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Azmi S, Ferdousi M, Kalteniece A, Petropoulos IN, Alam U, Ponirakis G, Asghar O, Marshall A, Boulton AJ, Efron N, Malik RA. Corneal confocal microscopy identifies early and definite diabetic cardiac autonomic neuropathy. Diabetes Res Clin Pract 2025; 224:112172. [PMID: 40220793 DOI: 10.1016/j.diabres.2025.112172] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2025] [Revised: 03/31/2025] [Accepted: 04/09/2025] [Indexed: 04/14/2025]
Abstract
OBJECTIVE Advanced cardiac autonomic neuropathy (CAN) is associated with increased mortality in people with diabetes. Early identification and reduction of risk factors can limit the progression of CAN. However, the diagnosis of early CAN relies on cardiac autonomic reflex testing (CART's) which is not widely available. We have compared the diagnostic utility of corneal confocal microscopy (CCM) to CART's in diagnosing CAN. RESEARCH DESIGN AND METHODS Two-hundred and thirty eight individuals with type 1 and type 2 diabetes and thirty seven healthy controls were assessed using CARTs and CCM. RESULTS There was a progressive and significant reduction in DB-HRV, E:I ratio, 30:15 ratio, corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fibre length (CNFL) with increasing severity of CAN. The receiver operating characteristic (ROC) area under the curve (AUC) and sensitivity/specificity of CCM were comparable to those of CARTs for identifying early and definite CAN. CONCLUSION CCM is a rapid, non-invasive ophthalmic test which could be used to detect early and established CAN.
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Affiliation(s)
- Shazli Azmi
- Diabetes, Endocrinology and Metabolism Centre, Manchester University NHS Foundation Trust, UK; Division of Cardiovascular Sciences, University of Manchester, UK
| | - Maryam Ferdousi
- Division of Cardiovascular Sciences, University of Manchester, UK
| | - Alise Kalteniece
- Division of Cardiovascular Sciences, University of Manchester, UK
| | | | - Uazman Alam
- Liverpool University Hospitals NHS Foundation Trust, Aintree Hospital, Liverpool, UK
| | | | - Omar Asghar
- Division of Cardiovascular Sciences, University of Manchester, UK
| | | | - Andrew Jm Boulton
- Diabetes, Endocrinology and Metabolism Centre, Manchester University NHS Foundation Trust, UK; Division of Cardiovascular Sciences, University of Manchester, UK
| | - Nathan Efron
- Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia
| | - Rayaz A Malik
- Division of Cardiovascular Sciences, University of Manchester, UK; Weill Cornell Medicine-Qatar, Doha, Qatar.
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Velmeden D, Söhne J, Schuch A, Zeid S, Schulz A, Troebs SO, Müller F, Heidorn MW, Buch G, Belanger N, Dinh W, Mondritzki T, Lackner KJ, Gori T, Münzel T, Wild PS, Prochaska JH. Role of Heart Rate Recovery in Chronic Heart Failure: Results From the MyoVasc Study. J Am Heart Assoc 2025; 14:e039792. [PMID: 40371587 DOI: 10.1161/jaha.124.039792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Accepted: 03/11/2025] [Indexed: 05/16/2025]
Abstract
BACKGROUND Cardiac autonomic dysfunction is associated with heart failure (HF). Reduced heart rate recovery (HRR) indicates impaired parasympathetic reactivation after physical activity. Heart rate recovery 60 seconds after peak effort (HRR60) is linked to autonomic dysfunction, but data on its relevance across HF phenotypes are scarce. This study aimed to identify clinical determinants of HRR60 in an HF cohort and assess its relationship with clinical outcomes. METHODS Data from the MyoVasc study (NCT04064450; N=3289) were analyzed. Participants underwent standardized clinical phenotyping including cardiopulmonary exercise testing. HRR60 was defined as the heart rate decline 60 seconds after exercise termination. Clinical determinants of HRR60 were evaluated using multivariate regression, whereas Cox regression analyses assessed all-cause death and worsening of HF. RESULTS The analysis sample comprised 1289 individuals (median age, 66.0 [interquartile range {IQR}, 58.0-73.0] years, 30.4% women) ranging from stage B to stage C/D according to the universal definition of HF. Age, sex, smoking, obesity, peripheral artery disease, and chronic kidney disease were identified as determinants of HRR60. HRR60 showed a strong association with all-cause death (hazard ratio [HR]HRR60 [10 bpm], 1.56 [95% CI, 1.32-1.85]; P<0.0001) and worsening of HF (HRHRR60 [10 bpm], 1.36 [95% CI, 1.10-1.69]; P=0.0052) independent of age, sex, and clinical profile. Sensitivity analysis showed a stronger association with worsening HF in HF with preserved left ventricular ejection fraction (Pinteraction=0.027). CONCLUSIONS HRR60 was associated with clinical outcome in chronic HF. Because it showed a stronger association with outcomes in HF with preserved ejection fraction, future research should consider phenotype-specific differences.
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Affiliation(s)
- David Velmeden
- Preventive Cardiology and Preventive Medicine, Department of Cardiology University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main Mainz Germany
- Department of Cardiology - Cardiology I University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
| | - Jakob Söhne
- Preventive Cardiology and Preventive Medicine, Department of Cardiology University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main Mainz Germany
- Department of Cardiology - Cardiology I University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
| | - Alexander Schuch
- Preventive Cardiology and Preventive Medicine, Department of Cardiology University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main Mainz Germany
- Department of Cardiology - Cardiology I University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
| | - Silav Zeid
- Preventive Cardiology and Preventive Medicine, Department of Cardiology University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main Mainz Germany
| | - Andreas Schulz
- Preventive Cardiology and Preventive Medicine, Department of Cardiology University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
| | - Sven-Oliver Troebs
- Preventive Cardiology and Preventive Medicine, Department of Cardiology University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main Mainz Germany
| | - Felix Müller
- Preventive Cardiology and Preventive Medicine, Department of Cardiology University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main Mainz Germany
- Department of Cardiology - Cardiology I University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
| | - Marc W Heidorn
- Preventive Cardiology and Preventive Medicine, Department of Cardiology University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main Mainz Germany
- Department of Cardiology - Cardiology I University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
| | - Gregor Buch
- Preventive Cardiology and Preventive Medicine, Department of Cardiology University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main Mainz Germany
- Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI) University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
| | - Noémie Belanger
- Preventive Cardiology and Preventive Medicine, Department of Cardiology University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main Mainz Germany
| | - Wilfried Dinh
- Bayer AG, Research and Development, Translational Clinical Medicine, Experimental Medicine 1 Wuppertal Germany
- School of Medicine University Witten/Herdecke Witten Germany
| | - Thomas Mondritzki
- Research & Early Development, Clinical Experimentation CV, BAYER AG Wuppertal Germany
| | - Karl J Lackner
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main Mainz Germany
- Institute for Clinical Chemistry and Laboratory Medicine University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
| | - Tommaso Gori
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main Mainz Germany
- Department of Cardiology - Cardiology I University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
| | - Thomas Münzel
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main Mainz Germany
- Department of Cardiology - Cardiology I University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
| | - Philipp S Wild
- Preventive Cardiology and Preventive Medicine, Department of Cardiology University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main Mainz Germany
- Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis (CTH) University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
- Institute for Molecular Biology (IMB), Mainz, Working Group Systems Medicine Mainz Germany
| | - Jürgen H Prochaska
- Preventive Cardiology and Preventive Medicine, Department of Cardiology University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Rhine-Main Mainz Germany
- Clinical Epidemiology and Systems Medicine, Center for Thrombosis and Hemostasis (CTH) University Medical Center of the Johannes Gutenberg University Mainz Mainz Germany
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Forkan CP, Shrestha A, Yu A, Chuang C, Pociot F, Yarani R. Could hypoxic conditioning augment the potential of mesenchymal stromal cell-derived extracellular vesicles as a treatment for type 1 diabetes? Stem Cell Res Ther 2025; 16:37. [PMID: 39901225 PMCID: PMC11792614 DOI: 10.1186/s13287-025-04153-4] [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: 11/04/2024] [Accepted: 01/16/2025] [Indexed: 02/05/2025] Open
Abstract
Type1 Diabetes (T1D) is an autoimmune disorder characterised by the loss of pancreatic β-cells. This β cell loss occurs primarily through inflammatory pathways culminating in apoptosis. Mesenchymal stromal cells (MSCs) have been heavily studied for therapeutic applications due to their regenerative, anti-apoptotic, immunomodulatory, and anti-inflammatory properties. The therapeutic effects of MSCs are mediated through cell-to-cell contact, differentiation, and the release of paracrine factors, which include the release of extracellular vesicles (EVs). Culturing MSCs in hypoxia, a low oxygen tension state more analogous to their physiological environment, seems to increase the therapeutic efficacy of MSC cell therapy, enhancing their immunomodulatory, anti-inflammatory, and anti-fibrotic properties. This is also the case with MSC-derived EVs, which show altered properties based on the parent cell preconditioning. In this review, we examine the evidence supporting the potential application of hypoxic preconditioning in strengthening MSC-EVs for treating the inflammatory and apoptotic causes of β cell loss in T1D.
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Affiliation(s)
- Cathal Patrick Forkan
- Translational Type 1 Diabetes Research, Department of Clinical and Translational Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Aruna Shrestha
- Translational Type 1 Diabetes Research, Department of Clinical and Translational Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
| | - Alfred Yu
- Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, 94304, USA
| | - Christine Chuang
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Flemming Pociot
- Translational Type 1 Diabetes Research, Department of Clinical and Translational Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Reza Yarani
- Translational Type 1 Diabetes Research, Department of Clinical and Translational Research, Steno Diabetes Center Copenhagen, Herlev, Denmark.
- Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University School of Medicine, Palo Alto, CA, 94304, USA.
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Barmpagianni A, Karamanakos G, Anastasiou IA, Kountouri A, Lambadiari V, Liatis S. The relationship between residual insulin secretion and subclinical cardiovascular risk indices in young adults with type 1 diabetes. J Diabetes Complications 2025; 39:108946. [PMID: 39731973 DOI: 10.1016/j.jdiacomp.2024.108946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 09/25/2024] [Accepted: 12/21/2024] [Indexed: 12/30/2024]
Abstract
BACKGROUND Patients with type 1 diabetes (DM1), even in the setting of adequate glycaemic control, have an excess risk for developing cardiovascular disease. Residual insulin secretion (RIS), measured by detectable C-peptide levels in patients with DM1, might protect against diabetes-related complications. This study aimed to examine the relationship between residual insulin secretion and prognostic markers of cardiovascular complications in patients with DM1. METHODS A total of 137 patients with DM1 were included in this analysis. They were of young age (<45 years), with an established diagnosis of over two years before the study entry and without a history of cardiovascular complications. All patients underwent complete clinical and laboratory evaluation. A c-peptide measurement of ≥0.05 ng/ml was used to identify the presence of RIS. Pulse wave velocity (PWV), cardiac autonomic function assessed both at rest, by total power of heart rate variability and dynamically, by the expiration to inspiration (e/i) index, albumin to creatinine ratio (ACR), and high sensitivity CRP (hs-CRP) were used as predictive biomarkers of cardiovascular complications. RESULTS Female participants represented 63.5% of the population [mean age: 29.7 (±8.1) years, mean HbA1c: 7.6% (±1.4), median diabetes duration:15 (10-21) years, median age at diabetes diagnosis: 13 (8-17) years]]. The median value of fasting c-peptide was 0.04 (0.03-0.05) ng/ml, and RIS was detected in 32 patients (23.4%). Patients with RIS had a shorter diabetes duration, an older age at diagnosis and a lower BMI, while no significant association was found between residual c-peptide and age or HbA1c. RIS was significantly associated with lower PWV values [8.1 m/s² (7-8.7) vs 9.2 m/s² (7.8-10.1), p <0,001], higher total power values [1124 Hz (600-3277) vs 577 Hz (207-2091), p <0,001], and higher E/I measurements [1.4 (1.2-1.5) vs. 1.3 (1.2-1.4), p=0.01]. No significant association was noted between RIS and either ACR or hs-CRP. In multivariable linear regression analysis, the association between RIS and lower PWV values remained significant (p= 0.007) regardless of age, sex, diabetes duration or age of diagnosis, blood pressure and BMI. Similarly, residual insulin secretion retained a significant independent association with total power (p= 0.032) and E/I (p=0.045). CONCLUSION In young patients with DM1, free of macrovascular complications, residual insulin secretion is independently associated with more favorable prognostic markers of subclinical atherosclerosis and cardiac autonomic function.
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Affiliation(s)
- Aikaterini Barmpagianni
- National and Kapodistrian University of Athens First Department of Propaedeutic and Internal Medicine, Laiko General Hospital Athens, Attiki, Greece.
| | - Georgios Karamanakos
- National and Kapodistrian University of Athens First Department of Propaedeutic and Internal Medicine, Laiko General Hospital Athens, Attiki, Greece
| | - Ioanna A Anastasiou
- National and Kapodistrian University of Athens First Department of Propaedeutic and Internal Medicine, Laiko General Hospital Athens, Attiki, Greece
| | - Aikaterini Kountouri
- National and Kapodistrian University of Athens First Department of Propaedeutic and Internal Medicine, Laiko General Hospital Athens, Attiki, Greece
| | - Vaia Lambadiari
- National and Kapodistrian University of Athens First Department of Propaedeutic and Internal Medicine, Laiko General Hospital Athens, Attiki, Greece
| | - Stavros Liatis
- National and Kapodistrian University of Athens First Department of Propaedeutic and Internal Medicine, Laiko General Hospital Athens, Attiki, Greece
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Ozde S, Yavuzyilmaz F, Ozel MA, Kayapinar O, Ozde C, Akture G, Arslanoglu I. Evaluation of Serum Soluble Lectin-like Oxidised Low-Density Lipoprotein Receptor-1 (sLOX-1) Level in Children with Non-Complicated Type-1 Diabetes Mellitus (T1DM) and Its Relationship with Carotid Intima Media Thickness (cIMT). J Clin Med 2025; 14:935. [PMID: 39941605 PMCID: PMC11818572 DOI: 10.3390/jcm14030935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 01/10/2025] [Accepted: 01/27/2025] [Indexed: 02/16/2025] Open
Abstract
Background: The objective of this study was to evaluate serum soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) levels in children with type-1 diabetes mellitus (T1DM) without any atherosclerotic complications and to investigate whether there was an association with early atherosclerotic processes in these children. Methods: The study's design entailed a prospective cross-sectional observational study methodology. The patient group consisted of 80 consecutive children aged 8-18 years who had been diagnosed with T1DM for at least ten years and had not developed any chronic clinical complications related to T1DM. The control group consisted of 72 completely healthy children with similar demographic characteristics. Serum levels of sLOX-1 were measured, and carotid intima-media thickness (cIMT) was evaluated using ultrasonography in all subjects. Results: A statistical analysis of the results was conducted. The serum sLOX-1 level was found to be significantly higher in the patient group than in the control group (0.49 ± 0.11 vs. 0.82 ± 0.35; p < 0.001). The statistical significance observed was maintained in the multivariable logistic regression analysis (p < 0.001). A significant correlation was identified between cIMT and serum sLOX-1 levels (r = 0.669, p < 0.001). The receiver operating characteristic curve for sLOX-1 indicated that a cutoff value greater than 0.65 ng/mL was associated with T1DM. Conclusions: Serum sLOX-1 levels were markedly elevated in children with T1DM who had not yet manifested chronic complications. These findings suggest that elevated serum sLOX-1 levels may be associated with the progression of atherosclerosis in children with T1DM.
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Affiliation(s)
- Sukriye Ozde
- Department of General Pediatric, Faculty of Medicine, Duzce University, 81620 Duzce, Turkey;
| | - Fatma Yavuzyilmaz
- Department of Pediatric Endocrinology, Faculty of Medicine, Duzce University, 81620 Duzce, Turkey; (F.Y.); (I.A.)
| | - Mehmet Ali Ozel
- Department of Radiology, Faculty of Medicine, Duzce University, 81620 Duzce, Turkey;
| | - Osman Kayapinar
- Department of Cardiology, Faculty of Medicine, Duzce University, 81620 Duzce, Turkey; (C.O.); (G.A.)
| | - Cem Ozde
- Department of Cardiology, Faculty of Medicine, Duzce University, 81620 Duzce, Turkey; (C.O.); (G.A.)
| | - Gulsah Akture
- Department of Cardiology, Faculty of Medicine, Duzce University, 81620 Duzce, Turkey; (C.O.); (G.A.)
| | - Ilknur Arslanoglu
- Department of Pediatric Endocrinology, Faculty of Medicine, Duzce University, 81620 Duzce, Turkey; (F.Y.); (I.A.)
