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Al-Beltagi M, Bediwy AS, Saeed NK. Insulin-resistance in paediatric age: Its magnitude and implications. World J Diabetes 2022; 13:282-307. [PMID: 35582667 PMCID: PMC9052009 DOI: 10.4239/wjd.v13.i4.282] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 03/12/2022] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
Insulin resistance (IR) is insulin failure in normal plasma levels to adequately stimulate glucose uptake by the peripheral tissues. IR is becoming more common in children and adolescents than before. There is a strong association between obesity in children and adolescents, IR, and the metabolic syndrome components. IR shows marked variation among different races, crucial to understanding the possible cardiovascular risk, specifically in high-risk races or ethnic groups. Genetic causes of IR include insulin receptor mutations, mutations that stimulate autoantibody production against insulin receptors, or mutations that induce the formation of abnormal glucose transporter 4 molecules or plasma cell membrane glycoprotein-1 molecules; all induce abnormal energy pathways and end with the development of IR. The parallel increase of IR syndrome with the dramatic increase in the rate of obesity among children in the last few decades indicates the importance of environmental factors in increasing the rate of IR. Most patients with IR do not develop diabetes mellitus (DM) type-II. However, IR is a crucial risk factor to develop DM type-II in children. Diagnostic standards for IR in children are not yet established due to various causes. Direct measures of insulin sensitivity include the hyperinsulinemia euglycemic glucose clamp and the insulin-suppression test. Minimal model analysis of frequently sampled intravenous glucose tolerance test and oral glucose tolerance test provide an indirect estimate of metabolic insulin sensitivity/resistance. The main aim of the treatment of IR in children is to prevent the progression of compensated IR to decompensated IR, enhance insulin sensitivity, and treat possible complications. There are three main lines for treatment: Lifestyle and behavior modification, pharmacotherapy, and surgery. This review will discuss the magnitude, implications, diagnosis, and treatment of IR in children.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Egypt
- Department of Pediatrics, University Medical Center, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Bahrain
| | - Adel Salah Bediwy
- Department of Chest Disease, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
- Department of Pulmonology, University Medical Center, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Manama 12, Bahrain
- Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Busaiteen 15503, Bahrain
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Lundqvist MH, Almby K, Abrahamsson N, Eriksson JW. Is the Brain a Key Player in Glucose Regulation and Development of Type 2 Diabetes? Front Physiol 2019; 10:457. [PMID: 31133864 PMCID: PMC6524713 DOI: 10.3389/fphys.2019.00457] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 04/01/2019] [Indexed: 01/08/2023] Open
Abstract
Ever since Claude Bernards discovery in the mid 19th-century that a lesion in the floor of the third ventricle in dogs led to altered systemic glucose levels, a role of the CNS in whole-body glucose regulation has been acknowledged. However, this finding was later overshadowed by the isolation of pancreatic hormones in the 20th century. Since then, the understanding of glucose homeostasis and pathology has primarily evolved around peripheral mechanism. Due to scientific advances over these last few decades, however, increasing attention has been given to the possibility of the brain as a key player in glucose regulation and the pathogenesis of metabolic disorders such as type 2 diabetes. Studies of animals have enabled detailed neuroanatomical mapping of CNS structures involved in glucose regulation and key neuronal circuits and intracellular pathways have been identified. Furthermore, the development of neuroimaging techniques has provided methods to measure changes of activity in specific CNS regions upon diverse metabolic challenges in humans. In this narrative review, we discuss the available evidence on the topic. We conclude that there is much evidence in favor of active CNS involvement in glucose homeostasis but the relative importance of central vs. peripheral mechanisms remains to be elucidated. An increased understanding of this field may lead to new CNS-focusing pharmacologic strategies in the treatment of type 2 diabetes.
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Affiliation(s)
| | - Kristina Almby
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | | | - Jan W Eriksson
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
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Abstract
PURPOSE OF REVIEW This review summarizes the current knowledge on the relationship of physical activity, exercise, and cardiorespiratory fitness (CRF) with cardiovascular autonomic neuropathy (CAN) based on epidemiological, clinical, and interventional studies. RECENT FINDINGS The prevalence of CAN increases with age and duration of diabetes. Further risk factors for CAN comprise poor glycemic control, dyslipidemia, abdominal obesity, hypertension, and the presence of diabetic complications. CAN has been also linked to reduced CRF. We recently showed that CRF parameters (e.g., maximal oxidative capacity or oxidative capacity at the anaerobic threshold) are associated with cardiac autonomic function in patients recently diagnosed with type 1 or type 2 diabetes. Exercise interventions have shown that physical activity can increase cardiovagal activity and reduce sympathetic overactivity. In particular, long-term and regularly, but also supervised, performed endurance and high-intense and high-volume exercise improves cardiac autonomic function in patients with type 2 diabetes. By contrast, the evidence in those with type 1 diabetes and also in individuals with prediabetes or metabolic syndrome is weaker. Overall, the studies reviewed herein addressing the question whether favorably modulating the autonomic nervous system may improve CRF during exercise programs support the therapeutic concept to promote physical activity and to achieve physical fitness. However, high-quality exercise interventions, especially in type 1 diabetes and metabolic syndrome including prediabetes, are further required to better understand the relationship between physical activity, fitness, and cardiac autonomic function.
