Increased serum pigment epithelium derived factor levels in Type 2 diabetes patients

Serum PEDF levels (mean (S.D.)) were increased in 96 Type 2 diabetic vs. 54 non-diabetic subjects; 5.3 (2.8) vs. 3.2 (2.0)mug/ml, p

Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study:preeclampsia

Objective: The purpose of this study was to examine associations of fasting C-peptide, body mass index (BMI), and maternal glucose with the risk of preeclampsia in a multicenter multinational study. Study Design: We conducted a secondary analysis of a blinded observational cohort study. Subjects underwent a 75-g oral glucose tolerance test at 24-32 weeks' gestation. Associations of preeclampsia with fasting C-peptide, BMI, and maternal glucose were assessed with the use of multiple logistic regression analyses and adjustment for potential confounders. Results: Of 21,364 women who were included in the analyses, 5.2% had preeclampsia. Adjusted odds ratios for preeclampsia for 1 SD higher fasting C-peptide (0.87 ug/L), BMI (5.1 kg/m), and fasting (6.9 mg/dL), 1-hour (30.9 mg/dL), and 2-hour plasma glucose (23.5 mg/dL) were 1.28 (95% confidence interval [CI], 1.20-1.36), 1.60 (95% CI, 1.60-1.71), 1.08 (95% CI, 1.00-1.16), 1.19 (95% CI, 1.11-1.28), and 1.21 (95% CI,1.13-1.30), respectively. Conclusion: Results indicate strong, independent associations of fasting C-peptide and BMI with preeclampsia. Maternal glucose levels (below diabetes mellitus) had weaker associations with preeclampsia, particularly after adjustment for fasting C-peptide and BMI. © 2010 Mosby, Inc. All rights reserved.

Pioglitazone protects HDL(2&3) against oxidation in overweight and obese men

The worldwide epidemic of obesity is a major public health concern and is persuasively linked to the rising prevalence of diabetes and cardiovascular disease. Obesity is often associated with an abnormal lipoprotein profile, which may be partly negated by pioglitazone intervention, as this can influence the composition and oxidation characteristics of low-density lipoprotein (LDL). However, as pioglitazone's impact on these parameters within high-density lipoprotein (HDL), specifically HDL(2&3), is absent from the literature, this study was performed to address this shortcoming.

A prospective cohort study of obesity and risk of oesophageal and gastric adenocarcinoma in the NIH-AARP Diet and Health Study

Objective: The incidence of oesophageal adenocarcinoma (EAC) has increased rapidly over the past 40 years and accumulating evidence suggests that obesity, as measured by body mass index (BMI), is a major risk factor. It remains unclear whether abdominal obesity is associated with EAC and gastric adenocarcinoma.

Design: Cox proportional hazards regression was used to examine associations between overall and abdominal obesity with EAC and gastric adenocarcinoma among 218 854 participants in the prospective NIHeAARP cohort.

Results: 253 incident EAC, 191 gastric cardia adenocarcinomas and 125 gastric non-cardia adenocarcinomas accrued to the cohort. Overall obesity (BMI) was positively associated with EAC and gastric
cardia adenocarcinoma risk (highest ($35 kg/m2) vs referent (18.5e<25 kg/m2); HR 2.11, 95% CI 1.09 to 4.09 and HR 3.67, 95% CI 2.00 to 6.71, respectively). Waist circumference was also positively associated with EAC and gastric cardia adenocarcinoma risk (highest vs referent; HR 2.01, 95% CI 1.35 to 3.00 and HR 2.22, 95% CI 1.43 to 3.47, respectively), whereas waist-to-hip ratio (WHR) was positively associated with EAC risk only (highest vs referent; HR 1.81, 95% CI 1.24 to 2.64) and persisted in patients with normal BMI (18.5e<25 kg/m2). Mutual adjustment of WHR and BMI attenuated
both, but did not eliminate the positive associations for either with risk of EAC. In contrast, the majority of the anthropometric variables were not associated with adenocarcinomas of the gastric non-cardia.

