Plasma retinol-binding protein 4 in the first and second trimester and risk of gestational diabetes mellitus in Chinese women: a nested case-control study.
ABSTRACT: Background:To assess the association between plasma retinol-binding protein 4 (RBP4) levels both in the first trimester and second trimester and risk of gestational diabetes mellitus (GDM). Methods:Plasma RBP4 levels and insulin were measured among 135 GDM cases and 135 controls nested within the Peking University Birth Cohort in Tongzhou. Multivariable linear regression analysis was conducted to assess the influence of RBP4 levels on insulin resistance. Conditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence interval (CI) between RBP4 levels and risk of GDM. Results:The GDM cases had significantly higher levels of RBP4 in the first trimester than controls (medians: 18.0??g/L vs 14.4??g/L; P?
Project description:OBJECTIVE:To examine the effects of dynamic change in fetuin-A levels before the diagnosis of gestational diabetes mellitus (GDM) on insulin resistance and GDM. RESEARCH DESIGN AND METHODS:A total of 135 women with GDM and 135 normal glucose tolerance (NGT) women with matched age (±2 years old) and gestational age at taking the oral glucose tolerance test (OGTT) were included in this nested case-control study. Fasting venous blood samples were collected at the prenatal visit of the first trimester and during OGTT of the second trimester. Plasma concentration of fetuin-A and insulin was determined. RESULTS:The plasma fetuin-A concentration in women with GDM was significantly higher than NGT controls in both the first trimester (medians: 403.0?pg/mL vs 273.4?pg/mL; p<0.05) and the second trimester (medians: 475.7?pg/mL vs 290.8?pg/mL; p<0.05) and notably increased from the first to the second trimester. Multivariate linear regression analysis showed that the change in fetuin-A concentration was associated with the changes in fasting insulin, homeostasis model assessment (HOMA) of insulin resistance, and HOMA of ?-cell function (HOMA-?) (p<0.05). The highest quartile of the increase in fetuin-A concentration from the first to the second trimester was associated with a higher risk of developing GDM compared with the lowest quartile (OR 2.14; 95%?CI 1.05 to 4.37). CONCLUSIONS:The dynamic change in fetuin-A levels was associated with the changes in insulin resistance and ?-cell function from the first to the second trimester, and was associated with an increased risk of the development of GDM, indicating that fetuin-A could be a biomarker to predict the risk of GDM. TRIAL REGISTRATION NUMBER:NCT03814395.
Project description:Retinol-binding protein-4 (RBP4) has been reported to be potentially involved in the pathogenesis of gestational diabetes mellitus (GDM); however, the findings are inconsistent. Our aims were to review the studies that investigated the association of serum levels and polymorphisms of RBP4 with GDM risk, and to provide recommendations for future research.The databases PubMed, EBSCO, ScienceDirect, and Web of Knowledge were searched up to October 2015 to find out studies evaluating the relationship between serum RBP4 level/ RBP4 polymorphisms and GDM risk. In the meta-analysis of serum RBP4 levels the key inclusion was that studies were designed as BMI-matched studies or had observed non-significant differences in BMI between cases and controls.Fourteen case-control studies (647 cases and 620 controls) reporting the association between serum RBP4 level and GDM risk, and three studies (1012 cases and 1605 controls) investigating the association between RBP4 polymorphisms and GDM risk were involved. Our results showed that high serum RBP4 levels represent a risk factor for GDM (pooled standardized mean difference =0.758, 95% confidence interval [0.387, 1.128]). The results of subgroup analyses based on "gestational age at blood sampling" or "diagnostic criteria" are consistent with the overall results. However, the postpartum subgroup and "before 24 weeks" subgroup both only include one article and indicate no association between serum RBP4 level and GDM risk. The meta-analysis on the association between rs3758539 polymorphism and GDM risk shows that RBP4 rs3758539 polymorphism is not associated with the development of GDM.The results of this meta-analysis support the hypothesis that RBP4 is a modest independent risk factor for GDM (i.e., nonobese patients with GDM might express RBP4 at abnormal levels). The serum RBP4 level is associated with the risk of GDM. However, the association in the first-trimester and postpartum period should be validated by further research. The association between RBP4 rs3758539 polymorphism and GDM risk was not confirmed.
