Effectiveness of high intensity interval training on cardiorespiratory fitness and endothelial function in type 2 diabetes: A systematic review

Table 1 Quality assessment of the included studies using the physiotherapy evidence database

	Balducci et al[20], 2012	Terada et al[21], 2013	Karstoft et al[22], 2013	Mitranun et al[23], 2014	Hollekim-Strand et al[24], 2014	Winding et al[25], 2018	Hwang et al[26], 2019	Suryanegara et al[27], 2019	Mortensen et al[28], 2019	Baasch-Skytte et al[29], 2020	Gildea et al[30], 2021	Li et al[31], 2022
Eligibility criteriaa	√	√	√	√		√	√			√	√	√
Random allocation	√	√	√	√	√	√	√	√	√	√	√	√
Concealed allocation									√		√
Baseline comparability	√	√	√	√	√	√	√	√	√	√	√	√
Blinded subjects
Blinded therapists
Blinded assessors		√	√									√
Adequate follow-up	√	√	√	√			√			√		√
Intention-to-treat analysis		√					√
Between-group comparisons	√	√	√	√	√	√	√	√	√	√	√	√
Point estimates and variability	√	√	√	√	√	√	√	√	√	√	√	√
Total score	5/10	7/10	6/10	5/10	4/10	4/10	6/10	4/10	5/10	5/10	5/10	6/10

^aEligibility criteria item does not contribute to total score.

Table 2 Main baseline characteristics among patients with type 2 diabetes mellitus of each study included in the systematic review

