XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

Muscle fatigue is an exercise-induced reduction in maximal voluntary muscle force. It may arise not only because of peripheral changes at the level of the muscle, but also because the central nervous system fails to drive the motoneurons adequately. Evidence for “central” fatigue and the neural mechanisms underlying it are reviewed, together with its terminology and the methods used to reveal it. Much data suggest that voluntary activation of human motoneurons and muscle fibers is suboptimal and thus maximal voluntary force is commonly less than true maximal force. Hence, maximal voluntary strength can often be below true maximal muscle force. The technique of twitch interpolation has helped to reveal the changes in drive to motoneurons during fatigue. Voluntary activation usually diminishes during maximal voluntary isometric tasks, that is central fatigue develops, and motor unit firing rates decline. Transcranial magnetic stimulation over the motor cortex during fatiguing exercise has revealed focal cha...

Spinal and Supraspinal Factors in Human Muscle Fatigue

Free radicals and other reactive species (RS) are thought to play an important role in many human diseases. Establishing their precise role requires the ability to measure them and the oxidative damage that they cause.


This article first reviews what is meant by the terms free radical, RS, antioxidant, oxidative damage and oxidative stress.


It then critically examines methods used to trap RS, including spin trapping and aromatic hydroxylation, with a particular emphasis on those methods applicable to human studies.


Methods used to measure oxidative damage to DNA, lipids and proteins and methods used to detect RS in cell culture, especially the various fluorescent ‘probes' of RS, are also critically reviewed.


The emphasis throughout is on the caution that is needed in applying these methods in view of possible errors and artifacts in interpreting the results.





Keywords: Cell culture, free radical, reactive species, antioxidant, oxidative stress, oxidative damage, fluorescent probe, lipid peroxidation, superoxide


Introduction
Free radicals and other ‘reactive oxygen (ROS)/nitrogen/chlorine species' (for an explanation of these terms see Table 1) are widely believed to contribute to the development of several age-related diseases, and perhaps, even to the aging process itself (Halliwell & Gutteridge, 1999; Sohal et al., 2002) by causing ‘oxidative stress' and ‘oxidative damage' (terms explained in Table 2). For example, many studies have shown increased oxidative damage to all the major classes of biomolecules in the brains of Alzheimer's patients (Halliwell, 2001; Butterfield, 2002; Liu et al., 2003). Other diseases in which oxidative damage has been implicated include cancer, atherosclerosis, other neurodegenerative diseases and diabetes (Hagen et al., 1994; Chowienczyk et al., 2000; Halliwell, 2000a, 2001, 2002a, 2002b; Parthasarathy et al., 2000). If oxidative damage contributes significantly to disease pathology (Table 3 lists the criteria needed to establish this), then actions that decrease it should be therapeutically beneficial (Halliwell, 2001; Lee et al., 2002a; Liu et al., 2003). If the oxidative damage is involved in the origin of a disease, then successful antioxidant treatment should delay or prevent the onset of that disease (Halliwell, 1991, 2002a, 2002b; Galli et al., 2002; Steinberg & Witztum, 2002). To establish the role of oxidative damage (Table 3), it is therefore essential to be able to measure it accurately. For example, the failure of interventions with antioxidants such as vitamin E, β-carotene or ascorbate to decrease disease incidence in several human intervention trials may have simply been due to the failure of these compounds to decrease oxidative damage in the subjects tested (Halliwell, 1999a, 2000c; Levine et al., 2001; Meagher et al., 2001). In this review, we will examine the methods available to measure reactive species (RS) and oxidative damage, with a particular emphasis on those applicable to human studies.



