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Retinol-Binding Protein 4 and Its Relation to Insulin Resistance in Obese Children before and after Weight Loss

Vestische Hospital for Children and Adolescents Datteln (T.R.), University of Witten/Herdecke, D-45711 Datteln, Germany; Department of Clinical Chemistry and Pharmacology (B.S.-W.), University Hospital of Bonn, D-53127 Bonn, Germany; and Seattle Children’s Hospital Research Institute (C.L.R.), University of Washington, Seattle, Washington 98101

Address all correspondence and requests for reprints to: PD Dr. Thomas Reinehr, Department of Pediatric Nutrition Medicine, Vestische Hospital for Children and Adolescents Datteln, University of Witten/Herdecke, Dr. F. Steiner Str. 5, D-45711 Datteln, Germany. E-mail: T.Reinehr{at}kinderklinik-datteln.de.

Context: There are limited and controversial data concerning the relationships between retinol-binding protein 4 (RBP4), weight status, and insulin resistance in obese humans and especially in children.

Objective: Our objective was to study the longitudinal relationships among RBP4, insulin resistance and weight status in obese children.

Design, Setting, and Patients: We conducted a 1-yr longitudinal follow-up study in a primary-care setting with 43 obese children (median age 10.8 yr) and 19 lean children of same the age and gender.

Intervention: Our outpatient 1-yr intervention program was based on exercise, behavior, and nutrition therapy.

Main Outcomes Measures: Changes of weight status (body mass index SD score), RBP4, molar RBP4/serum retinol (SR) ratio, insulin resistance index homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI).

Results: Obese children had significantly (P < 0.01) higher RBP4 concentrations and a higher RBP4/SR ratio compared with lean children. In multiple linear regression analyses adjusted to age, gender, and pubertal stage, RBP4 was significantly correlated to insulin and body mass index. Pubertal children demonstrated significantly decreased QUICKI and significantly increased HOMA index, insulin, and RBP4 concentrations compared with prepubertal children. Changes of RBP4 correlated significantly to changes of insulin (r = 0.29), HOMA index (r = 0.29), QUICKI (r = 0.22), and weight status (r = 0.31). Substantial weight loss in 25 children led to a significant (P < 0.001) decrease of RBP4, RBP4/SR, blood pressure, triglycerides, insulin, and HOMA index and an increase in QUICKI in contrast to the 18 children without substantial weight loss.

Conclusion: RBP4 levels were related to weight status and insulin resistance in both cross-sectional and longitudinal analyses, suggesting a relationship between RBP4, obesity, and insulin resistance in children.