. Longitudinal data yielded consistent findings with cross-sectional results. CONCLUSIONS This study suggests that diet quality may not function as an independent risk factor for arterial stiffening in YYA with T1D. These findings do not diminish the importance of consuming a quality diet for the management of diabetes, as demonstrated in previous work.
Collapse
Affiliation(s)
- Angela D Liese
- Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, United States of America.
| | - Sarah C Couch
- Department of Rehabilitation, Exercise and Nutrition Sciences, University of Cincinnati Medical Center, Cincinnati, OH, United States of America.
| | - Natalie S The
- Department of Health Sciences, Furman University, Greenville, SC, United States of America.
| | - Jamie L Crandell
- Department of Biostatistics, Gillings School of Global Public Health, School of Nursing, University of North Carolina, Chapel Hill, NC, United States of America.
| | - Jean M Lawrence
- Department of Research & Evaluation, Division of Epidemiologic Research Kaiser Permanente Research, Pasadena, CA, United States of America.
| | - Tessa L Crume
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO, United States of America.
| | - Elizabeth J Mayer-Davis
- Department of Nutrition, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States of America.
| | - Victor W Zhong
- Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States of America.
| | - Elaine M Urbina
- The Heart Institute, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati, Cincinnati, OH, United States of America.
| |
Collapse
|
|
24
|
Gourgari E, Stafford JM, D’Agostino R, Dolan LM, Lawrence JM, Marcovina S, Merjaneh L, Mottl AK, Shah AS, Dabelea D. The association of low-density lipoprotein cholesterol with elevated arterial stiffness in adolescents and young adults with type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth study. Pediatr Diabetes 2020; 21:863-870. [PMID: 32304144 PMCID: PMC7709736 DOI: 10.1111/pedi.13021] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 04/01/2020] [Accepted: 04/05/2020] [Indexed: 12/24/2022] Open
Abstract
AIM Our aim was to explore the relationship of Low-Density Lipoprotein Cholesterol (LDL-C) with subclinical cardiovascular disease (CVD) in youth with T1D and T2D. We hypothesized the association of LDL-C with elevated arterial stiffness (AS) would be partially accounted by the co-occurrence of other CVD factors. METHOD We included 1376 youth with T1D and 157 with T2D from the SEARCH study. CVD risk factors including LDL-C, waist to height ratio (WHtR), mean arterial pressure (MAP), HbA1c, albumin to creatinine ratio (ACR), and insulin sensitivity (IS) score were measured at both visits. At follow up, elevated carotid-femoral AS was defined as levels above 6.8 m/s. Multivariable logistic regression evaluated the odds of elevated AS as a function of the average CVD risk factors. RESULTS At follow up, age was 18.0 ± 4.1 and 21.6 ± 3.5 years and duration of diabetes was 7.8 ± 1.9 and 7.7 ± 1.9 years in T1D and T2D, respectively. Elevated AS was found in 8.4% of T1D and 49.0% of T2D participants. Each SD increase in LDL-C was associated with 1.28 increased odds (95% CI 1.05-1.54, P = .013) of elevated AS in youth with T1D. The association was similar but not statistically significant in T2D. WHtR, IS, and MAP were associated with elevated AS in both groups. Adjustment for WHtR or IS attenuated to non-significance the relationship between LDL-C and AS in T1D. CONCLUSIONS Obesity and insulin resistance attenuate the association of high LDL-C with AS suggesting they partially account for the adverse effects of LDL-C on cardiovascular health in youth with T1D.
Collapse
Affiliation(s)
- Evgenia Gourgari
- Division of Pediatric Endocrinology, Department of Pediatrics, Georgetown University, Washington, District of Columbia
- Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, Maryland
| | - Jeanette M. Stafford
- Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Ralph D’Agostino
- Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Lawrence M. Dolan
- Division of Endocrinology, Department of Pediatrics, Cincinnati Children’s Hospital and the University of Cincinnati, Cincinnati, Ohio
| | - Jean M. Lawrence
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California
| | - Santica Marcovina
- Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle, Washington
| | - Lina Merjaneh
- Division of Endocrinology, Department of Pediatrics, Seattle Children’s Hospital, Seattle, Washington
| | - Amy K. Mottl
- UNC Division of Nephrology and Hypertension, University of North Carolina School of Medicine, Chapel Hill, North Carolina
| | - Amy S. Shah
- Division of Endocrinology, Department of Pediatrics, Cincinnati Children’s Hospital and the University of Cincinnati, Cincinnati, Ohio
| | - Dana Dabelea
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado
| |
Collapse
|
|
25
|
Faulkner MS, Quinn L, Fritschi C, Tripp N, Hayat MJ. Heart Rate Variability and Cardiorespiratory Fitness in Non-Hispanic Black Versus Non-Hispanic White Adolescents With Type 1 Diabetes. J Cardiovasc Nurs 2020; 34:372-379. [PMID: 31343621 PMCID: PMC6690789 DOI: 10.1097/jcn.0000000000000590] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Evidence indicates that fewer non-Hispanic black versus non-Hispanic white youths with type 1 diabetes are meeting treatment goals for optimal glycemic outcomes, predisposing them to risks for cardiovascular (CV) morbidity and mortality in adulthood. PURPOSE We sought to assess the association of sex and race with heart rate variability (HRV) and cardiorespiratory fitness in adolescents with type 1 diabetes. The association between the HRV and cardiorespiratory outcomes with glucose control was also examined. METHODS A secondary data analysis of 95 adolescents with type 1 diabetes (n = 66 non-Hispanic white n = 29 non-Hispanic black) was used. Using 24-hour Holter recordings, spectral and time domain measures of HRV were obtained. Cardiorespiratory fitness using a graded exercise test was completed. Descriptive statistics and Pearson correlation coefficients were used to assess associations between glucose control and study outcomes, and general linear models were applied to explore and quantify associations of sex and race with HRV and cardiorespiratory fitness. RESULTS Body mass index (mean [standard deviation]) was similar between non-Hispanic black (23.5 [3.9]) and non-Hispanic white (22.7 [3.8]) adolescents. Females and non-Hispanic black adolescents had significantly lower HRV and cardiorespiratory fitness levels. Moderate associations were found between lower HRV and poorer glycemic control (HbA1c). Recent HbA1c was significantly higher in non-Hispanic black (9.7 [1.8]) than non-Hispanic white (8.2 [1.2]). CONCLUSION Findings support the importance of early identification of CV health risks in adolescents with type 1 diabetes, particularly for non-Hispanic black adolescents. Interventions focused on overall improvement in glycemic control for adolescents with type 1 diabetes are a priority for minimizing future CV complications.
Collapse
Affiliation(s)
| | - Laurie Quinn
- Department of Biobehavioral Health Science, College of Nursing, University of Illinois at Chicago
| | - Cynthia Fritschi
- Department of Biobehavioral Health Science, College of Nursing, University of Illinois at Chicago
| | - Natalie Tripp
- Department of Population Health Sciences, School of Public Health, Georgia State Univesity
| | - Matthew J. Hayat
- Department of Population Health Sciences, School of Public Health, Georgia State Univesity
| |
Collapse
|
|
26
|
Kristiansen E, Wanby P, Åkesson K, Blomstrand P, Brudin L, Thegerström J. Assessing heart rate variability in type 1 diabetes mellitus-Psychosocial stress a possible confounder. Ann Noninvasive Electrocardiol 2020; 25:e12760. [PMID: 32353221 PMCID: PMC7507550 DOI: 10.1111/anec.12760] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 03/14/2020] [Accepted: 03/23/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Autonomic neuropathy (AN) commonly arises as a long-term complication in diabetes mellitus and can be diagnosed from heart rate variability (HRV), calculated from electrocardiogram recordings. Psychosocial stress also affects HRV and could be one of several confounders for cardiac AN. The present work investigated the impact of psychosocial stress on HRV in individuals with type 1 diabetes mellitus (T1DM) and assessed the use of salivary cortisol as a biomarker for psychosocial stress in this context. METHODS A total of 167 individuals 6-60 years old (113 with T1DM and 54 healthy controls) underwent 24-hr ECG recordings with HRV analysis. Salivary cortisol was sampled thrice during the registration day. Perceived psychosocial stress along with other factors of possible importance for the interpretation of HRV was documented in a diary. RESULTS Heart rate variability (high-frequency power during sleep) was reduced (p < .05) with older age, longer diabetes duration, higher mean glucose levels, physical inactivity, and perceived psychosocial stress. Salivary cortisol levels in the evening were increased (p < .05) in women in ovulation phase, in individuals with preceding hypoglycemia or with hyperglycemia. The amplitude of salivary cortisol was reduced (p < .05) with the presence of perceived psychosocial stress, but only in adult healthy controls, not in individuals with diabetes. CONCLUSION Psychosocial stress might be a confounder for reduced HRV when diagnosing cardiac AN in T1DM. Salivary cortisol is, however, not a useful biomarker for psychosocial stress in diabetes since the physiological stress of both hypoglycemia and hyperglycemia seems to overrule the effect of psychosocial stress on cortisol.
