The association between serum selenium and gestational diabetes mellitus: A systematic review and meta-analysis

BackgroundResults of the studies about association between serum selenium concentration and gestational hyperglycemia are inconsistent. Some studies have demonstrated that women with gestational diabetes mellitus (GDM) have lower Se concentrations while contrary results are reported in other studies.AimThe aim of this study is to compare the serum Se concentration in women with GDM and normoglycemic pregnant women via a systematic review and meta-analysis.MethodsA computerized literature search on four databases (PubMed, Cochrane register of control trials, Scopus and Google scholar) was performed from inception through August 2013. Necessary data were extracted and random effects model was used to conduct the meta-analysis.ResultsSix observational studies (containing 147 women with GDM and 360 normoglycemic pregnant women) were found, which had compared serum Se concentration in women suffering from GDM with normal pregnant ones. Our meta-analysis revealed that serum Se concentration was lower in women with GDM compared to normoglycemic pregnant women (Hedges = −1.34; 95% CI: −2.33 to −0.36; P < 0.01). Stratified meta-analysis demonstrated that concentration of Se in the sera of women with GDM was lower than normal pregnant women both in second and third trimesters, but the result was not significant in second trimester (second trimester: Hedges = −0.68; 95% CI: −1.60−0.25; P = 0.15, third trimester: Hedges = −2.81; 95% CI: −5.21 to −0.42; P < 0.05). It was also demonstrated that serum Se status was lower in pregnant women with impaired glucose tolerance (IGT) compared to normoglycemic pregnant women (Hedges = −0.85; 95% CI: −1.18 to −0.52).ConclusionThe available evidences suggest that serum Se concentration is significantly lower in pregnant women with gestational hyperglycemia compared to normal pregnant women.     

High iron level in early pregnancy increased glucose intolerance

High iron stores in pregnancy are essential in preventing negative outcomes for both infants and mothers; however the risk of gestational diabetes mellitus (GDM) might also be increased. We intend to study the relationship between increased iron stores in early pregnancy and the risk of glucose intolerance and GDM. This prospective, observational, single-hospital study involved 104 non-anemic pregnant women, divided into 4 groups based on the quartile values for ferritin at the first trimester of pregnancy. All participants were screened for GDM with 75-g oral glucose tolerance test (OGTT) at 24–28 weeks’ gestation. We observed that ferritin levels at early pregnancy were significantly correlated to glucose level after OGTT at 1-h and 2-h (rho = 0.21, p < 0.05; rho = 0.43, p < 0.001 respectively). Furthermore, in the higher quartile for ferritin (>38.8 μg/L) glycemia at 2-h OGTT was significantly higher than in the others quartiles (p = 0.002). In multivariate regression analysis, serum ferritin was a significant determinant of glycemia at 2-h OGTT. Although we did not find a significant association in the incidence of GDM in women with higher serum ferritin levels, probably in reason to the limit power of our study, our data demonstrated that the role of iron excess is tightly involved in the pathogenesis of glucose intolerance. We report for the first time that high ferritin values in early pregnancy are predictors of impaired glucose tolerance in non-anemic women. Individual iron supplementation should be evaluated in order to minimize glucose impairment risk in women with high risk of diabetes.     

Association of serum amyloid A levels with adipocyte size and serum levels of adipokines: Differences between men and women

The aim of this study was to characterize the association between adipocyte enlargement and circulating levels of serum amyloid A (SAA). Furthermore, we wanted to search for possible associations with measures of glycemic control and levels of circulating adipokines and/or inflammatory markers in men and women with a large range in body mass index. The study cohort consisted of 167 subjects, 114 non-diabetic and 53 with Type 2 diabetes. Adipocyte diameter as well as circulating levels of SAA, C-reactive protein (CRP), adiponectin, leptin, interleukin-6, tumor necrosis factor alpha, glucose and insulin were measured. Women had higher serum levels of SAA than men (p = 0.044). SAA levels were weakly but positively correlated with BMI (p = 0.043) and % body fat (p = 0.027) in all subjects as well as subcutaneous adipocyte diameter (p = 0.034) in women. Furthermore, in all subjects we found correlations between SAA levels and levels of CRP (p < 0.001), interleukin-6 (p < 0.001), leptin (p = 0.003), insulin (p = 0.006), HbA1c (p = 0.02) and HOMA-IR (p = 0.002). A majority of the correlations were strongest in women. In conclusion, serum levels of SAA are strongly correlated with serum levels of inflammatory markers as well as measures of glycemic control. There seems to be large sex differences in these associations suggesting that sex-specific factors need to be considered when analyzing SAA levels in relation to metabolic disease.     

