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ObjectiveTo study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring.DesignCross-sectional comparison of serum biomarkers.SettingUniversity Medical Center Utrecht.PatientsHyperandrogenic PCOS women (HA-PCOS, n = 34), normoandrogenic PCOS women (NA-PCOS, n = 34), non-PCOS reference population (n = 32), PCOS offspring (n = 14, age 6–8 years), and a paedriatic reference population (n = 30).Main Outcome Measure(s)Clustering profile of adipocytokines (IL-1b, IL-6, IL-13, IL-17, IL-18, TNF-α, adiponectin, adipsin, leptin, chemerin, resistin, RBP4, DPP-IV/sCD26, CCL2/MCP-1), growth factors (PIGF, VEGF, sVEGF-R1), soluble cell adhesion molecules (sICAM-1/sCD54, sVCAM-1/sCD106), and other inflammatory related proteases (MMP-9, S100A8, Cathepsin S). Differences in median biomarker concentrations between groups, and associations with the free androgen index (FAI; Testosterone/SHBG x100).ResultsThe cluster analysis identified leptin, RBP-4, DPP-IV and adiponectin as potential discriminative markers for HA-PCOS with a specifically strong correlation in cases with increased BMI. Leptin (R2 = 0.219) and adiponectin (R2 = 0.182) showed the strongest correlation with the FAI. When comparing median protein concentrations adult PCOS women with or without hyperandrogenemia, the most profound differences were observed for leptin (P < 0.001), DPP-IV (P = 0.005), and adiponectin (P < 0.001). Adjusting for age, BMI and multiple testing attenuated all differences. In PCOS offspring, MMP-9 (P = 0.001) and S100A8 (P < 0.001) concentrations were significantly higher compared to a healthy matched reference population, even after correcting for age and BMI and adjustment for multiple testing.ConclusionIn this preliminary investigation we observed significant differences in adipocytokines between women with or without hyperandrogenic PCOS and non-PCOS controls, mostly influenced by BMI. Leptin and adiponectin showed the strongest correlation with the FAI in adult women with PCOS. In PCOS offspring other inflammatory biomarkers (MMP-9, S100A8) were increased, suggesting that these children may exhibit increased chronic low-grade inflammation. Additional research is required to confirm results of the current exploratory investigation.

For the first time it is demonstrated that increased general body mass and particularly waist circumference and intra-abdominal fat are related to thicker and stiffer arteries already early in life.

The aim of our study was to investigate the association between rapid weight gain in the first 3 months of life and the prevalence of wheeze in the first years of life and lung function at 5 yrs of age.The infants selected were participating in an ongoing birth cohort. Information on growth and respiratory symptoms was collected during the first year of life, and on primary care consultations during total follow-up. Forced expiratory volume in 1 s (FEV1) and forced expiratory flow at 25-75% of forced vital capacity (FEF25-75%) were measured at 5 yrs of age.Information on growth and respiratory symptoms was obtained for 1,431 infants, out of whom 235 children had already had 5 yrs of follow-up. Every one-point z-score increase in weight gain resulted in a 37% increase in days with wheeze (incidence rate ratio 1.37, 95% CI 1.27-1.47; p,0.001) and in associated consultations by 16% (incidence rate ratio 1.16, 95% CI 1.01-1.34; p50.04). Children with rapid weight gain reported significantly more physician-diagnosed asthma. FEV1 and FEF25-75% were reduced by 34 mL (adjusted regression coefficient -0.034, 95% CI -0.056--0.013; p50.002) and 82 mL (adjusted regression coefficient -0.082, 95% CI -0.140--0.024; p50.006) per every one-point z-score increase in weight gain, respectively. These associations were independent of birthweight.Rapid early weight gain is a risk factor for clinically relevant wheezing illnesses in the first years of life and lower lung function in childhood.

Excess early postnatal weight gain leads to vascular changes already in early childhood, characterized by thicker arterial walls. In children who are relatively thin at birth, excess early postnatal weight gain also leads to stiffer arteries. This supports the view that cardiovascular disease risk is associated with growth pattern early in life.