Role of Metabolic Risk Factors, Family History, and Genetic Polymorphisms (PPARγ and TCF7L2) on Type 2 Diabetes Mellitus Risk in an Asian Indian Population.

INTRODUCTION: Women with family history of diabetes (FHD) are at significantly increased risk of developing gestational diabetes mellitus which may eventually lead to type 2 diabetes mellitus (T2DM) in later life. OBJECTIVE: This study investigates the role of FHD on metabolic markers and gene polymorphisms and hence on T2DM susceptibility in nondiabetic pregnant women and the subsequent risks in their newborns. MATERIALS AND METHODS: The present study was conducted on 200 healthy (nondiabetic and normotensive) adult Asian Indian women, including 100 with and 100 without FHD, living in and around Kolkata, India. During the gestational period, they were studied twice and followed up till delivery. During delivery, both mothers' venous blood and cord blood were collected to estimate serum CRP, glucose, and lipid profiles of the respective mothers and their newborns. Genotyping of PPARγ and TCF7L2 polymorphisms was done from these blood samples. RESULTS: A comparison of the metabolic variables among the subjects with and without FHD revealed significant differences among them. We also found close relationship between mothers and their newborn babies in terms of both PPARγ (rs1801282) C/G and TCF7L2 (rs7903146) C/T polymorphisms. More specifically, genotyping results for mothers with FHD and their newborn babies showed high concordance in inheritance of alleles: (i) for PPARγ via the risk allele G (74.0%) which is carried over to the newborn babies (64.5%) and (ii) for TCF7L2 via the risk allele T (73.0%) which is carried over to the newborn babies (68.5%). CONCLUSION: This study leads to the conclusion that Asian Indian women population based in Kolkata, India, are ethnically and genetically predisposed to the risk factors of diabetes through FHD, which is reflected in their gestational phase, and it has a significant implication on their birth outcomes.

Mycobacterial heat shock protein 65 mediated metabolic shift in decidualization of human endometrial stromal cells.

Successful implantation is dependent on the appropriate decidualization of endometrial stromal cells for the establishment of pregnancy in women. Mycobacterial heat shock protein 65 (HSP65) is involved in pathogenesis of the genital tuberculosis (GTB), one of the common causes of infertility in emerging countries. Though implantation failure appears to be the major cause, understanding the status of decidualizaiton process in women diagnosed with GTB has not been thoroughly addressed. We, therefore, explored the effect of HSP65 protein on the endometrial cell metabolism during in vitro decidualization. In order to identify the cellular metabolism of decidual cells with and without HSP65 treatment, proton NMR based characterization of metabolites extracted from cells and culture media were performed. In presence of HSP65, significant reduction in the decidual phenotype of endometrial stromal cells and prolactin expression is suggestive of impairment in decidualization. The intracellular and extracellular metabolic changes in HSP65 treated endometrial stromal cells produced a distinct pattern, reflecting the interaction between the protein and cellular metabolism. HSP65 mediated dysregulation in cellular metabolism is associated with poor decidualization. Besides enriching the present knowledge on metabolic changes underlying stromal cells decidualization, these findings assist in identifying potential molecular causes for decidualization failure in GTB women.

Serum metabolomics of Indian women with polycystic ovary syndrome using 1H NMR coupled with a pattern recognition approach.