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Affiliation(s)
- Martin Röhling
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany
- Department of Sports Medicine, University of Wuppertal, Wuppertal, Germany
| | - Alexander Strom
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
| | - Gidon J Bönhof
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany
| | - Michael Roden
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Auf'm Hennekamp 65, 40225, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), München-Neuherberg, Germany
- Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
| | - Dan Ziegler
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Auf'm Hennekamp 65, 40225, 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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Hong JW, Noh JH, Kim DJ. The Association of Resting Heart Rate with the Presence of Diabetes in Korean Adults: The 2010-2013 Korea National Health and Nutrition Examination Survey. PLoS One 2016; 11:e0168527. [PMID: 27992613 PMCID: PMC5161480 DOI: 10.1371/journal.pone.0168527] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2016] [Accepted: 12/03/2016] [Indexed: 12/29/2022] Open
Abstract
Background Previous epidemiologic studies have shown that elevated resting heart rate (HR) is associated with higher cardiovascular disease (CVD) morbidity and mortality. Although the relationship between elevated HR and CVD is well established, the association between resting HR and diabetes has been relatively understudied, particularly in non-Western populations. Objectives We confirmed the association between the presence of type 2 diabetes and resting HR in the Korean adult population using data from the 2010–2013 Korea National Health and Nutrition Examination Survey (KNHANES). Methods Among 25,712 adults (≥ 19 years of age) who participated in the 2010–2013 KNHANES, a total of 22,512 subjects completed laboratory examinations and were included in this analysis. The fasting plasma glucose (FPG) level was categorized into the following five groups: normal fasting glucose (NFG) 1 (<90 mg/dL), NFG 2 (90–99 mg/dL), impaired fasting glucose (IFG) 1 (100–110 mg/dL), IFG 2 (111–125 mg/dL), and diabetes (≥ 126 mg/dL). Results The unadjusted weighted resting HRs were 69.6, 69.4, 69.8, 70.1, and 72.0 beats per minute (bpm) in the NFG 1, NFG 2, IFG 1, IFG 2, and diabetes groups, respectively (P<0.001). We assessed the adjusted weighted resting HR according to the FPG level after adjusting for age, sex, smoking history, high risk alcohol drinking, daily energy intake, waist circumference, serum total cholesterol level, serum triglyceride (TG) level, serum white blood cell (WBC) count, serum hemoglobin (Hb), and the presence of hypertension. The adjusted weighted resting HR significantly increased across the FPG groups (P<0.001). The weighted prevalence rates of diabetes were 6.8% (6.2–7.5%), 7.6% (6.7–8.5%), 8.0% (7.0–9.1%), and 11.8% (10.8–12.7%) in subjects with HR ≤ 64, 65–69, 70–75, and ≥ 76 bpm, respectively (P<0.001), after adjusting for the confounding factors mentioned above. Using resting HR ≤ 64 bpm as the control, resting HR ≥ 76 bpm was correlated with the presence of diabetes (adjusted OR 1.83, 95% CI 1.55–2.16, P<0.001). Each 10 bpm increment of HR increased the risk of the presence of diabetes by 35% (P<0.001). This association of high resting HR with the presence of diabetes was not influenced by the status of blood pressure (BP) medication. Conclusion We demonstrated that higher HR was associated with diabetes in a representative sample of Korean adults. These positive associations were independent of age, sex, current smoking, high risk alcohol drinking, daily energy intake, waist circumference, and the presence of hypertension and other potential confounders. This study suggests that individuals with higher resting HR are at risk of diabetes and that HR might provide an easy and simple surrogate marker for the risk of diabetes.
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Affiliation(s)
- Jae Won Hong
- Department of Internal Medicine, Ilsan-Paik Hospital, College of Medicine, Inje University, Koyang, Gyeonggi-do, Republic of Korea
| | - Jung Hyun Noh
- Department of Internal Medicine, Ilsan-Paik Hospital, College of Medicine, Inje University, Koyang, Gyeonggi-do, Republic of Korea
| | - Dong-Jun Kim
- Department of Internal Medicine, Ilsan-Paik Hospital, College of Medicine, Inje University, Koyang, Gyeonggi-do, Republic of Korea
- * E-mail:
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Wang L, Cui L, Wang Y, Vaidya A, Chen S, Zhang C, Zhu Y, Li D, Hu FB, Wu S, Gao X. Resting heart rate and the risk of developing impaired fasting glucose and diabetes: the Kailuan prospective study. Int J Epidemiol 2015; 44:689-99. [PMID: 26002923 DOI: 10.1093/ije/dyv079] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/20/2015] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND To investigate the association between resting heart rate and the risk of developing impaired fasting glucose (IFG), diabetes and conversion from IFG to diabetes. METHODS The prospective analysis included 73,357 participants of the Kailuan cohort (57,719 men and 15,638 women). Resting heart rate was measured via electrocardiogram in 2006. Incident diabetes was defined as either the fasting blood glucose (FBG) ≥ 7.0 mmol/l or new active use of diabetes medications during the 4-year follow-up period. IFG was defined as a FBG between 5.6 and 6.9 mmol/l. A meta-analysis including seven published prospective studies focused on heart rate and diabetes risk, and our current study was then conducted using random-effects models. RESULTS During 4 years of follow-up, 17,463 incident IFG cases and 4,649 incident diabetes cases were identified. The corresponding adjusted hazard ratios (HRs) for each 10 beats/min increase in heart rate were 1.23 [95% confidence interval (CI): 1.19, 1.27] for incident diabetes, 1.11 (95% CI: 1.09, 1.13) for incident IFG and 1.13 (95% CI: 1.08, 1.17) for IFG to diabetes conversion. The risks of incident IFG and diabetes were significantly higher among participants aged < 50 years than those aged ≥ 50 years (P-interaction < 0.02 for both). A meta-analysis confirmed the positive association between resting heart rate and diabetes risk (pooled HR for the highest vs lowest heart rate quintile = 1.59, 95% CI:1.27, 2.00; n = 8). CONCLUSION Faster resting heart rate is associated with higher risk of developing IFG and diabetes, suggesting that heart rate could be used to identify individuals with a higher future risk of diabetes.
