کد مقاله : EPP-2305-1017 (R1) بازدید : 172 صفحه: 0 - 0

نوع مقاله: پژوهشی

The effects of aerobic exercise on physical fitness indices and the amount of insulin consumption in boys with type 1 diabetes

محورهای موضوعی : Exercise Physiology and Performance

samira zaheri ¹ ( Department of Exercise Physiology, Faculty of Sport Sciences, University of Guilan, Rasht, Iran. )

تاریخ دریافت : 1402/02/22 تاریخ پذیرش : 1402/05/27 تاریخ انتشار : 1402/09/10

کلید واژه: Aerobic training, insulin, Fitness, Diabetes type 1,

چکیده مقاله :

Background: The term diabetes mellitus describes a metabolic disorder of hyperglycemia with disturbances of carbohydrate metabolism resulting from defects in secretion and action of insulin. The aim of this study was to investigate the effects of aerobic exercise on physical fitness indices and the amount of insulin taken in boys with type 1 diabetesMethods: For this purpose, 64 adolescents boy with diabetes type I were selected and were divided into 2 groups: Aerobic training group (AE) (n = 32) and control group (CO) (n = 32).Aerobic training group did aerobic exercises for 6 weeks (3 days a week), while the control group did not do any exercise. Training program consisted of: a) warm-up (10 minutes); b) the original class (30 minutes); c) cooling (5 minutes). At first both groups performed fitness physical tests that include of flexibility (sit and reach test), muscular endurance test (sit-up test), aerobic capacity test (run 6 minutes’ walk), agility test (T-test) and anaerobic capacity (Running-based Anaerobic SprintTest), also were recorded the amount of insulin consumption as a pre-test and then after six weeks both groups performed the same tests as a post-test.Result: The results showed that 6 weeks of aerobic training has a significant effect in increasing agility, flexibility, muscular endurance, aerobic power and anaerobic power in boys with type I diabetes (p<0.05). In addition, aerobic exercise group significantly reduced the amount of insulin than the control group (p<0.05).Conclusion: The result of this study showed that the application of aerobic exercise is effective for improvement of physical fitness indices. This may reduce the amount of insulin in children and adolescents with type 1 diabetes and they are more likely to participate in sports activities.

چکیده انگلیسی:

منابع و مأخذ:

Herold KC, Hagopian W, Auger JA, Poumian-Ruiz E, Taylor L, Donaldson D, et al. Anti-CD3 Monoclonal Antibody in New-Onset Type 1 Diabetes Mellitus. N Engl J Med. 2002; 346(22):1692-8.
Cooke DW and Leslie Plotnick. Type 1 Diabetes Mellitus in Pediatrics Type 1 Diabetes Mellitus in Pediatrics. Pediatr. Rev. 2008; 29:374-385.
Rewers M, Bugawan TL, Norris JM, Blair A, Beaty B, Hoffman M, McDuffie RS, Hamman RF, Klingensmith G, Eisenbarth GS, et al. Newborn screening for HLA markers associated with IDDM: diabetes autoimmunity study in the young (DAISY) Diabetologia. 1996;39:807–812.
Lévy-Marchal C, Patterson CC, Green A; EURODIAB ACE Study Group. Europe and Diabetes. Geographical variation of presentation at diagnosis of type I diabetes in children: the EURODIAB study. European and Dibetes. Diabetologia. 2001; 44 Suppl 3:B75–B80.
Patterson CC, Dahlquist GG, Gyürüs E, Green A, Soltész G. Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: a multicentre prospective registration study. Lancet. 2009;373:2027–2033.
Zipitis CS, Akobeng AK. Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis. Arch Dis Child. 2008;93:512–517.
Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001;358:1500–1503.
Schattner A. Consequence or coincidence? The occurrence, pathogenesis and significance of autoimmune manifestations after viral vaccines. Vaccine. 2005;23:3876–3886.
Michels AW, Eisenbarth GS. Immune intervention in type 1 diabetes. Semin Immunol. 2011; 23:214–219.
Bearse MA Jr, Han Y, Schneck ME, Barez S, Jacobsen C, et al. Local multifocal oscillatory potential abnormalities in diabetes and early diabetic retinopathy. Invest Ophthalmol Vis Sci.2004; 45: 3259-3265.
Gillett MJ. International Expert Committee report on the role of the A1c assay in the diagnosis of diabetes: Diabetes Care 2009; 32(7): 1327-1334. Clin Biochem Rev 30: 197-200.
Østergård T, Andersen JL, Nyholm B, Lund S, Nair KS, Saltin B and et al. Impact of exercise training on insulin sensitivity, physical fitness, and muscle oxidative capacity in first-degree relatives of type 2 diabetic patients. American Journal of Physiology - Endocrinology and Metabolism. 2006; 290(5): 998-1005.
Mortensen HB, Robertson KJ, Aanstoot HJ, Danne T, Holl RW, Hougaard P, et al. Hvidore Study Group on Childhood Diabetes, Insulin management and metabolic control of type 1 diabetes mellitus in childhood and adolescence in 18 countries. Diabet Med. 1998; 15:752- 59.
Lucidi P, Porcellati F, Andreoli AM, Carriero I, Candeloro P, Cioli P, Bolli GB, and Fanelli CG. Pharmacokinetics and Pharmacodynamics of NPH Insulin in Type 1 Diabetes Mellitus: The Importance of Appropriate Resuspension before Subcutaneous Injection. Diabetes Care Publish Ahead of Print, published online September 2015
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متن کامل:

1. Introduction

Type 1 diabetes (T1D) is a potentially life threatening illness. Type 1 diabetes mellitus ( T1DM) is a T-cell–mediated autoimmune disease that begins, many cases, (three to five years) before the onset of clinical symptoms, continues after diagnosis, and can recur after islet transplantation(1). T1D (also called juvenile-onset diabetes mellitus and insulin-dependent diabetes mellitus) is the result of an absolute insulin deﬁciency, that cause of a loss of the insulin-producing beta cells of the pancreas (2).

Epidemiology of T1D, the incidence rate varies significantly by geographical region. Sweden, Finland, Norway, United Kingdom, and Sardinia have the highest incidence of T1D. China and South America have the lowest incidence of T1D, reported as < 1/100000 patient years (3,4). Unlike most autoimmune diseases, T1D is more usual in males than females. The rate of T1D diagnosis is increasing in most countries, with rates dramatically increasing in children less than 5 years of age (5).

Risk factors for diabetes are genetic, environmental. One of factors of environment , mothers supplemented with vitamin D during pregnancy and young children supplemented with vitamin D have shown a reduced risk of T1D development that may be dose responsive(6,7). Other environmental factors that continue to be explored include nitrosamine compounds, maternal age, pre-eclampsia, and childhood obesity. There is no evidence to suggest that vaccines increase the risk of T1D development (8). Clinical trials with drugs aimed at modulating the immune response and preserving endogenous insulin secretion in patients with new-onset T1D are termed tertiary prevention trials (9). Some of the symptoms of T1D include weight loss, polydipsia, polyphagia, constipation fatigue, cramps, blurred vision, and candidiasis (10).

Diagnosing diabetes is done by fasting plasma glucose test. There should be eight hours fasting before taking this test. Blood glucose more than 126 mg/dl on two or more tests conducted on different days confirms a diabetes diagnosis (11).

Poor physical fitness is a strong indicator of an increased risk of developing diabetes (12). Physical Fitness can be categorized as cardiorespiratory ﬁtness, muscular strength, ﬂexibility, or balance. Fitness levels in youth with type 2 diabetes (T2D) are lower than in T1D youth (at about 25 mL/kg/min) and adolescents with T1DM more tend to gain obesity and girls with T1DM have a higher risk for gaining weight than are boys with T1DM (13).

These days, prevalent of T1D in adolescents and youth are growing and training can be a useful tool for regulation blood glucose. On the one hand, one of the best ways to treat T1D is physical activity, especially aerobic exercises, and on the other hand, physical fitness factors are also recommended to improve people's physical performance. Therefore, we decided to carry out this study. The aim of this study is investigation of the effect of aerobic training on parameters of physical fitness and consumption of insulin in boys with T1D.

2. Material and methods

2.1. Subjects

In this study, sixty four boys with T1D at age of 14 to 20 years were recruited voluntary in Guilan city from Iran and were trained instructions about diabetes, training procedures. At first, subjects were informed about the overall program of study and entry criteria. Entry criteria include of lack of some cardiovascular diseases, renal, visual and cerebral, non-smoker and non-alcoholic, lack of diabetic complications Such as diabetic foot ulcers. After completing the consent form, Height and weight were measured; history and insulin dose samples were collected through consultation with experts and study medical records in centers. Also, the exclusion criteria included the patients with other types of diabetes, thyroid disorders, iron deficiency anemia, blood pressure and coronary arterial diseases, chronic kidney diseases, infection, recent major surgery or illness, or those who were under treatment with steroids or lipid-lowering drugs, and those with orthopedic disorders leading to movement limitation.