Collapse
Affiliation(s)
- Eva Kristiansen
- Department of Pediatrics, Region Kalmar County, Kalmar, Sweden
| | - Pär Wanby
- Department of Medicine and Optometry, Linnaeus University, Kalmar, Sweden.,Department of Internal Medicine, Section of Endocrinology, Region Kalmar County, Kalmar, Sweden
| | - Karin Åkesson
- Futurum - Academy for Health and Care, Jönköping, Sweden.,Department of Pediatrics, Region Jönköping County, Jönköping, Sweden
| | - Peter Blomstrand
- Department of Natural Science and Biomedicine, School of Health and Welfare, Jönköping University, Jönköping, Sweden.,Department of Clinical Physiology, Region Jönköping County, Jönköping, Sweden
| | - Lars Brudin
- Department of Clinical Physiology, Region Kalmar County, Kalmar, Sweden
| | | |
Collapse
|
|
27
|
Riguetto CM, Takano CR, Admoni SN, Parisi MCR, Giannella MLC, Pavin EJ, Moura Neto A. Identification and performance of multiple clinical and laboratorial risk factors for diagnosis of cardiac autonomic neuropathy in type 1 diabetes patients. J Diabetes Metab Disord 2019; 18:565-573. [PMID: 31890683 DOI: 10.1007/s40200-019-00467-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2019] [Accepted: 11/05/2019] [Indexed: 01/05/2023]
Abstract
Purpose The incidence of cardiac autonomic neuropathy (CAN) in patients with type 1 diabetes (T1D) is frequently underestimated. Individuals with T1D and CAN have an increased mortality risk, mainly from cardiovascular causes. The objectives of the present study were to assess the clinical and laboratory characteristics associated with CAN in patients with T1D and verify the ability of multiple clinical factors to help identify patients with this condition. Methods 102 patients with T1D were evaluated for CAN using standardized cardiovascular reflex testing. Clinical characteristics were used to compute a numerical score for CAN diagnosis and a ROC curve elaborated for assessment of the best cutoff to predict CAN. This score was then applied to the second sample of 120 patients. The sensitivity, specificity, and positive and negative predictive values were calculated. Results Prevalence of CAN was around 35% in the first sample of patients and just below 20% in the second sample. Hypertension, total cholesterol, triglycerides, postprandial sweating, diastolic blood pressure, abnormal right and left 10 g monofilament, retinopathy, and nephropathy were considered independent predictors of CAN. The CAN-score cut-off was 16.88. This yielded a sensitivity of 50%, specificity 73.8%, positive predictive value 22.9%, and negative predictive value 90.5%. Conclusion The use of a subset of clinical and laboratory characteristics can be more accessible than the cardiac reflex tests and more accurate than a single isolated characteristic.
Collapse
Affiliation(s)
- Cinthia Minatel Riguetto
- 1Endocrinology Division, Internal Medicine Department, Faculty of Medical Sciences, University of Campinas, Rua Tessália Vieira de Camargo, 126 Campinas, São Paulo, 13084-971 Brazil
| | - Caroline Rigoleto Takano
- 1Endocrinology Division, Internal Medicine Department, Faculty of Medical Sciences, University of Campinas, Rua Tessália Vieira de Camargo, 126 Campinas, São Paulo, 13084-971 Brazil
| | - Sharon Nina Admoni
- 2Serviço de Endocrinologia e Metabologia do Hospital da Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo Brazil
| | - Maria Candida Ribeiro Parisi
- 1Endocrinology Division, Internal Medicine Department, Faculty of Medical Sciences, University of Campinas, Rua Tessália Vieira de Camargo, 126 Campinas, São Paulo, 13084-971 Brazil
| | - Maria Lucia Correa Giannella
- 2Serviço de Endocrinologia e Metabologia do Hospital da Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, São Paulo Brazil
| | - Elizabeth João Pavin
- 1Endocrinology Division, Internal Medicine Department, Faculty of Medical Sciences, University of Campinas, Rua Tessália Vieira de Camargo, 126 Campinas, São Paulo, 13084-971 Brazil
| | - Arnaldo Moura Neto
- 1Endocrinology Division, Internal Medicine Department, Faculty of Medical Sciences, University of Campinas, Rua Tessália Vieira de Camargo, 126 Campinas, São Paulo, 13084-971 Brazil
| |
Collapse
|
|
28
|
Bassil G, Chang M, Pauza A, Diaz Vera J, Tsalatsanis A, Lindsey BG, Noujaim SF. Pulmonary Vein Ganglia Are Remodeled in the Diabetic Heart. J Am Heart Assoc 2019; 7:e008919. [PMID: 30511897 PMCID: PMC6405566 DOI: 10.1161/jaha.118.008919] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Background Cardiac autonomic neuropathy is thought to cause adverse cardiovascular effects in diabetes mellitus. Pulmonary vein ganglia ( PVG ), which have been implicated in normal and abnormal heart rhythm regulation, have not been fully investigated in type 1 diabetes mellitus (T1D). We examined the functional and anatomical effects of T1D on PVG and studied the details of T1D-induced remodeling on the PVG structure and function. Methods and Results We used a mouse model of T1D (Akita mouse), immunofluorescence, isolated Langendorff-perfused hearts, and mathematical simulations to explore the effects of T1D on PVG . Whole-mount atrial immunofluorescence of choline acetyltransferase and tyrosine hydroxylase labeling showed that sympathetic and parasympathetic somas of the PVG neurons were significantly hypotrophied in T1D hearts versus wild type. Stimulation of PVG in isolated Langendorff-perfused hearts caused more pronounced P-P interval prolongation in wild type compared with Akita hearts. Propranolol resulted in a comparable P-P prolongation in both phenotypes, and atropine led to more pronounced P-P interval shortening in wild type compared with Akita hearts. Numerical modeling using network simulations revealed that a decrease in the sympathetic and parasympathetic activities of PVG in T1D could explain the experimental results. Conclusions T1D leads to PVG remodeling with hypotrophy of sympathetic and parasympathetic cell bodies and a concomitant decrease in the PVG sympathetic and parasympathetic activities.
Collapse
Affiliation(s)
- Guillaume Bassil
- 1 Department of Internal Medicine Weill Cornell Medical College New York NY
| | - Mengmeng Chang
- 2 Department of Molecular Pharmacology and Physiology Morsani College of Medicine University of South Florida Tampa FL
| | - Audrys Pauza
- 3 Laboratories for Integrative Neuroscience and Endocrinology University of Bristol United Kingdom
| | - Jesus Diaz Vera
- 2 Department of Molecular Pharmacology and Physiology Morsani College of Medicine University of South Florida Tampa FL
| | - Athanasios Tsalatsanis
- 4 Research Methodology and Biostatistics Morsani College of Medicine University of South Florida Tampa FL
| | - Bruce G Lindsey
- 2 Department of Molecular Pharmacology and Physiology Morsani College of Medicine University of South Florida Tampa FL
| | - Sami F Noujaim
- 2 Department of Molecular Pharmacology and Physiology Morsani College of Medicine University of South Florida Tampa FL
| |
Collapse
|
|
29
|
Gourgari E, Stafford JM, D'Agostino Jr R, Dolan LM, Lawrence JM, Mottl A, Pihoker C, Urbina EM, Wadwa RP, Dabelea D. Association of metformin and statin medications with surrogate measures of cardiovascular disease in youth with type 1 diabetes: the SEARCH for diabetes in youth study. Ann Pediatr Endocrinol Metab 2019; 24:187-194. [PMID: 31607112 PMCID: PMC6790871 DOI: 10.6065/apem.2019.24.3.187] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2019] [Accepted: 06/04/2019] [Indexed: 01/16/2023] Open
Abstract
PURPOSE Youth with type 1 diabetes mellitus (T1DM) are at risk of cardiovascular disease (CVD). We evaluated if metformin or statin use was associated with surrogate measures of improved CVD. METHODS We included participants from the SEARCH observational study. Participants treated with insulin plus metformin (n=42) or insulin plus statin (n=39) were matched with 84 and 78 participants, respectively, treated with insulin alone. Measures of arterial stiffness obtained were pulse wave velocity (PWV), augmentation index (AI75), and heart rate variability as standard deviation of the normal-to-normal interval (SDNN) and root mean square differences of successive NN intervals (RMSSD). RESULTS CVD measures were not significantly different among participants on insulin plus metformin versus those on insulin alone: PWV (5.9±1.0 m/sec vs. 5.8±1.5 m/sec, P=0.730), AI75 (1.8 [-6.0 to 8.0] vs. -2.4 [-10.7 to 3.8], P=0.157), SDNN (52.4 [36.8-71.1] m/sec vs. 51.8 [40.1-74.9] m/sec, P=0.592), and RMSSD (43.2 [29.4-67.6] vs. 47.4 [28.0-76.3], P=0.952). CVD measures were not different for statin users versus nonusers: PWV (5.7±0.8 m/sec vs. 5.9 ±1.1 m/sec, P=0.184), AI75 ( -4.0 [-9.5 to 1.7] vs. -6.7 [-11.3 to 5.7], P=0.998), SDNN (54.6 [43.5-77.2] m/sec vs. 63.1 [44.2-86.6] m/sec, P=0.369), and RMSSD (49.5 [31.2-74.8] vs. 59.2 [38.3-86.3], P=0.430). CONCLUSION We found no associations of statin or metformin use with surrogate measures of CVD. Future prospective pediatric clinical trials could address this issue.