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Affiliation(s)
- Liang Wang
- Department of Biostatistics and Epidemiology, East Tennessee State University, Johnson City, TN, USA, Department of Internal Medicine, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Division of Endocrinology, Diabetes, and Hypertension (A.V.), Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA, Department of Health Care Center, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Graduate School, Hebei United University, Tangshan, China, Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA and Department of Nutritional Science, Pennsylvania State University, University Park, PA, USA
| | - Liufu Cui
- Department of Biostatistics and Epidemiology, East Tennessee State University, Johnson City, TN, USA, Department of Internal Medicine, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Division of Endocrinology, Diabetes, and Hypertension (A.V.), Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA, Department of Health Care Center, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Graduate School, Hebei United University, Tangshan, China, Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA and Department of Nutritional Science, Pennsylvania State University, University Park, PA, USA
| | - Yanxue Wang
- Department of Biostatistics and Epidemiology, East Tennessee State University, Johnson City, TN, USA, Department of Internal Medicine, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Division of Endocrinology, Diabetes, and Hypertension (A.V.), Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA, Department of Health Care Center, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Graduate School, Hebei United University, Tangshan, China, Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA and Department of Nutritional Science, Pennsylvania State University, University Park, PA, USA
| | - Anand Vaidya
- Department of Biostatistics and Epidemiology, East Tennessee State University, Johnson City, TN, USA, Department of Internal Medicine, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Division of Endocrinology, Diabetes, and Hypertension (A.V.), Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA, Department of Health Care Center, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Graduate School, Hebei United University, Tangshan, China, Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA and Department of Nutritional Science, Pennsylvania State University, University Park, PA, USA
| | - Shuohua Chen
- Department of Biostatistics and Epidemiology, East Tennessee State University, Johnson City, TN, USA, Department of Internal Medicine, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Division of Endocrinology, Diabetes, and Hypertension (A.V.), Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA, Department of Health Care Center, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Graduate School, Hebei United University, Tangshan, China, Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA and Department of Nutritional Science, Pennsylvania State University, University Park, PA, USA
| | - Caifeng Zhang
- Department of Biostatistics and Epidemiology, East Tennessee State University, Johnson City, TN, USA, Department of Internal Medicine, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Division of Endocrinology, Diabetes, and Hypertension (A.V.), Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA, Department of Health Care Center, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Graduate School, Hebei United University, Tangshan, China, Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA and Department of Nutritional Science, Pennsylvania State University, University Park, PA, USA
| | - Ying Zhu
- Department of Biostatistics and Epidemiology, East Tennessee State University, Johnson City, TN, USA, Department of Internal Medicine, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Division of Endocrinology, Diabetes, and Hypertension (A.V.), Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA, Department of Health Care Center, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Graduate School, Hebei United University, Tangshan, China, Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA and Department of Nutritional Science, Pennsylvania State University, University Park, PA, USA
| | - Dongqing Li
- Department of Biostatistics and Epidemiology, East Tennessee State University, Johnson City, TN, USA, Department of Internal Medicine, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Division of Endocrinology, Diabetes, and Hypertension (A.V.), Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA, Department of Health Care Center, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Graduate School, Hebei United University, Tangshan, China, Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA and Department of Nutritional Science, Pennsylvania State University, University Park, PA, USA
| | - Frank B Hu
- Department of Biostatistics and Epidemiology, East Tennessee State University, Johnson City, TN, USA, Department of Internal Medicine, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Division of Endocrinology, Diabetes, and Hypertension (A.V.), Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA, Department of Health Care Center, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Graduate School, Hebei United University, Tangshan, China, Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA and Department of Nutritional Science, Pennsylvania State University, University Park, PA, USA
| | - Shouling Wu
- Department of Biostatistics and Epidemiology, East Tennessee State University, Johnson City, TN, USA, Department of Internal Medicine, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Division of Endocrinology, Diabetes, and Hypertension (A.V.), Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA, Department of Health Care Center, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Graduate School, Hebei United University, Tangshan, China, Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA and Department of Nutritional Science, Pennsylvania State University, University Park, PA, USA
| | - Xiang Gao
- Department of Biostatistics and Epidemiology, East Tennessee State University, Johnson City, TN, USA, Department of Internal Medicine, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Division of Endocrinology, Diabetes, and Hypertension (A.V.), Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA, Department of Health Care Center, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Graduate School, Hebei United University, Tangshan, China, Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA and Department of Nutritional Science, Pennsylvania State University, University Park, PA, USA Department of Biostatistics and Epidemiology, East Tennessee State University, Johnson City, TN, USA, Department of Internal Medicine, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Division of Endocrinology, Diabetes, and Hypertension (A.V.), Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA, Department of Health Care Center, Kailuan Hospital Affiliated to Hebei United University, Tangshan, China, Graduate School, Hebei United University, Tangshan, China, Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA and Department of Nutritional Science, Pennsylvania State University, University Park, PA, USA
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Ziegler D, Strom A, Strassburger K, Nowotny B, Zahiragic L, Nowotny PJ, Carstensen-Kirberg M, Herder C, Szendroedi J, Roden M. Differential Patterns and Determinants of Cardiac Autonomic Nerve Dysfunction during Endotoxemia and Oral Fat Load in Humans. PLoS One 2015; 10:e0124242. [PMID: 25893426 PMCID: PMC4403853 DOI: 10.1371/journal.pone.0124242] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2014] [Accepted: 02/27/2015] [Indexed: 11/24/2022] Open
Abstract
The autonomic nervous system (ANS) plays an important role in regulating the metabolic homeostasis and controlling immune function. ANS alterations can be detected by reduced heart rate variability (HRV) in conditions like diabetes and sepsis. We determined the effects of experimental conditions mimicking inflammation and hyperlipidemia on HRV and heart rate (HR) in relation to the immune, metabolic, and hormonal responses resulting from these interventions. Sixteen lean healthy subjects received intravenous (i.v.) low-dose endotoxin (lipopolysaccharide [LPS]), i.v. fat, oral fat, and i.v. glycerol (control) for 6 hours, during which immune, metabolic, hormonal, and five HRV parameters (pNN50, RMSSD, low-frequency (LF) and high-frequency (HF) power, and LF/HF ratio) were monitored and energy metabolism and insulin sensitivity (M-value) were assessed. LPS infusion induced an increase (AUC) in HR and LF/HF ratio and decline in pNN50 and RMSSD, while oral fat resulted in elevated HR and a transient (hours 1-2) decrease in pNN50, RMSSD, and HF power. During LPS infusion, ΔIL-1ra levels and ΔIL-1ra and ΔIL-1ß gene expression correlated positively with ΔLF/HF ratio and inversely with ΔRMSSD. During oral fat intake, ΔGLP-1 tended to correlate positively with ΔHR and inversely with ΔpNN50 and ΔRMSSD. Following LPS infusion, lipid oxidation correlated positively with HR and inversely with pNN50 and RMSSD, whereas HRV was not related to M-value. In conclusion, suppression of vagal tone and sympathetic predominance during endotoxemia are linked to anti-inflammatory processes and lipid oxidation but not to insulin resistance, while weaker HRV changes in relation to the GLP-1 response are noted during oral fat load.
