**7. Discussion**

ces between GrS and GrR.

**6,5**

**6,7**

**6,9**

**7,1**

**HbA1c [%]**

**7,3**

**7,5**

**7,7**

**incidents/day**

80 Glucose Homeostasis

**6-8 8-10 10-12 12-14 14-16 16-18 18-20 20-22 time of the day [hour]**

**\*\*\***

**\*\*\***

**\*\***

**\*\***

 **\*\***

**Hyperglycemia GrR Hyperglycemia GrS**

**GrS GrR**

**Figure 4.** Glycated hemoglobin concentrations (HbA1c%) in GrS and GrR before and after two weeks of study.

**HbA1c pre HbA1c post**

**Figure 3.** The number of hyperglycemic events at particular time of the day. \*\*p<0.01; \*\*\*p<0.001 significant differen‐

Children and adolescents engage in different types of exercise, most frequently in unplanned and spontaneous physical activities, which can, of course, be associated with immediate and long-term health benefits [36, 62, 85-86]. Children with T1DM gain similar health benefits from physical exercise as their healthy peers; however, due to several consequences of the disease, some specific characteristics of their adaptation to exercise should be considered. Diabetic children and adolescents differ from the healthy pediatric population in their physiological responses to exercise. They are characterized by impaired utilization of exogenous glucose as an energy source during exercise despite hyperinsulinemia and higher rates of perceived exertion, which persist after glucose ingestion [60, 87]. In patients with diabetes, exercise may increases insulin sensitivity and insulin absorption from the site of administration. Plasma glucose levels decrease during and after low-and moderate intensity exercise in response to enhanced glucose utilization in skeletal muscle [88]. In contrast, high-intensity exercise protocols may increase the risk of hyperglycemic episodes [51, 57, 62, 89].

In the present study we analyzed the level of physical activity of children and adolescents with type 1 diabetes and the effect of exercise intensity to compensate blood glucose level depending on the insulin treatment and the diet. Furthermore the aim of the study was to determine the energy expenditure associated with the programmed physical activity which is effective for maintaining normoglycemia in children with type 1 diabetes.

The major findings of our study are that: 1) physical activity in children with type 1 diabetes was lower than the standards for the population of healthy children and recommendations for health training, 2) programmed physical activity significantly increased daily energy expen‐ diture; however, may also increase the risk of hyperglycemia, 3) greater physical activity seemed to provide more effective control of glucose homeostasis as demonstrated by reduc‐ tions in HbA1c. Our results also show that children with T1DM do not meet the standards of consumption of basic nutrients; higher fat and protein intake with lower carbohydrate values might induce glucose imbalance.

not decrease during exercise in T1DM compared to healthy subjects. Quite the opposite-it may even rise, first due to the higher absorption, secondly due to the increased insulin sensitivity, and, finally, in the case when insulin injection is given shortly before exercise. Consequently, the ability to mobilize fat and carbohydrate fuels for exercise may be compromised [3] which facilitates the onset of hypoglycaemia during moderate-intensity exercise [92, 97]. As it was suggested, low-to-moderate intensity exercise was generally recommended for patients with type 1 diabetes since numerous benefits on glucose homeostasis had been observed [91, 95, 99]. However, hypoglycemia can be minimized by appropriately reducing insulin dosage or

The Effects of Energy Intake, Insulin Therapy and Physical Activity on Glucose Homeostasis in…

http://dx.doi.org/10.5772/57590

83

Processes regulated by insulin-independent mechanisms are generally preserved when people with diabetes engage in high-intensity exercise. These processes include normal increases in glucose production and disposal during and immediately after the exercise [63, 100-101]. After high-intensity exercise appropriate control of glycaemia is more challenging than in lowintensity exercise due to the role of insulin in modulating the postexercise decline in glucose disposal. Low circulating levels of insulin can prolong hyperglycemia during the recovery after high-intensity exercise, partially counteracting the beneficial effects of exercise on glucose control. If a patient recognizes that a given exercise leads to postexercise hyperglycemia, insulin should be administered shortly after the completion of high-intensity exercise. However, there is evidence that high-intensity exercise, used in combination with low-or moderate-intensity exercise, may maintain blood glucose levels within the normal physiolog‐

