Table 3

Summary of recent studies assessing exercise training effects on insulin sensitivity

Reference	Participants	Study type	Exercise mode	Outcome measure	Authors' conclusions and comments
Stuart et al15	Eleven participants with MetS and seven non-diabetic, sedentary controls.	Exercise intervention. Preintervention versus postintervention comparison.	Eight weeks of increasing intensity stationary cycle training.	Cycle training without weight loss did not change IR in MetS subjects or sedentary controls. Muscle insulin receptor expression increased in both MetS and sedentary groups, while GLUT4 expression also increased in the MetS subjects. The excess phosphorylation of IRS-1 at Ser337 in MetS muscle tended to increase further after training in spite of a decrease in total IRS-1.	In the absence of weight loss, the cycle training of MetS subjects increased the expression of insulin receptors and GLUT4 in muscle but did not decrease the IR.
Malin et al18	Twenty-four older, obese adults with IFG and/or IGT.	Exercise intervention.	Twelve weeks of exercise (60 min/day, 5 days/week at ∼85% HR_max).	Exercise increased clamp-derived peripheral and hepatic SI more in adults with IFG or IGT alone than with IFG + IGT.	Exercise increased peripheral but not hepatic SI.
Reichkendler et al19	Sixty-one, healthy, sedentary, moderately overweight young men.	Randomised, controlled trial.	Moderate (300 kcal/day) or high (600 kcal/day) physical exercise for 11 weeks, versus sedentary living (control). Pretraining and post-training, insulin-stimulated glucose uptake was assessed in five individual femoral muscle groups and four different adipose tissue regions.	Aerobic exercise training increased insulin-stimulated glucose uptake in skeletal muscle but not in adipose tissue.	Aerobic exercise training enhances glucose uptake in muscle but not adipose tissues, indicating a differential effect on these tissues.
Prior et al32	Sixteen sedentary overweight, obese, older men and women, with IGT	Preintervention versus postintervention comparison.	Six months of aerobic exercise and weight loss. Three sessions a week progressing from 20 min at 50% HRR to 45 min at 85% of HRR.	Hyperinsulinaemic-euglycaemic clamp and OGTT. Capillary density was measured via biopsies of the vastus lateralis.	Insulin sensitivity increased and 120 min postprandial glucose was lower postintervention. These changes were associated with increases in capillary density.
Malin et al34	Thirty-five older obese adults with prediabetes.	Exercise intervention.	Progressive 12-week exercise intervention (60 min at~85% HR_max 5 days/week).	Exercise increased first-phase and second-phase DI; β cell function = glucose-stimulated insulin secretion × clamp-derived SI).	Exercise training plus weight loss increased pancreatic β cell function in a linear dose-response manner in adults with prediabetes. Relatively high exercise doses (>2000 kcal/week) may be necessary to enhance β cell function in adults with poor insulin secretion capacity.
Madsen et al36	Ten, non-active patients with T2D(56±2 years) and 13 matched healthy participants.	Preintervention versus postintervention comparison.	Three sessions per week of HIIT (10 × 60 s) for 8 weeks for both patients with T2D and healthy participants. Glycaemic control was assessed using HOMA-IR and β cell function assessed.	Patients with T2D displayed significant improvements in HOMA-IR and β cell function. The healthy group, who displayed superior HOMA-IR and β cell function results at baseline, exhibited no change in these measures, which was not unexpected given their baseline values.	HIIT was effective in improving HOMA-IR and β cell function in patients with T2D.
Brennan et al35	Seventy-seven sedentary, obese men and women.	Repeated measures, intervention versus control condition.	Three to four months of aerobic exercise versus control	Hyperinsulinaemic-euglycaemic clamp and VO_{2 peak}.	Changes to insulin sensitivity were not associated with changes to VO_{2 peak}.
de Sousa et al96	Forty-four patients with T2D, aged 48–68 years (27 women, 17 men).	Randomised trial: diet versus football training plus diet.	Football training: 3 × 40 min/week for 12 weeks.	Football training plus diet group displayed improvements in HOMA-IR, whereas diet alone did not.	Football training plus diet was potentially better at preventing T2D complications than diet alone. It was also more effective than diet alone at improving other markers of metabolic and cardiovascular health, such as blood lipid profile and CRF.
