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Daliri EBM, Megur A, Mingaila J, Vijaya AK, Balnionytė T, Sakar D, Carnicero-Mayo Y, Behrends V, Costabile A, Burokas A. Fermented beetroot modulates gut microbial carbohydrate metabolism in prediabetes and prevents high-fat diet induced hyperglycemia in a prediabetic model. Curr Res Food Sci 2025; 10:101052. [PMID: 40290372 PMCID: PMC12022487 DOI: 10.1016/j.crfs.2025.101052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 03/26/2025] [Accepted: 04/11/2025] [Indexed: 04/30/2025] Open
Abstract
The global increase in prevalence of (pre-)diabetes demands immediate intervention strategies. In our earlier work, we demonstrated in vitro antidiabetic potential of a fermented beetroot product (PN39). Here, we examined the impact of PN39 on glucose tolerance and gut microbiota in C57BL/6J male mice and on prediabetic (PD) subjects' stool microbiota. In mice, high-fat diet (HFD) consumption for 9 weeks resulted in hyperglycemia and impaired glucose tolerance (GT) while concomitant consumption of PN39 and HFD (PN39+HFD) prevented GT impairment. Meanwhile, feeding the mice with HFD for 5 weeks to induce PD and later administering them with PN39 for 4 weeks (PD + PN39) neither improved fasting blood glucose nor GT. Relative to control groups, the gut microbiota of both PD mice and humans were characterized by decreased Clostridia UCG-014 and Lactobacilli as well as significantly altered gut microbial carbohydrate metabolism. Feeding PN39 together with HFD preserved Clostridia UCG-014 and Lactobacilli, increased short chain fatty acid production relative to mice fed with HFD only. Treating gut microbiota of PD subjects with PN39 however increased Clostridia UCG-014 and Lactobacilli populations and increased short chain fatty acids concentrations in the stools. In both mice and humans, PN39 treatment rectified the altered microbial carbohydrate metabolism observed in their PD counterparts. This suggests that the gut microbial modulatory effects of PN39 coupled with its capacity to regulate gut microbial glucose metabolism, likely played a role in preventing PD in mice receiving PN39+HFD. Taken together, our results indicate that PN39 could act as a potent antidiabetic functional food for preventing diabetes and its associated dysbiosis.
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Affiliation(s)
- Eric Banan-Mwine Daliri
- Department of Biological Models, Institute of Biochemistry, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257, Vilnius, Lithuania
| | - Ashwinipriyadarshini Megur
- Department of Biological Models, Institute of Biochemistry, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257, Vilnius, Lithuania
| | - Jonas Mingaila
- Department of Biological Models, Institute of Biochemistry, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257, Vilnius, Lithuania
| | - Akshay Kumar Vijaya
- Department of Biological Models, Institute of Biochemistry, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257, Vilnius, Lithuania
| | - Toma Balnionytė
- Department of Biological Models, Institute of Biochemistry, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257, Vilnius, Lithuania
| | - Debalina Sakar
- School of Life and Health Sciences, University of Roehampton, London, SW15 4JD, UK
| | - Yaiza Carnicero-Mayo
- Área de Microbiología, Facultad de Ciencias Biológicas y Ambientales, Universidad de León, 24007, León, Spain
| | - Volker Behrends
- School of Life and Health Sciences, University of Roehampton, London, SW15 4JD, UK
- School of Medicine and Biosciences, University of West London, St Mary's Road, Ealing, London, W5 5RF, UK
| | - Adele Costabile
- School of Life and Health Sciences, University of Roehampton, London, SW15 4JD, UK
| | - Aurelijus Burokas
- Department of Biological Models, Institute of Biochemistry, Life Sciences Center, Vilnius University, Sauletekio Ave. 7, LT-10257, Vilnius, Lithuania
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Mulla IG, Anjankar A, Pratinidhi S, Agrawal SV, Gundpatil D, Lambe SD. Prediabetes: A Benign Intermediate Stage or a Risk Factor in Itself? Cureus 2024; 16:e63186. [PMID: 39070421 PMCID: PMC11273947 DOI: 10.7759/cureus.63186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2024] [Accepted: 06/26/2024] [Indexed: 07/30/2024] Open
Abstract
Prediabetes is a condition when the blood glucose levels are above the normal range but below the threshold for defining diabetes. Previously considered benign, it is now recognized to be associated with various macrovascular and microvascular complications, with increases in the risk of cardiovascular events, nephropathy neuropathy, and retinopathy. Early identification of prediabetics may help detect the risk for these future complications at an earlier stage. Moreover, therapeutic options for prediabetes are available, which can retard its progression to diabetes and the subsequent development of complications. Hence, we make a case for the early identification of prediabetes through screening methods and appropriate institution of management strategies.
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Affiliation(s)
- Irfan G Mulla
- Biochemistry, Datta Meghe Institute of Higher Education & Research (DMIHER), Wardha, IND
| | | | - Shilpa Pratinidhi
- Biochemistry, Bharatratna Atalbihari Vajpayee Medical College, Pune, Pune, IND
| | - Sarita V Agrawal
- Biochemistry, Bharatratna Atalbihari Vajpayee Medical College, Pune, Pune, IND
| | - Deepak Gundpatil
- Biochemistry, Bharatratna Atalbihari Vajpayee Medical College, Pune, Pune, IND
| | - Sandip D Lambe
- Biochemistry, Smt Mathurabai Bhausaheb Thorat (SMBT) Institute of Medical Sciences and Research Centre, Nashik, IND
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Körei AE, Békeffy M, Menyhárt A, Osgyán K, Istenes I, Horváth VJ, Kempler P. No clear evidence of neuropathy among patients with high risk for the development of prediabetes/diabetes-a pilot study. Front Endocrinol (Lausanne) 2024; 15:1302013. [PMID: 38352713 PMCID: PMC10863448 DOI: 10.3389/fendo.2024.1302013] [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: 09/25/2023] [Accepted: 01/03/2024] [Indexed: 02/16/2024] Open
Abstract
Introduction Autonomic and sensory neuropathy have been observed in both prediabetes and manifest diabetes mellitus. However, there is a lack of available data regarding whether patients at a moderate or high risk of developing diabetes, yet without a current diagnosis of prediabetes or diabetes, exhibit an increased prevalence of neuropathy. Methods FINDRISC (Finnish Diabetes Risk Score) was used to classify individuals at risk (≥12 points, n = 44; control <12 points, n = 28). HbA1c levels >5.6% served as exclusion criteria, and patients with known medical conditions predisposing to neuropathy were also excluded. Cardiac autonomic function (Ewing tests) and peripheral sensory neuropathy (Neurometer and Q-sense) were assessed by standardized protocols, and their potential association with increased FINDRISC points was analyzed using a regression model. Results Mean age was 46.7 ± 14.3 years in the control and 55.7 ± 14.1 years in the increased risk group. Male/female ratio did not differ. Individuals with increased risk of diabetes were more obese (BMI: 29.9 ± 12.5 kg/m2 vs. 25.9 ± 8.9 kg/m2). Additionally, hypertension was more frequent among them (68.2% vs. 17.9%), and their lipid parameters were also less favorable. Parasympathetic neuropathy was present in both groups (56.8% vs. 32.1%, respectively). Sympathetic neuropathy was not found. Sensory nerve dysfunction was of low prevalence in the high-risk group and did not occur in healthy controls. In multiple logistic regression analysis, HbA1c exhibited an independent association with parasympathetic neuropathy (OR: 5.9; 95% CI: 1.08-32.68; p < 0.041). Discussion An increased risk of developing prediabetes/diabetes does not appear to have a strong correlation with an increased likelihood of developing autonomic or sensory neuropathy. However, the etiology behind the occurrence of parasympathetic autonomic neuropathy in healthy individuals remains unknown.
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Affiliation(s)
| | | | | | | | | | - Viktor J. Horváth
- Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary
| | - Péter Kempler
- Department of Internal Medicine and Oncology, Semmelweis University, Budapest, Hungary
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Ziegler D, Herder C, Papanas N. Neuropathy in prediabetes. Diabetes Metab Res Rev 2023; 39:e3693. [PMID: 37470302 DOI: 10.1002/dmrr.3693] [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: 02/23/2023] [Revised: 04/13/2023] [Accepted: 06/18/2023] [Indexed: 07/21/2023]
Abstract
Diabetic neuropathies are the most frequent complications of diabetes, contributing to high morbidity, excess mortality, reduced quality of life, and increased healthcare costs. Prediabetes is characterised by glucose levels within an intermediate range above normoglycaemia yet below the diagnostic threshold for diabetes. In 2021, 10.6% and 6.2% of adults worldwide were estimated to have impaired glucose tolerance and impaired fasting glucose, respectively, the majority of whom are unaware of having prediabetes. Evidence has accumulated suggesting that prediabetes is a predictor of cardiovascular disease (CVD) and increased mortality. The past 2 decades have witnessed an extensive debate, particularly among diabetologists and neurologists, as to whether prediabetes is associated with peripheral neuropathy. In this review, we elaborate on the current evidence, particularly from population-based studies supporting an increased risk of distal sensorimotor polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) in people with prediabetes. Moreover, we discuss whether lifestyle interventions showing efficacy in preventing or delaying the transition from prediabetes to diabetes in persons with prediabetes may also exert favourable effects on the development and progression of DSPN and CAN. This review should help in raising the awareness of and translating the current knowledge on neuropathies in people with prediabetes into clinical practice and public health. The current recommendation that adults who are overweight or obese should be screened for prediabetes and referred to or offered preventive interventions should ultimately culminate in preventing not only CVD but also prediabetic neuropathy.
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Affiliation(s)
- Dan Ziegler
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
| | - Christian Herder
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Nikolaos Papanas
- Diabetes Centre, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece
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Gujjar P, Ravikumar YS, Nagendra L, Boro H, Bhattacharya S. Cardiac Autonomic Neuropathy in Prediabetes: A Case-Control Study. Indian J Endocrinol Metab 2023; 27:325-329. [PMID: 37867983 PMCID: PMC10586559 DOI: 10.4103/ijem.ijem_50_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Revised: 03/13/2023] [Accepted: 04/02/2023] [Indexed: 10/24/2023] Open
Abstract
Introduction Early detection and diagnosis of diabetic autonomic neuropathy, especially cardiac autonomic neuropathy (CAN), have gained attention recently because of their elevated cardiovascular mortality risk. Although the connection between type 2 diabetes mellitus and autonomic neuropathy is well established, evidence is emerging that the association might predate the stage of prediabetes. Objective The present study was undertaken to compare the prevalence of CAN in prediabetes versus that in normoglycemic controls. Materials and Methods The study population was selected by purposive sampling from individuals attending a tertiary care hospital from January 2018 to June 2019. Fifty individuals with prediabetes diagnosed by the American Diabetes Association's glycated haemoglobin criteria and 50 age- and gender-matched healthy controls were recruited. CAN was assessed by standard cardiovascular reflex tests, as described by Ewing and Clarke. Changes in R-R with deep breathing, Valsalva manoeuver, and changes in blood pressure (BP) in response to standing and sustained handgrip were evaluated. Three-time domains [standard deviation of normal-to-normal intervals (SDNN), root mean square of successive RR intervals (rMSSD) and percentage of successive normal to normal R-R (NN) intervals that differ by more than 50 ms (pNN50)] and four frequency domain indices [very low-frequency band (VLF), low-frequency band (LF), high-frequency band (HF), LF/HF ratio) of heart rate variability (HRV)] were examined. Results The mean heart rate was 71.37 ± 7.94 and 65.59 ± 8.73 beats/min in patients with prediabetes and controls, respectively (P < 0.05). All three-time-domain indices of HRV were significantly lower in persons with prediabetes compared to controls. The peak frequency of LF, peak power of LF, normalised unit of LF, and LF/HF ratio was significantly lower in subjects with prediabetes than in controls. There was no difference in the traditional cardiovascular autonomic reflex testing. Conclusion Our study demonstrates the presence of subclinical autonomic dysfunction in persons with prediabetes. Early detection of CAN in prediabetes can have future implications for cardiovascular risk reduction.
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Affiliation(s)
- Pavan Gujjar
- Department of General Medicine, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, Karnataka, India
| | - Y. S. Ravikumar
- Department of General Medicine, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, Karnataka, India
| | - Lakshmi Nagendra
- Department of Endocrinology, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, Karnataka, India
| | - Hiya Boro
- Department of Endocrinology, Aadhar Health Institute, Hisar, Haryana, India
| | - Saptarshi Bhattacharya
- Department of Endocrinology, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi, India
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Menduni M, D'Amato C, Leoni M, Izzo V, Staltari M, Greco C, Abbatepassero A, Seminara G, D'Ippolito I, Lauro D, Spallone V. Clinical scoring systems for the risk of cardiovascular autonomic neuropathy in type 1 and type 2 diabetes: a simple tool. J Peripher Nerv Syst 2022; 27:259-270. [PMID: 36029134 DOI: 10.1111/jns.12510] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 08/01/2022] [Accepted: 08/19/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND AND AIMS This study was aimed at developing a clinical risk score for cardiovascular autonomic neuropathy (CAN) for type 1 and type 2 diabetes. METHODS In a retrospective cross-sectional one-centre study in an unselected population, 115 participants with type 1 diabetes (age 41.1±12.2 years), and 161 with type 2 diabetes (age 63.1±8.9 years), well-characterised for clinical variables, underwent standard cardiovascular reflex tests (CARTs). Strength of associations of confirmed CAN (based on 2 abnormal CARTs) with clinical variables was used to build a CAN risk score. RESULTS CAN risk score was based on resting heart rate, HbA1c, retinopathy, nephropathy, cardiovascular disease in both type 1 and type 2 diabetes, and on HDL cholesterol, systolic blood pressure, and smoking in type 1 diabetes or insulin treatment and physical activity in type 2 diabetes (range 0-10). In type 1 diabetes, CAN risk score showed an area under the ROC curve (AUC) of 0.890±0.034, and at cut-off of 4 sensitivity of 88%, specificity of 74.4%, and negative predictive value (NPV) of 95.7% for confirmed CAN. In type 2 diabetes, CAN risk score showed an AUC of 0.830±0.051 and at the cut-off of 4 sensitivity and specificity of 78.6% and 73.5%, respectively, and NPV of 97.3% for confirmed CAN. INTERPRETATION These newly developed CAN risk scores are accessible in clinical practice and, if confirmed in a validation study, they might identify asymptomatic individuals with diabetes at greater risk of CAN to be referred to CARTs, thus limiting the burden of a universal screening. This article is protected by copyright. All rights reserved.
