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Relationships between insulin sensitivity, skeletal muscle mass and muscle quality in obese adolescent boys

Abstract

We examined the relationships between insulin sensitivity (IS), skeletal muscle (SM) mass and SM quality in youth. Forty obese adolescent boys (body mass index 95th percentile, 12–18 years) participated in this study. IS and glucose tolerance was measured by a 3 h hyperinsulinemic−euglycemic clamp and a 2 h oral glucose tolerance test (OGTT), total SM mass and intermusular adipose tissue (IMAT) by whole-body magnetic resonance imaging, and muscular strength by one-repetition maximum leg and bench press. IMAT was associated (P<0.05) with IS (r=−0.53) and OGTT-insulin area under the curve (AUC; r=0.31). Similarly, muscular strength was associated (P<0.05) with both IS (r=0.39) and OGTT-insulin AUC (r=−0.32). By contrast, total SM mass was not associated with IS or any OGTT parameters (P>0.1). After accounting for race and tanner stage, IMAT and muscular strength remained significantly associated with IS, together explaining a total of 41% of the variance in IS. Our findings suggest that SM quality, but not SM mass, is associated with IS in obese adolescent boys.

Introduction

Skeletal muscle (SM) is the major site of glucose disposal during hyperinsulinemic−euglycemic conditions.1 It has been postulated that SM is an important determinant of glucose metabolism, and studies have expressed glucose disposal or insulin sensitivity (IS) per unit of SM or lean body mass. In line with this, studies in adults demonstrate that the improvement in IS2 or glucose tolerance3 after strength training is associated with corresponding increases in SM mass. However, it is unclear whether the increases in absolute SM, or the changes in SM characteristics were responsible for these changes.

Recently, a large epidemiological study4 demonstrated a significant association between homeostatic model assessment (HOMA)−insulin resistance (IR) and SM mass as estimated by bioimpedance. This is in contrast with a finding by Kuk et al.5 who reported that SM mass is not associated with IS or glucose tolerance in obese men and women when using criterion methods, such as whole-body magnetic resonance imaging (MRI), hyperinsulinemic−euglycemic clamp and oral glucose tolerance tests (OGTT).

Clearly there is a disagreement in the adult literature,4, 5 and no study to date has examined this issue in youth. Therefore, we examined the relationships between IS, total SM mass and SM quality as evaluated by intermuscular adipose tissue (IMAT) and muscular strength in obese adolescent boys. We hypothesized that SM quality, but not total SM mass, would be associated with IR in adolescents.

Materials and Methods

Subjects consisted of 40 obese (body mass index 95th percentile) adolescent boys (12–18 years) who were initially recruited for a lifestyle intervention study.6 Participants were recruited from November 2007 through April 2011 at Children’s Hospital of Pittsburgh. All subjects were pubertal (Tanner III−V), non-smokers, non-diabetic, sedentary and not taking any medications, known to affect the study outcomes. Participants were recruited via flyers posted in city public transportation, posters placed on campus and the Weight Management and Wellness Center at CHP. The study was approved by the University of Pittsburgh Institutional Review Board. Parental informed consent and child assent were obtained from all participants before participation. All participants underwent physical examination and pubertal development according to Tanner criteria (genital development and pubic hair) by a certified nurse practitioner.

Oral glucose tolerance test

Participants underwent a 2 h OGTT (1.75 g/kg, maximum 75 g) after a 10–12 h overnight fast. Glucose and insulin area under the curve (AUC) was determined using a trapezoid model.7 Hepatic IR was estimated using the equation published previously.8

Hepatic IR index=2.267+0.427log(HOMA−IR)8

Insulin sensitivity

Participants underwent a 3 h hyperinsulinemic (80 mU/m2/min)−euglycemic clamp, after a 10–12 h overnight fast, as shown previously.9 The insulin-stimulated glucose disposal rate was calculated using the average exogenous glucose infusion rate during the final 30 min of the clamp. IS was calculated by dividing insulin-stimulated glucose disposal rate by the steady-state insulin levels during the last 30 min of the clamp.

Whole-body MRI

Whole-body MRI data were obtained with a 3.0 Tesla magnet (Siemens Medical Systems, Erlangen, Germany) as shown previously.10 The images were obtained using T1-weighted spin-echo sequence (700-ms repetition time and 5.5-ms echo time) with a 48 × 36 field of view and a 320 × 240 matrix throughout the whole body. In two subjects, a 1.5 Tesla MRI system (GE Medical Systems, Milwaukee, WI, USA) was used owing to safety concerns associated with dental braces.