Project description:OBJECTIVE: This study aimed to examine possible genetic effects of some retinol binding protein-4 (RBP4) single nucleotide polymorphisms (SNPs) on the risk of gestational diabetes mellitus (GDM). In addition, the SNPs were examined for their possible association with insulin resistance at 6 weeks after delivery. METHODS: This was a prospective study of 100 women with GDM and 100 participants with normal gestation who were evaluated at gestational week 30 and 6 weeks postpartum. Three SNPs of RBP4 (rs3758539, rs116736522, and rs34571439) were genotyped using TaqMan assay. The genotype distributions between GDM patients and normal controls were analyzed using logistic regression models. In addition, differences in clinical characteristics among subjects grouped by genotype were assessed using the analysis of covariance test. RESULTS: The frequencies of the rare alleles were not significantly different between GDM patients and controls. However, we identified two variants rs3758539 and rs34571439 associated with insulin levels and insulin resistance in women with previous GDM. CONCLUSION: Noncoding SNPs of the RBP4 gene are not associated with GDM, but two SNPs showed associations with insulin resistance and insulin levels in women with prior GDM. Additional studies with increased sample size will be necessary in other GDM cohorts.
Project description:Background:Solute carrier family 2 member 4- (SLC2A4-) retinol binding protein-4- (RBP4-) phosphoenolpyruvate carboxykinase 1 (PCK1)/phosphoinositide 3-kinase (PI3K) is an adipocyte derived "signalling pathway" that may contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). We explored whether single nucleotide polymorphisms (SNPs) of these "signalling pathway" genes are associated with gestational diabetes mellitus (GDM). Methods:Case-control studies were conducted to compare GDM and control groups. A total of 334 cases and 367 controls were recruited. Seventeen candidate SNPs of the pathway were selected. Chi-square tests, logistic regression, and linear regression were used to estimate the relationships of SNPs with GDM risk and oral glucose tolerance test (OGTT), fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) levels. Model-based multifactor dimensionality reduction was used to estimate the adjusted interactions between genes. Regression and interaction analyses were adjusted by maternal age, prepregnancy BMI, and weekly BMI growth. The Bonferroni correction was applied for multiple comparisons. Results:RBP4 rs7091052 was significantly associated with GDM risk. SLC2A4 rs5435, RBP4 rs7091052, PCK1 rs1042531 and rs2236745, and PIK3R1 (coding gene of the PI3K P85 subunit) rs34309 were associated with OGTT, fasting insulin, and HOMA-IR levels in the linear regression analysis. The gene-gene interaction analysis showed that, compared with pregnant women with other genotype combinations, women with SLC2A4 rs5435 (CC/CT), RBP4 rs7091052 (CC), PCK1 rs1042531 (TT/TG) and rs2236745 (TT), and PIK3R1 rs34309 (AA) had lower GDM risk. Conclusion:SLC2A4, RBP4, PCK1, and PIK3R1 genes may be involved in the pathogenesis of GDM.
Project description:<h4>Objective</h4>Fatty acid-binding protein 4 (FABP4) has been proposed to be a potential predictive factor of gestational hypertension or preeclampsia (GH/PE) because of its integrating metabolic and inflammatory responses. Women with gestational diabetes mellitus (GDM) are more likely to develop both GH/PE, than the normal population. The aim of our study was to examine the relationship between plasma FABP4 in the second trimester of pregnancy and the risk of GH/PE in women with GDM.<h4>Methods</h4>This was a nested case-control study conducted within a large on-going prospective cohort study conducted at Peking University First Hospital. A total of 1344 women, who were diagnosed with GDM, according to a 75 g oral glucose tolerance test, participated in the GDM One-Day Clinic at Peking University First Hospital from February 24, 2016 to February 9, 2017. Of the 748 GDM women who agreed to the blood sample collection, 637 were followed until their delivery. The cases included GDM patients who developed gestational hypertension or preeclampsia (GDM-GH/PE group, n = 41). Another 41 matched GDM women without major complications were selected as the control group (GDM group).<h4>Results</h4>The incidence of GH/PE was 6.44% and 3.30% for preeclampsia. The level of the second trimester plasma FABP4 in the GDM-GH/PE group was significantly higher than the GDM group (17.53±11.35 vs. 12.79±6.04 ng/ml, P = 0.020). The AUC ROC for the second trimester plasma FABP4 predicted GH/PE in the GDM patients alone was 0.647 (95%CI 0.529-0.766). Multivariate analysis showed that the elevated second trimester FABP4 level was independently associated with GH/PE in the GDM patients (OR 1.136 [95% CI 1.003-1.286], P = 0.045).<h4>Conclusions</h4>Increased second trimester plasma FABP4 independently predicted GH/PE in GDM patients.