A glucometer is a medical device for determining the approximate concentration of glucose in the blood. A drop of blood, obtained by pricking the skin with a lancet, is placed on a disposable test strip that the meter reads and uses to calculate the blood glucose level. The meter then displays the level in units of mg/dl or mmol/l. Capillary blood samples were taken at room temperature 20 °C.

There are many types of insulin which the most common types of insulin are, Neutral Protamine Haledon (NPH) and regular insulin. Each type of insulin acts over a specific amount of time. Variability of NPH insulin might also be due to a lack of or insufficient resuspension before injection. In fact, NPH insulin is a two-phase solution, and the insulin of the insoluble, cloudy part has to be resuspended in the soluble, clear part by tipping the insulin vial or cartridge pen several times until a homogeneous suspension is obtained (14). Normal fasting patients received NPH and regular insulin. Regular insulin is a clear, colorless liquid, usually given 30 minutes before a meal. NPH insulin is Intermediate-acting which begin working 1 to 3 hours, is active 16 to 24 hours. Insulin is given by injection with single-use syringes with needles. Anthropometric features is shown in table 1 and the amounts of consumption insulin in morning and evening is shown in table 2.Then, subjects randomly divided into two groups: Aerobic training (AE) (n = 32) and control (CO) (n = 32) (Table 1). The exclusion criteria included the patients with other types of diabetes, thyroid disorders, iron deficiency anemia, blood pressure and coronary arterial diseases, chronic kidney diseases, infection, recent major surgery or illness, or those who were under treatment with steroids or lipid-lowering drugs, and those with orthopedic disorders leading to movement limitation.

Several times a day, the examiner pricks a finger to obtain a blood droplet and apply it to a plastic strip that’s inserted in a glucometer—a hand-held device that tells them if their glucose level is high, low, or right on target.

2.2. Testing

Both conducted fitness pretest that include aerobic capacity test (test run in 6 minutes’ walk), anaerobic capacity (Running-based Anaerobic Sprint Test), muscular endurance test (sit-up test), flexibility (sit and reach test hand), and agility (T-test). we also recorded the amount of insulin consumption .The experimental group protocol consisted of six weeks aerobic exercises training that each session are conducted 3 days a week. The intensity of aerobic training was determined by applying 60-70 percentage of maximum heart rate using the 220-age equation. The first training session was about 30 minutes. However, every 2-week, a 5-minute gradual increase was applied to the intensity of training. Each training session started with 10-minute warm up, 30-minute exercise training, and 5-minute final cooling down. The exercise training included 15-minute jugging, three sets of one minute walking with 1-minute rest in between, 3 sets of 1-minute rhythmic exercise accompanied by music with 60-70 percentage of maximum heart rate and 1-minute rest in between, and 3-minute rest between each exercise. During the 6 weeks training period, subjects in the control group did not participate in any regular training program, and the patients (at each session) did not participate in exercises in the case of hypoglycemia or glucose levels greater than 250 mg /dl (15).

Before each session, the subjects had blood sugar levels checked. In each session, the subjects were accompanied by a doctor or nurse with first aid supplies and medications (such as glucose 50% serum vials for the sharp drop in sugar). The consumption insulin time and the last meal time were controlled through a questionnaire. During the 6 weeks, the control group was asked not to do any physical activity. After the sixth week, all of the fitness tests which were taken at pre-test, were again replicated in post-test and implemented fully.

Aerobic capacity: Six-minute walk test (6MWT)

All patients performed a standardized, self-paced 6MWT in a 20-m-long corridor (16).

Anaerobic capacity: Running-based Anaerobic Sprint Test (RAST)

Subjects run with maximal pace from one end to the other, officers record the time spent to complete one track. The subjects rest for ten seconds and allowed turnaround run to the original end. They repeat running on the track for 6 times (17).

Endurance muscular: sit-up test

A full sit-up, in which the hips are flexed a full 90°, was for years the most widely used form of sit-up despite the stress placed on the lower back due to anterior pelvic tilt and despite reliance on the hip flexor muscles in the late stage of the test after the spine has been fully flexed by the abdominal muscles (18).