Collapse
Affiliation(s)
- Evgenia Gourgari
- Division of Pediatric Endocrinology, Department of Pediatrics, Georgetown University, Washington, DC, USA,Section on Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health, Bethesda, MD, USA,Address for correspondence: Evgenia Gourgari, MD Division of Pediatric Endocrinology, MedStar Georgetown University Hospital, 4200 Wisconsin Avenue, N.W, 4th Floor, Washington, D.C. 20016, USA Tel: +1-202-243-3560 Fax: +1-877-680-5507 E-mail:
| | - Jeanette M. Stafford
- Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Ralph D'Agostino Jr
- Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA
| | - Lawrence M. Dolan
- Department of Pediatrics, Cincinnati Children's Hospital and the University of Cincinnati, Cincinnati, OH, USA
| | - Jean M. Lawrence
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA, USA
| | - Amy Mottl
- UNC Division of Nephrology and Hypertension, University of North Carolina School of Medicine, Chapel Hill, NC, USA
| | - Catherine Pihoker
- Department of Pediatrics, University of Washington, Seattle, WA, USA
| | - Elaine M. Urbina
- Cincinnati Children's Hospital Medical Center & University of Cincinnati, Cincinnati, OH, USA
| | - R. Paul Wadwa
- Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO, USA
| | - Dana Dabelea
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO, USA
| |
Collapse
|
|
30
|
Kim HY, Jung HW, Lee YA, Shin CH, Yang SW. Cardiac autonomic neuropathy in nonobese young adults with type 1 diabetes. Ann Pediatr Endocrinol Metab 2019; 24:180-186. [PMID: 31607111 PMCID: PMC6790876 DOI: 10.6065/apem.2019.24.3.180] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2018] [Accepted: 01/16/2019] [Indexed: 12/30/2022] Open
Abstract
PURPOSE The aim of this study was to evaluate the prevalence and risk factors for cardiac autonomic neuropathy (CAN) in nonobese nonobese young type 1 diabetes mellitus (T1DM) patients without micro- or macrovascular complications. METHODS CAN was assessed in 95 patients with T1DM, aged 18-29 years, using standard cardiovascular reflex tests - heart rate response to deep breathing, standing, and the Valsalva maneuver and blood pressure response to standing. Furthermore, power spectral analyses of overall heart rate variability (HRV), standard deviation of NN intervals (SDNN), and total power (TP) were tested with DiCAN. CAN was defined as abnormal results for at least 1 of the 4 cardiovascular reflex tests. RESULTS The prevalence of CAN was 12.6%. The frequency of one and 2 abnormal reflex tests was 10.5% and 2.1%, respectively. No significant differences were observed in age, sex, mean hemoglobin A1c (HbA1c) level, and duration of diabetes with respect to presence of CAN. Patients with CAN exhibited lower overall HRV parameters (SDNN and TP) compared with those without CAN even though there was no statistical significance. In multivariable analyses, higher mean HbA1c level was significantly associated with lower overall HRV (β=-44.42, P=0.002 for SDNN and β=-2.82, P<0.001 for TP). CONCLUSION CAN can be detected in 12.6% of young adult T1DM patients even without other micro- or macrovascular complications. Glycemic control is the main determinant to maintain overall HRV and prevent CAN.
Collapse
Affiliation(s)
- Hwa Young Kim
- Department of Pediatrics, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea
| | - Hae Woon Jung
- Department of Pediatrics, Kyung Hee University Medical Center, Seoul, Korea
| | - Young Ah Lee
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea,Address for correspondence: Young Ah Lee, MD, PhD Division of Endocrinology and Metabolism, Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel: +82-2-2072-2308 Fax: +82-2-743-3455 E-mail:
| | - Choong Ho Shin
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
| | - Sei Won Yang
- Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
| |
Collapse
|
|
31
|
França da Silva AK, Destro Christofaro DG, Manata Vanzella L, Marques Vanderlei F, Lopez Laurino MJ, Marques Vanderlei LC. Relationship of the Aggregation of Cardiovascular Risk Factors in the Parasympathetic Modulation of Young People with Type 1 Diabetes. MEDICINA (KAUNAS, LITHUANIA) 2019; 55:E534. [PMID: 31454959 PMCID: PMC6780872 DOI: 10.3390/medicina55090534] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 08/20/2019] [Accepted: 08/21/2019] [Indexed: 11/20/2022]
Abstract
Background and objectives: In healthy individuals, autonomic alterations are associated with the aggregation of cardiovascular risk factors. However, in individuals with type 1 diabetes, who are known to present autonomic alterations, mainly characterized by a reduction in parasympathetic modulation, these associations have not yet been investigated. We assess whether the aggregation of cardiovascular risk factors influences parasympathetic indices of heart rate variability in young people with type 1 diabetes. Materials and methods: This cross-sectional study included 39 individuals with type 1 diabetes (22.54 ± 4.31), evaluated in relation to the risk factors: blood pressure, fat percentage, and resting heart rate. For heart rate variability analysis, heart rate was recorded beat-to-beat using a cardio frequency meter (PolarS810i) for 30 min with the volunteers in dorsal decubitus. The parasympathetic heart rate variability indices were calculated: rMSSD, pNN50, high frequency (HF) n.u (normalized units), SD1, 2LV, and 2ULV. Data collection was carried out in 2014 and analyzed in 2017. Results: Individuals with two aggregate risk factors present a reduction in the values of the indices that reflect parasympathetic autonomic modulation compared to individuals without the risk factors analyzed, regardless of sex and age. Conclusion: In young people with type 1 diabetes, the aggregation of cardiovascular risk factors is associated with parasympathetic autonomic impairment.
Collapse
Affiliation(s)
- Anne Kastelianne França da Silva
- Department of Physical Therapy, Faculty of Science and Technology, São Paulo State University (UNESP), Roberto Simonsen Street, 305, Presidente Prudente, São Paulo 19060-900, Brazil.
| | - Diego Giulliano Destro Christofaro
- Department of Physical Education, Faculty of Science and Technology, São Paulo State University (UNESP), Roberto Simonsen Street, 305, Presidente Prudente, São Paulo 19060-900, Brazil
| | - Laís Manata Vanzella
- Department of Physical Therapy, Faculty of Science and Technology, São Paulo State University (UNESP), Roberto Simonsen Street, 305, Presidente Prudente, São Paulo 19060-900, Brazil
| | - Franciele Marques Vanderlei
- Department of Physical Therapy, Faculty of Science and Technology, São Paulo State University (UNESP), Roberto Simonsen Street, 305, Presidente Prudente, São Paulo 19060-900, Brazil
| | - Maria Júlia Lopez Laurino
- Department of Physical Therapy, Faculty of Science and Technology, São Paulo State University (UNESP), Roberto Simonsen Street, 305, Presidente Prudente, São Paulo 19060-900, Brazil
| | - Luiz Carlos Marques Vanderlei
- Department of Physical Therapy, Faculty of Science and Technology, São Paulo State University (UNESP), Roberto Simonsen Street, 305, Presidente Prudente, São Paulo 19060-900, Brazil
| |
Collapse
|
|
32
|
Urbina EM, Isom S, Bell RA, Bowlby DA, D'Agostino R, Daniels SR, Dolan LM, Imperatore G, Marcovina SM, Merchant AT, Reynolds K, Shah AS, Wadwa RP, Dabelea D. Burden of Cardiovascular Risk Factors Over Time and Arterial Stiffness in Youth With Type 1 Diabetes Mellitus: The SEARCH for Diabetes in Youth Study. J Am Heart Assoc 2019; 8:e010150. [PMID: 31213111 PMCID: PMC6662363 DOI: 10.1161/jaha.118.010150] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Background The incidence of type 1 diabetes mellitus (T1DM) in children is increasing, resulting in higher burden of cardiovascular diseases due to diabetes mellitus-related vascular dysfunction. Methods and Results We examined cardiovascular risk factors ( CVRF s) and arterial parameters in 1809 youth with T1DM. Demographics, anthropometrics, blood pressure, and laboratory data were collected at T1DM onset and 5 years later. Pulse wave velocity and augmentation index were collected with tonometry. ANOVA or chi-square tests were used to test for differences in measures of arterial parameters by CVRF . Area under the curve of CVRF s was entered in general linear models to explore determinants of accelerate vascular aging. Participants at the time of arterial measurement were 17.6±4.5 years old, 50% female, 76% non-Hispanic white, and duration of T1DM was 7.8±1.9 years. Glycemic control was poor (glycated hemoglobin, 9.1±1.8%). All arterial parameters were higher in participants with glycated hemoglobin ≥9% and pulse wave velocity was higher with lower insulin sensitivity or longer duration of diabetes mellitus. Differences in arterial parameters were found by sex, age, and presence of obesity, hypertension, or dyslipidemia. In multivariable models, higher glycated hemoglobin, lower insulin sensitivity, body mass index, blood pressure, and lipid areas under the curve were associated with accelerated vascular aging. Conclusions In young people with T1DM, persistent poor glycemic control and higher levels of traditional CVRF s are independently associated with arterial aging. Improving glycemic control and interventions to lower CVRF s may prevent future cardiovascular events in young individuals with T1DM.
