Biomarker Profiles in Women with PCOS and PCOS Offspring; A Pilot Study

OBJECTIVE: To study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring. DESIGN: Cross-sectional comparison of serum biomarkers. SETTING: University Medical Center Utrecht. PATIENTS: Hyperandrogenic 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). RESULTS: The 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. CONCLUSION: In 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

Clinical Utility of Biomarkers in IBD

There is no gold standard for the diagnosis and monitoring of inflammatory bowel diseases (IBD). Biomarkers are useful tools for the management of patients suffering from IBD. However, they should be used only when their additional information is useful for clinical decision-making. In principal, four situations during the management of an individual IBD patient can be discriminated from a clinical standpoint in which biomarkers provide useful information. First, biomarkers may be helpful when the diagnosis of IBD is established and aid in the discrimination between ulcerative colitis (UC) and Crohn's disease (CD) is necessary. Second, biomarkers may be helpful in the prognostic evaluation of IBD severity or disease behavior and for early decisions on the best treatment. The third situation in which biomarkers are useful is the evaluation of disease activity during the disease course, for monitoring and for guidance of ongoing treatment. Finally, the fourth typical situation when biomarkers are of value is after surgery to predict or diagnose a relapse of the disease. From a clinical point of view, it may be more useful to discuss specific biomarkers and their individual value and impact in these four prototypic situations than to sum up advantages and disadvantages for each biomarker isolated from the clinical situation. Therefore, this overview is structured in chapters reflecting those four typical situations during the disease course of IBD patents to critically evaluate the potential and value of each of the biomarkers in the specific situation