Project description:<h4>Aims</h4>To determine the relationship between thyroid markers during pregnancy and gestational diabetes mellitus (GDM) or post-partum glucose metabolism.<h4>Materials and methods</h4>Based on pregnancy 75-g oral glucose tolerance test (OGTT) results, 1467 subjects were grouped into normal glucose tolerance (NGTp; n = 768) and GDM (n = 699) groups. Furthermore, based on post-partum 75-g OGTT results, 286 GDM subjects, screened for glucose metabolism after delivery, were grouped into NGTd (n = 241) and abnormal glucose tolerance (AGT; n = 45) groups.<h4>Results</h4>Maternal age, family history of diabetes, acanthosis nigricans, previous adverse pregnancy outcomes and caesarean section incidence, and thyroid positive antibody rates were higher in the GDM group than in the NGTp group. In the first trimester, free triiodothyronine (FT3), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels were higher in the GDM group than in the NGTp group. In the second trimester, free thyroxine (FT4) levels were lower and TPOAb and TgAb levels were higher in the GDM group than in the NGTp group. After adjusting for confounding factors, FT3, TPOAb and TgAb (first trimester), and FT4, TPOAb and TgAb (second trimester) were risk factors for GDM. TPOAb and TgAb levels were higher in the AGT group than in the NGTd group and were potential predictors of abnormal post-partum glucose tolerance.<h4>Conclusions</h4>GDM risk significantly increased with increased FT3 (first trimester), TPOAb and TgAb (first and second trimesters) or with decreased FT4 (second trimester). Presence of thyroid antibodies predicted post-partum glucose abnormalities in subjects with GDM.
Project description:<h4>Aims</h4>To evaluate the clinical utility of first and second trimester prenatal screening biomarkers for early pregnancy prediction of gestational diabetes mellitus (GDM) risk in nulliparous women.<h4>Methods</h4>We conducted a population-based cohort study of nulliparous women participating in the California Prenatal Screening Program from 2009 to 2011 (n = 105,379). GDM was ascertained from hospital discharge records or birth certificates. Models including maternal characteristics and prenatal screening biomarkers were developed and validated. Risk stratification and reclassification were performed to assess clinical utility of the biomarkers.<h4>Results</h4>Decreased levels of first trimester pregnancy-associated plasma protein A (PAPP-A) and increased levels of second trimester unconjugated estriol (uE<sub>3</sub>) and dimeric inhibin A (INH) were associated with GDM. The addition of PAPP-A only and PAPP-A, uE<sub>3</sub>, and INH to maternal characteristics resulted in small, yet significant, increases in area under the receiver operating characteristic curve (AUC) (maternal characteristics only: AUC 0.714 (95% CI 0.703-0.724), maternal characteristics + PAPP-A: AUC 0.718 (95% CI 0.707-0.728), maternal characteristics + PAPP-A, uE<sub>3</sub>, and INH: AUC 0.722 (0.712-0.733)); however, no net improvement in classification was observed.<h4>Conclusions</h4>PAPP-A, uE<sub>3</sub>, and INH have limited clinical utility for prediction of GDM risk in nulliparous women. Utility of other readily accessible clinical biomarkers in predicting GDM risk warrants further investigation.
