EFFECTS OF ACUTE EXERCISE WITH DIFFERENT INTENSITIES ON GLYCEMIC CONTROL IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

Abstract

Objective

Exercise intensity is one of the most important factors that determines the effects of exercise; however, there is little known about the acute glycemic control of different exercise intensities on patients with Type 2 Diabetes Mellitus (T2DM). Here we aimed at exploring the influence of a single bout of exercise with different intensities on blood glucose levels in T2DM patients.

Methods

Fifteen subjects (54.7 ± 5.8 years old) participated in a session of walking (WG), jogging (JG), or sedentary control (CG) in a randomized order on three different days. Distances in both WG and JG were set as 2 Km with a speed set as 4~4.5 Km/h for walking and 5~6 Km/h for jogging based on pretrial test. Blood glucose levels at fasting (~6:30am), pre-exercise (~8:30am), post-exercise (~9am), 11am and 4pm were detected.

Results

Walking and jogging reached approximately moderate and high intensity based on the immediate post-exercise heart rate and RPE scores. Blood glucose levels at fasting, pre-exercise and 4pm were not substantially different among all groups (p > 0.05). JG had a significantly lower post-exercise blood glucose level (p < 0.05) when compared with CG and WG. The blood glucose level at 11am was notably lower in WG and JG than in CG (p < 0.05).

Conclusions

Both a single bout of jogging and walking can lower postprandial blood glucose levels in T2DM patients. When matched for exercise distance, jogging represents a more effective strategy to immediately lower postprandial glucose levels than walking.

INTRODUCTION

Diabetes mellitus (DM) is a metabolic disorder disease characterized by chronic hyperglycemia resulting from defects in insulin secretion and/or insulin resistance (1). Type 2 Diabetes Mellitus (T2DM) is the most common type, accounting for 90%~95% of those patients with DM (1). Long-standing hyperglycemia is estimated to be a major risk factor bringing about various diabetic complications (2); whilst postprandial hyperglycemia is deemed to be an independent risk factor for diabetic cardiovascular complications (3), all of which are vital causes of death and disability in T2DM patients. Consequently, effective control of postprandial hyperglycemia is a critical goal in T2DM treatment (4).

Exercise training is a cornerstone of treatment regimens for T2DM patients (5). Regular exercise can increase glucose transporter 4 (GLUT4) protein content (6), promote glucose uptake into active muscles, improve insulin sensitivity and this effect could last for 3 days or longer after the last exercise bout (7). Moreover, it was also shown that exercise could reduce cardiovascular risk factors, contributing to weight control and mood improvement (8). American Diabetes Association guidelines in 2017 recommended that adults with T2DM should engage in moderate (MIE) to high intensity exercise (HIE) for at least 2.5 hours per week, spread over 3 days or longer, with no more than 2 days without activity (8). Up to now, the existing studies are still controversial about whether MIE or HIE exerts different effects on glycemic control in T2DM patients. From the perspective of the effects of long-term exercise, Liubaoerjijin et al. (9) suggested a significantly greater reduction of hemoglobin A1c (HbA1c) in HIE compared to MIE by reviewing results from clinical trials. While McGarrah et al. (10) reported that MIE improved insulin sensitivity better than HIE when controlled for total energy expenditure.

Exercise intensity is one of the most important factors that determines the effects of exercise (11), and it should neither be too low to achieve the goal of lowering blood glucose nor too high to be tolerated by patients. Some studies demonstrated that a single bout of MIE or HIE improved postprandial glucose control in patients with T2DM or prediabetes, e.g. van Dijk et al. (12) showed a single bout of MIE had a better impact on blood glucose homeostasis than repeated bouts of activities of daily living (ADL) in a randomized crossover study; Rynders et al. (13) presented that a single bout of HIE had a greater effect on improving postprandial glycemia and insulin sensitivity than an isocaloric bout of MIE in prediabetic adults. Other studies also indicated that an acute bout of MIE or HIE was effective in improving postprandial glycaemic control when compared to a sedentary condition (14,15). Nevertheless, there is still little known about the effects of acute glycemic control when compared MIE with HIE in T2DM subjects.

Fast walking and jogging are commonly applied aerobic exercise forms for T2DM individuals in China. Both of these two exercise modes involve repetitive and rhythmic contraction of large muscle groups in legs (16). Comparatively speaking, the intensity of jogging is usually higher than walking (17), resulting in more energy consumption. The present study examined the acute effects of exercise at different intensities (a single bout of walking and jogging) on glycemic control in T2DM patients, and blood glucose levels at different time points in T2DM patients were also tested.

