Elsevier

Metabolism

Volume 57, Issue 5, May 2008, Pages 683-690
Metabolism

The association between insulin resistance and cytokines in adolescents: the role of weight status and exercise

https://doi.org/10.1016/j.metabol.2008.01.005Get rights and content

Abstract

Increased adiposity is associated with insulin resistance (IR) and an inflammatory response in adults. We tested the hypotheses that cytokines associated with adiposity are also correlated with IR in early adolescents and that these relationships are moderated by weight status, levels of vigorous physical activity (VPA), or maximal aerobic power (pVO2max). Body mass, stature, and a fasting blood sample were obtained from 120 midpubertal adolescents (60 girls and 60 boys). Habitual VPA was obtained by a survey. Predicted VO2max was determined using a cycle ergometer test. Weight status was based on body mass index (BMI) percentiles (normal weight = BMI <75th percentile, overweight = BMI >95th percentile). Glucose, insulin, adiponectin, resistin, tumor necrosis factor–α (TNF-α), and interleukin-6 were measured; and IR index was based on the Homeostatic Model Assessment. Adiponectin, resistin, and TNF-α were associated with IR in all adolescents (R2 = 0.329, P < .001; R2 = 0.152, P = .001; and R2 = 0.141, P = .002; respectively); but interleukin-6 was not (R2 = 0.148, P = .114). The degree of association between adiponectin and IR was stronger in overweight than in normal-weight adolescents (P < .050). When regression models included weight status, neither TNF-α nor resistin was significantly related to IR (P > .050). Exercise did not moderate the association between these cytokines and IR. However, higher levels of VPA and/or pVO2max were associated with higher adiponectin, lower resistin, and lower TNF-α in at least one of the sexes. Our results indicate that the pathophysiology of obesity is already established in early adolescents. Increased adiposity, resulting in reduced adiponectin and increased resistin and TNF-α, may link these cytokines with IR in adolescents.

Introduction

Increased adiposity has been strongly associated with insulin resistance in youths [1]. However, the link between adipose tissue and the increased resistance to insulin is still unclear [2], [3]. Cytokines released by the adipose tissue, such as adiponectin, resistin, interleukin-6 (IL-6), and tumor necrosis factor–α (TNF-α), appear to link adiposity with insulin resistance in youths [4], [5], [6], [7], [8], as in adults [3], [9], [14]. Adiponectin increases glucose uptake and free fatty acid oxidation in skeletal muscle [15] and is associated with decreased insulin resistance in youths and adults [4], [5], [8], [9]. The association between resistin and insulin resistance is equivocal [2], [16]. Studies in youths have not shown this association [17], and studies in adults presented contradictory findings [10], [18], [19]. Tumor necrosis factor–α and IL-6 act to inhibit insulin signaling in the adipose tissue [12], [20]. Although TNF-α and IL-6 have been associated with insulin resistance in adults [12], [13], [14], there are little data in youths [6], [8], [14]. In prepubertal children, there was no association between TNF-α and insulin resistance [14], whereas in another group of children, soluble TNF-α receptor but not TNF-α was related to insulin resistance [6]. Similarly, IL-6 has been mostly related to adiposity and the metabolic syndrome [7], [21]; but no clear link has been made between insulin resistance and this cytokine in youths [21].

During puberty, there is an increase in insulin resistance [22] that may be related to changes in growth hormone, sex hormones, and increases and redistribution of body fat [1]. All 4 of the previously mentioned cytokines have been associated with body fat indicators in youths [4], [5], [7], [8], [18], [21]. Therefore, it could be expected that the strength of the association between cytokines and insulin resistance is higher in overweight compared with normal-weight youths. Similarly, decreased physical activity levels and maximal aerobic power have been associated with increased insulin resistance [23], [24]. Levels of these cytokines appear to respond favorably to sustained physical activity [25], [26] and exercise training [27], [28], [29] in youths and in adults. It is speculated that increased but not decreased physical activity or aerobic power, an indicator of cardiovascular fitness, might attenuate, if existent, the relationship between insulin resistance and resistin, TNF-α, and IL-6.

To our knowledge, this is the first study to explore associations between all 4 cytokines (adiponectin, resistin, IL-6, and TNF-α) and insulin resistance in male and female adolescents and to examine the effect of weight status, physical activity levels, and aerobic power as moderators of this association. In addition, this study included a multiethnic (mostly biracial) sample of adolescents in midpuberty, the critical stage for a high degree of insulin resistance and changes in body fat content. This study tested 2 hypotheses: (1) cytokines (adiponectin, resistin, IL-6, and TNF-α) are associated with insulin resistance in midpubertal adolescents as previously shown in adults, and (2) overweight status would have opposite moderating effects than physical activity or aerobic power with regard to the associations between these cytokines and insulin resistance.

Section snippets

Subjects

Participants from the Cardiovascular Health in Children and Youth Study III between the years 2000 and 2003 were the subjects for this cross-sectional study [30]. Sixty girls and 60 boys, ages 10 to 14 years, who were midpubertal (Tanner stages 2-4) were randomly selected from subgroups of 437 adolescents based on their weight status (normal weight vs overweight) and levels of habitual vigorous physical activity (VPA). Half of the adolescents selected were overweight (body mass index [BMI]

Results

The characteristics of the subjects are presented in Table 1. Racial distribution was 57% African American, 37% white, and 6% other ethnic groups. There were 60 girls and 60 boys participating in this study. The distribution of normal and overweight adolescents in the sample was the same, and the number of adolescents reporting high VPA or low VPA was equal.

African American youths were heavier and had higher BMI than white youths (P < .050). African American youths also had lower adiponectin (P

Insulin resistance, cytokines, and weight status

We chose to examine the association between selected cytokines and insulin resistance in adolescents. The selected 4 cytokines were studied because of existing data in adults suggesting that such associations existed [9], [10], [11], [12], [13]. Although many studies have demonstrated a negative association between adiponectin and insulin resistance [4], [5], [21], we hypothesized a different association between adiponectin and insulin resistance depending on weight status. We showed that, in

Acknowledgment

This study was supported by the Graduate Student Trust Fund University of North Carolina at Chapel Hill (to DAR); the Department of Exercise and Sport Science, University of North Carolina at Chapel Hill (to DAR); NIH-NINR-RO1-1837 (to JSH); and 1K23-RR-021979 (to AMH).

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