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Affiliation(s)
- Dan Ziegler
- Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany
- Department of Endocrinology and Diabetology, University Hospital, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany
- * E-mail:
| | - Alexander Strom
- Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany
| | - Klaus Strassburger
- Institute of Biometrics and Epidemiology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany
| | - Bettina Nowotny
- Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany
| | - Lejla Zahiragic
- Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany
- Department of Endocrinology and Diabetology, University Hospital, Düsseldorf, Germany
| | - Peter J. Nowotny
- Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany
| | - Maren Carstensen-Kirberg
- Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany
| | - Christian Herder
- Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany
| | - Julia Szendroedi
- Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany
- Department of Endocrinology and Diabetology, University Hospital, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany
| | - Michael Roden
- Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University, Leibniz Center for Diabetes Research, Düsseldorf, Germany
- Department of Endocrinology and Diabetology, University Hospital, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), Partner Düsseldorf, Düsseldorf, Germany
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Relationship of muscle sympathetic nerve activity to insulin sensitivity. Clin Auton Res 2014; 24:77-85. [PMID: 24577625 DOI: 10.1007/s10286-014-0235-0] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Accepted: 02/11/2014] [Indexed: 02/08/2023]
Abstract
PURPOSE An association between insulin resistance and activation of the sympathetic nervous system has been reported in previous studies. However, potential interactions between insulin sensitivity and sympathetic neural mechanisms in healthy people remain poorly understood. We conducted a study to determine the relationship between sympathetic activity and insulin resistance in young, healthy humans. METHODS Thirty-seven healthy adults (18-35 years, BMI <28 kg m(-2)) were studied. Resting muscle sympathetic nerve activity (MSNA) was measured with microneurography and insulin sensitivity of glucose and free fatty acid metabolism was measured during a hyperinsulinemic-euglycemic clamp with two levels of insulin. RESULTS During lower doses of insulin, we found a small association between lower insulin sensitivity and higher MSNA (P < 0.05) but age was a cofactor in this relationship. Overall, we found no difference in insulin sensitivity between groups of low and high MSNA, but when women were analyzed separately, insulin sensitivity was lower in the high MSNA group compared with the low MSNA group of women. CONCLUSIONS These data suggest that MSNA and insulin sensitivity are only weakly associated with young healthy individuals and that age and sex may be important modifiers of this relationship.
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Limberg JK, Taylor JL, Dube S, Basu R, Basu A, Joyner MJ, Wehrwein EA. Role of the carotid body chemoreceptors in baroreflex control of blood pressure during hypoglycaemia in humans. Exp Physiol 2014; 99:640-50. [PMID: 24414173 DOI: 10.1113/expphysiol.2013.076869] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Activation of the carotid body chemoreceptors with hypoxia alters baroreceptor-mediated responses. We aimed to examine whether this relationship can be translated to other chemoreceptor stimuli (i.e. hypoglycaemia) by testing the following hypotheses: (i) activation of the carotid body chemoreceptors with hypoglycaemia would reduce spontaneous cardiac baroreflex sensitivity (sCBRS) in healthy humans; and (ii) desensitization of the carotid chemoreceptors with hyperoxia would restore sCBRS to baseline levels during hypoglycaemia. Ten young healthy adults completed two 180 min hyperinsulinaemic [2 mU (kg fat-free mass)(-1) min(-1)], hypoglycaemic (∼ 3.2 μmol ml(-1)) clamps, separated by at least 1 week and randomized to normoxia (arterial partial pressure of O2, 122 ± 10 mmHg) or hyperoxia (arterial partial pressure of O2, 424 ± 123 mmHg; to blunt activation of the carotid body glomus cells). Changes in heart rate, blood pressure, plasma catecholamines, heart rate variability (HRV) and sCBRS were assessed. During hypoglycaemia, HRV and sCBRS were reduced (P < 0.05) and the baroreflex working range was shifted to higher heart rates. When hyperoxia was superimposed on hypoglycaemia, there was a greater reduction in blood pressure and a blunted rise in heart rate when compared with normoxic conditions (P < 0.05); however, there was no detectable effect of hyperoxia on sCBRS or HRV during hypoglycaemia (P > 0.05). In summary, hypoglycaemia-mediated changes in HRV and sCBRS cannot be attributed exclusively to the carotid chemoreceptors; however, the chemoreceptors appear to play a role in resetting the baroreflex working range during hypoglycaemia.