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Revathi TK, Sathiyabhama B, Kaliraj S, Sureshkumar V. Early Prediction of Cardio Vascular Disease (CVD) from Diabetic Retinopathy using improvised deep Belief Network (I-DBN) with Optimum feature selection technique. BMC Cardiovasc Disord 2025; 25:30. [PMID: 39827098 PMCID: PMC11748577 DOI: 10.1186/s12872-024-04374-0] [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: 08/14/2024] [Accepted: 11/25/2024] [Indexed: 01/22/2025] Open
Abstract
Cardio Vascular Disease (CVD) is one of the leading causes of mortality and it is estimated that 1 in 4 deaths happens due to it. The disease prevalence rate becomes higher since there is an inadequate system/model for predicting CVD at an earliest. Diabetic Retinopathy (DR) is a kind of eye disease was associated with increasing risk factors for all-causes of CVD events. The early diagnosis of DR plays a significant role in preventing CVD. However, there are many works have been carried out on classification of the disease but they focused less on feature selection and increasing the accuracy of the model. The proposed work introduces Improvised Deep Belief Network named I-DBN to resolve the above mentioned problems and mainly to concentrate on improving the entire performance of the model leading to the unbiased output. We used Principal Component Analysis (PCA) and Particle Swarm Optimization (PSO) algorithm for feature extraction and selection respectively. Five performance metrics have been used to assess the proposed model. The results of I-DBN outperform other state-of-the-art methods. The result validation ensures that I-DBN can deliver trustworthy recommendations to doctors to treat the patients by enhancing the accuracy of CVD prediction up to 98.95%.
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Affiliation(s)
- T K Revathi
- Department of CSE, Sona College of Technology, Salem, Tamilnadu, India
| | - B Sathiyabhama
- Department of CSE, Sona College of Technology, Salem, Tamilnadu, India
| | - S Kaliraj
- Department of Information and Communication Technology, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
| | - Vidhushavarshini Sureshkumar
- Department of Computer Science and Engineering, SRM Institute of Science and Technology, Vadapalani Campus, Chennai, India
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Ang L, Gunaratnam S, Huang Y, Dillon BR, Martin CL, Burant A, Reiss J, Blakely P, Vasbinder A, Zhao L, Mizokami‐Stout K, Tang Y, Feldman EL, Doria A, Spino C, Banerjee M, Hayek SS, Pop‐Busui R. Inflammatory Markers and Measures of Cardiovascular Autonomic Neuropathy in Type 1 Diabetes. J Am Heart Assoc 2025; 14:e036787. [PMID: 39727210 PMCID: PMC12054404 DOI: 10.1161/jaha.124.036787] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 10/28/2024] [Indexed: 12/28/2024]
Abstract
BACKGROUND Cardiovascular autonomic neuropathy (CAN) and inflammation predict more severe outcomes in type 1 diabetes (T1D). However, the link between CAN and inflammation in T1D remains unclear. We examined associations between CAN measures and inflammatory biomarkers in individuals with T1D. METHODS AND RESULTS In a cross-sectional study, we measured cardiovascular autonomic reflex tests and heart rate variability (established CAN measures) and a panel of 39 inflammatory biomarkers, including soluble urokinase plasminogen activator receptor (suPAR), in T1D participants of the TINSAL-T1DN (Targeting Inflammation with Salsalate in Individuals with T1D Neuropathy) trial (n=57, discovery), and the PERL (Preventing Early Renal Loss in Diabetes) trial (n=468, validation). Amongst 39 inflammatory biomarkers measured in TINSAL-T1DN, suPAR levels had the strongest negative correlations with CAN measures: expiration/inspiration (r=-0.48), Valsalva (r=-0.28), 30:15 (r=-0.37), SD of the normal RR interval (r=-0.37), and root mean square of differences of successive RR intervals (r=-0.31) (all P<0.05). Findings were validated in PERL. In unadjusted analyses, median suPAR levels significantly differed between the lowest and highest SD of the normal RR interval tertiles (3.79 versus 3.12 ng/mL, P<0.001) and root mean square of differences of successive RR intervals (3.76 versus 3.17 ng/mL, P<0.001). After adjusting for covariates (age, sex, hemoglobin A1c, and estimated glomerular filtration rate), median suPAR values remained significantly elevated in the lowest tertiles of SD of the normal RR interval (P=0.004) and root mean square of differences of successive RR intervals (P=0.006). CONCLUSIONS Amongst several inflammatory biomarkers, suPAR, an immune-mediated glycoprotein, has a singular association with CAN measures. The potential of targeting suPAR as a disease-modifying approach for CAN in T1D warrants further exploration. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02936843, NCT02017171.
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Affiliation(s)
- Lynn Ang
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and DiabetesUniversity of MichiganAnn ArborMIUSA
| | | | - Yiyuan Huang
- Department of BiostatisticsUniversity of MichiganAnn ArborMIUSA
| | | | - Catherine L. Martin
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and DiabetesUniversity of MichiganAnn ArborMIUSA
| | - Aaron Burant
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and DiabetesUniversity of MichiganAnn ArborMIUSA
| | - Jacob Reiss
- Quality DepartmentUniversity of MichiganAnn ArborMIUSA
| | - Pennelope Blakely
- Department of Internal Medicine, Division of CardiologyUniversity of Texas Medical BranchGalvestonTXUSA
| | - Alexi Vasbinder
- Biobehavioral Nursing and Health InformaticsUniversity of Washington School of NursingSeattleWAUSA
| | - Lili Zhao
- Corewell Health William Beaumont University HospitalRoyal OakMIUSA
| | - Kara Mizokami‐Stout
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and DiabetesUniversity of MichiganAnn ArborMIUSA
- Ann Arbor Veteran Affairs HospitalAnn ArborMIUSA
| | - Yaling Tang
- Department of EpidemiologyJoslin Diabetes CenterBostonMAUSA
| | - Eva L. Feldman
- Department of NeurologyUniversity of MichiganAnn ArborMIUSA
| | | | - Cathie Spino
- Department of BiostatisticsUniversity of MichiganAnn ArborMIUSA
| | | | - Salim S. Hayek
- Department of Internal Medicine, Division of CardiologyUniversity of Texas Medical BranchGalvestonTXUSA
- Department of Internal Medicine, Division of CardiologyUniversity of MichiganAnn ArborMIUSA
| | - Rodica Pop‐Busui
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and DiabetesUniversity of MichiganAnn ArborMIUSA
- Department of Internal Medicine, Division of Endocrinology, Diabetes and Clinical NutritionOregon Health and Science UniversityPortlandORUSA
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Zhong J, Li X, Yuan M, Chen D, Li Y, Lian X, Wang M. Metabolomics study of serum from patients with type 2 diabetes: Peripheral neuropathy could be associated with sphingosine and phospholipid molecules. Lipids 2025; 60:3-13. [PMID: 39243215 DOI: 10.1002/lipd.12412] [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: 03/29/2024] [Revised: 08/02/2024] [Accepted: 08/09/2024] [Indexed: 09/09/2024]
Abstract
Abnormal lipid metabolism is one of the risk factors for type 2 diabetes mellitus peripheral neuropathy (DPN). This study aimed to determine the differences in lipid metabolism in patients with type 2 diabetes and DPN and the possible pathogenesis caused by this difference. The participants comprised type 2 diabetes mellitus patients with DPN (N = 60) and healthy controls (N = 20). Blood samples were drawn from the participants in the morning in the fasting state, and then changes in serum lipids were explored using targeted metabolomics on the liquid chromatography-electrospray ionization-tandem mass spectrometry platform. Among the 1768 differentially abundant lipid metabolites, the results of orthogonal partial least squares-discriminant analysis combined with random forest analysis showed that the levels of sphingosine (SPH) (d18:0), carnitine 22:1, lysophosphatidylethanolamine (LPE) (18:0/0:0), LPC (16:0/0:0), lysophosphatidylcholine (LPC) (18:1/0:0), LPC (0:0/18:0) and LPE (0:0/18:1) were significantly different between the two groups. Spearman correlation analysis showed that SPH (d18:0), carnitine 22:1, LPE (18:0/0:0), and LPC (0:0/18:0) levels correlated highly with the patients' electromyography results. Kyoto Encyclopedia of Genes and Genomes pathway annotation and enrichment analysis of 538 differentially abundant lipid metabolites revealed that type 2 diabetes mellitus DPN was related to glycerophospholipid metabolism and glycerol metabolism. Our results further identified the dangerous lipid metabolites associated with DPN and abnormal lipid metabolism. The influence of lipid metabolites such as SPH and phospholipid molecules on DPN development in patients with type 2 diabetes mellitus were suggested and the possible pathogenic pathways were clarified, providing new insights into the clinical risk of DPN in patients with type 2 diabetes mellitus.
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Affiliation(s)
- Jingchen Zhong
- Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province of Chinese Medicine, Nanjing, China
| | - Xiaojie Li
- College of Integrative Chinese and Western Medicine, Jiangsu Health Vocational College, Nanjing, China
| | - Mengqian Yuan
- Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province of Chinese Medicine, Nanjing, China
| | - Dong Chen
- Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province of Chinese Medicine, Nanjing, China
| | - Yancai Li
- Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province of Chinese Medicine, Nanjing, China
| | - Xiaoyang Lian
- Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province of Chinese Medicine, Nanjing, China
| | - Ming Wang
- Geriatric Hospital of Nanjing Medical University, Jiangsu Province Official Hospital, Nanjing, China
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Di Santo R, Niccolini B, Rizzi A, Bertini L, Marafon DP, Vaccaro M, Cristallo F, Rosa E, Tartaglione L, Leo L, De Spirito M, Ciasca G, Pitocco D. Sensing Biomechanical Alterations in Red Blood Cells of Type 1 Diabetes Patients: Potential Markers for Microvascular Complications. BIOSENSORS 2024; 14:587. [PMID: 39727851 PMCID: PMC11674557 DOI: 10.3390/bios14120587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 10/28/2024] [Accepted: 11/22/2024] [Indexed: 12/28/2024]
Abstract
In physiological conditions, red blood cells (RBCs) demonstrate remarkable deformability, allowing them to undergo considerable deformation when passing through the microcirculation. However, this deformability is compromised in Type 1 diabetes mellitus (T1DM) and related pathological conditions. This study aims to investigate the biomechanical properties of RBCs in T1DM patients, focusing on identifying significant mechanical alterations associated with microvascular complications (MCs). We conducted a case-control study involving 38 T1DM subjects recruited from the Diabetes Care Unit at Fondazione Policlinico Gemelli Hospital, comprising 22 without MCs (control group) and 16 with MCs (pathological group). Atomic Force Microscopy was employed to assess RBC biomechanical properties in a liquid environment. We observed significant RBC stiffening in individuals with MCs, particularly during large indentations that mimic microcirculatory deformations. Univariate analysis unveiled significant differences in RBC stiffness (median difference 0.0006 N/m, p = 0.012) and RBC counts (median difference -0.39 × 1012/L, p = 0.009) between the MC and control groups. Bivariate logistic regression further demonstrated that combining these parameters could effectively discriminate between MC and non-MC conditions, achieving an AUC of 0.82 (95% CI: 0.67-0.97). These findings reveal the potential of RBC biomechanical properties as diagnostic and monitoring tools in diabetes research. Exploring RBC mechanical alterations may lead to the development of novel biomarkers, which, in combination with clinical markers, could facilitate the early diagnosis of diabetes-related complications.
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Affiliation(s)
- Riccardo Di Santo
- Department of Life Science, Health, and Health Professions, Link Campus University, 00165 Rome, Italy
- Dipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Benedetta Niccolini
- Dipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Alessandro Rizzi
- UOSA Diabetologia, Fondazione IRCCS, University Agostino Gemelli, 00168 Rome, Italy; (A.R.); (D.P.)
| | - Laura Bertini
- Dipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Denise Pires Marafon
- Section of Hygiene, Department of Life Sciences and Public Health, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Maria Vaccaro
- Dipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Fondazione Policlinico Universitario “A. Gemelli”, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy
| | - Federica Cristallo
- UOSA Diabetologia, Fondazione IRCCS, University Agostino Gemelli, 00168 Rome, Italy; (A.R.); (D.P.)
| | - Enrico Rosa
- Fondazione Policlinico Universitario “A. Gemelli”, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy
- Department of Theoretical and Applied Sciences, eCampus University, 22060 Novedrate, Italy
| | - Linda Tartaglione
- UOSA Diabetologia, Fondazione IRCCS, University Agostino Gemelli, 00168 Rome, Italy; (A.R.); (D.P.)
| | - Laura Leo
- UOSA Diabetologia, Fondazione IRCCS, University Agostino Gemelli, 00168 Rome, Italy; (A.R.); (D.P.)
| | - Marco De Spirito
- Dipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Fondazione Policlinico Universitario “A. Gemelli”, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy
| | - Gabriele Ciasca
- Dipartimento di Neuroscienze, Sezione di Fisica, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
- Fondazione Policlinico Universitario “A. Gemelli”, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy
| | - Dario Pitocco
- UOSA Diabetologia, Fondazione IRCCS, University Agostino Gemelli, 00168 Rome, Italy; (A.R.); (D.P.)
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10
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Wu L, Wang XJ, Luo X, Zhang J, Zhao X, Chen Q. Diabetic peripheral neuropathy based on Schwann cell injury: mechanisms of cell death regulation and therapeutic perspectives. Front Endocrinol (Lausanne) 2024; 15:1427679. [PMID: 39193373 PMCID: PMC11348392 DOI: 10.3389/fendo.2024.1427679] [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: 05/07/2024] [Accepted: 07/24/2024] [Indexed: 08/29/2024] Open
Abstract
Diabetic peripheral neuropathy (DPN) is a complication of diabetes mellitus that lacks specific treatment, its high prevalence and disabling neuropathic pain greatly affects patients' physical and mental health. Schwann cells (SCs) are the major glial cells of the peripheral nervous system, which play an important role in various inflammatory and metabolic neuropathies by providing nutritional support, wrapping axons and promoting repair and regeneration. Increasingly, high glucose (HG) has been found to promote the progression of DPN pathogenesis by targeting SCs death regulation, thus revealing the specific molecular process of programmed cell death (PCD) in which SCs are disrupted is an important link to gain insight into the pathogenesis of DPN. This paper is the first to review the recent progress of HG studies on apoptosis, autophagy, pyroptosis, ferroptosis and necroptosis pathways in SCs, and points out the crosstalk between various PCDs and the related therapeutic perspectives, with the aim of providing new perspectives for a deeper understanding of the mechanisms of DPN and the exploration of effective therapeutic targets.
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Affiliation(s)
- Lijiao Wu
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xiang Jin Wang
- School of Sports Medicine and Health, Chengdu Sports University, Chengdu, China
| | - Xi Luo
- Jiangsu Key Laboratory for Functional Substance of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jingqi Zhang
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Xinyi Zhao
- College of lntegrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Hunan, China
| | - Qiu Chen
- Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
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11
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Smith S, Ravikumar R, Carvalho C, Normahani P, Lane T, Davies AH. Neuromuscular electrical stimulation for the treatment of diabetic sensorimotor polyneuropathy: A prospective, cohort, proof-of-concept study. Neurophysiol Clin 2024; 54:102943. [PMID: 38422719 DOI: 10.1016/j.neucli.2024.102943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 01/03/2024] [Accepted: 01/03/2024] [Indexed: 03/02/2024] Open
Abstract
OBJECTIVE To assess a potential efficacy signal, safety and feasibility of neuromuscular electrical stimulation (NMES) therapy as an adjunct to standard care in patients with diabetic sensorimotor polyneuropathy (DSPN). METHODS In this single-centre, prospective, cohort, proof-of-concept study, 25 patients with DSPN consented to at least one daily 30-minute NMES therapy session (Revitive® IX) for 10 weeks, with 20 patients completing the study. The primary outcome measure was nerve conductivity assessed using a nerve conduction study of the sural, superficial peroneal, common peroneal and tibial nerves at 10 weeks compared to baseline. Secondary outcomes included superficial femoral artery (SFA) haemodynamics during NMES therapy compared to rest and quality-of-life at 10 weeks compared to baseline. RESULTS At 10 weeks, there were significant increases in sural sensory nerve action potential amplitude and conduction velocity (p < 0.001), superficial peroneal sensory nerve action potential amplitude (p = 0.001) and conduction velocity (p = 0.002), common peroneal nerve conduction velocity (p = 0.004) and tibial nerve compound muscle action potential amplitude (p = 0.002) compared to baseline. SFA volume flow and time-averaged mean velocity significantly increased (p ≤ 0.003) during NMES compared to rest. Patient-reported Michigan Neuropathy Screening Instrument scores significantly decreased (p = 0.028) at 10 weeks compared to baseline. Three unrelated adverse events occurred, and 15 participants adhered to treatment. CONCLUSIONS NMES therapy as an adjunct to standard care for 10 weeks significantly increased lower limb nerve conductivity in patients with DSPN and may be beneficial in the treatment of DSPN.
