It seems evident from our previous studies that the volume of exercise required to elicit a reduction in adipose tissue or induce weight loss with improvements in insulin sensitivity is quite cumbersome. For example, in our studies we recognized that for a middle-aged 82 kg female with a VO2peak
, exercise-induced weight loss of 0.5 kg/week necessitated 90 minutes cycle ergometer 5 days a week. As a result of this demanding volume of exercise training, dietary modification or caloric restriction are commonly implemented and utilized to reduce insulin resistance.
While caloric restriction-induced weight loss may have a large influence on insulin sensitivity, the subsequent loss of fat free mass may compromise glucose uptake, given that skeletal muscle is responsible for a larger portion of glucose uptake. This is observed in a study that implemented caloric restriction alone (-400 kcal/day or 2800 kcal/week) as well as with moderate (45-50% of HRR) and vigorous (70-75% of HRR) intensity exercise of progressing durations (moderate intensity=20-25 to 55 minutes/session, vigorous intensity=10-15 to 30 minutes/session) three days a week for 20 weeks. Although average weight loss was 13.4 ± 4.6% and included an approximate 25% reduction in visceral adipose tissue among all groups, plasma glucose at 120 minutes of an OGTT was unchanged. More importantly, fat and lean mass was reduced in each group but relative lean mass was reduced to a greater extent in the caloric restriction group (-36.2 ± 17.1%) compared to the moderate intensity exercise with caloric restriction group (-27.7 ± 14.8%) and the vigorous intensity exercise with caloric restriction group (-26.7 ± 12.1%). However, relative aerobic capacity increased within each group but significantly greater within the vigorous intensity exercise with caloric restriction (+24.2 ± 27.6%) group [36
When fat free mass was preserved following a 12 week aerobic exercise intervention with or without a caloric deficit (500 kcals/day), insulin-stimulated glucose disposal was significantly improved (20-28% increase in relative). The exercise included progressing vigorous intensity (60-65 to 80-85% HRmax
) for 50-60 minutes most days of the week (5 days/week) but the exercise alone group was eucaloric for the duration of the study. Weight loss occurred in both the aerobic exercise (3.8%) and aerobic exercise with caloric restriction (7.4%) group that was accompanied by similar reductions in abdominal adiposity and improvements in insulin sensitivity (~30%) [37
Since weight loss typically enhances insulin sensitivity especially when skeletal muscle is retained, it seems logical that resistance training with weight loss will improve in the same manner. In an intervention consisting of 6 exercises with progressing intensity (2-3 sets/15 repetitions progressed to 3-4 sets/10-12 repetitions) three days a week for 6 months, resistance training was combined with caloric restriction (-624 ± 133 kcals/day) and was compared to caloric restriction alone (-621 ± 128 kcals/day). Although significant reductions occurred in body mass visceral adipose tissue, abdominal subcutaneous adipose tissue occurred, no significant changes were observed for relative glucose disposal. Additionally, the intervention actually resulted in significant reductions in mean total lean body mass within the caloric restriction and resistance training with caloric restriction groups [37
Interestingly, another resistance training intervention lasting 12 weeks implemented 4 exercises at a low intensity just one day a week for 40 minutes while a 1600 kcals/day diet was provided. Notably, there was no significant weight loss but reductions in total cholesterol (-14.5 g/L) and triglycerides (-11 g/L) occurred. Although reductions of inflammatory markers were observed, insulin resistance remained, as HOMA-IR scores were not affected [38
]. Unfortunately, it seems resistance training, much like aerobic exercise, requires sufficient stimulus to drive reductions in body weight or fat mass and affect insulin resistance. However, the physiological responses from resistance training versus aerobic exercise or both together on insulin resistance remain unclear.