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Affiliation(s)
- Jacqueline K Limberg
- * Department of Anesthesiology, Mayo Clinic, 200 1st Street SW, SMH Joseph 4-184, Rochester, MN 55905, USA.
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Wang CJ, Li YQ, Li LL, Wang L, Zhao JZ, You AG, Guo YR, Li WJ. Relationship between resting pulse rate and lipid metabolic dysfunctions in Chinese adults living in rural areas. PLoS One 2012; 7:e49347. [PMID: 23145157 PMCID: PMC3492277 DOI: 10.1371/journal.pone.0049347] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2012] [Accepted: 10/10/2012] [Indexed: 12/03/2022] Open
Abstract
Background Resting pulse rate has been observed to be associated with cardiovascular diseases. However, its association with lipid metabolic dysfunctions remains unclear, especially resting pulse rate as an indicator for identifying the risk of lipid metabolic dysfunctions. The purpose of this study was to examine the association between resting pulse rate and lipid metabolic dysfunctions, and then evaluate the feasibility of resting pulse rate as an indicator for screening the risk of lipid metabolic dysfunctions. Methods A cross-sectional survey was performed, and 16,926 subjects were included in this study from rural community residents aged 35–78 years. Resting pulse rate and relevant covariates were collected from a standard questionnaire. The fasting blood samples were collected and measured for lipid profile. Predictive performance was analyzed by receiver operating characteristic (ROC) curve. Results A significant correlation was observed between resting pulse rate and TC (r = 0.102, P = 0.001), TG (r = 0.182, P = 0.001), and dyslipidemia (r = 0.037, P = 0.008). In the multivariate models, the adjusted odds ratios for hypercholesterolemia (from 1.07 to 1.15), hypertriglyceridemia (1.11 to 1.16), low HDL hypercholesterolemia (1.03 to 1.06), high LDL hypercholesterolemia (0.92 to 1.14), and dyslipidemia (1.04 to 1.07) were positively increased across quartiles of resting pulse rate (P for trend <0.05). The ROC curve indicated that resting pulse rate had low sensitivity (78.95%, 74.18%, 51.54%, 44.39%, and 54.22%), specificity (55.88%, 59.46%, 57.27%, 65.02%, and 60.56%), and the area under ROC curve (0.70, 0.69, 0.54, 0.56, and 0.58) for identifying the risk of hypercholesterolemia, hypertriglyceridemia, low HDL hypercholesterolemia, high LDL hypercholesterolemia, and dyslipidemia, respectively. Conclusion Fast resting pulse rate was associated with a moderate increased risk of lipid metabolic dysfunctions in rural adults. However, resting pulse rate as an indicator has limited potential for screening the risk of lipid metabolic dysfunctions.
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Affiliation(s)
- Chong-jian Wang
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China
- Research Centre, CHU Sainte-Justine, Montreal, Quebec, Canada
- * E-mail:
| | - Yu-qian Li
- Department of Clinical Pharmacology, School of Pharmaceutical Science, Zhengzhou University, Zhengzhou, Henan, PR China
| | - Lin-lin Li
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China
| | - Ling Wang
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China
| | - Jing-zhi Zhao
- Department of Endocrinology, Military Hospital of Henan Province, Zhengzhou, Henan, PR China
| | - Ai-guo You
- Department of Disease Control and Prevention, Henan Provincial Center for Disease Control and Prevention, Zhengzhou, Henan, PR China
| | - Yi-rui Guo
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China
| | - Wen-jie Li
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China
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Rodríguez-Colón SM, Li X, Shaffer ML, He F, Bixler EO, Vgontzas AN, Cai J, Liao D. Insulin resistance and circadian rhythm of cardiac autonomic modulation. Cardiovasc Diabetol 2010; 9:85. [PMID: 21134267 PMCID: PMC3017516 DOI: 10.1186/1475-2840-9-85] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2010] [Accepted: 12/06/2010] [Indexed: 12/19/2022] Open
Abstract
Background Insulin resistance (IR) has been associated with cardiovascular diseases (CVD). Heart rate variability (HRV), an index of cardiac autonomic modulation (CAM), is also associated with CVD mortality and CVD morbidity. Currently, there are limited data about the impairment of IR on the circadian pattern of CAM. Therefore, we conducted this investigation to exam the association between IR and the circadian oscillations of CAM in a community-dwelling middle-aged sample. Method Homeostasis models of IR (HOMA-IR), insulin, and glucose were used to assess IR. CAM was measured by HRV analysis from a 24-hour electrocardiogram. Two stage modeling was used in the analysis. In stage one, for each individual we fit a cosine periodic model based on the 48 segments of HRV data. We obtained three individual-level cosine parameters that quantity the circadian pattern: mean (M), measures the overall average of a HRV index; amplitude (Â), measures the amplitude of the oscillation of a HRV index; and acrophase time (θ), measures the timing of the highest oscillation. At the second stage, we used a random-effects-meta-analysis to summarize the effects of IR variables on the three circadian parameters of HRV indices obtained in stage one of the analysis. Results In persons without type diabetes, the multivariate adjusted β (SE) of log HOMA-IR and M variable for HRV were -0.251 (0.093), -0.245 (0.078), -0.19 (0.06), -4.89 (1.76), -3.35 (1.31), and 2.14 (0.995), for log HF, log LF, log VLF, SDNN, RMSSD and HR, respectively (all P < 0.05). None of the IR variables were significantly associated with  or θ of the HRV indices. However, in eight type 2 diabetics, the magnitude of effect due to higher HOMA-IR on M, Â, and θ are much larger. Conclusion Elevated IR, among non-diabetics significantly impairs the overall mean levels of CAM. However, the  or θ of CAM were not significantly affected by IR, suggesting that the circadian mechanisms of CAM are not impaired. However, among persons with type 2 diabetes, a group clinically has more severe form of IR, the adverse effects of increased IR on all three HRV circadian parameters are much larger.
