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Viggars MR, Berko HE, Hesketh SJ, Wolff CA, Gutierrez-Monreal MA, Martin RA, Jennings IG, Huo Z, Esser KA. Skeletal muscle BMAL1 is necessary for transcriptional adaptation of local and peripheral tissues in response to endurance exercise training. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2023.10.13.562100. [PMID: 37905004 PMCID: PMC10614785 DOI: 10.1101/2023.10.13.562100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/02/2023]
Abstract
Objectives In this investigation, we addressed the contribution of the core circadian clock factor, BMAL1, in skeletal muscle to both acute transcriptional responses to exercise and transcriptional remodelling in response to exercise training. Additionally, we adopted a systems biology approach to investigate how loss of skeletal muscle BMAL1 altered peripheral tissue homeostasis as well as exercise training adaptations in iWAT, liver, heart, and lung of male mice. Methods Combining inducible skeletal muscle specific BMAL1 knockout mice, physiological testing and standardized exercise protocols, we performed a multi-omic analysis (transcriptomics, chromatin accessibility and metabolomics) to explore loss of muscle BMAL1 on muscle and peripheral tissue responses to exercise. Results Muscle-specific BMAL1 knockout mice demonstrated a blunted transcriptional response to acute exercise, characterized by the lack of upregulation of well-established exercise responsive transcription factors including Nr4a3 and Ppargc1a. Six weeks of exercise training in muscle-specific BMAL1 knockout mice induced significantly greater and divergent transcriptomic and metabolomic changes in muscle. Surprisingly, liver, lung, inguinal white adipose and heart showed divergent exercise training transcriptomes with less than 5% of 'exercise-training' responsive genes shared for each tissue between genotypes. Conclusion Our investigation has uncovered the critical role that BMAL1 plays in skeletal muscle as a key regulator of gene expression programs for both acute exercise and training adaptations. In addition, our work has uncovered the significant impact that altered exercise response in muscle plays in the peripheral tissue adaptation to exercise training. We also note that the transcriptome adaptations to steady state training suggest that without BMAL1, skeletal muscle does not achieve the expected homeostatic program. Our work also demonstrates that if the muscle adaptations diverge to a more maladaptive state this is linked to increased inflammation across many tissues. Understanding the molecular targets and pathways contributing to health vs. maladaptive exercise adaptations will be critical for the next stage of therapeutic design for exercise mimetics.
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Affiliation(s)
- Mark R Viggars
- Department of Physiology and Aging, University of Florida, Gainesville, Florida, United States
- Myology Institute, University of Florida, Gainesville, Florida, United States
| | - Hannah E Berko
- Department of Physiology and Aging, University of Florida, Gainesville, Florida, United States
- Myology Institute, University of Florida, Gainesville, Florida, United States
| | - Stuart J Hesketh
- Department of Physiology and Aging, University of Florida, Gainesville, Florida, United States
- Myology Institute, University of Florida, Gainesville, Florida, United States
- School of Medicine, University of Central Lancashire, United Kingdom
| | - Christopher A Wolff
- Department of Physiology and Aging, University of Florida, Gainesville, Florida, United States
- Myology Institute, University of Florida, Gainesville, Florida, United States
| | - Miguel A Gutierrez-Monreal
- Department of Physiology and Aging, University of Florida, Gainesville, Florida, United States
- Myology Institute, University of Florida, Gainesville, Florida, United States
| | - Ryan A Martin
- Department of Physiology and Aging, University of Florida, Gainesville, Florida, United States
- Myology Institute, University of Florida, Gainesville, Florida, United States
| | - Isabel G Jennings
- Department of Physiology and Aging, University of Florida, Gainesville, Florida, United States
- Myology Institute, University of Florida, Gainesville, Florida, United States
| | - Zhiguang Huo
- Department of Biostatistics, University of Florida, Gainesville, Florida, United States
| | - Karyn A Esser
- Department of Physiology and Aging, University of Florida, Gainesville, Florida, United States
- Myology Institute, University of Florida, Gainesville, Florida, United States
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Almuraikhy S, Doudin A, Domling A, Althani AAJF, Elrayess MA. Molecular regulators of exercise-mediated insulin sensitivity in non-obese individuals. J Cell Mol Med 2024; 28:e18015. [PMID: 37938877 PMCID: PMC10805515 DOI: 10.1111/jcmm.18015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2023] [Revised: 10/16/2023] [Accepted: 10/18/2023] [Indexed: 11/10/2023] Open
Abstract
Insulin resistance is a significant contributor to the development of type 2 diabetes (T2D) and is associated with obesity, physical inactivity, and low maximal oxygen uptake. While intense and prolonged exercise may have negative effects, physical activity can have a positive influence on cellular metabolism and the immune system. Moderate exercise has been shown to reduce oxidative stress and improve antioxidant status, whereas intense exercise can increase oxidative stress in the short term. The impact of exercise on pro-inflammatory cytokine production is complex and varies depending on intensity and duration. Exercise can also counteract the harmful effects of ageing and inflamm-ageing. This review aims to examine the molecular pathways altered by exercise in non-obese individuals at higher risk of developing T2D, including glucose utilization, lipid metabolism, mitochondrial function, inflammation and oxidative stress, with the potential to improve insulin sensitivity. The focus is on understanding the potential benefits of exercise for improving insulin sensitivity and providing insights for future targeted interventions before onset of disease.
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Affiliation(s)
- Shamma Almuraikhy
- Biomedical Research CenterQatar UniversityDohaQatar
- Groningen Research Institute of Pharmacy, Drug DesignGroningen UniversityGroningenThe Netherlands
| | - Asmaa Doudin
- Biomedical Research CenterQatar UniversityDohaQatar
| | - Alexander Domling
- Groningen Research Institute of Pharmacy, Drug DesignGroningen UniversityGroningenThe Netherlands
| | - Asmaa Ali J. F. Althani
- Biomedical Research CenterQatar UniversityDohaQatar
- Department of Biomedical Sciences, College of Health Science, QU HealthQatar UniversityDohaQatar
| | - Mohamed A. Elrayess
- Biomedical Research CenterQatar UniversityDohaQatar
- College of Pharmacy, QU HealthQatar UniversityDohaQatar
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Syeda UA, Battillo D, Visaria A, Malin SK. The importance of exercise for glycemic control in type 2 diabetes. AMERICAN JOURNAL OF MEDICINE OPEN 2023; 9:100031. [PMID: 39035065 PMCID: PMC11256236 DOI: 10.1016/j.ajmo.2023.100031] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 12/01/2022] [Accepted: 01/10/2023] [Indexed: 07/23/2024]
Abstract
Exercise is a first-line therapy recommended for patients with type 2 diabetes (T2D). Although moderate to vigorous exercise (e.g. 150 min/wk) is often advised alongside diet and/or behavior modification, exercise is an independent treatment that can prevent, delay or reverse T2D. Habitual exercise, consisting of aerobic, resistance or their combination, fosters improved short- and long-term glycemic control. Recent work also shows high-intensity interval training is successful at lowering blood glucose, as is breaking up sedentary behavior with short-bouts of light to vigorous movement (e.g. up to 3min). Interestingly, performing afternoon compared with morning as well as post-meal versus pre-meal exercise may yield slightly better glycemic benefit. Despite these efficacious benefits of exercise for T2D care, optimal exercise recommendations remain unclear when considering, dietary, medication, and/or other behaviors.
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Affiliation(s)
- U.S. Afsheen Syeda
- Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ, United States
| | - Daniel Battillo
- Department of Kinesiology and Health, Rutgers University, New Brunswick, NJ, United States
| | - Aayush Visaria
- Center for Pharmacoepidemiology and Treatment Sciences, Rutgers Institute for Health, Health Care Policy, and Aging Research, New Brunswick, NJ, United States
| | - Steven K. Malin
- Department of Kinesiology and Health, Rutgers University, New Brunswick, NJ, United States
- Center for Pharmacoepidemiology and Treatment Sciences, Rutgers Institute for Health, Health Care Policy, and Aging Research, New Brunswick, NJ, United States
- New Jersey Institute for Food, Nutrition and Health, Rutgers University, New Brunswick, NJ, United States
- Institute of Translational Medicine and Science, Rutgers University, New Brunswick, NJ, United States
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4
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AlMuraikhy S, Anwardeen N, Naeem A, Sellami M, Domling A, Agouni A, Elrayess MA. Comparing the Metabolic Profiles Associated with Fitness Status between Insulin-Sensitive and Insulin-Resistant Non-Obese Individuals. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph191912169. [PMID: 36231474 PMCID: PMC9564877 DOI: 10.3390/ijerph191912169] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 09/17/2022] [Accepted: 09/19/2022] [Indexed: 05/27/2023]
Abstract
(1) Background: Young non-obese insulin-resistant (IR) individuals could be at risk of developing metabolic diseases including type 2 diabetes mellitus. The protective effect of physical activity in this apparently healthy group is expected but not well characterized. In this study, clinically relevant metabolic profiles were determined and compared among active and sedentary insulin-sensitive (IS) and IR young non-obese individuals. (2) Methods: Data obtained from Qatar Biobank for 2110 young (20-30 years old) non-obese (BMI ≤ 30) healthy participants were divided into four groups, insulin-sensitive active (ISA, 30.7%), insulin-sensitive sedentary (ISS, 21.4%), insulin-resistant active (IRA, 20%), and insulin-resistant sedentary (IRS, 23.3%), using the homeostatic model assessment of insulin resistance (HOMA-IR) and physical activity questionnaires. The effect of physical activity on 66 clinically relevant biochemical tests was compared among the four groups using linear models. (3) Results: Overall, non-obese IR participants had significantly (p ≤ 0.001) worse vital signs, blood sugar profiles, inflammatory markers, liver function, lipid profiles, and vitamin D levels than their IS counterparts. Physical activity was positively associated with left handgrip (p ≤ 0.01) and levels of creatine kinase (p ≤ 0.001) and creatine kinase-2 (p ≤ 0.001) in both IS and IR subjects. Furthermore, physical activity was positively associated with levels of creatinine (p ≤ 0.01) and total vitamin D (p = 0.006) in the IR group and AST (p = 0.001), folate (p = 0.001), and hematocrit (p = 0.007) in the IS group. Conversely, physical inactivity was negatively associated with the white blood cell count (p = 0.001) and an absolute number of lymphocytes (p = 0.003) in the IR subjects and with triglycerides (p = 0.005) and GGT-2 (p ≤ 0.001) in the IS counterparts. (4) Conclusions: An independent effect of moderate physical activity was observed in non-obese apparently healthy individuals a with different HOMA-IR index. The effect was marked by an improved health profile including higher vitamin D and lower inflammatory markers in IRA compared to IRS, and a higher oxygen carrying capacity and lipid profile in ISA compared to the ISS counterparts.