In the present study, we investigated weekly engagement of children and adolescents with type 1 diabetes in physical activity using an accelerometer. Data regarding their physical activity were obtained through the calculation of mean energy expenditure and com‐ pared to reference ranges for children and adolescents. The participants were asked to monitor their physical activity for 7 days during school classes (5 days) and weekend days (2 days). We observed that children and adolescents with T1DM did not adhere to recommended levels of physical activity. Sedentary time was higher on Sunday in all participants and higher in the older group. The proportion of diabetics who did not meet the physical activity recommendations in the present study is consistent with the results of previous studies. Sporting habits in children and adolescents with diabetes were ana‐ lyzed by Vanelli et al. [102] and Admon et al. [91]. Weekly levels of moderate/vigorous physical activity and sports participation were investigated using a questionnaire. The results showed that children with T1DM appeared to spend less time engaged in physi‐ cal activity than their non-diabetic peers. Regular physical activity was associated with better metabolic control and lipid profile [103-105]. The association between physical activities, sedentary behavior, and metabolic control in adolescents with T1DM was also observed by Åman et al. [11], who reported that PA was associated with positive health perception but not with glycaemic control, frequency of hypoglycemia or other beneficial effects. In youth with T1DM, prolonged moderate aerobic exercise results in a consistent reduction in plasma glucose and frequent occurrence of hypoglycemia when pre-exercise

ingesting additional carbohydrates [60, 90].

ical range and thus minimize the risk of hypoglycemia [62-63].

The American Diabetes Association recommends that young patients with diabetes should be given the opportunity to benefit from participating in every type of physical activity, including both recreational and competitive exercises. The understanding of the mechanism of glycemic changes in exercising muscles, modulation of both insulin dose and injection site and appro‐ priate dietary supplementation in T1DM patients prevent the occurrence of adverse events during physical activity [90]. Thus, a thorough understanding of the interactions between exogenous insulin and insulin secretagogues, diet and various forms and intensities of exercise seems to be of great importance to achieve tight metabolic control in diabetic patients. The dose and type of insulin administration (multiple injections/continuous subcutaneous insulin infusion), the site of injection and the timing of insulin dose and food intake before exercise may influence the metabolic and hormonal responses to physical activity among T1DM patients [32, 60, 91].

Plasma glucose concentration is a function of glucose supply, transport rate in the circulation, and metabolism [92-93]. The glucoregulatory hormones, of which insulin is the most impor‐ tant, are designed to maintain circulating glucose concentrations in the physiological range. Initially, insulin stimulates the cells of insulin-sensitive tissues, primarily skeletal muscle, to increase their glucose uptake [6, 43]. Secondly, insulin acts on the liver to inhibit glucose production [42]. The insulin dependent mechanism of glucose transport may be exacerbated by the skeletal muscle contractions. Insulin enhances translocation of specific transporter proteins (GLUT-4) which carry glucose into muscle and adipose cells. In patients with type 1 diabetes mellitus, the insulin-independent mechanism is the most important. Translocation of glucose transporter proteins to cell membrane is initiated by muscle contractions when calcium is released. Recent investigations also indicate that autocrine/paracrine mechanisms observed during exercise (e.g., nitric oxide, adenosine, bradykinin, insulin-like growth hormone-1 may exert alternative or parallel actions [2, 94-96].

It is well established that hypoglycemia is the most common response to exercise; however, in a diabetic patient blood glucose concentrations may also increase or remain unchanged. It is also possible that, even in well-controlled patients, exercise-induced increases in glucose utilization may lead to hypoglycemia [88] both during exercise and up to 31 hours of recovery [90, 97]. Conversely, excessive snacking before exercise, exercise protocols characterized by high intensity and sympathetic nervous systems activation may influence the metabolic response to exercise and increase the risk for hyperglycemia [36, 98]. Several factors may contribute to these adverse reactions during and after exercise [42]. In patients requiring exogenous insulin therapy, insulin levels are predominantly associated with medication; consequently, these levels do not decrease in response to exercise. At the normal exerciseinduced decrease in the portal insulin level, hepatic glucose production remains suppressed and cannot increase proportionally to the muscle glucose utilization. As a result, blood glucose declines to hypoglycemic levels [36]. As mentioned above, plasma insulin concentration does not decrease during exercise in T1DM compared to healthy subjects. Quite the opposite-it may even rise, first due to the higher absorption, secondly due to the increased insulin sensitivity, and, finally, in the case when insulin injection is given shortly before exercise. Consequently, the ability to mobilize fat and carbohydrate fuels for exercise may be compromised [3] which facilitates the onset of hypoglycaemia during moderate-intensity exercise [92, 97]. As it was suggested, low-to-moderate intensity exercise was generally recommended for patients with type 1 diabetes since numerous benefits on glucose homeostasis had been observed [91, 95, 99]. However, hypoglycemia can be minimized by appropriately reducing insulin dosage or ingesting additional carbohydrates [60, 90].