Conclusion Overall obesity was associated with a higher risk of EAC and gastric cardia adenocarcinoma, whereas abdominal obesity was found to be associated with increased EAC risk; even in people with normal BMI

Common variant at 16p11.2 conferring risk of psychosis

Epidemiological and genetic data support the notion that schizophrenia and bipolar disorder share genetic risk factors. In our previous genome-wide association (GWA) study, meta-analysis and follow-up (totaling as many as 18,206 cases and 42,536 controls), we identified four loci showing genome-wide significant association with schizophrenia. Here we consider a mixed schizophrenia and bipolar disorder (psychosis) phenotype (addition of 7,469 bipolar disorder cases, 1,535 schizophrenia cases, 333 other psychosis cases, 808 unaffected family members and 46,160 controls). Combined analysis reveals a novel variant at 16p11.2 showing genome-wide significant association (rs4583255[T], OR = 1.08, P = 6.6 × 10−11). The new variant is located within a 593 kb region that substantially increases risk of psychosis when duplicated. In line with the association of the duplication with reduced body mass index (BMI), rs4583255[T] is also associated with lower BMI (P = 0.0039 in the public GIANT consortium dataset; P = 0.00047 in 22,651 additional Icelanders).

Health status and 6 years survival of 552 90+ Italian sib-ships recruited within the EU Project GEHA (GEnetics of Healthy Ageing).

In a scenario of increasing life expectancy worldwide, it is mandatory to identify the characteristics of a healthy aging phenotype, including survival predictors, and to disentangle those related to environment/lifestyle versus those related to familiarity/genetics. To this aim we comprehensively characterised a cohort of 1,160 Italian subjects of 90 years and over (90+, mean age 93 years; age range 90-106 years) followed for 6 years survival, belonging to 552 sib-ships (familiar longevity) recruited (2005-2008) within the EU-funded GEHA project in three Italian geographic areas (Northern, Central and Southern Italy) different for urban/rural and socio-economical characteristics. On the whole, the following factors emerged as significant predictors of survival after 90 years of age: absence of cognitive impairment and physical disability, high hand grip strength scores and body mass index (BMI) values, "excellent/good" self-reported health, high haemoglobin and total cholesterol levels and low creatinine levels. These parameters, excluding BMI values, were also significantly associated within sib-ships, suggesting a strong familial/genetic component. Geographical micro-heterogeneity of survival predictors emerged, such as functional and physical status being more important in Southern than in Central and Northern Italy. In conclusion, we identified modifiable survival predictors related to specific domains, whose role and importance vary according to the geographic area considered and which can help in interpreting the genetic results obtained by the GEHA project, whose major aim is the comprehensive evaluation of phenotypic and genetic data.

The relationship between breastfeeding and postpartum weight change-a systematic review and critical evaluation

Pregnancy and the postpartum period is a time of increased vulnerability for retention of excess body fat in women. Breastfeeding (BF) has been shown to have many health benefits for both mother and baby; however, its role in postpartum weight management is unclear. Our aim was to systematically review and critically appraise the literature published to date in relation to the impact of BF on postpartum weight change, weight retention and maternal body composition. Electronic literature searches were carried out using MEDLINE, EMBASE, PubMed, Web of Science, BIOSIS, CINAHL and British Nursing Index. The search covered publications up to 12 June 2012 and included observational studies (prospective and retrospective) carried out in BF mothers (either exclusively or as a subgroup), who were 2 years postpartum and with a body mass index (BMI) >18.5 kg m(-2), with an outcome measure of change in weight (including weight retention) and/or body composition. Thirty-seven prospective studies and eight retrospective studies were identified that met the selection criteria; studies were stratified according to study design and outcome measure. Overall, studies were heterogeneous, particularly in relation to sample size, measurement time points and in the classification of BF and postpartum weight change. The majority of studies reported little or no association between BF and weight change (n=27, 63%) or change in body composition (n=16, 89%), although this seemed to depend on the measurement time points and BF intensity. However, of the five studies that were considered to be of high methodological quality, four studies demonstrated a positive association between BF and weight change. This systematic review highlights the difficulties of examining the association between BF and weight management in observational research. Although the available evidence challenges the widely held belief that BF promotes weight loss, more robust studies are needed to reliably assess the impact of BF on postpartum weight management.International Journal of Obesity advance online publication, 20 August 2013; doi:10.1038/ijo.2013.132.

Association of physical activity with future mental health in older, mid-life and younger women

Background: Mental ill-health, particularly depression and anxiety, is a leading and increasing cause of disability worldwide, especially for women.