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Affiliation(s)
- Sol M Rodríguez-Colón
- Department of Public Health Sciences, Penn State University College of Medicine, 600 Centerview Dr, Suite 2200, A210, Hershey, PA, USA
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11
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Zhang X, Shu XO, Xiang YB, Yang G, Li H, Cai H, Gao YT, Zheng W. Resting heart rate and risk of type 2 diabetes in women. Int J Epidemiol 2010; 39:900-6. [PMID: 20448009 DOI: 10.1093/ije/dyq068] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Resting heart rate has been shown to predict risk of cardiovascular disease; its association with diabetes remains unclear, particularly in non-Western populations. METHODS We evaluated the association between resting heart rate and risk of type 2 diabetes in the Shanghai Women's Health Study, a population-based prospective cohort study. The analysis included 47 571 Chinese women with no prior history of diabetes, cancer, cardiovascular disease or thyroid dysfunction at the time when resting heart rate was measured. Incident diabetes was ascertained through biennial in-person interviews. RESULTS During a mean follow-up of 4.9 years, 849 women developed type 2 diabetes. For heart rate categories of < or =68, 69-72, 73-76, 77-80 and >80 beats/min, the incidence rates of diabetes per 1000 person-years were 2.91, 3.31, 3.71, 4.16 and 5.34, respectively. The multivariable-adjusted hazard ratios (HRs) [95% confidence intervals (CIs)] for diabetes across increasing heart rate categories were 1, 1.21 (0.99-1.47), 1.30 (1.05-1.62), 1.37 (1.12-1.69) and 1.60 (1.28-2.00), respectively. Further analyses of the joint effects of heart rate with body mass index (BMI), waist-hip ratio (WHR) and blood pressure (BP) showed increased risk of diabetes with increasing heart rate in all categories of BMI, WHR or BP. The combinations of the highest heart rate category with highest BMI, WHR or BP category were associated with the highest HRs, ranging from 4.81 to 6.34. CONCLUSIONS A high resting heart rate is independently associated with an increased risk of type 2 diabetes in women. The combinations of high heart rate with high BMI, WHR or BP level are associated with a substantially increased risk.
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Affiliation(s)
- Xianglan Zhang
- Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
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12
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Schäffer L, Burkhardt T, Müller-Vizentini D, Rauh M, Tomaske M, Mieth RA, Bauersfeld U, Beinder E. Cardiac autonomic balance in small-for-gestational-age neonates. Am J Physiol Heart Circ Physiol 2008; 294:H884-90. [DOI: 10.1152/ajpheart.00318.2007] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
The cardiac sympathetic nervous system is one putative key factor involved in the intrauterine programming of adult cardiovascular disease. We therefore analyzed cardiac autonomic system activity in small for gestational age (SGA) neonates. Heart rate variability (HRV) from 24-h ECG recordings were analyzed for time-domain and frequency-domain parameters in 27 SGA neonates [median 261 (240–283) days of gestation] compared with 27 appropriate for gestational age (AGA) neonates [median 270 (239–293) days of gestation]. In addition, salivary α-amylase levels were analyzed during resting conditions and in response to a pain-induced stress event in 18 SGA [median 266 (240–292) days of gestation] and 34 AGA [median 271 (240–294) days of gestation] neonates. Overall HRV was not significantly different in SGA neonates compared with AGA neonates (SD of all valid NN intervals: P = 0.14; triangular index: P = 0.29), and the sympathovagal balance [low frequency (LF)/high frequency (HF)] was similar ( P = 0.62). Parameters mostly influenced by sympathetic activity did not reveal significant differences: (SD of the average of valid NN intervals: P = 0.27; average of the hourly means of SDs of all NN intervals: P = 0.66, LF: P = 0.83) as well as vagal tone-influenced parameters were unaltered (average of the hourly square root of the mean of the sum of the squares of differences between adjacent NN intervals: P = 0.59; proportion of pairs of adjacent NN intervals differing by >50 ms: P = 0.93; HF: P = 0.82). Median resting levels for α-amylase were not significantly different in SGA neonates ( P = 0.13), and a neonatal stress stimulus revealed similar stress response patterns ( P = 0.29). HRV and salivary α-amylase levels as indicators of cardiac autonomic activity were not altered in SGA neonates compared with AGA neonates. Thus, it appears that the intrauterine activation of the sympathetic system in SGA fetuses does not directly persist into postnatal life, and neonatal sympathovagal balance appears to be preserved.