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Affiliation(s)
- Sasha Smith
- Section of Vascular Surgery, Department of Surgery and Cancer, Imperial College London, Charing Cross Hospital, London, W6 8RF, United Kingdom; Imperial Vascular Unit, Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, W6 8RF, United Kingdom
| | - Raveena Ravikumar
- Section of Vascular Surgery, Department of Surgery and Cancer, Imperial College London, Charing Cross Hospital, London, W6 8RF, United Kingdom
| | - Catarina Carvalho
- Section of Vascular Surgery, Department of Surgery and Cancer, Imperial College London, Charing Cross Hospital, London, W6 8RF, United Kingdom
| | - Pasha Normahani
- Section of Vascular Surgery, Department of Surgery and Cancer, Imperial College London, Charing Cross Hospital, London, W6 8RF, United Kingdom; Imperial Vascular Unit, Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, W6 8RF, United Kingdom
| | - Tristan Lane
- Section of Vascular Surgery, Department of Surgery and Cancer, Imperial College London, Charing Cross Hospital, London, W6 8RF, United Kingdom; Cambridge Vascular Unit, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke's Hospital, Cambridge, CB2 0QQ, United Kingdom
| | - Alun H Davies
- Section of Vascular Surgery, Department of Surgery and Cancer, Imperial College London, Charing Cross Hospital, London, W6 8RF, United Kingdom; Imperial Vascular Unit, Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, W6 8RF, United Kingdom.
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12
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PING J, HAO H, WU Z, ZOU M, LI Z, CHENG G. Long-term efficacy and safety of Huangqi ()-based Traditional Chinese Medicine in diabetic peripheral neuropathy: a Meta-analysis of randomized controlled trials. J TRADIT CHIN MED 2024; 44:229-242. [PMID: 38504529 PMCID: PMC10927399 DOI: 10.19852/j.cnki.jtcm.2024.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Accepted: 07/20/2023] [Indexed: 03/21/2024]
Abstract
OBJECTIVE To assess the long-term effectiveness of Huangqi (Radix Astragali Mongolici, HQ)-based Traditional Chinese Medicine (TCM) in the treatment of diabetic peripheral neuropathy (DPN). METHODS Nine databases were searched to retrieve available randomized controlled trials that compared HQ-based TCM and Western Medicines in the treatment of DPN. The methodological quality of the included studies was assessed using the Cochrane bias risk tool, and RevMan 5.4 was used for data analysis. The effect estimates of interest were risk ratio (RR), mean difference (MD) or standardized mean difference (SMD) with 95% confidence interval (CI). RESULTS The results from 48 available studies assessing 3759 patients demonstrated that cases administered HQ-based TCM [RR = 1.30, 95% CI (1.21, 1.40), P < 0.000 01] or HQ-based TCM combined with Western Medicines [RR = 1.25, 95% CI (1.19, 1.31), P < 0.000 01] exhibited higher total efficacy rates than individuals who received Western Medicine alone. The results showed that the HQ-based TCM group had decreased Toronto Clinical Scoring System scores [MD =－1.50, 95% CI (－1.83, －1.17), P < 0.000 01], and reduced serum interleukin 6 [SMD = －0.57, 95% CI (－0.87, －0.27), P = 0.0002] and tumor necrosis factors-α levels [SMD = －0.60, 95% CI (－0.95, －0.25), P = 0.0009]. In addition, both HQ-based TCM and HQ-based TCM combined with Western Medicine increased nerve conduction velocity and decreased glycaemia compared with Western Medicine alone. In terms of blood lipids, oxidative stress and adverse drug reactions, there were no significant differences between the HQ-based TCM groups and the Western Medicine control group. CONCLUSION The current Meta-analysis revealed that HQ-based TCM yields higher efficacy and safety than Western Medicine alone for the treatment of DPN, although further well-designed RCTs are required to validate these findings.
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Affiliation(s)
- Jing PING
- 1 School of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110000, China
| | - Hongzheng HAO
- 2 Department of Endocrinology, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110000, China
| | - Zhenqi WU
- 3 Department of Research Administration, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang 110000, China
| | - Meijuan ZOU
- 4 School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110000, China
| | - Zuojing LI
- 4 School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110000, China
| | - Gang CHENG
- 4 School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110000, China
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13
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Davis TME, Tan E, Davis WA. Prevalence and prognostic significance of cardiac autonomic neuropathy in community-based people with type 2 diabetes: the Fremantle Diabetes Study Phase II. Cardiovasc Diabetol 2024; 23:102. [PMID: 38500197 PMCID: PMC10949593 DOI: 10.1186/s12933-024-02185-3] [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: 12/21/2023] [Accepted: 03/01/2024] [Indexed: 03/20/2024] Open
Abstract
BACKGROUND There is a paucity of contemporary data on the prevalence and prognostic significance of cardiac autonomic neuropathy (CAN) from community-based cohorts with type 2 diabetes assessed using gold standard methods. The aim of this study was to assess these aspects of CAN in the longitudinal observational Fremantle Diabetes Study Phase II (FDS2). METHODS FDS2 participants were screened at baseline using standardised cardiovascular reflex tests (CARTs) of heart rate variation during deep breathing, Valsalva manoeuvre and standing. CAN (no/possible/definite) was assessed from the number of abnormal CARTs. Multinomial regression identified independent associates of CAN status. Cox proportional hazards modelling determined independent baseline predictors of incident heart failure (HF) and ischaemic heart disease (IHD), and all-cause mortality. RESULTS Of 1254 participants assessed for CAN, 86 (6.9%) were outside CART age reference ranges and valid CART data were unavailable for 338 (27.0%). Of the remaining 830 (mean age 62.3 years, 55.3% males, median diabetes duration 7.3 years), 51.0%, 33.7% and 15.3% had no, possible or definite CAN, respectively. Independent associates of definite CAN (longer diabetes duration, higher body mass index and resting pulse rate, antidepressant and antihypertensive therapies, albuminuria, distal sensory polyneuropathy, prior HF) were consistent with those reported previously. In Kaplan-Meier analysis, definite CAN was associated with a lower likelihood of incident IHD and HF versus no/possible CAN (P < 0.001) and there was a graded increase in all-cause mortality risk from no CAN to possible and definite CAN (P < 0.001). When CAN category was added to the most parsimonious models, it was not a significant independent predictor of IHD (P ≥ 0.851) or HF (P ≥ 0.342). Possible CAN (hazard ratio (95% CI) 1.47 (1.01, 2.14), P = 0.046) and definite CAN (2.42 (1.60, 3.67), P < 0.001) increased the risk of all-cause mortality versus no CAN. CONCLUSIONS Routine screening for CAN in type 2 diabetes has limited clinical but some prognostic value.
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Affiliation(s)
- Timothy M E Davis
- Medical School, Fremantle Hospital, University of Western Australia, PO Box 480, Fremantle, WA, 6959, Australia.
- Department of Endocrinology and Diabetes, Fiona Stanley and Fremantle Hospitals, Murdoch, WA, Australia.
- Australian Centre for Accelerating Diabetes Innovations (ACADI), The University of Melbourne, Melbourne, VIC, Australia.
| | - Eva Tan
- Medical School, Fremantle Hospital, University of Western Australia, PO Box 480, Fremantle, WA, 6959, Australia
| | - Wendy A Davis
- Medical School, Fremantle Hospital, University of Western Australia, PO Box 480, Fremantle, WA, 6959, Australia
- Australian Centre for Accelerating Diabetes Innovations (ACADI), The University of Melbourne, Melbourne, VIC, Australia
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14
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Chase BA, Pocica S, Frigerio R, Markopoulou K, Maraganore DM, Aunaetitrakul N, Epshteyn A, Barboi AC. Mortality risk factors in newly diagnosed diabetic cardiac autonomic neuropathy. Clin Auton Res 2023; 33:903-907. [PMID: 37695385 DOI: 10.1007/s10286-023-00975-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Accepted: 08/13/2023] [Indexed: 09/12/2023]
Affiliation(s)
- Bruce A Chase
- Department of Neurology, University of Chicago Pritzker School of Medicine, NorthShore University HealthSystem, Evanston, IL, USA
| | - Sylwia Pocica
- Department of Neurology, University of Chicago Pritzker School of Medicine, NorthShore University HealthSystem, Evanston, IL, USA
| | - Roberta Frigerio
- Department of Neurology, University of Chicago Pritzker School of Medicine, NorthShore University HealthSystem, Evanston, IL, USA
| | - Katerina Markopoulou
- Department of Neurology, University of Chicago Pritzker School of Medicine, NorthShore University HealthSystem, Evanston, IL, USA
| | | | - Navamon Aunaetitrakul
- Department of Neurology, University of Chicago Pritzker School of Medicine, NorthShore University HealthSystem, Evanston, IL, USA
| | - Alexander Epshteyn
- Department of Health Information Technology, NorthShore University HealthSystem, Skokie, IL, USA
| | - Alexandru C Barboi
- Department of Neurology, University of Chicago Pritzker School of Medicine, NorthShore University HealthSystem, Evanston, IL, USA.
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15
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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.
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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
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16
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Rasmussen VF, Thrysøe M, Nyengaard JR, Tankisi H, Karlsson P, Hansen J, Krogh K, Brock C, Kamperis K, Madsen M, Singer W, Vestergaard ET, Kristensen K, Terkelsen AJ. Neuropathy in adolescents with type 1 diabetes: Confirmatory diagnostic tests, bedside tests, and risk factors. Diabetes Res Clin Pract 2023; 201:110736. [PMID: 37276985 DOI: 10.1016/j.diabres.2023.110736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 05/17/2023] [Accepted: 05/26/2023] [Indexed: 06/07/2023]
Abstract
AIMS To estimate the prevalence of large fiber (LFN), small fiber (SFN), and autonomic neuropathy in adolescents with type 1 diabetes using confirmatory tests known from adults and to identify risk factors and bedside methods for neuropathy. METHODS Sixty adolescents with type 1 diabetes (diabetes duration > five years) and 23 control subjects underwent neurological examination and confirmatory diagnostic tests for neuropathy, including nerve conduction studies, skin biopsies determining intraepidermal nerve fiber density, quantitative sudomotor axon reflex test (QSART), cardiovascular reflex tests (CARTs), and tilt table test. Possible risk factors were analyzed. Bedside tests (biothesiometry, DPNCheck®, Sudoscan, and Vagus®device) were compared with the confirmatory tests using ROC analysis. RESULTS The prevalence of neuropathies in the adolescents with diabetes (mean HbA1c 7.6% (60 mmol/mol)) was as follows: 14% confirmed/26% subclinical LFN, 2% confirmed/25% subclinical SFN, 20% abnormal QSART, 8% abnormal CARTs, and 14% orthostatic hypotension. Higher age, higher insulin dose, previous smoking, and higher triglycerides level were found to increase the relative risk for neuropathy. The bedside tests showed poor to acceptable concordance with the confirmatory tests (all, AUC ≤ 0.75). CONCLUSIONS The diagnostic tests confirmed the presence of neuropathy in adolescents with diabetes and underscore the importance of prevention and screening.
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Affiliation(s)
- Vinni Faber Rasmussen
- Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark; Department of Pediatrics and Adolescent Medicine, Randers Regional Hospital, Randers, Denmark.
| | - Mathilde Thrysøe
- Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Jens Randel Nyengaard
- Department of Pathology, Aarhus University Hospital, Aarhus, Denmark; Core Centre for Molecular Morphology, Section for Stereology and Microscopy, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - Hatice Tankisi
- Department of Neurophysiology, Department of Clinical Medicine, Aarhus University, Denmark
| | - Páll Karlsson
- Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Core Centre for Molecular Morphology, Section for Stereology and Microscopy, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
| | - John Hansen
- Institute of Health Science and Technology, Aalborg University, Denmark
| | - Klaus Krogh
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - Christina Brock
- Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Konstantinos Kamperis
- Department of Pediatric and Adolescent Medicine, Aarhus University Hospital, Denmark
| | - Mette Madsen
- Department of Pediatric and Adolescent Medicine, Aalborg University Hospital, Denmark; Steno Diabetes Center North Denmark, Aalborg, Denmark
| | | | - Esben Thyssen Vestergaard
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark; Department of Pediatric and Adolescent Medicine, Aarhus University Hospital, Denmark
| | - Kurt Kristensen
- Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark
| | - Astrid Juhl Terkelsen
- Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
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17
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Zanin A, Amah G, Chakroun S, Testard P, Faucher A, Le TYV, Slama D, Le Baut V, Lozeron P, Salmon D, Kubis N. Parasympathetic autonomic dysfunction is more often evidenced than sympathetic autonomic dysfunction in fluctuating and polymorphic symptoms of "long-COVID" patients. Sci Rep 2023; 13:8251. [PMID: 37217645 DOI: 10.1038/s41598-023-35086-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 05/12/2023] [Indexed: 05/24/2023] Open
Abstract
Several disabling symptoms potentially related to dysautonomia have been reported in "long-COVID" patients. Unfortunately, these symptoms are often nonspecific, and autonomic nervous system explorations are rarely performed in these patients. This study aimed to evaluate prospectively a cohort of long-COVID patients presenting severe disabling and non-relapsing symptoms of potential dysautonomia and to identify sensitive tests. Autonomic function was assessed by clinical examination, the Schirmer test; sudomotor evaluation, orthostatic blood pressure (BP) variation, 24-h ambulatory BP monitoring for sympathetic evaluation, and heart rate variation during orthostatism, deep breathing and Valsalva maneuvers for parasympathetic evaluation. Test results were considered abnormal if they reached the lower thresholds defined in publications and in our department. We also compared mean values for autonomic function tests between patients and age-matched controls. Sixteen patients (median age 37 years [31-43 years], 15 women) were included in this study and referred 14.5 months (median) [12.0-16.5 months] after initial infection. Nine had at least one positive SARS-CoV-2 RT-PCR or serology result. Symptoms after SARS-CoV-2 infection were severe, fluctuating and disabling with effort intolerance. Six patients (37.5%) had one or several abnormal test results, affecting the parasympathetic cardiac function in five of them (31%). Mean Valsalva score was significantly lower in patients than in controls. In this cohort of severely disabled long-COVID patients, 37.5% of them had at least one abnormal test result showing a possible contribution of dysautonomia to these nonspecific symptoms. Interestingly, mean values of the Valsalva test were significantly lower in patients than in control subjects, suggesting that normal values thresholds might not be appropriate in this population.
