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Exercise and Type 1 Diabetes (T1DM)

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Abstract

Physical exercise is firmly incorporated in the management of type 1 diabetes (T1DM), due to multiple recognized beneficial health effects (cardiovascular disease prevention being preeminent). When glycemic values are not excessively low or high at the time of exercise, few absolute contraindications exist; practical guidelines regarding amount, type, and duration of age‐appropriate exercise are regularly updated by entities such as the American Diabetes Association and the International Society for Pediatric and Adolescent Diabetes. Practical implementation of exercise regimens, however, may at times be problematic. In the poorly controlled patient, specific structural changes may occur within skeletal muscle fiber, which is considered by some to be a disease‐specific myopathy. Further, even in well‐controlled patients, several homeostatic mechanisms regulating carbohydrate metabolism often become impaired, causing hypo‐ or hyperglycemia during and/or after exercise. Some altered responses may be related to inappropriate exogenous insulin administration, but are often also partly caused by the “metabolic memory” of prior glycemic events. In this context, prior hyperglycemia correlates with increased inflammatory and oxidative stress responses, possibly modulating key exercise‐associated cardio‐protective pathways. Similarly, prior hypoglycemia correlates with impaired glucose counterregulation, resulting in greater likelihood of further hypoglycemia to develop. Additional exercise responses that may be altered in T1DM include growth factor release, which may be especially important in children and adolescents. These multiple alterations in the exercise response should not discourage physical activity in patients with T1DM, but rather should stimulate the quest for the identification of the exercise formats that maximize beneficial health effects. © 2013 American Physiological Society. Compr Physiol 3:1309‐1336, 2013.

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Figure 1. Figure 1.

Various blood glucose responses to exercise. Euglycemia occurs when there is a decrease in the insulin/counterregulatory hormone ratio (glucagon, catecholamines, etc.) that permits increased glucose production that matches the increase in glucose disposal into working muscle (top panel). Hypoglycemia occurs if insulin levels are not lowered at the onset of exercise in patients with T1DM (middle panel). Hyperglycemia occurs when the exercise intensity is very vigorous (>80% VO2max), if insulin administration is withheld, or if competition stress exists (bottom panel).

Figure 2. Figure 2.

Schematic of sequence of homeostatic events affecting carbohydrate metabolism during moderate, constant‐load exercise in healthy and T1DM subjects, showing the possible causes of exercise‐associated hypoglycemia in T1DM.

Figure 3. Figure 3.

Schematic of sequence of homeostatic events affecting carbohydrate metabolism during and immediately after intense exercise (above the anaerobic threshold, AT) in healthy and T1DM subjects, showing the possible causes of postexercise hyperglycemia in T1DM.

Figure 4. Figure 4.

Theoretical effects of blood glucose control on exercise performance in T1DM. A number of possible mechanisms exist that may explain deteriorated exercise performance during both hypoglycemia and hyperglycemia in individuals with T1DM.

Figure 5. Figure 5.

Increased inflammatory response to exercise in subjects with T1DM with worse glycemic control over the previous 3 days (). In 47 young adults with T1DM, the exercise‐induced increase in interleukin‐6 (IL‐6), a proinflammatory cytokine was progressively greater in subjects who had experienced higher mean average glycemic values over the prior 3 days (A). When the same IL‐6 responses were analyzed based only on morning hyperglycemia on the day of the exercise challenge, the half of the subject with higher morning glycemia had a greater IL‐6 response that the lower half (B), but within each half a close dose response was not observed. When the half with the highest morning hyperglycemia, however, was resubdivided in two quarters based on prior 3‐day glycemia, again a dose response with magnitude of prior hyperglycemia became evident (C). Our data indicate that a hierarchical proinflammatory effect is induced by prior hyperglycemia occurred at different times in the past: recent hyperglycemia seems to have the strongest effect, but among subject with similar recent hyperglycemia, hyperglycemia occurred at an earlier time seems to exert an additional proinflammatory reinforcement.

Figure 6. Figure 6.

Blunted counterregulatory responses to exercise in a group of 16 patients with T1DM during a 2‐day controlled study (). On day 1, subjects were exposed to 4 h (two 2‐h blocks) of hypoglycemia of varying depth, and on day 2 they exercise in euglycemic conditions. While in all experiments, when exercise started, prior hypoglycemia had been corrected for at least 16 h, a dose‐response blunting of major counterregulatory response to exercise occurred, proportional to the depth of hypoglycemia experienced the day before.

Figure 7. Figure 7.

Blunted counterregulatory responses to exercise in a group of 16 patients with T1DM during a 2‐day controlled study (). On day 1, subjects were exposed to 4 h (two 2‐h blocks) of hypoglycemia of varying depth, and on day 2 they exercise in euglycemic conditions. While in all experiments, when exercise started, prior hypoglycemia had been corrected for at least 16 h, a dose‐response blunting of major counterregulatory response to exercise occurred, proportional to the depth of hypoglycemia experienced the day before.

Figure 8. Figure 8.