A comparative study of aerobic exercise, resistance training, and caloric restriction has also been investigated. Aerobic exercise included a range of vigorous intensity (67-80% of HRmax
) with progressing duration (20 to 40 minutes/session) three days per week. Whereas the resistance training included 10 exercises performed at 80% of 1RM (1-2 sets/10 repetitions) three days per week. The exercise groups also took part in the 800 kcals/day meals that were also provided to the caloric restriction group. The goal of the exercise and/or caloric restriction was to reach a body mass index less than 25 kg/m2
. Following weight loss, subjects were instructed to maintain a balanced diet and the exercise groups continued activity until 1 year follow-up measurements. Although significant weight loss occurred, weight regain was observed within each group. All groups experienced significant reductions in intra-abdominal and subcutaneous adipose tissue following weight loss with increases after a year. Although lean mass was reduced in both aerobic and caloric restriction groups, insulin sensitivity was significantly improved within all groups after weight loss, but only continued to improve within the aerobic exercise group after weight loss and the one year evaluation [38
Interestingly, it seems that a 10% reduction in body weight following an intervention has a dramatic influence on insulin sensitivity. For instance, in a study that elicited a 10% reduction in body weight from caloric restriction (500-1000 kcals/day) or combined exercise with caloric restriction, significant increases in ISI-M were observed. The progressive aerobic exercise intensity (70% to 85% of HRpeak
) for 30 minutes and resistance training (65% to 80% of 1RM, 1-2 sets/8-12 repetitions to 2-3 sets/6-8 repetitions) three days per week with caloric deficit reduced body weight (-10±2%) and intrahepatic fat (-45 ± 8%) similar to the caloric restriction group. These reductions were accompanied by a 66 ± 25% and 68 ± 28% increase in ISI-M for the caloric restriction group and combined group, respectively [39
Similarly, a study by Schenk and colleagues compared the effects of caloric restriction alone (500-800 kcals/day) or with vigorous intensity (85% of HRmax) aerobic exercise (3-4 sessions per week for 45 minutes each) after a 12% reduction in weight was elicited [40
]. The aerobic exercise with caloric restriction group reached 12% weight loss quicker (20 ± 2 weeks) than the caloric restriction group (30 ± 3 weeks), and was followed by a weight maintenance period. Although the aerobic exercise with caloric restriction group demonstrated increased levels of resting whole-body fatty acid oxidation more than 20%, insulin sensitivity increased similarly by 60-70% within both groups [40
]. Additionally, skeletal muscle pro-inflammatory c-Jun N-Terminal Kinase (JNK) and fatty acid mobilization and uptake were 40% and 30% lower, respectively [40
]. These reductions were likely due to a significant loss of fat mass altogether.
The importance of significant weight loss was also supported by a study from Mason and colleagues that compared the amount of weight loss relative to changes in HOMA-IR scores [41
]. The intervention included aerobic exercise alone (70-85% of THR 5 days/week for 45 minutes each) or with caloric restriction, compared to caloric restriction alone to induce 10% weight reduction followed by 6 months of maintenance. Although weight loss was significant within the aerobic exercise group (-2.4%), the aerobic exercise with caloric restriction and caloric restriction groups demonstrated further weight loss (-10.8% and -8.5%, respectively) and significant HOMA-IR score reductions (-26% and -24%, respectively). The percent weight loss correlated with HOMA-IR score reductions with an r value of -0.23 for <5%, -0.69 for >5-10%, and -1.10 for >10% weight loss [41
However, the intervention responsible for the weight loss may elicit different physiological responses. For instance, weight lost solely from dietary intake reduction may affect fat depots but weight lost from a combination of both dietary intake reduction and increased energy expenditure may improve muscle metabolism while reducing adiposity. This concept is demonstrated in a study by Toledo and colleagues that compared caloric restriction (reduce intake by 25%) to that with aerobic exercise (60-70% of HRmax
for 30-40 minutes 3-5 days/week) to induce at least a 7% reduction in weight over a 16 week period [42
]. Fortunately, each group experienced ~10% weight loss accompanied by ~19% reduction in fat mass, but a ~17% of visceral adipose tissue in the aerobic exercise with caloric restriction group as opposed to the ~25% reduction in the caloric restriction group. However, the aerobic exercise with caloric restriction group demonstrated a 49 ± 16% increase in mitochondrial density supporting an improved mitochondrial oxidative capacity, versus the 17 ± 4% reduction in mitochondrial size observed in the caloric restriction group [42
Comparatively, in studies by Ryan et al. 2012 and Strasnicky et al. 2009, both interventions of similar structure comparing vigorous intensity aerobic exercise with caloric restriction to caloric restriction itself induced ~8% weight loss [43
]. However, Strasnicky and colleagues grouped the responses together, given that the weight loss was similar between the groups. Both groups experienced significant losses in fat mass (-6.4 ± 0.6 kg) and waist circumferences (-8.6 ± 0.8 cm) that was accompanied by a significant improvement in ISI-M of ~45% [44