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Affiliation(s)
- Adrien Zanin
- INSERM UMR1144, Université Paris Cité, 75018, Paris, France
- Service de Physiologie Clinique - Explorations Fonctionnelles, AP-HP, DMU DREAM, Hôpital Lariboisière, Université Paris Cité, 75010, Paris, France
| | - Guy Amah
- Service de Physiologie Clinique - Explorations Fonctionnelles, AP-HP, DMU DREAM, Hôpital Lariboisière, Université Paris Cité, 75010, Paris, France
| | - Sahar Chakroun
- Service de Physiologie Clinique - Explorations Fonctionnelles, AP-HP, DMU DREAM, Hôpital Lariboisière, Université Paris Cité, 75010, Paris, France
| | - Pauline Testard
- Service de Physiologie Clinique - Explorations Fonctionnelles, AP-HP, DMU DREAM, Hôpital Lariboisière, Université Paris Cité, 75010, Paris, France
| | - Alice Faucher
- Service de Physiologie Clinique - Explorations Fonctionnelles, AP-HP, DMU DREAM, Hôpital Lariboisière, Université Paris Cité, 75010, Paris, France
| | - Thi Yen Vy Le
- Service de Physiologie Clinique - Explorations Fonctionnelles, AP-HP, DMU DREAM, Hôpital Lariboisière, Université Paris Cité, 75010, Paris, France
| | - Dorsaf Slama
- Department of Immunology and Infectious Diseases, APHP, Cochin-Hôtel-Dieu Hospital, Université Paris Cité, 75004, Paris, France
| | - Valérie Le Baut
- Department of Immunology and Infectious Diseases, APHP, Cochin-Hôtel-Dieu Hospital, Université Paris Cité, 75004, Paris, France
| | - Pierre Lozeron
- INSERM UMR1144, Université Paris Cité, 75018, Paris, France
- Service de Physiologie Clinique - Explorations Fonctionnelles, AP-HP, DMU DREAM, Hôpital Lariboisière, Université Paris Cité, 75010, Paris, France
| | - Dominique Salmon
- Department of Immunology and Infectious Diseases, APHP, Cochin-Hôtel-Dieu Hospital, Université Paris Cité, 75004, Paris, France
| | - Nathalie Kubis
- INSERM UMR1144, Université Paris Cité, 75018, Paris, France.
- Service de Physiologie Clinique - Explorations Fonctionnelles, AP-HP, DMU DREAM, Hôpital Lariboisière, Université Paris Cité, 75010, Paris, France.
- Service de Physiologie Clinique - Explorations Fonctionnelles, Hôpital Lariboisière, 2 rue Ambroise Paré, 75475, Paris CEDEX10, France.
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Vági OE, Svébis MM, Domján BA, Körei AE, Tesfaye S, Horváth VJ, Kempler P, Tabák ÁG. The association between distal symmetric polyneuropathy in diabetes with all-cause mortality - a meta-analysis. Front Endocrinol (Lausanne) 2023; 14:1079009. [PMID: 36875485 PMCID: PMC9978416 DOI: 10.3389/fendo.2023.1079009] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 01/30/2023] [Indexed: 02/18/2023] Open
Abstract
BACKGROUND Distal symmetric polyneuropathy (DSPN) is a common microvascular complication of both type 1 and 2 diabetes with substantial morbidity burden and reduced quality of life. Its association with mortality is equivocal. PURPOSE To describe the association between DSPN and all-cause mortality in people with diabetes and further stratify by the type of diabetes based on a meta-analysis of published observational studies. DATA SOURCES We searched Medline from inception to May 2021. STUDY SELECTION Original data were collected from case-control and cohort studies that reported on diabetes and DSPN status at baseline and all-cause mortality during follow-up. DATA EXTRACTION was completed by diabetes specialists with clinical experience in neuropathy assessment. DATA SYNTHESIS Data was synthesized using random-effects meta-analysis. The difference between type 1 and 2 diabetes was investigated using meta-regression. RESULTS A total of 31 cohorts (n=155,934 participants, median 27.4% with DSPN at baseline, all-cause mortality 12.3%) were included. Diabetes patients with DSPN had an almost twofold mortality (HR: 1.96, 95%CI: 1.68-2.27, I2 = 91.7%), I2 = 91.7%) compared to those without DSPN that was partly explained by baseline risk factors (adjusted HR: 1.60, 95%CI: 1.37-1.87, I2 = 78.86%). The association was stronger in type 1 compared to type 2 diabetes (HR: 2.22, 95%CI: 1.43-3.45). Findings were robust in sensitivity analyses without significant publication bias. LIMITATIONS Not all papers reported multiple adjusted estimates. The definition of DSPN was heterogeneous. CONCLUSIONS DSPN is associated with an almost twofold risk of death. If this association is causal, targeted therapy for DSPN could improve life expectancy of diabetic patients.
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Affiliation(s)
- Orsolya E. Vági
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
- *Correspondence: Orsolya E. Vági, ; Ádám Gy. Tabák,
| | - Márk M. Svébis
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
- School of PhD studies, Semmelweis University Faculty of Medicine, Budapest, Hungary
| | - Beatrix A. Domján
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
| | - Anna E. Körei
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
| | - Solomon Tesfaye
- Diabetes Research Unit, Royal Hallamshire Hospital, University of Sheffield, Sheffield, United Kingdom
| | - Viktor J. Horváth
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
| | - Péter Kempler
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
| | - Ádám Gy. Tabák
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
- Department of Public Health, Semmelweis University Faculty of Medicine, Budapest, Hungary
- Department of Epidemiology and Public Health, University College London, London, United Kingdom
- *Correspondence: Orsolya E. Vági, ; Ádám Gy. Tabák,
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Sacchetta L, Chiriacò M, Nesti L, Leonetti S, Forotti G, Natali A, Solini A, Tricò D. Synergistic effect of chronic kidney disease, neuropathy, and retinopathy on all-cause mortality in type 1 and type 2 diabetes: a 21-year longitudinal study. Cardiovasc Diabetol 2022; 21:233. [DOI: 10.1186/s12933-022-01675-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 10/25/2022] [Indexed: 11/06/2022] Open
Abstract
Abstract
Background
The prognostic value of common and frequently associated diabetic microvascular complications (MVC), namely chronic kidney disease (CKD), cardiac autonomic neuropathy (CAN), peripheral neuropathy (DPN), and retinopathy (DR), is well established. However, the impact of their different combinations on long-term mortality has not been adequately assessed.
Methods
We retrospectively analyzed 21-year longitudinal data from 303 patients with long-standing type 1 (T1D) or type 2 diabetes (T2D), who were thoroughly characterized at baseline for the presence of MVC using 99mTc-DTPA dynamic renal scintigraphy, overnight urine collection, cardiovascular autonomic tests, monofilament testing, and dilated fundus oculi examination.
Results
After a 5,244 person-years follow-up, a total of 133 (43.9%) deaths occurred. The presence of CKD and CAN, regardless of other MVC, increased the adjusted all-cause mortality risk by 117% (HR 2.17 [1.45–3.26]) and 54% (HR 1.54 [1.01–2.36]), respectively. Concomitant CKD&CAN at baseline were associated with the highest mortality risk (HR 5.08 [2.52–10.26]), followed by CKD&DR (HR 2.95 [1.63–5.32]), and CAN&DR (HR 2.07 [1.11–3.85]). Compared with patients free from MVC, the mortality risk was only numerically higher in those with any isolated MVC (HR 1.52 [0.87–2.67]), while increased by 203% (HR 3.03 [1.62–5.68]) and 692% (HR 7.92 [2.93–21.37]) in patients with two and three concomitant MVC, respectively.
Conclusions
Our study demonstrates the long-term, synergistic, negative effects of single and concomitant diabetic MVC on all-cause mortality, which should encourage comprehensive screenings for MCV in both T1D and T2D to improve risk stratification and treatment.
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20
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Cardiac Autonomic Neuropathy in Type 1 and 2 Diabetes: Epidemiology, Pathophysiology, and Management. Clin Ther 2022; 44:1394-1416. [DOI: 10.1016/j.clinthera.2022.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 07/23/2022] [Accepted: 09/06/2022] [Indexed: 11/21/2022]
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Karamanakos G, Kokkinos A, Dalamaga M, Liatis S. Highlighting the Role of Obesity and Insulin Resistance in Type 1 Diabetes and Its Associated Cardiometabolic Complications. Curr Obes Rep 2022; 11:180-202. [PMID: 35931912 DOI: 10.1007/s13679-022-00477-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/29/2022] [Indexed: 11/30/2022]
Abstract
PURPOSE OF REVIEW This narrative review appraises research data on the potentially harmful effect of obesity and insulin resistance (IR) co-existence with type 1 diabetes mellitus (T1DM)-related cardiovascular (CVD) complications and evaluates possible therapeutic options. RECENT FINDINGS Obesity and IR have increasingly been emerging in patients with T1DM. Genetic, epigenetic factors, and subcutaneous insulin administration are implicated in the pathogenesis of this coexistence. Accumulating evidence implies that the concomitant presence of obesity and IR is an independent predictor of worse CVD outcomes. The prevalence of obesity and IR has increased in patients with T1DM. This increase can be partly attributed to general population trends but, additionally, to iatrogenic weight gain caused by insulin treatment. This association might be the missing link explaining the excess CVD burden observed in patients with T1DM despite optimal glycemic control. Data on newer agents for type 2 diabetes mellitus (T2DM) treatment are unraveling novel ways to challenge this aggravating coexistence.
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Affiliation(s)
- Georgios Karamanakos
- First Department of Propaedeutic Internal Medicine, Medical School, National Kapodistrian University of Athens, Laiko General Hospital, 17 Agiou Thoma Street, Athens, 11527, Greece.
| | - Alexander Kokkinos
- First Department of Propaedeutic Internal Medicine, Medical School, National Kapodistrian University of Athens, Laiko General Hospital, 17 Agiou Thoma Street, Athens, 11527, Greece
| | - Maria Dalamaga
- Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
| | - Stavros Liatis
- First Department of Propaedeutic Internal Medicine, Medical School, National Kapodistrian University of Athens, Laiko General Hospital, 17 Agiou Thoma Street, Athens, 11527, Greece
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22
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Poda A, Klevor R, Salym A, Sarih I, Salhi S, Nissrine L, Kissani N. Etiological profile of peripheral neuropathies in an academic hospital in southern Morocco. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2022; 58:97. [PMID: 36033924 PMCID: PMC9391624 DOI: 10.1186/s41983-022-00531-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 07/30/2022] [Indexed: 11/10/2022] Open
Abstract
Background Peripheral neuropathies constitute a common complaint in general and neurology practice, and are a source of handicap to patients. Epidemiological data in the Middle East and North Africa region as well as in the African continent are sparse. Nevertheless, regional etiological profiles are crucial in navigating the diagnostic maze of neuropathies. This study outlines the etiological profile of peripheral neuropathies in an academic hospital in southern Morocco. Results A total of 180 cases were recorded in a span of 8 years (22.5 cases per year). The mean age of patients was 42.35 years. Male gender was predominant (68.88%), with a sex ratio of 2.2. Motor symptoms were the most frequently reported (86.6%). The axonal form (40.56%) was the most frequently encountered electrophysiologic form. The most frequent etiologies in the study were diabetes (26.7%), acute polyradiculoneuropathy (26.1%) and amyotrophic lateral sclerosis (16.1%). Alcohol neuropathy was found in 2.2% of the cohort. No cause was found in 5% of cases. Outcome was mostly favorable under treatment, although 10 deaths due to acute polyradiculoneuropathy were recorded (mortality = 21.3%). Conclusions Knowledge of the etiological profile of peripheral neuropathies should guide clinicians to an early diagnosis and aid in an adapted management of patients. Supplementary Information The online version contains supplementary material available at 10.1186/s41983-022-00531-4.
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Wadhera S, Rastogi A, Dutta P, Gupta A, Bhadada SK. Age and Disease Duration Independent Cardiac Autonomic Neuropathy in Patients with Diabetic Foot Complications: Case-Control Study. Indian J Endocrinol Metab 2022; 26:362-371. [PMID: 36185960 PMCID: PMC9519835 DOI: 10.4103/ijem.ijem_99_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Revised: 07/15/2022] [Accepted: 07/21/2022] [Indexed: 12/02/2022] Open
Abstract
INTRODUCTION Cardiac autonomic neuropathy (CAN) in people with diabetes is associated with high mortality. We aimed to study age and disease duration, independent prevalence of CAN in people with diabetic foot complications. METHODS 530 patients with diabetes were screened to undergo CAN assessment (automated CANS-analyser). CAN was defined as "early", "definite," or "severe" according to the Toronto consensus. History pertaining to autonomic symptoms, prior cardiovascular events (CVE), and assessment for peripheral neuropathy was done. Participants were grouped into those with diabetic foot complication (group A, n = 82) [Charcot foot (n = 42), diabetic foot ulcer (n = 40)]; with DPN without foot complications (group B, n = 82); and without DPN or foot complications (group C, n = 82). RESULTS Symptoms of autonomic dysfunction were prominent in people with foot complications than the other groups. Resting heart rate was significantly greater in those with foot complications [99.89 ± 26.71 (group A) vs. 86.99 ± 22.24 (group B) vs. 88.32 ± 17.08 (group C); P = 0.001]. The prevalence of CAN was 75.6% in group A (51.2% early, 12.2% definite, 12.2% severe), 57.2% in group B (45.1% early, 12.2% severe) and 58.5% in group C (43.9% early, 1.2% definite, 13.4% severe) (P = 0.002). Patients with foot complications were more likely to have CAN (75.6% vs. 57.9%, P < 0.001). Charcot foot had higher prevalence of CAN (78.6%) as compared with those with DFU (72.5%) or without DFU or DPN (57.9%), P < 0.001. CONCLUSION CAN is present in more than two-third of patients with diabetes and foot complications with highest prevalence in Charcot neuroarthropathy.
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Affiliation(s)
- Sarthak Wadhera
- Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashu Rastogi
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Pinaki Dutta
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ankur Gupta
- Department of Cardiology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Sanjay K. Bhadada
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Soulimane S, Balkau B, Vogtschmidt YD, Toeller M, Fuller JH, Soedamah-Muthu SS. Incident cardiovascular disease by clustering of favourable risk factors in type 1 diabetes: the EURODIAB Prospective Complications Study. Diabetologia 2022; 65:1169-1178. [PMID: 35411407 PMCID: PMC9174122 DOI: 10.1007/s00125-022-05698-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 03/04/2022] [Indexed: 11/30/2022]
Abstract
AIMS The aim of this prospective study was to examine CVD risk reduction in type 1 diabetes (1) for people with favourable cardiovascular health metrics and (2) by clustering of these metrics. METHODS Data from 2313 participants from the EURODIAB Prospective Complications Study were analysed. All had type 1 diabetes (51% men, mean ± SD age 32 ± 9 years). Seven cardiovascular health metrics were studied-smoking, BMI, physical activity, a diet score, total cholesterol/HDL-cholesterol ratio, combined systolic and diastolic BP and HbA1c-divided into favourable/less favourable categories. Cox proportional hazards models were used to calculate HRs (95% CIs) of incident CVD for each metric. Clusters were made by scoring each individual by the number of favourable metrics. RESULTS A total of 163 people developed incident CVD during a mean ± SD follow-up of 7.2 ± 1.3 years. Participants with more favourable HbA1c levels of <57 mmol/mol (<7.4%) had a 37% significantly lower CVD risk than those with a less favourable HbA1c (HR [95% CI] 0.63 [0.44, 0.91]), and participants with a more favourable BP (systolic BP <112 mmHg and diastolic BP <70 mmHg) had a 44% significantly lower CVD risk than participants in the less favourable BP group (HR [95% CI] 0.56 [0.34, 0.92]). There was a dose-response relation with a lower HR observed with greater clustering of more favourable metrics: people with four or more favourable metrics had an HR of 0.37 (95% CI 0.18, 0.76), adjusted for sex and age at diabetes diagnosis, compared with those with no favourable metrics. CONCLUSIONS/INTERPRETATION Low HbA1c and low BP were protective cardiovascular health metrics in our study of people with type 1 diabetes. Targeting all cardiovascular health metrics could be more effective in preventing CVD than targeting single metrics.
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Affiliation(s)
- Soraya Soulimane
- Center of Research on Psychological disorders and Somatic diseases (CoRPS), Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands
| | - Beverley Balkau
- Clinical Epidemiology, Université Paris-Saclay, UVSQ, Inserm, CESP, Villejuif, France
| | - Yakima D Vogtschmidt
- Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading, UK
- Institute for Food, Nutrition and Health, University of Reading, Reading, UK
| | - Monika Toeller
- Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - John H Fuller
- Department of Epidemiology and Public Health, University College London, London, UK
| | - Sabita S Soedamah-Muthu
- Center of Research on Psychological disorders and Somatic diseases (CoRPS), Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands.
- Institute for Food, Nutrition and Health, University of Reading, Reading, UK.
