1. You at your best Loughborough Sports Day 2012 Dr Ian Gallen (Consultant Physician & Endocrinologist) AN11-1090A

2. Polite Notice The information presented here represents the view and opinions of the speaker & not necessarily those of Animas & LifeScan United Kingdom & Ireland. You at your best Loughborough Sports Day 2011 AN11-1090A

3. Basic Physiology How does the body work during exercise? Basis of fitness Managing diabetes to promote performance and reduce variation on blood sugar AN11-1090A

4. Exercise Terminology Duration of activity 0–20 minutesShort duration 20 minutes to 1 hourMedium duration Greater than 1 hourLong duration (or endurance) Intensity of activity Low intensityUp to 40% maximum heart rate in general activities from which an individual will not feel tired or out of breath, e.g. resting, activities of daily living Moderate intensity40–80% maximum heart rate in general activities from which an individual will feel warm and moderately out of breath, e.g., jogging, cycling, and fast walking High intensity80–100% maximum heart rate in general activities which an individual will not be able to maintain for longer than a few minutes, e.g. sprinting Intermittent high intensityTypically characterises many popular sports with periods of low or moderate exercise intensity interspersed with bursts of high-intensity activity, e.g. football, hockey, rugby, netball, etc. Likely also to reflect some fitness classes and gym work Key definitionsVO 2max = the maximum rate at which an individual can utilise oxygen = cardiac output (heart rate x stroke volume) x O 2 a-v (the arterial venous difference). Estimate for maximum heart rate = 220–age(years) Perry E, Gallen IW. Pract Diab Int. 2009;26:116–123. AN11-1090A

5. Muscles You at your best Loughborough Sports Day 2011 AN11-1090A

6. What are muscles? Muscles are the contractile tissue of the body, and produce all movement, and circulation in the body. are made of groups of cell, which contain the contractile proteins actin and myosin. contain structures to generate energy, the mitochondria and some fuel stores. are rich in arteries and veins to carry fuel and oxygen to the muscles and veins to carry waste products and carbon dioxide away. are the meat which we eat, and the red colour is due to another iron rich protein (myoglobin) which can store oxygen. contain a temporary store of energy in the form of creatine, and some fat and a starch (glycogen). AN11-1090A

7. Structure of muscles AN11-1090A

8. How do muscles contract? When you want to move, electrical impulses come from the brain, down through the spinal cord and are transmitted through the motor nerves to the muscles. At the junction between the nerve end and the muscle, chemical signals are released from the nerve endings. Calcium to enter the muscle cell, and this enable the troponin proteins to move the myosin up the actin molecule. This causes the whole structure to shorten, and this contraction is the fundamental basis of all muscle contraction. To release the bond between actin and myosin needs energy, to shorten the muscle further or to relax the muscle. When the signal for contraction ends, the calcium is pumped back into the sarcoplasmic reticulum, and the muscle relaxes. AN11-1090A

9. Contractile proteins of muscles AN11-1090A

10. Microscopic structure of muscle AN11-1090A

11. Comes from the high energy phosphorous containing compounds, adenosine triphosphate (ATP). ADP is returned to ATP, from another high energy phosphorous source creatine phosphate, and from the energy factory of the muscle, the mitochondrion. Another source is from enzymes which burn glucose in other parts of the muscle cells. In conditions of reduced oxygen availability, this is the source of energy in anaerobic exercise. A diet rich in creatine has the potential to increase the availability of creatine phosphate, which can increase high energy phosphate supply during intense exercise. Mitochondria can burn glucose, fats and ketones to make carbon dioxide and water. They will do so given an adequate supply of oxygen. How does the muscle get and use power? AN11-1090A

12. Mitochondrion, the power house of muscle AN11-1090A

13. Energy for exercise You at your best Loughborough Sports Day 2011 AN11-1090A

14. Glucose comes from –Glycogen stores in muscle –Liver glycogen via the cirulation –Glycerol –Lactate –Amino-acids Free fatty acids from fat stores Ketone bodies from the liver The ratio between CO 2 released (VCO 2 ) and oxygen consumed(VO 2 ). RER = VCO 2 /VO 2. RER for CHO is 1.0; RER for Fat is.70 The RER value at rest is usually 0.78 to 0.80. Energy for exercise AN11-1090A

15. GH/Cortisol EPI: epinephrine; FFA: free fatty acid; GH: growth hormone; NE: norepinephrine Glucagon Glucose Ketones EPI/NE Ian Gallen AN11-1090A