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Affiliation(s)
- Shamma AlMuraikhy
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
- Groningen Research Institute of Pharmacy, Drug Design, Groningen University, 9712 CP Groningen, The Netherlands
| | - Najeha Anwardeen
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
| | - Aisha Naeem
- Ministry of Public Health, Doha P.O. Box 42, Qatar
- Department of Oncology and Pathology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3800 Reservoir Rd., NW, Washington, DC 20007, USA
| | - Maha Sellami
- Physical Education Department (PE), College of Education, Qatar University, Doha P.O. Box 2713, Qatar
| | - Alexander Domling
- Groningen Research Institute of Pharmacy, Drug Design, Groningen University, 9712 CP Groningen, The Netherlands
| | - Abdelali Agouni
- College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
| | - Mohamed A. Elrayess
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
- College of Pharmacy, QU Health, Qatar University, Doha P.O. Box 2713, Qatar
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5
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O'Reilly CL, Uranga S, Fluckey JD. Culprits or consequences: Understanding the metabolic dysregulation of muscle in diabetes. World J Biol Chem 2021; 12:70-86. [PMID: 34630911 PMCID: PMC8473417 DOI: 10.4331/wjbc.v12.i5.70] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Revised: 06/21/2021] [Accepted: 08/03/2021] [Indexed: 02/06/2023] Open
Abstract
The prevalence of type 2 diabetes (T2D) continues to rise despite the amount of research dedicated to finding the culprits of this debilitating disease. Skeletal muscle is arguably the most important contributor to glucose disposal making it a clear target in insulin resistance and T2D research. Within skeletal muscle there is a clear link to metabolic dysregulation during the progression of T2D but the determination of culprits vs consequences of the disease has been elusive. Emerging evidence in skeletal muscle implicates influential cross talk between a key anabolic regulatory protein, the mammalian target of rapamycin (mTOR) and its associated complexes (mTORC1 and mTORC2), and the well-described canonical signaling for insulin-stimulated glucose uptake. This new understanding of cellular signaling crosstalk has blurred the lines of what is a culprit and what is a consequence with regard to insulin resistance. Here, we briefly review the most recent understanding of insulin signaling in skeletal muscle, and how anabolic responses favoring anabolism directly impact cellular glucose disposal. This review highlights key cross-over interactions between protein and glucose regulatory pathways and the implications this may have for the design of new therapeutic targets for the control of glucoregulatory function in skeletal muscle.
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Affiliation(s)
| | - Selina Uranga
- Health and Kinesiology, Texas A&M University, TX 77843, United States
| | - James D Fluckey
- Health and Kinesiology, Texas A&M University, TX 77843, United States
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6
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Salvadori G, Mirisola MG, Longo VD. Intermittent and Periodic Fasting, Hormones, and Cancer Prevention. Cancers (Basel) 2021; 13:cancers13184587. [PMID: 34572814 PMCID: PMC8472354 DOI: 10.3390/cancers13184587] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Accepted: 09/09/2021] [Indexed: 12/25/2022] Open
Abstract
The restriction of proteins, amino acids or sugars can have profound effects on the levels of hormones and factors including growth hormone, IGF-1 and insulin. In turn, these can regulate intracellular signaling pathways as well as cellular damage and aging, but also multisystem regeneration. Both intermittent (IF) and periodic fasting (PF) have been shown to have both acute and long-term effects on these hormones. Here, we review the effects of nutrients and fasting on hormones and genes established to affect aging and cancer. We describe the link between dietary interventions and genetic pathways affecting the levels of these hormones and focus on the mechanisms responsible for the cancer preventive effects. We propose that IF and PF can reduce tumor incidence both by delaying aging and preventing DNA damage and immunosenescence and also by killing damaged, pre-cancerous and cancer cells.
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Affiliation(s)
- Giulia Salvadori
- Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy;
- IFOM, FIRC Institute of Molecular Oncology, 20139 Milan, Italy
| | - Mario Giuseppe Mirisola
- Department of Surgical, Oncological, and Oral Sciences, University of Palermo, 90127 Palermo, Italy;
| | - Valter D. Longo
- IFOM, FIRC Institute of Molecular Oncology, 20139 Milan, Italy
- Department of Biological Sciences, Longevity Institute, Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA
- Correspondence:
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7
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Chung Y, Hsiao YT, Huang WC. Physiological and Psychological Effects of Treadmill Overtraining Implementation. BIOLOGY 2021; 10:biology10060515. [PMID: 34200732 PMCID: PMC8230380 DOI: 10.3390/biology10060515] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 06/06/2021] [Accepted: 06/08/2021] [Indexed: 11/16/2022]
Abstract
Simple Summary Overtraining occurs when an imbalance between training stress and recovery exists, and it is prevalent in athletes, soldiers, physical education, and health education undergraduates as well as a number of female and male adolescents. Despite a broad body of evidence concerning physiological and psychological correlates of this syndrome, the pathomechanisms of overtraining are still poorly understood. This illustrates the need to establish animal models of this disorder. This article outlines and discusses physiological and psychological effects of the current established overtraining model, based on an eight-week exhaustive treadmill exercise that reveals the involvement of imbalanced energy expenditure, exacerbated inflammatory response, increased intestinal permeability, and anxiety status in the development and onset of overtraining. This study highlights the maladaptation of overtraining and provides an animal model to determine the effectiveness of possible strategies, including nutrition and monitoring, for treatment and prevention of overtraining syndromes in future studies. Abstract Overtraining in athletes usually causes profound and lasting deleterious effects on the maintenance of health and exercise capacity. Here, we established an overtraining animal model to investigate the physiological modulation for future strategic applications in vivo. We subjected C57BL/6 mice to exhaustive treadmill exercises daily for 8 weeks (the exhaustive exercise group). Next, the physiological and psychological outcomes were compared with the regular exercise and sedentary groups. Outcome measures included growth, glucose tolerance, exercise metabolism profiles, cytokine levels, intestinal tight junction gene expression, and psychological behavioral changes. Our results revealed that overtraining negatively affected the physiological and psychological changes in the current model. The exhaustive exercise group exhibited significantly lower endurance performance and imbalanced energy expenditure, causing a decrease in body fat mass and slowing down the growth curve. In addition, the inflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, and interleukin-1β) and immune cells (neutrophils and monocytes) were significantly elevated after successive exhaustive exercise interventions. Furthermore, overtraining-induced stress resulted in increased anxiety status and decreased food intake. Our findings reinforce the idea that an imbalance between exercise and recovery can impair health and performance maintenance after overtraining. This study highlights the maladaptation of overtraining and provides an animal model to determine the effectiveness of possible strategies, including nutrition and monitoring, for treatment and prevention of overtraining syndromes in future studies.
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Affiliation(s)
- Yi Chung
- College of Human Development and Health, National Taipei University of Nursing and Health Sciences, Taipei 11219, Taiwan;
| | - Yi-Ting Hsiao
- Department of Exercise and Health Science, National Taipei University of Nursing and Health Sciences, Taipei 11219, Taiwan;
| | - Wen-Ching Huang
- Department of Exercise and Health Science, National Taipei University of Nursing and Health Sciences, Taipei 11219, Taiwan;
- Graduate Institute of Metabolism and Obesity Sciences, Taipei Medical University, Taipei 11031, Taiwan
- Correspondence: ; Tel.: +886-2-2822-7101 (ext. 7721)
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8
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Lewis MT, Kasper JD, Bazil JN, Frisbee JC, Wiseman RW. Quantification of Mitochondrial Oxidative Phosphorylation in Metabolic Disease: Application to Type 2 Diabetes. Int J Mol Sci 2019; 20:E5271. [PMID: 31652915 PMCID: PMC6862501 DOI: 10.3390/ijms20215271] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Revised: 10/17/2019] [Accepted: 10/22/2019] [Indexed: 12/17/2022] Open
Abstract
Type 2 diabetes (T2D) is a growing health concern with nearly 400 million affected worldwide as of 2014. T2D presents with hyperglycemia and insulin resistance resulting in increased risk for blindness, renal failure, nerve damage, and premature death. Skeletal muscle is a major site for insulin resistance and is responsible for up to 80% of glucose uptake during euglycemic hyperglycemic clamps. Glucose uptake in skeletal muscle is driven by mitochondrial oxidative phosphorylation and for this reason mitochondrial dysfunction has been implicated in T2D. In this review we integrate mitochondrial function with physiologic function to present a broader understanding of mitochondrial functional status in T2D utilizing studies from both human and rodent models. Quantification of mitochondrial function is explained both in vitro and in vivo highlighting the use of proper controls and the complications imposed by obesity and sedentary lifestyle. This review suggests that skeletal muscle mitochondria are not necessarily dysfunctional but limited oxygen supply to working muscle creates this misperception. Finally, we propose changes in experimental design to address this question unequivocally. If mitochondrial function is not impaired it suggests that therapeutic interventions and drug development must move away from the organelle and toward the cardiovascular system.
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Affiliation(s)
- Matthew T Lewis
- Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
| | - Jonathan D Kasper
- Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
- Present address: Molecular Physiology Institute, Duke University, Durham, NC 27701, USA.
| | - Jason N Bazil
- Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
| | - Jefferson C Frisbee
- Department of Medical Biophysics, University of Western Ontario, London, ON N6A 3K7, Canada.
| | - Robert W Wiseman
- Department of Physiology, Michigan State University, East Lansing, MI 48824, USA.
- Department of Radiology, Michigan State University, East Lansing, MI 48824, USA.
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Beaudry KM, Devries MC. Nutritional Strategies to Combat Type 2 Diabetes in Aging Adults: The Importance of Protein. Front Nutr 2019; 6:138. [PMID: 31555655 PMCID: PMC6724448 DOI: 10.3389/fnut.2019.00138] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 08/13/2019] [Indexed: 12/14/2022] Open
Abstract
The prevalence of pre-diabetes (PD) and type II diabetes (T2D) has risen dramatically in recent years affecting an estimated 422 million adults worldwide. The risk of T2D increases with age, with the sharpest rise in diagnosis occurring after age 40. With age, there is also a progressive decline in muscle mass starting after the age of 30. The decline in muscle mass and function due to aging is termed sarcopenia and immediately precedes the sharp rise in T2D. The purpose of the current review is to discuss the role of protein to attenuate declines in muscle mass and insulin sensitivity to prevent T2D and sarcopenia in aging adults. The current recommended dietary allowance for protein consumption is set at 0.8 g/kg/day and is based on dated studies on young healthy men and may not be sufficient for older adults. Protein consumption upwards of 1.0-1.5 g/kg/day in older adults is able to induce improvements in glycemic control and muscle mass. Obesity, particularly central or visceral obesity is a major risk factor in the development of PD and T2D. However, the tissue composition of weight loss in older adults includes both lean body mass and fat mass and therefore may have adverse metabolic consequences in older adults who are already at a high risk of lean body mass loss. High protein diets have the ability to increase weight loss while preserving lean body mass therefore inducing "high-quality weight loss," which provides favorable metabolic changes in older adults. High protein diets also induce beneficial outcomes on glycemic markers due to satiety, lowered post-prandial glucose response, increased thermogenesis, and the ability to decrease rates of muscle protein breakdown (MPB). The consumption of dairy specific protein consumption has also been shown to improve insulin sensitivity by improving body composition, enhancing insulin release, accelerating fat oxidation, and stimulating rates of muscle protein synthesis (MPS) in older adults. Exercise, specifically resistance training, also works synergistically to attenuate the progression of PD and T2D by further stimulating rates of MPS thereby increasing muscle mass and inducing favorable changes in glycemic control independent of lean body mass increases.