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Affiliation(s)
- Marika Menduni
- Department of Systems Medicine, Endocrinology Section, University of Rome Tor Vergata, Rome, Italy
| | - Cinzia D'Amato
- Department of Systems Medicine, Endocrinology Section, University of Rome Tor Vergata, Rome, Italy
| | - Martina Leoni
- Department of Systems Medicine, Endocrinology Section, University of Rome Tor Vergata, Rome, Italy
| | - Valentina Izzo
- Department of Systems Medicine, Endocrinology Section, University of Rome Tor Vergata, Rome, Italy
| | - Mariateresa Staltari
- Department of Systems Medicine, Endocrinology Section, University of Rome Tor Vergata, Rome, Italy
| | - Carla Greco
- Department of Systems Medicine, Endocrinology Section, University of Rome Tor Vergata, Rome, Italy
| | - Andrea Abbatepassero
- Department of Systems Medicine, Endocrinology Section, University of Rome Tor Vergata, Rome, Italy
| | - Giuseppe Seminara
- Department of Systems Medicine, Endocrinology Section, University of Rome Tor Vergata, Rome, Italy
| | - Ilenia D'Ippolito
- Department of Systems Medicine, Endocrinology Section, University of Rome Tor Vergata, Rome, Italy
| | - Davide Lauro
- Department of Systems Medicine, Endocrinology Section, University of Rome Tor Vergata, Rome, Italy
| | - Vincenza Spallone
- Department of Systems Medicine, Endocrinology Section, University of Rome Tor Vergata, Rome, Italy
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Gateva A, Kamenov Z. Cardiac Autonomic Neuropathy in Patients with Newly Diagnosed Carbohydrate Disturbances. Horm Metab Res 2022; 54:308-315. [PMID: 35325930 DOI: 10.1055/a-1775-8251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus that can predispose patients to higher risk for cardiovascular death. The aim of the present study was to evaluate the presence of cardiac autonomic neuropathy and sudomotor dysfunction in patients with newly diagnosed carbohydrate disturbances (prediabetes or diabetes) and to assess their relationship to metabolic disturbances and cardiovascular risk. In the present study, we included 160 patients -78 with obesity without carbohydrate disturbances, 52 with prediabetes, and 30 with newly diagnosed diabetes. CAN was diagnosed using cardiovascular reflex tests and sudomotor function was evaluated by SUDOSCAN. Cardiovascular risk was calculated using SCORE and FRMINGHAM risk scores. The prevalence of cardiac autonomic neuropathy was significantly higher in patients with newly diagnosed diabetes. Independently of their glycemic status, the patients who had blood glucose on the 60th-minute of OGTT>8.5 mmol/l had significantly higher prevalence of cardiac autonomic neuropathy (30.2% vs 15.6%, р=0.044). Patients with high cardiovascular risk according to FRAMINGHAM and SCORE had worse heart rate variability scores. Autonomic neuropathy risk assessed by SUDOSCAN was a good predictor for the presence of CAN. In conclusion, CAN has a higher prevalence on patients with newly diagnosed diabetes compared to prediabetic and normoglycemic subjects, while the patients with blood glucose>8.5 mmol/l on the 60th-minute of OGTT have higher prevalence of CAN independently of their glycemic status. SUDOSCAN testing can be used to assess the risk of CAN and to select patients that should undergo further testing.
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Affiliation(s)
- Antoaneta Gateva
- Department of Internal Medicine, Medical University, Sofia, Bulgaria
| | - Zdravko Kamenov
- Department of Internal Medicine, Medical University, Sofia, Bulgaria
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Bönhof GJ, Herder C, Ziegler D. Diagnostic Tools, Biomarkers, and Treatments in Diabetic polyneuropathy and Cardiovascular Autonomic Neuropathy. Curr Diabetes Rev 2022; 18:e120421192781. [PMID: 33845748 DOI: 10.2174/1573399817666210412123740] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Revised: 02/24/2021] [Accepted: 03/02/2021] [Indexed: 11/22/2022]
Abstract
The various manifestations of diabetic neuropathy, including distal symmetric sensorimotor polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN), are among the most prevalent chronic complications of diabetes. Major clinical complications of diabetic neuropathies, such as neuropathic pain, chronic foot ulcers, and orthostatic hypotension, are associated with considerable morbidity, increased mortality, and diminished quality of life. Despite the substantial individual and socioeconomic burden, the strategies to diagnose and treat diabetic neuropathies remain insufficient. This review provides an overview of the current clinical aspects and recent advances in exploring local and systemic biomarkers of both DSPN and CAN assessed in human studies (such as biomarkers of inflammation and oxidative stress) for better understanding of the underlying pathophysiology and for improving early detection. Current therapeutic options for DSPN are (I) causal treatment, including lifestyle modification, optimal glycemic control, and multifactorial risk intervention, (II) pharmacotherapy derived from pathogenetic concepts, and (III) analgesic treatment against neuropathic pain. Recent advances in each category are discussed, including non-pharmacological approaches, such as electrical stimulation. Finally, the current therapeutic options for cardiovascular autonomic complications are provided. These insights should contribute to a broader understanding of the various manifestations of diabetic neuropathies from both the research and clinical perspectives.
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Affiliation(s)
- Gidon J Bönhof
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Department of Endocrinology, Medical Faculty and University Hospital, Heinrich Heine University, Düsseldorf, Germany
| | - Christian Herder
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Department of Endocrinology, Medical Faculty and University Hospital, Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany
| | - Dan Ziegler
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Department of Endocrinology, Medical Faculty and University Hospital, Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research, Partner Düsseldorf, München-Neuherberg, Germany
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Jorge-Galarza E, Torres-Tamayo M, Martínez-Alvarado MDR, Peña-Aparicio B, González-Salazar C, Reyes-Barrera J, Sierra-Beltrán M, Fajardo-Flores E, Kostin A, González-Hermosillo JA. Cardiovascular autonomic responses during head-up tilt test in newly diagnosed type 2 diabetes. Ir J Med Sci 2021; 191:2077-2084. [PMID: 34750734 DOI: 10.1007/s11845-021-02825-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 10/21/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Autonomic dysfunction is commonly observed in patients with long-standing type 2 diabetes. Previous studies have confirmed the value of both subjectively assessed symptoms and objective measurements of autonomic nervous system function in diagnosing cardiovascular autonomic neuropathy. However, the head-up tilt test (HUTT) has been rarely used to investigate cardiovascular autonomic responses in subjects with high risk of newly diagnosed type 2 diabetes (nT2D). OBJECTIVE To evaluate autonomic cardiovascular responses through passive orthostatic challenge along the diabetes continuum. METHODS The study population was stratified as normoglycemic (n = 16), prediabetes (n = 20), and nT2D (n = 20). The prevalence of orthostatic intolerance and autonomic cardiovascular responses was evaluated with the Task Force Monitor during a 30-min passive HUTT. Spectral indices of heart rate and blood pressure variability and baroreceptor effectiveness index (BEI) were calculated through the HUTT. BEI was obtained by the sequence method. RESULTS There were no differences in the prevalence of orthostatic intolerance or in the indices of heart rate and blood pressure variability among the three groups of study. The BEI was attenuated in the nT2D group in supine rest and throughout HUTT compared with normoglycemic and prediabetes groups. The multivariable linear regression analysis showed that BEI was associated with fasting glucose (β = - 0.52, p < 0.001) and HbA1c (β = - 0.57, p < 0.001) independently of cardiovascular risk factors. CONCLUSION Cardiovascular autonomic neuropathy, expressed as blunted BEI, is the only abnormal autonomic nervous test detected in nT2D, and it was independently associated with fasting glucose and HbA1c values.
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Affiliation(s)
- Esteban Jorge-Galarza
- Endocrinology Department, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - Margarita Torres-Tamayo
- Endocrinology Department, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | | | - Berenice Peña-Aparicio
- Endocrinology Department, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - Carmen González-Salazar
- Endocrinology Department, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - Juan Reyes-Barrera
- Endocrinology Department, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - Manuel Sierra-Beltrán
- Dysautonomic Clinic, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - Erika Fajardo-Flores
- Dysautonomic Clinic, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - Andrey Kostin
- Dysautonomic Clinic, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico
| | - J Antonio González-Hermosillo
- Dysautonomic Clinic, National Institute of Cardiology "Ignacio Chávez", Mexico City, Mexico. .,, Mexico City, Mexico.
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Schroijen MA, de Mutsert R, Dekker FW, de Vries APJ, de Koning EJP, Rabelink TJ, Rosendaal FR, Dekkers OM. The association of glucose metabolism and kidney function in middle-aged adults. Clin Kidney J 2021; 14:2383-2390. [PMID: 34754434 PMCID: PMC8572983 DOI: 10.1093/ckj/sfab074] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Previous clinical studies have shown that various measures of glucose metabolism are associated with a risk of chronic kidney disease in different populations, but results were not consistent. In this study we assessed measures of glucose metabolism and their association with kidney function in a population-based study. METHODS The Netherlands Epidemiology of Obesity study is a population-based cohort study of middle-aged men and women. We categorized the study population according to glycaemic levels into normoglycaemia (reference group), pre-diabetes mellitus (pre-DM), known DM and newly diagnosed DM. Outcome variables were serum creatinine, estimated glomerular filtration rate (eGFR), glomerular hyperfiltration (defined as an eGFR >90th percentile; >102 mL/min/1.73 m2) and micro-albuminuria. We examined the association between measures of glucose metabolism [fasting glucose, haemoglobin A1c (HbA1c), fasting insulin, glucose area under the curve (AUC), insulin AUC, Homoeostatic Model Assessment of Insulin Resistance (HOMA-IR), HOMA of β-cell function (HOMA-B) and disposition index] and measures of kidney function. RESULTS Of the total population (N = 6338), 55% of participants were classified as normoglycaemic (reference), 35% as pre-DM, 7% as DM and 4% as newly diagnosed DM. Compared with the reference group, diagnosed and newly diagnosed DMs were associated with a slightly higher trend in eGFR {+2.1 mL/min/1.73 m2 [95% confidence interval (CI) -0.2-4.4] and +2.7 mL/min/1.73 m2 [95% CI -0.3-5.7], respectively}. A 1% higher HbA1c was associated with increased odds of hyperfiltration [odds ratio (OR) 1.41 (95% CI 1.06-1.88)]. Higher levels of fasting plasma glucose, AUC glucose and HOMA-B were associated with hyperfiltration. Fasting insulin, AUC insulin and HOMA-IR were not associated with hyperfiltration. The OR of microalbuminuria was 1.21 (95% CI 1.04-1.42) per mmol/L higher fasting glucose concentrations. CONCLUSIONS Both fasting and post-prandial glucose and HOMA-B, but not measures of insulin resistance, were associated with glomerular hyperfiltration, while fasting glucose was also associated with microalbuminuria.
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Affiliation(s)
- Marielle A Schroijen
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
| | - Renée de Mutsert
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Friedo W Dekker
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Aiko P J de Vries
- Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
| | - Eelco J P de Koning
- Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
| | - Ton J Rabelink
- Department of Internal Medicine, Division of Nephrology, Leiden University Medical Center, Leiden, The Netherlands
| | - Frits R Rosendaal
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
| | - Olaf M Dekkers
- Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
- Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
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11
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Baranowska-Jurkun A, Matuszewski W, Bandurska-Stankiewicz E. Chronic Microvascular Complications in Prediabetic States-An Overview. J Clin Med 2020; 9:E3289. [PMID: 33066307 PMCID: PMC7602111 DOI: 10.3390/jcm9103289] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 09/01/2020] [Accepted: 09/08/2020] [Indexed: 12/12/2022] Open
Abstract
A prediabetic state is a major risk factor for the development of diabetes, and, because of an identical pathophysiological background of both conditions, their prevalence increases parallelly and equally fast. Long-term hyperglycemia is the main cause inducing chronic complications of diabetes, yet the range of glucose levels at which they start has not been yet unequivocally determined. The current data show that chronic microvascular complications of diabetes can be observed in patients with abnormal glucose metabolism in whom glycaemia is higher than optimal but below diagnostic criteria for diabetes. Prediabetes is a heterogenous nosological unit in which particular types are differently characterized and show different correlations with particular kinds of complications. Analysis of the latest research results shows the need to continue studies in a larger population and can imply the need to verify the currently employed criteria of diagnosing diabetes and chronic complications of diabetes in people with prediabetes.
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Affiliation(s)
- Angelika Baranowska-Jurkun
- Clinic of Endocrinology, Diabetology and Internal Medicine, Department of Internal Medicine, School of Medicine, Collegium Medicum, University of Warmia and Mazury, Żołnierska 18, 10-561 Olsztyn, Poland; (W.M.); (E.B.-S.)