Project description:<b>Objective: </b>Inflammation-related factors have been shown to play a significant role throughout pregnancy. In this study, we aimed to explore the relationships between selected inflammatory cytokines and gestational diabetes (GDM) in Chinese pregnant women.<br><br><b>Design and methods: </b>This was a 1:1 matched case-control study that included 200 pairs of subjects in the second trimester and 130 pairs of subjects in the third trimester. Serum levels of nerve growth factor (NGF), Interleukin-6 (IL-6), leptin, Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-?) and Interleukin-1beta (IL-1?) were measured by enzyme immunoassay. The associations of these inflammatory factors with metabolic parameters were analysed.<br><br><b>Results: </b>In the second trimester, GDM patients had higher NGF levels and lower IL-8 levels than did normal controls (P?<?0.001 and P?=?0.015, respectively). However, in the third trimester, only lower leptin levels were observed in the GDM group (P?=?0.031). Additionally, in the second trimester, NGF levels were not only positively associated with fasting, 1-h and 2-h glucose levels and the area under curve of glucose, but also positively related to insulin sensitivity and secretion, as suggested by fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment index of ?-cell secretion (HOMA-?) (all P?<?0.05). Moreover, IL-6 and leptin levels were positively correlated with HOMA-IR and HOMA-?, and TNF-? levels were positively related to HOMA-IR (all P?<?0.05). Except for the relationships between NGF and HOMA-? and TNF-? and HOMA-IR, the other correlations still existed even after adjusting for confounding factors (all P?<?0.05).<br><br><b>Conclusion: </b>In addition to the positive associations of IL-6 and leptin with insulin resistance and secretion, NGF was higher in the GDM patients and strongly linked to glucose metabolism, insulin resistance and pancreatic ? cell function in Chinese pregnant women in the second trimester.
Project description:Screening for gestational diabetes mellitus (GDM) during pregnancy is cumbersome. Measurement of plasma fructosamine may help simplify the first step of detecting GDM. We aimed to assess the predictive value of mid-pregnancy fructosamine for GDM, and its association with postpartum glycemic indices. Among 1488 women from Project Viva (mean ± SD: 32.1 ± 5.0 years old; pre-pregnancy body mass index 24.7 ± 5.3 kg/m²), we measured second trimester fructosamine and assessed gestational glucose tolerance with a 50 g glucose challenge test (GCT) followed, if abnormal, by a 100 g oral glucose tolerance test (OGTT). Approximately 3 years postpartum (median 3.2 years; SD 0.4 years), we measured maternal glycated hemoglobin (n = 450) and estimated insulin resistance (HOMA-IR; n = 132) from fasting blood samples. Higher glucose levels 1 h post 50 g GCT were associated with higher fructosamine levels (Pearson's r = 0.06; p = 0.02). However, fructosamine ?222 µmol/L (median) had a sensitivity of 54.8% and specificity of 48.6% to detect GDM (area under the receiver operating characteristic curve = 0.52); other fructosamine thresholds did not show better predictive characteristics. Fructosamine was also weakly associated with 3-year postpartum glycated hemoglobin (per 1 SD increment: adjusted ? = 0.03 95% CI [0.00, 0.05] %) and HOMA-IR (per 1 SD increment: adjusted % difference 15.7, 95% CI [3.7, 29.0] %). Second trimester fructosamine is a poor predictor of gestational glucose tolerance and postpartum glycemic indices.
Project description:Retinol-binding protein 4 (RBP4) may play an important role in the origin of insulin resistance and metabolic syndrome. Few prospective data are available on the relationship between RBP4 and coronary heart disease (CHD). Furthermore, previous studies did not distinguish among full-length and truncated forms of RBP4 that might have various biological activities.We measured plasma levels of full-length and several C-terminally truncated subfractions of RBP4 among 468 women who developed CHD and 472 matched controls in the Nurses' Health Study cohort during 16 years of follow-up (1990-2006). We observed a temporal variation in the association of full-length RBP4 levels with CHD risk (P=0.04 for testing proportional hazard assumption). In the first 8 years of follow-up, after multivariate adjustment for covariates, the odds ratio of CHD risk comparing extreme quartiles of full-length RBP4 levels was 3.56 (95% confidence interval, 1.21-10.51; Ptrend=0.003), whereas this association was 0.77 (95% confidence interval, 0.38-1.56; Ptrend=0.44) in the follow-up period of 9 to 16 years. Results were similar for total RBP4 levels (summed levels of all RBP4 isoforms). Levels of the primary truncated isoform, RBP4-L, were not associated with CHD risk in any follow-up period; the odds ratios for extreme quartiles were 1.29 (95% confidence interval, 0.50-3.32) and 1.20 (95% confidence interval, 0.64-2.26) in the first and second 8 years of follow-up, respectively.In this cohort of women, higher circulating full-length and total RBP4 levels were associated with increased risk of CHD in a time-dependent fashion. Additional data are warranted to confirm the present findings.