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Affiliation(s)
- Kayleigh M Beaudry
- Department of Kinesiology, Faculty of Applied Health Sciences, University of Waterloo, Waterloo, ON, Canada
| | - Michaela C Devries
- Department of Kinesiology, Faculty of Applied Health Sciences, University of Waterloo, Waterloo, ON, Canada
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10
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Fealy CE, Nieuwoudt S, Foucher JA, Scelsi AR, Malin SK, Pagadala M, Cruz LA, Li M, Rocco M, Burguera B, Kirwan JP. Functional high-intensity exercise training ameliorates insulin resistance and cardiometabolic risk factors in type 2 diabetes. Exp Physiol 2019; 103:985-994. [PMID: 29766601 DOI: 10.1113/ep086844] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Accepted: 04/12/2018] [Indexed: 12/15/2022]
Abstract
NEW FINDINGS What is the central question of this study? Does short-duration, high-intensity exercise training that combines functional aerobic and resistance exercises into training sessions lasting 8-20 min benefit individuals with type 2 diabetes? What is the main finding and its importance? Functional high-intensity training improves insulin sensitivity and reduces cardiometabolic risk in individuals with type 2 diabetes. This type of exercise training may be an effective exercise mode for managing type 2 diabetes. The increase in insulin sensitivity addresses a key defect in type 2 diabetes. ABSTRACT Functional high-intensity training (F-HIT) is a novel fitness paradigm that integrates simultaneous aerobic and resistance training in sets of constantly varied movements, based on real-world situational exercises, performed at high-intensity in workouts that range from ∼8 to 20 min per session. We hypothesized that F-HIT would be an effective exercise mode for reducing insulin resistance in type 2 diabetes (T2D). We recruited 13 overweight/obese adults (5 males, 8 females; 53 ± 7 years; BMI 34.5 ± 3.6 kg m-2 , means ± SD) with T2D to participate in a 6-week (3 days week-1 ) supervised F-HIT programme. An oral glucose tolerance test was used to derive measures of insulin sensitivity. F-HIT significantly reduced fat mass (43.8 ± 83.8 vs. 41.6 ± 7.9 kg; P < 0.01), diastolic blood pressure (80.2 ± 7.1 vs. 74.5 ± 5.8; P < 0.01), blood lipids (triglyceride and VLDL, both P < 0.05) and metabolic syndrome z-score (6.4 ± 4.5 vs. -0.2 ± 5.2 AU; P < 0.001), and increased basal fat oxidation (0.08 ± 0.03 vs. 0.10 ± 0.04 g min-1 ; P = 0.05), and high molecular mass adiponectin (214.4 ± 88.9 vs. 288.8 ± 127.4 ng mL-1 ; P < 0.01). Importantly, F-HIT also increased insulin sensitivity (0.037 ± 0.010 vs. 0.042 ± 0.010 AU; P < 0.05). Increases in high molecular mass adiponectin and basal fat oxidation correlated with the change in insulin sensitivity (ρ, 0.75, P < 0.05 and ρ, 0.81, P < 0.01, respectively). Compliance with the training programme was >95% and no injuries or adverse events were reported. These data suggest that F-HIT may be an effective exercise mode for managing T2D. The increase in insulin sensitivity addresses a key defect in T2D and is consistent with improvements observed after more traditional aerobic exercise programmes in overweight/obese adults with T2D.
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Affiliation(s)
- Ciarán E Fealy
- Department of Pathobiology, Cleveland Clinic, Lerner Research Institute, Cleveland, OH, USA.,Department of Biomedical Sciences, Kent State University, Kent, OH, USA
| | - Stephan Nieuwoudt
- Department of Pathobiology, Cleveland Clinic, Lerner Research Institute, Cleveland, OH, USA.,Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA
| | - Julie A Foucher
- Department of Pathobiology, Cleveland Clinic, Lerner Research Institute, Cleveland, OH, USA
| | - Amanda R Scelsi
- Department of Pathobiology, Cleveland Clinic, Lerner Research Institute, Cleveland, OH, USA
| | - Steven K Malin
- Department of Pathobiology, Cleveland Clinic, Lerner Research Institute, Cleveland, OH, USA
| | - Mangesh Pagadala
- Department of Pathobiology, Cleveland Clinic, Lerner Research Institute, Cleveland, OH, USA.,Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Lauren A Cruz
- Department of Pathobiology, Cleveland Clinic, Lerner Research Institute, Cleveland, OH, USA
| | - Miranda Li
- Department of Pathobiology, Cleveland Clinic, Lerner Research Institute, Cleveland, OH, USA
| | - Michael Rocco
- Department of Cardiology, Cleveland Clinic, Cleveland, OH, USA
| | - Bartolome Burguera
- Endocrinology and Metabolism Institute, Cleveland Clinic, Cleveland, OH, USA
| | - John P Kirwan
- Department of Pathobiology, Cleveland Clinic, Lerner Research Institute, Cleveland, OH, USA.,Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, USA
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11
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Hagberg JM, Coyle EF, Baldwin KM, Cartee GD, Fontana L, Joyner MJ, Kirwan JP, Seals DR, Weiss EP. The historical context and scientific legacy of John O. Holloszy. J Appl Physiol (1985) 2019; 127:277-305. [PMID: 30730811 PMCID: PMC6732442 DOI: 10.1152/japplphysiol.00669.2018] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
John O. Holloszy, as perhaps the world's preeminent exercise biochemist/physiologist, published >400 papers over his 50+ year career, and they have been cited >41,000 times. In 1965 Holloszy showed for the first time that exercise training in rodents resulted in a doubling of skeletal muscle mitochondria, ushering in a very active era of skeletal muscle plasticity research. He subsequently went on to describe the consequences of and the mechanisms underlying these adaptations. Holloszy was first to show that muscle contractions increase muscle glucose transport independent of insulin, and he studied the mechanisms underlying this response throughout his career. He published important papers assessing the impact of training on glucose and insulin metabolism in healthy and diseased humans. Holloszy was at the forefront of rodent studies of caloric restriction and longevity in the 1980s, following these studies with important cross-sectional and longitudinal caloric restriction studies in humans. Holloszy was influential in the discipline of cardiovascular physiology, showing that older healthy and diseased populations could still elicit beneficial cardiovascular adaptations with exercise training. Holloszy and his group made important contributions to exercise physiology on the effects of training on numerous metabolic, hormonal, and cardiovascular adaptations. Holloszy's outstanding productivity was made possible by his mentoring of ~100 postdoctoral fellows and substantial NIH grant funding over his entire career. Many of these fellows have also played critical roles in the exercise physiology/biochemistry discipline. Thus it is clear that exercise biochemistry and physiology will be influenced by John Holloszy for numerous years to come.
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Affiliation(s)
- James M Hagberg
- Department of Kinesiology, University of Maryland School of Public Health, College Park, Maryland
| | - Edward F Coyle
- Department of Kinesiology and Health Education, University of Texas, Austin, Texas
| | - Kenneth M Baldwin
- Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, California
| | - Gregory D Cartee
- Muscle Biology Laboratory, School of Kinesiology; Department of Molecular and Integrative Physiology; and Institute of Gerontology, University of Michigan, Ann Arbor, Michigan
| | - Luigi Fontana
- Department of Medicine, Washington University School of Medicine, St. Louis, Missouri; Department of Clinical and Experimental Sciences, Brescia University Medical School, Brescia, Italy; and School of Medicine and Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia
| | - Michael J Joyner
- Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota
| | - John P Kirwan
- Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana
| | - Douglas R Seals
- Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado
| | - Edward P Weiss
- Department of Nutrition and Dietetics, Doisy College of Health Science, St. Louis University, St. Louis, Missouri
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Obesity and inactivity, not hyperglycemia, cause exercise intolerance in individuals with type 2 diabetes: Solving the obesity and inactivity versus hyperglycemia causality dilemma. Med Hypotheses 2019; 123:110-114. [DOI: 10.1016/j.mehy.2019.01.013] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Accepted: 01/15/2019] [Indexed: 12/29/2022]
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13
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Pickering C, Kiely J. Understanding Personalized Training Responses: Can Genetic Assessment Help? ACTA ACUST UNITED AC 2017. [DOI: 10.2174/1875399x01710010191] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:Traditional exercise prescription is based on the assumption that exercise adaptation is predictable and standardised across individuals. However, evidence has emerged in the past two decades demonstrating that large inter-individual variation exists regarding the magnitude and direction of adaption following exercise.Objective:The aim of this paper was to discuss the key factors influencing this personalized response to exercise in a narrative review format.Findings:Genetic variation contributes significantly to the personalized training response, with specific polymorphisms associated with differences in exercise adaptation. These polymorphisms exist in a number of pathways controlling exercise adaptation. Environmental factors such as nutrition, psycho-emotional response, individual history and training programme design also modify the inter-individual adaptation following training. Within the emerging field of epigenetics, DNA methylation, histone modifications and non-coding RNA allow environmental and lifestyle factors to impact genetic expression. These epigenetic mechanisms are themselves modified by genetic and non-genetic factors, illustrating the complex interplay between variables in determining the adaptive response. Given that genetic factors are such a fundamental modulator of the inter-individual response to exercise, genetic testing may provide a useful and affordable addition to those looking to maximise exercise adaption, including elite athletes. However, there are ethical issues regarding the use of genetic tests, and further work is needed to provide evidence based guidelines for their use.Conclusion:There is considerable inter-individual variation in the adaptive response to exercise. Genetic assessments may provide an additional layer of information allowing personalization of training programmes to an individual’s unique biology.
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Khazraee T, Fararouei M, Daneshmandi H, Mobasheri F, Zamanian Z. Maximal Oxygen Consumption, Respiratory Volume and Some Related Factors in Fire-fighting Personnel. Int J Prev Med 2017; 8:25. [PMID: 28479967 PMCID: PMC5404355 DOI: 10.4103/ijpvm.ijpvm_299_16] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2016] [Accepted: 02/19/2017] [Indexed: 12/25/2022] Open
Abstract
Background: Firefighters for difficult activities and rescue of damaged people must be in appropriate physical ability. Maximal oxygen capacity is an indicator for diagnosis of physical ability of workers. This study aimed to assess the cardiorespiratory system and its related factors in firefighters. Methods: This study was conducted on 110 firefighters from various stations. An self-administered questionnaire (respiratory disorders questionnaire, Tuxworth-Shahnavaz step test, and pulmonary function test) was used to collection of required data. Average of humidity and temperature was 52% and 17°C, respectively. Background average noise levels were between 55 and 65 dB. Data were analyzed using SPSS software (version 19). Results: The mean age of the study participants was 32 ± 6.2 years. The means of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1/FVC were 92% ±9.4%, 87% ±9.2%, and 80% ±6.1%, respectively. The participants’ mean VO2-max was 2.79 ± 0.29 L/min or 37.34 ± 4.27 ml/kg body weight per minute. The results revealed that weight has a direct association with vital capacity (VC), FVC, and peak expiratory flow. In addition, height was directly associated with VC, FVC, and VO2-max (P < 0.05). However, there was an inverse and significant association between height and FEV1/FVC (r = −0.23, P < 0.05). Height, weight, body mass index, and waist circumference were directly associated with VO2-max. Conclusions: The findings of this study showed that the amount of maximum oxygen consumption is close with the proposed range of this parameter among firefighters in other studies. Furthermore, the results of the study revealed that individuals had normal amounts of lung volume index. This issue can be attributed to the appropriate usage of respiratory masks.