Ref.	Groups	Males/Females (n)	Year after diagnosis	Age (yr)	Weight (kg)	Height (cm)	BMI (kg/m2)	HbA1C (%)
Balducci et al[20], 2012	HI (n = 152); LI (n = 136)	91/61; 83/53	7.8 ± 6.2; 5.9 ± 4.0	59.5 ± 8.3; 58.4 ± 8.9	NA	NA	31.2 ± 4.6; 31.9 ± 4.7	7.24 ± 1.39; 6.99 ± 1.39
Terada et al[21], 2013	HIIT (n = 7); MICT (n = 8)	4/4; 4/3	6 ± 4; 8 ± 4	62 ± 3; 63 ± 5	80.5 ± 9.9; 93.9 ± 18.3	NA	28.4 ± 4.1; 33.1 ± 4.5	6.6 ± 0.6; 6.7 ± 0.6
Karstoft et al[22], 2013	HIIT (n = 12); MICT (n = 12); CON (n = 8)	7/5; 8/4; 5/3	3.5 ± 0.7; 6.2 ± 1.5; 4.5 ± 1.5	57.5 ± 2.4; 60.8 ± 2.2; 57.1 ± 3	84.9 ± 4.9; 88.2 ± 4.7; 88.5 ± 4.7	NA	29.0 ± 1.3; 29.9 ± 1.6; 29.7 ± 1.9	6.9 ± 0.2; 6.6 ± 0.2; 6.4 ± 0.2
Mitranun et al[23], 2014	HIIT (n = 14); MICT (n = 14); CON (n = 15)	5/9; 5/9; 5/10	19.5 ± 0.4; 20.5 ± 0.4; 21.1 ± 0.6	61.2 ± 2.8; 61.7 ± 2.7; 60.9 ± 2.4	66.5 ± 3.7; 65.8 ± 3.1; 67.7 ± 3.2	149 ± 4; 149 ± 5; 152 ± 5	29.6 ± 0.5; 29.4 ± 0.7; 29.7 ± 0.4	60 ± 2a; 61 ± 2a; 62 ± 2a
Hollekim-Strand et al[24], 2014	HIIT (n = 20); MICT (n = 17)	12/8; 11/6	4.2 ± 2.3; 3 ± 2.6	58.6 ± 5; 54.7 ± 5.3	NA	NA	30.2 ± 2.8; 29.7 ± 3.7	7.0 ± 1.2; 6.7 ± 0.7
Winding et al[25], 2018	HIIT (n = 13); END (n = 12); CON (n = 7)	7/6; 7/5; 5/2	8 ± 4; 6 ± 4;7 ± 5	54 ± 6; 58 ± 8; 57 ± 7	84.2 ± 11.1; 82.1 ± 13.7; 87.7 ± 11.3	NA	28.1 ± 3.5; 27.4 ± 3.1; 28.0 ± 3.5	6.8 ± 0.8; 6.9 ± 0.9; 7.0 ± 1.2
Hwang et al[26], 2019	HIIT (n = 23); MICT (n = 19); CON (n = 16)	11/12; 11/8; 8/8	7.8 ± 1.3; 8.3 ± 1.5; 8.2 ± 1.5	65 ± 2; 62 ± 2; 61 ± 2	92.0 ± 4.7; 92.6 ± 4.5; 91.5 ± 3.9	170 ± 3; 170 ± 3; 164 ± 2	31.7 ± 1.3; 31.8 ± 1.4; 33.9 ± 1.4	7.1 ± 0.3; 7.2 ± 0.3; 7.4 ± 0.4
Suryanegara et al[27], 2019	HIIT (n = 13); CON (n = 13)	3/10; 3/10	4.8 ± 1.2; 4.3 ± 1.4	61.1 ± 8.6; 59.8 ± 8.6	90.5 ± 15.0; 91.0 ± 9.8	170.4 ± 7.6; 169.8 ± 8.6	31.3 ± 5.4; 31.9 ± 5.3	53.6 ± 10.5a; 55.5 ± 6.0a
Mortensen et al[28], 2019	HIIT (n = 11); END (n = 10)	6/5; 7/3	7 ± 4; 5 ± 4	53 ± 7; 57 ± 9	85 ± 12; 86 ± 11	NA	NA	6.8 ± 0.9; 6.9 ± 0.9
Baasch-Skytte et al[29], 2020	10-20-30 (n = 23); MICT (n = 21)	23/0; 21/0	8.0 ± 5.9; 7.0 ± 5.7	61.0 ± 6.2; 61.2 ± 7.1	101.9 ± 22.8; 100.3 ± 13.8	181.5 ± 6.5; 180.4 ± 7.2	30.6 ± 5.4; 30.7 ± 4.4	7.5 ± 1.6; 7.3 ± 1.1
Gildea et al[30], 2021	HIIT (n = 9); MICT (n = 10); CON (n = 9)	6/3; 7/3; 4/5	6.6 ± 3.5; 6.4 ± 3.8; 6.6 ± 3.3	52 ± 10; 53 ± 10; 54 ± 9	92.0 ± 4.7; 92.6 ± 4.5; 91.5 ± 3.9	NA	28.7 ± 3.0; 30.0 ± 5.7; 30.5 ± 3.6	7.3 ± 0.5; 6.9 ± 0.5; 6.8 ± 1.0
Li et al[31], 2022	HIIT (n = 13); MICT (n = 12); CON (n = 12)	13/0; 12/0; 12/0	1.95 ± 0.55; 1.79 ± 0.52; 1.84 ± 0.49	38 ± 6; 39 ± 5; 40 ± 7	75 ± 9.98; 73.1 ± 7.8; 71.76 ± 9.7	166.9 ± 6.25; 165.8 ± 5.56; 166.7 ± 6.86	27.4 ± 5.5; 26.8 ± 4.2; 26.5 ± 5.0	7.2 ± 0.5; 7.02 ± 0.44; 7.06 ± 0.38

^aExpressed in mmol/moL. CON: Control group; NA: Not available; HIIT: High-intensity interval training; HI: Moderate-to-high intensity; MICT: Moderate intensity continuous training; END: Endurance training; LI: Low-to-moderate intensity.