Collapse
Affiliation(s)
- Elaine M Urbina
- 1 Heart Institute Cincinnati Children's Hospital & University of Cincinnati OH
| | - Scott Isom
- 3 Department of Biostatistical Sciences Wake Forest School of Medicine Winston-Salem NC
| | - Ronny A Bell
- 4 Department of Public Health East Carolina University Greenville NC
| | - Deborah A Bowlby
- 5 Division of Pediatric Endocrinology & Diabetes Medical University of South Carolina Charleston SC USA
| | - Ralph D'Agostino
- 3 Department of Biostatistical Sciences Wake Forest School of Medicine Winston-Salem NC
| | - Stephen R Daniels
- 6 Department of Pediatrics University of Colorado School of Medicine Aurora CO
| | - Lawrence M Dolan
- 2 Department of Endocrinology Cincinnati Children's Hospital & University of Cincinnati OH
| | - Giuseppina Imperatore
- 8 Division of Diabetes Translation Centers for Disease Control and Prevention Atlanta GA
| | - Santica M Marcovina
- 9 Northwest Lipid Metabolism and Diabetes Research Laboratory University of Washington Seattle WA
| | - Anwar T Merchant
- 5 Division of Pediatric Endocrinology & Diabetes Medical University of South Carolina Charleston SC USA.,10 Department of Epidemiology and Biostatistics University of South Carolina Columbia SC USA
| | - Kristi Reynolds
- 11 Department of Research & Evaluation Kaiser Permanente Southern California Pasadena CA
| | - Amy S Shah
- 2 Department of Endocrinology Cincinnati Children's Hospital & University of Cincinnati OH
| | - R Paul Wadwa
- 7 Barbara Davis Center for Childhood Diabetes University of Colorado School of Medicine Aurora CO
| | - Dana Dabelea
- 12 Department of Epidemiology Colorado School of Public Health Aurora CO
| | | |
Collapse
|
|
33
|
Alman AC, Talton JW, Wadwa RP, Urbina EM, Dolan LM, Hamman RF, D'Agostino RB, Marcovina SM, Dabelea DM. Inflammation, adiposity, and progression of arterial stiffness in adolescents with type 1 diabetes: The SEARCH CVD Study. J Diabetes Complications 2018; 32:995-999. [PMID: 30209019 PMCID: PMC6174105 DOI: 10.1016/j.jdiacomp.2018.08.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Revised: 12/28/2017] [Accepted: 08/06/2018] [Indexed: 11/30/2022]
Abstract
AIMS We examined the association between inflammation and progression of arterial stiffness in a population of youth with type 1 diabetes (T1D). METHODS A total of 287 youth with T1D (median age 13 years) from SEARCH CVD, an ancillary study to the SEARCH for Diabetes in Youth, were included. Markers of inflammation (CRP, IL-6, fibrinogen, leptin, and adiponectin) and measures of pulse wave velocity (PWV) of the arm (PWV-R), trunk (PWV-T), and lower extremity (PWV-LE) were measured at baseline. Measures of PWV were repeated approximately five years later. RESULTS PWV-R (0.50 m/s), PWV-T (0.65 m/s), and PWV-LE (1.0 m/s) significantly increased over the follow-up (p < 0.001 for each). A significant interaction was found between waist circumference and fibrinogen (p = 0.036) on the progression of PWV-T, suggesting that fibrinogen is more strongly associated with PWV progression in lean participants. CONCLUSIONS Improved understanding of adiposity, inflammation, and functional changes in the vascular system in patients with T1D is crucial.
Collapse
Affiliation(s)
- Amy C Alman
- Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, USA.
| | - Jennifer W Talton
- Department of Biostatistical Sciences, Wake Forest School of Medicine, USA
| | - R Paul Wadwa
- Barbara Davis Center, University of Colorado Denver, USA
| | - Elaine M Urbina
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, USA
| | - Lawrence M Dolan
- Department of Pediatrics, Cincinnati Children's Hospital Medical Center, USA
| | - Richard F Hamman
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, USA
| | - Ralph B D'Agostino
- Department of Biostatistical Sciences, Wake Forest School of Medicine, USA
| | - Santica M Marcovina
- Department of Metabolism, Endocrinology and Nutrition, University of Washington, USA
| | - Dana M Dabelea
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, USA
| |
Collapse
|
|
34
|
Donaghue KC, Marcovecchio ML, Wadwa RP, Chew EY, Wong TY, Calliari LE, Zabeen B, Salem MA, Craig ME. ISPAD Clinical Practice Consensus Guidelines 2018: Microvascular and macrovascular complications in children and adolescents. Pediatr Diabetes 2018; 19 Suppl 27:262-274. [PMID: 30079595 PMCID: PMC8559793 DOI: 10.1111/pedi.12742] [Citation(s) in RCA: 185] [Impact Index Per Article: 26.4] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Accepted: 07/27/2018] [Indexed: 12/25/2022] Open
Affiliation(s)
- Kim C Donaghue
- The Children's Hospital at Westmead, Westmead, NSW, Australia
- Discipline of Child and Adolescent Health, University of Sydney, Camperdown, Australia
| | | | - R P Wadwa
- University of Colorado School of Medicine, Denver, Colorado
| | - Emily Y Chew
- Division of Epidemiology and Clinical Applications, the National Eye Institute, National Institutes of Health, Bethesda, Maryland
| | - Tien Y Wong
- Singapore Eye Research Institute, Singapore National Eye Center, Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
| | | | - Bedowra Zabeen
- Department of Paediatrics and Changing Diabetes in Children Program, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders, Dhaka, Bangladesh
| | - Mona A Salem
- Department of Pediatrics, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Maria E Craig
- The Children's Hospital at Westmead, Westmead, NSW, Australia
- Discipline of Child and Adolescent Health, University of Sydney, Camperdown, Australia
- School of Women's and Children's Health, University of New South Wales, Sydney, Australia
| |
Collapse
|
|
35
|
Guan L, Metzger DL, Lavoie PM, Collet JP. Glucose control and autonomic response during acute stress in youth with type 1 diabetes: A pilot study. Pediatr Diabetes 2018; 19:1020-1024. [PMID: 29654713 DOI: 10.1111/pedi.12680] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Revised: 02/20/2018] [Accepted: 02/20/2018] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Type 1 diabetes (T1D) is a chronic source of metabolic and neuropsychological stress, which may eventually lead to autonomic neuropathy and other complications related to micro- and macro-vasculopathies. We aimed to investigate the relationship between T1D chronic stress and autonomic response to acute stress testing that was expected being affected by chronic stress. METHODS Twenty youths with confirmed diagnosis of T1D were assessed. Chronic stress assessment included hemoglobin A1c (HbA1c) ≥7.5%, psychological stress assessed by perceived stress scale (PSS), hypoglycemic events, and proinflammatory cytokines. The acute stress testing used standardized stress video games. Autonomic response to acute stress was assessed by the amplitude and direction of changes in heart rate variability. Analyses determined correlations between changes in parasympathetic nervous system during stress testing and chronic diabetes stressors. RESULTS A strong correlation was found between the amplitude of high frequency (HF) changes and HbA1c values (ρ = 0.74, P < .001). Youths with HbA1c ≥7.5% showed a larger amplitude of HF changes during acute stress (49% vs 16%, P < .001) and a higher PSS score (22.5 vs 19.0, P = .003), compared to those with HbA1c <7.5%. Additionally, among youths with HbA1c ≥7.5%, those with positive changes in HF had a lower level of IL-8 than those with negative changes (5.40 vs 7.85 pg/mL, P = .009). CONCLUSIONS Study findings support the need for better understanding the health effects of stress-related autonomic dysfunction in youth with T1D.
Collapse
Affiliation(s)
- Ling Guan
- Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.,Department of Medicine, University of British Columbia, Vancouver, BC, Canada.,British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada
| | - Daniel L Metzger
- Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.,Division of Pediatric Endocrinology, British Columbia Children's Hospital, Vancouver, BC, Canada
| | - Pascal M Lavoie
- Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.,British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada.,Division of Neonatology, British Columbia Women's Hospital, Vancouver, BC, Canada
| | - Jean-Paul Collet
- Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.,Department of Medicine, University of British Columbia, Vancouver, BC, Canada.,British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, BC, Canada
| |
Collapse
|
|
36
|
Oliveira EAD, Silva AKFD, Christofaro DGD, Vanzella LM, Gomes RL, Vanderlei FM, Vanderlei LCM. Influence of Type 1 Diabetes on the Symbolic Analysis and Complexity of Heart Rate Variability in Young Adults. Arq Bras Cardiol 2018; 111:94-101. [PMID: 30020326 PMCID: PMC6078361 DOI: 10.5935/abc.20180117] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Accepted: 05/09/2018] [Indexed: 11/21/2022] Open
Abstract
Background Type 1 diabetes mellitus can cause autonomic changes, which can be assessed
by heart rate variability. Among the heart rate variability assessment
methods, the symbolic analysis and Shannon entropy, based on the Chaotic
dynamics, have gained prominence. Objective To compare heart rate variability indexes, obtained through symbolic analysis
and Shannon entropy, in young adults with type 1 diabetes mellitus and
healthy young individuals, associated with the analysis of linear indexes;
and to verify if there are associations between the indexes obtained by the
symbolic analysis and by Shannon entropy and linear indexes in diabetic
individuals. Methods Heart rate variability data from 39 young adults with type 1 diabetes
mellitus and 43 healthy young individuals were analyzed, using a
cardio-frequency meter. Linear indexes (standard deviation of all normal RR
intervals recorded in a time interval expressed in milliseconds; square root
of the mean of the squared differences between adjacent normal RR intervals
in a time interval expressed in milliseconds; low and high frequency
components in millisecond squared; and normalized units and ratio between
low and high frequency components) and nonlinear ones (Shannon entropy and
symbolic analysis - standard without variation; with one or two variations;
and with two different variations) of the heart rate variability were
calculated. The statistical significance was set at 5%, and the confidence
interval was 95%. Results Significantly lower values were observed in the DM1 group compared to healthy
young adults for the standard deviation indexes of all normal RR intervals
recorded in a time interval [37.30 (29.90) vs. 64.50 (36.20); p = 0.0001],
square root of the mean of the squared differences between adjacent normal
RR intervals in a time interval [32.73 (17.43) vs. 55.59 (21.60); p =
0.0001], low frequency component [402.00 (531.00) vs. 1,203.00 (1,148.00); p
= 0.0001], high frequency component [386.00 (583.00) vs. 963.00 (866.00); p
= 0.0001] and the pattern with two different variations [15,33 (9,22) vs.