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Affiliation(s)
- Touraj Khazraee
- Deputy of Occupational Health, Fasa University of Medical Science, Fasa, Iran
| | - Mohammad Fararouei
- Department of Occupational Health Engineering, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Epidemiology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hadi Daneshmandi
- Research Center for Health Sciences, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Farzane Mobasheri
- Department of Epidemiology, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Zahra Zamanian
- Department of Epidemiology, Shiraz University of Medical Sciences, Shiraz, Iran
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15
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Hespe GE, Kataru RP, Savetsky IL, García Nores GD, Torrisi JS, Nitti MD, Gardenier JC, Zhou J, Yu JZ, Jones LW, Mehrara BJ. Exercise training improves obesity-related lymphatic dysfunction. J Physiol 2016; 594:4267-82. [PMID: 26931178 PMCID: PMC4967732 DOI: 10.1113/jp271757] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Accepted: 02/24/2016] [Indexed: 01/04/2023] Open
Abstract
Key points
Obesity results in perilymphatic inflammation and lymphatic dysfunction. Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells. Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells. Abstract Although previous studies have shown that obesity markedly decreases lymphatic function, the cellular mechanisms that regulate this response remain unknown. In addition, it is unclear whether the pathological effects of obesity on the lymphatic system are reversible with behavioural modifications. The purpose of this study, therefore, was to analyse lymphatic vascular changes in obese mice and to determine whether these pathological effects are reversible with aerobic exercise. We randomized obese mice to either aerobic exercise (treadmill running for 30 min per day, 5 days a week, for 6 weeks) or a sedentary group that was not exercised and analysed lymphatic function using a variety of outcomes. We found that sedentary obese mice had markedly decreased collecting lymphatic vessel pumping capacity, decreased lymphatic vessel density, decreased lymphatic migration of immune cells, increased lymphatic vessel leakiness and decreased expression of lymphatic specific markers compared with lean mice (all P < 0.01). Aerobic exercise did not cause weight loss but markedly improved lymphatic function compared with sedentary obese mice. Exercise had a significant anti‐inflammatory effect, resulting in decreased perilymphatic accumulation of inflammatory cells and inducible nitric oxide synthase expression. In addition, exercise normalized isolated lymphatic endothelial cell gene expression of lymphatic specific genes, including VEGFR‐3 and Prox1. Taken together, our findings suggest that obesity impairs lymphatic function via multiple mechanisms and that these pathological changes can be reversed, in part, with aerobic exercise, independent of weight loss. In addition, our study shows that obesity‐induced lymphatic endothelial cell gene expression changes are reversible with behavioural modifications.
Obesity results in perilymphatic inflammation and lymphatic dysfunction. Lymphatic dysfunction in obesity is characterized by decreased lymphatic vessel density, decreased collecting lymphatic vessel pumping frequency, decreased lymphatic trafficking of immune cells, increased lymphatic vessel leakiness and changes in the gene expression patterns of lymphatic endothelial cells. Aerobic exercise, independent of weight loss, decreases perilymphatic inflammatory cell accumulation, improves lymphatic function and reverses pathological changes in gene expression in lymphatic endothelial cells.
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Affiliation(s)
- Geoffrey E Hespe
- The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Raghu P Kataru
- The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Ira L Savetsky
- The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Gabriela D García Nores
- The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jeremy S Torrisi
- The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Matthew D Nitti
- The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jason C Gardenier
- The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jie Zhou
- The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Jessie Z Yu
- The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Lee W Jones
- The Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Babak J Mehrara
- The Department of Surgery, Division of Plastic and Reconstructive Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
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16
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AbouAssi H, Slentz CA, Mikus CR, Tanner CJ, Bateman LA, Willis LH, Shields AT, Piner LW, Penry LE, Kraus EA, Huffman KM, Bales CW, Houmard JA, Kraus WE. The effects of aerobic, resistance, and combination training on insulin sensitivity and secretion in overweight adults from STRRIDE AT/RT: a randomized trial. J Appl Physiol (1985) 2016; 118:1474-82. [PMID: 25882384 DOI: 10.1152/japplphysiol.00509.2014] [Citation(s) in RCA: 59] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Most health organizations recommend a combination of aerobic training (AT) and resistance training (RT), yet few studies have compared their acute (within 24 h of the last exercise bout) and sustained (after 14 days of no exercise training) effects alone and in combination on glucose metabolism. The present study (Studies Targeting Risk Reduction Interventions through Defined Exercise-Aerobic Training and/or Resistance Training) compared the effects of AT, RT, and the combination (AT/RT) on insulin action at both acute and sustained phases. Subjects (N = 196) were 18-70 yr old (mean age = 50 yr), overweight (mean body mass index = 30 kg/m2), sedentary with moderate dyslipidemia, and were randomized into one of three 8-mo exercise groups: 1) RT: 3 days/wk, 8 exercises, 3 sets/exercise, 8-12 repetitions/set; 2) AT: equivalent to ∼19.2 km/wk (12 miles/wk) at 75% peak O2 consumption; 3) AT/RT: the combination of AT and RT. One hundred forty-four subjects completed the intervention. Eighty-eight subjects completed all pre- and postintervention testing visits. Insulin sensitivity, glucose effectiveness, and disposition index were measured via a frequently sampled intravenous glucose tolerance test with subsequent minimal model analyses. AT/RT resulted in greater improvements in insulin sensitivity, β-cell function (disposition index), and glucose effectiveness than either AT or RT alone (all P < 0.05). Approximately 52% of the improvement in insulin sensitivity by AT/RT was retained 14 days after the last exercise training bout. Neither AT or RT led to acute or chronic improvement in sensitivity index. In summary, only AT/RT (which required twice as much time as either alone) led to significant acute and sustained benefits in insulin sensitivity
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Malin SK, Liu Z, Barrett EJ, Weltman A. Exercise resistance across the prediabetes phenotypes: Impact on insulin sensitivity and substrate metabolism. Rev Endocr Metab Disord 2016; 17:81-90. [PMID: 27106830 DOI: 10.1007/s11154-016-9352-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Prediabetes is a heterogeneous term that encompasses different origins of insulin resistance and insulin secretion that contribute to distinct patterns of hyperglycemia. In fact, prediabetes is an umbrella term that characterizes individuals at high risk for developing type 2 diabetes (T2D) and/or cardiovascular disease (CVD). Based on current definitions there are at least 3 distinct phenotypes of prediabetes: impaired fasting glucose (IFG), impaired glucose tolerant (IGT), or the combination of both (IFG + IGT). Each phenotype is clinically relevant as they are uniquely recognized as having different levels of risk for progressing to T2D and CVD. Herein, we discuss the underlying pathophysiology that characterizes IFG, IGT and the combination, as well as examine how some of these phenotypes appear resistant to traditional exercise interventions. We propose that substrate metabolism differences between the prediabetes phenotypes may be a unifying mechanism that explains the inter-subject variation in response to exercise seen across obese, metabolic syndrome, pre-diabetic and T2D patients in the current literature. Ultimately, a better understanding of the pathophysiologic mechanisms that govern disturbances responsible for fasting vs. postprandial hyperglycemia and the combination of both is important for designing optimal and personalized exercise treatment strategies that treat and prevent hyperglycemia and CVD risk.
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Affiliation(s)
- Steven K Malin
- Applied Metabolism & Physiology Laboratory, Department of Kinesiology, University of Virginia, 210 Emmet St., 225A Memorial Gymnasium, Charlottesville, VA, USA.
- Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA, USA.
| | - Zhenqi Liu
- Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA, USA
| | - Eugene J Barrett
- Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA, USA
| | - Arthur Weltman
- Applied Metabolism & Physiology Laboratory, Department of Kinesiology, University of Virginia, 210 Emmet St., 225A Memorial Gymnasium, Charlottesville, VA, USA
- Division of Endocrinology and Metabolism, University of Virginia, Charlottesville, VA, USA
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18
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Böhm A, Weigert C, Staiger H, Häring HU. Exercise and diabetes: relevance and causes for response variability. Endocrine 2016; 51:390-401. [PMID: 26643313 PMCID: PMC4762932 DOI: 10.1007/s12020-015-0792-6] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2015] [Accepted: 10/28/2015] [Indexed: 12/31/2022]
Abstract
Exercise as a key prevention strategy for diabetes and obesity is commonly accepted and recommended throughout the world. Unfortunately, not all individuals profit to the same extent, some exhibit exercise resistance. This phenomenon of non-response to exercise is found for several endpoints, including glucose tolerance and insulin sensitivity. Since these non-responders are of notable quantity, there is the need to understand the underlying mechanisms and to identify predictors of response. This displays the basis to develop personalized training intervention regimes. In this review, we summarize the current knowledge on response variability, with focus on human studies and improvement of glucose homeostasis as outcome.
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Affiliation(s)
- Anja Böhm
- Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, University Hospital Tübingen, Eberhard Karls University Tübingen, 72076, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard Karls University Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), 85764, München-Neuherberg, Germany
| | - Cora Weigert
- Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, University Hospital Tübingen, Eberhard Karls University Tübingen, 72076, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard Karls University Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), 85764, München-Neuherberg, Germany
| | - Harald Staiger
- Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, University Hospital Tübingen, Eberhard Karls University Tübingen, 72076, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard Karls University Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), 85764, München-Neuherberg, Germany
| | - Hans-Ulrich Häring
- Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Angiology, Nephrology, and Clinical Chemistry, University Hospital Tübingen, Eberhard Karls University Tübingen, 72076, Tübingen, Germany.
- Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the Eberhard Karls University Tübingen, Tübingen, Germany.
- German Center for Diabetes Research (DZD), 85764, München-Neuherberg, Germany.