Motahari-Tabari, et al52	Fifty-three women with T2D.	Randomised clinical trial: exercise versus control.	Thirty minutes at a maximum intensity of 60% increase in heart rate, three times a week for 8 weeks.	HOMA-IR improved and fasting plasma glucose and insulin were lowered.	Exercise was effective at improving SI.
Ryan et al53	Seventy-seven overweight and obese, sedentary, postmenopausal women.	Prospective controlled study.	Six months of: ‘aerobic exercise (3 days/week) + weight loss’ versus ‘weight loss without exercise’.	IR decreased in both groups. Glucose utilisation increased by 10% with ‘aerobic exercise + weight loss’ and 8% with ‘weight loss without exercise’.	No statistically significant difference in changes to IR between ‘aerobic exercise + weight loss’ versus ‘weight loss without exercise’. However, exercise benefited other markers of metabolic health.
Mitranun et al54	Forty-three participants with T2D.	Randomised controlled trial.	Sedentary (control) versus continuous exercise versus INT. For 30 min/day and 40 min/day, three times/week for 12 weeks.	Fasting blood glucose levels decreased in both exercise groups. Glycosylated haemoglobin levels decreased only in the interval trainingINT group.	Both continuous training and INT were effective in improving glycaemic control, but the INT programme appears to confer greater improvements.
Skleryk et al55	Sixteen sedentary, obese men.	Exercise intervention.	Two weeks of reduced-volume SIT (three sessions of 8–12 × 10 s sprints/week) compared with TER (5 × 30 min sessions at 65% peak oxygen consumption/week).	HOMA-IR, AS160 phosphorylation and COX II, COX IV, GLUT-4, Nur77 and SIRT1 protein expression assessed at baseline and approximately 72 hours after the final training bout were unaltered in either group.	Two weeks of reduced-volume SIT or TER did not elicit any measurable metabolic adaptations in previously sedentary, obese men.
Trachta et al56	Fifteen obese women.	Intervention with comparison group comprising ‘healthy’ lean subjects who did not undertake the exercise intervention.	Three-month exercise programme consisting of 30 min of aerobic exercise, three times a week.	HOMA-IR improved in the obese group.	Three months of regular exercise improved blood glucose and HOMA-IR, but had no significant effect on lipid profile and blood pressure.
Many et al57	Eleven morbidly obese minority adolescents (BMI 41.4±1.8 kg/m²)	Exercise intervention.	Eight weeks of aerobic exercise training (~180 min/week at 40–55% VO_{2 peak}). Preintervention and postintervention, SI and inflammatory markers were assessed.	Insulin action improved in response to training, as indicated by a ~37% increase in SI.	This study supports the efficacy of exercise training interventions on improving MetSfeatures in morbidly obese minority youth.
Racil et al58	Thirty-four obese adolescent girls.	Randomised controlled trial.	Twelve- weeks of MIIT or HIIT exercise.	Significant decrease in IR (HOMA-IR) occurred in both HIIT and MIIT groups (−29.2±5.3 and −18.4±8.6%, respectively.	INT improved SI. High intensity interval exercise produced greater benefits than moderate intensity interval exercise.
Kurose, et al59	Forty three obese patients.	Exercise intervention.	Thirty minutes on a cycle ergometer or treadmill, three times per week for 6 months, with training intensity adjusted to anaerobic threshold.	HOMA-IR improved.	Aerobic exercise improved SI. Additionally, IR was the only independent factor influencing improvement in endothelial function.
Reichkendler et al60	Sixty-one healthy sedentary moderately overweight young men.	Randomised controlled trial.	Eleven weeks of PA at moderate dose (300 kcal/day), high dose (600 kcal/day) or sedentary living.	In both exercise groups, peripheral SI improved. HOMO-IR decreased.	Physical activity improved SI and small additional health benefits were found when exercising at ∼3800 kcal/week versus ∼2000 kcal/week in young moderately overweight men.
Di Raimondo et al61	One hundred and seventy-six subjects with MetS.	Exercise intervention.	Walking for 1 hour, 5 days a week for 24 weeks at an intensity higher than the one classified as 'comfortable' by the patient.	Mean fasting glucose improved.	Regular walking at a moderate to hard intensity improved glycaemic control.
