Introduction

2. Introduction • Visfatin and Adiponectin- Produced by adipose tissue • - Have opposite effects on insulin resistance -Visfatin: Increased in obesity & type 2 diabetes mellitus -Adiponectin: Reduced in obesity & type 2 diabetes mellitus

3. Introduction • Previous studies in gestational diabetes mellitus (GDM) • > Maternal serum adiponectin is reduced • > Maternal serum visfatin is increased or reduced

4. Introduction • Study aim • Determine whether in the first trimester of pregnancy: • Maternal serum concentrations of visfatin and adiponectin are altered in pregnancies that subsequently develop GDM • Visfatin and adiponectin can improve the performance of early screening for GDM by use of maternal factors

5. Question • Why is it important to identify in the first trimester pregnancies that will subsequently develop GDM?

6. Materials & Methods • Study population - Case-control study drawn from large observational study at 11-13 weeks’ gestation for early prediction of pregnancy complications - King’s College Hospital, London, UK • - Maternal serum visfatin and adiponectin measured in: • 100 cases who subsequently developed GDM • 300 controls who did not develop GDM

7. Materials & Methods • Outcome measure: Development of GDM • Diagnosis of GDM - Random blood sugar at 24-28 weeks’ gestation in all women and oral glucose tolerance test (OGTT) if >6.7 mmol/L - Positive OGTT (75g glucose): • Fasting plasma glucose > 6 mmol/L or • 2h plasma glucose ≥7.8 mmol/L

8. Materials & Methods • Sample analysis • > Visfatin ELISA technique (44-VISHU-E01.4, Alpco Diagnostics, • Salem NH03079, USA) • > Adiponectin • ELISA technique (DRP300, R&D Systems Europe Ltd., • Abingdon, United Kingdom)

9. Materials & Methods • Statistical analysis • - Visfatin and adiponectin were expressed as multiple of the median (MoM) in the nondiabetic group. Median MoMs in the two groups compared by Mann-Whitney U-test. • - Likelihood ratios (LRs) for GDM were calculated from the bivariate Gaussian distributions of adiponectin MoM and visfatin MoM in the GDM and nondiabetic groups. • - A-priori odds for GDM based on maternal factors were multiplied by the LR for adiponectin and visfatin to derive a-posteriori odds. The a-posteriori risks were used to calculate detection rates of GDM and false positive rates.

10. Question • In screening for GDM how can you combine maternal factors and biomarkers?

11. Results Table 1. Maternal and pregnancy characteristics in the outcome groups aP <0.05.

12. Results Table 2. Median (IQR) of maternal serum level of adiponectin and visfatin in the outcome groups aP <0.05. • In the GDM group, compared to nondiabetic controls, • median serum visfatin was higher and adiponectin was lower

13. Results Table 3. Performance of screening for GDM by maternal factors, maternal serum adiponectin MoM, visfatin MoM, and by their combinations a AUROC, area under the ROC curve. Detection rate of GDM (for a false-positive rate of 10%), improved from 58% in screening by maternal factors alone to 68% in screening by combination of maternal factors and serum visfatin and adiponectin

14. Conclusions At 11-13 weeks in pregnancies that develop GDM the serum concentration of adiponectin is decreased and visfatin is increased and these biomarkers can be combined with maternal factors to provide effective early screening for GDM. The estimated detection rate of GDM (for a false-positive rate of 10%), improved from 58% in screening by maternal factors alone to 68% in screening by a combination of maternal factors and serum visfatin and adiponectin.

15. Question • What is the estimated performance of early screening for GDM?