Table 3 Population, Intervention, Comparison, Outcomes and Study (PICOS) design of each study included in the systematic review

Ref.	Interventions by group	Frequency	Session duration	Intervention duration	Outcomes	Main results
Balducci et al[20], 2012	Both groups performed mixed aerobic (treadmill, step, elliptical, arm or cycle-ergometer) and resistance exercise [4 resistance exercises, i.e. thrust movement on the transverse plane (chest press or equivalent), traction movement on the frontal plane (lateral pull down or equivalent), squat movement (leg press or equivalent), and trunk flexion for the abdominals, plus three stretching positions]. HI: Aerobic training at 70% of predicted VO2 max and resistance training at 60% of predicted 1-RM. LI: Aerobic training at 55% of predicted VO2 max and resistance training at 60% of predicted 1-RM	2 times/wk	Varied to obtain the same caloric expenditure per kg body weight in the two groups, independent of intensity	12 mo	Peak VO2	↑ peak VO2 within HI (from 26.5 ± 5.3 to 31.1 ± 5.9 mL/min/kg, P < 0.001) and LI group (from 25.1 ± 5.4 to 29.6 ± 5.6 mL/min/kg, P < 0.001). No difference in peak VO2 between HI and LI groups [mean dif (95%CI): 0.14 (20.65, 0.92) P = 0.866]
Terada et al[21], 2013	HIIT: Treadmill training or cycling intervals 1’ (100% VO2 max). And 3’ (20% VO2 max). MICT: continuous treadmill training or cycling (40% VO2 max)	5 times/wk	30-60 min	12 wk	Peak VO2	No difference in peak VO2 within HIIT (from 22.8 ± 5.4 to 24.3 ± 7.4 mL/min/kg, P > 0.05) and MICT (from 18.1 ± 2.7 to 18.9 ± 4.1 mL/min/kg, P > 0.05) groups. No difference in peak VO2 between HIIT and MICT groups (P > 0.05)
Karstoft et al[22], 2013	HIIT: Interval walking training with 3-min repetitions at low (< 70% peak energy-expenditure rate) and high (> 70%) intensity. MICT: Continuous - walking training (< 55%). CON: No intervention	5 times/wk	60 min	16 wk	Peak VO2	↑ peak VO2 in HIIT group (from 27.1 ± 1.5 to 31.5 ± 2.2 mL/min/kg, P < 0.001). No difference in peak VO2 in MICT (from 26.1 ± 1.4 to 26.8 ± 1.9 mL/min/kg, P > 0.05) and CON groups (from 24.8 ± 1.8 to 25.2 ± 2.0 mL/min/kg, P > 0.05). Increase was higher in the HIIT compared to the MICT group (P < 0.05)
Mitranun et al[23], 2014	HIIT: 4-6 intervals (85% VO2 max) during 1 min following 4 min of active rest (50% VO2 max.). MICT: 50%-65% VO2 max. CON: No intervention	3 times/wk	30-40 min	12 wk	Peak VO2. FMD	Peak VO2: ↑ in HIIT (from 24.2 ± 1.6 to 30.3 ± 1.2 mL/min/kg, P < 0.05) and MICT groups (from 23.8 ± 1.0 to 27.1 ± 1.2 mL/min/kg, P < 0.05), no difference in CON group (from 24.4 ± 1.3 to 23.9 ± 1.0 mL/min/kg, P > 0.05). Increase was greater in the HIIT group compared to the MICT and the control group (P < 0.05). FMD: ↑ in HIIT (from 5.4 ± 1.1 to 7.4 ± 0.9%, P < 0.05) and MICT groups (from 4.8 ± 1.6 to 6.1 ± 1.8%, P < 0.05), no difference in CON group (from 5.1 ± 1.3 to 5.6 ± 1.8%, P > 0.05). Increase was higher in the MICT group compared to the control group (P < 0.05). Increase was higher in the HIIT group compared to the MICT and the control group (P < 0.05)