16. Upper limit of a person’s ability to increase oxygen uptake. Good indicator of cardiorespiratory endurance and aerobic fitness. Can differ according to sex, body size, age, and, to some degree, level of training. Expressed relative to body weight in ml of O 2 consumed per kg body weight per min (ml · kg -1 · min -1 ). College aged females and males approx. 38, 44, respectively Elite athletes are > 70 Maximal Oxygen Uptake (VO 2max ) AN11-1090A

17. Exercise Types You at your best Loughborough Sports Day 2011 AN11-1090A

18. Anaerobic (lactate inhibited) –Sprint running, speed climbing, sprint swimming. Mixed prolonged –Football, Rugby, Squash, Dancing. Prolonged aerobic Long distance running, cycling. Intense aerobic, limited by later anaerobic lactate build-up –Middle distance running, rowing, canoeing, cycling with hills/sprint finishes Exercise Types AN11-1090A

19. During the first few seconds of exercise, muscles use internal stores of high energy phosphate compounds (creatine phosphate) as the power source, Then switches to burning glucose from muscle glycogen by the mitochondria. If oxygen is plentiful, this continues, but the fuel comes from other parts of the body, and can be glucose, fats or ketones to make energy. Typically, endurance sports are aerobic. Training measures which improve the supply of oxgen to muscles, and the function of mitochondria will improve the aerobic capacity, and thus the endurance of exercise. Prolonged aerobic exercise at low intensity is the best for weight control. Any antigravity exercise such as running or using a treadmill with an incline in a gym for 40 minutes at a time will help burn fat. Aerobic Exercise AN11-1090A

20. Heart rate and Training You at your best Loughborough Sports Day 2011 AN11-1090A

21. Calculate your maximum heart rate –your age from 220 (e.g. for a 22 year old person it is 198 beats per minute). During your exercise, measure your heart rate over a minute at the wrist <60 % Maximum Heart Rate –You are in the non-training zone, either work harder or put your slippers on! 60-70% Maximum Heart Rate –You are training is in the aerobic zone, you will be able to do prolonged exercise. This is the zone to be in if you want to loose weight, but you will need to do prolonged and continuous exercise. 70-85% Maximum Heart Rate –Now we're talking, this is the standard training zone. This is the zone to be in to increase your endurance and maximum oxygen consumption. It will also maximize your cardiovascular workout. >85% Maximum Heart Rate. –This is in the anaerobic zone; you won't be able to do this for long. You should be doing bursts of this level of training to increase your lactate tolerance, and your high intensity work output. Understanding heart rate during training AN11-1090A

22. Heart rate and training AN11-1090A

23. It is the point at which blood lactate begins to accumulate above resting levels during exercise of increasing intensity. Sudden increase in blood lactate with increasing effort can be the result of an increase in the production of lactate or a decrease in the removal of lactate from the blood. It can indicate potential for endurance exercise; lactate formation contributes to fatigue. Lactate threshold AN11-1090A

24. Exercise Intensity and Blood Lactate Concentration AN11-1090A

25. Anaerobic exercise starts when there is not enough oxygen in the muscles, when the intensity of work increases. As a result, fats cannot be used for energy and glucose is not burnt completely, leaving behind a waste product called lactate. As tolerance of lactate is limited, anaerobic exercise is short. Sprint sports are anaerobic. Think back to when you last watched a 100-metre race. Often the sprinters breathe only once, or not at all. By the end of the race their muscles are very short of oxygen, are therefore working anaerobically and lactate is being formed. When lactate levels are too high, you will have to stop exercising, as you will feel very short of breath, perhaps even nauseous, and your heart rate will increase (generally above 140 beats per minute). Training can increase both your capacity for aerobic exercise. Repeated bursts of anaerobic exercise can increase the ability to tolerate and metabolize lactate, and can therefore increase the intensity and duration of maximum work. Anaerobic Exercise AN11-1090A

26. Oxygen Requirement During Exercise and Recovery AN11-1090A

27. Rebuilding depleted ATP supplies Clearing lactate produced by anaerobic metabolism Replenishing O 2 supplies borrowed from hemoglobin and myoglobin Removing CO 2 that has accumulated in body tissues Feeding increased metabolic and respiratory rates due to increased body temperature Factors Responsible for EPOC AN11-1090A

