Management  of diabetes, sport and exercise

Ian W Gallen BSc, MBBS, MD, FRCP, FRCPE. Consultant Physician Diabetes Centre, Wycombe
Hospital, Buckinghamshire. U.K.

People with type 1 diabetes are encouraged to increase physical activity, and for many exercise and sport are important parts of their lives. However, it is a paradox that any increase in physical activity is likely to be associated with disturbances in glycaemic control. Exercise may cause rapidly falling blood glucose levels which may lead to hypoglycaemia. Attempts to maintain blood glucose with extra food before exercise may cause hyperglycaemia during or following exercise. Perhaps of most concern is the increased rate of nocturnal hypoglycaemia following exercise. This article will outline the physiology of exercise in diabetes, and suggest appropriate management strategies which can be used to promote euglycaemia during and following exercise.

The effect of type 1 diabetes and insulin therapy on physical activity
A basic understanding of exercise physiology and in particular fuel sources and delivery is helpful to understanding both the challenges faced by individuals with type 1 diabetes and to plan management strategies to overcome these challenges. Exercise increases fuel demands and this is regulated by the endocrine system.
Energy for exercise is provided by aerobic and anaerobic metabolism Aerobic metabolism is essential for longer duration moderate intensity endurance activities, however, there is a maximal rate at which this energy can be produced, this point is known as the lactic threshold. Anaerobic metabolism typically provides energy for short bursts of high intensity activity lasting no more than several minutes before lactic acid build up results in fatigue.
Two main factors that influence the predominant fuel sources during exercise are exercise intensity and duration1,2,3. During early exercise carbohydrates oxidation (from glycogen) is predominant. Intramuscular glycogen is depleted first4 followed by plasma glucose derived from hepatic glycogenolysis, gluconeogenesis and intestinal absorption5. In high intensity anaerobic exercise (e.g. sprinting) these carbohydrate sources provide almost 100% of fuel1,3. However, in longer duration moderate intensity aerobic exercise (e.g. endurance running/cycling for several hours) other fuel sources can be utilised with circulating free fatty acids having an increasingly important contribution as the duration of exercise increases. During prolonged moderate intensity aerobic exercise typical of endurance activities, muscle glycogen stores are depleted and therefore hepatic glucose production is essential for homeostasis. This is controlled by reduced insulin and increase glucagon release2,3,5. During exercise a fall in insulin promotes hepatic glycogenolysis whereas a rise in glucagon is also required to achieve maximal hepatic glycogenolysis and gluconeogenesis6. The effects of insulin and glucagon are additive, indeed without the presence of glucagon a decrease in insulin alone will not stimulate hepatic glycogenolysis7. Increased levels of insulin independent GLUT 4 transporters then allow the glucose produced to be transported into muscle. Despite large increases in cellular glucose uptake required for exercise, the individual without diabetes maintains euglycaemia due to tight endocrine regulation. This regulation is impaired in insulin-deficient individuals with diabetes, so that there is mismatch between hepatic glucose output and muscle glucose uptake, which can produce hypo or hyperglycaemia.

For people with type 1 diabetes, subcutaneous insulin does not reduce on commencing exercise; indeed its levels may even increase as exercise promotes blood flow to and absorption from depots in subcutaneous tissues. Without a fall in insulin levels individuals with diabetes may have relative over-insulinisation3. Over-insulinisation then blocks hepatic glucose production and results in an increased risk of hypoglycaemia following 20-60 minutes of moderate intensity aerobic exercise8 when intramuscular glycogen stores are depleted and hepatic glucose is essential for glucose homeostasis. Exercise at the upper aerobic thresholds (usually in the region of 70% Maximal HR) result in highest rates of aerobic glucose oxidation and consequently highest risk of hypoglycaemia9. Increased transport of glucose into muscle secondary to up-regulation of insulin independent GLUT 4 transporters during exercise10 further increases the risk of hypoglycaemia in individuals with diabetes. These transporters are thought to be key both during exercise to enable glucose transport into muscle cells and post exercise to help replenish muscle and hepatic glycogen stores. Their persistence during the post-exercise phase may however further potentate relative over-insulinisation leading to increased risk of hypoglycaemia post exercise in the individual with diabetes3. This increase in insulin sensitivity is a significant cause of nocturnal hypoglycaemia when exercise is infrequent, and there is no adjustment of the basal insulin dose.
After several hours of endurance activities the risk of hypoglycaemia is reduced because fuel consumption shifts to free fatty acids as the major fuel source and because in the majority of falling insulin absorption from subcutaneous depots. Hyperglycaemia may occur if oral carbohydrate supplementation is continued at previous rates required earlier during exercise.