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12
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Zilliox LA, Russell JW. Is there cardiac autonomic neuropathy in prediabetes? Auton Neurosci 2020; 229:102722. [PMID: 33011523 DOI: 10.1016/j.autneu.2020.102722] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2019] [Revised: 06/09/2020] [Accepted: 08/24/2020] [Indexed: 02/09/2023]
Abstract
Although there is considerably more data showing an association between type 2 diabetes mellitus (T2DM) and autonomic neuropathy, accumulating evidence indicates that cardiovascular autonomic neuropathy (CAN) is common in persons with impaired glucose tolerance (IGT). Furthermore, CAN may occur early after a metabolic insult and obesity, especially among mean, and seems to play an important role in the early pathogenesis of CAN. Autonomic symptoms are common in subjects with IGT. In addition to defects in CAN, in subjects with IGT, there is impaired sudomotor function and abnormalities of endothelial peripheral vasoreactivity. At the present time, the only interventions that may be effective in preventing or reversing IGT associated autonomic neuropathy are lifestyle improvement. These include a tailored diet and exercise program. Other approaches that may be beneficial include modulation of oxidative stress and improvement of metabolic regulation in subjects with IGT. Interventions are most likely to be effective early in the course of disease and therefore it is extremely important to have early diagnosis of IGT and autonomic neuropathy.
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Affiliation(s)
- Lindsay A Zilliox
- Department of Neurology, University of Maryland and Maryland VA Healthcare System, Baltimore, MD, United States of America
| | - James W Russell
- Department of Neurology, University of Maryland and Maryland VA Healthcare System, Baltimore, MD, United States of America.
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13
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Coopmans C, Zhou TL, Henry RMA, Heijman J, Schaper NC, Koster A, Schram MT, van der Kallen CJH, Wesselius A, den Engelsman RJA, Crijns HJGM, Stehouwer CDA. Both Prediabetes and Type 2 Diabetes Are Associated With Lower Heart Rate Variability: The Maastricht Study. Diabetes Care 2020; 43:1126-1133. [PMID: 32161051 DOI: 10.2337/dc19-2367] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 02/22/2020] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Low heart rate variability (HRV), a marker for cardiac autonomic dysfunction, is a known feature of type 2 diabetes, but it remains incompletely understood whether this also applies to prediabetes or across the whole glycemic spectrum. Therefore, we investigated the association among prediabetes, type 2 diabetes, and measures of glycemia and HRV. RESEARCH DESIGN AND METHODS In the population-based Maastricht Study (n = 2,107; mean ± SD age 59 ± 8 years; 52% men; normal glucose metabolism [n = 1,226], prediabetes [n = 331], and type 2 diabetes [n = 550, oversampled]), we determined 24-h electrocardiogram-derived HRV in time and frequency domains (individual z-scores, based upon seven and six variables, respectively). We used linear regression with adjustments for age, sex, and major cardiovascular risk factors. RESULTS After adjustments, both time and frequency domain HRV were lower in prediabetes and type 2 diabetes as compared with normal glucose metabolism (standardized β [95% CI] for time domain: -0.15 [-0.27; -0.03] and -0.34 [-0.46; -0.22], respectively, P for trend <0.001; for frequency domain: -0.14 [-0.26; -0.02] and -0.31 [-0.43; -0.19], respectively, P for trend <0.001). In addition, 1-SD higher glycated hemoglobin, fasting plasma glucose, and 2-h postload glucose were associated with lower HRV in both domains (time domain: -0.16 [-0.21; -0.12], -0.16 [-0.21; -0.12], and -0.15 [-0.20; -0.10], respectively; frequency domain: -0.14 [-0.19; -0.10], -0.14 [-0.18; -0.09], and -0.13 [-0.18; -0.08], respectively). CONCLUSIONS Both prediabetes and type 2 diabetes were independently associated with lower HRV. This is further substantiated by independent continuous associations between measures of hyperglycemia and lower HRV. These data strongly suggest that cardiac autonomic dysfunction is already present in prediabetes.
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Affiliation(s)
- Charlotte Coopmans
- CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.,Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Tan Lai Zhou
- CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.,Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Ronald M A Henry
- CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.,Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands.,Heart+Vascular Center, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Jordi Heijman
- CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.,Department of Cardiology, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Nicolaas C Schaper
- CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.,Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands.,Care and Public Health Research Institute School for Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands
| | - Annemarie Koster
- Care and Public Health Research Institute School for Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands.,Department of Social Medicine, Maastricht University, Maastricht, the Netherlands
| | - Miranda T Schram
- CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.,Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands.,Heart+Vascular Center, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Carla J H van der Kallen
- CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.,Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Anke Wesselius
- Department of Complex Genetics, Maastricht University, Maastricht, the Netherlands
| | | | - Harry J G M Crijns
- CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.,Department of Cardiology, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Coen D A Stehouwer
- CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands .,Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands
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14
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Kück JL, Bönhof GJ, Strom A, Zaharia OP, Müssig K, Szendroedi J, Roden M, Ziegler D. Impairment in Baroreflex Sensitivity in Recent-Onset Type 2 Diabetes Without Progression Over 5 Years. Diabetes 2020; 69:1011-1019. [PMID: 32086289 DOI: 10.2337/db19-0990] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Accepted: 02/10/2020] [Indexed: 11/13/2022]
Abstract
Impaired baroreflex sensitivity (BRS) predicts cardiovascular mortality and is prevalent in long-term diabetes. We determined spontaneous BRS in patients with recent-onset diabetes and its temporal sequence over 5 years by recording beat-to-beat blood pressure and R-R intervals over 10 min. Four time domain and four frequency domain BRS indices were computed in participants from the German Diabetes Study baseline cohort with recent-onset type 1/type 2 diabetes (n = 206/381) and age-matched glucose-tolerant control subjects (control 1/control 2: n = 65/83) and subsets of consecutive participants with type 1/type 2 diabetes who reached the 5-year follow-up (n = 84/137). Insulin sensitivity (M-value) was determined using a hyperinsulinemic-euglycemic clamp. After appropriate adjustment, three frequency domain BRS indices were reduced in type 2 diabetes compared with control 2 and were positively associated with the M-value and inversely associated with fasting glucose and HbA1c (P < 0.05), whereas BRS was preserved in type 1 diabetes. After 5 years, a decrease in one and four BRS indices was observed in patients with type 1 and type 2 diabetes, respectively (P < 0.05), which was explained by the physiologic age-dependent decline. Unlike patients with well-controlled recent-onset type 1 diabetes, those with type 2 diabetes show early baroreflex dysfunction, likely due to insulin resistance and hyperglycemia, albeit without progression over 5 years.
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Affiliation(s)
- Jana-Luise Kück
- Institute for Clinical Diabetology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
| | - Gidon J Bönhof
- Institute for Clinical Diabetology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
| | - Alexander Strom
- Institute for Clinical Diabetology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Oana-Patricia Zaharia
- Institute for Clinical Diabetology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Karsten Müssig
- Institute for Clinical Diabetology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
| | - Julia Szendroedi
- Institute for Clinical Diabetology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
| | - Michael Roden
- Institute for Clinical Diabetology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
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15
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Williams SM, Eleftheriadou A, Alam U, Cuthbertson DJ, Wilding JPH. Cardiac Autonomic Neuropathy in Obesity, the Metabolic Syndrome and Prediabetes: A Narrative Review. Diabetes Ther 2019; 10:1995-2021. [PMID: 31552598 PMCID: PMC6848658 DOI: 10.1007/s13300-019-00693-0] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Indexed: 12/19/2022] Open
Abstract
Cardiac autonomic neuropathy (CAN) is a major complication of type 1 and type 2 diabetes mellitus (T1DM and T2DM). The increased morbidity, cardiovascular and all-cause mortality associated with CAN is established from numerous epidemiological studies. However, CAN is increasingly recognised in people with prediabetes (pre-DM) and the metabolic syndrome (MetS) with a reported prevalence up to 11% and 24% respectively. CAN is associated with components of MetS including hypertension and obesity, predating hyperglycaemia. The aetiology of CAN is multifactorial and there is a reciprocal relationship with insulin resistance and MetS. Obstructive sleep apnoea (OSA) is also associated with CAN possibly through MetS and an independent mechanism. An estimated global prevalence of the impaired glucose tolerance (IGT) form of pre-DM of 587 million people by 2045 means CAN will become a major clinical problem. CAN is independently associated with silent myocardial ischaemia, major cardiovascular events, myocardial dysfunction and cardiovascular mortality. Screening for CAN in pre-DM using risk scores with analysis of heart rate variability (HRV) or Sudoscan is important to allow earlier treatment at a reversible stage. The link between obesity and CAN highlights the therapeutic potential of lifestyle interventions including diet and physical activity to reverse MetS and prevent CAN. Weight loss achieved using these dietary and exercise lifestyle interventions improves the sympathetic and parasympathetic HRV indices of cardiac autonomic function. Further research is needed to identify high-risk populations of people with pre-DM or obesity that might benefit from targeted pharmacotherapy including metformin, sodium/glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) analogues. Bariatric surgery also improves HRV through weight loss which might also prevent CAN in severe obesity. This article reviews the literature on CAN in obesity, pre-DM and MetS, to help determine a rationale for screening, early intervention treatment and formulate future research questions in this highly prevalent condition.
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Affiliation(s)
| | | | - Uazman Alam
- Diabetes and Neuropathy Research, Department of Eye and Vision Sciences and Pain Research Institute, Institute of Ageing and Chronic Disease, University of Liverpool and Aintree University Hospital NHS Foundation Trust, Liverpool, UK
- Royal Liverpool and Broadgreen University NHS Hospital Trust, Liverpool, UK
- Division of Endocrinology, Diabetes and Gastroenterology, University of Manchester, Manchester, UK
| | - Daniel J Cuthbertson
- Obesity and Endocrinology Research, Institute of Ageing and Chronic Disease, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK
| | - John P H Wilding
- Obesity and Endocrinology Research, Institute of Ageing and Chronic Disease, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, UK
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16
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Sakamoto M, Matsutani D, Kayama Y. Clinical Implications of Baroreflex Sensitivity in Type 2 Diabetes. Int Heart J 2019; 60:241-246. [PMID: 30799384 DOI: 10.1536/ihj.18-455] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
The evaluation of baroreflex sensitivity (BRS), which maintains systemic circulatory homeostasis, is an established tool to assess cardiovascular autonomic neuropathy in type 2 diabetes mellitus (T2DM). As BRS plays an important function in blood pressure regulation, reduced BRS leads to an increase in blood pressure variability, which further leads to reduced BRS. This sequence of events becomes a vicious cycle. The major risk factors for reduced BRS are T2DM and essential hypertension, but many other risk factors have been reported to influence BRS. In recent years, reports have indicated that glycemic variability (GV), such as short- and long-term GV that are considered important risk factors for macrovascular and microvascular complications, is involved in reductions in BRS independently of blood glucose levels. In this review, we discuss reduced BRS in T2DM, its features, and the potential for its reversal.
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Affiliation(s)
- Masaya Sakamoto
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine
| | - Daisuke Matsutani
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine
| | - Yosuke Kayama
- Department of Cardiology, Jikei University School of Medicine
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17
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Spallone V. Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet. Diabetes Metab J 2019; 43:3-30. [PMID: 30793549 PMCID: PMC6387879 DOI: 10.4093/dmj.2018.0259] [Citation(s) in RCA: 170] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Accepted: 02/01/2019] [Indexed: 12/15/2022] Open
Abstract
The burden of diabetic cardiovascular autonomic neuropathy (CAN) is expected to increase due to the diabetes epidemic and its early and widespread appearance. CAN has a definite prognostic role for mortality and cardiovascular morbidity. Putative mechanisms for this are tachycardia, QT interval prolongation, orthostatic hypotension, reverse dipping, and impaired heart rate variability, while emerging mechanisms like inflammation support the pervasiveness of autonomic dysfunction. Efforts to overcome CAN under-diagnosis are on the table: by promoting screening for symptoms and signs; by simplifying cardiovascular reflex tests; and by selecting the candidates for screening. CAN assessment allows for treatment of its manifestations, cardiovascular risk stratification, and tailoring therapeutic targets. Risk factors for CAN are mainly glycaemic control in type 1 diabetes mellitus (T1DM) and, in addition, hypertension, dyslipidaemia, and obesity in type 2 diabetes mellitus (T2DM), while preliminary data regard glycaemic variability, vitamin B12 and D changes, oxidative stress, inflammation, and genetic biomarkers. Glycaemic control prevents CAN in T1DM, whereas multifactorial intervention might be effective in T2DM. Lifestyle intervention improves autonomic function mostly in pre-diabetes. While there is no conclusive evidence for a disease-modifying therapy, treatment of CAN manifestations is available. The modulation of autonomic function by SGLT2i represents a promising research field with possible clinical relevance.
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Affiliation(s)
- Vincenza Spallone
- Division of Endocrinology, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.