seemed to provide more effective control of glucose homeostasis as demonstrated by reduc‐ tions in HbA1c. Our results also show that children with T1DM do not meet the standards of consumption of basic nutrients; higher fat and protein intake with lower carbohydrate values

The American Diabetes Association recommends that young patients with diabetes should be given the opportunity to benefit from participating in every type of physical activity, including both recreational and competitive exercises. The understanding of the mechanism of glycemic changes in exercising muscles, modulation of both insulin dose and injection site and appro‐ priate dietary supplementation in T1DM patients prevent the occurrence of adverse events during physical activity [90]. Thus, a thorough understanding of the interactions between exogenous insulin and insulin secretagogues, diet and various forms and intensities of exercise seems to be of great importance to achieve tight metabolic control in diabetic patients. The dose and type of insulin administration (multiple injections/continuous subcutaneous insulin infusion), the site of injection and the timing of insulin dose and food intake before exercise may influence the metabolic and hormonal responses to physical activity among T1DM

Plasma glucose concentration is a function of glucose supply, transport rate in the circulation, and metabolism [92-93]. The glucoregulatory hormones, of which insulin is the most impor‐ tant, are designed to maintain circulating glucose concentrations in the physiological range. Initially, insulin stimulates the cells of insulin-sensitive tissues, primarily skeletal muscle, to increase their glucose uptake [6, 43]. Secondly, insulin acts on the liver to inhibit glucose production [42]. The insulin dependent mechanism of glucose transport may be exacerbated by the skeletal muscle contractions. Insulin enhances translocation of specific transporter proteins (GLUT-4) which carry glucose into muscle and adipose cells. In patients with type 1 diabetes mellitus, the insulin-independent mechanism is the most important. Translocation of glucose transporter proteins to cell membrane is initiated by muscle contractions when calcium is released. Recent investigations also indicate that autocrine/paracrine mechanisms observed during exercise (e.g., nitric oxide, adenosine, bradykinin, insulin-like growth hormone-1 may

It is well established that hypoglycemia is the most common response to exercise; however, in a diabetic patient blood glucose concentrations may also increase or remain unchanged. It is also possible that, even in well-controlled patients, exercise-induced increases in glucose utilization may lead to hypoglycemia [88] both during exercise and up to 31 hours of recovery [90, 97]. Conversely, excessive snacking before exercise, exercise protocols characterized by high intensity and sympathetic nervous systems activation may influence the metabolic response to exercise and increase the risk for hyperglycemia [36, 98]. Several factors may contribute to these adverse reactions during and after exercise [42]. In patients requiring exogenous insulin therapy, insulin levels are predominantly associated with medication; consequently, these levels do not decrease in response to exercise. At the normal exerciseinduced decrease in the portal insulin level, hepatic glucose production remains suppressed and cannot increase proportionally to the muscle glucose utilization. As a result, blood glucose declines to hypoglycemic levels [36]. As mentioned above, plasma insulin concentration does

might induce glucose imbalance.

82 Glucose Homeostasis

patients [32, 60, 91].

exert alternative or parallel actions [2, 94-96].

Processes regulated by insulin-independent mechanisms are generally preserved when people with diabetes engage in high-intensity exercise. These processes include normal increases in glucose production and disposal during and immediately after the exercise [63, 100-101]. After high-intensity exercise appropriate control of glycaemia is more challenging than in lowintensity exercise due to the role of insulin in modulating the postexercise decline in glucose disposal. Low circulating levels of insulin can prolong hyperglycemia during the recovery after high-intensity exercise, partially counteracting the beneficial effects of exercise on glucose control. If a patient recognizes that a given exercise leads to postexercise hyperglycemia, insulin should be administered shortly after the completion of high-intensity exercise. However, there is evidence that high-intensity exercise, used in combination with low-or moderate-intensity exercise, may maintain blood glucose levels within the normal physiolog‐ ical range and thus minimize the risk of hypoglycemia [62-63].