20.24 (12.73); p = 0.0114], with the effect of this difference being
considered large (standard deviation of all normal RR intervals recorded in
a time interval, square root of the mean of the squared differences between
adjacent normal RR intervals in a time interval and low frequency
component), medium (high frequency component) and small (standard with two
different variations). The agreement of the associations between the linear
and non-linear indexes was considered elevated for the high frequency
component index - normalized units (r = -0.776), with the standard index
without variation, and moderate for the indexes square root of the mean of
the squared differences between adjacent normal RR intervals in a time
interval (r = 0.550), standard deviation of all normal RR intervals recorded
in a time interval (r = 0.522), high frequency component - normalized units
(r = 0.638) with the index standard with two similar variations, as well as
for the indexes square root of the mean of the squared differences between
adjacent normal RR intervals in a time interval (r = 0.627) and high
frequency component - normalized units (r = 0.601) with the index standard
with two different variations. Conclusion Type 1 diabetes mellitus influenced linear indexes and symbolic analysis, but
not yet in the complexity of heart rate variability. Additionally, heart
rate variability indexes correlated with the symbolic dynamics.
Collapse
Affiliation(s)
| | | | | | - Laís Manata Vanzella
- Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Presidente Prudente, SP - Brazil
| | - Rayana Loch Gomes
- Universidade Estadual Paulista Júlio de Mesquita Filho (UNESP), Presidente Prudente, SP - Brazil
| | | | | |
Collapse
|
|
37
|
Rivarola EW, Scanavacca MI. How to Evaluate Cardiac Autonomic Modulation. Arq Bras Cardiol 2018; 111:102-103. [PMID: 30110051 PMCID: PMC6078378 DOI: 10.5935/abc.20180127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
|
|
38
|
Cho YH, Craig ME, Jopling T, Chan A, Donaghue KC. Higher body mass index predicts cardiac autonomic dysfunction: A longitudinal study in adolescent type 1 diabetes. Pediatr Diabetes 2018; 19:794-800. [PMID: 29383813 DOI: 10.1111/pedi.12642] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2017] [Revised: 12/04/2017] [Accepted: 12/25/2017] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Obesity is associated with an increased risk of cardiovascular morbidity in adults with diabetes. OBJECTIVE To examine the predictive role of body mass index (BMI) and adiposity on cardiac autonomic function in childhood onset type 1 diabetes. SUBJECTS Two hundred and fifty-three participants with type 1 diabetes (aged 8-30 years) were assessed for diabetes complications at a tertiary hospital, and followed over 7 years (total 922 visits). METHODS Heart rate variability (HRV) measures assessed by 10-minute electrocardiography recording using LabChart Pro were standard deviation of RR intervals, time between consecutive QRS complexes, [SDNN], root mean squared difference of successive RR intervals (RMSSD), triangular index (TI), and low to high frequency ratio [LF:HF]. Multivariable generalized estimating equations were used to model the longitudinal associations between HRV measures and clinical variables (BMI standard deviation scores [SDS], waist:height ratio, total daily insulin dose/kg (TDD) and hemoglobin A1c [HbA1c]). RESULTS At baseline, mean age was 14.4 ± 2.7 years, diabetes duration 7.1 ± 3.7 years, HbA1c 8.3% ± 1.5% (67 ± 16 mmol/mol), and 33% were overweight/obese (BMI ≥85th percentile). At final visit, mean age was 18.5 ± 2.7 years, duration 11.3 ± 3.9 years, HbA1c 9.0% ± 1.8% (75 ± 20 mmol/mol), and 40% were overweight/obese. Adiposity (higher BMI SDS or waist: height ratio) was a significant predictor of worse HRV (lower SDNN, RMSSD; P < .05), while higher HbA1c and TDD predicted all adverse HRV measures (lower SDNN, RMSSD, TI; P < .05) and abnormal sympathovagal balance (higher LF:HF ratio; P < .05). CONCLUSIONS Higher BMI and central adiposity are associated with cardiac autonomic dysfunction in childhood onset type 1 diabetes, after adjusting for HbA1c. Interventions targeting overweight/obesity during adolescence may optimize long-term vascular health in type 1 diabetes.
Collapse
Affiliation(s)
- Yoon H Cho
- The Children's Hospital at Westmead, Institute of Endocrinology and Diabetes, Westmead, Australia.,University of Sydney, Discipline of Child and Adolescent Health, Camperdown, Australia
| | - Maria E Craig
- The Children's Hospital at Westmead, Institute of Endocrinology and Diabetes, Westmead, Australia.,University of Sydney, Discipline of Child and Adolescent Health, Camperdown, Australia.,University of New South Wales, School of Women's and Children's Health, Randwick, Australia
| | - Tracey Jopling
- The Children's Hospital at Westmead, Institute of Endocrinology and Diabetes, Westmead, Australia
| | - Albert Chan
- The Children's Hospital at Westmead, Institute of Endocrinology and Diabetes, Westmead, Australia
| | - Kim C Donaghue
- The Children's Hospital at Westmead, Institute of Endocrinology and Diabetes, Westmead, Australia.,University of Sydney, Discipline of Child and Adolescent Health, Camperdown, Australia
| |
Collapse
|
|
39
|
Jaiswal M, Divers J, Urbina EM, Dabelea D, Bell RA, Pettitt DJ, Imperatore G, Pihoker C, Dolan LM, Liese AD, Marcovina S, Linder B, Feldman EL, Pop-Busui R. Cardiovascular autonomic neuropathy in adolescents and young adults with type 1 and type 2 diabetes: The SEARCH for Diabetes in Youth Cohort Study. Pediatr Diabetes 2018; 19:680-689. [PMID: 29292558 PMCID: PMC5938122 DOI: 10.1111/pedi.12633] [Citation(s) in RCA: 60] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2017] [Revised: 10/26/2017] [Accepted: 12/07/2017] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE To estimate the prevalence of and risk factors for cardiovascular autonomic neuropathy (CAN) in adolescents and young adults with type 1 and type 2 diabetes enrolled in the SEARCH for Diabetes in Youth Study. METHODS The study included 1646 subjects with type 1 diabetes (age 18 ± 4 years, diabetes duration 8 ± 2 years, HbA1c 9.1 ± 1.9%, 76% non-Hispanic Whites) and 252 with type 2 diabetes (age 22 ± 4 years, diabetes duration 8 ± 2 years, HbA1c 9.2 ± 3.0%, 45% non-Hispanic Blacks). Cross-sectional and longitudinal risk factors were assessed at baseline and follow-up visits. Area under the curve (AUC) was used to assess the longitudinal glycemic exposure and cardiovascular risk factors. CAN was assessed by time and frequency domain indices of heart rate variability (HRV). CAN was defined as the presence of ≥3 of 5 abnormal HRV indices. RESULTS The prevalence of CAN was 12% in adolescents and young adults with type 1 diabetes and 17% in those with type 2 diabetes. Poor long-term glycemic control (AUC HbA1c), high blood pressure, and elevated triglyceride levels were correlates of CAN in subjects with type 1 diabetes. In those with type 2 diabetes, CAN was associated with elevated triglycerides and increased urinary albumin excretion. CONCLUSIONS The prevalence of CAN in this multiethnic cohort of adolescents and young adults with type 1 and type 2 diabetes are comparable to those reported in adults with diabetes. Suboptimal glycemic control and elevated triglycerides were the modifiable risk factors associated with CAN.