Lee et al62	Forty-four obese adolescent girls.	Randomised controlled trial.	Three months of 180 min/week aerobic exercise versus resistance exercise versus a non-exercising control group. SI was evaluated by a 3-hour hyperinsulinamic (80 mU·m²/min) euglycaemic clamp.	Compared with control, aerobic exercise improved SI but resistance exercise did not.	In obese, adolescent girls, aerobic exercise but not resistance exercise was effective in improving SI and did so independently of weight loss or calorie restriction.
Bacchi et al63	Thirty-one sedentary adults with T2D, and non-alcoholic fatty liver disease.	Randomised controlled trial.	Effects of 4 months of aerobic or resistance training on SI.	Post-training, SI was increased and hepatic fat content reduced in both groups.	Resistance training and AER were both effective in improving SI and reducing hepatic fat content in patients with non-alcoholic fatty liver disease.
Motahari-Tabari et al64	Fifty-three women with T2D.	Exercise intervention versus non-exercise control condition.	Eight weeks of walking for 30 min three times a week.	Exercise improved HOMA-IR, fasting plasma insulin and glucose.	The exercise intervention was effective in lowering plasma glucose, insulin levels and IR.
Herzig et al65	One hundred and thirteen men and women with prediabetes.	Exercise intervention versus non-exercise control condition.	Three sessions of 60 min walking per week, for 3 months versus non-exercise control.	The exercise intervention improved HOMA-IR, fasting insulin and glucose.	Compared with controls, the exercise group improved HOMA-IR and fasting insulin, but did not improve VO_{2 max} or fasting glucose.
Damirchi, et al66	Twenty-one middle-aged men with MetS.	Exercise intervention versus control condition.	Six weeks of aerobic exercise: three sessions per week, for 25–40 min of walking or running at 50–60% VO_{2 peak}. Followed by 6 weeks of detraining.	HOMA-IR improved after 6 weeks of training, but had returned to baseline after 6 weeks of detraining.	Regular exercise improved insulin sensitivity, but needs to be maintained as SI is lost if regular exercise ceases.
Solomon et al67	One hundred and five participants, with IGT or T2D.	Observational clinical study.	Twelve to 16 weeks of aerobic exercise training.	Glycosylated haemoglobin, fasting glucose and 2-hour OGTT were improved postintervention in 69%, 62% and 68% of subjects, respectively, while SI improved in 90% of the participants.	Training-induced changes in glycaemic control were related to changes in glucose-stimulated insulin secretion, but not SI. Training-induced changes in β cell function may be a key determinant of training-induced improvements in glycaemic control.
Grieco et al68	Forty-five healthy recreationally active young adults.	Randomised controlled trial.	Six-week exercise intervention. Four groups: moderate intensity (50% HRR), vigorous intensity (75% HRR), maximal intensity intervals (95/50% HRR) and non-exercising control group.	There were no significant changes in insulin effectiveness (HOMA and QUICKI in any exercise group.	The exercise intervention did not significantly affect insulin effectiveness in a young adult population as assessed by HOMA or QUICKI.
Chen et al69	Twenty-three men and women with MetS and 87 men and women without MetS; mean age 48 and 49 years, respectively.	Pre-exercise versus postexercise intervention comparison.	Three months home-based exercise programme of three x 30-min sessions per week at a moderate intensity of either ‘stepper’ or ‘cardio-dance’.	HOMA-IR was maintained in the non-MetS group (1.8 vs 1.9), but deteriorated in the MetS group (3.6 vs 4.3).	The authors reported that 72% of the non-MetS group but only 39% of the MetS group achieved the minimum exercise compliance, and suggested that this may have affected the poor outcome in the MetS group.
Duvivier et al74	Eighteen healthy subjects.	Cross-over design to compare daily regimens of activity and exercise.	Four days of each of the following regimens: (1) 14 hours/day sitting, (2) 13 hours/day sitting +1 hour/day vigorous exercise, (3) 8 hours/day sitting +4 hours/day walking +2 hours/day standing.	OGTTs were undertaken the morning after 4 days on each regimen. AUC for insulin was lower following the walking and standing regimen compared with the others.	Reducing sitting time by walking and standing was more effective than 1 hour of vigorous exercise in maintaining SI.