29. Some sports require short periods of intense effort. Aerobic capacity is rapidly exceeded, and exercise is aerobic. Your lactate threshold is low. You will know that you are in this range because you will not be able to talk, and you heart rate is higher than 80% predicted maximum. If you are unfit, you will reach this level quickly, and to correct this you need to deal with your aerobic capacity. If you are fit, you will have a high lactate threshold. To improve the duration of high intensity exercise, you need to build your lactate tolerance. This is achieved by repeated and increasing short burst of maximum effort with short periods of rest between them. A typical example would be 1 minute of sprinting, with 2 minutes of rest repeated 10 times. Increasing intensity of effort AN11-1090A

31. Better training and performance The key to better training is to identify what you are trying to get out of your exercise. Performance is the product of technique coupled with physical fitness, endurance and strength. Clearly individual practice and coaching will improve technique, and this will be specific to each individual sport. AN11-1090A

32. The bulk and strength of muscle groups are built through repeated rounds of effort, with increasing load. Typically weight training will increase muscle strength. Caution is required as there is a fine line between increasing load, and the potential for muscle and ligament strain. Strength training must be preceded and followed by stretching exercises, and advice sought from your coach or gym trainer. Increasing strength AN11-1090A

33. Aerobic capacity is highest when young, and does decline with age, but studies of elders who regularly perform endurance sports show that any decline in VO2max can be limited. VO2max it can be increased by training. If you are physically unfit, you will soon exceed your aerobic capacity at low effort levels, and will start to exercise aerobically. To build your aerobic capacity, you need to do prolonged sub-maximal exercise. You will know that you are in this range because you can talk easily, and your heart rate will be less than 70% maximum predicted for your age. Exercise at least every 2-3 days. And if you can do it daily, your fitness will improve rapidly. As you become fitter, you can then start to have periods within your exercise when you work harder and aim to raise your heart rate up to 70- 80% maximum predicted. Increasing endurance AN11-1090A

34. If you are training to be an elite athlete, you will have the time and youth to combine all of the above into a tailored program. You will have endurance training, training to increase your lactate threshold and tolerance and gym work to increase strength. Training for elite athletes AN11-1090A

35. You want to control or loose weight –Morning exercise, before eating, staring with 10 minutes of exercise which raises heat rate to 70-80% maximum predicted, dropping down to lower effort level for a further 30 minutes at least with a heart rate 70% max predicted. Take water throughout exercise. You want to improve your endurance, and want to improve your heart and lung function –Start at a lower level of effort, and taper up to 70-80% maximum predicted, and finish with 5 minutes of maximum effort. Drink either water or glucose containing drink throughout (lucozade sport). You want to improve muscle strength or change body shape –Focused gym work with weights, or sit ups to deal with that belly. Training for the rest of us! AN11-1090A

36. If one of your goals is weight control, you want to augment the hormones which break down fat, growth hormone and glucagon. This takes about 20 minutes of exercise to become active, exercise to burn fat should be initially intensive, but then drop down to less intensive, but be maintained for at least a further 20 minutes. It is helpful to perform any exercise at a time of day when these hormone levels are already high, and so exercise in the morning before will be more effective than in the evening to burn fat. It is important not to take food before exercise as this will reduce the fat burning by the muscles, which will use the energy from food ingested. Any post exercise meal should be in largely protein based and any carbohydrate taken as complex starches of low glycaemic index. Fat Burning AN11-1090A

37. Strategies to maintaining glycaemia during exercise Causes of and avoidance of late hypoglycaemia following exercise Hypoglycaemic unawareness Reducing fatigue and improving performance The role CSII in exercise Diabetes management aspects of endurance sport AN11-1090A

38. Food storage –Athletes require high energy intake of high glycaemic index foods. Usually excessive background insulin levels Endocrinology of exercise –Abnormal glucagon response –Abnormal portal insulin regulation of gluconeogenesis and ketogenesis –Impaired catecholamine response Diabetic complications –Autonomic neuropathy/microvascular disease What is different about exercise in diabetes? AN11-1090A

39. Available free glucose space is 20% lean person total weight 1mm/l measured glucose is 0.18g free glucose or total 2.5g in 70 kg person Thus raising bg to 15mmol/l, will only provide 25g readily available glucose. At 60%VO 2 max glucose oxidation typically 130 μmol/kg/min. Thus approximately 2g/min or 12 minutes! Why not just start with a high glucose? Some mathematics AN11-1090A

