Glycemic behavior in patients with type 2 diabetes during a short period of a combined training program

Aim: The present study investigated the behavior of glycemia in subjects with type 2 diabetes (T2DM) during 36 sessions of a combined training program. Methods: This is a single arm clinical study with 20 patients with T2DM submitted to combined exercise training (strength and aerobic exercise). The sessions occurred on alternate days, 3x/week, lasting ~ 80 minutes, totaling ~ 240 minutes/week, for 12 weeks, over a total of 36 sessions. Capillary glycemia was measured before and 10 to 15 minutes after the end of each combined exercise session. Results: There was a significant reduction (p<0.05) in glycemia after application of the combined training program in 27 (75%) of the 36 sessions. Regarding the maintenance of this reduction after about 48 hours, no significant differences were identified (p>0.05). When investigating the cumulative effect of the 36 sessions of combined training program on capillary glycemia, no significant differences were observed (p>0.05). Conclusion: Glycemia exhibits a behavior of reduction immediately after concurrent strength and aerobic training programs in patients with T2DM. However, the immediate reduction of glycemia is not maintained until 48 hours, nor is there a cumulative effect of the 36 training sessions on baseline glycemia.


Introduction
The literature is robust regarding the practice of physical activities for the management of patients with diabetes mellitus, especially type 2 diabetes mellitus (T2DM) 1,2 .The positive effect of physical activity programs can be identified by the improvement in glycemic control according to the glycated hemoglobin (HbA1c) exam, since glycemia is evaluated over a long period, reflecting the glucose concentrations within of the last 120 days 3 .
It is already well established that both types of physical exercise, i.e. aerobic and strength, bring innumerable benefits to patients with T2DM 4,5 , such as increased maximal oxygen utilization (VO 2 max) and cardiopulmonary fitness, as well as peripheral adaptations, represented by the increased transport and oxidation of fatty acids, improved capillary density 6 and mitochondrial capacity 7 .
Additionally, combined training has shown positive results for glycemic control, as seen by HbA1c analysis 2,8 .However, it is known that hyperglycemic peaks experienced on a day to day basis and between physical training sessions have been strongly associated with the development of diabetes complications 9 , regardless of the values of fasting glycemia and HbA1c 10 .In this sense, little is known about the effects of successive physical training sessions, especially of the programs that combine strength and aerobic in the same session, on the capillary glycemia of patients with T2DM.In view of the above, the present study investigated the behavior of glycemia in subjects with T2DM during 36 sessions of a combined training program.responded to the advertisements were prescreened by phone to confirm interest in, followed by in person with the aim of verifying the criteria of eligibility for, the study prior to clinic-based enrollment visits.All of the enrolled subjects provided written informed consent.Participants with T2DM, of both sexes, were recruited to this study.Of these, 20 subjects agreed to participate in combined physical training, consisting of strength and aerobic exercise.
Sample size was calculated based on a previous study by Mikus, Oberlin, Libla, Boyle, Thyfault 11 .Sample size was determined using Ene Software, version 3.0 (Autonomous University of Barcelona, Spain), considering a significance level of 0.05 and a power of 0.80.We considered for the calculation the difference between the mean of 0.3 mmol/L and the standard deviation of 0.4 mmol/L.Based on these criteria, at least 16 participants were necessary.
The inclusion criteria were: 1) individuals with T2DM with a sedentary lifestyle for at least 6 months according to the American Heart Association criteria 12 .The exclusion criteria were: 1) a confirmed diagnosis of any heart disease, 2) uncontrolled hypertension, 3) any musculoskeletal disorders, 4) any confirmed diagnosis of respiratory disease, and 5) confirmed autonomic neuropathy.
All participants were instructed to maintain their usual medical care and received dietary advice on healthy eating by a nutritionist; however, there was no specific dietary intervention with regard to eating habits.

Strength and endurance training program
Combined exercise training consisted of individually supervised sessions under the supervision of exercise specialists.Sessions occurred on alternate days, 3x/week, lasting ~ 80 minutes, totaling ~ 240 minutes/week, for 12 weeks, over a total of 36 sessions.
The sessions included: 1) 5 min warm-up; 2) combined training protocol for 60 min; and 3) 5 min of cool-down.The determination of the loads for the 1 repetition maximal test (1RM) was applied, gradually increasing the resistance until the volunteer could perform no more than one repetition 13 .The equipment was familiarized by the individuals, for three previous sessions of the 1RM determination.The order of training was alternated with each session, meaning that the aerobic training was followed by strength training in the first session, and in the next session the strength training was followed by aerobic training; this was in order to avoid any bias.
The aerobic training was performed with heart rate corresponding to 60-70% of peak VO 2 for a period of 30 minutes per session on a stationary bicycle 14 .Strength training was performed with the intensity of 60-80% of 1RM, as recommended by the American College of Sports Medicine 12,15 .The program consisted of eight strength exercises, with the major muscle groups being worked out, as recommended by the American Diabetes Association 16 .The subjects performed four exercises for the upper limbs: biceps with free weights, seated paddling, triceps and supine; and four exercises for the lower limbs: leg press, extensor chair, calf, and flexor chair.Each exercise consisted of three sets of 10-12 repetitions.The amount of weight lifted was progressively increased at each session in order to maintain consistent repetitions, that is, with correct and complete movements during the training program.A rest period of 2-3 minutes between the sets was performed allowing maximum muscle recovery.

Capillary glycemia
Capillary glycemia was measured before and 10 to 15 minutes after the end of each combined exercise session using an Accu-Chek Active portable gauge (Roche Diagnostics GmbH, Mannheim, Germany), according to the manufacturer's instructions.If the blood glucose was >13.9 mmol/L (or 250 mg/dL) before starting the exercise, the session would be cancelled, and if it was >13.9 mmol/L more than twice in one week, the patient would be referred for a medical visit.