Table 1

Nomenclature of reactive species





Table 2

Some key definitions





Table 3

Criteria for implicating RS as a significant mechanism of tissue injury in human disease




Measuring RS in vivo: basic principles

Some fascinating techniques such as L-band electron spin resonance (ESR) with nitroxyl probes and magnetic resonance imaging spin trapping are under development to measure RS directly in whole animals (e.g. Berliner et al., 2001; Han et al., 2001; Utsumi & Yamada, 2003), but no probes are currently suitable for human use. Most RS persist for only a short time in vivo and cannot be measured directly. There are a few exceptions: examples include H2O2 (discussed below), and perhaps, NO•, in the sense that serum levels of NO2− have been claimed to measure vascular endothelial NO• synthesis (Kelm et al., 1999), despite the fact that NO2− is quickly oxidized to NO3− in vivo (Kelm et al., 1999; Oldreive & Rice-Evans, 2001). Essentially, there are two approaches to detecting transient RS: 


attempting to trap these species and measure the levels of the trapped molecules and


measuring the levels of the damage done by RS, that is, the amount of oxidative damage.




Sometimes other approaches are used. They include measurements of erythrocyte antioxidant defences and of total antioxidant activity of body fluids; falls in these parameters are often taken as evidence of oxidative stress. Erythrocytes cannot synthesize proteins, however, and their antioxidant enzyme levels may drop as they ‘age' in the circulation (Denton et al., 1975). Thus changes in their levels are more likely to reflect changes in the rates of red blood cell turnover: if this slows down, the circulating erythrocytes will be older on average and so levels of antioxidant enzymes in them will appear to fall. Vice versa, if an intervention accelerates red cell removal or increases erythropoiesis, levels of antioxidants in red cells will seem to rise. Hence, such data should be interpreted with caution.

Depending on the method that is used to measure it, the plasma or serum ‘total antioxidant capacity' (TAC) usually involves major contributions from urate, ascorbate and sometimes albumin −SH groups (Benzie & Strain, 1996; Halliwell & Gutteridge, 1999; Prior & Cao, 1999; Rice-Evans, 2000; Bartosz, 2003), although different methods measure different things (Schlesier et al., 2002; Bartosz, 2003). Thus, for example, if plasma albumin levels fall, TAC will fall. If urate levels rise, TAC will rise. The multiple changes in blood chemistry that occur in sick people mean that TAC changes should be interpreted with caution. TAC is also influenced by diet, often because consumption of certain foods may produce changes in plasma ascorbate and/or urate levels (Halliwell, 2003b).

/pdf/measuring-reactive-species-and-oxidative-damage-in-vivo-and-5a9iiwcjlt.pdf

Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean?

Mammalian skeletal muscle comprises different fiber types, whose identity is first established during embryonic development by intrinsic myogenic control mechanisms and is later modulated by neural and hormonal factors. The relative proportion of the different fiber types varies strikingly between species, and in humans shows significant variability between individuals. Myosin heavy chain isoforms, whose complete inventory and expression pattern are now available, provide a useful marker for fiber types, both for the four major forms present in trunk and limb muscles and the minor forms present in head and neck muscles. However, muscle fiber diversity involves all functional muscle cell compartments, including membrane excitation, excitation-contraction coupling, contractile machinery, cytoskeleton scaffold, and energy supply systems. Variations within each compartment are limited by the need of matching fiber type properties between different compartments. Nerve activity is a major control mechanism of the fiber type profile, and multiple signaling pathways are implicated in activity-dependent changes of muscle fibers. The characterization of these pathways is raising increasing interest in clinical medicine, given the potentially beneficial effects of muscle fiber type switching in the prevention and treatment of metabolic diseases.

Fiber types in mammalian skeletal muscles.