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18
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Londero TM, Giaretta LS, Farenzena LP, Manfro RC, Canani LH, Lavinsky D, Leitão CB, Bauer AC. Microvascular Complications of Posttransplant Diabetes Mellitus in Kidney Transplant Recipients: A Longitudinal Study. J Clin Endocrinol Metab 2019; 104:557-567. [PMID: 30289492 DOI: 10.1210/jc.2018-01521] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 10/01/2018] [Indexed: 12/26/2022]
Abstract
OBJECTIVE To assesses microvascular complications in renal transplant recipients with posttransplant diabetes mellitus (PTDM). RESEARCH DESIGN AND METHODS In this observational study, patients with ≥5 years of PTDM were included from a cohort of 895 kidney recipients transplanted from 2000 through 2011. Diabetic retinopathy was evaluated by fundus photographs and optical coherence tomography (OCT). Diabetes kidney disease was evaluated by protein to creatinine ratio (PCR) and estimated glomerular filtration rate (eGFR). Distal polyneuropathy was assessed by Michigan Protocol and 10 g-monofilament feet examinations. The Ewing protocol identified cardiovascular autonomic neuropathy. Renal transplant recipients without PTDM diagnosis (NPTDM) were considered controls. RESULTS After 144.5 months of follow-up, 135 (15%) patients developed PTDM, and 64 had a PTDM duration ≥5 years. None of the patients with PTDM presented diabetic retinopathy at fundus photographs, but thinning of inner retinal layers was observed with OCT. More than 60% of patients with PTDM had distal polyneuropathy (OR, 1.55; 95% CI, 1.26 to 1.91; P < 0.001). Cardiovascular reflex tests abnormalities were similar between patients with PTDM and NPTDM (P = 0.26). During the first year and 8.5 ± 3.0 years after renal transplantation, eGFR and PCR did not differ significantly between patients with PTDM or NPTDM. CONCLUSIONS This longitudinal study assesses microvascular complications in renal transplant patients with PTDM. A lower than expected prevalence as well as a different clinical course of the complications was observed. PTDM seems to be a unique type of diabetes, and its consequences may be milder than expected in type 1 and type 2 diabetes.
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Affiliation(s)
- Thizá Massaia Londero
- Post-Graduate Program in Medical Sciences, Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
| | - Luana Seminotti Giaretta
- Endocrinology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Luisa Penso Farenzena
- Endocrinology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Roberto Ceratti Manfro
- Nephrology Division, Hospital de Clínicas de Porto Alegre, Port Alegre, Rio Grande do Sul, Brazil
| | - Luis Henrique Canani
- Post-Graduate Program in Medical Sciences, Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Endocrinology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Daniel Lavinsky
- Post-Graduate Program in Medical Sciences, Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Ophthalmology Division, Hospital de Clínicas de Porto Alegre, Port Alegre, Rio Grande do Sul, Brazil
| | - Cristiane Bauermann Leitão
- Post-Graduate Program in Medical Sciences, Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Endocrinology Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil
| | - Andrea Carla Bauer
- Post-Graduate Program in Medical Sciences, Endocrinology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
- Nephrology Division, Hospital de Clínicas de Porto Alegre, Port Alegre, Rio Grande do Sul, Brazil
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19
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Yang X, Lin Q, Li X, Wu L, Xu W, Zhu Y, Deng H, Zhang Y, Yao B. Cystatin C Is an Important Biomarker for Cardiovascular Autonomic Dysfunction in Chinese Type 2 Diabetic Patients. J Diabetes Res 2019; 2019:1706964. [PMID: 31011584 PMCID: PMC6442484 DOI: 10.1155/2019/1706964] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 01/25/2019] [Accepted: 02/06/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Cardiovascular autonomic dysfunction is closely related to increased mortality in patients with diabetes. Previous studies have proved that cystatin C (CysC) is an important predictor of both peripheral neuropathy and cardiovascular events. However, whether CysC is also associated with cardiovascular autonomic dysfunction remains unclear. Therefore, the aim of this study was to investigate the relationship between CysC and cardiovascular autonomic dysfunction in type 2 diabetic patients without renal dysfunction. METHODS A total of 161 type 2 diabetic patients with normal serum creatinine (less than 133 μmol/l) and estimated glomerular filtration rate (eGFR) higher than 60 ml/min per 1.73 m2 were recruited in our study. Cardiovascular autonomic dysfunction was determined by heart rate variability (HRV) measured by a 24-hour Holter monitor. Serum CysC was tested by particle-enhanced turbidimetric immunoassay, and subjects were divided into three groups based on the tertiles of CysC. Pearson correlation analysis was used to evaluate the association between different indexes, and the association of CysC with HRV indexes was assessed by multivariate linear regression analysis. RESULTS The HRV parameters were lower in the group with the highest CysC concentration than in the groups with lower levels of CysC (P < 0.05). Pearson correlation analysis showed a negative relationship between CysC and the HRV parameters, including SDNN (r = -0.31, P < 0.001), SDANN (r = -0.25, P = 0.002), and logLF (r = -0.18, P = 0.023). Furthermore, multivariate linear regression analysis revealed that CysC was independently correlated with SDNN (β = -24.11, P = 0.015) and SDANN (β = -19.88, P = 0.047) after adjusting for the confounding factors of gender, age, blood pressure, body mass index, eGFR, and hemoglobin A1c. CONCLUSIONS Serum CysC levels are associated with cardiovascular autonomic dysfunction; furthermore, CysC may be a reliable and convenient biomarker for detecting cardiovascular autonomic dysfunction.
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Affiliation(s)
- Xubin Yang
- Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, Guangdong 510630, China
| | - Qiongyan Lin
- Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, Guangdong 510630, China
| | - Xiaoshan Li
- Department of Ultrasonography, Traditional Chinese Medicine Hospital of Yuexiu District, Guangzhou, Guangdong, China
| | - Lin Wu
- Department of Cardiovasology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, Guangdong 510630, China
| | - Wen Xu
- Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, Guangdong 510630, China
| | - Yanhua Zhu
- Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, Guangdong 510630, China
| | - Hongrong Deng
- Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, Guangdong 510630, China
| | - Yao Zhang
- Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, Guangdong 510630, China
| | - Bin Yao
- Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, Guangdong 510630, China
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20
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Visit-to-visit HbA1c variability is inversely related to baroreflex sensitivity independently of HbA1c value in type 2 diabetes. Cardiovasc Diabetol 2018; 17:100. [PMID: 29991356 PMCID: PMC6038306 DOI: 10.1186/s12933-018-0743-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2018] [Accepted: 07/04/2018] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND The relationship between long-term glycemic variability (GV) represented by visit-to-visit HbA1c variability and baroreflex sensitivity (BRS) in type 2 diabetes mellitus (T2DM) has not been clarified by previous literature. The present study is the first to examine the relationships between visit-to-visit HbA1c variability and BRS. METHODS This retrospective study initially analyzed data on 94 patients with T2DM. Visit-to-visit HbA1c variability was evaluated using the intrapersonal coefficient of variation (CV), standard deviation (SD), and adjusted SD of 8 or more serial measurements of HbA1c during a 2-year period. The BRS was analyzed using the sequence method. Short-term GV was assessed by measuring the glucose CV during 24-h continuous glucose monitoring (CGM). The primary objective was to determine if there was a relationship between visit-to-visit HbA1c variability (HbA1c CV) and BRS. Secondary objectives were to examine the relationship between other variables and BRS and the respective and combined effects of long-term GV (HbA1c CV) and short-term GV (CGM CV) on BRS. RESULTS A total of 57 patients (mean age 67.2 ± 7.7 years, mean HbA1c 7.3 ± 1.0%) who met this study's inclusion criteria were finally analyzed. In the univariate analysis, HbA1c CV (r = - 0.354, p = 0.007), HbA1c SD (r = - 0.384, p = 0.003), and adjusted HbA1c SD (r = - 0.391, p = 0.003) were significantly related to low levels of BRS. Multiple regression analysis showed that HbA1c CV, HbA1c SD, and adjusted HbA1c SD were inversely related to BRS. Furthermore, although the increase in either long-term GV (HbA1c CV) or short-term GV (CGM CV) as determined by 24-h CGM was inversely correlated with BRS, additional reductions in BRS were not shown in participants with both HbA1c CV and CGM CV values above the median. CONCLUSIONS Visit-to-visit HbA1c variability was inversely related to BRS independently of the mean HbA1c in patients with T2DM. Therefore, visit-to-visit HbA1c variability might be a marker of reduced BRS in T2DM.
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Matsutani D, Sakamoto M, Iuchi H, Minato S, Suzuki H, Kayama Y, Takeda N, Horiuchi R, Utsunomiya K. Glycemic variability in continuous glucose monitoring is inversely associated with baroreflex sensitivity in type 2 diabetes: a preliminary report. Cardiovasc Diabetol 2018. [PMID: 29514695 PMCID: PMC5840775 DOI: 10.1186/s12933-018-0683-2] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background It is presently unclear whether glycemic variability (GV) is associated with baroreflex sensitivity (BRS), which is an early indicator of cardiovascular autonomic neuropathy. The present study is the first to examine the relationships between BRS and GV measured using continuous glucose monitoring (CGM). Methods This was a multicenter, prospective, open-label clinical trial. A total of 102 patients with type 2 diabetes were consecutively recruited for this study. GV was assessed by measuring the standard deviation (SD), glucose coefficient of variation (CV), and the mean amplitude of glycemic excursions (MAGE) during CGM. The BRS was analyzed from electrocardiogram and blood pressure recordings using the sequence method on the first day of hospitalization. Results A total of 94 patients (mean diabetes duration 9.7 ± 9.6 years, mean HbA1c 61.0 ± 16.8 mmol/mol [7.7 ± 1.5%]) were analyzed. In the univariate analysis, CGM-SD (r = − 0.375, p = 0.000), CGM-CV (r = − 0.386, p = 0.000), and MAGE (r = − 0.395, p = 0.000) were inversely related to BRS. In addition to GV, the level of BRS correlated with the coefficient of variation in the R–R intervals (CVR-R) (r = 0.520, p = 0.000), heart rate (HR) (r = − 0.310, p = 0.002), cardio-ankle vascular index (CAVI) (r = − 0.326, p = 0.001), age (r = − 0.519, p = 0.000), and estimated glomerular filtration rate (eGFR) (r = 0.276, p = 0.007). Multiple regression analysis showed that CGM-CV and MAGE were significantly related to a decrease in BRS. These findings remained after adjusting the BRS for age, sex, hypertension, dyslipidemia, HR, eGFR, CAVI, and CGM-mean glucose. Additionally, BRS was divided according to quartiles of the duration of diabetes (Q1–4). BRS decreased after a 2-year duration of diabetes independently of age and sex. Conclusions GV was inversely related to BRS independently of blood glucose levels in type 2 diabetic patients. Measurement of BRS may have the potential to predict CV events in consideration of GV. Trial registration UMIN Clinical Trials Registry UMIN000025964, 28/02/2017 Electronic supplementary material The online version of this article (10.1186/s12933-018-0683-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Daisuke Matsutani
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Masaya Sakamoto
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
| | - Hiroyuki Iuchi
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Souichirou Minato
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Hirofumi Suzuki
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Yosuke Kayama
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Norihiko Takeda
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Ryuzo Horiuchi
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Kazunori Utsunomiya
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, 3-25-8, Nishi-Shinbashi, Minato-ku, Tokyo, 105-8461, Japan
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22
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Sensory and autonomic function and structure in footpads of a diabetic mouse model. Sci Rep 2017; 7:41401. [PMID: 28128284 PMCID: PMC5269750 DOI: 10.1038/srep41401] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Accepted: 12/19/2016] [Indexed: 12/12/2022] Open
Abstract
Sensory and autonomic neuropathy affects the majority of type II diabetic patients. Clinically, autonomic evaluation often focuses on sudomotor function yet this is rarely assessed in animal models. We undertook morphological and functional studies to assess large myelinated and small unmyelinated axons in the db/db type II diabetes mouse model. We observed that autonomic innervation of sweat glands in the footpads was significantly reduced in db/db mice compared to control db/+ mice and this deficit was greater compared to reductions in intraepidermal sensory innervation of adjacent epidermis. Additionally, db/db mice formed significantly fewer sweat droplets compared to controls as early as 6 weeks of age, a time when no statistical differences were observed electrophysiologically between db/db and db/+ mice studies of large myelinated sensory and motor nerves. The rate of sweat droplet formation was significantly slower and the sweat droplet size larger and more variable in db/db mice compared to controls. Whereas pilocarpine and glycopyrrolate increased and decreased sweating, respectively, in 6 month-old controls, db/db mice did not respond to pharmacologic manipulations. Our findings indicate autonomic neuropathy is an early and prominent deficit in the db/db model and have implications for the development of therapies for peripheral diabetic neuropathy.
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Straznicky NE, Grima MT, Sari CI, Lambert EA, Phillips SE, Eikelis N, Mariani JA, Kobayashi D, Hering D, Dixon JB, Lambert GW. Comparable Attenuation of Sympathetic Nervous System Activity in Obese Subjects with Normal Glucose Tolerance, Impaired Glucose Tolerance, and Treatment Naïve Type 2 Diabetes following Equivalent Weight Loss. Front Physiol 2016; 7:516. [PMID: 27857694 PMCID: PMC5093133 DOI: 10.3389/fphys.2016.00516] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2016] [Accepted: 10/19/2016] [Indexed: 11/30/2022] Open
Abstract
Background and Purpose: Elevated sympathetic nervous system (SNS) activity is a characteristic of obesity and type 2 diabetes (T2D) that contributes to target organ damage and cardiovascular risk. In this study we examined whether baseline metabolic status influences the degree of sympathoinhibition attained following equivalent dietary weight loss. Methods: Un-medicated obese individuals categorized as normal glucose tolerant (NGT, n = 15), impaired glucose tolerant (IGT, n = 24), and newly-diagnosed T2D (n = 15) consumed a hypocaloric diet (29% fat, 23% protein, 45% carbohydrate) for 4-months. The three groups were matched for baseline age (56 ± 1 years), body mass index (BMI, 32.9 ± 0.7 kg/m2), and gender. Clinical measurements included whole-body norepinephrine kinetics, muscle sympathetic nerve activity (MSNA, by microneurography), spontaneous cardiac baroreflex sensitivity (BRS), and oral glucose tolerance test. Results: Weight loss averaged −7.5 ± 0.8, −8.1 ± 0.5, and −8.0 ± 0.9% of body weight in NGT, IGT, and T2D groups, respectively. T2D subjects had significantly greater reductions in fasting glucose, 2-h glucose and glucose area under the curve (AUC0−120) compared to NGT and IGT (group effect, P <0.001). Insulinogenic index decreased in IGT and NGT groups and increased in T2D (group × time, P = 0.04). The magnitude of reduction in MSNA (−7 ± 3, −8 ± 4, −15 ± 4 burst/100 hb, respectively) and whole-body norepinephrine spillover rate (−28 ± 8, −18 ± 6, and −25 ± 7%, respectively), time effect both P <0.001, did not differ between groups. After adjustment for age and change in body weight, Δ insulin AUC0−120 was independently associated with reduction in arterial norepinephrine concentration, whilst Δ LDL-cholesterol and improvement in BRS were independently associated with decrease in MSNA. Conclusions: Equivalent weight loss through hypocaloric diet is accompanied by similar sympathoinhibition in matched obese subjects with different baseline glucose tolerance. Attenuation of hyperinsulinemia and hyperlipidemia, rather than glycemic indices, is associated with reduction in SNS activity following weight loss intervention.