Earnest et al75	Men at risk for IR.	Randomised, controlled, exercise intervention trial.	Three months of eucaloric (12 kcal/kg/week) steady state AER compared with INT.	Twenty-four-hour and 72-hour postexercise fasting OGTT improved. HOMA-IR was improved with INT and AER. Stratification of participants based on pretraining values for HOMA-IR revealed that both low and high HOMA-IR participants demonstrated significant reductions with INT, whereas only high HOMA-IR showed significant improvements with AER.	Eucaloric AER and INT appear to affect fasting glucose OGTT similarly. Both INT and AER benefited those with high HOMA-IR, while INT also benefited those with low HOMA-IR, thereby suggesting that INT may have a greater impact by benefiting across a wider spectrum of HOMA-IR.
Gillen et al76	Twenty-five sedentary men (27±8 years).	Randomised control trial.	For 12 weeks, three sessions per week of either: (1) SIT (3 × 20 s maximal sprint, interspersed with 2 min cycling recovery at 50 W), (2) 45 min of moderate intensity cycling at ~75% HR_max (~110W) or (3) non-exercise control. SI was assessed via intravenous glucose tolerance tests.	Both exercise regimens produced significant and similar improvements in SI as measured via intravenous glucose tolerance tests performed before and 72 hours postexercise. Likewise VO_{2 peak} improved (~19%) in both exercise groups, as did skeletal muscle mitochondrial content. There were no statistically significant changes in the control group.	SIT produced similar fitness and SI improvements to prolonged moderate intensity exercise, despite requiring a fivefold lower exercise volume and time commitment.
Shepherd et al77	Ninety previously inactive volunteers.	Randomised control trial.	Ten weeks, three sessions per week of either: (1) HIIT (15–60 s with target HR >90% HR_max, with 45–120 s active recovery for a total of 18–25 min, including warm-up) or (2) 30–45 min continuous exercise at an intensity ~70% HR_max.	HOMA improved in both groups, but was achieved with less time commitment and greater adherence in the HIIT group.	HIIT may provide a time-efficient alternative to continuous moderate intensity exercise.
Arad et al80	Twenty-eight overweight/obese African American women.	Randomised control trial, with diet determined to maintain body weight. Exercise intervention n=14; control n=14.	For 14-weeks, three sessions per week of HIIT (4 × 30–60s at 75–90% HRR with 180–210s at 50% HRR between high intensity bouts) or non-exercise control. SI was assessed using 3-hour euglycaemic-hyperinsulinaemic clamp.	While some parameters of exercise metabolism improved, there were no improvements in SI compared with the control group.	HIIT did not improve SI when weight was maintained.
Lanzi et al81	Nineteen obese men.	Randomised control trial.	Two-week exercise intervention, four sessions per week of either: (1) HIIT (10 × 60 s at 90% HR_max, with 60s recovery) or (2) 40–50 min continuous exercise at an intensity identified as that eliciting Fat_max.	Aerobic fitness improved in both groups, but HOMA2-IR only improved in the Fat_max group.	In the short term (2 weeks) exercise training of a continuous moderate intensity (Fat_max) was more effective than HIIT at improving glycaemic control.
Fisher et al82	Twenty-eight sedentary overweight/obese men (20±1.5 years).	Randomised control trial.	Six weeks, five sessions per week of either: (1) HIIT (20 minutes comprising repeated bouts of 30 s at 85% of peak Wingate power with 4 min recovery at 15% of peak Wingate power) or (2) 45–60 min continuous exercise at an intensity of 55–65% VO_{2 max}.	Postintervention, both exercise groups displayed improvements in SI but neither exercise group displayed statistically significant improvements in HOMA-IR.	Both exercise regimens improved SI, as determined by OGGT, but not HOMA-IR (fasting insulin (µU/ml) x fasting glucose (mmol/L)).
Matsuo et al83	Twenty-six men with metabolic risk factors.	Randomised control trial.	Eight-week exercise intervention, three sessions per week of either: (1) HIIT, (3 × 3 min at~80–85% VO_{2 peak} with 2 min recovery at 50% VO_{2 peak} or (2) 40 min at 60–65% VO_{2 peak}, followed by 4 weeks of a low-calorie diet.	Both exercise interventions showed trends for improving HOMA-IR, and this was statistically significant in the HIIT group after the subsequent 4-week low-calorie diet.	SI trended towards improvement with both HIIT and moderate intensity exercise, and was further improved with the low-calorie diet in the HIIT group.