Intermusular adipose tissue and skeletal muscle

IMAT was defined as adipose tissue (AT) intertwined between the bundles of SM fibers and beneath the fascia lata.10, 11 AT and SM volume was converted to mass units (kg) by multiplying the volumes by the assumed constant density for AT (0.92 kg/l) and SM (1.04 kg/l).12

Muscular strength

Muscular strength was assessed with a one-repetition maximum (1-RM) test for the supine bench press and seated leg press using weight stack equipment (Life fitness, Schiller Park, IL, USA). Resistance was progressively increased by 2.5−20 kg until a maximal lift was achieved with a full range of motion within four attempts with rest periods of 3–5 min between trials. Muscular strength was calculated as the sum of the 1-RM scores for the bench and leg press expressed per kg of body weight.13

Statistical analysis

Statistical procedures were performed using SPSS (Version 15; SPSS Inc., Chicago, IL, USA). Pearson’s correlation coefficients were used to determine the association between SM, IMAT and muscular strength with IS. Multiple regression analyses were used to determine the independent associations between SM, IMAT and muscular strength (independent predictors) with IS (dependent variable), adjusting for Tanner stage and race.

Results

Subject characteristics are shown in Table 1. SM mass was not associated (P>0.1) with IS, whether it is expressed as per kg body weight (Figure 1a) or per total body weight (r=0.15, P=0.37), any OGTT parameters (Figure 1b) or hepatic IR index (r=−0.04, P=0.81). By contrast, IMAT was inversely associated with IS (r=−0.53, P<0.01; Figure 1c) and positively associated with OGTT-insulin AUC (r=0.31, P<0.05; Figure 1d), but not hepatic IR index (r=0.21, P=0.21). Further, muscular strength was associated with IS (r=0.39, P=0.01) and OGTT-insulin AUC (r=−0.32, P=0.04), but not hepatic IR index (r=−0.21, P=0.20). After accounting for race and Tanner, IMAT and muscular strength remained significantly associated with IS, together explaining a total of 41% of the variance in IS.

Table 1 Subject characteristics
Figure 1
figure1

Relationships between SM mass, IMAT and in vivo IS (left panel) and OGTT-insulin AUC (right panel) in obese adolescent boys.

Discussion

We observed that SM quality, as evaluated by IMAT, and muscular strength, but not SM mass, is an important determinant of IS in obese adolescent boys. Consistent with the previous observations in adults,5 we did not find significant relationships between total SM mass and IS in adolescents. Although it has been suggested that SM is the major site of glucose disposal,1 SM quality, rather than SM mass per se, may be more important in determining IS in obesity. Whether this is the case in non-obese adolescents, remains to be determined. Previous studies in adults report that IMAT and muscle oxidative capacity14 are significantly associated with IS. Further, our finding that muscular strength is an independent correlate of IS is consistent with others, reporting that muscular strength is an independent predictor of HOMA−IR15, 16 in youth, and that a 1-RM bench press or leg press is associated with IS17 and metabolic syndrome13 in adults. These findings suggest that there may be a link between metabolic and mechanical muscle functions, or that strength may be a good surrogate of insulin-sensitizing physical activity.17

It is important to note that our cross-sectional observation does not allow us to infer a causal relationship between IMAT, muscular strength and IS. Because of significant gender differences in both body composition and muscular strength, confirmation of these findings in females is required. In our study, neither SM or strength are significantly associated with IS after controlling for AT. Though this study only demonstrates cross-sectional associations, it may suggest that obesity reduction may be more important for obese youth than interventions that increase SM or strength. This is interesting given our previous results6 that resistance exercise was superior to aerobic exercise for improving IS. Further studies are needed to determine if interventions that improve muscle strength and quality are as beneficial in improving IS as interventions that are aimed at reducing obesity in youth.

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Acknowledgements

This research was funded by grants 7-08-JF-27 (Lee, American Diabetes Association Junior Faculty Award), Department of Defense (Lee and Arslanian), Children’s Hospital of Pittsburgh Cochrane-Weber Foundation (Lee) and UL1 RR024153 CTSA. The authors express their gratitude to the study participants and their parents, to Nancy Guerra and the PCTRC nursing staff for their excellent contributions. This work was presented at the Obesity Society Annual Meeting, October 1–5, 2011 in Orlando, FL, USA.

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Lee, S., Kim, Y., White, D. et al. Relationships between insulin sensitivity, skeletal muscle mass and muscle quality in obese adolescent boys. Eur J Clin Nutr 66, 1366–1368 (2012). https://doi.org/10.1038/ejcn.2012.142

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Keywords

  • SM mass
  • intermuscular adipose tissue
  • muscular strength
  • IS
  • childhood obesity

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