Cord blood nesfatin-1 in large for gestational age pregnancies

ObjectiveTo investigate possible alterations in cord blood levels of adipokine nesfatin-1 (secreted by adipose tissue and pancreatic β-cells and implicated in glucose metabolism and insulin resistance), as well as insulin, in large (LGA) and appropriate for gestational age (AGA) pregnancies, granted that these groups differ in body fat mass and metabolic/endocrine mechanisms.Materials and methodsCord blood nesfatin-1 and insulin concentrations were prospectively measured in 40 LGA (9 born from diabetic and 31 from non-diabetic mothers) and 20 AGA singleton full-term infants as well as their mothers.ResultsCord blood nesfatin-1 concentrations were significantly lower in LGA compared to AGA neonates (b = ?0.206, SE 0.07, p = 0.005). However, cord blood nesfatin-1 concentrations were elevated in infants born from mothers with gestational diabetes mellitus (GDM), compared to those born from non-diabetic mothers, after controlling for group (b = 0.190, SE 0.10, p = 0.05). Finally, cord blood nesfatin-1 concentrations were lower in cases of vaginal delivery (b = 0.11, SE 0.05, p = 0.042). Insulin levels were significantly elevated, as customized centiles increased (b = 0.004, SE = 0.002, p = 0.016). No significant correlation was found between insulin and nesfatin-1 in maternal and umbilical cord levels.ConclusionsIn this study nesfatin-1 levels are decreased in LGA compared to AGA fetuses. Fetal nesfatin-1 concentrations are higher in cases of GDM and cord blood nesfatin-1 concentrations are lower in cases of vaginal delivery.     

Anthropometric and body composition characteristics during pregnancy: A study from West Bengal,India

The present cross-sectional study was aimed at investigating changes in anthropometric, body composition and blood pressure characteristics during pregnancy. A total of 406 healthy, pregnant women aged between 16 and 33 years participated in the study. Pregnant women were recruited from the outpatient department of the two-referral hospital in Bolpur subdivision of Birbhum district, West Bengal, India. Anthropometric measures such as height, weight, three circumferences and skinfold thickness at four sites (biceps, triceps, subscapular and suprailaic) were obtained using standard techniques. Percentages of body fat (%BF), intra abdominal visceral fat (IVF), basal metabolic rate (BMR) and body mass index (BMI) were measured using an Omron body fat analyser. Two forenoon blood pressure measurements were also taken and averaged for analysis. Subjects were categorized into three trimester groups: Group I, n = 30; Group II, n = 163; and Group III, n = 213. ANOVA with Scheffe's post-hoc test revealed that Group I had significantly lower mean than both Group II and Group III for systolic blood pressure and IVF, whereas Group I had significantly lower mean than Group III for BMI, BMR, %BF, diastolic blood pressure and skinfolds. The mean change in maternal weight from the first to the third trimester was merely 3 kg. Mean waist circumference varied from the first to the third trimester but not from the first to the second trimester. Furthermore, significantly increased systolic and diastolic blood pressure was observed across the trimesters. However, longitudinal studies involving interaction of body fat topography and pregnancy-induced hormones are required to further our understanding of gestation mechanism.     

Insertion and deletion polymorphism in the alpha-2B adrenoceptor gene in pregnant women ripens gestational diabetes mellitus

There are no earlier studies that reported the association of the 12Glu9 polymorphism in the alpha-2B adrenoceptor (ADRA2B) gene with gestational diabetes mellitus (GDM). We examined the potential association between the ADRA2B gene insertion/deletion (I/D) polymorphism in the Saudi population with GDM. Pregnant women with GDM have been reported to exhibit the same susceptibility as that observed in type 2 diabetes mellitus (T2DM). We have selected I/D polymorphism of the ADRA2B gene located in chromosome 2q11.1 that has been extensively related to T2DM and cardiovascular diseases. This case–control study was conducted with 200 GDM and 300 non-GDM pregnant women. Genotyping of I/D polymorphism was performed by conventional PCR method. Biochemical analyses were found to be significantly different between GDM and non-GDM subjects (p < 0.05). Genotype (ID + DD vs II, p = 0.0002) and allele (D vs I, p = 0.0002) frequencies of the 12Glu9 polymorphism were found to be statistically significant. However, a significant difference was found between allele and genotypes of I/D polymorphism of the ADRA2B gene or the clinical characteristics of the subjects. Our results obtained in this study indicate the ADRA2B gene in the Saudi women was associated with the development of GDM.     

