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.Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0707-y) contains supplementary material, which is available to authorized users.

Background The role of adipokine dysregulation in determining the metabolic fate of obesity is not well studied. We aimed to examine whether the matricellular protein osteonectin and the profiles of certain adipokines could differentiate metabolically healthy obese ( MHO ) versus metabolically unhealthy obese phenotypes in childhood. Methods and Results This study included 1137 obese children and 982 normal‐weight healthy ( NWH ) controls recruited from the BCAMS (Beijing Child and Adolescent Metabolic Syndrome) study. MHO was defined by the absence of insulin resistance and/or any metabolic syndrome components. Six adipokines—osteonectin, leptin, adiponectin, resistin, FGF21 (fibroblast growth factor 21), and RBP‐4 (retinol binding protein 4)—were assessed. Approximately 20% of obese children displayed the MHO phenotype. MHO children had a more favorable adipokine profile than metabolically unhealthy obese children, with lower osteonectin, leptin, and RBP ‐4 and higher adiponectin (all P <0.05). Compared with normal‐weight healthy controls, MHO children displayed increased leptin, resistin, and RBP ‐4 levels and reduced adiponectin concentrations (all P <0.05) but similar osteonectin and FGF 21 levels. Among obese subjects, decreased osteonectin (odds ratio [OR]: 0.82; 95% confidence interval [CI] per standard deviation, 0.70–0.97), RBP ‐4 (OR: 0.77; 95% CI per standard deviation, 0.64–0.93), and leptin/adiponectin ratio (OR: 0.58; 95% CI per standard deviation, 0.43–0.77) were independent predictors of MHO . In addition, compared with children without abnormalities, those with any 3 adipokine abnormalities were 80% less likely to exhibit the MHO phenotype ( OR : 0.20; 95% CI , 0.10–0.43) and 3 times more likely to have metabolic syndrome ( OR : 2.77; 95% CI , 1.52–5.03). Conclusions These findings suggest that dysregulation of adipokines might govern the metabolic consequences of obesity in children. Low osteonectin levels, along with a healthy adipokine profile, might be used as an early marker of the MHO phenotype.

ObjectiveImpaired fasting glucose (IFG) and impaired glucose tolerance (IGT) may convey disparate risks of metabolic consequences. Fasting plasma glucose (FPG), while an expedient screening procedure, may not adequately assess metabolic risk, particularly among youths. In order to inform a strategy for screening Chinese youth for pre-diabetes, we examined the relative value of IFG versus IGT to define metabolic risk by assessing their association with insulin resistance, beta-cell dysfunction, adverse adipokine profiles and other cardiometabolic risk factors.Research design and methodsWe recruited 542 subjects (age 14–28 years) from the Beijing Child and Adolescent Metabolic Syndrome study for an in-depth assessment of cardiometabolic risk factors, including a 2-hour oral glucose tolerance test, liver ultrasound and serum levels of four adipokines.ResultsFPG failed to identify nearly all (32/33) youths with IGT, whereas 2-hour plasma glucose (2 h PG) missed 80.8% (21/26) of subjects with IFG. Impaired beta-cell function was evident from decreased oral disposition indices in those with isolated impaired fasting glucose (iIFG) or isolated impaired glucose tolerance (iIGT) versus normal glucose tolerance (NGT) (all p<0.001), whereas reduced insulin sensitivity (Matsuda) index was most pronounced in the iIGT group (p<0.01). Moreover, alterations in adipokine levels (fibroblast growth factor 21, adiponectin and leptin/adiponectin ratio) were associated with iIGT (p<0.05) but not iIFG. Youths with iIGT had a 2-fold to 32-fold increased incidence of hypertriglyceridemia, hypertension and metabolic syndrome (MetS) compared with those with NGT. In addition, subgroup analyses of participants with normal FPG revealed that the odds of having IGT increased 3-fold to 18-fold among those with elevated TGs, hypertension, moderate-to-severe non-alcoholic fatty liver disease or MetS.ConclusionsChinese youth with iIGT exhibit a higher cardiometabolic risk profile than those with iIFG. Thus, 2 h PG is preferred over FPG to identify the pre-diabetes phenotype at greatest risk of subsequent development of cardiovascular disease.Trial registration numberNCT03421444.