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Affiliation(s)
- Nora E Straznicky
- Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute Melbourne, VIC, Australia
| | - Mariee T Grima
- Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute Melbourne, VIC, Australia
| | - Carolina I Sari
- Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute Melbourne, VIC, Australia
| | - Elisabeth A Lambert
- Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes InstituteMelbourne, VIC, Australia; Department of Physiology, Monash UniversityMelbourne, VIC, Australia; Department of Physiology, University of MelbourneMelbourne, VIC, Australia
| | - Sarah E Phillips
- Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute Melbourne, VIC, Australia
| | - Nina Eikelis
- Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute Melbourne, VIC, Australia
| | - Justin A Mariani
- Heart Failure Research Group, Baker IDI Heart and Diabetes InstituteMelbourne, VIC, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash UniversityMelbourne, VIC, Australia
| | - Daisuke Kobayashi
- Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute Melbourne, VIC, Australia
| | - Dagmara Hering
- Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes Institute Melbourne, VIC, Australia
| | - John B Dixon
- Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes InstituteMelbourne, VIC, Australia; Department of Primary Health Care, Monash UniversityMelbourne, VIC, Australia
| | - Gavin W Lambert
- Human Neurotransmitters Laboratory, Baker IDI Heart and Diabetes InstituteMelbourne, VIC, Australia; Faculty of Medicine, Nursing and Health Sciences, Monash UniversityMelbourne, VIC, Australia
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Keerthi GS, Pal P, Pal GK, Sahoo JP, Sridhar MG, Balachander J. Attenuated baroreflex sensitivity in normotensive prediabetes and diabetes in Indian adults. Endocr Res 2016; 41:89-97. [PMID: 26513377 DOI: 10.3109/07435800.2015.1076454] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
PURPOSE/AIM OF THE STUDY Though attenuated baroreflex sensitivity (BRS) is known to promote cardiovascular disease (CVD) risk in diabetics, its status in prediabetes has not been reported. Also, the link of BRS to CVD risk in normotensive diabetics has not been reported. This study aimed to evaluate the association of BRS to CVD risk in normotensive prediabetics and diabetics. MATERIALS AND METHODS Participants (n = 154) of 18-45 years were divided into normoglycemics (n = 52), prediabetics (n = 64) and diabetics (n = 38) based on American Diabetes Association criteria. Body mass index, waist-hip ratio, waist-height ratio, body fat mass index, basal heart rate, systolic blood pressure, diastolic blood pressure, rate pressure product, BRS, heart rate variability (HRV), fasting plasma glucose, fasting insulin, lipid profile and atherogenic index of plasma (AIP) were measured. Indian Diabetes Risk Score (IDRS) and homeostatic model assessment of insulin resistance were calculated. RESULTS There was significant increase in all the parameters except BRS, HRV and high-density lipoprotein in prediabetics and diabetics compared to normoglycemics. All these parameters were significantly altered in prediabetics compared to diabetics. Significant negative correlation was found between BRS and other parameters in prediabetics and diabetics. CONCLUSIONS BRS was attenuated in normotensive prediabetics and diabetics with high IDRS, insulin resistance, AIP, dyslipidemia and reduced HRV that predisposes them to CVD risk. The study demonstrates CVD risk quite early in the prediabetics with reduced HRV, high body fat, hyperinsulinemia, insulin resistance, AIP and rate pressure product.
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Affiliation(s)
| | | | | | | | | | - Jayaraman Balachander
- d Department of Cardiology , Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) , Puducherry , India
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25
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Cardiac autonomic nervous dysfunction detected by both heart rate variability and heart rate turbulence in prediabetic patients with isolated impaired fasting glucose. Anatol J Cardiol 2016; 16:762-769. [PMID: 27025199 PMCID: PMC5324936 DOI: 10.14744/anatoljcardiol.2015.6654] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Objective: Cardiac autonomic nervous dysfunction (CAND), a severe complication of diabetes, has also been shown to affect prediabetic patients. The role of isolated impaired fasting plasma glucose (IFG), a subtype of prediabetes, is not clear in the pathogenesis of CAND. The aim of this study was to examine the relationship between isolated IFG and cardiac autonomic function using heart rate variability (HRV) and heart rate turbulence (HRT) indices derived from 24-h Holter–electrocardiogram recordings. Methods: This observational, prospective, cross-sectional study examined 400 consecutive subjects divided into three groups according to oral glucose tolerance test results: the control group [Group I, fasting plasma glucose (FPG) <100 mg/dL and normal glucose tolerance, n=193], the isolated IFG group (Group II, FPG ≥100 and <126 mg/dL, n=134), and the isolated impaired glucose tolerance (IGT), both IFG and IGT, or newly diagnosed diabetes’ group (Group III, n=73). Patients with non-sinus rhythm, known diabetes mellitus, coronary artery disease, heart failure, severe valvular disease, or receiving medical therapy that may affect HRV and HRT indices were excluded. Time domain HRV parameters, turbulence onset (TO), turbulence slope (TS), and HRT category were examined. Chi-square, one-way analysis of variance, Kruskal–Wallis H, and Mann–Whitney U tests were used to compare variables where appropriate. The correlation between Holter data and FPG levels was analyzed using the Spearman’s test. Multiple linear regression analysis was performed to identify independent predictors of the HRV and HRT parameters. Results: Median (interquartile range 25–75) FPG levels in Groups I, II, and III were 89 (83/93) mg/dL, 109 (104/116) mg/dL, and 174 (150.5/197) mg/dL, respectively. There were significant differences in HRV and HRT parameters between and among all groups. While HRV parameters and TS decreased from Group I to Group III, TO and HRT category gradually increased. Additionally, FPG level was significantly correlated with SDNN, r=–0.220; SDNN index, r=–0.192; SDANN, r=–0.207; RMSSD, r=–0.228; pNN50, r=–0.226; TO, r=0.354; and TS, r=–0.331 (all p<0.001). Conclusion: CAND, as detected by both HRV and HRT, appear to be present in the isolated IFG subtype of prediabetes.
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Meyer ML, Gotman NM, Soliman EZ, Whitsel EA, Arens R, Cai J, Daviglus ML, Denes P, González HM, Moreiras J, Talavera GA, Heiss G. Association of glucose homeostasis measures with heart rate variability among Hispanic/Latino adults without diabetes: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Cardiovasc Diabetol 2016; 15:45. [PMID: 26983644 PMCID: PMC4793505 DOI: 10.1186/s12933-016-0364-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2015] [Accepted: 03/09/2016] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Reduced heart rate variability (HRV), a measure of cardiac autonomic function, is associated with an increased risk of cardiovascular disease (CVD) and mortality. Glucose homeostasis measures are associated with reduced cardiac autonomic function among those with diabetes, but inconsistent associations have been reported among those without diabetes. This study aimed to examine the association of glucose homeostasis measures with cardiac autonomic function among diverse Hispanic/Latino adults without diabetes. METHODS The Hispanic community Health Study/Study of Latinos (HCHS/SOL; 2008-2011) used two-stage area probability sampling of households to enroll 16,415 self-identified Hispanics/Latinos aged 18-74 years from four USA communities. Resting, standard 12-lead electrocardiogram recordings were used to estimate the following ultrashort-term measures of HRV: RR interval (RR), standard deviation of all normal to normal RR (SDNN) and root mean square of successive differences in RR intervals (RMSSD). Multivariable regression analysis was used to estimate associations between glucose homeostasis measures with HRV using data from 11,994 adults without diabetes (mean age 39 years; 52 % women). RESULTS Higher fasting glucose was associated with lower RR, SDNN, and RMSSD. Fasting insulin and the homeostasis model assessment of insulin resistance was negatively associated with RR, SDNN, and RMSSD, and the association was stronger among men compared with women. RMSSD was, on average, 26 % lower in men with higher fasting insulin and 29 % lower in men with lower insulin resistance; for women, the corresponding estimates were smaller at 4 and 9 %, respectively. Higher glycated hemoglobin was associated with lower RR, SDNN, and RMSSD in those with abdominal adiposity, defined by sex-specific cut-points for waist circumference, after adjusting for demographics and medication use. There were no associations between glycated hemoglobin and HRV measures among those without abdominal adiposity. CONCLUSIONS Impairment in glucose homeostasis was associated with lower HRV in Hispanic/Latino adults without diabetes, most prominently in men and individuals with abdominal adiposity. These results suggest that reduced cardiac autonomic function is associated with metabolic impairments before onset of overt diabetes in certain subgroups, offering clues for the pathophysiologic processes involved as well as opportunity for identification of those at high risk before autonomic control is manifestly impaired.
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Affiliation(s)
- Michelle L. Meyer
- />University of North Carolina at Chapel Hill, 137 E. Franklin St, Suite 306, Chapel Hill, NC 27514 USA
| | - Nathan M. Gotman
- />University of North Carolina at Chapel Hill, 137 E. Franklin St, Suite 306, Chapel Hill, NC 27514 USA
| | | | - Eric A. Whitsel
- />University of North Carolina at Chapel Hill, 137 E. Franklin St, Suite 306, Chapel Hill, NC 27514 USA
| | - Raanan Arens
- />Division of Respiratory and Sleep Medicine, The Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY USA
| | - Jianwen Cai
- />University of North Carolina at Chapel Hill, 137 E. Franklin St, Suite 306, Chapel Hill, NC 27514 USA
| | - Martha L. Daviglus
- />University of Illinois at Chicago College of Medicine, Chicago, IL USA
| | | | | | | | | | - Gerardo Heiss
- />University of North Carolina at Chapel Hill, 137 E. Franklin St, Suite 306, Chapel Hill, NC 27514 USA
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Hattori Y, Hattori K, Suzuki T. Differential Modulation of Cardiac Sympathetic Neural Control and β-Adrenoceptor-G Protein Signaling Cascade in Rats With Type 1 and Type 2 Diabetes. Diabetes 2015. [PMID: 26207035 DOI: 10.2337/db15-0503] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Affiliation(s)
- Yuichi Hattori
- Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
| | - Kohshi Hattori
- Anesthesiology and Pain Relief Center, The University of Tokyo Hospital, Tokyo, Japan
| | - Tokiko Suzuki
- Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan
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Zoppini G, Cacciatori V, Raimondo D, Gemma M, Trombetta M, Dauriz M, Brangani C, Pichiri I, Negri C, Stoico V, Bergamini C, Targher G, Santi L, Thomaseth K, Bellavere F, Bonadonna RC, Bonora E. Prevalence of Cardiovascular Autonomic Neuropathy in a Cohort of Patients With Newly Diagnosed Type 2 Diabetes: The Verona Newly Diagnosed Type 2 Diabetes Study (VNDS). Diabetes Care 2015; 38:1487-93. [PMID: 26068862 DOI: 10.2337/dc15-0081] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2015] [Accepted: 05/07/2015] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Cardiovascular autonomic diabetic neuropathy (CAN) is a serious complication of diabetes. No reliable data on the prevalence of CAN among patients with newly diagnosed type 2 diabetes are available. Therefore, the aim of this study was to estimate the prevalence of CAN among patients with newly diagnosed type 2 diabetes. RESEARCH DESIGN AND METHODS A cohort of 557 patients with newly diagnosed type 2 diabetes with cardiovascular autonomic test results available was selected. Early and confirmed neuropathy were assessed using a standardized methodology and their prevalences determined. A multivariate logistic regression analysis was modeled to study the factors associated with CAN. RESULTS In the entire cohort, the prevalence of confirmed CAN was 1.8%, whereas that of early CAN was 15.3%. Prevalence did not differ between men and women. In the multivariate analyses BMI results were independently and significantly associated with CAN after adjusting for age, sex, hemoglobin A1c, pulse pressure, triglyceride-to-HDL cholesterol ratio, kidney function parameters, and antihypertensive treatment. CONCLUSIONS CAN could be detected very early in type 2 diabetes. This study may suggest the importance of performing standardized cardiovascular autonomic tests after diagnosis of type 2 diabetes.