Levels of serum pentraxin 3, IL-6, fetuin A and insulin in patients with rheumatoid arthritis

ObjectiveThe aim of this study was to investigate the relationship between disease severity and biochemical parameters such as pentraxin-3, fetuin-A, IL-6, insulin and HOMA-IR levels in patients with rheumatoid arthritis.MethodsThis study included 60 patients with RA and 20 healthy controls. Serum pentraxin-3, fetuin-A, IL-6 and insulin concentrations were measured. Also, HOMA-IR values were calculated. Disease activity was assessed with Disease Activity Score (DAS28). To evaluate quality of life, the Health Assessment Questionnaire disability index was applied.ResultsThe serum values for ESR, CRP, pentraxin-3 and fetuin-A in patients with RA were found to be higher than control subjects (p values = 0.001, 0.001, 0.000, 0.000, 0.01, 0.02, respectively). A positive correlation was evident between the DAS 28 score and IL6 levels (r = 0.263, p = 0.045). We found no correlation between the DAS28 score and HOMA-IR, the levels of pentraxin 3, fetuin A, insulin (p < 0.05). Fetuin A levels were positively correlated with cumulative steroid dose (r = 0.382, p = 0.035). A statistically significant correlation was evident between presence of cardiovascular disease and HOMA-IR values in RA patients (r = 0.437, p = 0.032).ConclusionElevated levels of pentraxin-3, fetuin-A, CRP, ESR might play a role in the pathogenesis of RA. Levels of fetuin-A, insulin HOMA-IR, pentraxin-3, CRP and ESR were not associated with clinical severity of the RA.     

Concentrations of preptin,salusins and hepcidins in plasma and milk of lactating women with or without gestational diabetes mellitus

This study was undertaken to ascertain whether human milk contains preptin, salusin-alpha (salusin-α) and -beta (salusin-β) and pro-hepcidin and hepcidin-25, and whether there are relationships between plasma and milk preptin, salusin-α and -β and pro-hepcidin and hepcidin-25 concentrations in lactating mothers with and without gestational diabetes mellitus (GDM). Blood was obtained from non-lactating women (n = 12), non-diabetic lactating women (n = 12), and GDM lactating women (n = 12). Colostrum, transitional milk, and mature milk samples were collected just before suckling from healthy and GDM lactating women. Peptides concentrations were determined by ELISA and EIA. Mammary gland tissues were screened immunohistochemically for these peptides. Women with GDM had significantly higher plasma and colostum preptin concentrations than healthy lactating women during the colostral and transitional milk period. Salusin-alpha and -beta levels in milk and plasma were lower in women with GDM. Salusin-α and -β were significantly lower in both plasma and colostrums of GDM than of healthy lactating women. Women with GDM had significantly higher colostum prohepcidin and hepcidin-25 concentrations than healthy lactating women during the colostral period. Plasma prohepcidin was also higher in women with GDM than in healthy lactating women during the colostral period, but plasma prohepcidin and hepcidin-25 levels decreased during mature milk period. Transitional milk pro-hepcidin and hepcidin-25 levels in women with GDM were higher than in healthy lactating women. All these results revealed that the mammary gland produces those peptides, which were present in milk at levels correlating with plasma concentrations.     

Hígado graso no alcohólico y su asociación con variables clínicas y bioquímicas en niños y adolescentes obesos: efecto de un año de intervención en el estilo de vida