Collapse
Affiliation(s)
- Mamta Jaiswal
- Department of Neurology, University of Michigan, Ann Arbor, Michigan
| | - Jasmin Divers
- Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Elaine M. Urbina
- Preventive Cardiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
| | - Dana Dabelea
- Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado
| | - Ronny A. Bell
- Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | | | - Giuseppina Imperatore
- Division of Diabetes Translation, Centers of Disease Control and Prevention, Atlanta, Georgia
| | - Catherine Pihoker
- Department of Pediatrics, University of Washington, Seattle Washington
| | - Lawrence M. Dolan
- Division of Endocrinology, Children’s Hospital Medical Center, Cincinnati, Ohio
| | - Angela D. Liese
- Department of Epidemiology and Biostatistics and Center for Research in Nutrition and Health Disparities, Arnold School of Public Health, University of South Carolina, South Carolina
| | - Santica Marcovina
- Northwest Lipid Research Laboratory, University of Washington, Seattle, Washington
| | - Barbara Linder
- Division of Diabetes, Endocrinology and Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland
| | - Eva L. Feldman
- Department of Neurology, University of Michigan, Ann Arbor, Michigan
| | - Rodica Pop-Busui
- Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | | |
Collapse
|
|
40
|
Lu L, Marcovecchio ML, Dalton RN, Dunger D. Cardiovascular autonomic dysfunction predicts increasing albumin excretion in type 1 diabetes. Pediatr Diabetes 2018; 19:464-469. [PMID: 29171134 DOI: 10.1111/pedi.12614] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2017] [Revised: 11/01/2017] [Accepted: 11/01/2017] [Indexed: 02/02/2023] Open
Abstract
OBJECTIVE To determine the potential role of cardiovascular autonomic dysfunction in the development of renal complications in young people with type 1 diabetes (T1D). METHODS In this prospective study, 199 children and adolescents recruited to the Oxford Regional Prospective Study underwent assessment of autonomic function ~5 years after diagnosis, and were subsequently followed with longitudinal assessments of HbA1c and urine albumin-creatinine ratio (ACR) over 8.6 ± 3.4 years. Autonomic function was assessed with 4 standardized tests of cardiovascular reflexes: heart rate (HR) response to (1) Valsalva Maneuver, (2) deep breathing, (3) standing, and (4) blood pressure (BP) response to standing. Linear mixed models were used to assess the association between autonomic parameters and future changes in ACR. RESULTS Independent of HbA1c , each SD increase in HR response to Valsalva Maneuver predicted an ACR increase of 2.16% [95% CI: 0.08; 4.28] per year (P = .04), while each SD increase in diastolic BP response to standing predicted an ACR increase of 2.55% [95% CI: 0.37; 4.77] per year (P = .02). The effect of HR response to standing on ACR reached borderline significance (-2.07% [95% CI: -4.11; 0.01] per year per SD increase, P = .051). CONCLUSIONS In this cohort of young people with T1D, enhanced cardiovascular reflexes at baseline predicted future increases in ACR. These results support a potential role for autonomic dysfunction in the pathogenesis of diabetic nephropathy.
Collapse
Affiliation(s)
- Liangjian Lu
- Department of Paediatrics, MRL Wellcome Trust-MRC Institute of Metabolic Science, NIHR Cambridge Comprehensive Biomedical Research Centre, University of Cambridge, Cambridge, UK.,Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore
| | - M Loredana Marcovecchio
- Department of Paediatrics, MRL Wellcome Trust-MRC Institute of Metabolic Science, NIHR Cambridge Comprehensive Biomedical Research Centre, University of Cambridge, Cambridge, UK
| | - R Neil Dalton
- WellChild Laboratory, Evelina London Children's Hospital, London, UK
| | - David Dunger
- Department of Paediatrics, MRL Wellcome Trust-MRC Institute of Metabolic Science, NIHR Cambridge Comprehensive Biomedical Research Centre, University of Cambridge, Cambridge, UK
| |
Collapse
|
|
41
|
The Influence of Glycemic Control on Heart Rate Variability and Blood Pressure in Adult Patients with the Type 1 Diabetes. ROMANIAN JOURNAL OF DIABETES NUTRITION AND METABOLIC DISEASES 2018. [DOI: 10.2478/rjdnmd-2018-0007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
Background and aims: to identify heart rate variability (HRV) and blood pressure (BP) in patients with type 1 diabetes depending on the duration of disease and glycemic control.
Materials and methods: 43 patients were examined. All patients were divided into 2 groups according to the level of НвА1с: group 1 (n=21) with НвА1с ≤ 7.5% and group 2 (n=22) with НвА1с > of 7.5%. All patients underwent daily monitoring of electrocardiogram Holter and ambulatory BP monitoring within 24 hours in parallel with long term monitoring of blood glucose.
Results: Hyppoglycemia is characterized by significant decrease root mean square difference between adjacent RR intervals (RMSSD) (r = −0.531; p = 0.003) and number of consecutive RR intervals, the difference between them is more than 50 ms expressed as a percentage of total number of RR-intervals (pNN50%) (r = the −0.503; p = 0.005) and increase of Low Frequency/High Frequency Ratio (LF/HF) (r = 0552; p = 0.002). Patients with hypoglycemia had significantly higher daily diastolic pressure area index (DPAI24) (p = 0.016), and daily diastolic pressure time index DPTI24 (p = 0.025).
Conclusion: our findings demonstrate the need to reduce the frequency of hypoglycemia episodes in patients with T1DM.
Collapse
|
|
42
|
Didangelos T, Moralidis E, Karlafti E, Tziomalos K, Margaritidis C, Kontoninas Z, Stergiou I, Boulbou M, Papagianni M, Papanastasiou E, Hatzitolios AI. A Comparative Assessment of Cardiovascular Autonomic Reflex Testing and Cardiac 123I-Metaiodobenzylguanidine Imaging in Patients with Type 1 Diabetes Mellitus without Complications or Cardiovascular Risk Factors. Int J Endocrinol 2018; 2018:5607208. [PMID: 29721015 PMCID: PMC5867537 DOI: 10.1155/2018/5607208] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2017] [Accepted: 01/31/2018] [Indexed: 02/08/2023] Open
Abstract
AIM To compare the cardiovascular autonomic reflex tests (CARTs) with cardiac sympathetic innervation imaging with 123I-metaiodobenzylguanidine (MIBG) in patients with type 1 diabetes mellitus (T1DM). PATIENTS AND METHODS Forty-nine patients (29 males, mean age 36 ± 10 years, mean T1DM duration 19 ± 6 years) without cardiovascular risk factors were prospectively enrolled. Participants were evaluated for autonomic dysfunction by assessing the mean circular resultant (MCR), Valsalva maneuver (Vals), postural index (PI), and orthostatic hypotension (OH). Within one month from the performance of these tests, patients underwent cardiac MIBG imaging and the ratio of the heart to upper mediastinum count density (H/M) at 4 hours postinjection was calculated (abnormal values, H/M < 1.80). RESULTS Twenty-nine patients (59%) had abnormal CARTs, and 37 (76%) patients had an H/M_4 < 1.80 (p = 0.456). MCR, PI, Vals, and OH were abnormal in 29 (59%), 8 (16%), 5 (10%), and 11 (22%) patients, respectively. When using H/M_4 < 1.80 as the reference standard, a cutoff point of ≥2 abnormal CARTs had a sensitivity of 100% but a specificity of only 33% for determining CAN. CONCLUSIONS CARTs are not closely associated with 123I-MIBG measurements, which can detect autonomic dysfunction more efficiently than the former. In comparison to semiquantitative cardiac MIBG assessment, the recommended threshold of ≥2 abnormal CARTs to define cardiovascular autonomic dysfunction is highly sensitive but of limited specificity and is independently determined by the duration of T1DM.
Collapse
Affiliation(s)
- Triantafyllos Didangelos
- Diabetes Center, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Efstratios Moralidis
- Laboratory of Nuclear Medicine, Medical School, Aristotle University of Thessaloniki, Papageorgiou Hospital, Thessaloniki, Greece
| | - Eleni Karlafti
- Diabetes Center, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Konstantinos Tziomalos
- Diabetes Center, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Charalambos Margaritidis
- Diabetes Center, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Zisis Kontoninas
- Diabetes Center, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Ioannis Stergiou
- Diabetes Center, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | - Maria Boulbou
- Department of Internal Medicine, Medical School, University of Thessaly, Larissa, Greece
| | - Marianthi Papagianni
- Diabetes Center, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| | | | - Apostolos I. Hatzitolios
- Diabetes Center, First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece
| |
Collapse
|
|
43
|
Gourgari E, Dabelea D, Rother K. Modifiable Risk Factors for Cardiovascular Disease in Children with Type 1 Diabetes: Can Early Intervention Prevent Future Cardiovascular Events? Curr Diab Rep 2017; 17:134. [PMID: 29101482 PMCID: PMC5670186 DOI: 10.1007/s11892-017-0968-y] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
PURPOSE OF REVIEW Patients with type 1 diabetes have increased risk for cardiovascular disease. The purpose of this review is to examine the following: i) current evidence for subclinical cardiovascular disease (CVD) in children with type 1 diabetes (T1DM) ii) known modifiable risk factors for CVD and their relationship to subclinical CVD in this population iii) studies that have addressed these risk factors in order to improve CVD outcomes in children with T1DM RECENT FINDINGS: Subclinical CVD presents in children as increased carotid intima-media thickness, increased arterial stiffness, and endothelial and myocardial dysfunction. Modifiable risk factors for CVD include hyperglycemia, hyperlipidemia, obesity, hypertension, depression, and autonomic dysfunction. Very few randomized controlled studies have been done in children with T1DM to examine how modification of these risk factors can affect their CVD. Children with T1DM have subclinical CVD and multiple modifiable risk factors for CVD. More research is needed to define how modification of these factors affects the progression of CVD.
