Insulin-like growth factor-1 and resistance exercise in community dwelling old adults

Abstract

Background

Insulin-like growth factor-1 (IGF-1) is related to the preservation of lean body mass. Its decline during ageing is thought to make old adults more susceptible to sarcopenia and functional dependency. The aim of the present study was to investigate circulating total IGF-1 in old adults who engaged in a 12-weeks of progressive resistance training.

Design

Intervention study.

Setting

Community.

Participants

Old Icelandic adults (N = 235, 73.7 ± 5.7 years, 58.2% female). Intervention: Twelve-week resistance exercise program (3 times/week; 3 sets, 6-8 repetitions at 75-80% of the 1-repetition maximum) designed to increase strength and muscle mass of major muscle groups.

Measurements

IGF-1.

Results

At baseline IGF-1 was significantly associated with lean body mass and appendicular muscle mass (also when corrected for age, gender and various covariates). After the training IGF-1 decreased significantly from 112.1 ± 35.6 to 106.1 ± 35.2 µg/L during the course of the study. On and individual level, IGF-1 decreased in 59% and increased in 39% of the participants. Changes in IGF-1 were inversely related to changes in lean body mass (rho = -0.176, P = 0.013 ) and appendicular muscle mass (rho = −0.162, P = 0.019) also when corrected for protein intake, age, gender, and other covariates.

Conclusion

Serum total IGF-1 decreases after 12 weeks of resistance exercise in community dwelling old adults. When looked at IGF-1 changes for participants individually it becomes clear that IGF-1 response to resistances exercise is highly variable. Changes in IGF-1 are negatively related to changes in lean body mass during training, which supports the hypothesis that IGF-1 is redistributed from circulation into tissue during periods of active muscle building.

Introduction

Aging is associated with a decline in physical function (1) as well as with a decline in the concentration of hormones, such as insulin-like growth factor-1 (IGF-1) (2). IGF-1 plays an important role in the regulation of growth and is known to exert anabolic effects on skeletal muscle (3) important for normal body functioning (1, 4). Circulating IGF-1 is mainly produced by the liver in response to increased levels of growth hormone, but can also be produced in various tissues, including skeletal muscle and bone (5). In blood, only about 2% of IGF-1 circulates in free bioactive form, whereas the rest is bound to various IGF-1 binding proteins (6).

As IGF-1 is strongly related to the preservation of lean body mass, its decline is thought to make elderly individuals more susceptible to sarcopenia, disease, and functional dependency (7, 8). Accordingly, increased concentrations of IGF-1 have been associated with fitness (9), lean body mass (3), decreased risk of heart disease (8) and decreased mortality (10). However, high levels of IGF-1 are not always considered beneficial and have been associated with the development or progression of cancer (11).

Both acute and chronic resistance exercise has consistently been shown to increase intramuscular levels of IGF-1 (5). Conversely, prospective studies investigating the effect of resistance training on circulating levels of IGF-1 have provided inconsistent results. Studies have found resistance exercise to cause a decline (12, 13), an increase (14., 15., 16.) or to have no effects on circulating total IGF-1 (5, 15, 17, 18., 19., 20.). The reason for this discrepancy is still unresolved.

In order to gain more knowledge on this matter, the aim of the present study was to investigate the response of circulating total IGF-1 to 12 weeks of progressive resistance training in elderly Icelandic people. We also investigated whether gender, body composition or dietary intake were associated to IGF-1 or changes observed after the training.

Methods

Subjects

A total of 236 participants (ages 65-91, 58.2% female), were recruited by advertisements in the capital area of Iceland. Exclusion criteria were age younger than 65 years, low cognitive function (Mini-Mental State Examination (MMSE) < 19 points), musculoskeletal disorders or other disorders that could have affected their ability to complete their training and testing and pharmacological treatment with medications known to influence lean body mass. Enrolled subjects were apparently healthy, although some had hypertension, hyperlipidaemia or diabetes type II. The study was approved by the Icelandic National Bioethics Committee (VSNb2008060007/03-15) and informed written consent was obtained from all participants.

Study design and resistance training

The current study is a part of a randomized and controlled dietary intervention study originally designed to investigate the effects of different dietary supplement drinks on the efficacy of resistance training among older adults (21) (see below). The 12-week resistance exercise program was designed to increase strength and muscle mass of all major muscle groups. All data were obtained at baseline and again at the end of the study period.