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Yapanis M, James S, Craig ME, O’Neal D, Ekinci EI. Complications of Diabetes and Metrics of Glycemic Management Derived From Continuous Glucose Monitoring. J Clin Endocrinol Metab 2022; 107:e2221-e2236. [PMID: 35094087 PMCID: PMC9113815 DOI: 10.1210/clinem/dgac034] [Citation(s) in RCA: 124] [Impact Index Per Article: 41.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Indexed: 11/19/2022]
Abstract
CONTEXT Although glycated hemoglobin A1c is currently the best parameter used clinically to assess risk for the development of diabetes complications, it does not provide insight into short-term fluctuations in glucose levels. This review summarizes the relationship between continuous glucose monitoring (CGM)-derived metrics of glycemic variability and diabetes-related complications. EVIDENCE ACQUISITION PubMed and Embase databases were searched from January 1, 2010 to August 22, 2020, using the terms type 1 diabetes, type 2 diabetes, diabetes-related microvascular and macrovascular complications, and measures of glycaemic variability. Exclusion criteria were studies that did not use CGM and studies involving participants who were not diabetic, acutely unwell (post stroke, post surgery), pregnant, or using insulin pumps. EVIDENCE SYNTHESIS A total of 1636 records were identified, and 1602 were excluded, leaving 34 publications in the final review. Of the 20 852 total participants, 663 had type 1 diabetes (T1D) and 19 909 had type 2 diabetes (T2D). Glycemic variability and low time in range (TIR) showed associations with all studied microvascular and macrovascular complications of diabetes. Notably, higher TIR was associated with reduced risk of albuminuria, retinopathy, cardiovascular disease mortality, all-cause mortality, and abnormal carotid intima-media thickness. Peripheral neuropathy was predominantly associated with standard deviation of blood glucose levels (SD) and mean amplitude of glycemic excursions (MAGE). CONCLUSION The evidence supports the association between diabetes complications and CGM-derived measures of intraday glycemic variability. TIR emerged as the most consistent measure, supporting its emerging role in clinical practice. More longitudinal studies and trials are required to confirm these associations, particularly for T1D, for which there are limited data.
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Affiliation(s)
- Michael Yapanis
- Department of Medicine, the University of Melbourne, Parkville 3052, Victoria, Australia
- Department of Endocrinology, Austin Health, Heidelberg 3084, Victoria, Australia
| | - Steven James
- School of Nursing, Midwifery and Paramedicine, the University of the Sunshine Coast, Petrie 4052, Queensland, Australia
| | - Maria E Craig
- School of Clinical Medicine, UNSW Medicine and Health, Discipline of Paediatrics and Child Health, UNSW 2052, NSW, Australia
- The University of Sydney Children’s Hospital Westmead Clinical School, Westmead 2145, NSW, Australia
| | - David O’Neal
- Department of Medicine, the University of Melbourne, Parkville 3052, Victoria, Australia
- Department of Endocrinology, St Vincent’s Hospital, Fitzroy 3065, Victoria, Australia
| | - Elif I Ekinci
- Department of Medicine, the University of Melbourne, Parkville 3052, Victoria, Australia
- Department of Endocrinology, Austin Health, Heidelberg 3084, Victoria, Australia
- Correspondence: Elif I. Ekinci, PhD, Level 1 Centaur Building, Heidelberg Repatriation Hospital, 330 Waterdale Rd, Heidelberg Heights 3081, Victoria, Australia.
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Chowdhury M, Nevitt S, Eleftheriadou A, Kanagala P, Esa H, Cuthbertson DJ, Tahrani A, Alam U. Cardiac autonomic neuropathy and risk of cardiovascular disease and mortality in type 1 and type 2 diabetes: a meta-analysis. BMJ Open Diabetes Res Care 2021; 9:9/2/e002480. [PMID: 34969689 PMCID: PMC8719152 DOI: 10.1136/bmjdrc-2021-002480] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Accepted: 11/14/2021] [Indexed: 01/24/2023] Open
Abstract
We aimed to determine the prognostic association between cardiac autonomic neuropathy (CAN) and cardiovascular disease events (CVE) and mortality in type 1 and type 2 diabetes through a systematic review and meta-analysis. This systematic review and meta-analysis was registered with PROSPERO (CRD42020216305) and was conducted with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodological criteria. CAN was defined on the basis of 1 (early/possible CAN) or ≥2 (definite CAN) positive autonomic function tests as per the Toronto Consensus guidelines. Studies included those with prospective CVE or mortality data. Methodological variables/risk of bias were assessed using ROBINS-I (Risk Of Bias In Non-randomized Studies - of Interventions) and RoB-2 (Risk-Of-Bias tool for randomized trials) appraisal tools. Electronic database searches yielded 18 467 articles; 84 articles were screened full-text, 26 articles fulfilled the inclusion criteria for quantitative synthesis. Sixteen studies from patients with (n=2875) and without (n=11 722) CAN demonstrated a pooled relative risk (RR) of 3.16 (95%CI 2.42 to 4.13; p<0.0001) of future CVE in favour of CAN. Nineteen studies provided all-cause mortality data from patients with (n=3679) and without (n=12 420) CAN, with a pooled RR of 3.17 (95%CI 2.11 to 4.78; p<0.0001) in favour of CAN. The risk of both future CVE and mortality was higher in type 1 compared with type 2 diabetes and with a definite CAN (vs possible CAN) diagnosis. Three studies were considered to have risk of serious bias. This study confirms the significant association between CAN and CVE and all-cause mortality. The implementation of population-based CAN screening will identify a subgroup with disproportionately higher cardiovascular and mortality risk that will allow for earlier targeted intervention.
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Affiliation(s)
- Mahin Chowdhury
- Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK
| | - Sarah Nevitt
- Department of Health Data Science, University of Liverpool, Liverpool, UK
| | | | - Prathap Kanagala
- Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK
- Department of Medicine, University Hospital Aintree, Liverpool University NHS Foundation Trust, Liverpool, UK
| | - Hani Esa
- Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK
- Department of Medicine, University Hospital Aintree, Liverpool University NHS Foundation Trust, Liverpool, UK
| | - Daniel J Cuthbertson
- Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK
- Department of Medicine, University Hospital Aintree, Liverpool University NHS Foundation Trust, Liverpool, UK
| | - Abd Tahrani
- Centre of Endocrinology, Diabetes and Metabolism, University of Birmingham, Birmingham, UK
- Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
- Department of Diabetes and Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Uazman Alam
- Department of Cardiovascular and Metabolic Medicine, University of Liverpool, Liverpool, UK
- Department of Medicine, University Hospital Aintree, Liverpool University NHS Foundation Trust, Liverpool, UK
- Division of Diabetes, Endocrinology and Gastroenterology, Institute of Human Development, University of Manchester, Manchester, UK
- Department of Cardiovascular & Metabolic Medicine, Institute of Life Course and Medical Sciences and Pain Research Institute, University of Liverpool and Liverpool University Hospital NHS Foundation Trust, Liverpool, UK
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Greco C, Nascimbeni F, Carubbi F, Andreone P, Simoni M, Santi D. Association of Nonalcoholic Fatty Liver Disease (NAFLD) with Peripheral Diabetic Polyneuropathy: A Systematic Review and Meta-Analysis. J Clin Med 2021; 10:4466. [PMID: 34640482 PMCID: PMC8509344 DOI: 10.3390/jcm10194466] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 09/16/2021] [Accepted: 09/24/2021] [Indexed: 12/29/2022] Open
Abstract
AIMS The relationship between nonalcoholic fatty liver disease (NAFLD) and diabetic polyneuropathy (DPN) has been demonstrated in many studies, although results were conflicting. This meta-analysis aims to summarize available data and to estimate the DPN risk among NAFLD patients. MATERIALS AND METHODS We performed a comprehensive literature review until 4 June 2021. Clinical trials analyzing the association between NAFLD and DPN were included. RESULTS Thirteen studies (9614 participants) were included. DPN prevalence was significantly higher in patients with NALFD, compared to patients without NAFLD (OR (95%CI) 2.48 (1.42-4.34), p = 0.001; I2 96%). This finding was confirmed in type 2 diabetes (OR (95%CI) 2.51 (1.33-4.74), p = 0.005; I2 97%), but not in type 1 diabetes (OR (95%CI) 2.44 (0.85-6.99), p = 0.100; I2 77%). Also, body mass index and diabetes duration were higher in NAFLD subjects compared to those without NAFLD (p < 0.001), considering both type 2 and type 1 diabetes. CONCLUSION Despite a high heterogeneity among studies, a significantly increased DPN prevalence among type 2 diabetes subjects with NAFLD was observed. This result was not found in type 1 diabetes, probably due to the longer duration of disease. Physicians should pay more attention to the early detection of DPN, especially in patients with NAFLD.
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Affiliation(s)
- Carla Greco
- Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 42121 Modena, Italy; (M.S.); (D.S.)
- Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Ospedale Civile di Baggiovara, 41125 Modena, Italy
| | - Fabio Nascimbeni
- Division of Internal Medicine and Metabolism, Department of Internal Medicine, Azienda Ospedaliero-Universitaria of Modena, Ospedale Civile di Baggiovara, 41125 Modena, Italy; (F.N.); (F.C.); (P.A.)
| | - Francesca Carubbi
- Division of Internal Medicine and Metabolism, Department of Internal Medicine, Azienda Ospedaliero-Universitaria of Modena, Ospedale Civile di Baggiovara, 41125 Modena, Italy; (F.N.); (F.C.); (P.A.)
- Unit of Internal and Metabolic Medicine, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 42121 Modena, Italy
| | - Pietro Andreone
- Division of Internal Medicine and Metabolism, Department of Internal Medicine, Azienda Ospedaliero-Universitaria of Modena, Ospedale Civile di Baggiovara, 41125 Modena, Italy; (F.N.); (F.C.); (P.A.)
- Unit of Internal and Metabolic Medicine, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 42121 Modena, Italy
| | - Manuela Simoni
- Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 42121 Modena, Italy; (M.S.); (D.S.)
- Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Ospedale Civile di Baggiovara, 41125 Modena, Italy
| | - Daniele Santi
- Unit of Endocrinology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 42121 Modena, Italy; (M.S.); (D.S.)
- Unit of Endocrinology, Department of Medical Specialties, Azienda Ospedaliero-Universitaria of Modena, Ospedale Civile di Baggiovara, 41125 Modena, Italy
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Smigoc Schweiger D, Battelino T, Groselj U. Sex-Related Differences in Cardiovascular Disease Risk Profile in Children and Adolescents with Type 1 Diabetes. Int J Mol Sci 2021; 22:ijms221910192. [PMID: 34638531 PMCID: PMC8508122 DOI: 10.3390/ijms221910192] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 09/13/2021] [Accepted: 09/14/2021] [Indexed: 01/09/2023] Open
Abstract
Cardiovascular disease (CVD) is the primary cause of higher and earlier morbidity and mortality in people with type 1 diabetes (T1D) compared to people without diabetes. In addition, women with T1D are at an even higher relative risk for CVD than men. However, the underlying pathophysiology is not well understood. Atherosclerotic changes are known to progress early in life among people with T1D, yet it is less clear when excess CVD risk begins in females with T1D. This review explores the prevalence of classical CVD risk factors (such as glycemic control, hypertension, dyslipidemia, obesity, albuminuria, smoking, diet, physical inactivity), as well as of novel biomarkers (such as chronic inflammation), in children and adolescents with T1D with particular regard to sex-related differences in risk profile. We also summarize gaps where further research and clearer clinical guidance are needed to better address this issue. Considering that girls with T1D might have a more adverse CVD risk profile than boys, the early identification of and sex-specific intervention in T1D would have the potential to reduce later CVD morbidity and excess mortality in females with T1D. To conclude, based on an extensive review of the existing literature, we found a clear difference between boys and girls with T1D in the presence of individual CVD risk factors as well as in overall CVD risk profiles; the girls were on the whole more impacted.
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Affiliation(s)
- Darja Smigoc Schweiger
- Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia; (D.S.S.); (T.B.)
- Department of Endocrinology, Diabetes and Metabolic Diseases, University Children’s Hospital, University Medical Centre Ljubljana, Bohoriceva 20, 1000 Ljubljana, Slovenia
| | - Tadej Battelino
- Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia; (D.S.S.); (T.B.)
- Department of Endocrinology, Diabetes and Metabolic Diseases, University Children’s Hospital, University Medical Centre Ljubljana, Bohoriceva 20, 1000 Ljubljana, Slovenia
| | - Urh Groselj
- Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia; (D.S.S.); (T.B.)
- Department of Endocrinology, Diabetes and Metabolic Diseases, University Children’s Hospital, University Medical Centre Ljubljana, Bohoriceva 20, 1000 Ljubljana, Slovenia
- Department of Cardiovascular Medicine, School of Medicine, Stanford University, 870 Quarry Road, Stanford, CA 94305, USA
- Correspondence: ; Tel.: +386-1-522-9235; Fax: +386-1-232-0190
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29
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Ang L, Kidwell KM, Dillon B, Reiss J, Fang F, Leone V, Mizokami-Stout K, Pop-Busui R. Dapagliflozin and measures of cardiovascular autonomic function in patients with type 2 diabetes (T2D). J Diabetes Complications 2021; 35:107949. [PMID: 34024686 DOI: 10.1016/j.jdiacomp.2021.107949] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 05/03/2021] [Accepted: 05/07/2021] [Indexed: 01/08/2023]
Abstract
AIMS Sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduce blood pressure without compensatory heart rate elevation, possibly by modulating sympathetic/parasympathetic activity. This may contribute to their cardiovascular benefits in type 2 diabetes (T2D). We evaluated the effects of dapagliflozin (DAPA) on measures of cardiovascular autonomic neuropathy (CAN), cardiac function, and glucose variability (GV) in T2D. METHODS Pilot, randomized, two-period crossover trial comparing 12-week DAPA versus 12-week glimepiride treatment on CAN measures (cardiovascular autonomic reflex tests and heart rate variability), B-type natriuretic peptide (BNP), and GV (Abbott's Libre Pro devices) using signed rank tests and mixed models from baseline to 12 weeks within and between each period. RESULTS Forty-five T2D participants on metformin monotherapy (mean age 57 ± 8 years, duration 7 ± 6 years, HbA1c 7.8 ± 1.3%) were enrolled with 41 completing the trial. There were no differences in CAN indices or BNP with each drug compared to baseline and each other. Participants on DAPA demonstrated greater weight loss, reduced time in hypoglycemia, and improved GV compared to glimepiride. CONCLUSIONS Short term treatment with DAPA did not affect CAN measures or BNP in uncomplicated and relatively healthy T2D participants. Longer prospective studies in patients with advanced disease are needed to better understand relationships between SGLT-2 inhibitors and CAN. CLINICAL TRIAL REGISTRATION NCT02973477.
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Affiliation(s)
- Lynn Ang
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, United States of America.
| | - Kelley M Kidwell
- School of Public Health, Department of Biostatistics, University of Michigan, Ann Arbor, MI, United States of America
| | - Brendan Dillon
- University of Michigan Medical School, Ann Arbor, MI, United States of America
| | - Jacob Reiss
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, United States of America
| | - Fang Fang
- School of Public Health, Department of Biostatistics, University of Michigan, Ann Arbor, MI, United States of America
| | - Virginia Leone
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, United States of America
| | - Kara Mizokami-Stout
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, United States of America; Ann Arbor Veteran Affairs Hospital, Ann Arbor, MI, United States of America
| | - Rodica Pop-Busui
- Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, United States of America
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30
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Kristófi R, Bodegard J, Norhammar A, Thuresson M, Nathanson D, Nyström T, Birkeland KI, Eriksson JW. Cardiovascular and Renal Disease Burden in Type 1 Compared With Type 2 Diabetes: A Two-Country Nationwide Observational Study. Diabetes Care 2021; 44:1211-1218. [PMID: 33653822 PMCID: PMC8132335 DOI: 10.2337/dc20-2839] [Citation(s) in RCA: 43] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 02/04/2021] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Type 1 diabetes (T1D) and type 2 diabetes (T2D) increase risks of cardiovascular (CV) and renal disease (CVRD) compared with diabetes-free populations. Direct comparisons between T1D and T2D are scarce. We examined this by pooling full-population cohorts in Sweden and Norway. RESEARCH DESIGN AND METHODS A total of 59,331 patients with T1D and 484,241 patients with T2D, aged 18-84 years, were followed over a mean period of 2.6 years from 31 December 2013. Patients were identified in nationwide prescribed drug and hospital registries in Norway and Sweden. Prevalence and event rates of myocardial infarction (MI), heart failure (HF), stroke, chronic kidney disease (CKD), all-cause death, and CV death were assessed following age stratification in 5-year intervals. Cox regression analyses were used to estimate risk. RESULTS The prevalence of CV disease was similar in T1D and T2D across age strata, whereas CKD was more common in T1D. Age-adjusted event rates comparing T1D versus T2D showed that HF risk was increased between ages 65 and 79 years, MI between 55 and 79 years, and stroke between 40 and 54 years (1.3-1.4-fold, 1.3-1.8-fold, and 1.4-1.7-fold, respectively). CKD risk was 1.4-3.0-fold higher in T1D at all ages. The all-cause death risk was 1.2-1.5-fold higher in T1D at age >50 years, with a similar trend for CV death. CONCLUSIONS Adult patients with T1D compared with those with T2D had an overall greater risk of cardiorenal disease (HF and CKD) across ages, MI and all-cause death at middle-older ages, and stroke at younger ages. The total age-adjusted CVRD burden and risks were greater among patients with T1D compared with those with T2D, highlighting their need for improved prevention strategies.