Flexibility test: Sit-and-reach

Tests in which a fingertips-to-tangent feet distance is measured are probably the most widely used lineal measures of flexibility (19).

Agility test: T-Test

The T-Test was administered using a version standardized from previous literature. The units of measurement were changed from yards to meters, creating a 10 ×10 m course. The course procedure of having the participant touch each cone is not standardized in the literature; therefore, the task was eliminated. The directions adopted for this study were based on Miller et al. (20).

2.3. Statistical Analysis

Statistical analysis of this survey was done both via descriptive and inferential methods. We used analysis of variance (ANOVA) to test for any differences in physical activity between groups at baseline (pre intervention) and follow-up (post intervention) (F=17.5, P=0.001). Paired samples t-tests were used to investigate whether there had been a change in physical fitness parameters and amount of consumption insulin between baseline and follow-up test program in two groups. All calculations were performed using SPSS software, version 21.

3. Results

The average and standard deviations were incorporated for the following variables: flexibility, muscular endurance, and aerobic power and insulin consumption amount before and after tests. These variables are shown for control and experiment groups in Table3.

These results indicate that a significant increase in the experimental group in post-test compared to the pre-test in flexibility, muscular endurance, and aerobic power. There was a significant decrease in insulin consumption after the test. In addition, the amount of the flexibility, muscular endurance and aerobic power was significantly higher in experiment group compared with the control group (p (0.05>, the amount of insulin was significantly lower in the experimental group compared with the control group (p (05/0>.

Table1. The amounts of consumption of insulin. Data are mean ± SD

Group		time	Vial of insulin	AE	CO
Insulin (unit)	Morning		clear	4.23±8.47	2.43±7.91
	Morning		crystal	9.13±24.19	5.19±21.84
	Evening		clear	3.57±8.16	1.76±7.44
	Evening		crystal	7.29±17.31	5.89±18.72

Table2. Baseline Anthropometric Characteristics. Data are mean ± SD

Group	Aerobic training (AE)		Control (CO)
	Pre-test	Post-test	Pre-test	Post-test
Agility	1.39± 14.1	†*1.70 ± 13.5	1.52 ± 13.8	1.16 ± 13.8
Anaerobic capacity	4.36 ± 23.4	†*3.97 ± 24.8	6.29 ± 23.8	4.70 ± 22.9
Flexibility	7.26 ± 21.6	†*7.21 ± 23.6	5.17 ± 21.1	4.79 ± 21.0
Muscular endurance	4.39 ± 21.4	†*3.81 ± 23.0	3.83 ± 20.6	3.24± 20.6
Aerobic capacity	156.96 ± 944.7	†*173.49 ± 1076.4	134.06 ± 935.9	139.89 ± 935.9
Insulin consumption	15.35±48.18	†*15.18± 44.36	14.87±47.44	14.05±47.98

Table3. The average and standard deviation of the measured variables in both groups. Data are mean ± SD

Group	AE (n=32)		CO (n=32)
Age (yr)	2.05±17.31		2.15±17.22
Height (cm)	8.68±154.8		9.21±156.8
Weight (gr)	7.16±54.3		9.82±54.3
BMI	4.08±22.82	3.15±22.00
History (yr)	3.03±6.41		2.90±7.27

Data are Presented as mean ± SD; * indicates significant difference (P <0 .05) within a group between pre and post-training, † significantly different from control. Aerobic training group (AE) and Control group (CO).

4. Discussion

In this study, we want to examine the effect of aerobic training exercises on indices of physical fitness such as flexibility, muscular endurance and aerobic power, also in the amount of insulin in in adolescent boys with T1D after 6 weeks training program consisting of 3 times per week.

According to our results, there are significant increases in following variables; flexibility, muscular endurance, aerobic power, there are significant decrease in amount of insulin consumption after performing 6 weeks of aerobic training.

Physical ﬁtness, a broad concept encompassing several speciﬁc types of ﬁtness including aerobic power, strength, ﬂexibility, and balance is important for persons with diabetes and also is closely related to all-cause mortality (21). Physical fitness parameters in patients with T1D are less satisfactory but suggest that, despite similar levels of physical activity, young adults (17–44 years of age) with T1D are less fit than matched individuals without diabetes (22).

zachezeweskil has defined muscle flexibility as "the ability of a muscle to lengthen, allowing one joint (or more than one joint in a series) to move through a range of motion (ROM) (23). Our results showed that, training aerobic may have affection on muscle-tendon units and reduce stiffness. This possibility requires more studies.

improvements in maximal oxygen uptake (VO2max) without accompanying changes in glycemic control have been reported by Rowland and Zinman and associates, after 12 weeks of bicycle and treadmill exercise, respectively (24,25).