Statistical analysis
Initially, the normality of the data was verified by means of histograms.After normal distribution was determined, the comparisons between glycemia values throughout the 36 treatment sessions were performed using the repeated measures analysis of variance (ANOVA) post hoc Bonferroni.Data processing was performed in SPSS, version 17.0 (Chicago, IL, USA), assuming a significance level of 5%.

Results
Table 1 shows the anthropometric and sociodemographic characteristics of the sample.Regarding the comparisons between training sessions, as shown in Table 2, there was a significant reduction (p<0.05) in glycemia after application of the combined training program in 27 (75%) of the 36 sessions.In addition, HbA1c also showed significant reduction after the training period, as shown in Table 2. Regarding the maintenance of this reduction after about 48 hours, Table 3 presents the blood glucose comparisons before each training session; no significant differences were identified (p>0.05).Finally, when investigating the cumulative effect of the combined training program on capillary glycemia, Table 4 presents the comparisons after each training session, and no significant differences were observed (p>0.05).

Discussion
We observed in the present study that capillary glycemia presents an immediate reduction after performing the combined training.However, there is no maintenance of this reduction over time, that is, in a period of time equal to or greater than 48 hours.
The global literature has presented favorable results in the context of the improvement of long-term glycemic control evaluated by means of HbA1c in subjects with T2DM 2,12 and practitioners of combined physical exercise programs 2,8,17 .However, in the present study, we observed that the efficacy of the hypoglycemic effects evaluated through capillary glycemia during a physical training program, even when combined, are limited to a short period of time, that is, a maximum of 48 hours.
Corroborating our study, another investigation aimed to evaluate the glycemic behavior of individuals with T2DM after a single exercise session with mild to moderate intensity and identified that both the capillary glycemia levels and the amplitude of their fluctuation were lower after the session of exercise.Thus, this study was conclusive in showing the beneficial effects of physical exercise within 24 hours after the session 5.
Systematic review and meta-analysis with the objective of identifying the effect of strength training on glycemic control of individuals with T2DM suggests that such exercise modality can be recommended even in the early stages of the disease, especially for those with poor glycemic control evaluated by HbA1c 12 .However, even in the case of a systematic review, there were no reports of glycemic control in the intra-training period (over successive training sessions).
The present study expected to find a glycemic control window longer than 48 hours, since the combination of aerobic exercises, which are known to improve fasting glycemia 18,19 , and strength exercises, which are better at glycemic control over time evaluated by HbA1c 2,8 .In this scenario, an interesting recent study conducted with children with type 1 diabetes mellitus aimed to evaluate the association of cardiorespiratory fitness with glycemic variability, and observed that the two are negatively correlated.Thus, lower glycemic variability indicates the better physical fitness of the individual 20 .
In the present study, we observed that capillary glycemia decreases after each combined training session, but is not maintained for more than 48 hours.This fact can be explained by exercise stimulates blood glucose disposal, in addition, induces a transient increase in whole-body insulin sensitivity for 48 h 18 .Holloszy (2005) shows that the acute glucose lowering effect of exercise results from high muscle glucose uptake determined by increased insulin sensitivity induced by muscle contraction 21 , in addition, King; Baldus, Sharp et al. (1995) 22 already showed this effect it lasted up to 72 h after a single exercise bout 22 .Afterwards, Figueira et al. (2013) 23 using continuous glucose monitoring, does not confirm the long glucose reduction after the combined exercise sessions (strength and aerobic exercises), corroborating our study 23 .It is known that physical exercise determines the increase in insulin sensitivity, which is achieved by the increase of the GLUT4 protein, which is determined by the AMPK activity in the increased skeletal muscle 21,24 .It has already been demonstrated in literature, for a long time these changes occur very rapidly after the exercise onset and can last 16 h after the intervention 24 .It is noteworthy that a high carbohydrate diet is associated with the development of glycogen super compensation, preventing an increase in the insulin response 25 , while the carbohydrate free diet maintains an increase in GLUT4 and insulin response for days after exercise 26 .In the present study, patients were instructed to maintain their usual carbohydrate intake, which could justify the reduced duration of the exercise-induced hypoglycemic effect.However, it is emphasized that HbA1c at the end of the same training program was significantly reduced according to a previous study carried out by our group 2, suggesting that the beneficial effects of exercise on long-term glycaemic control, showed by HbA1c, can be ascribed to the cumulative effects of the succeeding bouts of exercise.Due to the implications of glycemic variation in patients with T2DM, it is still necessary to search for more specific physical exercises and/or different loads or forms of performance that aim to reduce glycemic variations and maintain glycemic capillaries at values close to normal for a longer period of time.
There are some limitations to the current study, including the non-use of continuous glucose monitoring.It is known that the continuous monitoring equipment of blood glucose would be the most indicated, but it is worth noting the high cost of the equipment.However, capillary glycemia was measured before and after each training session.

Conclusion
Glycemia exhibits a behavior of reduction immediately after concurrent strength and aerobic training programs in patients with T2DM.However, the immediate reduction of glycemia is not maintained until 48 hours, nor is there a cumulative effect of the 36 training sessions on baseline glycemia.

Table 1 .
Demographical and clinical characteristics for individuals with type 2 diabetes mellitus (T2DM) at baseline.

Table 3 .
Comparison of blood glucose values (mg/dL) before each session of strength and aerobic training program.

Table 4 .
Comparison of blood glucose values (mg/dL) after each session of strength and aerobic training program.
MD: Mean difference; CI: Confidence interval of difference.No significant difference (p > 0.05, Repeated measures ANOVA post hoc Bonferroni).