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High Intensity Interval Training Improves Glycaemic Control and Pancreatic β Cell Function of Type 2 Diabetes Patients. PLoS One 2015; 10:e0133286. [PMID: 26258597 PMCID: PMC4530878 DOI: 10.1371/journal.pone.0133286] [Citation(s) in RCA: 96] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2015] [Accepted: 06/19/2015] [Indexed: 11/19/2022] Open
Abstract
Physical activity improves the regulation of glucose homeostasis in both type 2 diabetes (T2D) patients and healthy individuals, but the effect on pancreatic β cell function is unknown. We investigated glycaemic control, pancreatic function and total fat mass before and after 8 weeks of low volume high intensity interval training (HIIT) on cycle ergometer in T2D patients and matched healthy control individuals. Study design/method: Elderly (56 yrs±2), non-active T2D patients (n = 10) and matched (52 yrs±2) healthy controls (CON) (n = 13) exercised 3 times (10×60 sec. HIIT) a week over an 8 week period on a cycle ergometer. Participants underwent a 2-hour oral glucose tolerance test (OGTT). On a separate day, resting blood pressure measurement was conducted followed by an incremental maximal oxygen uptake (V˙ O2max) cycle ergometer test. Finally, a whole body dual X-ray absorptiometry (DXA) was performed. After 8 weeks of training, the same measurements were performed. Results: in the T2D-group, glycaemic control as determined by average fasting venous glucose concentration (p = 0.01), end point 2-hour OGTT (p = 0.04) and glycosylated haemoglobin (p = 0.04) were significantly reduced. Pancreatic homeostasis as determined by homeostatic model assessment of insulin resistance (HOMA-IR) and HOMA β cell function (HOMA-%β) were both significantly ameliorated (p = 0.03 and p = 0.03, respectively). Whole body insulin sensitivity as determined by the disposition index (DI) was significantly increased (p = 0.03). During OGTT, the glucose continuum was significantly reduced at -15 (p = 0.03), 30 (p = 0.03) and 120 min (p = 0.03) and at -10 (p = 0.003) and 0 min (p = 0.003) with an additional improvement (p = 0.03) of its 1st phase (30 min) area under curve (AUC). Significant abdominal fat mass losses were seen in both groups (T2D: p = 0.004 and CON: p = 0.02) corresponding to a percentage change of -17.84%±5.02 and -9.66%±3.07, respectively. Conclusion: these results demonstrate that HIIT improves overall glycaemic control and pancreatic β cell function in T2D patients. Additionally, both groups experienced abdominal fat mass losses. These findings demonstrate that HIIT is a health beneficial exercise strategy in T2D patients.
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Abstract
There is a general perception that increased physical activity will improve glucose homeostasis in all individuals. While this is an attractive concept, this conclusion may be overly simplistic and even misleading. The topic was reviewed extensively over 30 years ago and it was concluded that acute exercise enhances glucose uptake. However, in some cases the chronic influence of interventions utilizing exercise may have little effect on glucose metabolism. Moreover, insulin resistance often returns to near baseline levels within a couple of days following cessation of the exercise bout; leaving the overall effectiveness of the intervention in question. Since improving glucose homeostasis should be the focal endpoint of any intervention designed to mitigate the overwhelming degree of insulin resistance in individuals at risk for metabolic disease, it is essential to evaluate the key components of a successful approach.
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Affiliation(s)
- Tyler E Keshel
- Institute of Arctic Biology, University of Alaska-Fairbanks, Fairbanks, AK, USA
| | - Robert H Coker
- Institute of Arctic Biology, University of Alaska-Fairbanks, Fairbanks, AK, USA ; Center for Translational Research in Aging and Longevity, Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
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Venkatasamy VV, Pericherla S, Manthuruthil S, Mishra S, Hanno R. Effect of Physical activity on Insulin Resistance, Inflammation and Oxidative Stress in Diabetes Mellitus. J Clin Diagn Res 2013; 7:1764-6. [PMID: 24086908 PMCID: PMC3782965 DOI: 10.7860/jcdr/2013/6518.3306] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2013] [Accepted: 07/02/2013] [Indexed: 11/24/2022]
Abstract
Diabetes Mellitus is a growing health concern projected to affect 366 million people worldwide by around 2030. Multiple approaches to address this health concern are documented; amongst which increased the habitual physical activity has been shown to be beneficial. Various mechanisms demonstrated show improvement of cellular insulin sensitivity. The interplay between insulin sensitivity and insulin resistance plays a key role in development and persistence of the diabetic state, which can be directly linked to the levels of physical activity. Regulation of adiponectin and leptin levels are also linked to physical activity via reduction of central obesity. Inflammatory markers, free radical reduction and up-regulation of physiological antioxidant processes are also observed in subjects with increased physical activity schedules, all of which play a significant role in the pathogenesis of Diabetes Mellitus.
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Affiliation(s)
| | | | | | | | - Ram Hanno
- Graduate, Kasturba Medical College, Manipal, India
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Slentz CA, Tanner CJ, Bateman LA, Durheim MT, Huffman KM, Houmard JA, Kraus WE. Effects of exercise training intensity on pancreatic beta-cell function. Diabetes Care 2009; 32:1807-11. [PMID: 19592624 PMCID: PMC2752909 DOI: 10.2337/dc09-0032] [Citation(s) in RCA: 144] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Insulin resistance and beta-cell dysfunction both are important contributors to the pathogenesis of type 2 diabetes. Exercise training improves insulin sensitivity, but its effects on beta-cell function are less well studied. RESEARCH DESIGN AND METHODS Sedentary, overweight adults were randomized to control or one of three 8-month exercise programs: 1) low amount/moderate intensity, 2) low amount/vigorous intensity, or 3) high amount/vigorous intensity. Of 387 randomized, 260 completed the study and 237 had complete data. Insulin sensitivity (S(i)), acute insulin response to glucose (AIRg), and the disposition index (DI = S(i) x AIRg) were modeled from an intravenous glucose tolerance test. RESULTS Compared with control subjects, all three training programs led to increases in DI. However, the moderate-intensity group experienced a significantly larger increase in DI than either of the vigorous-intensity groups and through a different mechanism. The high-amount/vigorous-intensity group improved S(i) and had a compensatory reduction in AIRg, whereas the moderate-intensity group had a similar improvement in S(i) but almost no reduction in AIRg. Importantly, the inactive control group experienced a significant increase in fasting glucose. CONCLUSIONS To the extent that the DI accurately reflects beta-cell function, we observed that both moderate- and vigorous-intensity exercise training improved beta-cell function, albeit through distinct mechanisms. It is not clear which of these mechanisms is preferable for maintenance of metabolic health. While moderate-intensity exercise led to a larger improvement in DI, which may reflect a transition toward a more normal DI, longer-term investigations would be necessary to determine which was more effective at reducing diabetes risk.
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Affiliation(s)
- Cris A Slentz
- Division of Cardiovascular Medicine, Duke University Medical Center, Durham, North Carolina, USA.
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Abstract
Swimming is an exercise modality that is highly suitable for health promotion and disease prevention, and is one of the most popular, most practiced and most recommended forms of physical activity. Yet little information is available concerning the influence of regular swimming on coronary heart disease (CHD). Exercise recommendations involving swimming have been generated primarily from unjustified extrapolation of the data from other modes of exercise (e.g. walking and cycling). Available evidence indicates that, similarly to other physically active adults, the CHD risk profile is more favourable in swimmers than in sedentary counterparts and that swim training results in the lowering of some CHD risk factors. However, the beneficial impact of regular swimming may be smaller than land-based exercises. In some cases, regular swimming does not appear to confer beneficial effects on some CHD risk factors. Moreover, swimming has not been associated with the reduced risks of developing CHD. Thus, extrapolation of research findings using land-based exercises into swimming cannot be justified, based on the available research. Clearly, more research is required to properly assess the effects of regular swimming on CHD risks in humans.
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Affiliation(s)
- Hirofumi Tanaka
- Department of Kinesiology and Health Education, The University of Texas at Austin, Austin, Texas 78712, USA.
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Bhashyam S, Parikh P, Bolukoglu H, Shannon AH, Porter JH, Shen YT, Shannon RP. Aging is associated with myocardial insulin resistance and mitochondrial dysfunction. Am J Physiol Heart Circ Physiol 2007; 293:H3063-71. [PMID: 17873028 DOI: 10.1152/ajpheart.00163.2007] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Aging is associated with insulin resistance, often attributable to obesity and inactivity. Recent evidence suggests that skeletal muscle insulin resistance in aging is associated with mitochondrial alterations. Whether this is true of the senescent myocardium is unknown. Twelve young (Y, 4 years old) and 12 old (O, 11 years old) dogs, matched for body mass, were instrumented with left-ventricular pressure gauges, aortic and coronary sinus catheters, and flow probes on left circumflex artery. Before surgery, all dogs participated in a 6-wk exercise program. Dogs underwent measurements of hemodynamics and plasma substrates before and during a 2-h hyperinsulinemic-euglycemic clamp to measure whole body and myocardial glucose and nonesterified fatty acid uptake. Following the protocol, myocardial and skeletal samples were obtained to measure components of the insulin-signaling cascade and mitochondrial structure. There was no difference in plasma glucose (Y, 90 +/- 4 mg/dl; O, 87 +/- 4 mg/dl), but old dogs had higher (P < 0.02) nonesterified fatty acids (Y, 384 +/- 48 micromol/l; O, 952 +/- 97 micromol/l) and plasma insulin (Y, 39 +/- 11 pmol/l; O, 108 +/- 18 pmol/l). Old dogs had impaired total body glucose disposition (Y, 11.5 +/- 1 mg x kg(-1) x min(-1); O, 8.0 +/- 0.5 mg x kg(-1) x min(-1); P < 0.05) and insulin-stimulated myocardial glucose uptake (Y, 3.5 +/- 0.3 mg x min(-1) x g(-1); O, 1.8 +/- 0.3 mg x min(-1) x g(-1); P < 0.05). The impaired insulin action was associated with altered insulin signaling and glucose transporter (GLUT4) translocation. There were myocardial mitochondrial structural changes observed in association with decreased expression of uncoupling protein-3. Aging is associated with both whole body and myocardial insulin resistance, independent of obesity and inactivity, but involving altered mitochondrial structure and impaired cellular insulin action.
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Affiliation(s)
- Siva Bhashyam
- Department of Medicine, Allegheny General Hospital, The University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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Foy CG, Foley KL, D'Agostino RB, Goff DC, Mayer-Davis E, Wagenknecht LE. Physical activity, insulin sensitivity, and hypertension among US adults: findings from the Insulin Resistance Atherosclerosis Study. Am J Epidemiol 2006; 163:921-8. [PMID: 16554349 DOI: 10.1093/aje/kwj113] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Although regular physical activity is associated with less hypertension and improved insulin sensitivity, there is debate regarding the role of insulin sensitivity in hypertension. Thus, in this cross-sectional study, the authors investigated whether physical activity and insulin sensitivity were associated with hypertension. The sample consisted of 1,599 persons aged 40-69 years who participated in the Insulin Resistance Atherosclerosis Study. The outcome measure was hypertension as measured by a standard protocol. Energy expended in vigorous physical activity was calculated from a recall interview on past-year physical activity. Descriptive statistics revealed that 590 (37%) participants had prevalent hypertension. In adjusted logistic regression analysis, participants expending >or=150 kcal/day in vigorous physical activity had an odds ratio for hypertension of 0.73 (95% confidence interval (CI): 0.55, 0.98) in comparison with participants who were sedentary. Further adjustment for insulin sensitivity resulted in attenuation of the effect of vigorous physical activity on hypertension (odds ratio = 0.97, 95% CI: 0.71, 1.33), while the effect of insulin sensitivity was significant (odds ratio = 0.33, 95% CI: 0.26, 0.41). These results suggest that longitudinal studies are warranted to determine whether insulin sensitivity is a mediator of the relation between physical activity and hypertension.
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Affiliation(s)
- Capri Gabrielle Foy
- Department of Public Health Sciences, School of Medicine, Wake Forest University, Winston-Salem, NC 27104, USA.