SUBJECTS AND METHODS

Subjects

A total of 15 persons (9 males, 6 females) with a mean age of 54.7 ± 5.8 years, who had been diagnosed with T2DM for 5.3 ± 4.4 years, participated in this study. All subjects were currently treated with exogenous insulin and 12 of them with additional oral glucose-lowering medicines (e.g. biguanides, alpha-glucosidase inhibitors, sulfonylureas, and non-sulfonylureas insulinotropic agents). They were recruited from Changshu No.2 People’s Hospital, Jiangsu, China (From Jan. 2016 to March 2016). Exclusion criteria included: (1) a history of severe heart disease, such as heart failure, acute myocardial infarction and unstable angina; (2) fasting blood glucose >16.7 mmol/L; (3) DM complicated or accompanied by severely diseased kidney, brain, eye, feet lesion and ketoacidosis; (4) resting heart rate (HR) >120 bpm or uncontrolled hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg); (5) suffered from nerve, muscle and joint diseases. Subjects were fully informed about the research nature and possible risks involved before they provided signed consent. This study conformed to the standards of the Declaration of Helsinki and was approved by the Medical Ethical Committee of Changshu No.2 People’s Hospital.

Experimental protocol

All patients participated in two exercise trials (walking and jogging) and one control trial (seated condition) on three different days. The three trials, defined as walking group (WG), jogging group (JG) and control group (CG), were separated by at least three days at a randomized order. The randomized order was determined through random numbers which produced by IBM SPSS 20.0 software and assigned to the 15 subjects in the order of their recruitment. Based on the random numbers, the patients with the smaller 7 numbers performed the trails with the order of CG-WG-JG, and the patients with the larger 8 numbers had the order of JG-WG-CG.

Distances in exercise trials were set as 2 Km and performed on an open space 3 min away from the general ward. On the basis of our pretrial test, the speeds were set as 4~4.5 Km/h in WG and 5~6 Km/h in JG to achieve MIE and HIE, respectively. With the specified speed and distance, the duration of WG and JG lasted for approximately 30 min and 20 min, respectively. Both WG and JG included an additional 5 min warm-up and cool-down with stretching and flexibility exercises.

In the evening before three trials, each subject had a standardized supper containing 50~60% carbohydrates, 15~20% protein and < 25% fat, and was restricted from alcohol, coffee and tea. Following a 12h fast, a fingertip capillary blood sample was taken from each one and the concentration of fasting blood glucose was detected by glucose peroxidase method with a blood glucose meter (Rightest GM300, China) at about 6:30 am (Fasting). Then each subject accepted a standard breakfast which contained ~550 kilocalorie of energy. Two hours after breakfast, subjects started walking, jogging or doing exercise at about 8:30 am (pre-exercise, Pre). They were asked to wear loose clothes and suitable shoes during exercise trials and carry candies or biscuits in case of hypoglycemia. Water could be freely drunk at any time during the exercises. In a control trial, subjects were restricted to a general ward and seated in a chair or bed while reading, listening to music, watching TV or chatting.

Blood glucose levels in all trials were detected at Fasting, Pre, post-exercise (Post), 11 am and 4 pm except the time point at Post in CG was missing. The study protocol is shown schematically in Figure 1.

Figure 1.

Experimental intervention and test procedures (arrows indicate different time points for detection of blood glucose levels).

Physical activity recording and monitoring

Each subject wore a Polar HR monitor (FT1, Finland) and HR was recorded at pre-exercise (HR-0), 0.5 Km (HR-1), 1 Km (HR-2), 1.5 Km (HR-3) and 2 Km (HR-4). The ratings of perceived exertion (RPE) scale (ranged from 6 to 20, where 6 meant “no exertion at all” and 20 meant “maximal exertion”) (18) was also recorded at 0.5 Km (RPE-1), 1 Km (RPE-2), 1.5 Km (RPE-3) and 2 Km (RPE-4).

All subjects passed medical safety examinations, with no exercise contraindications and maintained original treatments during the trials. If subjects experienced dyspnea, dizziness, chest pain, palpitations, profuse sweating, pallor, falls, or self-reported extreme fatigue (unable or unwilling to continue exercise) during the exercises, then exercises would be immediately terminated. If symptoms did not relieve in 5~10 minutes, urgent medical care would be provided. The whole exercise process was monitored by rehabilitation physicians and medical personnel.