Methods: We examined the prospective association between physical activity and symptoms of mental ill-health in younger, mid-life and older working women. Participants were 26 913 women from the ongoing cohort Finnish Public Sector Study with complete data at two phases, excluding those who screened positive for mental ill-health at baseline. Mental health was assessed using the 12-item General Health Questionnaire. Self-reported physical activity was expressed in metabolic equivalent task (MET) hours per week. Logistic regression models were used to analyse associations between physical activity levels and subsequent mental health.

Results: There was an inverse dose–response relationship between physical activity and future symptoms of mental ill-health. This association is consistent with a protective effect of physical activity and remained after adjustments for socio-demographic, work-related and lifestyle factors, health and body mass index. Furthermore, those mid-life and older women who reported increased physical activity by more than 2 MET hours per week demonstrated a reduced risk of later mental ill-health in comparison with those who did not increase physical activity. This protective effect of increased physical activity did not hold for younger women.

Conclusions: This study adds to the evidence for the protective effect of physical activity for later mental health in women. It also suggests that increasing physical activity levels may be beneficial in terms of mental health among mid-life and older women. The alleviation of menopausal symptoms may partly explain age effects but further research is required.

Obesity and kidney disease in type 1 and 2 diabetes: an analysis of the National Diabetes Audit

Background: Obesity is increasingly prevalent in many countries. Obesity is a major risk factor for the development of type 2 diabetes but its relationship with diabetic kidney disease (DKD) remains unclear. Some studies have suggested that the metabolic syndrome (including obesity) may be associated with DKD in type 1 diabetes. Aim: To investigate the association between obesity and DKD. Design: Retrospective cross-sectional study. Methods: National Diabetes Audit data were available for the 2007–08 cycle. Type 1 and 2 diabetes patients with both a valid serum creatinine and urinary albumin:creatinine ratio were included. DKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2, albuminuria or both. Logistic regression was used to analyse associations of obesity (body mass index ≥30 kg/m2) and other variables including year of birth, year of diagnosis, ethnicity and stage of kidney disease. Results: A total of 58 791 type 1 and 733 769 type 2 diabetes patients were included in the analysis. After adjustment, when compared with type 1 diabetes patients with normal renal function those with DKD were up to twice as likely to be obese. Type 2 DKD patients were also more likely to be obese. For example, type 2 diabetes patients with an eGFR <15 ml/min/1.73 m2 and normoalbuminuria, microalbuminuria or macroalbuminuria were all more likely to be obese; odds ratios (95% CI) 1.65 (1.3–2.1), 1.56 (1.28–1.92) and 1.27 (1.05–1.54), respectively. Conclusions: This study has highlighted a strong association between obesity and kidney disease in type 1 diabetes and confirmed their association in type 2 diabetes.

Evaluation of the effect of wheat aleurone-rich foods on markers of antioxidant status, inflammation and endothelial function in apparently healthy men and women

Observational data show an inverse association between the consumption of whole-grain foods, and inflammation and related diseases. Although the underlying mechanisms are unclear, whole grains, and in particular the aleurone layer, contain a wide range of components with putative antioxidant and anti-inflammatory effects. We evaluated the effects of a diet high in wheat aleurone on plasma antioxidants status, markers of inflammation and endothelial function. In this parallel, participant-blinded intervention, seventy-nine healthy, older, overweight participants (45-65 years, BMI>25 kg/m²) incorporated either aleurone-rich cereal products (27 g aleurone/d), or control products balanced for fibre and macronutrients, into their habitual diets for 4 weeks. Fasting blood samples were taken at baseline and on day 29. Results showed that, compared to control, consumption of aleurone-rich products provided substantial amounts of micronutrients and phytochemicals which may function as antioxidants. Additionally, incorporating these products into a habitual diet resulted in significantly lower plasma concentrations of the inflammatory marker, C-reactive protein (P = 0·035), which is an independent risk factor for CVD. However, no changes were observed in other markers of inflammation, antioxidant status or endothelial function. These results provide a possible mechanism underlying the beneficial effects of longer-term whole-grain intake. However, it is unclear whether this effect is owing to a specific component, or a combination of components in wheat aleurone.