Subjects exercised for three non-consecutive days per week for 12 weeks in groups of 20 to 30 individuals. Each session was supervised by study staff, an athletic trainer, and occasionally a physical therapist. Ten different exercises were performed in weight machines during each training session; seated leg extension, seated leg curl, seated leg press, seated chest fly, seated row, seated pull-down, seated biceps curl, seated triceps curl, seated lower back extension, and seated abdominal curl. Before the intervention started, 1-repetition maximum (1-RM) was assessed using weight machines and by progressively increasing the weight lifted until the participant failed to lift the weight. Prior to the 1-RM test, most of the participants were not experienced with the weight machine equipment, however they performed two familiarization sessions before the application of 1-RM test. The first week of the 12-week training period was used to teach correct exercise techniques at lower loads (60% of 1- RM). Thereafter, resistance training involved 3 sets, where each exercise was repeated 6 to 8 times, at 75-80% of their 1-RM. The training load was systematically increased by 5 to 10% each week in order to keep the number of repetitions per set between six and eight. Each exercise session started with a moderate, 10-to 15-minute aerobic warm-up on a treadmill or a stationary exercise bicycle, after which resistance training with weight machines was performed. Stretching exercises were performed at the end of each session.

Participants were randomly assigned to one of three different dietary supplements that were consumed after each training session. The dietary supplements were 1) a whey protein drink (20 g whey protein isolate + 20 g carbohydrates), 2) a milk protein drink (20 g milk protein isolate + 20 g carbohydrates) or 3) a carbohydrate drink (40 g carbohydrates).

Dietary intake

A three-day weighed food record was used to assess dietary intake. Participants weighed and recorded their food intake for three consecutive days; two week-days and one weekend day. The food records were analyzed using data from the Icelandic food composition database (ISGEM).

Physical activity assessment

Leisure time physical activity was assessed by a self-report questionnaire that asked about the duration and frequency of physical activity during the previous 12 months. Physical activity was converted to metabolic equivalents (METs) and reported as MET kilocalories per day (22).

Energy balance

Energy balance was calculated using energy intake data, assessed by a three-day weighted food record and calculated energy need, using the Harris-Benedict equation, with added METs (kcal/day) and adjustment for overweight and obese individuals. Adjustment in overweight and obese individuals was conducted using ideal body weight, calculated with the Robinson’s formula, and by adding 50% of the difference between ideal body weight and actual body weight.

Body composition

Body composition was assessed by dual energy x-ray absorptiometry (DXA, Hologic QDR-2000 plus®, Hologic Inc., Waltham, MA, USA). The DXA measurements were conducted at the Icelandic Heart Association, Kopavogur, Iceland.

Six minute walk for distance (6MWD)

To assess physical performance, participants were asked to complete a 6MWD test. The test was performed indoors in a spacious gym hall and conducted according to the guidelines from the American Thoracic Society (2002) (23).

IGF-1 analysis

Participants were instructed to avoid strenuous exercise and alcohol consumption the day before the drawing of fasting blood samples at baseline and endpoint. The blood samples were centrifuged, aliquoted and stored at -80°C until they were analysed at the laboratory of the Icelandic University Hospital, Reykjavik, Iceland. Total serum IGF-1 was analyzed with a solid-phase, enzyme-labeled chemiluminescent immunometric assay on an Immulite 1000 system from Siemens Healthcare Diagnostics.

Statistical analysis

Analyses were conducted using SPSS for Windows version 20.0 (SPSS, Chicago, IL, USA), and the level of significance was set at P < 0.05. Data are shown as mean ± standard deviation (SD). Bivariate correlations were calculated using Pearson correlation for parametric variables and Spearman rank correlation for non-parametric variables. Participants were split into two groups, based on whether IGF-1 decreased or increased, and the difference between groups with regard to relevant variables was estimated using Independent-samples T-test for parametric variables or Mann-Whitney U test for non-parametric variables. Change in variables during the study (A) was calculated by subtracting baseline values from endpoint values, so that an increase in an variable would be a positive value and a decrease would be a negative value.

Results

At baseline 235 (male = 98, female = 137, age range = 65 - 92 years) participants started the 12-week program, Changes in body composition, strength, physical function and dietary intake can be seen in Table 1. On average, levels of IGF-1 decreased significantly (-5.4%) in both genders during the course of the study. On an individual base, IGF-1 decreased in 123 participants (59.3%), increased in 82 participants (39.3%), but did not change in 3 participants (1.4%). No significant gender difference in IGF-1 levels was detected, neither in baseline IGF-1 (P = 0.329) nor change in IGF-1 during the study (P = 0.729).