Hollekim-Strand et al[24], 2014	HIIT: 4 × 4’ (90%-95% HR max). MICT: according to guidelines	HIIT: 3 times/wk. MICT: 210 min/wk	HIIT: 40 min. MICT: ≥ 10 min	12 wk	Peak VO2; FMD	Peak VO2: ↑ in HIIT (from 31.5 ± 6.1 to 35.6 ± 6.3 mL/min/kg, P < 0.001) and MICT groups (from 33.2 ± 7.4 to 34.4 ± 7.7 mL/min/kg, P = 0.04). Increase was greater in the HIIT group compared to the MICT group (difference: 4.1 ± 2.9 vs 1.2 ± 2.2 mL/min/kg, respectively; P = 0.002). FMD: ↑ in HIIT group (from 9.2 ± 9.6 to 18.5 ± 9.6%, P = 0.004), no difference in MICT group (from 13.0 ± 9.8 to 13.0 ± 9.9%, P = 0.99). Increase was higher in the HIIT group compared to the MICT group (difference: 9.2 ± 11.2 vs 0.0 ± 6.2%, respectively; P = 0.03)
Winding et al[25], 2018	HIIT: 10 × 1 min intervals cycling at 95% of peak workload interspersed by 1 min active recovery. END: 40 min cycling at 50% of peak workload. CON: No intervention	3 times/wk	HIIT: 20 min. END: 40 min	11 wk	Peak VO2	↑ in HIIT (from 28.4 ± 6.1 to 34.2 ± 6.3 mL/min/kg, P < 0.05) and END groups (from 27.8 ± 5.5 to 30.3 ± 7.5 mL/min/kg, P < 0.05), no difference in CON group (from 27.2 ± 9.1 to 26.3 ± 6.8 mL/min/kg, P > 0.05). Increase was greater in the HIIT group compared to the control group (P < 0.05), but no significant difference between HIIT and END groups (P > 0.05)
Hwang et al[26], 2019	HIIT: 10-min warm-up and a 5-min cooldown at 70% of HR peak, 4 × 4-min intervals at 90% of HR peak interspersed by 3 × 3-min active recovery at 70% of HR peak. MICT: 10-min warm-up and a 5-min cooldown at 70% of HR peak, 32 min at 70% HR peak. CON: No intervention	4 times/wk	HIIT: 40 min. MICT: 47 min	8 wk	Peak VO2	↑ in HIIT group (from 22.3 ± 1.0 to 24.6 ± 1.3 mL/min/kg, P < 0.0001) and MICT group (from 21.6 ± 1.2 to 23.3 ± 1.2 mL/min/kg, P < 0.005), no difference in CON group (from 21.4 ± 1.3 to 20.9 ± 1.2 mL/min/kg, P = 0.4). No difference between HIIT and MICT groups (increase by 10% in HIIT and 8% in MICT, P > 0.99)
Suryanegara et al[27], 2019	HIIT: Cycle ergometry sessions, exercise intensity with scale ranging from 6 to 20 (5 min of warm up of increasing intensity from 9 to 13, then intensity 16-17 with pedal rate > 80 rev/min for five intervals of 2 min for the first week. It inclined 10s for every week until it reached 3 min and 50s of interval after 12 weeks of training. Each interval was followed with 3 min recovery cycle including 90s of passive recovery. CON: No intervention	3 times/wk	40-60 min	12 wk	Peak VO2	No difference in peak VO2 within HIIT (from 15.4 ± 2.9 to 15.2 ± 2.2 mL/min/kg, P = 0.52) and within CON group (from 15.5 ± 3.1 to 15.0 ± 2.4 mL/min/kg, P = 0.37). No difference in peak VO2 between HIIT and the control group (P = 0.71)
Mortensen et al[28], 2019	HIIT: 20 min of cycling consisting of 10 times 1 min at 95% Wpeak and 1 min of active recovery 20% Wpeak). END: 40 minutes of cycling at 50% of Wpeak	3 times/wk	HIIT: 20 min. END: 40 min	11 wk	Peak VO2. Leg blood flow	Peak VO2: ↑ in HIIT (from 29 ± 6 to 35 ± 7 mL/min/kg, P < 0.01) and END groups (from 28 ± 6 to 31 ± 8 mL/min/kg, P < 0.05). Leg blood flow: No difference within HIIT (from 1.56 ± 0.09 to 1.44 ± 0.09 L/min, P > 0.05) and END group (from 1.42 ± 0.13 to 1.26 ± 0.18 L/min, P > 0.01)