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Affiliation(s)
- Robin Kristófi
- Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
| | | | - Anna Norhammar
- Cardiology Unit, Department of Medicine, Solna, Karolinska Institute, Stockholm, Sweden.,Capio Saint Göran Hospital, Stockholm, Sweden
| | | | - David Nathanson
- Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden
| | - Thomas Nyström
- Department of Clinical Science and Education, Karolinska Institutet, Södersjukhuset, Stockholm, Sweden
| | | | - Jan W Eriksson
- Department of Medical Sciences, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
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31
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Helliwell R, Warnes H, Kietsiriroje N, Campbell M, Birch R, Pearson SM, Ajjan RA. Body mass index, estimated glucose disposal rate and vascular complications in type 1 diabetes: Beyond glycated haemoglobin. Diabet Med 2021; 38:e14529. [PMID: 33502032 DOI: 10.1111/dme.14529] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 01/14/2021] [Accepted: 01/21/2021] [Indexed: 12/16/2022]
Abstract
AIMS To understand the relationship between insulin resistance (IR), assessed as estimated glucose disposal rate (eGDR), and microvascular/macrovascular complications in people with type 1 diabetes. MATERIALS AND METHODS Individuals with a confirmed diagnosis of type 1 diabetes were included in this cross-sectional study. BMI was categorised into normal weight (18.0-24.9 kg m-2 ), overweight (25.0-29.9 kg m-2 ) and obese groups (≥30.0 kg m-2 ). We categorised eGDR into four groups: eGDR >8, 6-7.9, 4-5.9 and <4 mg kg-1 min-1 . Multiple logistic regression was used to identify associations with vascular complications, after adjusting for relevant confounders. RESULTS A total of 2151 individuals with type 1 diabetes were studied. Median [interquartile range (IQR)] age was 41.0 [29.0, 55.0] with diabetes duration of 20.0 [11, 31] years. Odds ratio (OR) for retinopathy and nephropathy in obese compared with normal weight individuals was 1.64 (95% CI: 1.24-2.19; p = 0.001) and 1.62 (95% CI: 1.10-2.39; p = 0.015), while the association with cardiovascular disease just failed to reach statistical significance (OR 1.66 [95% CI: 0.97-2.86; p = 0.066]). Comparing individuals with eGDR ≥8 mg kg-1 min-1 and <4 mg kg-1 min-1 showed OR for retinopathy, nephropathy and macrovascular disease of 4.84 (95% CI: 3.36-6.97; p < 0.001), 8.35 (95% CI: 4.86-14.34; p < 0.001) and 13.22 (95% CI: 3.10-56.38; p < 0.001), respectively. Individuals with the highest eGDR category (≥8 mg kg-1 min-1 ) had the lowest complication rates irrespective of HbA1c levels. CONCLUSIONS Obesity is prevalent in type 1 diabetes and diabetes complications are not only related to glucose control. IR, assessed as eGDR, is strongly associated with both microvascular and macrovascular complications, regardless of HbA1c levels.
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Affiliation(s)
| | | | - Noppadol Kietsiriroje
- Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK
- Endocrinology and Metabolism Unit, Internal Medicine Department, Faculty of Medicine, Prince of Songkla University, Songkhla, Thailand
| | - Matthew Campbell
- Faculty of Health Sciences and Wellbeing, University of Sunderland, Sunderland, UK
| | - Rebecca Birch
- Division of Pathology and Data analytics, University of Leeds, Leeds, UK
| | - Sam M Pearson
- School of Medicine, University of Leeds, Leeds, UK
- Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK
| | - Ramzi A Ajjan
- Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK
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32
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Østergaard JA, Jansson Sigfrids F, Forsblom C, Dahlström EH, Thorn LM, Harjutsalo V, Flyvbjerg A, Thiel S, Hansen TK, Groop PH. The pattern-recognition molecule H-ficolin in relation to diabetic kidney disease, mortality, and cardiovascular events in type 1 diabetes. Sci Rep 2021; 11:8919. [PMID: 33903634 PMCID: PMC8076270 DOI: 10.1038/s41598-021-88352-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Accepted: 03/31/2021] [Indexed: 01/14/2023] Open
Abstract
H-ficolin recognizes patterns on microorganisms and stressed cells and can activate the lectin pathway of the complement system. We aimed to assess H-ficolin in relation to the progression of diabetic kidney disease (DKD), all-cause mortality, diabetes-related mortality, and cardiovascular events. Event rates per 10-unit H-ficolin-increase were compared in an observational follow-up of 2,410 individuals with type 1 diabetes from the FinnDiane Study. DKD progression occurred in 400 individuals. The unadjusted hazard ratio (HR) for progression was 1.29 (1.18–1.40) and 1.16 (1.05–1.29) after adjustment for diabetes duration, sex, HbA1c, systolic blood pressure, and smoking status. After adding triglycerides to the model, the HR decreased to 1.07 (0.97–1.18). In all, 486 individuals died, including 268 deaths of cardiovascular causes and 192 deaths of complications to diabetes. HRs for all-cause mortality and cardiovascular mortality were 1.13 (1.04–1.22) and 1.05 (0.93–1.17), respectively, in unadjusted analyses. These estimates lost statistical significance in adjusted models. However, the unadjusted HR for diabetes-related mortality was 1.19 (1.05–1.35) and 1.18 (1.02–1.37) with the most stringent adjustment level. Our results, therefore, indicate that H-ficolin predicts diabetes-related mortality, but neither all-cause mortality nor fatal/non-fatal cardiovascular events. Furthermore, H-ficolin is associated with DKD progression, however, not independently of the fully adjusted model.
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Affiliation(s)
- Jakob Appel Østergaard
- Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.,Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark
| | - Fanny Jansson Sigfrids
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Carol Forsblom
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Emma H Dahlström
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - Lena M Thorn
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Valma Harjutsalo
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.,National Institute for Health and Welfare, Helsinki, Finland
| | - Allan Flyvbjerg
- Steno Diabetes Center Copenhagen, The Capital Region of Denmark, Copenhagen, Denmark
| | - Steffen Thiel
- Department of Biomedicine, Aarhus University, Aarhus, Denmark
| | | | - Per-Henrik Groop
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland. .,Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. .,Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland. .,Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia.
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33
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Bud ES, Vlasa A, Bud A. Diabetes Mellitus is Associated with Severe Infection and Mortality in Patients with COVID-19: A Systematic Review and Meta-analysis. Arch Med Res 2021; 52:356. [PMID: 33220933 PMCID: PMC7654319 DOI: 10.1016/j.arcmed.2020.11.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Accepted: 11/06/2020] [Indexed: 11/16/2022]
Affiliation(s)
- Eugen Silviu Bud
- Faculty of Dental Medicine, University of Medicine and Pharmacy, Science and Technology G.E. Palade, Tirgu-Mures, Romania
| | - Alexandru Vlasa
- Faculty of Dental Medicine, University of Medicine and Pharmacy, Science and Technology G.E. Palade, Tirgu-Mures, Romania.
| | - Anamaria Bud
- Faculty of Dental Medicine, University of Medicine and Pharmacy, Science and Technology G.E. Palade, Tirgu-Mures, Romania
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Kornum DS, Terkelsen AJ, Bertoli D, Klinge MW, Høyer KL, Kufaishi HHA, Borghammer P, Drewes AM, Brock C, Krogh K. Assessment of Gastrointestinal Autonomic Dysfunction: Present and Future Perspectives. J Clin Med 2021; 10:jcm10071392. [PMID: 33807256 PMCID: PMC8037288 DOI: 10.3390/jcm10071392] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 03/25/2021] [Accepted: 03/27/2021] [Indexed: 11/16/2022] Open
Abstract
The autonomic nervous system delicately regulates the function of several target organs, including the gastrointestinal tract. Thus, nerve lesions or other nerve pathologies may cause autonomic dysfunction (AD). Some of the most common causes of AD are diabetes mellitus and α-synucleinopathies such as Parkinson’s disease. Widespread dysmotility throughout the gastrointestinal tract is a common finding in AD, but no commercially available method exists for direct verification of enteric dysfunction. Thus, assessing segmental enteric physiological function is recommended to aid diagnostics and guide treatment. Several established assessment methods exist, but disadvantages such as lack of standardization, exposure to radiation, advanced data interpretation, or high cost, limit their utility. Emerging methods, including high-resolution colonic manometry, 3D-transit, advanced imaging methods, analysis of gut biopsies, and microbiota, may all assist in the evaluation of gastroenteropathy related to AD. This review provides an overview of established and emerging assessment methods of physiological function within the gut and assessment methods of autonomic neuropathy outside the gut, especially in regards to clinical performance, strengths, and limitations for each method.
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Affiliation(s)
- Ditte S. Kornum
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, DK8200 Aarhus, Denmark; (M.W.K.); (K.L.H.); (K.K.)
- Steno Diabetes Centre Aarhus, Aarhus University Hospital, DK8200 Aarhus, Denmark
- Correspondence:
| | - Astrid J. Terkelsen
- Department of Neurology, Aarhus University Hospital, DK8200 Aarhus, Denmark;
| | - Davide Bertoli
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, DK9100 Aalborg, Denmark; (D.B.); (A.M.D.); (C.B.)
| | - Mette W. Klinge
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, DK8200 Aarhus, Denmark; (M.W.K.); (K.L.H.); (K.K.)
| | - Katrine L. Høyer
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, DK8200 Aarhus, Denmark; (M.W.K.); (K.L.H.); (K.K.)
- Steno Diabetes Centre Aarhus, Aarhus University Hospital, DK8200 Aarhus, Denmark
| | - Huda H. A. Kufaishi
- Steno Diabetes Centre Copenhagen, Gentofte Hospital, DK2820 Gentofte, Denmark;
| | - Per Borghammer
- Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital, DK8200 Aarhus, Denmark;
| | - Asbjørn M. Drewes
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, DK9100 Aalborg, Denmark; (D.B.); (A.M.D.); (C.B.)
- Steno Diabetes Centre North Jutland, Aalborg University Hospital, DK9100 Aalborg, Denmark
| | - Christina Brock
- Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, DK9100 Aalborg, Denmark; (D.B.); (A.M.D.); (C.B.)
- Steno Diabetes Centre North Jutland, Aalborg University Hospital, DK9100 Aalborg, Denmark
| | - Klaus Krogh
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, DK8200 Aarhus, Denmark; (M.W.K.); (K.L.H.); (K.K.)
- Steno Diabetes Centre Aarhus, Aarhus University Hospital, DK8200 Aarhus, Denmark
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Bjerg L, Gudbjörnsdottir S, Franzén S, Carstensen B, Witte DR, Jørgensen ME, Svensson AM. Duration of diabetes-related complications and mortality in type 1 diabetes: a national cohort study. Int J Epidemiol 2021; 50:1250-1259. [PMID: 33452524 DOI: 10.1093/ije/dyaa290] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2020] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND People with type 1 diabetes often live for many years with different combinations of diabetes-related complications. We aimed to quantify how complication duration and total complication burden affect mortality, using data from national registers. METHODS This study included 33 396 individuals with type 1 diabetes, registered in the Swedish National Diabetes Register at any time between 2001 and 2012. Each individual was followed and classified according to their time-updated diabetes-related complication status. The main outcomes were all-cause mortality, cardiovascular (CV) mortality and non-CV mortality. Poisson models were used to estimate the rate of these outcomes as a function of the time-updated complication duration. RESULTS Overall, 1748 of the 33 396 individuals died during 198 872 person-years of follow-up. Overall, the time-updated all-cause mortality rate ratio (MRR) was 2.25 [95% confidence interval (CI): 1.99-2.54] for patients with diabetic kidney disease, 0.98 (0.82-1.18) for patients with retinopathy and 4.00 (3.56-4.50) for patients with cardiovascular disease relative to individuals without complications. The excess rate was highest in the first period after a diagnosis of CVD, with an 8-fold higher mortality rate, and stabilized after some 5 years. After diagnosis of diabetic kidney disease, we observed an increase in all-cause mortality with an MRR of around 2 compared with individuals without diabetic kidney disease, which stabilized after few years. CONCLUSIONS In this cohort we show that duration of diabetes-related complications is an important determinant of mortality in type 1 diabetes, for example the MRR associated with CVD is highest in the first period after diagnosis of CVD. A stronger focus on time-updated information and thorough consideration of complication duration may improve risk stratification in routine clinical practice.
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Affiliation(s)
- Lasse Bjerg
- Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark.,Section for General Medical Practice, Department of Public Health, Aarhus University, Aarhus, Denmark.,Danish Diabetes Academy, Odense, Denmark.,Steno Diabetes Center Aarhus, Aarhus, Denmark
| | - Soffia Gudbjörnsdottir
- Swedish National Diabetes Register, Västra Götalandsregionen, Gothenburg, Sweden.,Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
| | - Stefan Franzén
- Swedish National Diabetes Register, Västra Götalandsregionen, Gothenburg, Sweden
| | - Bendix Carstensen
- Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | - Daniel R Witte
- Danish Diabetes Academy, Odense, Denmark.,Steno Diabetes Center Aarhus, Aarhus, Denmark.,Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark
| | - Marit E Jørgensen
- Clinical Epidemiology, Steno Diabetes Center Copenhagen, Gentofte, Denmark.,National Institute of Public Health, University of Southern Denmark, Denmark
| | - Ann-Marie Svensson
- Swedish National Diabetes Register, Västra Götalandsregionen, Gothenburg, Sweden.,Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
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36
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Volsky SK, Shalitin S, Fridman E, Yackobovitch-Gavan M, Lazar L, Bello R, Oron T, Tenenbaum A, Vries LD, Lebenthal Y. Dyslipidemia and cardiovascular disease risk factors in patients with type 1 diabetes: A single-center experience. World J Diabetes 2021; 12:56-68. [PMID: 33520108 PMCID: PMC7807252 DOI: 10.4239/wjd.v12.i1.56] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 11/03/2020] [Accepted: 11/18/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Type 1 diabetes (T1D) contributes to altered lipid profiles and increases the risk of cardiovascular disease (CVD). Youth with T1D may have additional CVD risk factors within the first decade of diagnosis.
AIM To examine risk factors for dyslipidemia in young subjects with T1D.
METHODS Longitudinal and cross-sectional retrospective study of 170 young subjects with T1D (86 males; baseline mean age 12.2 ± 5.6 years and hemoglobin A1c 8.4% ± 1.4%) were followed in a single tertiary diabetes center for a median duration of 15 years. Predictors for outcomes of lipid profiles at last visit (total cholesterol [TC], triglycerides [TGs], low-density lipoprotein-cholesterol [LDL-c], and high-density lipoprotein-cholesterol [HDL-c]) were analyzed by stepwise linear regression models.
RESULTS At baseline, 79.5% of the patients had at least one additional CVD risk factor (borderline dyslipidemia/dyslipidemia [37.5%], pre-hypertension/hypertension [27.6%], and overweight/obesity [16.5%]) and 41.6% had multiple (≥ 2) CVD risk factors. A positive family history of at least one CVD risk factor in a first-degree relative was reported in 54.1% of the cohort. Predictors of elevated TC: family history of CVD (β[SE] = 23.1[8.3], P = 0.006); of elevated LDL-c: baseline diastolic blood pressure (DBP) (β[SE] = 11.4[4.7], P = 0.003) and family history of CVD (β[SE] = 20.7[6.8], P = 0.017); of elevated TGs: baseline DBP (β[SE] = 23.8[9.1], P = 0.010) and family history of CVD (β[SE] = 31.0[13.1], P = 0.020); and of low HDL-c levels: baseline DBP (β[SE] = 4.8[2.1], P = 0.022]).
