Identification of Proteomic Biomarkers in Maternal Plasma in the Early Second Trimester That Predict the Subsequent Development of Gestational Diabetes

Kim, Sun Min; Park, Joong Shin; Norwitz, Errol R.; Lee, Seoung Mi; Kim, Byoung Jae; Park, Chan-Wook; Jun, Jin Yong; Kim, Chul Woo; Syn, Hee Chul

doi:10.1177/1933719111417889

Cited by 25 publications

(24 citation statements)

References 36 publications

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“…Mass spectrometry affords a more sensitive method than standard biochemical approaches (eg, ELISA assays) to evaluate more subtle changes in protein composition [18]. Our results are concordant with a recent study by Kim and colleagues reporting early changes in apolipoproteins in GDM cases using a comparable mass spectrometry approach [19]. Studies in biomarker development have increasingly highlighted the need for multiple diagnostic targets to improve detection [3].…”

Section: Discussionsupporting

confidence: 82%

Impaired lipid transport in gestational diabetes mellitus

Nichols¹,

Lutgendorf²,

Mesngon³

et al. 2013

J Diab Res Clin Met

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Background: Gestational diabetes mellitus (GDM) complicates 5-6% of pregnancies, placing affected individuals at higher risk for pregnancy-related complications and persistent metabolic and cardiovascular disorders later in life. In this study, we evaluated the association between apolipoproteins and plasma cholesterol levels in patients with gestational diabetes compared to uncomplicated controls over the course of pregnancy. Methods: Plasma was prospectively collected from 311 nulligravid women during 3 time periods during pregnancy (4-12, 16-22 and 24-28 weeks gestation). Mass spectrometry and enzyme-linked immunosorbant assays (ELISA) were used to measure the relative and absolute changes in apolipoprotein abundance. High density lipoprotein (HDL) and very low/low density lipoprotein (LDL/VLDL) cholesterol levels were quantified by enzymatic assay. Mann Whitney U tests were used to determine statistical significance (p<0.05). Results: Five cases of GDM were identified (mean 1-hour blood glucose concentration = 163.2 +/-7.3 mg/dL). In the control subjects, plasma concentrations of Apo A-II measured by ELISA marginally increased from 4-12 weeks to 24-28 weeks, while concentrations did not significantly increase in GDM subjects. Likewise, VLDL/LDL cholesterol levels increased in the controls but not in the GDM cohort (p=0.005). HDL cholesterol was not significantly different between cohorts. Mass spectrometry spectral patterns identified Apo A-II dimers, Apo A-II monomers and 3 forms of Apo C-III (asialylated Apo C-III 0 , monosialylated Apo C-III 1 and disialylated Apo C-III 2 ) in patient plasma. In GDM cases, Apo A-II dimers were significantly lower than controls in the second trimester (p<0.05). While both Apo A-II monomer and asialylated Apo C-III 0 increased steadily over gestational time in the control subjects (p<0.05), GDM cases showed no statistical change in either protein between trimesters 1, 2 and 3. Conclusions: The rate of change over gestational time for the apolipoproteins and VLDL/LDL cholesterol was significantly lower in GDM cases than uncomplicated controls, indicating that the normal hyperlipidemia of pregnancy is disrupted in GDM. Our results support a role for impaired lipid transport and homeostasis in GDM and may suggest a potential diagnostic and therapeutic target.

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Section: Discussionsupporting

confidence: 82%

Impaired lipid transport in gestational diabetes mellitus

Nichols¹,

Lutgendorf²,

Mesngon³

et al. 2013

J Diab Res Clin Met

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“…2) [37][38][39]. The best independent predictive apolipoproteins were Apo M, Apo D and Apo L1 (Tables 2 and 3); the performance of Apo M and Apo L1 depended on BMI grouping.…”

Section: Discussionmentioning

confidence: 95%

First-trimester multimarker prediction of gestational diabetes mellitus using targeted mass spectrometry

et al. 2016

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Aims/hypothesis Gestational diabetes mellitus (GDM) is associated with an increased risk of pre-eclampsia, macrosomia and the future development of type 2 diabetes mellitus in both mother and child. Although an early and accurate prediction of GDM is needed to allow intervention and improve perinatal outcome, no single protein biomarker has yet proven useful for this purpose. In the present study, we hypothesised that multimarker panels of serum proteins can improve firsttrimester prediction of GDM among obese and non-obese women compared with single markers. Methods A nested case-control study was performed on firsttrimester serum samples from 199 GDM cases and 208 controls, each divided into an obese group (BMI ≥27 kg/m 2 ) and a non-obese group (BMI <27 kg/m 2 ). Based on their biological relevance to GDM or type 2 diabetes mellitus or on their previously reported potential as biomarkers for these diseases, a number of proteins were selected for targeted nano-flow liquid chromatography (LC) MS analysis. This resulted in the development and validation of a 25-plex multiple reaction monitoring (MRM) MS assay. Results After false discovery rate correction, six proteins remained significantly different (p<0.05) between obese GDM patients (n=135) and BMI-matched controls (n=139). These included adiponectin, apolipoprotein M and apolipoprotein D. Multimarker models combining protein levels and clinical data were then constructed and evaluated by receiver operating characteristic (ROC) analysis. For the obese, nonobese and all GDM groups, these models achieved marginally higher AUCs compared with adiponectin alone. Conclusions/interpretation Multimarker models combining protein markers and clinical data have the potential to predict women at a high risk of developing GDM.

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“…Three dysregulated protein markers including haptoglobin, protein SMG8 and apoptosis inducing factor-1were identified indicating their association with both GDM and PIH [51]. Another study using SELDI-TOF and ESI/Tandem MS identified two apolipoproteins, apoCIII and apoAII as potential proteomic biomarkers in plasma of GDM patients since the two proteins varied considerably in their concentration between normal and diseased patients [52]. It is worthwhile to mention that increased level of apoCIII is associated with dyslipidemia, a condition often found in women with GDM.…”

Section: Proteomic Biomarkers Of Gdmmentioning

confidence: 99%