Pancreatic Beta Cell Function in Infants Varies by Maternal Weight.

The Asian Indian Beta Cell function (ABCs) in Infants Study examined the associations of maternal weight on infant pancreatic beta cell function across 7 months postpartum. Pregnant women aged 18-35 years were recruited in Hyderabad, India. Women were classified by first trimester weight as underweight (UW), BMI < 18.5 kg/m2; normal weight (NW), BMI 18.5-22.9 kg/m2; or overweight (OW), BMI 23.0 through <28.5 kg/m2. At age > 7 months, infants had an oral glucose tolerance test (OGTT, 1.75 g glucose/kg bodyweight) following a 3 h fast. Infant blood samples were assayed for C-peptide and glucose. Infant beta cell function (HOMA2-B; disposition index, DI) and insulin resistance (HOMA2-IR) were compared across maternal weight groups. Mothers (UW n = 63; NW n = 43; OW n = 29) had similar age at delivery and second trimester 50 g glucose challenge test results. Cord HOMA2-B values were 51% greater for IUW (83.5, SD 55.2) and 44% greater for IOW (79.9, SD 60.8) vs. INW (55.4, SD 51.5), forming a U-shaped relationship between maternal weight and HOMA2-B. No qualitative differences in HOMA2-IR were found at birth. However, at 7 months postpartum, HOMA2-IR changed most within IUW (-64% median reduction) and changed the least in IOW (-7% median reduction). At seven months postpartum, DI was higher in IUW vs. the other groups (geometric mean IUW 1.9 SD 2.5; INW 1.3 SD 2.6 or vs. IOW mean 1.2 SD 3.7), reflecting a +49% difference in DI. Evidence from this study illustrates adaptations in the pancreatic functional response of infants associated with the maternal nutritional environment.

Correlation of plasma nitrite/nitrate levels and inducible nitric oxide gene expression among women with cervical abnormalities and cancer.

Cervical cancer is caused by infection with high risk human papillomavirus (HR-HPV). Inducible nitric oxide synthase (iNOS), a soluble factor involved in chronic inflammation, may modulate cervical cancer risk among HPV infected women. The aim of the study was to measure and correlate plasma nitrite/nitrate levels with tissue specific expression of iNOS mRNA among women with different grades of cervical lesions and cervical cancer. Tissue biopsy and plasma specimens were collected from 120 women with cervical neoplasia or cancer (ASCUS, LSIL, HSIL and invasive cancer) and 35 women without cervical abnormalities. Inducible nitric oxide synthase (iNOS) mRNA from biopsy and plasma nitrite/nitrate levels of the same study subjects were measured. Single nucleotide polymorphism (SNP) analysis was performed on the promoter region and Ser608Leu (rs2297518) in exon 16 of the iNOS gene. Differences in iNOS gene expression and plasma nitrite/nitrate levels were compared across disease stage using linear and logistic regression analysis. Compared to normal controls, women diagnosed with HSIL or invasive cancer had a significantly higher concentration of plasma nitrite/nitrate and a higher median fold-change in iNOS mRNA gene expression. Genotyping of the promoter region showed three different variations: A pentanucleotide repeat (CCTTT) n, -1026T > G (rs2779249) and a novel variant -1153T > A. These variants were associated with increased levels of plasma nitrite/nitrate across all disease stages. The higher expression of iNOS mRNA and plasma nitrite/nitrate among women with pre-cancerous lesions suggests a role for nitric oxide in the natural history of cervical cancer.

Shedding of Epstein-Barr virus and cytomegalovirus from the genital tract of women in a periurban community in Andhra Pradesh, India.

We found a large number of false-positive readings by visual inspection with acetic acid (VIA) in a study of cervical cancer screening strategies (VIA, human papillomavirus HPV DNA testing, and Pap cytology) in a periurban community in Andhra Pradesh, India. We evaluated whether these false-positive readings might be occurring as a result of infections with Epstein-Barr virus (EBV) or cytomegalovirus (CMV), prevalent latent herpesviruses known to be shed from the female genital tract. While we found that there was no association between VIA results and the presence of EBV or CMV in the cervix, we did find a high prevalence of both viruses: 20% for EBV and 26% for CMV. In multivariate analyses, CMV prevalence was associated with younger age, lack of running water in the home, and visually apparent cervical inflammation. EBV prevalence was associated with older age and a diagnosis of cervical intraepithelial neoplasia grade 1 or greater. The biological and clinical implications of these viruses at the cervix remain to be determined. The strong association between the presence of EBV and cervical disease warrants future exploration to determine whether EBV plays a causal role in disease development or if it is merely a bystander in the process.

Effectiveness of VIA, Pap, and HPV DNA testing in a cervical cancer screening program in a peri-urban community in Andhra Pradesh, India.

BACKGROUND: While many studies have compared the efficacy of Pap cytology, visual inspection with acetic acid (VIA) and human papillomavirus (HPV) DNA assays for the detection cervical intraepithelial neoplasia and cancer, few have evaluated the program effectiveness. METHODS AND FINDINGS: A population-based sample of 5603 women from Medchal Mandal in Andhra Pradesh, India were invited to participate in a study comparing Pap cytology, VIA, and HPV DNA screening for the detection of CIN3+. Participation in primary screening and all subsequent follow-up visits was rigorously tracked. A 20% random sample of all women screened, in addition to all women with a positive screening test result underwent colposcopy with directed biopsy for final diagnosis. Sensitivity, specificity, positive and negative predictive values were adjusted for verification bias. HPV testing had a higher sensitivity (100%) and specificity (90.6%) compared to Pap cytology (sensitivity  =  78.2%; specificity = 86.0%) and VIA (sensitivity = 31.6%; specificity = 87.5%). Since 58% of the sample refused involvement and another 28% refused colposcopy or biopsy, we estimated that potentially 87.6% of the total underlying cases of CIN3 and cancer may have been missed due to program failures. CONCLUSIONS: We conclude that despite our use of available resources, infrastructure, and guidelines for cervical cancer screening implementation in resource limited areas, community participation and non-compliance remain the major obstacles to successful reduction in cervical cancer mortality in this Indian population. HPV DNA testing was both more sensitive and specific than Pap cytology and VIA. The use of a less invasive and more user-friendly primary screening strategy (such as self-collected swabs for HPV DNA testing) may be required to achieve the coverage necessary for effective reduction in cervical cancer mortality.