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Objective: To examine the association of early-pregnancy serum C-peptide with incident gestational diabetes mellitus (GDM) and the predictive ability of maternal C-peptide for GDM. Methods: A nested case–control study of 332 GDM cases and 664 controls was established based on the Tongji-Shuangliu Birth Cohort. The GDM cases and controls were matched at 1:2 on maternal age (± 3 years) and gestational age (± 4 weeks). Multivariable conditional logistic regression was applied to assess the association of C-peptide with risk of GDM. Partial Spearman's correlation coefficients were estimated for the correlations between C-peptide and multiple metabolic biomarkers. C-statistics were calculated to assess the predictive ability of early-pregnancy C-peptide for GDM. Results: Of 996 pregnant women, median maternal age was 28.0 years old and median gestational age was 11.0 weeks. After adjustment for potential confounders, the odds ratio of GDM comparing the extreme quartiles of C-peptide was 2.28 (95% confidence interval, 1.43, 3.62; P for trend < 0.001). Partial correlation coefficients ranged between 0.07 and 0.77 for the correlations of C-peptide with fasting insulin, homeostatic model of insulin resistance, leptin, fasting blood glucose, triglycerides, glycosylated hemoglobin, waist–hip ratio, systolic blood pressure, and low-density lipoprotein cholesterol (P ≤ 0.025), and were − 0.11 and − 0.17 for high-density lipoprotein cholesterol and adiponectin (P < 0.001). Serum C-peptide slightly improved the predictive performance of the model with conventional predictive factors (0.66 vs. 0.63; P = 0.008). Conclusion: While the predictive value for subsequent GDM should be validated, early-pregnancy serum C-peptide may be positively associated with risk of GDM. [ABSTRACT FROM AUTHOR]

Aims: We prospectively evaluated the association of circulating retinol-binding protein 4 (RBP4) levels in early pregnancy and risk of incident gestational diabetes mellitus (GDM) in pregnant women.Methods: A nested case-control study was conducted among 332 women who developed GDM and 664 matched controls based on the Tongji-Shuangliu Birth Cohort. GDM was diagnosed during 24-28 weeks of gestation according to the International Association of Diabetes and Pregnancy Study Group criteria. Serum RBP4 levels in early pregnancy (6-15 weeks of gestation) were determined by ELISA assay. Multivariable conditional logistic regression models were used to analyse the association and generated the odds ratio (OR) and 95% confidence interval (CI). EMBASE and PubMed were searched up to 30 November 2020 to identify studies investigating the association between blood RBP4 levels in early pregnancy and incident GDM.Results: In the multivariable model with adjustment of potential risk factors, the OR comparing the extreme quartiles of serum RBP4 levels was 2.26 (95% CI: 1.34, 3.81; p for trend <0.001), and each standard deviation (SD) increment of RBP4 was associated with 1.39-fold (95% CI: 1.15, 1.69) higher risk of GDM. The results were confirmed in a meta-analysis that included additional four studies with an overall OR of 1.47 (95% CI: 1.18, 1.83) per 1-SD increment of RBP4.Conclusions: Serum RBP4 levels in early pregnancy, independent of metabolic risk factors, are positively associated with the risk of GDM in pregnant women. Our findings may provide new insights into the mechanisms underlying the aetiology of GDM. [ABSTRACT FROM AUTHOR]

Background Lipid metabolism plays an important role in the pathogenesis of diabetes. There is little evidence regarding the prospective association of the maternal lipidome with gestational diabetes mellitus (GDM), especially in Chinese populations. Objectives We aimed to identify novel lipid species associated with GDM risk in Chinese women, and assess the incremental predictive capacity of the lipids for GDM. Methods We conducted a nested case–control study using the Tongji-Shuangliu Birth Cohort with 336 GDM cases and 672 controls, 1:2 matched on age and week of gestation. Maternal blood samples were collected at 6–15 wk, and lipidomes were profiled by targeted ultra-HPLC–tandem MS. GDM was diagnosed by oral-glucose-tolerance test at 24–28 wk. The least absolute shrinkage and selection operator is a regression analysis method that was used to select novel biomarkers. Multivariable conditional logistic regression was used to estimate the associations. Results Of 366 detected lipids, 10 were selected and found to be significantly associated with GDM independently of confounders: there were positive associations with phosphatidylinositol 40:6, alkylphosphatidylcholine 36:1, phosphatidylethanolamine plasmalogen 38:6, diacylglyceride 18:0/18:1, and alkylphosphatidylethanolamine 40:5 (adjusted ORs per 1 log-SD increment range: 1.34–2.86), whereas there were inverse associations with sphingomyelin 34:1, dihexosyl ceramide 24:0, mono hexosyl ceramide 18:0, dihexosyl ceramide 24:1, and phosphatidylcholine 40:7 (adjusted ORs range: 0.48–0.68). Addition of these novel lipids to the classical GDM prediction model resulted in a significant improvement in the C-statistic (discriminatory power of the model) to 0.801 (95% CI: 0.772, 0.829). For every 1-point increase in the lipid risk score of the 10 lipids, the OR of GDM was 1.66 (95% CI: 1.50, 1.85). Mediation analysis suggested the associations between specific lipid species and GDM were partially explained by glycemic and insulin-related indicators. Conclusions Specific plasma lipid biomarkers in early pregnancy were associated with GDM in Chinese women, and significantly improved the prediction for GDM. [ABSTRACT FROM AUTHOR]

Little is known about the genetic influence on BMI trajectory throughout adulthood. We created a genetic risk score (GRS) comprising 97 adult BMI-associated variants among 9,971 women and 6,405 men of European ancestry. Serial measures of BMI were assessed from 18 (women) or 21 (men) years to 85 years of age. We also examined BMI change in early (from 18 or 21 to 45 years of age), middle (from 45 to 65 years of age), and late adulthood (from 65 to 80 years of age). GRS was positively associated with BMI across all ages, with stronger associations in women than in men. The associations increased from early to middle adulthood, peaked at 45 years of age in men and at 60 years of age in women (0.91 and 1.35 kg/m2 per 10-allele increment, respectively) and subsequently declined in late adulthood. For women, each 10-allele increment in the GRS was associated with an average BMI gain of 0.54 kg/m2 in early adulthood, whereas no statistically significant association was found for BMI change in middle or late adulthood or for BMI change in any life period in men. Our findings indicate that genetic predisposition exerts a persistent effect on adiposity throughout adult life and increases early adulthood weight gain in women. [ABSTRACT FROM AUTHOR]