Blood samples analysis

Fasting venous blood samples were collected in the morning. One vacuum tube with anticoagulation was used to collect blood sample for HbA1c assay by an automatic glycosylated hemoglobin analyzer (Tosoh HLC-723G7, Japan). The other blank vacuum tube contained the blood sample for separation of serum. Blood samples were centrifuged at 4000 rev/min for 10 min and the supernatant serum were used for later analysis of biochemical parameters. Plasma triglycerides and cholesterol were detected with an automatic biochemical analyzer (Hitachi 7170A, Japan); concentrations of serum fasting insulin and c-peptide were tested using an automatic chemiluminescence analyzer (Bayer, Germany).

Statistical analysis

Data were analyzed using IBM SPSS 16.0 software package (USA). Descriptive statistics were presented as mean ± SD unless specified. A two-way repeated measures ANOVA with intervention and time as within-subject factors was used to compare differences between interventions over time (concentrations of blood glucose). The missing values at Post in CG were filled by multiple imputation method (SAS 9.0, USA.). In case of interaction between time and intervention, pairwise comparisons with Bonferroni correction were applied. Differences of HR (or RPE scores) at different monitoring points in intra-WG (or intra-JG) were assayed by one-way ANOVA. Differences of speed, duration and HR (or RPE scores) at the same monitoring points between WG and JG were performed using paired-samples t test. Nonparametric tests would be used if the data did not meet normal distribution. The significance level was set at p < 0.05.

RESULTS

Subjects

All subjects successfully completed three trials, no adverse cardiovascular events, syncope, falls and other accidents occurred during the exercises. Table 1 showed all subjects’ general clinical characteristics.

Table 1.

Subjects’ general information and clinical characteristics

	Total	Males	Females
Participants (n)	15	9	6
Age (years)	54.7 ± 5.8	54.1 ± 6.1	55.7 ± 5.8
T2DM diagnosis time (years)	5.3 ± 4.4	4.4 ± 3.8	6.7 ± 5.2
Height (cm)	164.8 ± 6.7	169.2 ± 3.0	158.2 ± 5.0
Weight (kg)	60.3 ± 6.3	60.4 ± 7.6	60.0 ± 4.0
BMI (kg/m2)	22.2 ± 2.3	21.1 ± 2.2	24.0 ± 1.1
HbA1c (%)	10.4 ± 3.0	10.4 ± 3.6	10.6 ± 2.2
Fasting C-peptide (ng/mL)	1.32 ± 0.68	1.25 ± 0.59	1.43 ± 0.85
Fasting insulin (ng/mL)	6.21 ± 6.57	3.38 ± 1.90	10.45 ± 8.90
Triglyceride (mmol/L)	2.28 ± 2.07	2.53 ± 2.58	1.91 ± 1.05
Total cholesterol (mmol/L)	4.53 ± 1.60	4.41 ± 1.96	4.71 ± 0.99
Complications (n)
Hypertension	3	2	1
Fatty liver	1	1	0
Retinopathy	2	1	1
Peripheral neuropathy	3	2	1

Values are mean ± SD or frequencies. BMI: body mass index.

Speed and duration

The speed in JG (5.80 ± 0.51 Km/h) was significantly faster than in WG (4.33 ± 0.24 Km/h), thereby JG (20.33 ± 1.72 min) spent shorter time than WG (27.80 ± 1.66 min) during the exercises (p < 0.01).

HR

HR at different monitoring points in WG and JG were reported in Table 2. There was no obvious difference at HR-0 between WG and JG (p > 0.05). The HR-1~HR-4 in JG were significantly higher than those in WG (p < 0.01). The immediate post-exercise HR in WG and JG were 72.8% ± 4.1% and 85.5% ± 3.7% of the age-predicted maximal HR (HRmax, HRmax = 220-age (19)), respectively. The HR-1~HR-4 in both groups were considerably higher than intragroup HR-0 (p < 0.01). However, there were no significant differences among HR-1 to HR-4 within each group (p > 0.05).

Table 2.

Heart rate at different monitoring points in WG and JG (bpm)

	WG	JG	t (or Z)	p
HR-0	82.7 ± 9.3	83.6 ± 10.4	-0.795	0.440
HR-1	117.9 ± 10.8 *	135.5 ± 9.8 *#	-25.95	< 0.001
HR-2	118.1 ± 7.6 *	136.8 ± 6.9 *#	-3.354	0.001
HR-3	119.2 ± 8.7 *	138.1 ± 7.7 *#	-3.356	0.001
HR-4	120.3 ± 7.7 *	141.2 ± 6.9 *#	-17.408	< 0.001
F	49.626	124.096
p	< 0.001	< 0.001

Intergroup comparison, #: compared with WG, p < 0.01; Intragroup comparison, *: compared with HR-0, p < 0.01.