ObjectiveTo study the frequency of non-alcoholic fatty liver disease (NAFLD), its relationship to clinical and biochemical variables, and the effect 12-month's lifestyle intervention in obese children and adolescents.MethodsThirty-six obese patients aged 7 to 18 years, 42% female and 58% male, 72.2% prepubertal and 27.8% pubertal, were selected. Anthropometric measurements and glucose, insulin (baseline and after a glucose load), lipid profile, C-reactive protein, and aminotransferase tests were performed before and 12 months after dietary and physical activity intervention. Liver ultrasound was performed to determine the presence of NAFLD.ResultsNAFLD was found in 66.7% (n = 24), and was mild in 30.6%, moderate in 27.8%, and severe in 8.3%. Subjects with NAFLD had higher body mass index (BMI, p = 0.007), waist (p = 0.005), fat area (p = 0.002), basal insulin (p = 0.01), and HOMA-IR (p = 0.008) values and lower QUICKI (p = 0.02) values than those with no NAFLD. After intervention, physical activity increased (p = 0.0001) and calorie intake remained unchanged. NAFLD disappeared in 9 patients (37.5%, p = 0.02) and disease severity decreased in 3 patients (12.5%). In addition, BMI Z-score (p = 0.005), fat area (p = 0.0001), basal insulin (p < 0.05), insulin resistance (p < 0.005), lipid profile (p < 0.03), and transaminases decreased. Weight loss was the main variable accounting for NAFLD improvement.ConclusionThis group of obese children and adolescents showed a high frequency of NAFLD. The lifestyle intervention with weight reduction is effective for the treatment of NAFLD.     

Treatment with pioglitazone is associated with decreased preprandial ghrelin levels: A randomized clinical trial

The effects of metformin and pioglitazone on ghrelin, a physiologic regulator of appetite and food intake, have not been clearly established. In a randomized clinical trial, we randomly assigned 60 type 2 diabetic patients to either metformin (Group A; n = 30) or pioglitazone (Group B; n = 30) treatment groups. The groups were similar in their baseline characteristics. A standard fasting 75 g oral glucose tolerance test was performed at time zero before starting metformin or pioglitazone, and 3 months later. After 3 months of treatment, pioglitazone, but not metformin, was significantly associated with weight gain. Both groups experienced a significant reduction in fasting plasma glucose (p < 0.01), hemoglobin A1c (p < 0.01 in Group A and p < 0.05 in Group B), and insulin resistance (p < 0.01). The effect of metformin on preprandial ghrelin and its response to glucose challenge was not significant, while the pioglitazone group had a significant reduction in preprandial ghrelin levels after treatment (p < 0.05). The effect of pioglitazone on ghrelin was independent of changes in body weight, body mass index, glucose control, insulin resistance, and plasma insulin. In conclusion, treatment with pioglitazone is associated with a decrease in preprandial ghrelin levels and therefore, the weight gain and increased food intake related to pioglitazone use cannot be explained by its effects on ghrelin. The effect of pioglitazone on ghrelin is independent of changes in body weight, body mass index, plasma insulin, insulin resistance, or glucose control.     

Zinc transporter gene expression and glycemic control in post-menopausal women with Type 2 diabetes mellitus

Type 2 diabetes mellitus (DM) is associated often with underlying zinc deficiency and nutritional supplements such as zinc may be of therapeutic benefit in the disease. In a randomized, double-blind, placebo-controlled, 12-week trial in postmenopausal women (n = 48) with Type 2 DM we investigated the effects of supplementation with zinc (40 mg/d) and flaxseed oil (FSO; 2 g/d) on the gene expression of zinc transporters (ZnT1, ZnT5, ZnT6, ZnT7, ZnT8, Zip1, Zip3, Zip7, and Zip10) and metallothionein (MT-1A, and MT-2A), and markers of glycemic control (glucose, insulin, glycosylated hemoglobin [HbA1c]). The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. No significant effects of zinc or FSO supplementation were observed on glycemic marker concentrations, HOMA-IR or fold change over 12 weeks in zinc transporter and metallothionein gene expression. In multivariate analysis, the change over 12 weeks in serum glucose concentrations (P = 0.001) and HOMA-IR (P = 0.001) predicted the fold change in Zip10. In secondary analysis, marginal statistical significance was observed with the change in both serum glucose concentrations (P = 0.003) and HOMA-IR (P = 0.007) being predictive of the fold change in ZnT6. ZnT8 mRNA expression was variable; HbA1c levels were higher (P = 0.006) in participants who exhibited ZnT8 expression compared to those who did not. The significant predictive relationships between Zip10, ZnT6, serum glucose and HOMA-IR are preliminary, as is the relationship between HbA1c and ZnT8; nevertheless the observations support an association between Type 2 DM and zinc homeostasis that requires further exploration.     