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13
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Fiorentini A, Perciaccante A, Paris A, Serra P, Tubani L. Circadian rhythm of autonomic activity in non diabetic offsprings of type 2 diabetic patients. Cardiovasc Diabetol 2005; 4:15. [PMID: 16197556 PMCID: PMC1266389 DOI: 10.1186/1475-2840-4-15] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2005] [Accepted: 10/01/2005] [Indexed: 11/16/2022] Open
Abstract
The aim of the present study was to evaluate, by heart rate variability (HRV) with 24-hours ECG Holter (HRV), the circadian autonomic activity in offspring of type 2 diabetic subjects and the relation with insulin-resistance. METHODS: 50 Caucasian offsprings of type 2 diabetic subjects were divided in two groups: insulin-resistant offsprings (IR) and non insulin-resistant offsprings (NIR). Autonomic nervous activity was studied by HRV. Time domain and spectral analysis (low frequency, LF, and high frequency, HF, provide markers of sympathetic and parasympathetic modulation when assessed in normalized units) were evaluated. RESULTS. Time domain showed a reduction of total SDNN in IR (p < 0.001) and NIR (p 0.047) versus controls. Spectral analysis showed a total and night LF higher in IR and NIR than in control group (all p < 0.001). CONCLUSION. In frequency domain, the analysis of sympathetic (LF) and parasympathetic (HF) component evidenced an association between the offspring of type 2 diabetic subjects and a sympathetic overactivity. A global reduction and alteration of circadian rhythm of autonomic activity are present in offspring of type 2 diabetic patients with and without insulin resistance. The data of our study suggested that an autonomic impairment is associated with the familiarity for type 2 diabetes independently to insulin resistance and that an impairment of autonomic system activity could precede the insulin resistance.
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Affiliation(s)
- A Fiorentini
- III Clinica Medica, Department of Clinical Medicine, University "La Sapienza", Rome, Italy
| | - A Perciaccante
- III Clinica Medica, Department of Clinical Medicine, University "La Sapienza", Rome, Italy
| | - A Paris
- III Clinica Medica, Department of Clinical Medicine, University "La Sapienza", Rome, Italy
| | - P Serra
- III Clinica Medica, Department of Clinical Medicine, University "La Sapienza", Rome, Italy
| | - L Tubani
- Medicina Interna E, Department of Clinical Medicine, University "La Sapienza", Rome, Italy
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14
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McMillen IC, Robinson JS. Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev 2005; 85:571-633. [PMID: 15788706 DOI: 10.1152/physrev.00053.2003] [Citation(s) in RCA: 1309] [Impact Index Per Article: 65.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
The "fetal" or "early" origins of adult disease hypothesis was originally put forward by David Barker and colleagues and stated that environmental factors, particularly nutrition, act in early life to program the risks for adverse health outcomes in adult life. This hypothesis has been supported by a worldwide series of epidemiological studies that have provided evidence for the association between the perturbation of the early nutritional environment and the major risk factors (hypertension, insulin resistance, and obesity) for cardiovascular disease, diabetes, and the metabolic syndrome in adult life. It is also clear from experimental studies that a range of molecular, cellular, metabolic, neuroendocrine, and physiological adaptations to changes in the early nutritional environment result in a permanent alteration of the developmental pattern of cellular proliferation and differentiation in key tissue and organ systems that result in pathological consequences in adult life. This review focuses on those experimental studies that have investigated the critical windows during which perturbations of the intrauterine environment have major effects, the nature of the epigenetic, structural, and functional adaptive responses which result in a permanent programming of cardiovascular and metabolic function, and the role of the interaction between the pre- and postnatal environment in determining final health outcomes.
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Affiliation(s)
- I Caroline McMillen
- Discipline of Physiology, School of Molecular and Biomeducal Sciences, and Department of Obstetrics and Gynaecology, University of Adelaide, Australia.
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15
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Hanson MA, Gluckman PD. Developmental processes and the induction of cardiovascular function: conceptual aspects. J Physiol 2005; 565:27-34. [PMID: 15731193 PMCID: PMC1464499 DOI: 10.1113/jphysiol.2004.082339] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
The epidemiological basis of the developmental origins of disease concept is now widely accepted. The current impetus in research concerns establishing the underlying mechanisms. We discuss the wider biological nature of the phenomenon, with particular reference to 'maternal effects', the processes observed in many species by which the mother can induce phenotypic effects in her offspring. Animal models permit investigation of the induction of cardiovascular phenotypic attributes which resemble pathological effects in humans. We discuss the importance of transitions in aspects of the pre- versus the postnatal environment, with emphasis on nutrition and energy expenditure, and the critical role which the timing of environmental cues plays in inducing effects on the offspring. Coupled with the effects of specific maternal dietary components, the effects on the offspring are argued to involve epigenetic mechanisms. In this review we provide a conceptual framework for synthesising experimental and clinical data, important for considering the impact of the developmental origins concept in a life-course approach to the prevention of cardiovascular disease.
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Affiliation(s)
- Mark A Hanson
- Centre for Developmental Origins of Health and Disease, University of Southampton, Princess Anne Hospital Level F (887), Coxford Road, Southampton S016 5YA, UK.
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16
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Danielson L, McMillen IC, Dyer JL, Morrison JL. Restriction of placental growth results in greater hypotensive response to alpha-adrenergic blockade in fetal sheep during late gestation. J Physiol 2005; 563:611-20. [PMID: 15649982 PMCID: PMC1665578 DOI: 10.1113/jphysiol.2004.080523] [Citation(s) in RCA: 80] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Placental insufficiency resulting in restriction of fetal substrate supply and fetal hypoxaemia is a major cause of restricted fetal growth and increased neonatal morbidity. Fetal adaptations to placental restriction (PR) include increases in circulating catecholamines and cortisol and decreased fetal body growth, with relative sparing of brain growth. The mechanisms underlying the redistribution of fetal cardiac output in PR fetuses are not known and the aim of this study was to determine whether maintenance of fetal blood pressure (BP) in the PR fetus is dependent on alpha-adrenergic stimulation. PR was induced by removing the majority of uterine caruncles in the ewe before conception. Sterile vascular surgery was performed on seven PR and six control fetuses at 113-120 days' gestation (term = 150 +/- 3 days). Fetuses with a mean arterial PO2 < 17 mmHg between 123 and 127 days' gestation were defined as hypoxic. There was a greater fall (P < 0.05) in fetal BP during phentolamine infusion (i.v: 5 mg bolus, 0.2 mg kg(-1) min(-1) for 2 h) in the hypoxic PR group (-15 +/- 2 mmHg) compared with normoxic controls (-5 +/- 1 mmHg). The fall in fetal BP during phentolamine infusion was directly related to the level of fetal PO2. Fetal BP and HR responses to phenylephrine (i.v.: 40 microg kg(-1)) were not different between PR and control fetuses. The maintenance of BP in the chronically hypoxic fetus is therefore dependent on alpha-adrenergic activation, and this fetal adaptation to a suboptimal intrauterine environment pre-dates the development of significant growth restriction. While this adaptation may play a critical role in the redistribution of fetal cardiac output to ensure the sparing of brain growth, it may have adverse consequences for peripheral vascular function in the neonatal period and in adult life.