Physical Activity, Gender, Weight Status, and Wellbeing in 9- to 11-Year-Old Children: A Cross-Sectional Survey

Background: The aim of this study was to examine the relationship between physical activity and wellbeing in children, and to further explore the extent to which this may vary by gender and weight status. Method: A representative sample of 1424 9- to 11-year-olds completed a self-report measure of physical activity, the Child Health and Illness Profile, KIDSCREEN, and a self-esteem scale. Body Mass Index (BMI) measurements were also obtained. Results: 24% of children achieved the recommended level of 60 minutes of moderate-tovigorous intensity physical activity (MVPA) per day, with more boys than girls achieving this level. Children achieving the recommended level of MVPA scored significantly higher on measures of the Child Health and Illness Profile (F(5, 1354) = 5.03; P < .001), KIDSCREEN (F(3, 1298) = 4.68; P = .003), and self-esteem (F(1,1271) = 18.73; P = .003) than less active children although the effect sizes were small (ηp2 ≈ .01). Substantial gender differences in wellbeing were found reflecting gender specific behaviors and socialization. Weight status had negligible influence on wellbeing. Conclusions: Children who meet the recommended guidelines of MVPA were more likely to have better wellbeing. When attempting to raise children’s physical activity levels consideration should be given to the specific relationships between wellbeing and physical activity.

Seasonality of cardiovascular risk factors: an analysis including over 230 000 participants in 15 countries

Objective: To assess the seasonality of cardiovascular risk factors (CVRF) in a large set of population-based studies.

Methods: Cross-sectional data from 24 population-based studies from 15 countries, with a total sample size of 237 979 subjects. CVRFs included Body Mass Index (BMI) and waist circumference; systolic (SBP) and diastolic (DBP) blood pressure; total, high (HDL) and low (LDL) density lipoprotein cholesterol; triglycerides and glucose levels. Within each study, all data were adjusted for age, gender and current smoking. For blood pressure, lipids and glucose levels, further adjustments on BMI and drug treatment were performed.

Results: In the Northern and Southern Hemispheres, CVRFs levels tended to be higher in winter and lower in summer months. These patterns were observed for most studies. In the Northern Hemisphere, the estimated seasonal variations were 0.26 kg/m2 for BMI, 0.6 cm for waist circumference, 2.9 mm Hg for SBP, 1.4 mm Hg for DBP, 0.02 mmol/L for triglycerides, 0.10 mmol/L for total cholesterol, 0.01 mmol/L for HDL cholesterol, 0.11 mmol/L for LDL cholesterol, and 0.07 mmol/L for glycaemia. Similar results were obtained when the analysis was restricted to studies collecting fasting blood samples. Similar seasonal variations were found for most CVRFs in the Southern Hemisphere, with the exception of waist circumference, HDL, and LDL cholesterol.

Conclusions: CVRFs show a seasonal pattern characterised by higher levels in winter, and lower levels in summer. This pattern could contribute to the seasonality of CV mortality.

The role of adiposity in cardiometabolic traits:a Mendelian randomization analysis

The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Alcohol and the Risk of Barrett's Esophagus: A Pooled Analysis from the International BEACON Consortium

OBJECTIVES: Results from studies examining the association between alcohol consumption and the risk of Barrett's esophagus have been inconsistent. We assessed the risk of Barrett's esophagus associated with total and beverage-specific alcohol consumption by pooling individual participant data from five case–control studies participating in the international Barrett's and Esophageal Adenocarcinoma Consortium.
METHODS: For analysis, there were 1,282 population-based controls, 1,418 controls with gastroesophageal reflux disease (GERD), and 1,169 patients with Barrett's esophagus (cases). We estimated study-specific odds ratios (ORs) and 95% confidence intervals (95% CI) using multivariable logistic regression models adjusted for age, sex, body mass index (BMI), education, smoking status, and GERD symptoms. Summary risk estimates were obtained by random-effects models. We also examined potential effect modification by sex, BMI, GERD symptoms, and cigarette smoking.
RESULTS: For comparisons with population-based controls, although there was a borderline statistically significant inverse association between any alcohol consumption and the risk of Barrett's esophagus (any vs. none, summary OR=0.77, 95% CI=0.60–1.00), risk did not decrease in a dose-response manner (Ptrend=0.72). Among alcohol types, wine was associated with a moderately reduced risk of Barrett's esophagus (any vs. none, OR=0.71, 95% CI=0.52–0.98); however, there was no consistent dose–response relationship (Ptrend=0.21). We found no association with alcohol consumption when cases were compared with GERD controls. Similar associations were observed across all strata of BMI, GERD symptoms, and cigarette smoking.
CONCLUSIONS: Consistent with findings for esophageal adenocarcinoma, we found no evidence that alcohol consumption increases the risk of Barrett's esophagus.