ADA/JDRF Type 1 Diabetes Sourcebook, Excerpt #21: Physical Activity, Part 3

Hypoglycemia Associated with Physical Activity

Hypoglycemia risk. Hypoglycemia is the most common negative side effect of exercise, ranging from mild to life threatening in severity. The incidence of hypoglycemia during or after a single bout of moderate-intensity exercise in children and adolescents with T1D is reported to be as high as 30%.¹²¹ Based on a small sample of athletes with T1D attending a vigorous sports camp, ~7% of an individual’s time will be spent in hypoglycemia and about 11% in hyperglycemia.⁹² In extreme cases, hypoglycemia during exercise or sports can be detrimental to performance, cause premature fatigue, and result in loss of consciousness during the activity and permanent organ damage.^115,122,123….

A number of factors appear to increase the risk for exercise-associated hypoglycemia, including the timing of the exercise, the duration and intensity of the activity, and having experienced an episode of hypoglycemia in the previous 24–48 h. Limited evidence also suggests that unfamiliarity with the activity may also increase the risk, while endurance training may lower risk.¹²⁴ As mentioned, normally, at the onset of exercise, insulin secretion is lowered and levels drop in the portal circulation rapidly.⁷⁷ This drop in portal insulin sensitizes the liver to glucagon, thereby increasing glucose production via glycogen breakdown. Since exercise often occurs in a time frame of 0–4 h after insulin administration, patients taking regular or rapid-acting insulin analogs are typically exercising when circulating insulin levels are simply too high, relatively speaking, for aerobic exercise.¹²⁵ In these situations, corrections in insulin dosage and/or additional carbohydrates are typically needed.

People with T1D have multiple impairments in the counterregulatory response to hypoglycemia and exercise, placing then at high risk for severe hypoglycemia (i.e., hypoglycemia requiring assistance from another). After the first few years of onset of diabetes, the glucagon response to hypoglycemia is typically diminished or lost, although its response to exercise may still be intact.^86,126,127 Increases in epinephrine are also blunted in people with T1D both during exercise and hypoglycemia.⁸⁶ Even if counterregulatory responses to hypoglycemia (and to exercise) occur, excessive exogenous insulin administration by the patient can blunt hepatic glucose production and increase peripheral glucose disposal, thereby resulting in rapid hypoglycemia.^77,86 Other factors such as inadequate carbohydrate intake, failure to monitor blood glucose levels, exercise in warm environments, prolonged exercise activities, and unfamiliarity with the exercise activity may also increase risk. Finally, a vicious cycle appears to exist between exercise and hypoglycemia in which antecedent hypoglycemia or exercise cause reduced neuroendocrine, metabolic, and symptom responses to subsequent hypoglycemia or exercise.⁸⁰ For more details on the proposed mechanisms of this vicious cycle, the interested reader may refer to an excellent review article.⁷⁴

Hypoglycemia treatment. Hypoglycemia treatment during exercise depends on its severity and whether the individual plans to continue exercising. Mild to moderate hypoglycemia can generally be treated with 15–20 g of simple carbohydrate (or ~0.3 g carbohydrate/kg body mass) using glucose tablets, soft drinks, dextrose gels, or juice.¹²⁸ It is recommended that the carbohydrate source be low in fat to increase the rate of absorption. Individuals should check glucose levels again after 15 min and retreat if glucose levels have not elevated to a normal range. In situations in which exercise is to be continued, higher amounts of fast-acting carbohydrate should be consumed, along with a lower glycemic index snack once euglycemia is attained. In the postexercise period, a meal containing complex carbohydrate should be consumed, with an appropriate (albeit likely reduced) amount of bolus insulin so that muscle and liver glycogen stores may be repleted.

Hypoglycemia prevention. The risk for exercise-associated hypoglycemia is greatest during prolonged moderate- to high-intensity aerobic exercise, particularly if circulating insulin levels are elevated during the activity. Intermittent high-intensity exercise may pose less risk for hypoglycemia because of the associated increases in catecholamine levels.¹²⁹ Performing resistance exercise before aerobic exercise helps limit the risk of hypoglycemia compared with performing aerobic before resistance exercise.⁴⁸ The carbohydrates eaten to enhance glycogen storage and replacement before and after physical activity are frequently different from the ones used to rapidly treat a hypoglycemic event, since hyperglycemia prevention is also a concern.