Repeated, intense use of muscles leads to a decline in performance known as muscle fatigue. Many muscle properties change during fatigue including the action potential, extracellular and intracellular ions, and many intracellular metabolites. A range of mechanisms have been identified that contribute to the decline of performance. The traditional explanation, accumulation of intracellular lactate and hydrogen ions causing impaired function of the contractile proteins, is probably of limited importance in mammals. Alternative explanations that will be considered are the effects of ionic changes on the action potential, failure of SR Ca2+ release by various mechanisms, and the effects of reactive oxygen species. Many different activities lead to fatigue, and an important challenge is to identify the various mechanisms that contribute under different circumstances. Most of the mechanistic studies of fatigue are on isolated animal tissues, and another major challenge is to use the knowledge generated in these studies to identify the mechanisms of fatigue in intact animals and particularly in human diseases.

/pdf/skeletal-muscle-fatigue-cellular-mechanisms-d0dzk4w31g.pdf

Skeletal Muscle Fatigue: Cellular Mechanisms

The aim of this study was to assess physical fitness, match performance and development of fatigue during competitive matches at two high standards of professional soccer. Computerized time-motion analyses were performed 2-7 times during the competitive season on 18 top-class and 24 moderate professional soccer players. In addition, the players performed the Yo-Yo intermittent recovery test. The top-class players performed 28 and 58% more (P < 0.05) high-intensity running and sprinting, respectively, than the moderate players (2.43 +/- 0.14 vs 1.90 +/- 0.12 km and 0.65 +/- 0.06 vs 0.41 +/- 0.03 km, respectively). The top-class players were better (11%; P < 0.05) on the Yo-Yo intermittent recovery test than the moderate players (2.26 +/- 0.08 vs 2.04 +/- 0.06 km, respectively). The amount of high-intensity running, independent of competitive standard and playing position, was lower (35-45%; P < 0.05) in the last than in the first 15 min of the game. After the 5-min period during which the amount of high-intensity running peaked, performance was reduced (P < 0.05) by 12% in the following 5 min compared with the game average. Substitute players (n = 13) covered 25% more (P < 0.05) ground during the final 15 min of high-intensity running than the other players. The coefficient of variation in high-intensity running was 9.2% between successive matches, whereas it was 24.8% between different stages of the season. Total distance covered and the distance covered in high-intensity running were higher (P < 0.05) for midfield players, full-backs and attackers than for defenders. Attackers and full-backs covered a greater (P < 0.05) distance in sprinting than midfield players and defenders. The midfield players and full-backs covered a greater (P < 0.05) distance than attackers and defenders in the Yo-Yo intermittent recovery test (2.23 +/- 0.10 and 2.21 +/- 0.04 vs 1.99 +/- 0.11 and 1.91 +/- 0.12 km, respectively). The results show that: (1) top-class soccer players performed more high-intensity running during a game and were better at the Yo-Yo test than moderate professional players; (2) fatigue occurred towards the end of matches as well as temporarily during the game, independently of competitive standard and of team position; (3) defenders covered a shorter distance in high-intensity running than players in other playing positions; (4) defenders and attackers had a poorer Yo-Yo intermittent recovery test performance than midfielders and full-backs; and (5) large seasonal changes were observed in physical performance during matches.

/pdf/match-performance-of-high-standard-soccer-players-with-5f9b0ayrca.pdf

Match performance of high-standard soccer players with special reference to development of fatigue

The two Yo-Yo intermittent recovery (IR) tests evaluate an individual's ability to repeatedly perform intense exercise. The Yo-Yo IR level 1 (Yo-Yo IR1) test focuses on the capacity to carry out intermittent exercise leading to a maximal activation of the aerobic system, whereas Yo-Yo IR level 2 (Yo-Yo IR2) determines an individual's ability to recover from repeated exercise with a high contribution from the anaerobic system. Evaluations of elite athletes in various sports involving intermittent exercise showed that the higher the level of competition the better an athlete performs in the Yo-Yo IR tests. Performance in the Yo-Yo IR tests for young athletes increases with rising age. The Yo-Yo IR tests have shown to be a more sensitive measure of changes in performance than maximum oxygen uptake. The Yo-Yo IR tests provide a simple and valid way to obtain important information of an individual's capacity to perform repeated intense exercise and to examine changes in performance.

https://www.fedecoltenis.com/userfiles/Capacitacion/2013/YOYO%20RECOVERY%20TEST.pdf

The Yo-Yo intermittent recovery test : a useful tool for evaluation of physical performance in intermittent sports.