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Affiliation(s)
- Giacomo Zoppini
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy
| | - Vittorio Cacciatori
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy
| | - Daniele Raimondo
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy
| | - Marialuisa Gemma
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy
| | - Maddalena Trombetta
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy
| | - Marco Dauriz
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy
| | - Corinna Brangani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy
| | - Isabella Pichiri
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy
| | - Carlo Negri
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy
| | - Vincenzo Stoico
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy
| | - Corinna Bergamini
- Section of Cardiology, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy
| | - Lorenza Santi
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy
| | - Karl Thomaseth
- National Research Council, Institute of Bioengineering, Padua, Italy
| | | | - Riccardo C Bonadonna
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy
| | - Enzo Bonora
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy
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Downs CA, Faulkner MS. Toxic stress, inflammation and symptomatology of chronic complications in diabetes. World J Diabetes 2015; 6:554-565. [PMID: 25987953 PMCID: PMC4434076 DOI: 10.4239/wjd.v6.i4.554] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 12/30/2014] [Accepted: 02/12/2015] [Indexed: 02/05/2023] Open
Abstract
Diabetes affects at least 382 million people worldwide and the incidence is expected to reach 592 million by 2035. The incidence of diabetes in youth is skyrocketing as evidenced by a 21% increase in type 1 diabetes and a 30.5% increase in type 2 diabetes in the United States between 2001 and 2009. The effects of toxic stress, the culmination of biological and environmental interactions, on the development of diabetes complications is gaining attention. Stress impacts the hypothalamus-pituitary-adrenal axis and contributes to inflammation, a key biological contributor to the pathogenesis of diabetes and its associated complications. This review provides an overview of common diabetic complications such as neuropathy, cognitive decline, depression, nephropathy and cardiovascular disease. The review also provides a discussion of the role of inflammation and stress in the development and progression of chronic complications of diabetes, associated symptomatology and importance of early identification of symptoms of depression, fatigue, exercise intolerance and pain.
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Ziegler D, Voss A, Rathmann W, Strom A, Perz S, Roden M, Peters A, Meisinger C. Increased prevalence of cardiac autonomic dysfunction at different degrees of glucose intolerance in the general population: the KORA S4 survey. Diabetologia 2015; 58:1118-28. [PMID: 25724570 DOI: 10.1007/s00125-015-3534-7] [Citation(s) in RCA: 70] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2014] [Accepted: 01/30/2015] [Indexed: 02/08/2023]
Abstract
AIMS/HYPOTHESIS Cardiac autonomic nervous dysfunction (CAND) raises the risk of mortality, but the glycaemic threshold at which it develops is unclear. We aimed to determine the prevalence of, risk factors for and impact of CAND in glucose intolerance and diabetes. METHODS Among 1,332 eligible participants aged 55-74 years in the population-based cross-sectional KORA S4 study, 130 had known diabetes mellitus (k-DM), and the remaining 1,202 underwent an OGTT. Heart rate variability (HRV) and QT variability were computed from supine 5 min ECGs. RESULTS In all, 565 individuals had normal glucose tolerance (NGT), 336 had isolated impaired fasting glucose (i-IFG), 72 had isolated impaired glucose tolerance (i-IGT), 151 had combined IFG-IGT (IFG-IGT) and 78 had newly detected diabetes mellitus (n-DM). Adjusted normal HRV limits were defined in the NGT population (5th and 95th percentiles). Three HRV measures were more frequently abnormal in those with k-DM, n-DM, IFG-IGT and i-IFG than in those with NGT (p < 0.05). The rates of CAND (≥2 of 4 HRV indices abnormal) were: NGT, 4.5%; i-IFG, 8.1%; i-IGT, 5.9%; IFG-IGT, 11.4%; n-DM, 11.7%; and k-DM, 17.5% (p < 0.05 vs NGT, except for i-IGT). Reduced HRV was associated with cardiovascular risk factors used to construct a simple screening score for CAND. Mortality was higher in participants with reduced HRV (p < 0.05 vs normal HRV). CONCLUSIONS/INTERPRETATION In the general population aged 55-74 years, the prevalence of CAND is increased not only in individuals with diabetes, but also in those with IFG-IGT and, to a lesser degree, in those with i-IFG. It is associated with mortality and modifiable cardiovascular risk factors which may be used to screen for diminished HRV in clinical practice.
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Affiliation(s)
- Dan Ziegler
- Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany,
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Bansal N. Prediabetes diagnosis and treatment: A review. World J Diabetes 2015; 6:296-303. [PMID: 25789110 PMCID: PMC4360422 DOI: 10.4239/wjd.v6.i2.296] [Citation(s) in RCA: 317] [Impact Index Per Article: 31.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Revised: 10/10/2014] [Accepted: 12/31/2014] [Indexed: 02/05/2023] Open
Abstract
Prediabetes is an intermediate state of hyperglycemia with glycemic parameters above normal but below the diabetes threshold. While, the diagnostic criteria of prediabetes are not uniform across various international professional organizations, it remains a state of high risk for developing diabetes with yearly conversion rate of 5%-10%. Observational evidence suggests as association between prediabetes and complications of diabetes such early nephropathy, small fiber neuropathy, early retinopathy and risk of macrovascular disease. Several studies have shown efficacy of lifestyle interventions with regards to diabetes prevention with a relative risk reduction of 40%-70% in adults with prediabetes. While there is increasing evidence to prove the efficacy of pharmacotherapy in prevention of diabetes in adults with prediabetes, pharmaceutical treatment options other than metformin are associated with adverse effects that limit their use for prediabetes. There are no reports of systematic evaluation of health outcomes related to prediabetes in children. The effects of pharmacotherapy of prediabetes on growth and pubertal development in children remains unknown. Secondary intervention with pharmacotherapy with metformin is advocated for high-risk individuals but criteria for such consideration benefit of early intervention, long term cost effectiveness of such interventions and the end point of therapy remain unclear. Pharmacotherapy must be used with caution in children with prediabetes. Prediabetes is a condition defined as having blood glucose levels above normal but below the defined threshold of diabetes. It is considered to be an at risk state, with high chances of developing diabetes. While, prediabetes is commonly an asymptomatic condition, there is always presence of prediabetes before the onset of diabetes. The elevation of blood sugar is a continuum and hence prediabetes can not be considered an entirely benign condition. This aim of this review is to describe the challenges associated with diagnosis of prediabetes, the possible adverse medical outcomes associated with prediabetes and the treatment options and rationale for their use in context of prediabetes.
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Hillebrand S, Swenne CA, Gast KB, Maan AC, le Cessie S, Jukema JW, Rosendaal FR, den Heijer M, de Mutsert R. The role of insulin resistance in the association between body fat and autonomic function. Nutr Metab Cardiovasc Dis 2015; 25:93-99. [PMID: 25171899 DOI: 10.1016/j.numecd.2014.07.009] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2013] [Revised: 07/21/2014] [Accepted: 07/22/2014] [Indexed: 10/25/2022]
Abstract
BACKGROUND AND AIM Excess body fat is associated with altered autonomic function. We investigated whether this association is mediated by insulin resistance. METHODS AND RESULTS Cross-sectional analysis of a subgroup of the Netherlands Epidemiology of Obesity study with measurements of autonomic function (heart rate variability calculated as mean interbeat interval, standard deviation of all normal intervals (SDNN), low frequency (LF) power and high frequency (HF) power). We measured BMI(kg/m²), total body fat(%) and waist circumference(cm), and calculated the HOMA-index of insulin resistance (HOMA-IR). We examined the association between body fat and heart rate variability with multivariate linear regression analysis. To investigate whether the association was mediated by insulin resistance, we additionally adjusted for HOMA-IR. After exclusion of participants with glucose lowering medication (n = 19), 466 participants were included. Per SD of BMI, the difference in SDNN was -2.7% (95%CI: -5.5, 0.1) in the multivariate model. Additional adjustment for HOMA-IR attenuated this association to -1.2% (95%CI: -4.2, 1.7), suggesting that 55% of the association between BMI and SDNN was mediated by HOMA-IR. All measures of body fat were associated with mean interbeat interval, SDNN and LF power. Depending on the parameter of body fat or heart rate variability, 29-81% of the association was mediated by HOMA-IR. CONCLUSION In this cross-sectional study, body fat was associated with heart rate variability. This association may at least partially be mediated by insulin resistance. Future studies should investigate whether a reduction in obesity and insulin resistance may prevent the adverse cardiovascular consequences of altered autonomic function.
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Affiliation(s)
- S Hillebrand
- Department of Clinical Epidemiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands.
| | - C A Swenne
- Department of Cardiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands
| | - K B Gast
- Department of Clinical Epidemiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands; Department of Internal Medicine, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands
| | - A C Maan
- Department of Cardiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands
| | - S le Cessie
- Department of Clinical Epidemiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands; Department of Medical Statistics, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands
| | - J W Jukema
- Department of Cardiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, PO Box 19258, 3501 DG Utrecht, The Netherlands
| | - F R Rosendaal
- Department of Clinical Epidemiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands; Department of Thrombosis and Hemostasis, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands
| | - M den Heijer
- Department of Clinical Epidemiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands; Department of Internal Medicine, VU Medical Centre, PO Box 7057, 1007 MB Amsterdam, The Netherlands
| | - R de Mutsert
- Department of Clinical Epidemiology, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands
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Wu JS, Lu FH, Yang YC, Chang SH, Huang YH, Chen JJJ, Chang CJ. Impaired baroreflex sensitivity in subjects with impaired glucose tolerance, but not isolated impaired fasting glucose. Acta Diabetol 2014; 51:535-41. [PMID: 24408773 DOI: 10.1007/s00592-013-0548-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2013] [Accepted: 12/13/2013] [Indexed: 01/08/2023]
Abstract
Impaired baroreflex sensitivity (BRS) is associated with adverse cardiovascular outcomes. There are currently no studies on BRS changes in subjects with different glycemic statuses, including normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and newly diagnosed diabetes (NDD). The aim of this study was to investigate the effects of NDD, IGT and isolated IFG on BRS, based on a community-based data. A total of 768 subjects were classified as NGT (n = 498), isolated IFG (n = 61), IGT (n = 126) and NDD (n = 83). Spontaneous BRS was determined by the spectral α coefficient method, i.e., the square root of the ratio between the power of the RR interval and the power of systolic blood pressure in the LF frequency region (0.04-0.15 Hz) after the subjects had rested in a supine position for 5 min. Valsalva ratio was calculated as the longest RR interval after release of the Valsalva maneuver, divided by the shortest RR interval during the maneuver. As compared with NGT subjects, NDD (p = 0.039) and IGT (p = 0.041) subjects had a reduced spontaneous BRS in multivariate analysis based on analysis of covariance. NDD subjects exhibited a lower Valsalva ratio than NGT subjects (p = 0.043). However, there were no significant differences in spontaneous BRS and Valsalva ratio between subjects with isolated IFG and NGT. In conclusion, NDD and IGT subjects had an impaired BRS as compared to NGT subjects. However, reduced BRS was not apparent in subjects with isolated IFG.
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Affiliation(s)
- Jin-Shang Wu
- Department of Family Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC
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Hillebrand S, de Mutsert R, den Heijer M, le Cessie S, Stehouwer C, Nijpels G, Dekker J. Autonomic function is not associated with the incidence of type 2 diabetes in a high-risk population: The Hoorn study. DIABETES & METABOLISM 2014; 40:128-36. [DOI: 10.1016/j.diabet.2013.10.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/09/2013] [Revised: 09/27/2013] [Accepted: 10/21/2013] [Indexed: 10/26/2022]
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Guía de práctica clínica de la ESC sobre diabetes, prediabetes y enfermedad cardiovascular, en colaboración con la European Association for the Study of Diabetes. Rev Esp Cardiol 2014. [DOI: 10.1016/j.recesp.2013.10.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Rydén L, Grant PJ, Anker SD, Berne C, Cosentino F, Danchin N, Deaton C, Escaned J, Hammes HP, Huikuri H, Marre M, Marx N, Mellbin L, Ostergren J, Patrono C, Seferovic P, Uva MS, Taskinen MR, Tendera M, Tuomilehto J, Valensi P, Zamorano JL, Zamorano JL, Achenbach S, Baumgartner H, Bax JJ, Bueno H, Dean V, Deaton C, Erol C, Fagard R, Ferrari R, Hasdai D, Hoes AW, Kirchhof P, Knuuti J, Kolh P, Lancellotti P, Linhart A, Nihoyannopoulos P, Piepoli MF, Ponikowski P, Sirnes PA, Tamargo JL, Tendera M, Torbicki A, Wijns W, Windecker S, De Backer G, Sirnes PA, Ezquerra EA, Avogaro A, Badimon L, Baranova E, Baumgartner H, Betteridge J, Ceriello A, Fagard R, Funck-Brentano C, Gulba DC, Hasdai D, Hoes AW, Kjekshus JK, Knuuti J, Kolh P, Lev E, Mueller C, Neyses L, Nilsson PM, Perk J, Ponikowski P, Reiner Z, Sattar N, Schächinger V, Scheen A, Schirmer H, Strömberg A, Sudzhaeva S, Tamargo JL, Viigimaa M, Vlachopoulos C, Xuereb RG. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J 2013; 34:3035-87. [PMID: 23996285 DOI: 10.1093/eurheartj/eht108] [Citation(s) in RCA: 1429] [Impact Index Per Article: 119.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Affiliation(s)
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- The disclosure forms of the authors and reviewers are available on the ESC website www.escardio.org/guidelines
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Tannus LRM, Sperandei S, Montenegro Júnior RM, Carvalho VR, Pedrosa HC, Félix MT, Canani L, Zucatti ATN, de Oliveira DHA, Rea RR, Gomes MDB. Reproducibility of methods used for the assessment of autonomous nervous system's function. Auton Neurosci 2013; 177:275-9. [PMID: 23770193 DOI: 10.1016/j.autneu.2013.05.444] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2013] [Revised: 05/21/2013] [Accepted: 05/28/2013] [Indexed: 11/19/2022]
Abstract
OBJECTIVE The objective of this study is to investigate the influence of the day-to-day variability of the measures of heart rate variability (HRV) on the sample size calculation for the study of cardiac autonomic neuropathy. MATERIAL AND METHODS We analyzed HRV in the frequency domain [very low (VLF), low (LF), and high frequency (HF) bands] and in the time domain [the root mean squared of successive RR intervals differences (RMSSD); the mean RR intervals (RRNN); the standard deviation of RR intervals (SDNN) and the coefficient of variation (CV)] during a 5-min electrocardiogram record. We also analyzed the heart rate response to deep breathing [expiration:inspiration ratio], to the Valsalva maneuver and to standing [maximum:minimum ratio] and the blood pressure response to standing. The day-to-day variability was assessed by calculating the within-subject standard deviations (WSSD), limits of agreement, typical errors and the ratio of the WSSD to the mean values obtained on days 1 and 2 (WSSD/GM). RESULTS Sixty-seven healthy subjects (45 females), aged 27 (19-39) years, were recruited. The RMSSD, CV, VLF, LF, HF and blood pressure response to standing showed marked variability (WSDD/GM (%)=237.7, 455.1, 69.9, 126.5, 81.3 and 380.5, respectively), while the RRNN, SDNN, Valsalva, expiration:inspiration and maximum:minimum ratio showed less variability (WSSD/GM (%)=6.4, 24.5, 18.6, 11.0 and 14.1, respectively). The minimum differences expected to be statistically significant for the autonomic measurements were calculated. CONCLUSION Some tests that assess HRV showed adequate reproducibility. This study allows the determination of a sample size calculation for longitudinal or drug-testing studies.