In contrast to endurance exercise, high intensity exercise includes activities above the lactic threshold with a greater reliance on anaerobic metabolism2. Cathecholamines are thought to take over primary control of hepatic glucose production from insulin and glucagon during exercise of high intensity2. This is recognised to cause hyperglycaemia even in individuals without diabetes; it is thought that dramatically increased cathecholamines trigger a relative overproduction of glucose2. This can then be compensated for by an increase in endogenous insulin production. People with type 1 diabetes are unable to compensate by an increase in endogenous insulin production, hyperglycaemia is common following short high intensity exercise in athletes with type 1 diabetes.
The main concern for people with diabetes is hypoglycaemia. It is well understood that hypoglycaemia breeds further hypoglycaemia, but hypoglycaemia also impairs counter-regulatory responses with exercise11. Interestingly women show relatively preserved counter-regulatory responses following antecedent hypoglycaemia which may confer greater protection from further hypoglycaemia12,13. In practical terms exercising following a recent episode of hypoglycaemia, particularly in men increases the individuals’ risk of hypoglycaemia during exercise, this risk is proportionally higher if the degree of hypoglycaemia preceding exercise was more severe.
Consideration for the physiological challenges to glucose homeostasis, in particular the nature of exercise including intensity, duration and the potential impact of counter-regulatory hormones are critical in the management of type 1 diabetes and exercise. Typical responses are summarised in the table 1. It is however important to recognise that this table does not include every factor that impacts on glucose homeostasis and individuals will vary in their responses. Our physiological understanding can help guide individuals but it cannot replace the importance of individuals monitoring their own blood sugars and learning to predict their normal responses to a particular exercise.

Strategies to promote euglycaemia during and following exercise
Alteration in the timing and dose of insulin administration, and taking extra carbohydrate remain the mainstays of management of diabetes and exercise. Most individuals will require multiple daily injections with short acting or analogue insulin and appropriate basal support overnight to allow the greatest flexibility to adjust their insulin to exercise14. Continuous subcutaneous insulin infusion therapy seems to offer many advantages, with the potential of near-physiological insulin replacement and rapid adjustment. The use of these may be limited by personal choice, cost and they may not be, suitable for all sports5,14.
Attention to injection technique and site is important. Insulin should be injected into the subcutaneous space using a short needle, into skin over non-exercising limb because of the potential to vary insulin absorption rate5,15. Care must also be taken to avoid intramuscular injection which can cause hypoglycaemia particularly if followed by exercise16. Newer analogue insulin (e.g. lispro, aspart and glulisine) are recommended as the bolus component because of the more rapid onset and shorter duration 17,18.

There is controversy regarding which basal insulin is most appropriate14. Many diabetologists now use one of the new analogues (insulin glargine or detemir) as their preferred basal insulin. However, although exercise does not appear to alter the rate of absorption of glargine a rapid fall in blood glucose has been reported on exertion19. Although yet to be quantified, it is thought likely the pharmacological characteristics of newer analogues (prolonged action and control of gluconeogenesis) that optimise glycaemic control also have an impact on fuel metabolism in a way which can be detrimental during exercise to a greater degree than NPH insulin. As a consequence such newer analogues may be more likely to predispose to hypoglycaemia during exercise14. In the individual exercising with diabetes it may therefore be necessary to switch from analogue insulin to NPH insulin if problems are encountered with hypoglycaemia.

Insulin Dose Adjustment
If exercise takes place within 90 minutes of pre-meal analog bolus injection, the risk of hypoglycaemia can be reduced by reducing the dose of insulin. The extent of this dose reduction studies depend on the anticipated exercise duration and intensity, and does require pre-planning (table 2)18. Furthermore, reductions of morning insulin dose of 50-90% prior to moderate intensity endurance activities have been successful in both basal bolus regimes and twice daily insulin regimen (30% regular/70% NPH insulin), without worsening metabolic control20. Basal insulin levels may also need to be adjusted especially if exercise is not performed on a daily basis.