Blunted counterregulatory responses to exercise in a group of 16 patients with T1DM during a 2‐day controlled study (). On day 1, subjects were exposed to 4 h (two 2‐h blocks) of hypoglycemia of varying depth, and on day 2 they exercise in euglycemic conditions. While in all experiments, when exercise started, prior hypoglycemia had been corrected for at least 16 h, a dose‐response blunting of major counterregulatory response to exercise occurred, proportional to the depth of hypoglycemia experienced the day before.

Figure 9. Figure 9.

Blunted counterregulatory responses to exercise in a group of 16 patients with T1DM during a 2‐day controlled study (). On day 1, subjects were exposed to 4 h (two 2‐h blocks) of hypoglycemia of varying depth, and on day 2 they exercise in euglycemic conditions. While in all experiments, when exercise started, prior hypoglycemia had been corrected for at least 16 h, a dose‐response blunting of major counterregulatory response to exercise occurred, proportional to the depth of hypoglycemia experienced the day before.



Figure 1.

Various blood glucose responses to exercise. Euglycemia occurs when there is a decrease in the insulin/counterregulatory hormone ratio (glucagon, catecholamines, etc.) that permits increased glucose production that matches the increase in glucose disposal into working muscle (top panel). Hypoglycemia occurs if insulin levels are not lowered at the onset of exercise in patients with T1DM (middle panel). Hyperglycemia occurs when the exercise intensity is very vigorous (>80% VO2max), if insulin administration is withheld, or if competition stress exists (bottom panel).



Figure 2.

Schematic of sequence of homeostatic events affecting carbohydrate metabolism during moderate, constant‐load exercise in healthy and T1DM subjects, showing the possible causes of exercise‐associated hypoglycemia in T1DM.



Figure 3.

Schematic of sequence of homeostatic events affecting carbohydrate metabolism during and immediately after intense exercise (above the anaerobic threshold, AT) in healthy and T1DM subjects, showing the possible causes of postexercise hyperglycemia in T1DM.



Figure 4.

Theoretical effects of blood glucose control on exercise performance in T1DM. A number of possible mechanisms exist that may explain deteriorated exercise performance during both hypoglycemia and hyperglycemia in individuals with T1DM.



Figure 5.

Increased inflammatory response to exercise in subjects with T1DM with worse glycemic control over the previous 3 days (). In 47 young adults with T1DM, the exercise‐induced increase in interleukin‐6 (IL‐6), a proinflammatory cytokine was progressively greater in subjects who had experienced higher mean average glycemic values over the prior 3 days (A). When the same IL‐6 responses were analyzed based only on morning hyperglycemia on the day of the exercise challenge, the half of the subject with higher morning glycemia had a greater IL‐6 response that the lower half (B), but within each half a close dose response was not observed. When the half with the highest morning hyperglycemia, however, was resubdivided in two quarters based on prior 3‐day glycemia, again a dose response with magnitude of prior hyperglycemia became evident (C). Our data indicate that a hierarchical proinflammatory effect is induced by prior hyperglycemia occurred at different times in the past: recent hyperglycemia seems to have the strongest effect, but among subject with similar recent hyperglycemia, hyperglycemia occurred at an earlier time seems to exert an additional proinflammatory reinforcement.



Figure 6.

Blunted counterregulatory responses to exercise in a group of 16 patients with T1DM during a 2‐day controlled study (). On day 1, subjects were exposed to 4 h (two 2‐h blocks) of hypoglycemia of varying depth, and on day 2 they exercise in euglycemic conditions. While in all experiments, when exercise started, prior hypoglycemia had been corrected for at least 16 h, a dose‐response blunting of major counterregulatory response to exercise occurred, proportional to the depth of hypoglycemia experienced the day before.



Figure 7.

Blunted counterregulatory responses to exercise in a group of 16 patients with T1DM during a 2‐day controlled study (). On day 1, subjects were exposed to 4 h (two 2‐h blocks) of hypoglycemia of varying depth, and on day 2 they exercise in euglycemic conditions. While in all experiments, when exercise started, prior hypoglycemia had been corrected for at least 16 h, a dose‐response blunting of major counterregulatory response to exercise occurred, proportional to the depth of hypoglycemia experienced the day before.



Figure 8.

Blunted counterregulatory responses to exercise in a group of 16 patients with T1DM during a 2‐day controlled study (). On day 1, subjects were exposed to 4 h (two 2‐h blocks) of hypoglycemia of varying depth, and on day 2 they exercise in euglycemic conditions. While in all experiments, when exercise started, prior hypoglycemia had been corrected for at least 16 h, a dose‐response blunting of major counterregulatory response to exercise occurred, proportional to the depth of hypoglycemia experienced the day before.



Figure 9.

Blunted counterregulatory responses to exercise in a group of 16 patients with T1DM during a 2‐day controlled study (). On day 1, subjects were exposed to 4 h (two 2‐h blocks) of hypoglycemia of varying depth, and on day 2 they exercise in euglycemic conditions. While in all experiments, when exercise started, prior hypoglycemia had been corrected for at least 16 h, a dose‐response blunting of major counterregulatory response to exercise occurred, proportional to the depth of hypoglycemia experienced the day before.

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Pietro Galassetti, Michael C. Riddell. Exercise and Type 1 Diabetes (T1DM). Compr Physiol 2013, 3: 1309-1336. doi: 10.1002/cphy.c110040