Circulating IL-6 concentrations and associated anthropometric and metabolic parameters in South Asian men and women in comparison to European whites

ObjectiveTo determine any ethnic differences in circulating interleukin (IL)-6 concentrations among SAs and Europeans, and to assess their relationship with body composition and insulin resistance measures.MethodsBody composition was assessed among 80 SA and European men and women using anthropometry, dual-energy X-ray absorptiometry and abdominal CT scan. Oral glucose tolerance tests with insulin response were performed to assess insulin resistance measures. IL-6 levels were measured by high sensitivity ELISA.ResultsMedian IL-6 values were higher in SA compared with European women: 1.94 mg/l versus 1.51 mg/l, p = 0.041, but not so in men (1.56 mg/l versus 1.57 mg/l). Only measures of obesity, in particular percentage fat area (r = 0.6, p = 0.003), were positively correlated with IL-6 in SAs. Differences in body fat percentage (visceral and total) could explain up to 30% of the IL-6 difference between Asian and European women.ConclusionSA women have elevated circulating IL-6 levels, in part due to greater visceral and percent fat levels compared with European women. This observation may in part explain why Asians are at elevated cardiovascular disease risk. Future studies should address the effects of lifestyle factors (physical activity, diet) on plasma IL-6 concentrations in SA women.     

Plasma levels of kisspeptins in postmenopausal Chinese women do not show substantial elevation

The menopause, defined as the permanent cessation of menstruation resulting from ovarian failure, is characterized by elevated levels of serum gonadotropins. Recent studies have demonstrated that the gonadotropin hypersecretion in postmenopausal women is secondary to increase of KiSS-1 mRNA from the hypothalamus neurons, which encoded kisspeptin peptides. The present study was designed to determine whether plasma kisspeptins levels are altered in postmenopausal women. Blood samples were taken from 145 postmenopausal women, 35 young women and 30 pregnant women control in the first trimester. The plasma concentration of kisspeptins, follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E₂) was measured using immunoassay kits. Results indicated that plasma kisspeptins levels in postmenopausal women had higher than those in young women (5.25 ± 0.36; 4.48 ± 0.34 pmol/L), but no significant difference was found between the two groups (p = 0.179). Plasma FSH and LH levels were significantly higher in postmenopausal women (124.67 ± 12.78, 57.14 ± 3.57 mIu/mL) than those in young women (9.23 ± 2.78, 7.56 ± 2.71 mIu/mL, p < 0.001). However, Plasma kisspeptins levels were not significantly correlated to FSH and LH in postmenopausal women (r = ?0.23, 0.324; p = 0.927, 0.176, respectively), and also there was no any correlation between plasma kisspeptins and E₂ in postmenopausal women (r = ?0.065; p = 0.792). Collectively, there was no significant difference in plasma kisspeptins levels between postmenopausal and young women. Our result suggested that kisspeptins’ role during menopause might mainly act in central rather than peripheral system and it could not be currently used as a clinical marker for menopause.     

Acquired coenzyme Q10 deficiency in children with recurrent food intolerance and allergies

The current study evaluated 23 children (ages 2–16 years) with recurrent food intolerance and allergies for CoQ10 deficiency and mitochondrial abnormalities. Muscle biopsies were tested for CoQ10 levels, pathology, and mitochondrial respiratory chain (MRC) activities. Group 2 (age > 10 years; n = 9) subjects had significantly decreased muscle CoQ10 than Group 1 (age < 10 y; n = 14) subjects (p = 0.001) and 16 controls (p < 0.05). MRC activities were significantly lower in Group 2 than in Group 1 (p < 0.05). Muscle CoQ10 levels in study subjects were significantly correlated with duration of illness (adjusted r² = 0.69; p = 0.012; n = 23). Children with recurrent food intolerance and allergies may acquire CoQ10 deficiency with disease progression.     