Collapse
Affiliation(s)
- Evgenia Gourgari
- Department of Pediatrics, Georgetown University, Washington DC, USA
- Section on Endocrinology and Genetics, Program on Developmental Endocrinology & Genetics (PDEGEN) and Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD USA
| | - Dana Dabelea
- Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, CO USA
| | - Kristina Rother
- Section on Pediatric Diabetes and Metabolism, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD USA
| |
Collapse
|
|
44
|
Bhaskar L, Kharya C, Deepak KK, Kochupillai V. Assessment of Cardiac Autonomic Tone Following Long Sudarshan Kriya Yoga in Art of Living Practitioners. J Altern Complement Med 2017; 23:705-712. [PMID: 28691853 DOI: 10.1089/acm.2016.0391] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVE The breathing processes are known to modulate cardiac autonomic tone and improve psychological status. We investigated cardiac autonomic tone following long Sudarshan Kriya Yoga (SKY) using heart rate variability (HRV) and skin conductance level (SCL). METHODS Thirty healthy volunteers (age 28.3 ± 8.4 years; 23 M: 7 F) participated in the study. Electrocardiogram (ECG) and SCL were recorded for 5 min each, before and after long SKY. Long SKY is a combination of pranayama and cyclic rhythmic breathing and is performed by following the guided audio instructions. HRV analysis was used for the assessment of cardiac autonomic tone. Time and frequency domain parameters of HRV were calculated by using RR interval of ECG. SCL was acquired using Galvanic skin response (GSR) amplifier of PowerLab in microSeimens (μS). RESULTS Time domain parameters of HRV, including mean RR interval (p = 0.000), respiratory sinus arrhythmia (RSA) (p = 0.037), standard deviation of all NN intervals (SDNN) (p = 0.013), NN50 count divided by the total number of all NN intervals (pNN50) (p = 0.004), and square root of the mean of the sum of the squares of differences between adjacent NN intervals (RMSSD) (p = 0.002) increased, and mean heart rate decreased (p = 0.000) following long SKY. In frequency domain analysis, power of low-frequency (LF) component (p = 0.010) and LF/HF ratio (p = 0.008) decreased significantly, whereas power of high frequency (HF) significantly increased (p = 0.010). SCL decreased following long SKY, although it did not attain statistical significance. CONCLUSIONS The results suggest that long SKY induces significant oscillations in cardiac autonomic tone. Parasympathetic activity increases and sympathetic activity decreases and sympathovagal balance improves following long SKY. Decrease in sympathetic activity is also demonstrated by decrease in conductance although it did not reach statistical significance. From this study it can be concluded that long SKY has a beneficial effect on cardiac autonomic tone, and psychophysiological relaxation. It may serve as a tool to improve HRV, which is the marker of cardiovascular health.
Collapse
Affiliation(s)
- Lakshmi Bhaskar
- 1 Sri Sri Institute of Advanced Research , Ved Vignan Maha Vidya Peeth, Bengaluru, India
| | - Chhaya Kharya
- 1 Sri Sri Institute of Advanced Research , Ved Vignan Maha Vidya Peeth, Bengaluru, India
| | - K K Deepak
- 2 Department of Physiology, All India Institute of Medical Sciences , New Delhi, India
| | - Vinod Kochupillai
- 1 Sri Sri Institute of Advanced Research , Ved Vignan Maha Vidya Peeth, Bengaluru, India
| |
Collapse
|
|
45
|
Silva AKFD, Christofaro DGD, Bernardo AFB, Vanderlei FM, Vanderlei LCM. Sensitivity, Specificity and Predictive Value of Heart Rate Variability Indices in Type 1 Diabetes Mellitus. Arq Bras Cardiol 2017; 108:255-262. [PMID: 28443958 PMCID: PMC5389875 DOI: 10.5935/abc.20170024] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2016] [Accepted: 11/17/2016] [Indexed: 11/20/2022] Open
Abstract
Background Heart rate variability (HRV) indices may detect autonomic changes with good
diagnostic accuracy. Type diabetes mellitus (DM) individuals may have
changes in autonomic modulation; however, studies of this nature in this
population are still scarce. Objective To compare HRV indices between and assess their prognostic value by
measurements of sensitivity, specificity and predictive values in young
individuals with type 1 DM and healthy volunteers. Methods In this cross-sectional study, physical and clinical assessment was performed
in 39 young patients with type 1 DM and 43 young healthy controls. For HRV
analysis, beat-to-beat heart rate variability was measured in dorsal
decubitus, using a Polar S810i heart rate monitor, for 30 minutes. The
following indices were calculated: SDNN, RMSSD, PNN50, TINN, RRTri, LF
ms2, HF ms2, LF un, HF un, LF/HF, SD1, SD2,
SD1/SD2, and ApEn. Results Type 1 DM subjects showed a decrease in sympathetic and parasympathetic
activities, and overall variability of autonomic nervous system. The RMSSD,
SDNN, PNN50, LF ms2, HF ms2, RRTri, SD1 and SD2
indices showed greater diagnostic accuracy in discriminating diabetic from
healthy individuals. Conclusion Type 1 DM individuals have changes in autonomic modulation. The SDNN, RMSSD,
PNN50, RRtri, LF ms2, HF ms2, SD1 and SD2 indices may
be alternative tools to discriminate individuals with type 1 DM.
Collapse
|
|
46
|
Thuy TD, Phan NN, Wang CY, Yu HG, Wang SY, Huang PL, Do YY, Lin YC. Novel therapeutic effects of sesamin on diabetes-induced cardiac dysfunction. Mol Med Rep 2017; 15:2949-2956. [PMID: 28358428 PMCID: PMC5428537 DOI: 10.3892/mmr.2017.6420] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Accepted: 10/27/2016] [Indexed: 12/19/2022] Open
Abstract
Diabetes is a risk factor that increases the occurrence and severity of cardiovascular events. Cardiovascular complications are the leading cause of mortality of 75% of patients with diabetes >40 years old. Sesamin, the bioactive compound extracted from Sesamum indicum, is a natural compound that has diverse beneficial effects on hypoglycemia and reducing cholesterol. The aim of this study is to investigate sesamin effects to diabetes-inducing cardiac hypertrophy. In the present study bioinformatics analysis demonstrated cardiac hypertrophy signaling may be the most important pathway for upregulating genes in sesamin-treated groups. To verify the bioinformatics prediction, sesamin was used as the main bioactive compound to attenuate the impact of diabetes induced by streptozotocin (STZ) on cardiac function in a rat model. The results revealed that oral administration of sesamin for 4 weeks (100 and 200 mg/kg body weight) marginally improved blood glucose levels, body weight and significantly ameliorated the effects on heart rate and blood pressure in rats with type 1 diabetes relative to control rats. The QT interval of sesamin was also reduced relative to the control group. The findings indicated that sesamin has potential cardioprotective effects in the STZ-induced diabetes model. This suggested that this can be used as a novel treatment for patients with diabetes with cardiac dysfunction complication.
Collapse
Affiliation(s)
- Tran Duong Thuy
- Graduate Institute of Biotechnology, Chinese Culture University, YangMingShan, Taipei 11114, Taiwan, R.O.C
| | - Nam Nhut Phan
- Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City 70000, Vietnam
| | - Chih-Yang Wang
- Department of Anatomy, University of California San Francisco, San Francisco, CA 94143, USA
| | - Han-Gang Yu
- Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV 26506, USA
| | - Shu-Yin Wang
- Graduate Institute of Biotechnology, Chinese Culture University, YangMingShan, Taipei 11114, Taiwan, R.O.C
| | - Pung-Ling Huang
- Graduate Institute of Biotechnology, Chinese Culture University, YangMingShan, Taipei 11114, Taiwan, R.O.C
| | - Yi-Yin Do
- Department of Horticulture and Landscape Architecture, National Taiwan University, Taipei 10617, Taiwan, R.O.C
| | - Yen-Chang Lin
- Graduate Institute of Biotechnology, Chinese Culture University, YangMingShan, Taipei 11114, Taiwan, R.O.C
| |
Collapse
|
|
47
|
Dabelea D, Stafford JM, Mayer-Davis EJ, D'Agostino R, Dolan L, Imperatore G, Linder B, Lawrence JM, Marcovina SM, Mottl AK, Black MH, Pop-Busui R, Saydah S, Hamman RF, Pihoker C. Association of Type 1 Diabetes vs Type 2 Diabetes Diagnosed During Childhood and Adolescence With Complications During Teenage Years and Young Adulthood. JAMA 2017; 317:825-835. [PMID: 28245334 PMCID: PMC5483855 DOI: 10.1001/jama.2017.0686] [Citation(s) in RCA: 439] [Impact Index Per Article: 54.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Importance The burden and determinants of complications and comorbidities in contemporary youth-onset diabetes are unknown. Objective To determine the prevalence of and risk factors for complications related to type 1 diabetes vs type 2 diabetes among teenagers and young adults who had been diagnosed with diabetes during childhood and adolescence. Design, Setting, and Participants Observational study from 2002 to 2015 in 5 US locations, including 2018 participants with type 1 and type 2 diabetes diagnosed at younger than 20 years, with single outcome measures between 2011 and 2015. Exposures Type 1 and type 2 diabetes and established risk factors (hemoglobin A1c level, body mass index, waist-height ratio, and mean arterial blood pressure). Main Outcomes and Measures Diabetic kidney disease, retinopathy, peripheral neuropathy, cardiovascular autonomic neuropathy, arterial stiffness, and hypertension. Results Of 2018 participants, 1746 had type 1 diabetes (mean age, 17.9 years [SD, 4.1]; 1327 non-Hispanic white [76.0%]; 867 female patients [49.7%]), and 272 had type 2 (mean age, 22.1 years [SD, 3.5]; 72 non-Hispanic white [26.5%]; 181 female patients [66.5%]). Mean diabetes duration was 7.9 years (both groups). Patients with type 2 diabetes vs those with type 1 had higher age-adjusted prevalence of diabetic kidney disease (19.9% vs 5.8%; absolute difference [AD], 14.0%; 95% CI, 9.1%-19.9%; P < .001), retinopathy (9.1% vs 5.6%; AD, 3.5%; 95% CI, 0.4%-7.7%; P = .02), peripheral neuropathy (17.7% vs 8.5%; AD, 9.2%; 95% CI, 4.8%-14.4%; P < .001), arterial stiffness (47.4% vs 11.6%; AD, 35.9%; 95% CI, 29%-42.9%; P < .001), and hypertension (21.6% vs 10.1%; AD, 11.5%; 95% CI, 6.8%-16.9%; P < .001), but not cardiovascular autonomic neuropathy (15.7% vs 14.4%; AD, 1.2%; 95% CI, -3.1% to 6.5; P = .62). After adjustment for established risk factors measured over time, participants with type 2 diabetes vs those with type 1 had significantly higher odds of diabetic kidney disease (odds ratio [OR], 2.58; 95% CI, 1.39-4.81; P=.003), retinopathy (OR, 2.24; 95% CI, 1.11-4.50; P = .02), and peripheral neuropathy (OR, 2.52; 95% CI, 1.43-4.43; P = .001), but no significant difference in the odds of arterial stiffness (OR, 1.07; 95% CI, 0.63-1.84; P = .80) and hypertension (OR, 0.85; 95% CI, 0.50-1.45; P = .55). Conclusions and Relevance Among teenagers and young adults who had been diagnosed with diabetes during childhood or adolescence, the prevalence of complications and comorbidities was higher among those with type 2 diabetes compared with type 1, but frequent in both groups. These findings support early monitoring of youth with diabetes for development of complications.