Table 1.

Baseline and endpoint characteristics of participants

		All (N = 235)			male (n = 98)	female (n =)	137)
		Mean	±	SD	Mean	±	SD	Mean	±	SD
Height (cm)	baseline	169.1	±	9.5	177.1	±	7.3	163.1	±	5.7
	endpoint	169.2	±	9.4	177.2	±	7.2	163.2	±	5.8
Body weight (kg)	baseline	82.7	±	17.2	93.0	±	16.4	74.8	±	13.1
	endpoint	83.1	±	17.3*	93.7	±	16.5*	75.1	±	13.0*
Waist (cm)	baseline	100.1	±	14.2	108.5	±	11.4	94.0	±	12.9
	endpoint	99.4	±	13.8*	107.6	±	11.5*	93.5	±	12.3
BMI (kg/m2)	baseline	28.8	±	4.8	29.6	±	4.6	28.2	±	4.9
	endpoint	28.9	±	4.8*	29.8	±	4.6*	28.3	±	4.8
ASM (kg)**	baseline	24.7	±	5.3	29.6	±	3.8	21.0	±	2.5
	endpoint	25.2	±	5.4*	30.2	±	3.9*	21.4	±	2.5*
Body fat (%)	baseline	37.9	±	7.3	33.5	±	5.7	41.3	±	6.5
	endpoint	37.1	±	7.1*	32.9	±	5.9*	40.4	±	6.1*
Grip strength (pounds)	baseline	63.2	±	19.0	80.2	±	14.2	49.7		8.8
	endpoint	66.2	±	19.6*	83.4	±	15.2*	52.7		9.4*
6MWD (m)***	baseline	462	±	73	466	±	77	459		70
	endpoint	496	±	76*	497	±	86*	495		67*
TUG (sec)	baseline	7.7	±	1.7	7.8	±	1.7	7.7	±	1.8
	endpoint	7.1	±	1.7*	7.3	±	1.7*	6.9		1.8*
IGF-1 (µg/L)	baseline	113.9	±	44.0	115.1	±	36.1	113.1		49.2
	endpoint	107.0	±	37.5	108.4	±	33.6*	106.0		40.4*

^*difference between baseline and endpoint P < 0.05;

^**ASM = Appendicular skeletal muscle mass;

^***6MWD = 6 minute walk for distance and 208 (male = 90, female = 118) participants completed the study. The dropout rate was 12%, and the reasons for dropping out were illness and falls at home; some participants did not like the program, while others had to quit because of previously diagnosed musculoskeletal problems. Dropouts were significantly older (P = 0.001), had less grip strength (P = 0.016), less 6MWD (P = 0.006) and a slower TUG-test (P = 0.003). There was no gender difference.

Of the variables included in the correlation analysis, only appendicular skeletal muscle mass (ASM) correlated significantly with IGF-1 at baseline (rho = 0.138, P = 0.037, similar in both genders), but not functional variables. Lean body mass tended to correlate with IGF-1 (rho = 0.112, P = 0.096).

Changes in IGF-1 after the training were inversely related with change in lean body mass (rho = -0.176, P = 0.013) and ASM (rho = -0.162, P = 0.019) (similar in both genders). Accordingly, the increase in lean body mass was significantly lower in those participants that had an increase in IGF-1 levels during the intervention (0.56 vs. 1.01 kg, P = 0.017).

A linear model (GLM) which included gender as a fixed factor and baseline IGF-1, changes in lean body mass and changes in fat mass as covariates, was constructed. Changes in lean body mass turned out to be significant predictors of change in IGF-1 (Table 2).

Table 2.

Parameter Estimates Dependent Variable: A IGF-1(/µg/L) Parameter B	95% CI	P-value
Intercept	37.277	−7.796	82.350	0.104
Male*	3.375	−3.313	10.063	0.321
Age (years)	−0.078	−0.671	0.515	0.795
IGF-1 at baseline (µg/L)	−0.323	−0.397	−0.249	<0.001
Δ Lean body mass (kg)	−3.665	−6.297	−1.033	0.007
Δ Fatmass (kg)	1.273	−1.428	3.974	0.354

^*as opposed to female

Discussion

The present study investigated the response of circulating total IGF-1 to 12 weeks of progressive resistance training in mostly overweight old adults. Overall, serum total IGF-1 decreased significantly during the course of the study, despite training induced-improvements in physical performance, strength, and lean body mass. The changes in IGF-1 were negatively related to changes in lean body mass.