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Franks PW, Luan J, Barroso I, Brage S, Gonzalez Sanchez JL, Ekelund U, Ríos MS, Schafer AJ, O'Rahilly S, Wareham NJ. Variation in the eNOS gene modifies the association between total energy expenditure and glucose intolerance. Diabetes 2005; 54:2795-801. [PMID: 16123371 DOI: 10.2337/diabetes.54.9.2795] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Endothelium-derived nitric oxide (NO) facilitates skeletal muscle glucose uptake. Energy expenditure induces the endothelial NO synthase (eNOS) gene, providing a mechanism for insulin-independent glucose disposal. The object was to test 1) the association of genetic variation in eNOS, as assessed by haplotype-tagging single nucleotide polymorphisms (htSNPs) with type 2 diabetes, and 2) the interaction between eNOS haplotypes and total energy expenditure on glucose intolerance. Using multivariate models, we tested associations between eNOS htSNPs and diabetes (n = 461 and 474 case and control subjects, respectively) and glucose intolerance (two cohorts of n = 706 and 738 U.K. and Spanish Caucasians, respectively), and we tested eNOS x total energy expenditure interactions on glucose intolerance. An overall association between eNOS haplotype and diabetes was observed (P = 0.004). Relative to the most common haplotype (111), two haplotypes (121 and 212) tended to increase diabetes risk (OR 1.22, 95% CI 0.96-1.55), and one (122) was associated with decreased risk (0.58, 0.39-0.86). In the cohort studies, no association was observed between haplotypes and 2-h glucose (P > 0.10). However, we observed a significant total energy expenditure-haplotype interaction (P = 0.007). Genetic variation at the eNOS locus is associated with diabetes, which may be attributable to an enhanced effect of total energy expenditure on glucose disposal in individuals with specific eNOS haplotypes. Gene-environment interactions such as this may help explain why replication of genetic association frequently fails.
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Affiliation(s)
- Paul W Franks
- National Institute of DiabetesDigestiveKidney Diseases, 1550 E. Indian School Rd., Phoenix, AZ 85014, USA.
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Evans EM, Racette SB, Peterson LR, Villareal DT, Greiwe JS, Holloszy JO. Aerobic power and insulin action improve in response to endurance exercise training in healthy 77-87 yr olds. J Appl Physiol (1985) 2005; 98:40-5. [PMID: 15591302 DOI: 10.1152/japplphysiol.00928.2004] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Previous studies have demonstrated that frail octogenarians have an attenuated capacity for cardiovascular adaptations to endurance exercise training. In the present study, we determined the magnitude of cardiovascular and metabolic adaptations to high-intensity endurance exercise training in healthy, nonfrail elderly subjects. Ten subjects [8 men, 2 women, 80.3 yr (SD2.5)] completed 10-12 mo (108 exercise sessions) of a supervised endurance exercise training program consisting of 2.5 sessions/wk (SD 0.2), 58 min/session (SD 6), at an intensity of 83% (SD 5) of peak heart rate. Primary outcomes were maximal attainable aerobic power [peak aerobic capacity (Vo(2peak))]; serum lipids, oral glucose tolerance, and insulin action during a hyperglycemic clamp; body composition by dual-energy X-ray absorptiometry, and energy expenditure using doubly labeled water and indirect calorimetry. The training program resulted in an increase in Vo(2peak) of 15% (SD 7) [22.9 (SD 3.3) to 26.2 ml.kg(-1).min(-1) (SD 4.0); P < 0.0001]. Favorable lipid changes included reductions in total cholesterol (-8%; P = 0.002) and LDL cholesterol (-10%; P = 0.003), with no significant change in HDL cholesterol or triglycerides. Insulin action improved, as evidenced by a 29% increase in glucose disposal rate relative to insulin concentration during the hyperglycemic clamp. Fat mass decreased by 1.8 kg (SD 1.4) (P = 0.003); lean mass did not change. Total energy expenditure increased by 400 kcal/day because of an increase in physical activity. No change occurred in resting metabolism. In summary, healthy nonfrail octogenarians can adapt to high-intensity endurance exercise training with improvements in aerobic power, insulin action, and serum lipid and lipoprotein risk factors for coronary heart disease; however, the adaptations in aerobic power and insulin action are attenuated compared with middle-aged individuals.
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Affiliation(s)
- Ellen M Evans
- Section of Applied Physiology, Division of Geriatrics and Nutritional Sciences, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
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Boulé NG, Weisnagel SJ, Lakka TA, Tremblay A, Bergman RN, Rankinen T, Leon AS, Skinner JS, Wilmore JH, Rao DC, Bouchard C. Effects of exercise training on glucose homeostasis: the HERITAGE Family Study. Diabetes Care 2005; 28:108-14. [PMID: 15616242 DOI: 10.2337/diacare.28.1.108] [Citation(s) in RCA: 238] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To determine the effect of a 20-week endurance training program in healthy, previously sedentary participants on measures derived from an intravenous glucose tolerance test (i.v.GTT). RESEARCH DESIGN AND METHODS An i.v.GTT was performed before and after a standardized training program in 316 women and 280 men (173 blacks and 423 whites). Participants exercised on cycle ergometers 3 days per week for 60 sessions. The exercise intensity was progressively increased from 55% VO2max for 30 min per session to 75% VO2max for 50 min per session. RESULTS Mean insulin sensitivity increased by 10% (P < 0.001) following the intervention, but the variability in the changes was high. Men had larger improvements than women (P = 0.02). Improvements in fasting insulin were transitory, disappearing 72 h after the last bout of exercise. There were also significant mean increases in the glucose disappearance index (3%, P = 0.02) and in glucose effectiveness (11%, P < 0.001), measures of glucose tolerance and of the capacity of glucose to mediate its own disposal, respectively. The acute insulin response to glucose, a measure of insulin secretion, increased by 7% in the quartile with the lowest baseline glucose tolerance and decreased by 14% in the quartile with the highest baseline glucose tolerance (P < 0.001). The glucose area below fasting levels during the i.v.GTT was reduced by 7% (P = 0.02). CONCLUSIONS Although the effects of structured regular exercise were highly variable, there were improvements in virtually all i.v.GTT-derived variables. In the absence of substantial weight loss, regular exercise is required for sustained improvements in glucose homeostasis.
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Affiliation(s)
- Normand G Boulé
- Division of Kinesiology, Laval University, Sainte-Foy, Québec, Canada
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Green DJ, Maiorana A, O'Driscoll G, Taylor R. Effect of exercise training on endothelium-derived nitric oxide function in humans. J Physiol 2004; 561:1-25. [PMID: 15375191 PMCID: PMC1665322 DOI: 10.1113/jphysiol.2004.068197] [Citation(s) in RCA: 670] [Impact Index Per Article: 31.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Vascular endothelial function is essential for maintenance of health of the vessel wall and for vasomotor control in both conduit and resistance vessels. These functions are due to the production of numerous autacoids, of which nitric oxide (NO) has been the most widely studied. Exercise training has been shown, in many animal and human studies, to augment endothelial, NO-dependent vasodilatation in both large and small vessels. The extent of the improvement in humans depends upon the muscle mass subjected to training; with forearm exercise, changes are restricted to the forearm vessels while lower body training can induce generalized benefit. Increased NO bioactivity with exercise training has been readily and consistently demonstrated in subjects with cardiovascular disease and risk factors, in whom antecedent endothelial dysfunction exists. These conditions may all be associated with increased oxygen free radicals which impact on NO synthase activity and with which NO reacts; repeated exercise and shear stress stimulation of NO bioactivity redresses this radical imbalance, hence leading to greater potential for autacoid bioavailability. Recent human studies also indicate that exercise training may improve endothelial function by up-regulating eNOS protein expression and phosphorylation. While improvement in NO vasodilator function has been less frequently found in healthy subjects, a higher level of training may lead to improvement. Regarding time course, studies indicate that short-term training increases NO bioactivity, which acts to homeostatically regulate the shear stress associated with exercise. Whilst the increase in NO bioactivity dissipates within weeks of training cessation, studies also indicate that if exercise is maintained, the short-term functional adaptation is succeeded by NO-dependent structural changes, leading to arterial remodelling and structural normalization of shear. Given the strong prognostic links between vascular structure, function and cardiovascular events, the implications of these findings are obvious, yet many unanswered questions remain, not only concerning the mechanisms responsible for NO bioactivity, the nature of the cellular effect and relevance of other autacoids, but also such practical questions as the optimal intensity, modality and volume of exercise training required in different populations.
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Affiliation(s)
- Daniel J Green
- School of Human Movement and Exercise Science, University of Western Australia, Mailbag Delivery M408, 35 Stirling Highway, Crawley WA 6009, Australia.
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Affiliation(s)
- Judith G Regensteiner
- Department of Medicine, Program for Women's Health Research, Section of Vascular Medicine, Divisions of Internal Medicine and Cardiology, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
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Abstract
In the past two decades, normal endothelial function has been identified as integral to vascular health. The endothelium produces numerous vasodilator and vasoconstrictor compounds that regulate vascular tone; the vasodilator, nitric oxide (NO), has additional antiatherogenic properties, is probably the most important and best characterised mediator, and its intrinsic vasodilator function is commonly used as a surrogate index of endothelial function. Many conditions, including atherosclerosis, diabetes mellitus and even vascular risk factors, are associated with endothelial dysfunction, which, in turn, correlates with cardiovascular mortality. Furthermore, clinical benefit and improved endothelial function tend to be associated in response to interventions. Shear stress on endothelial cells is a potent stimulus for NO production. Although the role of endothelium-derived NO in acute exercise has not been fully resolved, exercise training involving repetitive bouts of exercise over weeks or months up-regulates endothelial NO bioactivity. Animal studies have found improved endothelium-dependent vasodilation after as few as 7 days of exercise. Consequent changes in vasodilator function appear to persist for several weeks but may regress with long-term training, perhaps reflecting progression to structural adaptation which may, however, have been partly endothelium-dependent. The increase in blood flow, and change in haemodynamics that occur during acute exercise may, therefore, provide a stimulus for both acute and chronic changes in vascular function. Substantial differences within species and within the vasculature appear to exist. In humans, exercise training improves endothelium-dependent vasodilator function, not only as a localised phenomenon in the active muscle group, but also as a systemic response when a relatively large mass of muscle is activated regularly during an exercise training programme. Individuals with initially impaired endothelial function at baseline appear to be more responsive to exercise training than healthy individuals; that is, it is more difficult to improve already normal vascular function. While improvement is reflected in increased NO bioactivity, the detail of mechanisms, for example the relative importance of up-regulation of mediators and antioxidant effects, is unclear. Optimum training schedules, possible sequential changes and the duration of benefit under various conditions also remain largely unresolved. In summary, epidemiological evidence strongly suggests that regular exercise confers beneficial effects on cardiovascular health. Shear stress-mediated improvement in endothelial function provides one plausible explanation for the cardioprotective benefits of exercise training.
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Affiliation(s)
- Andrew Maiorana
- Department of Human Movement and Exercise Science, The University of Western Australia, Crawley, Western Australia, Australia.