In this study, aerobic training leads metabolic pathways toward aerobic processes and facilate access and transport of glucose and O2 to required muscles, so result in improving in aerobic power (VO2 max) and anaerobic power.

Many studies investigated the effect of exercise on treatment improvement in adolescents and youth with T1D. In one study in 2006, DirecNet group found that in youth with T1DM, prolonged moderate aerobic exercise results in a consistent reduction in plasma glucose and the frequent occurrence of hypoglycemia when pre-exercise glucose concentrations are <120 mg/dl (26). Guelﬁ et al. compared the effects of exercise on a bicycle ergometer over 30-min period with and without brief maximal sprints in seven children with T1D. Exercise, which was performed in the late morning when the blood glucose was 200 mg/dl following breakfast and a pre-breakfast insulin dose, resulted in a 25-mg/dl-greater fall in blood glucose when exercise did not include the interspersed sprints. There was a larger increase in counter regulatory hormone concentrations that may have blunted the fall in glucose concentrations when exercise included the sprints (27).Furthermore, Ramalho et al. evaluated the effect of aerobic versus resistance training on metabolic control in T1D patients and found that neither resistance nor aerobic training had improved glycosylated hemoglobin in T1D patients (28).

Similar to our finding, Heyman et al. found that 13 to18 years old girls with diabetes had a PWC170 ranging from 1.66 to 2.28 w/kg. Although studies have shown that improvements in body composition occur after 3 months of physical activity in T1D adolescent boys (or most boys) (29). Compared with boys, the cardiovascular disease risk factors are further increased among T1D adolescent girls and are evident in the lipid profile , insulin resistance, and body composition.

Herbst et al. Studied the cardiovascular risk factors among 251 patients (3-18 years) with T1D, found that mean glycosylated hemoglobin (HbA1c) was 7.9%. (30). the intensity and duration, physical activity appears to reduce HbA1c levels in these patients about 4.2 mmol/mol (0.6%) (22).

The reduction in HbA1c level over time is clinically significant, as the Diabetes Control and Complications Trial (DCCT) reported a 21% to 49% decreased risk for micro vascular complications with every 1% decrease in HbA1c (31).Insulin resistance is independently associated with the risk of developing both macro and micro vascular complications in T1D (22). In a study of 196 adults with T1D, those that exercised moderately once to three times per week signiﬁcantly reduced the HbA1c levels and insulin requirements (32).

Studies on T1D have consistently demonstrated that physical activity is associated with reduced insulin requirements. This reduction varies from 6% to over 15% (22).

In our study, patients showed a significant decrease in insulin. During aerobic training changes occurred in providing fuel energy. In early time of exercise, glycogen provides glucose which is major fuel for active muscles, the amount of utilization of non-esterified fatty acid in adipose tissues increase graduated. At the same time, hormonal and nervous responses increase and result in increasing hepatic glucose production. These processes cause a fall in insulin concentrations. After exercise, for a short time, regulatory hormone levels such as glucagon, Adrenalin and cortisol remain elevated and create hyperglycemia. In this situation, insulin sensitivity increases and glycogen starts to be resynthesized in muscle.

There are some factors that play an important role in glucose transform into muscular cells that consist of AMP-ACTIVATED PROTEIN KINASE (AMPK), Glucose transporter type 4 (GLUT4) proteins, Nitric oxide (NO).

AMPK is a serine-threonine was initially found to be an important regulator of fatty acid oxidation in heart and skeletal muscle but has also emerged as an important mediator of glucose metabolism. AMPK is also known to be activated during exercise in both heart and skeletal muscle; although it remains uncertain how important a role AMPK has in modulating glucose transport during exercise. AMPK increases glucose transport by stimulating translocation of GLUT4 to the sarcolemma in heart and skeletal muscle (33).

In skeletal muscle of rats made diabetic by injection of a: cell toxin, streptozotocin, levels of GLUT4 mRNA decrease before GLUT4 protein levels fall. Besides the acute effects of exercise on AMPK-induced GLUT4 trafficking, a positive correlation was observed between acute exercise induced increase in CaMKII levels and glucose transport in muscle cell (34).