In the present study, we investigated weekly engagement of children and adolescents with type 1 diabetes in physical activity using an accelerometer. Data regarding their physical activity were obtained through the calculation of mean energy expenditure and com‐ pared to reference ranges for children and adolescents. The participants were asked to monitor their physical activity for 7 days during school classes (5 days) and weekend days (2 days). We observed that children and adolescents with T1DM did not adhere to recommended levels of physical activity. Sedentary time was higher on Sunday in all participants and higher in the older group. The proportion of diabetics who did not meet the physical activity recommendations in the present study is consistent with the results of previous studies. Sporting habits in children and adolescents with diabetes were ana‐ lyzed by Vanelli et al. [102] and Admon et al. [91]. Weekly levels of moderate/vigorous physical activity and sports participation were investigated using a questionnaire. The results showed that children with T1DM appeared to spend less time engaged in physi‐ cal activity than their non-diabetic peers. Regular physical activity was associated with better metabolic control and lipid profile [103-105]. The association between physical activities, sedentary behavior, and metabolic control in adolescents with T1DM was also observed by Åman et al. [11], who reported that PA was associated with positive health perception but not with glycaemic control, frequency of hypoglycemia or other beneficial effects. In youth with T1DM, prolonged moderate aerobic exercise results in a consistent reduction in plasma glucose and frequent occurrence of hypoglycemia when pre-exercise glucose concentrations are < 120 mg/dl. It also seems that treatment with 15 g of oral glucose is insufficient to reliably treat hypoglycemia during exercise in children and adolescents [88].

of long term glycaemic control (HbA1c%) compared to pretraining levels. This study has limitations that need to be considered before interpreting the findings. The rehabilitation programme might have been too short to significantly improve glycemic control which could be documented by decrease HbA1c level. Also, since the baseline HbA1C levels were slightly over the reference range, ie., below 7.2%, the effects of physical activity in GrR were not so

The Effects of Energy Intake, Insulin Therapy and Physical Activity on Glucose Homeostasis in…

http://dx.doi.org/10.5772/57590

85

There is evidence that high-intensity exercise along with low-or moderate-intensity exercise might be recommended to diabetic patients. The most important exercise-related benefits in patients with T1DM include reduced serum glucose levels, improved insulin sensitivity and lipid profile, reduced daily dosage of insulin, improved cardiovascular function, reduced body weight and fat accumulation, increase in physical efficiency, and quality of life improvement. Thus, parents, physical education teachers and physical therapists should motivate type 1 diabetic children to engage in physical activity, and supervise them during exercise in order to create a proper approach to physical exercise and reduce the risk for exercise-related

It should be emphasized that, general exercise recommendations for children and adolescents with T1DM are that they should exercise systematically, for about 30 to 60 minutes, four to five times a week at a low to moderate intensity [115]. In this way they utilize glucose slowly and the effects of preferential fat oxidation improve. Apart from aerobic exercises, diabetics should perform intermittent high-intensity exercise to minimize the occurrence of hypogly‐ cemic events. High-intensity physical exercise causes severe lactic acidosis and increases adrenergic system activation as compared to low-intensity exercise. Consequently, endurance sports activities performed under aerobic threshold are recommended for T1DM patients [98]. On the other hand, a combination of moderate-and high-intensity exercise, a pattern of physical activity referred to as intermittent high-intensity exercise, may also be recommended for youth with T1DM [61, 63, 116]. It is worth to point out that, individual insulin administra‐ tion scheme (insulin injections and pump) and blood glucose monitoring are of great impor‐ tance [91]. The authors mentioned that the pump should be removed or turned off during

Regular physical activity is an essential element in blood glucose regulation for children and adolescents with type 1 diabetes mellitus. The obtained results indicate that children with type 1 diabetes are not meeting recommended physical activity and dietary guidelines, and especially regarding fat intake. Regular physical activity with high energy expenditure may effectively control glucose homeostasis as documented by HbA1c reduction. However, incorrect dietary behaviors and/or exercise load in T1DM patients may increase the risk of

unplanned prolonged exercise to reduce the risk of hypoglycemia.

hypo-or hyperglycemia and long-term metabolic complications.

spectacular.

complications [110-114].

**8. Conclusions**

Our results showed significantly higher frequency of hyperglycemic events in GrR compared to GrS, with similar amount of hypoglycemic events. It is worth pointing out that GrR exhibited lower glucose levels in the morning whereas hyperglycemia usually appeared in the after‐ noons and evenings. This coincided with the distribution of physical activities during the camp. In the morning children performed low-intensity exercise of longer duration while the intensity of afternoon exercise was higher.