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Goodpaster BH, Katsiaras A, Kelley DE. Enhanced fat oxidation through physical activity is associated with improvements in insulin sensitivity in obesity. Diabetes 2003; 52:2191-7. [PMID: 12941756 DOI: 10.2337/diabetes.52.9.2191] [Citation(s) in RCA: 226] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Skeletal muscle insulin resistance entails dysregulation of both glucose and fatty acid metabolism. This study examined whether a combined intervention of physical activity and weight loss influences fasting rates of fat oxidation and insulin-stimulated glucose disposal. Obese (BMI >30 kg/m(2)) volunteers (9 men and 16 women) without diabetes, aged 39 +/- 4 years, completed 16 weeks of moderate-intensity physical activity combined with caloric reduction. Body composition was determined by dual-energy X-ray absorptiometry and computed tomography. Glucose disposal rates (R(d)) were measured during euglycemic hyperinsulinemia (40 mU x m(-2) x min(-1)), and substrate oxidation was determined via indirect calorimetry. Fat mass and regional fat depots were reduced and VO(2max) improved by 19%, from 38.8 +/- 1.2 to 46.0 +/- 1.0 ml x kg fat-free mass (FFM)(-1) x min(-1) (P < 0.05). Insulin sensitivity improved 49 +/- 10% (6.70 +/- 0.40 to 9.51 +/- 0.51 mg x min(-1) x kg FFM(-1); P < 0.05). Rates of fat oxidation following an overnight fast increased (1.16 +/- 0.06 to 1.36 +/- 0.05 mg x min(-1) x kg FFM(-1); P < 0.05), and the proportion of energy derived from fat increased from 38 to 52%. The strongest predictor of the improved insulin sensitivity was enhanced fasting rates of fat oxidation, accounting for 52% of the variance. In conclusion, exercise combined with weight loss enhances postabsorptive fat oxidation, which appears to be a key aspect of the improvement in insulin sensitivity in obesity.
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Affiliation(s)
- Bret H Goodpaster
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
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Wong MY, Day NE, Luan JA, Chan KP, Wareham NJ. The detection of gene-environment interaction for continuous traits: should we deal with measurement error by bigger studies or better measurement? Int J Epidemiol 2003; 32:51-7. [PMID: 12690008 DOI: 10.1093/ije/dyg002] [Citation(s) in RCA: 164] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND The search for biologically relevant gene-environment interactions has been facilitated by technological advances in genotyping. The design of studies to detect interactions on continuous traits such as blood pressure and insulin sensitivity is attracting increasing attention. We have previously described power calculations for such studies, and this paper describes the extension of those calculations to take account of measurement error. METHODS The model considered in this paper is a simple linear regression relating a continuous outcome to a continuously distributed exposure variable in which the ratio of slopes for each genotype is considered as the interaction parameter. The classical measurement error model is used to describe the uncertainty in measurement in the outcome and the exposure. The sample size to detect differing magnitudes of interaction with varying frequencies of the minor allele are calculated for a given main effect observed with error both in the exposure and the outcome. The sample size to detect a given interaction for a given minor allele frequency is calculated for differing degrees of measurement error in the assessment of the exposure and the outcome. RESULTS The required sample size is dependent upon the magnitude of the interaction, the allele frequency and the strength of the association in those with the common allele. As an example, we take the situation in which the effect size in those with the common allele was a quarter of a standard deviation change in the outcome for a standard deviation change in the exposure. If a minor allele with a frequency of 20% leads to a doubling of that effect size, then the sample size is highly dependent upon the precision with which the exposure and outcome are measured. rho(Tx) and rho(Ty) are the correlation between the measured exposure and outcome, respectively and the true value. If poor measures of the exposure and outcome are used, (e.g. rho(Tx) = 0.3, rho(Ty) = 0.4), then a study size of 150 989 people would be required to detect the interaction with 95% power at a significance level of 10(-4). Such an interaction could be detected in study samples of under 10 000 people if more precise measurements of exposure and outcome were made (e.g. rho(Tx) = 0.7, rho(Ty) = 0.7), and possibly in samples of under 5000 if the precision of estimation were enhanced by taking repeated measurements. CONCLUSIONS The formulae for calculating the sample size required to study the interaction between a continuous exposure and a genetic factor on a continuous outcome variable in the face of measurement error will be of considerable utility in designing studies with appropriate power. These calculations suggest that smaller studies with repeated and more precise measurement of the exposure and outcome will be as powerful as studies even 20 times bigger, which necessarily employ less precise measures because of their size. Even though the cost of genotyping is falling, the magnitude of the effect of measurement error on the power to detect interaction on continuous traits suggests that investment in studies with better measurement may be a more appropriate strategy than attempting to deal with error by increasing sample sizes.
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Affiliation(s)
- M Y Wong
- Department of Mathematics, The Hong Kong University of Science & Technology, Hong Kong
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Geffken DF, Cushman M, Burke GL, Polak JF, Sakkinen PA, Tracy RP. Association between physical activity and markers of inflammation in a healthy elderly population. Am J Epidemiol 2001; 153:242-50. [PMID: 11157411 DOI: 10.1093/aje/153.3.242] [Citation(s) in RCA: 367] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Higher levels of physical activity are associated with lower risk of cardiovascular disease. There is growing evidence that the development of the atherosclerotic plaque is associated with inflammation. In this study, the authors investigated the cross-sectional association between physical activity and markers of inflammation in a healthy elderly population. Data obtained in 1989-1990 and 1992-1993 from the Cardiovascular Health Study, a cohort of 5,888 men and women aged >/=65 years, were analyzed. Concentrations of the inflammation markers-C-reactive protein, fibrinogen, Factor VIII activity, white blood cells, and albumin-were compared cross-sectionally by quartile of self-reported physical activity. Compared with persons in the lowest quartile, those in the highest quartile of physical activity had 19%, 6%, 4%, and 3% lower concentrations of C-reactive protein, white blood cells, fibrinogen, and Factor VIII activity, respectively, after adjustment for gender, the presence of cardiovascular disease, age, race, smoking, body mass index, diabetes, and hypertension. Multivariate regression models suggested that the association of higher levels of physical activity with lower levels of inflammation markers may be mediated by body mass index and glucose. There was no association between physical activity and albumin. Higher levels of physical activity were associated with lower concentrations of four out of five inflammation markers in this elderly cohort. These data suggest that increased exercise is associated with reduced inflammation. Prospective studies will be required for verification of these findings.
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Affiliation(s)
- D F Geffken
- Department of Pathology, College of Medicine, University of Vermont, Burlington, VT, USA
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Abstract
Hypertension is a very prevalent cardiovascular (CV) disease risk factor in developed countries. All current treatment guidelines emphasise the role of nonpharmacological interventions, including physical activity, in the treatment of hypertension. Since our most recent review of the effects of exercise training on patients with hypertension, 15 studies have been published in the English literature. These results continue to indicate that exercise training decreases blood pressure (BP) in approximately 75% of individuals with hypertension, with systolic and diastolic BP reductions averaging approximately 11 and 8mm Hg, respectively. Women may reduce BP more with exercise training than men, and middle-aged people with hypertension may obtain greater benefits than young or older people. Low to moderate intensity training appears to be as, if not more, beneficial as higher intensity training for reducing BP in individuals with hypertension. BP reductions are rapidly evident although, at least for systolic BP, there is a tendency for greater reductions with more prolonged training. However, sustained BP reductions are evident during the 24 hours following a single bout of exercise in patients with hypertension. Asian and Pacific Island patients with hypertension reduce BP, especially systolic BP, more and more consistently than Caucasian patients. The minimal data also indicate that African-American patients reduce BP with exercise training. Some evidence indicates that common genetic variations may identify individuals with hypertension likely to reduce BP with exercise training. Patients with hypertension also improve plasma lipoprotein-lipid profiles and improve insulin sensitivity to the same degree as normotensive individuals with exercise training. Some evidence also indicates that exercise training in hypertensive patients may result in regression of pathological left ventricular hypertrophy. These results continue to support the recommendation that exercise training is an important initial or adjunctive step that is highly efficacious in the treatment of individuals with mild to moderate elevations in BP.
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Affiliation(s)
- J M Hagberg
- Department of Kinesiology, University of Maryland, College Park 20742-2611, USA.
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Folsom AR, Kushi LH, Hong CP. Physical activity and incident diabetes mellitus in postmenopausal women. Am J Public Health 2000; 90:134-8. [PMID: 10630154 PMCID: PMC1446129 DOI: 10.2105/ajph.90.1.134] [Citation(s) in RCA: 75] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
OBJECTIVES This study determined whether the incidence of diabetes is reduced among physically active older women. METHODS We assessed physical activity by mailed questionnaire and 12-year incidence of diabetes (ostensibly type 2 diabetes) in a cohort of 34257 women aged 55 to 69 years. RESULTS After adjustment for age, education, smoking, alcohol intake, estrogen use, dietary variables, and family history of diabetes, women who reported any physical activity had a relative risk of diabetes of 0.69 (95% confidence interval = 0.63, 0.77) compared with sedentary women. CONCLUSIONS These findings suggest that physical activity is important for type 2 diabetes prevention among older women.
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Affiliation(s)
- A R Folsom
- Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis 55454, USA.
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Caplan LS, May DS, Richardson LC. Time to diagnosis and treatment of breast cancer: results from the National Breast and Cervical Cancer Early Detection Program, 1991-1995. Am J Public Health 2000; 90:130-4. [PMID: 10630153 PMCID: PMC1446126 DOI: 10.2105/ajph.90.1.130] [Citation(s) in RCA: 99] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
OBJECTIVES This study examined times to diagnosis and treatment for medically underserved women screened for breast cancer. METHODS Intervals from first positive screening test to diagnosis to initiation of treatment were determined for 1659 women 40 years and older diagnosed with breast cancer. RESULTS Women with abnormal mammograms had shorter diagnostic intervals than women with abnormal clinical breast examinations and normal mammograms. Women with self-reported breast symptoms had shorter diagnostic intervals than asymptomatic women. Diagnostic intervals were less than 60 days in 78% of cases. Treatment intervals were generally 2 weeks or less. CONCLUSIONS Most women diagnosed with breast cancer were followed up in a timely manner after screening. Further investigation is needed to identify and then address factors associated with longer diagnostic and treatment intervals to maximize the benefits of early detection.
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Affiliation(s)
- L S Caplan
- Epidemiology and Health Services Research Branch, Centers for Disease Control and Prevention, Atlanta, Ga. 30341, USA.