CONCLUSION Our findings suggest that elevated lipid profiles are associated with DBP and a positive family history of CVD. It is of utmost importance to prevent and control modifiable risk factors such as these, as early as childhood, given that inadequate glycemic control and elevation in blood pressure intensify the risk of dyslipidemia.
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Affiliation(s)
- Sari Krepel Volsky
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
| | - Shlomit Shalitin
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Elena Fridman
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
| | - Michal Yackobovitch-Gavan
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
| | - Liora Lazar
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Rachel Bello
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
| | - Tal Oron
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
| | - Ariel Tenenbaum
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Liat de Vries
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
| | - Yael Lebenthal
- National Center for Childhood Diabetes, The Jesse Z and Sara Lea Shafer Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, Petach-Tikva 4920235, Israel
- Sackler School of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel
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A systematic review and meta-analysis of the serum lipid profile in prediction of diabetic neuropathy. Sci Rep 2021; 11:499. [PMID: 33436718 PMCID: PMC7804465 DOI: 10.1038/s41598-020-79276-0] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 12/04/2020] [Indexed: 12/19/2022] Open
Abstract
Whether the lipid profile in diabetic patients is associated with diabetic neuropathy (DN) development remains ambiguous, as does the predictive value of serum lipid levels in the risk of DN. Here, we performed the first meta-analysis designed to investigate the relationship between DN and the serum levels of triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL), and low-density lipoprotein cholesterol (LDL). Candidate studies were comprehensively identified by searching PubMed, Embase, Cochrane Library and Web of Science databases up to May 2020. Observational methodological meta-analysis was conducted to assess the relationships of TG, TC, HDL, and LDL levels with DN. Changes in blood lipids were used to estimate the effect size. The results were pooled using a random-effects or fixed-effects model. Potential sources of heterogeneity were explored by subgroup analysis. Various outcomes were included, and statistical analyses were performed using STATA (Version 12.0). Mean differences (MDs) and odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. The Newcastle–Ottawa Scale (NOS) was applied to assess the methodological quality. I2 statistics were calculated to evaluate statistical heterogeneity. Funnel plots were utilized to test for publication bias. A sensitivity analysis was performed by omitting each study one by one. Thirty-nine clinical trials containing 32,668 patients were included in the meta-analysis. The results demonstrated that DN patients showed higher TG and lower HDL levels (MD = 0.34, 95% CI: 0.20–0.48 for TG; MD = -0.05, 95% CI: -0.08–-0.02, I2 = 81.3% for HDL) than controls. Subgroup analysis showed that patients with type 1 diabetes mellitus (T1DM) neuropathy had elevated TG levels in their serum (MD = 0.25, 95% CI: 0.16–0.35,I2 = 64.4% for T1DM). However, only patients with T1DM neuropathy had reduced serum HDL levels, and there was no significant difference in serum HDL levels between patients with T2DM neuropathy and controls (MD = -0.07, 95% CI: -0.10–-0.03, I2 = 12.4% for T1DM; MD = -0.02, 95% CI: -0.07–0.03, I2 = 80.2% for T2DM). TC and LDL levels were not significantly different between DN patients and controls (MD = -0.03, 95% CI: -0.14–0.09, I2 = 82.9% for TC; MD = -0.00, 95% CI: -0.08–0.08, I2 = 78.9% for LDL). In addition, compared with mild or painless DN patients, those with moderate or severe pain DN pain had significantly reduced serum TC and LDL levels (MD = -0.31, 95% CI: -0.49–-0.13, I2 = 0% for TC; MD = -0.19, 95% CI: -0.32–-0.08, I2 = 0% for LDL). TG levels and HDL levels did not vary considerably between patients with mild or painless DN and those with moderate or severe DN pain patients (MD = 0.12, 95% CI: -0.28–0.51, I2 = 83.2% for TG; MD = -0.07, 95% CI:-0.14–0.01, I2 = 58.8% for HDL). Furthermore, people with higher TG and LDL levels had higher risk of DN (OR = 1.36, 95% CI: 1.20–1.54, I2 = 86.1% for TG and OR = 1.10, 95% CI: 1.02–1.19, I2 = 17.8% for LDL). Conversely, high serum HDL levels reduced the risk of DN (OR = 0.85, 95% CI: 0.75–0.96, I2 = 72.6%), while TC levels made no significant difference with the risk of DN (OR = 1.02, 95% CI: 1.00–1.04, I2 = 84.7%). This meta-analysis indicated that serum lipid profile changes are among the biological characteristics of DN. Lipid levels should be explored as routine laboratory markers for predicting the risk of DN, as they will help clinicians choose appropriate therapies, and thus optimize the use of available resources.
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Elgdhafi E, Elmiladi S, Shukri A. Diagnosis, staging, and associated conditions of cardiovascular autonomic neuropathy in Libyan patients with diabetes. IBNOSINA JOURNAL OF MEDICINE AND BIOMEDICAL SCIENCES 2021. [DOI: 10.4103/ijmbs.ijmbs_68_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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Vági OE, Svébis MM, Domján BA, Körei AE, Istenes I, Putz Z, Mészáros S, Hajdú N, Békeffy M, Tesfaye S, Kempler P, Horváth VJ, Tabák AG. Association of Cardiovascular Autonomic Neuropathy and Distal Symmetric Polyneuropathy with All-Cause Mortality: A Retrospective Cohort Study. J Diabetes Res 2021; 2021:6662159. [PMID: 34195293 PMCID: PMC8181184 DOI: 10.1155/2021/6662159] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2020] [Revised: 04/23/2021] [Accepted: 05/23/2021] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND People with diabetic cardiovascular autonomic neuropathy (CAN) have increased cardiovascular mortality. However, the association between distal symmetric polyneuropathy (DSPN) or CAN with all-cause mortality is much less investigated. Thus, we set out to examine the effect of CAN and DSPN on all-cause mortality in a well-phenotyped cohort. METHODS All diabetes cases (n = 1,347) from the catchment area of a secondary diabetes care centre who had medical examination including neuropathy assessment between 1997 and 2016 were followed up for all-cause mortality in the NHS Hungary reimbursement database until 2018. We investigated the association of CAN (Ewing tests) and DSPN (Neurometer) with all-cause mortality using Cox models stratified by diabetes type. RESULTS Altogether, n = 131/1,011 persons with type 1/type 2 diabetes were included. Of the participants, 53%/43% were male, mean age was 46 ± 12/64 ± 10 years, diabetes duration was 13 ± 10/7 ± 8 years, 42%/29% had CAN, and 39%/37% had DSPN. During the 9 ± 5/8 ± 5-year follow-up, n = 28/494 participants died. In fully adjusted models, participants with type 1 diabetes patients with versus without DSPN had an increased mortality (HR 2.99, 95% CI 1.4-8.63), while no association with CAN was observed. In type 2 diabetes, both DSPN and CAN independently increased mortality (HR 1.32, 95% CI: 1.07-1.64, and HR 1.44, 95% CI: 1.17-1.76). CONCLUSIONS Our results are compatible with an increased risk of mortality in people with type 1 diabetes and DSPN. Furthermore, we report a similarly strong association between DSPN and CAN and all-cause mortality in type 2 diabetes mellitus.
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Affiliation(s)
- Orsolya E. Vági
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
| | - Márk M. Svébis
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
| | - Beatrix A. Domján
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
| | - Anna E. Körei
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
| | - Ildikó Istenes
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
| | - Zsuzsanna Putz
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
| | - Szilvia Mészáros
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
| | - Noémi Hajdú
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
| | - Magdolna Békeffy
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
| | | | - Péter Kempler
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
| | - Viktor J. Horváth
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
| | - Adam G. Tabák
- Department of Internal Medicine and Oncology, Semmelweis University Faculty of Medicine, Budapest, Hungary
- Department of Epidemiology and Public Health, University College London, London, UK
- Department of Public Health, Semmelweis University Faculty of Medicine, Budapest, Hungary
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Performance analysis of noninvasive electrophysiological methods for the assessment of diabetic sensorimotor polyneuropathy in clinical research: a systematic review and meta-analysis with trial sequential analysis. Sci Rep 2020; 10:21770. [PMID: 33303857 PMCID: PMC7730399 DOI: 10.1038/s41598-020-78787-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2020] [Accepted: 11/12/2020] [Indexed: 12/13/2022] Open
Abstract
Despite the availability of various clinical trials that used different diagnostic methods to identify diabetic sensorimotor polyneuropathy (DSPN), no reliable studies that prove the associations among diagnostic parameters from two different methods are available. Statistically significant diagnostic parameters from various methods can help determine if two different methods can be incorporated together for diagnosing DSPN. In this study, a systematic review, meta-analysis, and trial sequential analysis (TSA) were performed to determine the associations among the different parameters from the most commonly used electrophysiological screening methods in clinical research for DSPN, namely, nerve conduction study (NCS), corneal confocal microscopy (CCM), and electromyography (EMG), for different experimental groups. Electronic databases (e.g., Web of Science, PubMed, and Google Scholar) were searched systematically for articles reporting different screening tools for diabetic peripheral neuropathy. A total of 22 studies involving 2394 participants (801 patients with DSPN, 702 controls, and 891 non-DSPN patients) were reviewed systematically. Meta-analysis was performed to determine statistical significance of difference among four NCS parameters, i.e., peroneal motor nerve conduction velocity, peroneal motor nerve amplitude, sural sensory nerve conduction velocity, and sural sensory nerve amplitude (all p < 0.001); among three CCM parameters, including nerve fiber density, nerve branch density, and nerve fiber length (all p < 0.001); and among four EMG parameters, namely, time to peak occurrence (from 0 to 100% of the stance phase) of four lower limb muscles, including the vastus lateralis (p < 0.001), tibialis anterior (p = 0.63), lateral gastrocnemius (p = 0.01), and gastrocnemius medialis (p = 0.004), and the vibration perception threshold (p < 0.001). Moreover, TSA was conducted to estimate the robustness of the meta-analysis. Most of the parameters showed statistical significance between each other, whereas some were statistically nonsignificant. This meta-analysis and TSA concluded that studies including NCS and CCM parameters were conclusive and robust. However, the included studies on EMG were inconclusive, and additional clinical trials are required.
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Azmi S, Ferdousi M, Kalteniece A, Petropoulos IN, Ponirakis G, Alam U, Asghar O, Marshall A, Sankar A, Boulton AJM, Soran H, Efron N, Malik RA. Protection from neuropathy in extreme duration type 1 diabetes. J Peripher Nerv Syst 2020; 26:49-54. [PMID: 33236478 PMCID: PMC7983958 DOI: 10.1111/jns.12423] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Revised: 11/17/2020] [Accepted: 11/22/2020] [Indexed: 12/17/2022]
Abstract
A proportion of individuals with type 1 diabetes mellitus for more than 50 years (medallists) may be protected from developing nephropathy, retinopathy and neuropathy. Detailed neuropathy phenotyping was undertaken in a cohort of 33 medallists aged 63.7 ± 1.4 years with diabetes for 58.5 ± 0.8 years and HbA1c of 65.9 ± 2.1 mmol/mmol. Medallists had a significantly higher HbA1c (P < .001), lower estimated glomerular filtration rate (eGFR) (P = .005) and higher albumin creatinine excretion ratio (ACR) (P = .01), but a lower total cholesterol (P < .001), triacylglycerols (P = .001), low density lipoprotein‐cholesterol (P < .001) and higher high density lipoprotein‐cholesterol (P = .03), compared to controls. Twenty‐four percent of participants were identified as “escapers” without confirmed diabetic neuropathy. They had a lower neuropathy symptom profile (P = .002), vibration perception threshold (P = .02), warm threshold (P = .05), higher peroneal amplitude (P = .005), nerve conduction velocity (P = .03), heart rate variability (P = .001), corneal nerve fibre density (P = 0.001), branch density (P < .001) and length (P = .001), compared to medallists with diabetic neuropathy. Escapers had a shorter duration of diabetes (P = .006), lower alcohol consumption (P = .04), lower total cholesterol (P = .04) and LDL (P = .02), higher eGFR (P = .001) and lower ACR (P < .001). Patients with extreme duration diabetes without diabetic neuropathy have a comparable HbA1c, blood pressure and body mass index, but a more favourable lipid profile and consume less alcohol compared to those with diabetic neuropathy.
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Affiliation(s)
- Shazli Azmi
- Faculty of Biology, Medicine and Health, University of Manchester and Manchester University Foundation Trust, Manchester, UK
| | - Maryam Ferdousi
- Faculty of Biology, Medicine and Health, University of Manchester and Manchester University Foundation Trust, Manchester, UK
| | - Alise Kalteniece
- Faculty of Biology, Medicine and Health, University of Manchester and Manchester University Foundation Trust, Manchester, UK
| | | | | | - Uazman Alam
- Diabetes & Endocrinology Research, Institute of Cardiovascular and Metabolic Medicine and The Pain Research Institute, University of Liverpool and Liverpool University NHS Hospital Trust, Liverpool, UK
| | - Omar Asghar
- Faculty of Biology, Medicine and Health, University of Manchester and Manchester University Foundation Trust, Manchester, UK
| | - Andrew Marshall
- Institute of Life course and Medical Sciences, University of Liverpool, Liverpool, UK
| | - Adhithya Sankar
- Faculty of Biology, Medicine and Health, University of Manchester and Manchester University Foundation Trust, Manchester, UK
| | - Andrew J M Boulton
- Faculty of Biology, Medicine and Health, University of Manchester and Manchester University Foundation Trust, Manchester, UK
| | - Handrean Soran
- Faculty of Biology, Medicine and Health, University of Manchester and Manchester University Foundation Trust, Manchester, UK
| | - Nathan Efron
- Institute of Health and Biomedical Innovation, Queensland University of Technology, Queensland, Australia
| | - Rayaz A Malik
- Faculty of Biology, Medicine and Health, University of Manchester and Manchester University Foundation Trust, Manchester, UK.,Department of Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar
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Lin YK, Fisher SJ, Pop‐Busui R. Hypoglycemia unawareness and autonomic dysfunction in diabetes: Lessons learned and roles of diabetes technologies. J Diabetes Investig 2020; 11:1388-1402. [PMID: 32403204 PMCID: PMC7610104 DOI: 10.1111/jdi.13290] [Citation(s) in RCA: 47] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 05/01/2020] [Accepted: 05/07/2020] [Indexed: 12/18/2022] Open
Abstract
Impaired awareness of hypoglycemia (IAH) is a reduction in the ability to recognize low blood glucose levels that would otherwise prompt an appropriate corrective therapy. Identified in approximately 25% of patients with type 1 diabetes, IAH has complex pathophysiology, and might lead to serious and potentially lethal consequences in patients with diabetes, particularly in those with more advanced disease and comorbidities. Continuous glucose monitoring systems can provide real-time glucose information and generate timely alerts on rapidly falling or low blood glucose levels. Given their improvements in accuracy, affordability and integration with insulin pump technology, continuous glucose monitoring systems are emerging as critical tools to help prevent serious hypoglycemia and mitigate its consequences in patients with diabetes. This review discusses the current knowledge on IAH and effective diagnostic methods, the relationship between hypoglycemia and cardiovascular autonomic neuropathy, a practical approach to evaluating cardiovascular autonomic neuropathy for clinicians, and recent evidence from clinical trials assessing the effects of the use of CGM technologies in patients with type 1 diabetes with IAH.