Our investigations revealed that, compared to dietary standards for children, our study participants showed an excessive intake of proteins and fats and very low carbohydrate intake. Children with T1DM do not meet the standards of basic nutrients consumption [106]. The energy intake from proteins, fat and of carbohydrates compared to dietary standards for children showed an excessive intake of proteins and fats and very low carbohydrate intake. The analysis of variance showed a significant effect of age on the level of fat consumption and positive correlation between the value of energy intake and insulin dose.

Increased intake of fat and protein and lower carbohydrate values can cause problems with insulin administration in response to diet and/or physical activity.

It should be mentioned, that proper nutrition is important in the prevention and treatment of chronic complications of diabetes [107-110]. According to clinical guidelines [71] 40-50% of energy should provide carbohydrate diet, especially a low glycemic index (<50 IG), the fats should provide 30-35% of the energy value of the diet; and protein should be 15-20 %. The ratio of animal protein to vegetable protein should be at least 50/50%. For important recommenda‐ tions should supplement meals with fluids, vitamins, minerals and fiber [32]. Despite the important role of a balanced diet in the treatment of T1DM, standard recommendations that could help clinicians manage glycemia during exercise are still lacking [111]. The type, duration, and timing of exercise as well as its temporal relation to meals and premeal insulin doses may affect glucose homeostasis during and after exercise. Moreover, regulation of blood glucose associated with physical exercise and anabolic hormonal secretion could be important for long-term glycemic control [112-113]. In the above mentioned studies glycated hemoglobin (HbA1c) could be a better index of long-term glucose homeostasis than measuring fasting and/ or post-challenge glucose [69-70, 73].

The results of the previous study suggested improvement in long-term glycemic control in T1DM youth after a programme of physical activity [10, 105] associated with an increase in aerobic capacity or fitness. Austin et al. [103] also observed a negative correlation between aerobic physical effort and HgA1c levels and daily insulin doses in diabetic patients.

Consistent with these findings, our data also indicated a tendency to HbA1c levels increase in children with lower physical activity (GrS) compared to summer camp participants (GrR).

Our results also demonstrate that participation in an organized rehabilitation programme increased the daily energy expenditure and was associated with tendency to lowering indices of long term glycaemic control (HbA1c%) compared to pretraining levels. This study has limitations that need to be considered before interpreting the findings. The rehabilitation programme might have been too short to significantly improve glycemic control which could be documented by decrease HbA1c level. Also, since the baseline HbA1C levels were slightly over the reference range, ie., below 7.2%, the effects of physical activity in GrR were not so spectacular.

There is evidence that high-intensity exercise along with low-or moderate-intensity exercise might be recommended to diabetic patients. The most important exercise-related benefits in patients with T1DM include reduced serum glucose levels, improved insulin sensitivity and lipid profile, reduced daily dosage of insulin, improved cardiovascular function, reduced body weight and fat accumulation, increase in physical efficiency, and quality of life improvement. Thus, parents, physical education teachers and physical therapists should motivate type 1 diabetic children to engage in physical activity, and supervise them during exercise in order to create a proper approach to physical exercise and reduce the risk for exercise-related complications [110-114].

It should be emphasized that, general exercise recommendations for children and adolescents with T1DM are that they should exercise systematically, for about 30 to 60 minutes, four to five times a week at a low to moderate intensity [115]. In this way they utilize glucose slowly and the effects of preferential fat oxidation improve. Apart from aerobic exercises, diabetics should perform intermittent high-intensity exercise to minimize the occurrence of hypogly‐ cemic events. High-intensity physical exercise causes severe lactic acidosis and increases adrenergic system activation as compared to low-intensity exercise. Consequently, endurance sports activities performed under aerobic threshold are recommended for T1DM patients [98]. On the other hand, a combination of moderate-and high-intensity exercise, a pattern of physical activity referred to as intermittent high-intensity exercise, may also be recommended for youth with T1DM [61, 63, 116]. It is worth to point out that, individual insulin administra‐ tion scheme (insulin injections and pump) and blood glucose monitoring are of great impor‐ tance [91]. The authors mentioned that the pump should be removed or turned off during unplanned prolonged exercise to reduce the risk of hypoglycemia.