Collapse
Affiliation(s)
- Dana Dabelea
- Department of Epidemiology, Colorado School of Public Health, Aurora
| | - Jeanette M Stafford
- Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | | | - Ralph D'Agostino
- Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina
| | - Lawrence Dolan
- Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Giuseppina Imperatore
- Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Barbara Linder
- Division of Diabetes, Endocrinology and Metabolic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland
| | - Jean M Lawrence
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena
| | | | - Amy K Mottl
- UNC Division of Nephrology and Hypertension, University of North Carolina School of Medicine, Chapel Hill
| | - Mary Helen Black
- Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena
| | - Rodica Pop-Busui
- Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor
| | - Sharon Saydah
- Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Richard F Hamman
- Department of Epidemiology, Colorado School of Public Health, Aurora
| | | |
Collapse
|
|
48
|
França da Silva AK, Penachini da Costa de Rezende Barbosa M, Marques Vanderlei F, Destro Christofaro DG, Marques Vanderlei LC. Application of Heart Rate Variability in Diagnosis and Prognosis of Individuals with Diabetes Mellitus: Systematic Review. Ann Noninvasive Electrocardiol 2017; 21:223-35. [PMID: 27226209 DOI: 10.1111/anec.12372] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND The use of heart rate variability as a tool capable of discriminating individuals with diabetes mellitus is still little explored, as its use has been limited to comparing those with and without the disease. Thus, the purpose of this study was to verify the use of heart rate variability as a tool for diagnostic and prognostic evaluation in person with diabetes and to identify whether there are cutoff points generated from the use of this tool in these individuals. METHODS A search was conducted in the electronic databases MEDLINE, Cochrane Library, Web of Science, EMBASE, and LILACS starting from the oldest records until January 2015, by means of descriptors related to the target condition, evaluated tool, and evaluation method. All the studies were evaluated for methodological quality using the QUADAS-2 instrument. RESULTS Eight studies were selected. In general, the studies showed that the heart rate variability is useful to discriminate cardiac autonomic neuropathy in person with diabetes, and the sample entropy, SD1/SD2 indices, SDANN, HF, and slope of TFC have better discriminatory power to detect autonomic dysfunction, with sensitivity and specificity values ranging from 72% to 100% and 71% to 97%, respectively. CONCLUSION Although there are methodological differences in indices used, in general, this tool demonstrated good sensitivity and specificity and can be used as an additional and/or complementary tool to the conventional autonomic tests, in order to obtain safer and more effective diagnostic, collaborating for better risk stratification conditions of these patients.
Collapse
Affiliation(s)
| | | | - Franciele Marques Vanderlei
- Department of Physical Therapy, Faculty of Science and Technology, Paulista State University, Presidente Prudente, São Paulo, Brazil
| | - Diego Giuliano Destro Christofaro
- Department of Physical Education, Faculty of Science and Technology, Paulista State University, Presidente Prudente, São Paulo, Brazil
| | - Luiz Carlos Marques Vanderlei
- Department of Physical Therapy, Faculty of Science and Technology, Paulista State University, Presidente Prudente, São Paulo, Brazil
| |
Collapse
|
|
49
|
Razanskaite-Virbickiene D, Danyte E, Mockeviciene G, Dobrovolskiene R, Verkauskiene R, Zalinkevicius R. Can coefficient of variation of time-domain analysis be valuable for detecting cardiovascular autonomic neuropathy in young patients with type 1 diabetes: a case control study. BMC Cardiovasc Disord 2017; 17:34. [PMID: 28103812 PMCID: PMC5244586 DOI: 10.1186/s12872-016-0467-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2016] [Accepted: 12/29/2016] [Indexed: 02/07/2023] Open
Abstract
Background Cardiovascular autonomic neuropathy (CAN) increases morbidity and mortality in diabetes through association with a high risk of cardiac arrhythmias and sudden death, possibly related to silent myocardial ischemia. During the sub-clinical stage, CAN can be detected through reduction in heart rate variability (HRV). The aim of our study was to estimate if the time and frequency-domain analysis can be valuable for detecting CAN in young patients with type 1 diabetes mellitus (T1DM). Methods For this case control study of evaluation of cardiovascular autonomic function the 15–25 years age group of patients with duration of T1DM more than 9 years (n = 208, 89 males and 119 females) were selected. 67 patients with confirmed CAN were assigned to the “case group” and 141 patients without CAN served as a control group, the duration of T1DM was similar (15.07 ± 4.89 years vs.13.66 ± 4.02 years; p = 0.06) in both groups. Cardiovascular autonomic reflex tests and time and frequency domains analysis of HRV were performed for all subjects. Results Time domain measures were significantly lower in CAN group compared with control (p < 0.05). R-R max / R-R min ratio and coefficient of variation (CV) were the lowest during deep breathing among T1DM patients with CAN. Receivers operating characteristic (ROC) curves were constructed to compare the accuracies of the parameters of time-domain analysis for diagnosing CAN. We estimated a more reliable cut-off value of parameters of time-domain. The CV values in supine position <1.65, reflected sensitivity 94.3%, specificity 91.5%. The CV values during deep breathing <1.45 reflected sensitivity 97.3%, specificity 96.2%. The CV values in standing position <1.50 reflected sensitivity 96.2%, specificity 93.0%. The most valuable CV was during deep breathing (AUC 0.899). The results of frequency-domain (spectral analysis) analysis showed significant decrease in LF power and LFPA, HF Power and HFPA, total power among subjects with CAN than compared with subjects without CAN (p < 0.05). Conclusions Time and frequency domain analysis of HRV permits a more accurate evaluation of cardiovascular autonomic function, providing more information about sympathetic and parasympathetic activity. The coefficient of variation (time-domain analysis) especially during deep breathing could be valuable for detecting CAN.
Collapse
Affiliation(s)
| | - Evalda Danyte
- Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, LT-44307, Kaunas, Lithuania
| | - Giedre Mockeviciene
- Department of Endocrinology Medical Academy, Lithuanian University of Health Sciences, LT-44307, Kaunas, Lithuania
| | - Rimante Dobrovolskiene
- Department of Endocrinology Medical Academy, Lithuanian University of Health Sciences, LT-44307, Kaunas, Lithuania
| | - Rasa Verkauskiene
- Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, LT-44307, Kaunas, Lithuania
| | - Rimantas Zalinkevicius
- Institute of Endocrinology, Medical Academy, Lithuanian University of Health Sciences, LT-44307, Kaunas, Lithuania
| |
Collapse
|
|
50
|
Association of cardiac autonomic modulation with physical and clinical features of young people with type 1 diabetes. Cardiol Young 2017; 27:37-45. [PMID: 26980053 DOI: 10.1017/s1047951116000044] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVE The objective of this study was to verify possible associations between heart rate variability indices and physical activity, body composition, and metabolic and cardiovascular parameters in individuals with type 1 diabetes. METHOD A total of 39 young patients with type 1 diabetes were included. Body composition, physical activity, cardiovascular parameters, and metabolic parameters were assessed. For the heart rate variability analysis, heart rate was recorded beat-by-beat using a Polar S810i heart rate monitor for 30 minutes, with the volunteers in the supine position; subsequently, the following indices were considered: standard deviation of all normal RR intervals; root-mean square of differences between adjacent normal RR intervals in a time interval; percentage of adjacent RR intervals with a difference of duration >50 ms; high frequency component in milliseconds squared; high frequency component in normalised units; standard deviation of the instantaneous variability beat-to-beat; and standard deviation of the long-term variability. The association between the heart rate variability indices and independent variables was verified through linear regression in unadjusted and adjusted models (considering gender and age). The statistical significance was set at 5% and the confidence interval at 95%. RESULTS High values of at-rest heart rate were associated with reduced parasympathetic activity and global heart rate variability, and higher values of waist-to-hip ratio were related to lower parasympathetic activity, independent of age or gender. CONCLUSION For young patients with type 1 diabetes, increases in at-rest heart rate values are associated with reduced parasympathetic activity and global heart rate variability, whereas higher waist-to-hip ratio values are related to lower parasympathetic activity, both independent of age and gender.
Collapse
|