Polycystic ovary syndrome (PCOS) is one of the most commonly occurring metabolic and endocrinological disorders affecting women of reproductive age. Metabolomics is an emerging field that holds promise in understanding disease pathophysiology. Recently, a few metabolomics based studies have been attempted in PCOS patients; however, none of them have included patients from the Indian population. The main objective of this study was to investigate the serum metabolomic profile of Indian women with PCOS and compare them with controls. Proton nuclear magnetic resonance (1H NMR) was used to first identify the differentially expressed metabolites among women with PCOS from the Eastern region of India during the discovery phase and further validated in a separate cohort of PCOS and control subjects. Multivariate analysis of the binned spectra indicated 16 dysregulated bins in the sera of these women with PCOS. Out of these 16 bins, 13 identified bins corresponded to 12 metabolites including 8 amino acids and 4 energy metabolites. Amongst the amino acids, alanine, valine, leucine and threonine and amongst the energy metabolites, lactate and acetate were observed to be significantly up-regulated in women with PCOS when compared with controls. The remaining 4 amino acids, l-glutamine, proline, glutamate and histidine were down-regulated along with 2 energy metabolites: glucose and 3-hydroxybutyric acid. Our findings showed dysregulations in the expression of different metabolites in the serum of women with PCOS suggesting the involvement of multiple pathways including amino acid metabolism, carbohydrate/lipid metabolism, purine and pyrimidine metabolism and protein synthesis.

Mass spectrometry and bioinformatics analysis data.

2DE and 2D-DIGE based proteomics analysis of serum from women with endometriosis revealed several proteins to be dysregulated. A complete list of these proteins along with their mass spectrometry data and subsequent bioinformatics analysis are presented here. The data is related to "Investigation of serum proteome alterations in human endometriosis" by Dutta et al. [1].

Investigation of serum proteome alterations in human endometriosis.

Endometriosis is a common benign gynecological disease, characterized by proliferation of functional endometrial glands and stroma outside the uterine cavity. The present study involves investigation of alterations in the serum proteome of endometriosis patients compared to healthy controls using 2DE and 2D-DIGE combined with MALDI TOF/TOF-MS. Comparison of serum proteome of endometriosis patients and healthy subjects revealed 25 significant differentially expressed proteins. Gene ontology and network analysis, performed using PANTHER, DAVID, WebGestalt and STRING, revealed that the differentially expressed proteins are majorly involved in response to stimulus, immune system, metabolic, localization and cellular processes. For serum diagnostic marker identification, several robust statistical screening procedures were applied to identify the set of the most significant proteins responsible for successful diagnosis of different endometriosis stages. Partial least squares (PLS) based marker selection tool and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to identify the most significant proteins for disease prediction. Western blotting validation in a separate cohort of patients revealed that haptoglobin (HP), Ig kappa chain C region (IGKC), alpha-1B-glycoprotein (A1BG) can be considered effective serum protein markers for the diagnosis of Stage II, III and IV endometriosis. For diagnosis of Stage I, only IGKC and HP seemed promising. BIOLOGICAL SIGNIFICANCE: Globally, about 12 in 100 women of reproductive age are diagnosed with endometriosis. The pathogenesis of the disease still remains unclear, leading to non-specific therapeutic approaches for disease management. Moreover, there is a delay of 8-12years in correct diagnosis after the initial onset of symptoms leading to a considerable impact on the woman's lifestyle. Also, the gold standard for diagnosis of endometriosis, laparoscopy, is an invasive procedure. The value of a noninvasive or semi-invasive diagnostic test for endometriosis with easily accessible fluids such as plasma, serum, urine, and saliva is, therefore, rightfully recognized. The present study is expected to considerably improve the understanding of the disease pathogenesis along with improved diagnostics and therapeutic approaches leading to better management of the disease.

A metabonomics approach as a means for identification of potential biomarkers for early diagnosis of endometriosis.

Our present study focuses on the identification of predictive biomarkers in serum for the early diagnosis of endometriosis in a minimally invasive manner using (1)H-NMR based metabonomics. PLS-DA modeling of bins obtained from CPMG spectra of serum samples discriminated endometriosis patients from controls with sensitivity and specificity levels of about 80% and 90%, respectively. Compared with those from controls, serum samples from endometriosis patients showed increased levels of lactate, 3-hydroxybutyrate, alanine, leucine, valine, threonine, lysine, glycerophosphatidylcholine, succinic acid and 2-hydroxybutyrate as well as decreased levels of lipids, glucose, isoleucine and arginine. Our work offers valuable information for non-invasive diagnosis of endometriosis and may be of potential benefit to understand pathogenesis of the disease.