Difficulties with emotion regulation moderate the association between childhood history of maltreatment and cortisol reactivity to psychosocial challenge in postpartum women

Exposure to child maltreatment can lead to long-term emotional difficulties and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. However, no prior work has examined emotion regulation as a moderator of the association between childhood history of maltreatment and cortisol response to psychosocial challenge. Amongst a sample of 140 postpartum women, associations between childhood maltreatment, emotion regulation, and cortisol response to a computerized Emotional Stroop paradigm were examined using structural equation modeling. Three saliva samples (baseline, 20- and 40-min post-challenge) were collected and later assayed for cortisol. Stepwise regression analyses revealed that difficulties with emotion regulation significantly moderated the association between maternal history of child maltreatment and cortisol reactivity (β = − 0.17, CI_.95 = − 0.31, − 0.04, t = − 2.51, p = 0.01). Specifically, women with higher child maltreatment scores and greater difficulties with emotion regulation displayed reduced cortisol reactivity. This finding suggests that diminished emotion regulation capacity may uniquely contribute to blunted physiological reactivity in postpartum women exposed to higher levels of child maltreatment. As the postpartum period has significant implications for maternal well-being and infant development, these findings are discussed in terms of adaptive responsivity, maternal behaviour, and clinical practice.     

Recreational physical activity and risk of papillary thyroid cancer among women in the California Teachers Study

Purpose: Little is known about the relationship between physical activity and thyroid cancer risk, and few cohort data on this association exist. Thus, the present study aimed to prospectively examine long-term activity and risk of papillary thyroid cancer among women. Methods: 116,939 women in the California Teachers Study, aged 22–79 years with no history of thyroid cancer at cohort entry, were followed from 1995–1996 through 2009; 275 were diagnosed with invasive papillary thyroid cancer. Cox proportional-hazards regression provided relative risk (RR) estimates and 95% confidence intervals (CI) for associations between thyroid cancer and combined strenuous and moderate recreational physical activity both in the long-term (high school through age 54 years or current age if younger than 54 years) and recently (during the three years prior to joining the cohort). Results: Overall, women whose long-term recreational physical activity averaged at least 5.5 MET-hours/week (i.e. were active) had a non-significant 23% lower risk of papillary thyroid cancer than inactive women (RR = 0.77, 95% CI: 0.57, 1.04). RR estimates were stronger among normal weight or underweight women (body mass index, BMI < 25.0 kg/m², trend p = 0.03) than among overweight or obese women (trend p = 0.35; homogeneity-of-trends p = 0.03). A similar pattern of risk was observed for recent activity (BMI < 25 kg/m², trend p = 0.11; BMI ≥ 25 kg/m², trend p = 0.16; homogeneity-of-trends p = 0.04). Associations for long-term activity did not appear to be driven by activity in any particular life period (e.g. youth, adulthood). Conclusions: Long-term physical activity may reduce papillary thyroid cancer risk among normal weight and underweight women.     

Oxidative stress and apoptosis in preeclampsia

We aimed to determine the oxidative stress and antioxidant status in preeclamptic placenta. Also, we investigated the apoptotic index of villous trophoblast and proliferation index of cytotrophoblasts. The study included 32 pregnant with preeclampsia and 31 normotensive healthy pregnant women. Malondialdehyde (MDA) and total antioxidant status (TAS) levels were measured in the placenta. For detection of apoptosis and proliferation in trophoblast, apoptosis protease activating factor 1 (APAF-1) and Ki-67 were used. Placental MDA levels in preeclamptic women were significantly higher than normal pregnancies (p = 0.002). There was no significant difference between the groups in the TAS levels of placenta (p = 0.773). Also, the apoptotic index in villous trophoblasts increased (p < 0.001), but proliferation index did not change in preeclampsia (p = 0.850). Increased oxidative stress and apoptosis in pathological placenta are not balanced by antioxidant systems and proliferation mechanisms.     

Diabetes,metformin use,and colorectal cancer survival in postmenopausal women

Background: Observational studies have associated metformin use with lower colorectal cancer (CRC) incidence but few studies have examined metformin's influence on CRC survival. We examined the relationships among metformin use, diabetes, and survival in postmenopausal women with CRC in the Women's Health Initiative (WHI) clinical trials and observational study. Methods: 2066 postmenopausal women with CRC were followed for a median of 4.1 years, with 589 deaths after CRC diagnosis from all causes and 414 deaths directly attributed to CRC. CRC-specific survival was compared among women with diabetes with metformin use (n = 84); women with diabetes with no metformin use (n = 128); and women without diabetes (n = 1854). Cox proportional hazard models were used to estimate associations among metformin use, diabetes and survival after CRC. Strategies to adjust for potential confounders included: multivariate adjustment with known predictors of colorectal cancer survival and construction of a propensity score for the likelihood of receiving metformin, with model stratification by propensity score quintile. Results: After adjusting for age and stage, CRC specific survival in women with diabetes with metformin use was not significantly different compared to that in women with diabetes with no metformin use (HR 0.75; 95% CI 0.40–1.38, p = 0.67) and to women without diabetes (HR 1.00; 95% CI 0.61–1.66, p = 0.99). Following propensity score adjustment, the HR for CRC-specific survival in women with diabetes with metformin use compared to non-users was 0.78 (95% CI 0.38–1.55, p = 0.47) and for overall survival was 0.86 (95% CI 0.49–1.52; p = 0.60). Conclusions: In postmenopausal women with CRC and DM, no statistically significant difference was seen in CRC specific survival in those who used metformin compared to non-users. Analyses in larger populations of colorectal cancer patients are warranted.     