40. Trends in glucose production and use in T1DM during prolonged aerobic exercise Meal 60 min training run Counter-regulatory hormone response Glucose use Glucose production Blood glucose AN11-1090A

41. What Happens to Blood Glucose in exercise in T1 DM? Data from Buckinghamshire Hospitals Diabetes Sports clinic AN11-1090A

42. What tools can be employed to reduce hypoglycaemia with exercise? Reducing ambient insulin levels - But which insulin and by how much? Give extra glucose or carbohydrate before or with exercise - But how much and when? Stimulate counter-regulatory response to exercise - Can this be done? The effect of antecedent hypoglycaemia on later risk of hypoglycaemia with exercise. AN11-1090A

43. % Dose reduction Exercise intensity (% VO2max) 30 min of exercise 60-min of exercise 25 50 75 - R. Rabasa-Lhoret, et al. Diabetes Care, 2001; 24(4): 625 - 630. AN11-1090A

44. Effect of Carbohydrate Ingestion on glucose in Type 1 Diabetic Adolescents During Exercise Perrone et al. Diabetes Care 28:2537-2538, 2005 AN11-1090A

45. West et al, 2011 75g Isomaltulose or dextrose before exercise in T1DM AN11-1090A

46. Lucozade –15 grams of glucose per 100 ml, and no salts, is good for raising glucose quickly and replacing glucose when you want to reduce fluid intake Lucozade sports –6 grams of glucose per 100 ml, and has some salt, and is better for replacing fluids Gatorade –(not widely available in the UK) is a carbohydrate-rich fluid (6-8% carbohydrate), with sodium and potassium. Powdered sports drinks –made up to vary glucose and water content, to deal with each persons requirements, PSP22 –complex carbohydrate energy fuel for high-energy performance Sports drinks AN11-1090A

47. Strategies for Glucose Replacement During Exercise AN11-1090A

48. Biphasic response in glucose requirement with exercise Responses of glucose infusion rate (mg/kg{middle dot}min) (A), difference in glucose infusion rate (GIR) between exercise and rest studies (mg/kg{middle dot}min) (B), rate of carbohydrate oxidation (mg/kg{middle dot}min) (C), and rate of lipid oxidation (D) to exercise (solid lines) and rest (dashed lines) studies Increased glucose up take during exercise, but also late after exercise AN11-1090A

49. Delayed hypoglycaemia CGMS following exercise in T1DM AN11-1090A

50. Glucose oxidation is increased Endogenous glucose production is reduced Muscle glycogen mobilization and derived glucose oxidation increased Exogenous glucose oxidation in increased Glucose oxidation highest during hyperglycaemia Physical performance- the role of fuel oxidation in T1DM AN11-1090A

51. Enables normal basal insulin to be markedly reduced or suspended whist performing exercise. Enables rapid post exercise increase in insulin to deal with post exercise glycogenic peak. Enables lower post exercise nocturnal basal rate with intermittent exercise patterns. The gold standard for serious athletes where practical Role of CSII AN11-1090A

52. Blood glucose with 1 hour of exercise at 50% VO 2 MAX AN11-1090A

53. The Effect of Caffeine (5 mg/kg) on Blood Glucose During Prolonged Exercise Gallen IW, et al. Diabetes Care. 2010;Abstract 1184−P Ian Gallen AN11-1090A

54. Summary of Clinical Strategies to Maintain Glycaemic Control With Exercise StrategyAdvantagesDisadvantages Reducing pre-exercise bolus insulin Reduces hypoglycaemia during and following exercise; reduces CHO requirement Needs pre-planning; not helpful for spontaneous exercise or for late post-prandial exercise Reducing pre-exercise basal insulin As aboveAs above, causes pre- and late post-exercise hyperglycaemia Taking extra CHO with exercise Useful for unplanned or prolonged exercise May not be possible with some exercises; not helpful where weight control is important; easy to over- replace causing hyperglycaemia Pre- or post-exercise sprint Reduces hypoglycaemia following exercise Effect limited to shorter and less intense exercise Insulin pump therapyOffers flexibility and rapid change in insulin infusion rates postexercise Expensive; may not be practical for contact sports (e.g., rugby/ football/judo) Reducing basal insulin postexercise Reduces nocturnal hypoglycaemiaMay cause morning hyperglycaemia Lumb AN, Gallen IW. Curr Opin Endocrinol Diabetes Obes. 2009;16:150–155. Ian Gallen AN11-1090A