The ADA guidelines on exercise and T1D published in 1994 recommended consuming 10–15 g of carbohydrate to prevent exercise-induced hypoglycemia.¹³⁰ However, findings of recent research estimate that 40 g of a liquid glucose supplement may be necessary to prevent hypoglycemia during and after 1 h of late postprandial exercise in people using rapid-acting analog (lispro) in basal-bolus therapy.¹³¹ Even higher amounts of glucose may be needed if peak insulin levels are in circulation and hepatic glucose production is at a minimum. For example, one study in youth with diabetes showed that matching glucose intake with endogenous carbohydrate utilization (~1 g carbohydrate/kg body mass/h) prevented blood glucose levels from dropping during 60 min of exercise.⁵² To estimate carbohydrate utilization in youth who differ in size and energy expenditure based on the activity, a table of exercise exchanges (ExCarbs) may be a useful starting point (see Table 11.3).^46,132 It is important to note that the carbohydrate requirements progressively decreased when 1 h of exercise was performed 1, 2.5, 4, and 5.5 h after a meal preceded by an injection of a standard dose (1 U/kg) of regular insulin.¹³³

Table 11.3 Total Amount of Carbohydrates Utilized during 30 Min of Various Sporting Activities of Children Weighing Differing Amounts. These values can be used to estimate the amount of additional carbohydrate that could be consumed for 30 min of a given sport when peak insulin levels are high and if no reductions in insulin were made in anticipation of the activity.

Even if insulin adjustments are not made in anticipation of the activity, patients will be able to exercise if they consume extra carbohydrates to compensate. For example, consuming a carbohydrate beverage (6% carbohydrate solution) before the start of exercise (~1.0 g carbohydrate/kg body mass/h of exercise), without taking any additional insulin, is effective in limiting the drop in glycemia during prolonged exercise in youth with T1D.⁵² Based on one study, consuming fast-acting carbohydrate (dextrose) is preferable to those with a lower glycemic index (i.e., isomaltulose) for the prevention of hypoglycemia.¹³⁴

However, there is no clear consensus on the amount of additional carbohydrate required to limit exercise-associated hypoglycemia. Recommendations for carbohydrate consumption before or during exercise in T1D individuals range from amounts based on pre-exercise blood glucose concentration to amounts based on exercise duration (e.g., 20–60 g every 30 min) or body mass (1–2 g/kg body mass).^{117,132,135–138} Based on these and other studies, it is clear that the carbohydrate requirements to prevent hypoglycemia need to be individualized based on the size of the individual, the energy expenditure of the activity, and the type of insulin regimen that the patient is on.

Reductions in insulin administration are effective in preventing hypoglycemia during exercise in individuals with T1D, although the reductions in insulin levels range between 10 and 90%, based on several factors including the type of insulin used and the type and timing of the exercise performed.^139–142 Although it is generally recommended that exercise be avoided in the 2-h window after rapid-acting insulin is injected because of an increased risk for hypoglycemia, the administration of a reduced dose of rapid-acting insulin by 25–75% along with the ingestion of carbohydrates within this window of elevated risk is effective in limiting dysglycemia.^{46,134,140,142} A useful starting point, Table 11.4 is based on a study that describes bolus reductions in insulin dose, taking into consideration the duration and intensity of the activity.

Hyperglycemia Associated with Physical Activity

Hyperglycemia risk. Although exercise is typically associated with hypoglycemia, it can also induce hyperglycemia because of increases in stress hormones caused either by

vigorous exercise or by the stress of competition.¹⁶ In some cases, hyperglycemia may result from excessive carbohydrate intake or because insulin was withheld in an attempt to prevent hypoglycemia. On occasion, illness or a block in an insulin pump infusion set can also promote hyperglycemia. Excessive pre-exercise carbohydrate consumption provokes mild to moderate hyperglycemia pre-exercise, but this usually resolves once the exercise begins.¹⁴³ Moreover, if a high-glycemic carbohydrate (i.e., dextrose) is ingested just prior to vigorous exercise, it can increase the risk for postexercise hyperglycemia.¹³⁴ In any case, if hyperglycemia occurs in association with elevations in ketone levels, the exercise should be postponed until these are resolved, as exercise may exacerbate the condition.^130,144

Treatment of hyperglycemia at the time of exercise is challenging since insulin sensitivity may be elevated because of exercise-mediated increases in GLUT-4 translocation in skeletal muscle.¹⁴⁵ Although no studies have been conducted to date, correction of hyperglycemia with small amounts of rapid-acting insulin analogs via injection or infusion may be desirable to help prevent dehydration and impaired sports performance. In these situations, about half the normal insulin correction factor should be used and frequent glucose monitoring should be encouraged. Hydration is also an important consideration as individuals may be prone to rapid dehydration because of the combined effects of exercise and polyuria.