Risk factors associated with human papillomavirus prevalence and cervical neoplasia among Cameroonian women

BackgroundThis study used community-based cervical cancer screening for high-risk human-papillomavirus (HPV) to determine demographic and lifestyle factors associated with HPV prevalence and cervical intraepithelial neoplasia grade 2 or worse (CIN2+).MethodsWomen (n = 838) aged 25–65 years were recruited in two sequential studies in Cameroon. Demographic and historical data were obtained from participants and specimens were self-collected for HPV-testing using real-time PCR. HPV-positive women underwent biopsy and endocervical curettage. Associations were determined using bivariate analysis and logistic regression.ResultsHPV and self-reported HIV prevalence were 39.0% and 9.2%, respectively. Eighteen (9.3%) CIN2+ lesions were found among HPV-positive women. Housewives had a higher risk of being HPV infected (OR = 1.60, p = 0.010). HIV co-infection (aOR = 3.44, p < 0.001) and hormonal contraception (aOR = 1.97, p = 0.007) were associated with increased HPV prevalence. HPV-positive women who used condoms during sexual intercourse were at lower risk of CIN2+ (aOR = 0.15, p = 0.029). CIN2–3 lesions were found in women younger than 50 years, with a median age of 36 years (31–44). HPV-16/18-positive women had a 4.65-fold increased risk of CIN2+ (p = 0.015).ConclusionsYoung, single women and housewives were at higher risk of HPV infection. Preventive strategies for cervical cancer in low-resource settings should target women aged 30–50 years for HPV screening, and should focus treatment and follow-up on HPV-16/18-positive women. Further studies are needed to clarify if other risk factors require attention.     

Do adipokines underlie the association between known risk factors and breast cancer among a cohort of United States women?

Introduction: Obesity is a well-established risk factor for postmenopausal breast cancer, but mechanisms underlying the association are unclear. Adipocyte-derived, cytokine-like adipokines have been suggested as contributory factors. To evaluate their association with breast cancer risk factors and breast cancer risk, we conducted a nested case-control study of 234 postmenopausal breast cancer cases and 234 controls in a cohort of U.S. women with prospectively-collected serum samples obtained in the mid 1970s and followed for up to 25 years. Methods: Adiponectin, absolute plasminogen activator inhibitor-1 (aPAI-1), and resistin were measured by a multiplex immunoassay. Sex hormones were available for 67 cases and 67 controls. Results: Among controls, we found that lower levels of adiponectin and higher levels of aPAI-1 were correlated with increasing levels of estradiol (Spearman r = ?0.26, p-value = 0.033; r = 0.42, p = 0.0003), decreasing levels of sex hormone binding globulin (r = 0.38, p = 0.0013; r = ?0.32, p = 0.0076), and increasing body mass index (BMI) (r = ?0.31, p =  < 0.0001; r = 0.39, p =  < 0.0001). Hormones were not associated with resistin. Among the relatively small percentage of women using postmenopausal hormones at the time of blood collection (13.7%), aPAI-1 levels were higher than in non-users (p = 0.0054). Breast cancer risk was not associated with circulating levels of adiponectin (age-adjusted p for linear trend = 0.43), aPAI-1 (p = 0.78), or resistin (p = 0.91). The association was not confounded by BMI, parity, age at first full-term birth, age at menopause, current postmenopausal hormone use, and circulating sex steroid hormones. Furthermore, adipokine associations were not modified by BMI (p > 0.05). The lack of association with risk may be due to measurement error of the laboratory assays. Discussion: lower levels of adiponectin and higher levels of aPAI-1 measured in prospectively-collected serum from postmenopausal women were associated with increasing BMI but not breast cancer risk.