Background In 2010, overweight and obesity were estimated to cause 3.4 million deaths, 3.9% of years of life lost, and 3.8% of DALYs globally. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparative, up-to-date information on levels and trends is essential both to quantify population health effects and to prompt decision-makers to prioritize action. Methods We systematically identified surveys, reports, and published studies (n = 1,769) that included information on height and weight, both through physical measurements and self-reports. Mixed effects linear regression was used to correct for the bias in self-reports. Age-sex-country-year observations (n = 19,244) on prevalence of obesity and overweight were synthesized using a spatio-temporal Gaussian Process Regression model to estimate prevalence with 95% uncertainty intervals. Findings Globally, the proportion of adults with a body mass index (BMI) of 25 or greater increased from 28.8% (95% UI: 28.4-29.3) in 1980 to 36.9% (36.3-37.4) in 2013 for men and from 29.8% (29.3-30.2) to 38.0% (37.5-38.5) for women. Increases were observed in both developed and developing countries. There have been substantial increases in prevalence among children and adolescents in developed countries, with 23.8% (22.9-24.7) of boys and 22.6% (21.7-23.6) of girls being either overweight or obese in 2013. The prevalence of overweight and obesity is also rising among children and adolescents in developing countries as well, rising from 8.1% (7.7-8.6) to 12.9% (12.3-13.5) in 2013 for boys and from 8.4% (8.1-8.8) to 13.4% (13.0-13.9) in girls. Among adults, estimated prevalence of obesity exceeds 50% among men in Tonga and women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has stabilized. Interpretation Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Contrary to other major global risks, there is little evidence of successful population-level intervention strategies to reduce exposure. Not only is obesity increasing, but there are no national success stories over the past 33 years. Urgent global action and leadership is required to assist countries to more effectively intervene.

We performed a meta-analysis of 2 genome-wide association studies of coronary artery disease comprising 1,515 cases with coronary artery disease and 5,019 controls, followed by de novo replication studies in 15,460 cases and 11,472 controls, all of Chinese Han descent. We successfully identified four new loci for coronary artery disease reaching genome-wide significance (P < 5 × 10−8), which mapped in or near TTC32-WDR35, GUCY1A3, C6orf10-BTNL2 and ATP2B1. We also replicated four loci previously identified in European populations (PHACTR1, TCF21, CDKN2A/B and C12orf51). These findings provide new insights into biological pathways for the susceptibility of coronary artery disease in Chinese Han population.

Objectives To estimate the percentage of excess death for US Black and White men and women associated with high body mass, we examined the combined effects of age variation in the obesity–mortality relationship and cohort variation in age-specific obesity prevalence. Methods We examined 19 National Health Interview Survey waves linked to individual National Death Index mortality records, 1986–2006, for age and cohort patterns in the population-level association between obesity and US adult mortality. Results The estimated percentage of adult deaths between 1986 and 2006 associated with overweight and obesity was 5.0% and 15.6% for Black and White men, and 26.8% and 21.7% for Black and White women, respectively. We found a substantially stronger association than previous research between obesity and mortality risk at older ages, and an increasing percentage of mortality attributable to obesity across birth cohorts. Conclusions Previous research has likely underestimated obesity's impact on US mortality. Methods attentive to cohort variation in obesity prevalence and age variation in obesity's effect on mortality risk suggest that obesity significantly shapes US mortality levels, placing it at the forefront of concern for public health action.

Type 2 diabetes (T2D) arises when pancreatic ␤-cells fail to compensate for systemic insulin resistance with appropriate insulin secretion. However, the link between insulin resistance and ␤-cell failure in T2D is not fully understood. To explore this association, we studied transgenic MKR mice that initially develop insulin resistance in skeletal muscle but by 8 weeks of age have T2D. In the present study, global islet protein and gene expression changes were characterized in diabetic MKR versus non-diabetic control mice at 10 weeks of age. Using a quantitative proteomics approach (isobaric tags for relative and absolute quantification (iTRAQ)), 159 proteins were differentially expressed in MKR compared with control islets. Marked up-regulation of protein biosynthesis and endoplasmic reticulum stress pathways and parallel down-regulation in insulin processing/secretion, energy utilization, and metabolism were observed. A fraction of the differentially expressed proteins identified (including GLUT2, DNAJC3, VAMP2, RAB3A, and PC1/3) were linked previously to insulin-secretory defects and T2D. However, many proteins for the first time were associated with islet dysfunction, including the unfolded protein response proteins (ERP72, ERP44, ERP29, PPIB, FKBP2, FKBP11, and DNAJB11), endoplasmic reticulumassociated degradation proteins (VCP and UFM1), and multiple proteins associated with mitochondrial energy metabolism (NDUFA9, UQCRH, COX2, COX4I1, COX5A, ATP6V1B2, ATP6V1H, ANT1, ANT2, ETFA, and ETFB). The mRNA expression level corresponding to these proteins was examined by microarray, and then a small subset was validated using quantitative real time PCR and Western blot analyses. Importantly ϳ54% of differentially expressed proteins in MKR islets (including proteins involved in proinsulin processing, protein biosynthesis, and mitochondrial oxidation) showed changes in the proteome but not transcriptome, suggesting post-transcriptional regulation. These results underscore the importance of integrated mRNA and protein expression measurements and validate the use of the iTRAQ method combined with microarray to assess global protein and gene changes involved in the development of T2D.

While PrPC rearranges in the area of codons 104 -113 to form PrP Sc during prion infections, the events that initiate sporadic Creutzfeldt-Jakob disease are undefined. As Cu(II) is a putative ligand for PrP C and has been implicated in the pathogenesis of Creutzfeldt-Jakob disease and other neurodegenerative diseases, we investigated the structural effects of binding. Incubation of brain microsomes with Cu(II) generated ϳ30-kDa proteinase K-resistant PrP. Cu(II) had little effect on fresh recombinant PrP23-231, but aged protein characterized by conversion of Asn-107 to Asp decreased ␣-helical content by ϳ30%, increased ␤-sheet content 100%, formed aggregates, and acquired proteinase K resistance in the presence of Cu(II). These transitions took place without need for acid pH, organic solvents, denaturants, or reducing agents. Since conversion of Asn to Asp proceeds by a spontaneous pathway involving deamidation, our data suggest that covalent variants of PrP C arising in this manner may, in concert with Cu(II), generate PrP Sc -like species capable of initiating sporadic prion disease.

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Given documented links between individual socioeconomic status (SES) and health, it is likely that—in addition to its impacts on individuals’ wallets and bank accounts—the Great Recession also took a toll on individuals’ disease and mortality risk. Exploiting a quasi-natural experiment design, this study utilizes nationally representative, longitudinal data from the National Social Life, Health, and Aging Project (NSHAP) (2005-2011) (N=930) and individual fixed effects models to examine how household-level wealth shocks experienced during the Great Recession relate to changes in biophysiological functioning in older adults. Results indicate that wealth shocks significantly predicted changes in physiological functioning, such that losses in net worth from the pre- to the post-Recession period were associated with increases in systolic blood pressure and C-reactive protein over the six year period. Further, while the association between wealth shocks and changes in blood pressure was unattenuated with the inclusion of other indicators of SES, psychosocial well-being, and health behaviors in analytic models, we document some evidence of mediation in the association between changes in wealth and changes in C-reactive protein, which suggests specificity in the social and biophysiological mechanisms relating wealth shocks and health at older ages. Linking macro-level conditions, meso-level household environments, and micro-level biological processes, this study provides new insights into the mechanisms through which economic inequality contributes to disease and mortality risk in late life.