RPE scores

As viewed in Table 3, the RPE-1~RPE-4 scores in JG were substantially higher than those in WG (p < 0.01), indicating the subjective fatigue of JG was more obvious than of WG. Intragroup comparisons showed that RPE scores at different monitoring points in intra-WG and intra-JG were significantly different (p < 0.01): with the increase of distance, the RPE scores gradually increased. When compared with intragroup RPE-1, the RPE-4 score in WG and JG increased by 3.7 ± 1.9 points and 5.7 ± 0.9 points, respectively.

Table 3.

RPE scores at different monitoring points in WG and JG (points)

	WG	JG	t	p
RPE-1	8.9 ± 1.0	11.0 ± 1.0 #	-5.323	< 0.001
RPE-2	10.2 ± 0.9	13.3 ± 0.7 #	-10.213	< 0.001
RPE-3	11.4 ± 1.2	15.3 ± 0.8 #	-10.597	< 0.001
RPE-4	12.6 ± 1.4	16.7 ± 0.7 #	-10.985	< 0.001
χ 2	38.525 *	44.718 *
p	< 0.001	< 0.001

Intergroup comparison, #: compared with WG, p < 0.01; Intragroup comparison, *: k-related samples of nonparametric test, p < 0.01.

Blood glucose levels

Blood glucose levels at different time points in three groups were presented in Table 4. All groups did not differ among glucose levels at Fasting, Pre and 4 pm (p > 0.05). Compared with CG and WG, JG had a significantly lower blood glucose level at Post (p < 0.05). The blood glucose level at 11 am was obviously lower in WG and JG when compared to CG (p < 0.05). Intragroup comparisons showed that blood glucose levels at Pre and 4 pm in all groups were notably higher than in intragroup Fasting (p < 0.05); blood glucose levels at Post, 11 am and 4 pm in all groups were significantly lower than in intragroup Pre (p < 0.05). The blood glucose level at Post in CG and WG were substantially higher than intragroup Fasting (p < 0.05). Besides, the blood glucose level at 11 am in CG was significantly higher than intragroup Fasting (p < 0.05), only the blood glucose level at 11 am in WG was considerably lower than in intragroup Post (p < 0.05). The blood glucose level at 4 pm in JG was notably higher than at 11 am (p < 0.05).

Table 4.

Blood glucose levels at different time points in all groups (mmol/L)

Group	Fasting	Pre	Post	11am	4pm	F	p
CG	6.84 ± 1.38	12.40 ± 2.74 a	10.23 ± 1.78 a,b	8.86 ± 1.92 a,b	8.66 ± 2.25 a,b	20.680	< 0.001
WG	7.21 ± 1.70	12.77 ± 2.12 a	9.71 ± 2.06 a,b	6.83 ± 1.79 1,b,c	8.95 ± 1.71 a,b	30.233	< 0.001
JG	6.45 ± 1.03	11.87 ± 2.59 a	8.00 ± 1.87 1,2,b	6.63 ± 1.91 1,b	9.28 ± 2.47 a,b,d	22.030	< 0.001
F	2.305	0.433	6.805	13.085	0.340
p	0.118	0.653	0.004	< 0.001	0.715

Intergroup comparison: ¹: compared with CG, p < 0.05; ²: compared with WG, p < 0.05. Intragroup comparison: ^a: compared with Fasting, p < 0.05; ^b: compared with Pre, p < 0.05; ^c: compared with Post, p < 0.05; ^d: compared with 11am, p < 0.05.

DISCUSSION

The current study compared the acute regulation effects of different exercise intensities on blood glucose levels through applying walking and jogging in the same group of T2DM patients. Meanwhile, sedentary condition was also included as control. The main finding was that both a single bout of walking and jogging can lower postprandial blood glucose levels in T2DM patients. Furthermore, jogging represented a more effective strategy to immediately lower postprandial glucose levels than walking when matched for the same exercise distance.