]. Additionally sympathetic responsiveness was assessed by measuring norepinephrine spill over rate during an OGTT using a radioisotope dilution method. Weight loss promoted resting norepinephrine to decrease, but only the aerobic exercise with caloric restriction group experienced significant sympathetic responsiveness to glucose at 90 minutes of OGTT. This suggests weight loss may also reverse the blunted sympathetic responsiveness to glucose ingestion commonly seen in glucose intolerant individuals [43
]. Whereas in the study by Ryan and colleagues, significant reductions in fat mass (-14%), visceral fat area (-13%), and subcutaneous abdominal fat area (-12%) were observed within each group [44
]. This supported the overall improvement in glucose utilization and non oxidative glucose disposal during the hyperinsulinemic-euglycemic clamp procedure, 14% and 24% respectively. However, insulin-stimulated glycogen synthase activity was significantly higher in the aerobic exercise with caloric restriction group of impaired glucose tolerant individuals only. This suggests that for individuals with glucose intolerance, weight loss from caloric restriction combined with aerobic exercise improves fitness that may have an effect on insulin to increase glycogen synthase activity greater than weight loss from caloric restriction alone [44
Under rare circumstances, weight loss from a combined effort of dietary modification with exercise may not result in an enhanced insulin sensitivity. For instance, a study by Oh and colleagues examined various forms of exercise (Tae-Bo, Yoga, Walking) for 6 months that consisted of various intensities performed 2 to 3 days per week for 40 minutes while maintaining a diet less than 1500 kcals/day [45
]. Although significant weight loss occurred at 6 months (-5 kg) and at a one year re-evaluation (-4.3 kg), insulin resistance, as assessed by HOMA-IR, remained unchanged [45
]. Although this intervention was new to a group of community residing individuals, the prescribed amount of exercise seemed inadequate and uncontrolled.
Differences in weight loss
A collective amount of studies using the same fixed amount of vigorous intensity aerobic exercise with or without caloric restriction have been able to identify differences in responses from the context to which the weight was lost. For example, several studies have utilized 12 weeks of vigorous intensity (65-75% of VO2max
) aerobic exercise five days a week for 50 to 60 minutes [46
]. In this study by Haus and colleagues, they observed significant reductions in weight within each group, but 4.7 kg more in the aerobic exercise with caloric restriction group. Total abdominal fat was reduced in the aerobic exercise group (-9 ± 4%) but more in the aerobic exercise with caloric restriction (-20 ± 4%) [46
]. Total subcutaneous fat, superficial, deep subcutaneous and visceral adipose tissue was reduced similarly between groups. Suppression of hepatic glucose production was examined during a two-stage hyperinsulinemic-euglycemic clamp that included an infusion of artificial lipids to simulate baseline levels of circulating free fatty acids. Each group demonstrated a significant improvement to suppress hepatic glucose production during hyperinsulinemia (-45 ± 22% in aerobic exercise and -50 ± 20% in aerobic exercise with caloric restriction) but the aerobic exercise with caloric restriction group had greater suppression of hepatic glucose production than the aerobic exercise group when artificial lipids were infused [46
Additionally, the study by Kelly and colleagues revealed more weight loss and fat mass loss in the aerobic exercise with caloric restriction group, which is practical. However, ISI-M was only significantly increased (2.69 ± 0.5 to 4.16 ± 0.55) in the aerobic exercise with caloric restriction group [49
]. There was also a significant reduction in glucose-dependent insulinotropic polypeptide in response to an OGTT in the aerobic exercise and caloric restriction group. This finding was attributed to improving gut peptide release, which may help mediate glucose-stimulated insulin responses [49
However, in one study by Solomon and colleagues, significant reductions in leptin were observed for the aerobic exercise group (-12.2 ± 3.8%) but greater in the aerobic exercise with caloric restriction group (-31.6 ± 6.0%) were accompanied by similar reductions in weight and fat mass. Interestingly, insulin-stimulated glucose disposal, as assessed by the hyperinsulinemic-euglycemic clamp procedure, was significantly greater in both the aerobic exercise group (55.1 ± 19%) and the aerobic exercise with caloric restriction group (65.1 ± 14.4%) of similar nature [47
]. Although greater body compositional changes occurred in the aerobic exercise with caloric restriction group, the changes in insulin sensitivity seem to be driven by the exercise. Similarly, the other study by Solomon and colleagues revealed greater body compositional changes in the aerobic exercise and caloric restriction group than the aerobic exercise group. However, the improvements in insulin-stimulated glucose disposal, assessed by the hyperinsulinemic-euglycemic clamp procedure, were similar within each group (30.7 ± 12.2% in aerobic exercise group and 31.5 ± 23.7% in the aerobic exercise and caloric restriction group). Interestingly, fatty acid oxidation was assessed as well and revealed the non plasma lipid derived contribution of free fatty acids in the basal state increased [48
]. This suggests the utilization of lipids from fat depots and reduced adiposity, which was similar between both groups.
