Low after converting. We did not get confirmation from the original authors by email. Thus, to be conservative, we did not include these studies in the main analysis which calculated the LCZ696 solubility pooled WMD. Instead, we included them in a sensitivity analysis using pooled SMD as the metric. In another study [36], adiponectin levels were reported as geometric means and ratios, without values in the absolute scale, and therefore it was omitted in the meta-analysis. Our meta-analysis of the other nine studies showed that adiponectin levels in the first or early second trimester were significantly lower in women who later developed GDM compared to women who later did not, yet with significant between-study heterogeneity (random-effects pooled WMD [95 CI], -2.25 [-2.75 to -1.75] g/ml; I2 = 86 ; Figure 2). Egger test for publication bias did not reach statistical significance (P = 0.49). In stratified analyses (Supplementary Table 2), the pooled WMDs were not differentiated appreciably by geographical location (North America versus HMPL-013 site others), sample size (< 100 versus 100), average timing of blood samples collection for adiponectin measurement (first versus second trimester), assay methods for adiponectin measurement (EIA versus RIA), and diagnostic criteria for GDM (WHO criteria versus others). We did not stratify by time for GDM diagnosis because almost all included studies reported the diagnosis at 24?8 weeks of gestation. Meta-regression analysis including the above variables in the model alsoAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptMetabolism. Author manuscript; available in PMC 2016 June 01.Bao et al.Pagedid not identify significant contributors to the source of heterogeneity. Sensitivity analysis by omitting one study at a time did not alter the results (Supplementary Figure 1). In addition, we calculated the pooled SMD which allows including the results from all studies regardless of units. The pooled random-effects SMD (95 CI) was -1.20 (-1.63 to -0.78) (Supplementary Figure 2). 3.2.2 Leptin--Among the nine studies, one study [36] reported leptin adiponectin levels as geometric means and ratios, without values in the absolute scale, and therefore it was omitted in the meta-analysis. A meta-analysis of the remaining eight prospective studies showed that leptin levels in the first or early second trimester were significantly higher in women who later developed GDM compared to women who later did not, yet with significant between-study heterogeneity (random-effects WMD [95 CI], 7.25 [3.27 to 11.22] ng/ml; I2 = 94 ; Figure 3). Egger test for publication bias did not provide evidence of significant effect (P = 0.41). Similar to adiponectin, there was no evidence of heterogeneity in pooled WMDs for leptin levels by average timing of blood collection for leptin measurement (first versus second trimester), assay methods for leptin measurement (EIA versus RIA), and diagnostic criteria for GDM (Carpenter and Coustan criteria versus others) (Supplementary Table 3). Sensitivity analysis by omitting one study at a time did not alter the results materially (Supplementary Figure 3). 3.3 Findings of adipokines not suitable for a pooling of summary statistics We did not pool studies that investigated visfatin, RBP-4, resistin, TNF-, interleukin-6 (IL-6), or vaspin, because too few independent prospective studies have been published on these adipokines. Findings on their association with GDM risk have been conflicting (Table 3).Low after converting. We did not get confirmation from the original authors by email. Thus, to be conservative, we did not include these studies in the main analysis which calculated the pooled WMD. Instead, we included them in a sensitivity analysis using pooled SMD as the metric. In another study [36], adiponectin levels were reported as geometric means and ratios, without values in the absolute scale, and therefore it was omitted in the meta-analysis. Our meta-analysis of the other nine studies showed that adiponectin levels in the first or early second trimester were significantly lower in women who later developed GDM compared to women who later did not, yet with significant between-study heterogeneity (random-effects pooled WMD [95 CI], -2.25 [-2.75 to -1.75] g/ml; I2 = 86 ; Figure 2). Egger test for publication bias did not reach statistical significance (P = 0.49). In stratified analyses (Supplementary Table 2), the pooled WMDs were not differentiated appreciably by geographical location (North America versus others), sample size (< 100 versus 100), average timing of blood samples collection for adiponectin measurement (first versus second trimester), assay methods for adiponectin measurement (EIA versus RIA), and diagnostic criteria for GDM (WHO criteria versus others). We did not stratify by time for GDM diagnosis because almost all included studies reported the diagnosis at 24?8 weeks of gestation. Meta-regression analysis including the above variables in the model alsoAuthor Manuscript Author Manuscript Author Manuscript Author ManuscriptMetabolism. Author manuscript; available in PMC 2016 June 01.Bao et al.Pagedid not identify significant contributors to the source of heterogeneity. Sensitivity analysis by omitting one study at a time did not alter the results (Supplementary Figure 1). In addition, we calculated the pooled SMD which allows including the results from all studies regardless of units. The pooled random-effects SMD (95 CI) was -1.20 (-1.63 to -0.78) (Supplementary Figure 2). 3.2.2 Leptin--Among the nine studies, one study [36] reported leptin adiponectin levels as geometric means and ratios, without values in the absolute scale, and therefore it was omitted in the meta-analysis. A meta-analysis of the remaining eight prospective studies showed that leptin levels in the first or early second trimester were significantly higher in women who later developed GDM compared to women who later did not, yet with significant between-study heterogeneity (random-effects WMD [95 CI], 7.25 [3.27 to 11.22] ng/ml; I2 = 94 ; Figure 3). Egger test for publication bias did not provide evidence of significant effect (P = 0.41). Similar to adiponectin, there was no evidence of heterogeneity in pooled WMDs for leptin levels by average timing of blood collection for leptin measurement (first versus second trimester), assay methods for leptin measurement (EIA versus RIA), and diagnostic criteria for GDM (Carpenter and Coustan criteria versus others) (Supplementary Table 3). Sensitivity analysis by omitting one study at a time did not alter the results materially (Supplementary Figure 3). 3.3 Findings of adipokines not suitable for a pooling of summary statistics We did not pool studies that investigated visfatin, RBP-4, resistin, TNF-, interleukin-6 (IL-6), or vaspin, because too few independent prospective studies have been published on these adipokines. Findings on their association with GDM risk have been conflicting (Table 3).
