Abstract

BackgroundElevated retinol-binding protein 4 (RBP4) levels may contribute to the development of metabolic abnormalities, but prospective studies evaluating the association between childhood RBP4 levels and metabolic syndrome (MS) in adulthood are lacking. We investigated whether RBP4 levels during childhood predict cardiometabolic risk at 10-year follow-up.MethodsThe relationships between RBP4 levels, the established adipokines (leptin and adiponectin) and the components of MS were examined in 3445 school-aged children recruited in 2004 for the Beijing Child and Adolescent Metabolic Syndrome study. In 2015, 352 of these individuals completed an in-depth follow-up examination.ResultsParticipants with higher childhood RBP4 levels had adverse cardiometabolic profiles at follow-up. Those with incident or persistent MS had higher baseline RBP4 levels than those who never exhibited the elements of MS. Moreover, baseline RBP4 predicted hyperglycemia (OR per SD increase = 1.48, P = 0.009), elevated triglyceride (OR = 1.54, P < 0.001), elevated blood pressures (OR = 1.46, P = 0.015), MS (OR = 1.68, P = 0.002) and insulin resistance (OR = 1.44, P = 0.015) in the 10-year follow-up phase, independent of baseline BMI. Significant improvements were seen for the net reclassification improvement and integrated discrimination index after adding childhood RBP4 levels into the risk models using conventional cardiometabolic risk factors in predicting MS at follow-up (P < 0.05). Leptin and adiponectin demonstrated the expected associations with metabolic disorders.ConclusionsChildhood RBP4 serves as a risk factor for subsequent development of MS and its components, independent of pediatric obesity. Incorporating childhood RBP4 into conventional cardiometabolic risk assessment models significantly improves the prediction of MS.

Highlights

  • Elevated retinol-binding protein 4 (RBP4) levels may contribute to the development of metabolic abnormalities, but prospective studies evaluating the association between childhood RBP4 levels and metabolic syndrome (MS) in adulthood are lacking

  • RBP4 may play a role in the pathogenesis of type 2 diabetes (T2D) by upregulating hepatic expression of the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK) and inhibiting insulin signaling in muscle [6]

  • Leveraging the large cohort within the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study, we aimed to examine the role of circulating RBP4 in the development of insulin resistance (IR), MS and its components from crosssectional data collected in childhood and longitudinal analysis into young adulthood

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Summary

Introduction

Elevated retinol-binding protein 4 (RBP4) levels may contribute to the development of metabolic abnormalities, but prospective studies evaluating the association between childhood RBP4 levels and metabolic syndrome (MS) in adulthood are lacking. In two longitudinal studies of overweight or obese youth, reductions in RBP4 were reported to accompany weight loss, improvement of triglyceride (TG) levels and IR [18, 19], while a small study of Korean boys reported that baseline RBP4 levels did not predict the development of MS over a 3-year follow-up [20]. These existing pediatric studies are significantly limited by their small sample sizes and relatively short follow-up periods

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