Generally speaking, walking and jogging belong to low to moderate intensity of aerobic exercise. However, the relative intensity depends on exercise speed and subjects’ aerobic capacity. Our results showed that the immediate post-exercise HR in WG and JG were 72.8% ± 4.1% and 85.5% ± 3.7% of the HRmax, respectively, which indicated that walking and jogging reached approximately MIE and HIE (20), respectively. The RPE scores during the exercises (~9-13 in WG and ~11-17 in JG) showed consistent intensities with the one evaluated by HR. Actually, most of subjects in this study have no regular exercise training habits or only carry out a small amount of low intensity exercise in daily life. In addition to the long-term disease history, the exercise capacity or physical fitness level in these patients is quite low. Not surprisingly, all subjects reported that greater effort was needed in the process of jogging, with more laborious breathing, sweating and there appeared muscle soreness in the afternoon of the jogging day rather than in walking session.

Blood glucose monitoring is an important task in T2DM management, including patients self-monitoring of blood glucose and regular detection of HbA1c (8). HbA1c is a marker that quantifies the average plasma glucose concentration in the last 3 months (21) instead of the blood glucose fluctuations in a short time, so we chose to detect fingertip capillary blood glucose at different time points to make clear the blood glucose fluctuations during all trials. We found that the blood glucose level at Post in all groups were significantly lower than in the intragroup Pre and intergroup comparisons showed that the blood glucose levels at Post in JG was considerably lower than CG and WG, suggesting the jogging had a greater immediate hypoglycemic effect. This may be related to the following reasons: (1) Higher intensity exercise is more effective in increasing GLUT4 protein content of skeletal muscle (22), promoting glucose transport and utilization, and contributing to a greater depletion of muscle glycogen (23), thereby increasing the uptake of glucose in muscle tissue to provide energy supply. (2) Higher intensity exercise could significantly elevate the abundance of peroxisomal bioactive receptor γ coactivator 1α (PGC-1α) mRNA in skeletal muscle (24), and the latter binds to and coactivates myocyte enhancer factor 2C (MEF2C) to up-regulate expression of GLUT4 (25); (3) With the increase of exercise intensity, body’s energy supply gradually change from carbohydrates and nonesterified fatty acids to carbohydrates (26), leading to further carbohydrate consumption. Based on these facts, higher intensity exercise is prone to have a better hypoglycemic effect in a short time, which is consistent with findings of Gillen et al. (15). Nevertheless, Kjaer et al. (27) presented that a single bout of maximal exercise resulted in 1-hour of post-exercise hyperglycemia and this effect may be owing to exaggerated counterregulatory hormonal responses following extremely HIE. It may also be relevant to the fasting condition when the exercise was performed.

The blood glucose level at 11 am was significantly lower in WG and JG than CG, and the level at 11 am was substantially higher than Fasting in intra-CG but not in intra-WG and intra-JG. This result demonstrated that ~2 hours after the end of exercise, the blood glucose levels in WG and JG were still on decline, which may be related to the utilization of blood glucose for muscle glycogen resynthesis and restoration. As mentioned by Rynders et al. (13) that muscle glycogen resynthesis rates following HIE were higher than MIE, partially because of greater recruitment of glycolytic-type II muscle fibers. The blood glucose levels at 11 am in WG and JG were very close (both of them were significantly lower than in CG), indicating that the two exercise intensities were equally effective in lowering blood glucose levels at ~2 hours from the end of exercise. It is really hard to conclude from our study whether the rate of glycogen resynthesis or fatty acid utilization is different under these two exercise intensities. The blood glucose level at 4pm increased when comparing with that at 11 am in two exercise groups (although the significance was only shown in JG), and had no difference among three groups. The restoration of blood glucose level at 4 pm might be relevant to the timeliness of the hypoglycemic effect in a single bout of acute exercise and patients had the intake of lunch.

There are several limitations in the current study. Firstly, blood glucose level at Post in CG was not detected and the missing data were filled by multiple imputation method, which may lead to certain deviation. Secondly, no continuous glucose monitoring system (CGMS) was available to detect blood glucose levels. Thirdly, the intervention (walking or jogging) was only performed once in this study and the sample size was small. Efforts should be made to improve the study in these aspects in the future. In addition, it is worth studying the long-term cumulative effects of exercise of different intensities on blood glucose regulation in T2DM patients.

In conclusion, a single bout of high intensity exercise has a better hypoglycemic effect on T2DM patients than that of moderate intensity when exercise volumes are equal. According to our results, higher intensity exercise is preferred if patients expect to have a greater decrease of postprandial blood glucose levels.

Conflict of interest

The authors declare that they have no conflict of interest.