IGF-1 levels were similar to that reported in other studies (14), or lower (5, 12, 13).Our results are consistent with several studies that have previously shown an overall decrease in levels of total IGF-1 in response to exercise (12, 13, 24), although other studies either found no significant change (5, 17., 18., 19., 20., 25), or even an increase (14., 15., 16.). This discrepancy between studies is still unresolved. Different study protocols and subject characteristics make comparison between studies difficult, but the observed change in IGF-1 during exercise has been suggested to depend on several factors, including the type of exercise, exercise training volume, length of the intervention period, and participants’ age, fitness level, training background and nutritional status (5, 13).

Eliakim et al. first put forth the hypothesis of a biphasic response pattern for circulating IGF-1 (24), which is partly supported by short- and long-term exercise interventions (12, 13, 26). It has been suggested that a decline in circulating IGF-1 levels may be the usual response to short-term physical exercise (12). Long-term exercise studies indicate that the decrease in IGF-1 is only temporary during the initial stages of physical exercise, and that levels of IGF-1 may increase beyond pre-training levels if exercise is continued (13, 26).

When we looked at IGF-1 changes for each participant individually we saw that IGF-1 decreased in the majority of our participants (59%), but increased in 39% of participants. It is obvious that there is intra-individual variability in the response of IGF-1 to resistance exercise. Interestingly, individuals who had an increase in IGF-1 during training, gained less lean mass during the training program as compared to those who had a decrease in IGF-1.

In our participants oveweight and obesity were not related to changes in IGF-1 during training. No caloric restriction during the study as well as the relative short period of training explain why the changes in body fat were only small. Potentionally, body fat or changes in body fat can affect circulating IGF-1 due to altered growth homrone secretion (27).

A negative correlation between change in IGF-1 and change in lean body mass during resistance exercise may seem paradoxical because of the well established positive correlation between lean body mass and IGF-1 (as also seen in our study when only using baseline data). In an attempt to explain this phenomenon, Schmitz et al. (13) hypothesized that IGF-1 decreased during periods of active muscle building. It has also been suggested that the decrease in circulating total IGF-1 may be due to a redistribution of IGF-1 from the circulation into tissue (12, 24). If such a sequestration of IGF-1 into tissue increases during exercise, it may be speculated that the effect would be more pronounced in individuals experiencing greater gain in lean body mass, potentially explaining the inverse correlation between change in IGF-1 and lean body mass in the present study.

It is well known that energy or protein deficit, with or without exercise training, is associated with a decrease in IGF-1 levels (28., 29., 30., 31.). Nemet et al. demonstrated that overfed subjects could maintain their IGF-1 levels during 7 days of strenuous physical exercise whereas energy deficient subjects showed significant reductions in IGF-1 levels (28). However, in the current study we did not find any significant association between change in IGF-1 with energy intake or energy balance. As assessed by 3-day weighted food records, most of our participants appeared to have adequate energy intakes, and none were severely energy deficient, which might explain the lack of association. Corroborating our findings, previous research indicates that moderate changes in energy balance combined with exercise do not affect levels of IGF-1 (32).

Limitation

A limitation of our study is that we only measured total (immuno-reactive) circulating IGF-1, which limits our ability to draw clear conclusions . Total IGF-1 is the sum of free IGF-1 and IGF-1 attached to binding proteins which are different with respect to physiological function and possible bioactivity (33). It has been suggested that it is the composition of different IGF-1 complexes rather than absolute levels of serum IGF-1 that determine IGF-1 bioactivity within tissues (34). However, quantification of total IGF-1 is widely used in the literature and has provided important and meaningful information about the IGF-1 system in many clinical conditions (33). It would

Linear model for the prediction of change (A) in IGF-1 during the course of the intervention also have been interesting to evaluate growth hormone or insulin-like growth factor-binding protein 3, however, these measurements were not available.

Conclusion

Our study shows that serum total IGF-1 decreases after 12 weeks of resistance exercise in community dwelling mostly overweight old adults. When looked at IGF-1 changes for participants individually it becomes clear that IGF-1 response to resistances exercise is highly variable. Changes in IGF-1 are negatively related to changes in lean body mass during training, which supports the hypothesis that IGF-1 is redistributed from circulation into tissue during periods of active muscle building.

Ethical standards

This study was ethically approved by the relevant local authority and all authors followed accepted ethical standards.

Conflict of interest

None