Commonly, aerobic exercise is coupled with caloric restriction and compared to exercise alone, in a eucaloric state. Comparing interventions in this context cannot definitively distinguish beneficial differences. However, in a study by Murphy and colleagues caloric restriction was compared to aerobic exercises which were controlled to elicit a similar deficit [50
]. The aerobic exercise was to expend 16% of energy for 3 months, then 20% until the final 12 months. This consisted of vigorous intensity (~71% of HRmax
) most days of the week (6 sessions/week) for ~62 minutes each. The caloric restriction was to reduce intake by 16% for 3 months, then 20% (-318 kcals/day) for the duration of the intervention. Significant reductions in body weight and fat mass occurred similarly between groups, which was accompanied by similar improvements in ISI-M [50
]. However, the aerobic exercise group experienced significant reductions in both intermuscular adipose tissue and visceral adipose tissue versus the caloric restriction group that experienced visceral adipose tissue reductions only. Interestingly, the reductions in visceral adipose tissue within the caloric restriction group correlated with changes in ISI-M (r=-0.64). Whereas only the reductions intermuscular adipose tissue within the aerobic exercise group correlated with reductions in ISI-M (r=-0.71) [50
]. Since visceral adipose tissue and intermuscular adipose tissue is commonly linked to oxidative stress, exercise-induced weight loss may have advantage over weight lost from caloric restriction.
For example, in a well-controlled exercise and feeding study, aerobic exercise of moderate intensity (50% of VO2peak
) was progressively increased (1000 kcals/week gradually to 2500 kcals/week) to elicit a similar deficit as caloric restriction (1000 kcals/week minus 500 kcals until 2500 kcals/week). A control group was included, as well as an aerobic exercise group that received calories to maintain body weight. Following a 4 week weight stabilization period, weight reduction was only significant within the exercise-induced weight loss and caloric restriction (~6% each) groups. Visceral adipose tissue was reduced in the exercise group (-17 ± 7 cm2
), caloric restriction group (-36 ± 10 cm2
), and two-fold greater in the exercise-induced weight loss group (-71 ± 15 cm2
). Interestingly, the improvements in insulin-stimulated glucose disposal were similar between the caloric restriction (+2.4 ± 0.9 mg/kgFFM/min) and exercise-induced weight loss (+2.5 ± 0.4 mg/kgFFM/min) groups. Notably, the caloric restriction group experienced significant reductions in lean thigh tissue (-7±1 cm2
) as opposed to the increase found within the exercise-induced weight loss (+7 ± 1 cm2
) group. Furthermore, significant insulin-stimulated suppression of glucose production was observed in the exercise group (+12 ± 2%), caloric restriction group (+10 ± 2%) and 3 times greater in the exercise-induced weight loss group (+27 ± 2%) [51
]. The findings from this study illustrates that similar weight loss from caloric restriction or exercise does not yield the same physiological responses. Exercise-induced weight loss in this context reduced adiposity and systemic insulin resistance most effectively.