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Wallberg-Henriksson H, Rincon J, Zierath JR. Exercise in the management of non-insulin-dependent diabetes mellitus. Sports Med 1998; 25:25-35. [PMID: 9458525 DOI: 10.2165/00007256-199825010-00003] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The incidence of non-insulin-dependent diabetes mellitus (NIDDM) has increased worldwide during the last decades, despite the development of effective drug therapy and improved clinical diagnoses. NIDDM is one of the major causes of disability and death due to the complications accompanying this disease. For the well-being of the patient, and from a public healthcare perspective, the development of effective intervention strategies is essential in order to reduce the incidence of NIDDM and its resulting complications. For the patient, and for society at large, early intervention programmes are beneficial, especially from a cost-benefit perspective. Physical activity exerts pronounced effects on substrate utilisation and insulin sensitivity, which in turn potentially lowers blood glucose and lipid levels. Exercise training also improves many other physiological and metabolic abnormalities that are associated with NIDDM such as lowering body fat, reducing blood pressure and normalising dyslipoproteinaemia. Clearly, regular physical activity plays an important role in the prevention and treatment of NIDDM. Since physical activity has been shown in prospective studies to protect against the development of NIDDM, physical training programmes suitable for individuals at risk for NIDDM should be incorporated into the medical care system to a greater extent. One general determinant in a strategy to develop a preventive programme for NIDDM is to establish a testing programme which includes VO2max determinations for individuals who are at risk of developing NIDDM. Before initiating regular physical training for people with NIDDM, a complete physical examination aimed at identifying any long term complications of diabetes is recommended. All individuals above the age of 35 years should perform an exercise stress test before engaging in an exercise programme which includes moderate to vigorously intense exercise. The stress test will identify individuals with previously undiagnosed ischaemic heart disease and abnormal blood pressure responses. It is important to diagnose proliferative retinopathy, microalbuminuria, peripheral and/or autonomic neuropathy in patients with NIDDM before they participate in an exercise programme. If any diabetic complications are present, the exercise protocol should be modified accordingly. The exercise programme should consist of moderate intensity aerobic exercise. Resistance training and high intensity exercises should only be performed by individuals without proliferative retinopathy or hypertension. Once enrolled in the exercise programme, the patient must be educated with regard to proper footwear and daily foot inspections. Fluid intake is of great importance when exercising for prolonged periods or in warm and humid environments. With the proper motivation and medical supervision, people with NIDDM can enjoy regular physical exercise as a means of enhancing metabolic control and improving insulin sensitivity.
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Affiliation(s)
- H Wallberg-Henriksson
- Department of Clinical Physiology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden
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Ivy JL. Role of exercise training in the prevention and treatment of insulin resistance and non-insulin-dependent diabetes mellitus. Sports Med 1997; 24:321-36. [PMID: 9368278 DOI: 10.2165/00007256-199724050-00004] [Citation(s) in RCA: 226] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Recent epidemiological studies indicate that individuals who maintain a physically active lifestyle are much less likely to develop impaired glucose tolerance and non-insulin-dependent diabetes mellitus (NIDDM). Moreover, it was found that the protective effect of physical activity was strongest for individuals at highest risk of developing NIDDM. Reducing the risk of insulin resistance and NIDDM by regularly performed exercise is also supported by several aging studies. It has been found that older individuals who vigorously train on a regular basis exhibit a greater glucose tolerance and a lower insulin response to a glucose challenge than sedentary individuals of similar age and weight. While the evidence is substantial that aerobic exercise training can reduce the risk of impaired glucose tolerance and NIDDM, the evidence that exercise training is beneficial in the treatment of NIDDM is not particularly strong. Many of the early studies investigating the effects of exercise training on NIDDM could not demonstrate improvements in fasting plasma glucose and insulin levels, or glucose tolerance. The adequacy of the training programmes in many of these studies, however, is questionable. More recent studies using prolonged, vigorous exercise-training protocols have produced more favourable results. There are several important adaptations to exercise training that may be beneficial in the prevention and treatment of insulin resistance, impaired glucose tolerance and NIDDM. An increase in abdominal fat accumulation and loss of muscle mass are highly associated with the development of insulin resistance. Exercise training results in preferential loss of fat from the central regions of the body and should therefore contribute significantly in preventing or alleviating insulin resistance due to its development. Likewise, exercise training can prevent muscle atrophy and stimulate muscle development. Several months of weight training has been found to significantly lower the insulin response to a glucose challenge without affecting glucose tolerance, and to increase the rate of glucose clearance during a euglycaemic clamp. Muscle glucose uptake is equal to the product of the arteriovenous glucose difference and the rate of glucose delivery or muscle blood flow. While it has been known for many years that insulin will accelerate blood glucose extraction by insulin-sensitive peripheral tissues, recent evidence suggests that it can also acutely vasodilate skeletal muscle and increase muscle blood flow in a dose-dependent manner. A reduced ability of insulin to stimulate muscle blood flow is a characteristic of insulin-resistant obese individuals and individuals with NIDDM. Exercise training, however, has been found to help alleviate this problem, and substantially improve the control of insulin over blood glucose. Improvements in insulin resistance and glucose tolerance with exercise training are highly related to an increased skeletal muscle insulin action. This increased insulin action is associated with an increase in the insulin-regulatable glucose transporters, GLUT4, and enzymes responsible for the phosphorylation, storage and oxidation of glucose. Changes in muscle morphology may also be important following training. With exercise training there is an increase in the conversion of fast twitch glycolytic IIb fibres to fast twitch oxidative IIa fibres, as well as an increase in capillary density. IIa fibres have a greater capillary density and are more insulin-sensitive and -responsive than IIb fibres. Evidence has been provided that morphological changes in muscle, particularly the capillary density of the muscle, are associated with changes in fasting insulin levels and glucose tolerance. Furthermore, significant correlations between glucose clearance, muscle capillary density and fibre type have been found in humans during a euglycaemic clamp. Exercise training may also improve control over hepatic glucose production by increasin
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Affiliation(s)
- J L Ivy
- Department of Kinesiology and Health, University of Texas at Austin, USA.
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Clausen JO, Borch-Johnsen K, Ibsen H, Bergman RN, Hougaard P, Winther K, Pedersen O. Insulin sensitivity index, acute insulin response, and glucose effectiveness in a population-based sample of 380 young healthy Caucasians. Analysis of the impact of gender, body fat, physical fitness, and life-style factors. J Clin Invest 1996; 98:1195-209. [PMID: 8787683 PMCID: PMC507542 DOI: 10.1172/jci118903] [Citation(s) in RCA: 177] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Insulin sensitivity and insulin secretion are traits that are both genetically and environmentally determined. AIM The aim of this study was to describe the distribution of the insulin sensitivity index (Si), the acute insulin response, and glucose effectiveness (Sg) in young healthy Caucasians and to estimate the relative impact of anthropometric and environmental determinants on these variables. METHODS The material included 380 unrelated Caucasian subjects (18-32 yr) with measurement of Si, Sg and insulin secretion during a combined intravenous glucose (0.3 grams/kg body weight) and tolbutamide (3 mg/kg body weight) tolerance test. RESULTS The distributions of Si and acute insulin response were skewed to the right, whereas the distribution of Sg was Gaussian distributed. Sg was 15% higher in women compared with men (P < 0.001). Waist circumference, body mass index, maximal aerobic capacity, and women's use of oral contraceptives were the most important determinants of Si. Approximately one-third of the variation of Si could be explained by these factors. Compared with individuals in the upper four-fifths of the distribution of Si, subjects with Si in the lowest fifth had higher waist circumference, higher blood pressure, lower VO2max, and lower glucose tolerance and fasting dyslipidemia and dysfibrinolysis. Only 10% of the variation in acute insulin response could be explained by measured determinants. CONCLUSION Estimates of body fat, maximal aerobic capacity, and women's use of oral contraceptives explain about one-third of the variation in Si in a population-based sample of young healthy Caucasians.
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Affiliation(s)
- J O Clausen
- Medical Department C, Glostrup Hospital, University of Copenhagen, Denmark
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Eidemak I, Feldt-Rasmussen B, Kanstrup IL, Nielsen SL, Schmitz O, Strandgaard S. Insulin resistance and hyperinsulinaemia in mild to moderate progressive chronic renal failure and its association with aerobic work capacity. Diabetologia 1995; 38:565-72. [PMID: 7489839 DOI: 10.1007/bf00400725] [Citation(s) in RCA: 70] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Tissue sensitivity to insulin and aerobic work capacity was measured in patients with mild to moderate progressive chronic renal failure. Twenty-nine non-diabetic patients with a glomerular filtration rate of 25 ml.min-1.1.73 m-2 (11-43) (median, range) and 15 sex, age, and body mass index matched control subjects with normal renal function were studied. Fasting blood glucose was comparable and in the non-diabetic range in the two groups as was the oral glucose tolerance test. Patients demonstrated hyperinsulinaemia both during fasting (p < 0.01) and during the test (p < 0.02). The tissue sensitivity to insulin, expressed by the amount of glucose infused during the last 60 min of a 120-min hyperinsulinaemia euglycaemic clamp (M-value) and the M/I ratio, was significantly lower in the patients than in the control subjects (M-value 404 +/- 118 vs 494 +/- 85 mg glucose/kg body weight, p < 0.02) (M/I ratio 1.77 +/- 0.71 vs 2.57 +/- 0.70 (mg/(kgBW.min) per pmol/l.100, p < 0.001). The maximal aerobic work capacity was significantly lower in the patients than in the control subjects (24 +/- 8 vs 32 +/- 11 ml O2/(kg body weight.min), p < 0.02) and positively correlated to the M-value and the M/I ratio in both groups. In conclusion, not only patients with end-stage chronic renal failure but also those with mild to moderate progressive chronic renal failure are insulin resistant and hyperinsulinaemic. The tissue sensitivity to insulin is correlated to the maximal aerobic work capacity suggesting that these patients might benefit from physical training programmes.
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Affiliation(s)
- I Eidemak
- Department of Nephrology, Herlev University Hospital, Copenhagen, Denmark
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Abstract
Regular exercise has been recognised as an important component in the management of patients with diabetes mellitus. In addition to acutely lowering blood glucose, exercise training improves glucose tolerance and peripheral insulin sensitivity, contributes to weight loss and reduces several risk factors for cardiovascular disease. When proper precautions are taken to prevent hypoglycaemia, individuals with diabetes can enjoy the same benefits from exercise as nondiabetic healthy individuals. As a guideline, moderate intensity, aerobic endurance activities should be performed for 20 to 40 minutes at least 3 times a week. Blood glucose should be monitored, and insulin dose and carbohydrate intake adjusted based on the blood glucose response to the type and duration of exercise. This review will summarise current understanding of the therapeutic role of exercise in the treatment of diabetes and will present guidelines for prescribing exercise in diabetic patients.
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Affiliation(s)
- J C Young
- Department of Kinesiology, University of Nevada, Las Vegas, USA
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Simonsick EM, Lafferty ME, Phillips CL, Mendes de Leon CF, Kasl SV, Seeman TE, Fillenbaum G, Hebert P, Lemke JH. Risk due to inactivity in physically capable older adults. Am J Public Health 1993; 83:1443-50. [PMID: 8214236 PMCID: PMC1694862 DOI: 10.2105/ajph.83.10.1443] [Citation(s) in RCA: 154] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
OBJECTIVES This study examined the association between recreational physical activity among physically capable older adults and functional status, incidence of selected chronic conditions, and mortality over 3 and 6 years. METHODS Data are from three sites of the Established Populations for Epidemiologic Studies of the Elderly. RESULTS A high level of recreational physical activity reduced the likelihood of mortality over both 3 and 6 years. Moderate to high activity reduced the risk of physical impairments over 3 years; this effect diminishes after 6 years. A consistent relationship between activity and new myocardial infarction or stroke or the incidence of diabetes or angina was not found after 3 or 6 years. CONCLUSIONS Findings suggest that physical activity offers benefits to physically capable older adults, primarily in reducing the risk of functional decline and mortality. Future work must use more objective and quantifiable measures of activity and assess changes in activity levels over time.
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Affiliation(s)
- E M Simonsick
- Epidemiology, Demography and Biometry Program, National Institute on Aging, Bethesda, Md. 20892
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