The degree of change required is again going to vary depending on the intensity and duration of activity. As a general guide reductions of 20% on the night following exercise and 10% on the night after that may be required to cover the period of increased residual insulin sensitivity following an episode of unaccustomed exercise that would otherwise lead to an inappropriately high insulin level. Generally if exercise frequency is greater than once every 2 days no adjustment in basal insulin is required on a day to day basis although overall basal insulin requirements are likely to change over time with training and fitness. It is important to recognise that hypoglycaemia is one of the commonest and potentially most serious complications during participation in sport and exercise, particularly as it may occur in remote or dangerous environments. Its detection however, can prove difficult as symptoms may be similar to those of exercise itself. In this respect the importance of closely monitoring blood glucose pre, during and post-exercise cannot be overemphasised.

Carbohydrate Supplementation and Diet
The overall dietary requirements of athletes with or without diabetes are essentially similar, ideally with 60-70% of energy taken as carbohydrate 5-10% protein and less than 30% as fat21. Consideration must be given to whether exercise is part of a weight control plan as carbohydrate supplementation may hinder weight loss and goals are different to nutrition for athletic performance. In both circumstances involvement of a specialist dietician is often helpful if available. As it is not always possible to plan for exercise, or exercise may take place in the late post-prandial period, additional carbohydrate intake increases flexibility to manage exercise.
Extra carbohydrate during exercise both prevents hypoglycaemia and improves exercise capacity, as a rough guide up to 1g/kg/hr may be required22 but once more this will need to be tailored to the individual. Although no exact formulae is available recent studies suggest that heart rate at aerobic thresholds (up to approximately 75% maximum HR) follows a linear relationship with the amount of glucose oxidised23. Therefore, the higher the heart rate whilst working aerobically the more carbohydrate is likely to be required to maintain euglycaemia23. Furthermore, just as with insulin dose adjustments ambient insulin level is critical, carbohydrate requirement to prevent hypoglycaemia decreases as time elapses from the period of maximum action of the last insulin injection if other key physiological factors are controlled for9. Sports drinks containing 6-10g of carbohydrate per 100ml can be used to provide carbohydrate and replace fluids and electrolytes when glucose is stable (commercially available sports drinks typically contain 6-8g carbohydrate/100ml). In the absence of reductions in insulin dose, concentrations closer to 10g/100ml have been shown to be most affective in preventing hypoglycaemia individuals with type 1 diabetes without gastro-intestinal side effects24. However, higher concentrations for example 15g/100ml may be needed to correct falling blood sugars14, unfortunately gastric discomfort is more likely at these levels25. The need to maintain adequate hydration must not be overlooked and many individuals supplement sports drinks with water or squash to achieve this particularly in warm conditions. Over reliance on sports drinks with no regard for blood glucose in an individual with type 1 diabetes could lead to hyperglycaemia. After exercise typically 60-120g of carbohydrate is needed depending on level of depletion to replenish muscle and liver glycogen stores26 and a further bolus of insulin may be required to cover this.

The 10 second maximum sprint
A 10 second maximal sprint either immediately before or after exercise is an effective, well tolerated, novel strategy to prevent hypoglycaemia following moderate intensity exercise. The effect is limited to short duration (20minutes), moderate intensity (40% VO2 Max) exercise only27,28, however, this provides another option for athletes following unplanned short duration moderate intensity exercise that is effective without the need to adjust insulin or carbohydrate intake.

Conclusion
There is currently no single best strategy to prevent hypoglycaemia for individuals with type 1 diabetes participating in moderate intensity endurance activities. Table 3 summarizes the strategies discussed and the relative advantages and disadvantages currently recognised. For each strategy there is no exact formula for adjustments. Health care professionals need to ascertain from people with diabetes the timing in relationship to insulin injection, duration and type of physical activity to best advise on insulin dose adjustment and carbohydrate injection. These can then be adjusted using knowledge of variables known to impact on glucose homeostasis. The person with diabetes needs to take care with glucose measurements before and following exercise, and measure carbohydrate ingestion to increase awareness of their usual responses to a particular type of exercise. Guidelines to help individuals with type 1 diabetes participate in sport and exercise safely are detailed in table 4.
If applied, these strategies will improve glycaemic control and have the potential to enable the most outstanding physical performance in people with diabetes29.

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ian.gallen@buckshosp.nhs.uk

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