Osteocalcin Serum Levels in Gestational Diabetes Mellitus and Their Intrinsic and Extrinsic Determinants: Systematic Review and Meta-Analysis

Background. Undercarboxylated osteocalcin (ucOC) increases insulin release and insulin resistance in mice. In humans, evidence is scarce but a correlation of ucOC and total osteocalcin (tOC) with glycemic status markers has been demonstrated. The relationship of ucOC and tOC with gestational diabetes mellitus (GDM) has been even less characterized. Objective. To assess the mean difference of tOC and ucOC serum concentrations among nondiabetic pregnant women and women diagnosed as GDM in the second trimester of pregnancy and to determine the possible intrinsic and extrinsic contributors to this difference. Methods. A systematic search was performed to identify relevant studies published in English and Spanish using PubMed, SCOPUS, ISI Web of Knowledge, and PROSPERO database for meta-analysis. Observational studies measuring mean serum levels of osteocalcin among GDM, with at least 10 subjects analyzed in each group were selected. Mean difference (MD) by random effects model was used. Heterogeneity between studies was assessed using Cochran's Q, H, and I2 statistics. Results. From 38 selected studies, 5 were retained for analysis for a total of 1119 pregnant women. Serum concentrations of tOC were not significantly different among women with GDM and nondiabetic pregnant controls (MD: 1.56; 95% CI: -0.70 to 3.82; p=0.175). Meanwhile, ucOC serum levels were significantly higher among women with GDM (MD: 1.17; 95% CI: 0.24 to 2.11; p=0.013). The only factor influencing tOC was the UV index, showing a reduction in mean difference between GDM and controls when exposed to higher concentrations of UV rays. Conclusions. This meta-analysis provides evidence to support the use of ucOC as a potential marker for GDM rather than tOC, yielding very little variability among studies and no difference among methods or brands used for its analysis.