The protein kinase C (PKC) is known as a mediator of the glucose transporter, which is released in response to exercise training. Chen and et al found that the consumption of glucose in muscle cells leads to the activation of protein kinase (34).

NO stimulates glucose transport in isolated skeletal muscle, where it is thought to have a role in mediating both insulin and exercise-stimulated glucose uptake (33). NO causes the release of LKB1, which LKB1 activity of AMPK increases. The possible explanation of the relationship between PKC and AMPK in the signal pathway is that with the increase of LKB1, the activity of AMPK increases and finally GLUT4 storage vesicles (GSV) is also activated, which GSV plays an important role in the activation of the GLUT4 (34).

5. Conclusion

Aerobic training may cause to improve glucose metabolism thought providing facilitation to glucose transporter in cellular muscle membrane in T1D. So, people with diabetes perform fitness parameters with maintaining blood glucose level. When fitness parameters such as strength promote in this people, they can perform and endure more activity in longer time.

Declarations

Ethical Considerations

Compliance with ethical guidelines

We considerate ethical guidelines

Funding

I do not have any funding resources

Conflicts of interest

I have no conflicts of interest

Acknowledgments

I appreciated from my professor and my coworker that they coordinate in this study

References

1- Herold KC, Hagopian W, Auger JA, Poumian-Ruiz E, Taylor L, Donaldson D, et al. Anti-CD3 Monoclonal Antibody in New-Onset Type 1 Diabetes Mellitus. N Engl J Med. 2002; 346(22):1692-8.

2- Cooke DW and Leslie Plotnick. Type 1 Diabetes Mellitus in Pediatrics Type 1 Diabetes Mellitus in Pediatrics. Pediatr. Rev. 2008; 29:374-385.

3- Rewers M, Bugawan TL, Norris JM, Blair A, Beaty B, Hoffman M, McDuffie RS, Hamman RF, Klingensmith G, Eisenbarth GS, et al. Newborn screening for HLA markers associated with IDDM: diabetes autoimmunity study in the young (DAISY) Diabetologia. 1996;39:807–812. [PubMed] [Google Scholar]

4- Lévy-Marchal C, Patterson CC, Green A; EURODIAB ACE Study Group. Europe and Diabetes. Geographical variation of presentation at diagnosis of type I diabetes in children: the EURODIAB study. European and Dibetes. Diabetologia. 2001; 44 Suppl 3:B75–B80. [PubMed] [Google Scholar]

5-Patterson CC, Dahlquist GG, Gyürüs E, Green A, Soltész G. Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: a multicentre prospective registration study. Lancet. 2009;373:2027–2033. [PubMed] [Google Scholar]

6- Zipitis CS, Akobeng AK. Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis. Arch Dis Child. 2008;93:512–517. [PubMed] [Google Scholar]

7- Hyppönen E, Läärä E, Reunanen A, Järvelin MR, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet. 2001;358:1500–1503. [PubMed] [Google Scholar]

8- Schattner A. Consequence or coincidence? The occurrence, pathogenesis and significance of autoimmune manifestations after viral vaccines. Vaccine. 2005;23:3876–3886. [PubMed] [Google Scholar]

9- Michels AW, Eisenbarth GS. Immune intervention in type 1 diabetes. Semin Immunol. 2011; 23:214–219. [PMC free article] [PubMed] [Google Scholar]

10- Bearse MA Jr, Han Y, Schneck ME, Barez S, Jacobsen C, et al. Local multifocal oscillatory potential abnormalities in diabetes and early diabetic retinopathy. Invest Ophthalmol Vis Sci.2004; 45: 3259-3265.

11- Gillett MJ. International Expert Committee report on the role of the A1c assay in the diagnosis of diabetes: Diabetes Care 2009; 32(7): 1327-1334. Clin Biochem Rev 30: 197-200.

12-Østergård T, Andersen JL, Nyholm B, Lund S, Nair KS, Saltin B and et al. Impact of exercise training on insulin sensitivity, physical fitness, and muscle oxidative capacity in first-degree relatives of type 2 diabetic patients. American Journal of Physiology - Endocrinology and Metabolism. 2006; 290(5): 998-1005.

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The effects of aerobic exercise on physical fitness indices and the amount of insulin consumption in boys with type 1 diabetes

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