No current guidelines exist for the prevention of exercise-associated hyperglycemia caused by vigorous exercise and the associated increases in catecholamine levels. If the exercise duration is short (i.e., <30 min), it may be safer to attempt to correct any hyperglycemia following exercise rather than to try to prevent it by taking more insulin before the activity. Some limited laboratory data suggest that a doubling in circulating insulin levels immediately postexercise, relative to the pre-exercise state, may be needed.⁹⁵ The occurrence of postexercise hyperglycemia is less dramatic following prolonged aerobic exercise if a low-glycemic–index carbohydrate is consumed prior to exercise, rather than dextrose; however, the risk for hypoglycemia during the exercise may be marginally increased.¹³⁴

Blood glucose monitors. Frequent self-monitoring of blood glucose (SMBG) is critical to better understand the glycemic responses to exercise and to try to limit the amount of dysglycemia. Prior to exercise, it is recommended to take at least two glucose measurements, spaced 15–30 min apart, so that directional changes in glucose can be determined.¹³⁰ Knowing that glucose is stable at 110 mg/dl before exercise likely requires a different strategy than seeing that it has dropped from 215 mg/dl to 100 mg/dl in the last 30 min. It is also recommended to test blood glucose levels every 30 min during the activity so that carbohydrate and insulin intake strategies can be modified if needed. Blood glucose monitoring in late recovery is also recommended as increased insulin sensitivity typically occurs 7–11 h later in recovery (often during sleep).⁸⁸

Insulin pumps. Insulin pump devices (see chapter 12) offer a number of advantages and disadvantages for the active individual with T1D.^46,146,147 In general, pump users can adjust both the bolus insulin and the basal rate infusion before, during, and after exercise, thereby offering more flexibility in insulin dosing compared to fixed insulin injections. The insulin pump can be suspended or disconnected during exercise, if required. One major advantage is that basal insulin reductions following exercise can occur automatically during discrete hours during sleep (i.e., bedtime to 3 a.m.) to help prevent nocturnal hypoglycemia.⁹⁴ Internal calculators can be used to estimate the amount of on board insulin during the activity and can help prevent excessive insulin dosing at meal times.¹⁴⁸ In contrast, however, insulin pumps may interfere or be damaged during contact sports and there may be an increased risk for rapid development of hyperglycemia and ketosis if the pump is disconnected or if the infusion set is blocked. Indeed, postexercise hyperglycemia often occurs if the pump is removed (or if the infusion is reduced to zero) for exercise.⁹⁷ Insulin infusion sets may become displaced in conditions of heavy perspiration or water exposure (e.g., swimming) and skin irritation may result at the site of infusion, although strategies exist to help ameliorate these issues.

Continuous glucose monitoring (CGM). A number of relatively small studies have examined the utility of using CGM (see chapter 12) with exercise. In most studies, CGM has been demonstrated to accurately track the change in glycemia during exercise in patients with T1D.^91,149,150 However, real-time CGM tends to overestimate blood glucose levels if hypoglycemia is developing, likely because of the 10–20 min time delay in equilibrium between interstitial fluid and capillary glucose.¹⁴⁷ In one study, CGM was shown to be effective in detecting between ~65–70% of exercise-induced hypoglycemia, depending on the number of calibrations that were used (3 vs. 4/day).¹⁵¹ Similarly, during vigorous exercise, CGM may fail to capture hyperglycemia if the changes are rapid.¹⁵²

Real-time CGM use may help reduce the fear of exercise-associated hypoglycemia if directional arrows and alerts are used.¹⁵³ CGM may be very useful in situations in which SMBG is impractical (e.g., cycling road racing) or impossible, such as with scuba diving and when subjects are sleeping, to help reveal nocturnal hypoglycemia.^93,154 CGM may hold the promise of preventing hyperglycemia altogether during sports by keeping users more aware of their glucose concentrations and thus better prepared to take preventative actions. Indeed, a new carbohydrate intake algorithm designed to be used with glucose directional alters has been shown effective in preventing hypoglycemia altogether in a T1D youth sports camp setting.¹⁵⁵ Since glucose changes during exercise can be rapid, increasing the low-glucose-alert alarms from ~3.5 to 5.5 confers additional protection against exercise-induced hypoglycemia, without promoting false alarms.

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