Association of serum retinol binding protein 4 and insulin resistance in apparently healthy adolescents

Abstract

Insulin resistance constitutes a pathophysiologic link between obesity, atherosclerosis, and/or cardiovascular complications. Retinol binding protein 4 (RBP4) is a newly discovered adipocyte product that modulates glucose metabolism and consequently induces insulin resistance. We investigated the association between serum RBP4 levels and insulin resistance in obese and nonobese adolescents. A total of 87 nonobese (60 males and 27 females) and 85 obese (62 males and 23 females) apparently healthy adolescents, 12 to 18 years old, were included in this study. A questionnaire was used to obtain participant medical history and lifestyle information, such as smoking and alcohol ingestion habits. Subjects' anthropometric measurements were taken to calculate for body mass index and waist-to-hip ratio. Serum RBP4 levels were measured by an enzyme immunoassay kit. High-sensitivity C-reactive protein, fasting glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and fasting insulin were measured. Low-density lipoprotein cholesterol level and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. Males had significantly higher RBP4 levels than females. Serum RBP4 levels were significantly higher in the obese group compared with the nonobese group. In all subjects, RBP4 was positively correlated with adiposity index (body mass index, waist circumference, waist-to-hip ratio), systolic and diastolic blood pressures, glucose tolerance index (fasting glucose, insulin, HOMA-IR), lipid profile (total cholesterol, triglycerides), and inflammatory indices (high-sensitivity C-reactive protein, white blood cell count). In multiple linear regression analysis, RBP4 was independently associated with age, HOMA-IR, and triglyceride levels in the nonobese group and with sex and triglyceride levels in the obese group. These results suggest that serum RBP4 might have clinical implications for lipid metabolism and insulin action in adolescents.

Introduction

The association of insulin resistance with an increased risk of cardiovascular disease (CVD) is well known [1] and constitutes a pathophysiologic link between obesity, atherosclerosis, and/or cardiovascular complications [2], [3], [4].

Retinol binding protein 4 (RBP4) is a newly discovered fat-derived peptide that modulates glucose metabolism and consequently induces insulin resistance [5]. A recent report by Yang et al [6] suggests that RBP4 is a central mediator of obesity-induced insulin resistance in mice and humans. The discovery of RBP4 provides a new link between obesity and insulin resistance. Given that the prevalence of obesity has been increasing rapidly [7] and that risk factors for CVD may initiate the process of atherosclerosis during childhood [8], the role of RBP4 as a mediator for increased insulin resistance in young individuals has clinical implications.

At the same time, clinical implications of RBP4 levels in obese humans are far from clear. The number of such studies on humans [6], [9] is relatively small, making it difficult to draw conclusions. Moreover, to our knowledge, no other study of the general population, especially of adolescent subjects, has been published.

Accordingly, we investigated the association between serum RBP4 levels and insulin resistance in obese and nonobese adolescents.