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Affiliation(s)
- Lucianne R M Tannus
- Department of Medicine, Unit of Diabetes, State University of Rio de Janeiro (UERJ), Brazil.
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Grantham NM, Magliano DJ, Tanamas SK, Söderberg S, Schlaich MP, Shaw JE. Higher heart rate increases risk of diabetes among men: The Australian Diabetes Obesity and Lifestyle (AusDiab) Study. Diabet Med 2013; 30:421-7. [PMID: 23088496 DOI: 10.1111/dme.12045] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2012] [Revised: 09/03/2012] [Accepted: 10/15/2012] [Indexed: 12/01/2022]
Abstract
AIMS A very limited number of prospective studies have reported conflicting data on the relation between heart rate and diabetes risk. Our aim therefore was to determine in a large, national, population-based cohort if heart rate predicts the development of diabetes. METHODS The Australian Diabetes Obesity and Lifestyle study followed up 6537 people over 5 years. Baseline measurements included questionnaires, anthropometrics and blood and urine collection. Heart rate was recorded in beats per min (Dinamap). An oral glucose tolerance test was performed at baseline and follow-up, and diabetes was defined using World Health Organization criteria. RESULTS A total of 5817 participants were eligible for analysis, 221 of whom developed diabetes. Compared with participants with a heart rate < 60 b min(-1), those with a heart rate ≥ 80 b min(-1) were more likely to develop diabetes (odds ratio 1.89, 95% CI 1.07-3.35) over 5 years, independent of traditional risk factors. This relationship was highly significant, particularly in non-obese men (odds ratio 5.61, 95% CI 1.75-17.98), but not in their obese counterparts or in women. CONCLUSIONS Resting heart rate is associated with an increased risk of diabetes over a 5-year period, particularly among non-obese men. This suggests that sympathetic overactivity may be a contributing factor to the development of diabetes, and that resting heart rate may be useful in predicting risk of Type 2 diabetes in non-obese men.
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Affiliation(s)
- N M Grantham
- Baker IDI Heart and Diabetes Institute, Melbourne, Vic., Australia
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Putz Z, Németh N, Istenes I, Martos T, Gandhi RA, Körei AE, Hermányi Z, Szathmári M, Jermendy G, Tesfaye S, Tabák ÁG, Kempler P. Autonomic dysfunction and circadian blood pressure variations in people with impaired glucose tolerance. Diabet Med 2013; 30:358-62. [PMID: 23278478 DOI: 10.1111/dme.12111] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/18/2012] [Indexed: 12/11/2022]
Abstract
AIMS To assess circadian blood pressure variability in people with impaired glucose tolerance and a healthy control population. METHODS Seventy-five people with impaired glucose tolerance and 40 healthy volunteers (frequency matched on 10-year age bands and sex) underwent a detailed neurological assessment. Autonomic neuropathy was detected by the five standard cardiovascular autonomic tests and heart rate variability was characterized by the triangle index. Diurnal indices were assessed by 24-h ambulatory blood pressure monitoring. Systolic and diastolic diurnal indices were defined as: (mean daytime blood pressure - mean night-time blood pressure) × 100/mean daytime blood pressure. RESULTS Mean 24-h systolic and diastolic blood pressure was significantly higher in the group with impaired glucose tolerance compared with the control group [126 ± 12 (mean ± SD) vs. 117 ± 10, 75 ± 7 vs. 71 ± 6 mmHg, both P < 0.05). Systolic and diastolic diurnal indices and heart rate variability triangular index were significantly lower in people with impaired glucose tolerance compared with control subjects (9.1 ± 7.8 vs. 13.2 ± 5.4, 14.5 ± 9.7 vs. 18.4 ± 7.1 mmHg, 28.0 ± 8.4 vs. 39.5 ± 9.3, all P < 0.05). Differences in mean diastolic blood pressure, heart rate variability triangular index and the frequency of non-dippers between those with impaired glucose tolerance and control subjects seemed to be independent of BMI and the presence of cardiovascular autonomic neuropathy, as simultaneous adjustment for BMI and cardiovascular autonomic neuropathy had no major effect on the results. CONCLUSION Our data suggest that people with impaired glucose tolerance have increased diastolic blood pressure and abnormal circadian blood pressure regulation, independent of obesity and the presence of cardiovascular autonomic neuropathy.
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Affiliation(s)
- Z Putz
- 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
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Wang W, Redline S, Khoo MCK. Autonomic markers of impaired glucose metabolism: effects of sleep-disordered breathing. J Diabetes Sci Technol 2012; 6:1159-71. [PMID: 23063043 PMCID: PMC3570851 DOI: 10.1177/193229681200600521] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
BACKGROUND The association between diabetes and abnormalities in autonomic function is well-known, but it is not clear if this association can be extended to subjects with prediabetic impaired glucose metabolism (IGM). Sleep-disordered breathing (SDB), which commonly occurs in this population, is often overlooked. We sought to determine how autonomic function, monitored in an overnight sleep study setting, may be impaired in subjects with IGM and/or SDB. METHODS Polysomnograms (PSGs) selected from the Cleveland Family Study database were categorized into four groups: normal, SDB (respiratory disturbance index > 5/h), IGM, and both SDB and IGM. Impaired glucose metabolism was defined as an oral glucose tolerance test (OGTT) level > 140 mg/dl. Time-domain and frequency-domain indices of heart rate variability were used to quantify autonomic impairment. Baroreflex sensitivity determined using pulse transit time (BRS(PTT)), an indirect measure of baroreflex sensitivity based on spontaneous pulse transit time fluctuations, was used as a surrogate measure of baroreflex sensitivity. RESULTS Based on 31 PSGs from subjects (16 males, 15 females) ages 20.8-61.2 years, both SDNN and BRS(PTT) were found to be 20-25% lower in SDB and ~40% lower in IGM and SDB + IGM as compared to subjects without either condition. In analyses of continuous measures, mean standard deviation of 5 min R-R intervals (SDNN) and BRS(PTT) were found to be negatively correlated with OGTT following adjustment for age and body mass index. Oral glucose tolerance test and age were the two most significant factors for predicting SDNN and BRS(PTT). CONCLUSIONS Our analyses suggest that cardiac autonomic control is impaired in IGM, regardless of whether SDB is present. The abnormal autonomic function involves degradation of baroreflex regulation.
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Affiliation(s)
- Wenli Wang
- Department of Biomedical Engineering, University of Southern California, Los Angeles, California
| | - Susan Redline
- Department of Medicine, Harvard Medical School, Boston, Massachusetts
| | - Michael C. K. Khoo
- Department of Biomedical Engineering, University of Southern California, Los Angeles, California
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Abstract
It is now increasingly being appreciated that a substantial proportion of subjects with prediabetes may exhibit peripheral neuropathy and/or neuropathic pain. The reverse is also true, inasmuch as examining patients with idiopathic peripheral neuropathy will frequently reveal prediabetes. In the general population, the prevalence of neuropathy in prediabetes is intermediate between overt diabetes and subjects with normoglycemia. This prediabetic neuropathy is, generally, milder in comparison to diabetic neuropathy and mainly affects small fibers mediating sensory function. Hyperglycemia, microangiopathy, dyslipidemia and the metabolic syndrome have been implicated as pathogenic mechanisms. In practice, therapy of prediabetic neuropathy should be addressed towards normoglycemia and correction of cardiovascular risk factors. However, additional work is needed to establish the long-term results of this approach.
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Affiliation(s)
- Nikolaos Papanas
- Institute for Clinical Diabetology, German Diabetes Center at the Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany.
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Association between cardiac autonomic function, oxidative stress and inflammatory response in impaired fasting glucose subjects: cross-sectional study. PLoS One 2012; 7:e41889. [PMID: 22860025 PMCID: PMC3409206 DOI: 10.1371/journal.pone.0041889] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2012] [Accepted: 06/28/2012] [Indexed: 01/02/2023] Open
Abstract
Background The worldwide burden of diabetes in 2030 is projected around 552 million. Diabetes leads to higher risk for cardiovascular diseases (CVD). Altered cardiac autonomic function (CAF) measured by heart rate variability (HRV) is observed in early stages of diabetes but the relationship between impaired fasting glucose (IFG) and HRV is still debatable. The aim of the study was to evaluate the association between CAF, oxidative stress, insulin resistance (IR), and inflammatory response in IFG subjects. Subjects and Methods Cross-sectional blinded study. Volunteers recruited from health awareness camps underwent CAF and biochemical tests. Based on fasting plasma glucose (FPG) participants (n = 123) were divided into two groups, normal fasting glucose (n = 76) and IFG (n = 47). The comparison of parameters between the groups was carried out using student t test and Mann-Whitney U test for parametric and non-parametric data respectively. The correlation between the parameters was analyzed by Spearman’s rank correlation using SPSS 13.0. Results The resting cardiovagal modulation parameters, heart rate response to forced timed breathing, and orthostatic stress were reduced in IFG subjects. Fasting plasma lipid profile, coronary atherogenic lipid risk factors, IR, thiobarbituric acid reactive substance (TBARS), high sensitive C-reactive protein, and tumor necrosis factor alpha were increased and total antioxidant capacity (TAC) was decreased significantly in IFG group but no significant alteration was observed in high-density lipoprotein (HDL-c). Cardiovagal modulation parameters were negatively correlated with triglycerides, FPG, insulin, IR, TBARS, and inflammatory markers and positively with TAC. Conclusion There is a continuous interplay between the altered CAF, hyperinsulinemia, IR, oxidative stress parameters, inflammatory response, and IFG in which one factor perpetuates another leading to the progression of disease.
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Abstract
Prediabetes (intermediate hyperglycaemia) is a high-risk state for diabetes that is defined by glycaemic variables that are higher than normal, but lower than diabetes thresholds. 5-10% of people per year with prediabetes will progress to diabetes, with the same proportion converting back to normoglycaemia. Prevalence of prediabetes is increasing worldwide and experts have projected that more than 470 million people will have prediabetes by 2030. Prediabetes is associated with the simultaneous presence of insulin resistance and β-cell dysfunction-abnormalities that start before glucose changes are detectable. Observational evidence shows associations between prediabetes and early forms of nephropathy, chronic kidney disease, small fibre neuropathy, diabetic retinopathy, and increased risk of macrovascular disease. Multifactorial risk scores using non-invasive measures and blood-based metabolic traits, in addition to glycaemic values, could optimise estimation of diabetes risk. For prediabetic individuals, lifestyle modification is the cornerstone of diabetes prevention, with evidence of a 40-70% relative-risk reduction. Accumulating data also show potential benefits from pharmacotherapy.
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Affiliation(s)
- Adam G Tabák
- Department of Epidemiology and Public Health, University College London, London, UK.
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Ren L, Fang X, Wang Y, Qi G. T-wave alternans and heart rate variability: a comparison in patients with myocardial infarction with or without diabetes mellitus. Ann Noninvasive Electrocardiol 2011; 16:232-8. [PMID: 21762250 DOI: 10.1111/j.1542-474x.2011.00437.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND The aim of this study was to investigate the differences in T-wave alternans (TWA) and heart rate variability (HRV) among patients with myocardial infarction with or without diabetes mellitus and the relationship between TWA and HRV. METHODS The study population included 133 patients: 59 patients with myocardial infarction (MI) (group post-MI without diabetes); 40 myocardial infarction with diabetes (group post-MI with diabetes); and 34 controls (group control). Cardiac autonomic neuropathy assessment was made using frequency domain (low-frequency [LF] power, high-frequency [HF] power, LF/HF) and time domain (SDNN, standard deviation of the averaged normal sinus RR intervals for all 5-minute segments [SDANN]) of HRV indexes. Both TWA and HRV were measured on the Holter monitor, and TWA was calculated automatically using the time-domain modified moving average method. RESULTS TWA values differed significantly between controls (40 ± 16 μV) and group post-MI with (62 ± 17 μV, P < 0.05) or without (60 ± 15 μV, P < 0.05) diabetes. In addition, group post-MI with diabetes had lower standard deviation of all normal sinus RR intervals (SDNN), standard deviation of the averaged normal sinus RR intervals for all 5-minute segments (SDANN), and HF, indicating depressed vagus nerve activity, and higher LF/HF ratio, indicating elevated sympathetic nerve activity, than controls and group post-MI without diabetes (P < 0.05). TWA correlated with SDNN and SDANN (r = 0.29, 0.31; P < 0.001). CONCLUSIONS TWA was elevated in patients following myocardial infarction, both in those with or without diabetes. Myocardial infarction patients had a lower time domain, HF, and a higher LF/HF ratio HRV, especially in those with diabetes. The analysis of modified moving agerage (MMA)-based TWA and HRV can be a useful tool for identifying post-myocardial infarction patients at high risk of arrhythmic events.