Inoue et al87	Forty-five postpubertal, obese adolescents.	Preintervention versus postintervention comparing an aerobic exercise regimen (AT), with two exercise regimens that included both aerobic exercise and resistance exercise (LP and DUP).	Twenty-six weeks of exercise intervention, 3 × 60 min sessions a week.	SI (HOMA-IR) improved in both the groups undertaking combined aerobic and resistance training, but statistically significant improvements were not found in the group undertaking aerobic exercise without resistance training (AT).	The combination of aerobic plus resistance exercise improved SI more effectively than aerobic exercise alone.
Dâmaso et al88	One hundred and sixteen obese adolescents.	Preintervention versus postintervention comparing: (1) aerobic exercise regimen with (2) aerobic exercise plus resistance exercise regimen.	One year of: (1) an aerobic exercise regimen or (2) aerobic exercise plus resistance exercise.	SI measured as HOMA-IR.	While both exercise regimens improved important clinical parameters, the ‘aerobic plus resistance exercise’ regimen produced better metabolic outcomes than aerobic exercise alone.
Nikseresht et al89	Thirty-four sedentary, obese, middle-aged men.	Exercise, interventions versus control condition.	Twelve weeks of three sessions per week of: (1) 40–65 min of resistance training; (2) aerobic INT (4 × 4 min at 80–90% HR_max, with 3 min recovery between intervals); (3) non-exercise control.	Fasting HOMA-IR.	Compared with control condition, both aerobic interval training and resistance training were equally effective in reducing IR.
Conceição et al90	Twenty postmenopausal women.	Exercise intervention, randomised controlled trial.	Resistance training: 10 exercises, with 3 × 8–10 maximal repetitions three times per week.	Compared with the control group, the resistance training group displayed decreases in fasting blood glucose.	Resistance training performed three times a week may reduce the MetS Z-score with concomitant decreases in fasting blood glucose.
Molsted et al91	Twenty-three patients treated by dialysis, with (n=14) and without (n=9) IGT.	Control period, followed by the exercise intervention.	Sixteen weeks of strength training three times a week.	After the strength training, fasting insulin, 2-hour insulin and ‘area under the curve’ insulin were significantly lower in patients with IGT or T2D.	Strength training was associated with a significant improvement in glucose tolerance in patients with IGT or T2D undergoing dialysis. The effect was not associated with muscle hypertrophy.
Mavros et al92	One-hundred and three older adults with T2D.	Participants were randomised to the resistance training intervention or non-exercise control group.	Twelve months of resistance training 3 days per week, or sham exercise.	Within the resistance training group, changes in HOMA2-IR were associated with changes in skeletal muscle mass and fat mass. Changes in visceral adipose tissue tended to be related to changes in HOMA2-IR.	Improvements in metabolic health in older adults with T2D were mediated through improvements in body composition, only if they were achieved through high intensity progressive resistance training.
Garnett et al93	One hundred and eleven obese adolescents with prediabetes and IR.	Repeated measures, exercise intervention with groups differing in dietary regimen.	Twelve weeks of 45–60 min, moderate to vigorous circuit training, twice a week.	OGTT following an overnight fast.	SI improved within 12 weeks of commencing the exercise intervention and was still improved compared with baseline at 12 months.
Trussardi Fayh et al97	Forty-eight obese individuals, aged 31.8±6.0 years.	Randomised clinical trial.	Participants were allocated to a diet-only group or a diet and exercise group. The intervention was maintained until 5% of the initial body weight was lost.	Both regimens produced significant and similar decreases of visceral adipose tissue and HOMA-IR.	Five per cent weight loss reduced abdominal fat and IR in obese individuals, but exercise did not add to the effect of weight loss on the outcome variables.

AER, aerobic training; AUC, area under the curve; CRF, cardiorespiratory fitness; DI, Disposition Index; Fat_max, maximal fat utilisation; HIIT, high intensity interval training; HOMA-IR, homoeostasis model of assessment-insulin resistance; HRR, heart rate reserve; INT, interval training; IR, insulin resistance; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; IRS-1, insulin receptor substrate 1; MetS, metabolic syndrome; MIIT, moderate intensity interval training; OGTT, oral glucose tolerance test; PA, physical activity; QUICKI, Quantitative SI Check Index; SI, insulin sensitivity; SIT, sprint interval training; T2D, type 2 diabetes; TER, traditional exercise recommendation.