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Affiliation(s)
- Li Danielson
- Centre for the Early Origins of Adult Health, Discipline of Physiology, School of Molecular and Biomedical Sciences, University of Adelaide, Adelaide, SA 5005, Australia
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Kazumi T, Kawaguchi A, Sakai K, Hirano T, Yoshino G. Young men with high-normal blood pressure have lower serum adiponectin, smaller LDL size, and higher elevated heart rate than those with optimal blood pressure. Diabetes Care 2002; 25:971-6. [PMID: 12032101 DOI: 10.2337/diacare.25.6.971] [Citation(s) in RCA: 202] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Three measures--heart rate, a global index of the influence of the autonomic nervous system on the heart; circulating concentrations of adiponectin, an adipose-specific protein; and C-reactive protein (CRP), a sensitive marker of inflammation--have been reported to be closely associated with insulin resistance. Patients with borderline hypertension are known to be more insulin resistant and dyslipidemic than those with normal blood pressure (BP). BP can be classified into three categories: optimal, normal, and high-normal. The present study examined whether those with high-normal BP have any of these three conditions as compared with those with optimal BP in young healthy men. RESEARCH DESIGN AND METHODS Anthropometric, blood pressure, heart rate, and blood tests, including tests for adiponectin and CRP, were conducted in 198 male students, ages 18-26 years, who had fasted overnight. Insulin resistance (IR) and insulin secretion (beta-cell levels) were calculated using the homeostasis model assessment (HOMA), and LDL size was measured by PAGE. RESULTS Compared with the 90 men who had optimal BP, the 46 men with high-normal BP had increased heart rate, BMI, percent body fat, and serum leptin levels. In addition, they had greater serum insulin, HOMA IR, and beta-cell levels, lower adiponectin levels, and comparable CRP levels. Furthermore, the 46 men with high-normal BP had higher serum triglyceride and apolipoprotein (apo) B levels, and smaller LDL size; however, there was no difference in LDL and HDL cholesterol and apoA-I between men with optimal and high-normal BP. After adjusting for BMI, differences were still significant in serum adiponectin, heart rate, and LDL particle size. As BP rose, there was an increase in heart rate (BMI-adjusted least square means were 63, 65, and 70 bpm in men with optimal, normal, and high-normal BP, respectively; P = 0.005), whereas serum adiponectin (7.5, 6.6, and 6.4 mg/l; P = 0.007) and LDL particle size (271, 269, and 269 A; P = 0.008) decreased. CONCLUSIONS Young men with high-normal BP have a faster heart rate, lower serum adiponectin levels, and smaller LDL size than men with optimal BP, even after adjustment for BMI. These results suggest the necessity of preventing further development of cardiac and metabolic diseases in young people who have high-normal BP.
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Affiliation(s)
- Tsutomu Kazumi
- Department of Medicine, Hyogo Rehabilitation Center Hospital, Kobe, Japan.
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Colhoun HM, Francis DP, Rubens MB, Underwood SR, Fuller JH. The association of heart-rate variability with cardiovascular risk factors and coronary artery calcification: a study in type 1 diabetic patients and the general population. Diabetes Care 2001; 24:1108-14. [PMID: 11375379 DOI: 10.2337/diacare.24.6.1108] [Citation(s) in RCA: 76] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To examine the association of heart-rate variability with cardiovascular risk factors and coronary calcification in type 1 diabetic and nondiabetic subjects without a history of cardiovascular disease. Reduced heart-rate variability is associated with increased risk of coronary events. Whether it is associated with coronary atherosclerosis is unknown. RESEARCH DESIGN AND METHODS Power spectral analysis was used to define heart-rate variability in a cross-sectional study of 160 type 1 diabetic patients and 163 randomly selected nondiabetic adults from the general population aged 30-55 years. Coronary artery calcification was measured using electron beam-computed tomography. RESULTS Reduced heart-rate variability was associated with similar risk factors in the diabetic and nondiabetic subjects, namely higher HbA(1c), triglycerides, systolic blood pressure, BMI, and albumin excretion rate. Reduced heart-rate variability was significantly associated with coronary artery calcification in all subjects (odds ratio per tertile lower total power = 1.5, P = 0.01). This association was not independent of blood pressure or BMI (odds ratio on adjustment = 1.3, P = 0.1). CONCLUSIONS Reduced heart-rate variability clusters with other cardiovascular disease risk factors, especially those that are more common in the insulin resistance syndrome, and is associated with increased coronary calcification in asymptomatic young adults. Whether reduced heart-rate variability leads to other risk factor disturbances or mediates the effects of other risk factors on atherosclerosis deserves further study.
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Affiliation(s)
- H M Colhoun
- Deparetment of Epidemiology and Public Health, Royal Free and University College London Medical School, 1-19 Torrington Place, London WC1E 6BT, U.K.
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