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Affiliation(s)
- LiNa Ren
- Department of Cardiology, the First Hospital of China Medical University, Shenyang, China
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Abstract
Between 25% and 62% of patients with idiopathic peripheral neuropathy are reported to have prediabetes, and among individuals with prediabetes 11-25% are thought to have peripheral neuropathy, and 13-21% have neuropathic pain. Population-based studies suggest a gradient for the prevalence of neuropathy, being highest in patients with manifest diabetes mellitus, followed by individuals with impaired glucose tolerance then impaired fasting glucose and least in those with normoglycemia. The most sensitive test to assess glucose metabolism status is the oral glucose tolerance test. Pathogenesis involves hyperglycemia, microvascular abnormalities, dyslipidemia and the metabolic syndrome. Individuals with prediabetes have less severe neuropathy than those with manifest diabetes mellitus. Sensory modalities are more frequently affected than motor modalities, but impairment of small nerve fibers could be the earliest detectable sign. Diagnosis should rely on careful clinical examination, with emphasis on the evaluation of small fibers. An oral glucose tolerance test should be performed in patients with idiopathic neuropathy. The only treatment with any efficacy is lifestyle modification to improve control of hyperglycemia and cardiovascular risk factors, but long-term efficacy of this approach has not been established. This Review summarizes the current evidence on the association between prediabetes and neuropathy.
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Sucharita S, Bantwal G, Idiculla J, Ayyar V, Vaz M. Autonomic nervous system function in type 2 diabetes using conventional clinical autonomic tests, heart rate and blood pressure variability measures. Indian J Endocrinol Metab 2011; 15:198-203. [PMID: 21897898 PMCID: PMC3156541 DOI: 10.4103/2230-8210.83406] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND There are currently approximately 40.9 million patients with diabetes mellitus in India and this number is expected to rise to about 69.9 million by the year 2025. This high burden of diabetes is likely to be associated with an increase in associated complications. MATERIALS AND METHODS A total of 23 (15 male and 8 female) patients with type 2 diabetes of 10-15 years duration and their age and gender matched controls (n=23) were recruited. All subjects underwent detailed clinical proforma, questionnaire related to autonomic symptoms, anthropometry, peripheral neural examination and tests of autonomic nervous system including both conventional and newer methods (heart rate and blood pressure variability). RESULTS Conventional tests of cardiac parasympathetic and sympathetic activity were significantly lower in patients with diabetes compared to the controls (P<0.05). The diabetic patients group had significantly lower high frequency and low-frequency HRV when expressed in absolute units (P<0.05) and total power (P<0.01) compared to the controls. CONCLUSION Data from the current study demonstrated that diabetics had both cardiac sympathetic and cardiac parasympathetic nervous system involvement. The presence of symptoms and involvement of both components of the autonomic nervous system suggest that dysfunction has been present for a while in these diabetics. There is a strong need for earlier and regular evaluation of autonomic nervous system in type 2 diabetics to prevent further complications.
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Affiliation(s)
- S Sucharita
- Department of Physiology, St. John's Medical College and Hospital, Bangalore, India
| | - Ganapathi Bantwal
- Department of Endocrinology, St. John's Medical College and Hospital, Bangalore, India
| | - Jyothi Idiculla
- Department of Medicine, St. John's Medical College and Hospital, Bangalore, India
| | - Vageesh Ayyar
- Department of Endocrinology, St. John's Medical College and Hospital, Bangalore, India
| | - Mario Vaz
- Department of Physiology, St. John's Medical College and Hospital, Bangalore, India
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Laitinen T, Lindström J, Eriksson J, Ilanne-Parikka P, Aunola S, Keinänen-Kiukaanniemi S, Tuomilehto J, Uusitupa M. Cardiovascular autonomic dysfunction is associated with central obesity in persons with impaired glucose tolerance. Diabet Med 2011; 28:699-704. [PMID: 21388444 DOI: 10.1111/j.1464-5491.2011.03278.x] [Citation(s) in RCA: 67] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
AIMS The aim of this study was to investigate the prevalence of cardiovascular autonomic neuropathy in persons with previously diagnosed impaired glucose tolerance and to characterize associations between components of metabolic syndrome and cardiovascular autonomic neuropathy in the Finnish Diabetes Prevention Study cohort. METHODS Two hundred and sixty-eight individuals with impaired glucose tolerance at baseline in the Finnish Diabetes Prevention Study, but not diagnosed with diabetes during follow-up, were studied for cardiovascular autonomic neuropathy. At the second annual follow-up visit after the end of lifestyle intervention, we performed deep-breathing and active orthostatic tests to detect possible parasympathetic and sympathetic dysfunction. To describe metabolic characteristics, anthropometric measurements, an oral glucose tolerance test and assessments for HbA(1c,) serum lipids and blood pressure were carried out. RESULTS Prevalence of parasympathetic dysfunction was 25% and prevalence of sympathetic dysfunction was 6%, with no difference between the former intervention and control group participants or between men and women. Subjects with parasympathetic dysfunction were older, more obese (weight, waist circumference, body mass index) and had higher triglyceride concentration compared with those with normal parasympathetic function (P<0.01 for all). Parasympathetic dysfunction was not significantly associated with other characteristics of metabolic syndrome; for example, high cholesterol, glucose and insulin levels or HbA(1c) . Correlations between the Expiration/Inspiration (E/I) ratio (the longest heart beat duration in expiration divided by the shortest heart beat duration in inspiration) and measures reflecting obesity were statistically significant in the pooled population and in men but not in women. CONCLUSIONS Cardiovascular autonomic neuropathy is common in persons with impaired glucose tolerance. Obesity, especially among men, seems to play an important role in the early pathogenesis of cardiovascular autonomic neuropathy.
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Affiliation(s)
- T Laitinen
- Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Puijonlaaksontie2, Kuopio,
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Valensi P, Extramiana F, Lange C, Cailleau M, Haggui A, Maison Blanche P, Tichet J, Balkau B. Influence of blood glucose on heart rate and cardiac autonomic function. The DESIR study. Diabet Med 2011; 28:440-9. [PMID: 21204961 DOI: 10.1111/j.1464-5491.2010.03222.x] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
OBJECTIVES To evaluate in a general population, the relationships between dysglycaemia, insulin resistance and metabolic variables, and heart rate, heart rate recovery and heart rate variability. METHODS Four hundred and forty-seven participants in the Data from an Epidemiological Study on the Insulin Resistance syndrome (DESIR) study were classified according to glycaemic status over the preceding 9 years. All were free of self-reported cardiac antecedents and were not taking drugs which alter heart rate. During five consecutive periods: rest, deep breathing, recovery, rest and lying to standing, heart rate and heart rate varability were evaluated and compared by ANCOVA and trend tests across glycaemic classes. Spearman correlation coefficients quantified the relations between cardio-metabolic risk factors, heart rate and heart rate varability. RESULTS Heart rate differed between glycaemic groups, except during deep breathing. Between rest and deep-breathing periods, patients with diabetes had a lower increase in heart rate than others (P(trend) < 0.01); between deep breathing and recovery, the heart rate of patients with diabetes continued to increase, for others, heart rate decreased (P(trend) < 0.009). Heart rate was correlated with capillary glucose and triglycerides during the five test periods. Heart rate variability differed according to glycaemic status, especially during the recovery period. After age, sex and BMI adjustment, heart rate variability was correlated with triglycerides at two test periods. Change in heart rate between recovery and deep breathing was negatively correlated with heart rate variability at rest, (r=-0.113, P < 0.05): lower resting heart rate variability was associated with heart rate acceleration. CONCLUSIONS Heart rate, but not heart rate variability, was associated with glycaemic status and capillary glucose. After deep breathing, heart rate recovery was altered in patients with known diabetes and was associated with reduced heart rate variability. Being overweight was a major correlate of heart rate variability.
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Affiliation(s)
- P Valensi
- Department of Endocrinology-Diabetology-Nutrition, Paris-Nord University, Jean Verdier Hospital, Bondy, France
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Süfke S, Djonlagić H, Kibbel T. [Impairment of cardiac autonomic nervous system and incidence of arrhythmias in severe hyperglycemia]. ACTA ACUST UNITED AC 2011; 105:858-70. [PMID: 21240584 DOI: 10.1007/s00063-010-1150-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2010] [Accepted: 09/06/2010] [Indexed: 01/08/2023]
Abstract
BACKGROUND AND PURPOSE Deterioration of cardiac autonomic nervous system in diabetics is associated with increased cardiac and arrhythmogenic mortality. Therefore, the present study engaged in the question how heart rate variability is acutely changed in diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome. Moreover was evaluated how blood pressure, heart rate and incidence of arrhythmias can be explained by figures of heart rate variability. PATIENTS AND METHODS In a prospective observation of time course we investigated in 4 years consecutively 12 intensive care patients with DKA and 2 with HHS (10 male, 4 female, 19-62 years, initial plasma glucose 404-1192 mg/dl). All patients received a standardized treatment to international current guidelines. In addition to hemodynamic and clinical-chemical monitoring HRV analysis was performed continuously for at least 48 hours. Simultaneously, we determined supraventricular and ventricular arrhythmic episodes. RESULTS HRV was diminished over the whole spectrum in dependence on blood glucose concentration. Thus, sympathovagal balance (LF/HF ratio) was initially sympathetic predominated in blood glucose levels < 600 mg/dl (relatively prevailing LF power) and vagal predominated in blood glucose levels > 600 mg/dl (relatively prevailing HF power). In correlation analysis of HRV parameters with blood glucose rS-coefficients from -0.934 to -0.821 were achieved (p < 0.001). Further, the initial mean blood pressure correlated with the LF/HF ratio in HRV minimum (rS = 0.711, p = 0.004). The initial heart rate in relation to assumed intrinsic frequency correlated with minimal found Total Power (rS = -0.656, p = 0.011). In the period of whole 48 hours, more arrhythmic events occurred in consequence to initial glucose levels (rS = 0.693, p = 0.006). But the maximum of arrhythmic episodes was usually later ascertained than the minimum of HRV (p < 0.001). At the time of each arrhythmic maximum the sympathovagal balance (LF/HF) showed no uniform figures. Only similar in all cases was that the LF/HF ratio was found either > 4 or < 1. CONCLUSION Clinical complications in high glucose levels must be seen in the context of a nearly complete blockade of sympathetic and parasympathetic activity. Basically to extreme autonomic restriction, sympathetic and vagal predominance can change rapidly into each other. This retarded vulnerable predisposition may declare the arrhythmic potential. An important progress in the monitoring of patients could be achieved by implementation of a continuous HRV measurement because hereby the actual risk potential can be ascertained timely and reliably.
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Affiliation(s)
- Sven Süfke
- Medizinische Klinik I, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany
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Ciolac EG, Greve JMD. Exercise-induced improvements in cardiorespiratory fitness and heart rate response to exercise are impaired in overweight/obese postmenopausal women. Clinics (Sao Paulo) 2011; 66:583-9. [PMID: 21655751 PMCID: PMC3093788 DOI: 10.1590/s1807-59322011000400011] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2010] [Revised: 12/25/2010] [Accepted: 01/10/2011] [Indexed: 01/26/2023] Open
Abstract
OBJECTIVE The purpose of this study was to compare the heart rate response to exercise and the exercise-induced improvements in muscle strength, cardiorespiratory fitness and heart rate response between normal-weight and overweight/obese postmenopausal women. METHODS Sedentary women (n = 155) were divided into normal-weight (n = 79; BMI <25 kg/m(2); 58.3 ± 8.6 years) and overweight/obese (n = 76; BMI >25 kg/m(2); 58.3 ± 8.6 years) groups, and have their 1-repetition maximum strength (adjusted for body mass), cardiorespiratory fitness and heart rate response to a graded exercise test compared before and after 12 months of a three times-per-week exercise-training program. RESULTS Overweight/obese women displayed decreased upper and lower extremity muscle strengths, decreased cardiorespiratory fitness, and lower peak and reserve heart rates compared to normal-weight women. After follow-up, both groups improved their upper (32.9% and 41.5% in normal-weight and overweight/obese women, respectively) and lower extremity(49.5% and 47.8% in normal-weight and overweight/obese women, respectively) muscle strength. However, only normal-weight women improved their cardiorespiratory fitness (6.6%) and recovery heart rate (5 bpm). Resting, reserve and peak heart rates did not change in either group. CONCLUSIONS Overweight/obese women displayed impaired heart rate response to exercise. Both groups improved muscle strength, but only normal-weight women improved cardiorespiratory fitness and heart rate response to exercise. These results suggest that exercise-induced improvements in cardiorespiratory fitness and heart rate response to exercise may be impaired in overweight/obese postmenopausal women.
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Affiliation(s)
- Emmanuel Gomes Ciolac
- Laboratory of Kinesiology, Institute of Orthopedics and Traumatology, School of Medicine, University of São Paulo, Brazil.
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