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Affiliation(s)
- Yu Kuei Lin
- Division of Metabolism, Endocrinology and DiabetesDepartment of Internal MedicineUniversity of Michigan Medical SchoolAnn ArborMichiganUSA
| | - Simon J Fisher
- Division of Endocrinology, Metabolism and DiabetesDepartment of Internal MedicineUniversity of Utah School of MedicineSalt Lake CityUtahUSA
| | - Rodica Pop‐Busui
- Division of Metabolism, Endocrinology and DiabetesDepartment of Internal MedicineUniversity of Michigan Medical SchoolAnn ArborMichiganUSA
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Pietraszek A. Cardiovascular Effects of Hypoglycemic Agents in Diabetes Mellitus. Curr Drug Saf 2020; 16:32-51. [PMID: 32881674 DOI: 10.2174/1574886315666200902154736] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 06/01/2020] [Accepted: 06/26/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Despite substantial improvements over the years, diabetes mellitus is still associated with cardiovascular disease, heart failure, and excess mortality. OBJECTIVE The objective of this article is to examine existing data on the reduction of cardiovascular morbidity and mortality in diabetes. Control of glycemia, lipid levels, and blood pressure are described in brief. The main scope of this article is, however, to review the glucose-independent cardiovascular effect of antidiabetic pharmacological agents (mainly other than insulin). METHODS The article is a narrative review based on recently published reviews and meta-analyses complemented with data from individual trials, when relevant. RESULTS AND DISCUSSION Older data suggest a cardioprotective role of metformin (an inexpensive and safe drug); a role to date not convincingly challenged. The cardiovascular effects of thiazolidinediones, sulphonylurea, and glinides are debatable. Recent large-scale cardiovascular outcome trials suggest a neutral profile of dipeptidyl peptidase 4 inhibitors, yet provide compelling evidence of cardioprotective effects of glucagon-like 1 receptor antagonists and sodium-glucose transporter 2 inhibitors. CONCLUSION Metformin may have a role in primary and secondary prevention of cardiovascular disease; glucagon-like 1 receptor antagonists and sodium-glucose co-transporter 2 inhibitors play a role in secondary prevention of atherosclerotic cardiovascular disease. Sodium-glucose transporter 2 inhibitors have a role to play in both primary and secondary prevention of heart failure; yet, they carry a small risk of the potentially dangerous adverse effect, euglycemic diabetic ketoacidosis.
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Affiliation(s)
- Anna Pietraszek
- Steno Diabetes Center North Jutland, Aalborg University Hospital, Aalborg, Aalborg, Denmark
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Laursen JC, Hansen CS, Bordino M, Vistisen D, Zobel EH, Winther SA, Groop PH, Frimodt-Møller M, Bernardi L, Rossing P. Hyperoxia improves autonomic function in individuals with long-duration type 1 diabetes and macroalbuminuria. Diabet Med 2020; 37:1561-1568. [PMID: 32353914 DOI: 10.1111/dme.14315] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/27/2020] [Indexed: 01/05/2023]
Abstract
AIM Acute oxygen inhalation and slow deep breathing improve measures of autonomic function transiently in individuals with short-duration type 1 diabetes. Our aims were to examine these interventions and changes in autonomic function in individuals with long-duration type 1 diabetes and to explore interactions with the presence of macroalbuminuria or existing cardiovascular autonomic neuropathy. METHODS Individuals with type 1 diabetes (n = 54) were exposed to acute oxygen inhalation, slow deep breathing and a combination of both (hereafter 'the combination'). Primary outcomes were change in baroreflex sensitivity and heart rate variability. Associations between changes in outcomes were evaluated using mixed effects models. RESULTS Mean age ± sd was 60 ± 10 years and diabetes duration was 38 ± 14 years. Changes are presented as per cent difference from baseline with 95% confidence intervals. Acute oxygen inhalation, slow deep breathing and the combination increased baroreflex sensitivity by 21 (10, 34)%, 32 (13, 53)% and 30 (10, 54)%, respectively. Acute oxygen inhalation trended towards increasing heart rate variability 8 (-1, 17)% (P = 0.056), and slow deep breathing and the combination increased heart rate variability by 33 (18, 49)% and 44 (27, 64)% respectively. Macroalbuminuria or cardiovascular autonomic neuropathy did not modify results. CONCLUSION Autonomic function is improved transiently in individuals with long-duration type 1 diabetes and normoalbuminuria or macroalbuminuria by acute oxygen inhalation and slow deep breathing. There is a risk of survival bias. Autonomic dysfunction might be a reversible condition, and hypoxia might represent a target of intervention.
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Affiliation(s)
- J C Laursen
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
- University of Copenhagen, Copenhagen, Denmark
| | - C S Hansen
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | - M Bordino
- Folkhälsen Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
- Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Research Program for Clinical and Molecular Medicine, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - D Vistisen
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | - E H Zobel
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | - S A Winther
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | - P-H Groop
- Folkhälsen Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
- Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Research Program for Clinical and Molecular Medicine, Faculty of Medicine, University of Helsinki, Helsinki, Finland
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia
| | | | - L Bernardi
- Folkhälsen Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland
- Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Research Program for Clinical and Molecular Medicine, Faculty of Medicine, University of Helsinki, Helsinki, Finland
| | - P Rossing
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
- University of Copenhagen, Copenhagen, Denmark
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Park JW, Okamoto LE, Shibao CA, Biaggioni I. Pharmacologic treatment of orthostatic hypotension. Auton Neurosci 2020; 229:102721. [PMID: 32979782 DOI: 10.1016/j.autneu.2020.102721] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 08/18/2020] [Accepted: 08/23/2020] [Indexed: 12/20/2022]
Abstract
Neurogenic orthostatic hypotension (OH) is a disabling disorder caused by impairment of the normal autonomic compensatory mechanisms that maintain upright blood pressure. Nonpharmacologic treatment is always the first step in the management of this condition, but a considerable number of patients will require pharmacologic therapies. Denervation hypersensitivity and impairment of baroreflex buffering makes these patients sensitive to small doses of pressor agents. Understanding the underlying pathophysiology can help in selecting between treatment options. In general, patients with low "sympathetic reserve", i.e., those with peripheral noradrenergic degeneration (pure autonomic failure, Parkinson's disease) and low plasma norepinephrine, tend to respond better to "norepinephrine replacers" (midodrine and droxidopa). On the other hand, patients with relatively preserved "sympathetic reserve", i.e., those with impaired central autonomic pathways but spared peripheral noradrenergic fibers (multiple system atrophy) and normal or slightly reduced plasma norepinephrine, tend to respond better to "norepinephrine enhancers" (pyridostigmine, atomoxetine, and yohimbine). There is, however, a spectrum of responses within these extremes, and treatment should be individualized. Other nonspecific treatments include fludrocortisone and octreotide. The presence of associated clinical conditions, such as supine hypertension, heart failure, postprandial hypotension, PD, MSA, and diabetes need to be considered in the pharmacologic management of these patients.
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Affiliation(s)
- Jin-Woo Park
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America; Institute for Inflammation Control, Korea University, Seoul, Republic of Korea
| | - Luis E Okamoto
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America
| | - Cyndya A Shibao
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America
| | - Italo Biaggioni
- Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America; Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN, United States of America.
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Ang L, Dillon B, Mizokami-Stout K, Pop-Busui R. Cardiovascular autonomic neuropathy: A silent killer with long reach. Auton Neurosci 2020; 225:102646. [PMID: 32106052 DOI: 10.1016/j.autneu.2020.102646] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Revised: 01/30/2020] [Accepted: 02/11/2020] [Indexed: 02/07/2023]
Abstract
Cardiovascular autonomic neuropathy (CAN) is a common and deadly complication of diabetes mellitus, which is frequently overlooked in clinical practice due to its characteristic subtle presentation earlier in disease. Yet, timely detection of CAN may help implementation of tailored interventions to prevent its progression and mitigate the risk of associated complications, including cardiovascular disease (CVD), cardiac arrhythmias, myocardial dysfunction leading to congestive heart failure and all-cause mortality. This review highlights current CAN epidemiology trends, novel mechanisms linking CAN with other diabetes complications and current recommendations for diagnosis and management of the disease in the clinical setting.
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Affiliation(s)
- Lynn Ang
- Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, United States of America
| | - Brendan Dillon
- University of Michigan Medical School, Ann Arbor, MI, United States of America
| | - Kara Mizokami-Stout
- Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, United States of America
| | - Rodica Pop-Busui
- Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor, MI, United States of America.
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48
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Rawshani A, Rawshani A, Sattar N, Franzén S, McGuire DK, Eliasson B, Svensson AM, Zethelius B, Miftaraj M, Rosengren A, Gudbjörnsdottir S. Relative Prognostic Importance and Optimal Levels of Risk Factors for Mortality and Cardiovascular Outcomes in Type 1 Diabetes Mellitus. Circulation 2020; 139:1900-1912. [PMID: 30798638 DOI: 10.1161/circulationaha.118.037454] [Citation(s) in RCA: 110] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND The strength of association and optimal levels for risk factors related to excess risk of death and cardiovascular outcomes in type 1 diabetes mellitus have been sparsely studied. METHODS In a national observational cohort study from the Swedish National Diabetes Register from 1998 to 2014, we assessed relative prognostic importance of 17 risk factors for death and cardiovascular outcomes in individuals with type 1 diabetes mellitus. We used Cox regression and machine learning analyses. In addition, we examined optimal cut point levels for glycohemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol. Patients with type 1 diabetes mellitus were followed up until death or study end on December 31, 2013. The primary outcomes were death resulting from all causes, fatal/nonfatal acute myocardial infarction, fatal/nonfatal stroke, and hospitalization for heart failure. RESULTS Of 32 611 patients with type 1 diabetes mellitus, 1809 (5.5%) died during follow-up over 10.4 years. The strongest predictors for death and cardiovascular outcomes were glycohemoglobin, albuminuria, duration of diabetes mellitus, systolic blood pressure, and low-density lipoprotein cholesterol. Glycohemoglobin displayed ≈2% higher risk for each 1-mmol/mol increase (equating to ≈22% per 1% glycohemoglobin difference), whereas low-density lipoprotein cholesterol was associated with 35% to 50% greater risk for each 1-mmol/L increase. Microalbuminuria or macroalbuminuria was associated with 2 to 4 times greater risk for cardiovascular complications and death. Glycohemoglobin <53 mmol/mol (7.0%), systolic blood pressure <140 mm Hg, and low-density lipoprotein cholesterol <2.5 mmol/L were associated with significantly lower risk for outcomes observed. CONCLUSIONS Glycohemoglobin, albuminuria, duration of diabetes mellitus, systolic blood pressure, and low-density lipoprotein cholesterol appear to be the most important predictors for mortality and cardiovascular outcomes in patients with type 1 diabetes mellitus. Lower levels for glycohemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than contemporary guideline target levels appear to be associated with significantly lower risk for outcomes.
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Affiliation(s)
- Aidin Rawshani
- Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Sweden (A. Rawshani, A. Rawshani, B.E., A. Rosengren, S.G.).,Swedish National Diabetes Register, Center of Registers in Region, Gothenburg, Sweden (A. Rawshani, A. Rawshani, S.F., B.E., A.-M.S., M.M., S.G.)
| | - Araz Rawshani
- Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Sweden (A. Rawshani, A. Rawshani, B.E., A. Rosengren, S.G.).,Swedish National Diabetes Register, Center of Registers in Region, Gothenburg, Sweden (A. Rawshani, A. Rawshani, S.F., B.E., A.-M.S., M.M., S.G.)
| | - Naveed Sattar
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.)
| | - Stefan Franzén
- Swedish National Diabetes Register, Center of Registers in Region, Gothenburg, Sweden (A. Rawshani, A. Rawshani, S.F., B.E., A.-M.S., M.M., S.G.).,Health Metrics Unit, Sahlgrenska Academy, University of Gothenburg, Sweden (S.F.)
| | - Darren K McGuire
- Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (D.K.M.)
| | - Björn Eliasson
- Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Sweden (A. Rawshani, A. Rawshani, B.E., A. Rosengren, S.G.).,Swedish National Diabetes Register, Center of Registers in Region, Gothenburg, Sweden (A. Rawshani, A. Rawshani, S.F., B.E., A.-M.S., M.M., S.G.)
| | - Ann-Marie Svensson
- Swedish National Diabetes Register, Center of Registers in Region, Gothenburg, Sweden (A. Rawshani, A. Rawshani, S.F., B.E., A.-M.S., M.M., S.G.)
| | - Björn Zethelius
- Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Sweden (B.Z.)
| | - Mervete Miftaraj
- Swedish National Diabetes Register, Center of Registers in Region, Gothenburg, Sweden (A. Rawshani, A. Rawshani, S.F., B.E., A.-M.S., M.M., S.G.)
| | - Annika Rosengren
- Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Sweden (A. Rawshani, A. Rawshani, B.E., A. Rosengren, S.G.)
| | - Soffia Gudbjörnsdottir
- Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Sweden (A. Rawshani, A. Rawshani, B.E., A. Rosengren, S.G.).,Swedish National Diabetes Register, Center of Registers in Region, Gothenburg, Sweden (A. Rawshani, A. Rawshani, S.F., B.E., A.-M.S., M.M., S.G.)
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Rahmani B, Gandhi J, Joshi G, Smith NL, Reid I, Khan SA. The Role of Diabetes Mellitus in Diseases of the Gallbladder and Biliary Tract. Curr Diabetes Rev 2020; 16:931-948. [PMID: 32133965 DOI: 10.2174/1573399816666200305094727] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Revised: 02/18/2020] [Accepted: 02/21/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND The increasing prevalence of diabetes mellitus worldwide continues to pose a heavy burden. Though its gastrointestinal impact is appropriately recognized, the lesser known associations may be overlooked. OBJECTIVE We aim to review the negative implications of diabetes on the gallbladder and the biliary tract. METHODS A MEDLINE® database search of literature was conducted with emphasis on the previous five years, combining keywords such as "diabetes," "gallbladder," and "biliary". RESULTS The association of diabetes to the formation of gallstones, gallbladder cancer, and cancer of the biliary tract are discussed along with diagnosis and treatment. CONCLUSION Though we uncover the role of diabetic neuropathy in gallbladder and biliary complications, the specific individual diabetic risk factors behind these developments is unclear. Also, in addition to diabetes control and surgical gallbladder management, the treatment approach also requires further focus.
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Affiliation(s)
- Benjamin Rahmani
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook,
NY, USA
| | - Jason Gandhi
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook,
NY, USA
- Medical Student Research Institute, St. George’s University School of Medicine, Grenada, West Indies
| | - Gunjan Joshi
- Department of Internal Medicine, Stony Brook Southampton Hospital, Southampton, NY, USA
| | | | - Inefta Reid
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook,
NY, USA
| | - Sardar Ali Khan
- Department of Physiology and Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook,
NY, USA
- Department of Urology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, USA
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50
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Kietsiriroje N, Pearson S, Campbell M, Ariëns RAS, Ajjan RA. Double diabetes: A distinct high-risk group? Diabetes Obes Metab 2019; 21:2609-2618. [PMID: 31373146 DOI: 10.1111/dom.13848] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 07/23/2019] [Accepted: 07/29/2019] [Indexed: 01/06/2023]
Abstract
The term double diabetes (DD) has been used to refer to individuals with type 1 diabetes (T1D) who are overweight, have a family history of type 2 diabetes and/or clinical features of insulin resistance. Several pieces of evidence indicate that individuals who display features of DD are at higher risk of developing future diabetes complications, independently of average glucose control, measured as glycated haemoglobin (HbA1c) concentration. Given the increased prevalence of individuals with features of DD, pragmatic criteria are urgently required to identify and stratify this group, which will help with subsequent implementation of more effective personalized interventions. In this review, we discuss the potential criteria for the clinical identification of individuals with DD, highlighting the strengths and weaknesses of each definition. We also cover potential mechanisms of DD and how these contribute to increased risk of diabetes complications. Special emphasis is placed on the role of estimated glucose disposal rate (eGDR) in the diagnosis of DD, which can be easily incorporated into clinical practice and is predictive of adverse clinical outcome. In addition to the identification of individuals with DD, eGDR has potential utility in monitoring response to different interventions. T1D is a more heterogeneous condition than initially envisaged, and those with features of DD represent a subgroup at higher risk of complications. Pragmatic criteria for the diagnosis of individuals with DD will help with risk stratification, allowing a more personalized and targeted management strategy to improve outcome and quality of life in this population.
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Affiliation(s)
- Noppadol Kietsiriroje
- Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hatyai, Songkhla, Thailand
| | - Sam Pearson
- Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK
| | - Matthew Campbell
- School of Food Science and Nutrition, University of Leeds, Leeds, UK
| | - Robert A S Ariëns
- Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK
| | - Ramzi A Ajjan
- Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, UK
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