KRUSTRUP, P, M MOHR, T AMSTRUP, T RYSGAARD, J JOHANSEN, A STEENSBERG, P K PEDERSEN, and J BANGSBO The Yo-Yo Intermittent Recovery Test: Physiological Response, Reliability, and Validity Med Sci Sports Exerc, Vol 35, No 4, pp 697–705, 2003PurposeTo examine the physiological

The yo-yo intermittent recovery test: physiological response, reliability, and validity.

This review is focused on anthropometric and physiological characteristics of soccer players with a view to establishing their roles within talent detection, identification and development programmes. Top-class soccer playershave to adapt to the physical demandsof the game, which are multifactorial. Players may not need to have an extraordinary capacity within any of the areas of physical performance but must possess a reasonably high level within all areas. This explains why there are marked individual differences in anthropometric and physiological characteristics among top players. Various measurements have been used to evaluate specific aspects of the physical performance of both youth and adult soccer players.The positional role of a player is related to his or her physiological capacity. Thus, midfield players and full-backs have the highest maximal oxygen intakes (> 60 ml·kg -1 ·min -1 ) and perform best in intermittent exercise tests. On the other hand, midfield players tend to have the lowest mus...

Anthropometric and physiological predispositions for elite soccer

The present thesis is based on 14 original articles published in international journals (I-XIV, see page 8) and a summarizing review. The thesis deals with the physiological demands of soccer, with a particular focus on the physiological response to repeated intense exercise. In chapter I the specific issues are presented and in chapter II the physiological demands in soccer are discussed based on the results of the studies performed. Chapter III contains a short survey of the experiments performed to study specifically muscle metabolism and muscle fatigue with repeated intense muscle contractions. With reference to the topics covered in chapters II and III, fatigue during a soccer match is discussed in chapter IV, and chapter V deals with applications for physical training in soccer. Measurements have been performed during soccer matches and training, as well as in experiments simulating the activities of a soccer match. The information obtained has been compared to results from studies of the physical capacity of top-class soccer players and from laboratory experiments aimed at investigating metabolism and fatigue in intermittent exercise. Studies with whole-body and single muscle group exercises have been performed, the latter mainly with the application of a knee-extension model. In the studies on isolated muscle groups, biopsies taken from exercising muscles as well as arterial and femoral venous blood samples have allowed for detailed analysis of muscle ionic transportation and metabolism. In addition, the magnetic resonance technique has been used for the continuous determination of changes in muscle metabolites and pH during intermittent exercise. Analysis of activities during soccer matches showed that a top-class soccer player covers an average distance of approximately 11 km during a match. The distance differs highly between players and is partly related to the position in a team. Midfield players run more at low speed than defenders and forwards, whereas no difference appears to exist between groups when comparing the distance covered at high speed. The distance covered at high speed is the same in the beginning as in the end of a match. The total distance covered by a player during a soccer match is only to a limited extent a measure of the physiological demands on the player during the match. In addition to running, a player is engaged in many other energy demanding activities, i.e. tackling, jumping, accelerating and turning. A more precise evaluation of the total energy demand during a soccer match may be achieved by performing physiological measurements in connection with soccer matches (I).(ABSTRACT TRUNCATED AT 400 WORDS)

Jens Bangsbo

Papers

Match performance of high-standard soccer players with special reference to development of fatigue

The Yo-Yo intermittent recovery test : a useful tool for evaluation of physical performance in intermittent sports.

The yo-yo intermittent recovery test: physiological response, reliability, and validity.

Anthropometric and physiological predispositions for elite soccer

The Physiology of Soccer : With Special Reference to Intense Intermittent Exercise