Baasch-Skytte et al[29], 2020	10-20-30: 10-min low-intensity warmup before completing three 5-min sessions of 10-20-30 training interspersed by 2 min of passive recovery. 5 consecutive 1-min exercise periods divided into 30, 20 and 10 s at low (approximately 30–100 W), moderate (approximately 60–180 W) and maximal (≥ 400 W) intensity. MICT: 50 minutes of moderate-intensity continuous cycling at an intensity of 60%–75% of HR reserve	3 times/wk	10-20-30: 31 min. MICT: 50 min	10 wk	Peak VO2	Peak VO2 increased within 10-20-30 and MICT groups after exercise training by 1.8 ± 2.9 and 2.2 ± 3.2 mL/min/kg, respectively (P < 0.01). No difference in peak VO2 between 10-20-30 and MICT groups (P = 0.86)
Gildea et al[30], 2021	5 min warm up and 5 min cool down before and after each session on an aerobic machine (elliptical, treadmill, rowing, or cycle ergometer) in both groups. HIIT: 10 × 60-s bouts of high-intensity cycling interspersed with 60 sec of light cycling at a power output equivalent to 70% of the difference between participant’s peak power output (PO peak) and the power output at ventilatory threshold (VT). Target heart rate of 90% HR max. MICT: 50 min of cycling at a power output equivalent to 80%-90% of ventilatory threshold. CON: No intervention	3 times/wk	HIIT: 30 min. MICT: 60 min	12 wk	Peak VO2. Muscle fractional O2 extraction [%Δ (HHb+Mb]) versus %PO slope of the first linear segment (slope1)]	Peak VO2: ↑ in HIIT (from 26.4 ± 4.0 to 30.0 ± 4.0 mL/min/kg, P < 0.05) and MICT groups (from 22.1 ± 4.4 to 27.6 ± 5.1 mL/min/kg, P < 0.05). It remained unchanged in the control group (from 21.5 ± 3.6 to 22.0 ± 3.4 mL/min/kg, P > 0.05). Increase was greater in the HIIT group compared to the control group (P < 0.05), but no significant difference between HIIT and MICT groups (P > 0.05). Muscle fractional O2 extraction: Improvement within HIIT (from 1.89 ± 0.63 to 1.31 ± 0.12, P < 0.05) and MICT groups (from 1.96 ± 0.60 to 1.37 ± 0.22, P < 0.05). No difference in the control group (from 1.80 ± 0.49 to 1.85 ± 0.25, P > 0.05). Improvement was higher in the HIIT and MICT groups compared to the control group (P < 0.05), but no significant difference between HIIT and MICT groups (P > 0.05)
Li et al[31], 2022	5 min warm-up and 5 min to complete the relaxation and finishing process in both groups. HIIT: 1 min power cycling (80%–95% maximal oxygen uptake (VO2 max), 1 min passive or active rest (25%–30% VO2 max), and 2 min rounds of eight groups. MICT: Power bike for 30 min of continuous training (50%–70% VO2 max). CON: Relevant medicine, exercise, and nutrition knowledge	5 times/wk	HIIT: 25 min. MICT: 40 min	12 wk	Peak VO2 (L/min)	HIIT (from 3.4 ± 0.4 to 3.9 ± 0.4 L/min, P = 0.001) and MICT groups (from 3.5 ± 0.4 to 3.7 ± 0.5 L/min, P = 0.001). It remained unchanged in the control group (from 3.5 ± 0.4 to 3.5 ± 0.5 L/min, P > 0.05). Increase was higher in the HIIT group compared to the MICT group (difference: 0.52 ± 0.06 vs 0.31 ± 0.13, P < 0.001)

CON: Control group; END: Endurance training; HI: Moderate-to-high intensity; HIIT: High-intensity interval training; HR: Heart rate; HHb: Hemoglobin; MICT: Moderate intensity continuous training; Mb: Myoglobin; LI: low-to-moderate intensity; PO: Power output; NA: Not available.