Diabetes in pregnancy among indigenous women in Australia, Canada, New Zealand, and the United States: a method for systematic review of studies with different designs

<p>Abstract</p> <p>Background</p> <p>Diabetes in pregnancy, which includes gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM), is associated with poor outcomes for both mother and infant during pregnancy, at birth and in the longer term. Recent international guidelines recommend changes to the current GDM screening criteria. While some controversy remains, there appears to be consensus that women at high risk of T2DM, including indigenous women, should be offered screening for GDM early in pregnancy, rather than waiting until 24-28 weeks as is current practice. A range of criteria should be considered before changing screening practice in a population sub-group, including: prevalence, current practice, acceptability and whether adequate treatment pathways and follow-up systems are available. There are also specific issues related to screening in pregnancy and indigenous populations. The evidence that these criteria are met for indigenous populations is yet to be reported. A range of study designs can be considered to generate relevant evidence for these issues, including epidemiological, observational, qualitative, and intervention studies, which are not usually included within a single systematic review. The aim of this paper is to describe the methods we used to systematically review studies of different designs and present the evidence in a pragmatic format for policy discussion.</p> <p>Methods/Design</p> <p>The inclusion criteria will be broad to ensure inclusion of the critical perspectives of indigenous women. Abstracts of the search results will be reviewed by two persons; the full texts of all potentially eligible papers will be reviewed by one person, and 10% will be checked by a second person for validation. Data extraction will be standardised, using existing tools to identify risks for bias in intervention, measurement, qualitative studies and reviews; and adapting criteria for appraising risk for bias in descriptive studies. External validity (generalisability) will also be appraised. The main findings will be synthesised according to the criteria for population-based screening and summarised in an adapted "GRADE" tool.</p> <p>Discussion</p> <p>This will be the first systematic review of all the published literature on diabetes in pregnancy among indigenous women. The method provides a pragmatic approach for synthesizing relevant evidence from a range of study designs to inform the current policy discussion.</p

Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, Glucose Intolerance and Fatty Liver Disease

Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II), blood vessel recruitment (Vegfa) and autocrine/paracrine IGF-I signaling (Igf1). As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness

Diabetes in pregnancy among indigenous women in Australia, Canada, New Zealand and the United States: a systematic review of the evidence for screening in early pregnancy

Recently proposed international guidelines for screening for gestational diabetes mellitus (GDM) recommend additional screening in early pregnancy for sub-populations at a high risk of type 2 diabetes mellitus (T2DM), such as indigenous women. However, there are criteria that should be met to ensure the benefits outweigh the risks of population-based screening. This review examines the published evidence for early screening for indigenous women as related to these criteria. Any publications were included that referred to diabetes in pregnancy among indigenous women in Australia, Canada, New Zealand and the United States (n = 145). The risk of bias was appraised. There is sufficient evidence describing the epidemiology of diabetes in pregnancy, demonstrating that it imposes a significant disease burden on indigenous women and their infants at birth and across the lifecourse (n = 120 studies). Women with pre-existing T2DM have a higher risk than women who develop GDM during pregnancy. However, there was insufficient evidence to address the remaining five criteria, including the following: understanding current screening practice and rates (n = 7); acceptability of GDM screening (n = 0); efficacy and cost of screening for GDM (n = 3); availability of effective treatment after diagnosis (n = 6); and effective systems for follow-up after pregnancy (n = 5). Given the impact of diabetes in pregnancy, particularly undiagnosed T2DM, GDM screening in early pregnancy offers potential benefits for indigenous women. However, researchers, policy makers and clinicians must work together with communities to develop effective strategies for implementation and minimizing the potential risks. Evidence of effective strategies for primary prevention, GDM treatment and follow-up after pregnancy are urgently neede

Diabetes in pregnancy among indigenous women in Australia, Canada, New Zealand and the United States: a systematic review of the evidence for screening in early pregnancy

Recently proposed international guidelines for screening for gestational diabetes mellitus (GDM) recommend additional screening in early pregnancy for sub-populations at a high risk of type 2 diabetes mellitus (T2DM), such as indigenous women. However, there are criteria that should be met to ensure the benefits outweigh the risks of population-based screening. This review examines the published evidence for early screening for indigenous women as related to these criteria. Any publications were included that referred to diabetes in pregnancy among indigenous women in Australia, Canada, New Zealand and the United States (n = 145). The risk of bias was appraised. There is sufficient evidence describing the epidemiology of diabetes in pregnancy, demonstrating that it imposes a significant disease burden on indigenous women and their infants at birth and across the lifecourse (n = 120 studies). Women with pre-existing T2DM have a higher risk than women who develop GDM during pregnancy. However, there was insufficient evidence to address the remaining five criteria, including the following: understanding current screening practice and rates (n = 7); acceptability of GDM screening (n = 0); efficacy and cost of screening for GDM (n = 3); availability of effective treatment after diagnosis (n = 6); and effective systems for follow-up after pregnancy (n = 5). Given the impact of diabetes in pregnancy, particularly undiagnosed T2DM, GDM screening in early pregnancy offers potential benefits for indigenous women. However, researchers, policy makers and clinicians must work together with communities to develop effective strategies for implementation and minimizing the potential risks. Evidence of effective strategies for primary prevention, GDM treatment and follow-up after pregnancy are urgently neede

Multi-Site Evaluation of Community-Based Efforts to Improve Engagement in HIV Care Among Populations Disproportionately Affected by HIV in the United States

This study assesses effects of a community-based intervention across seven sites in the United States on HIV care utilization and study retention, among people living with HIV (PLWH). A two-armed study was conducted from 2013 to 2016 in each of seven community-based agencies across the United States. Each site conducted interventions involving community engagement approaches in the form of case management or patient navigation. Control conditions were standard of care involving referral to HIV clinical care. Participants (N = 583) were adults reporting erratic or no HIV care in the past 6 months. Longitudinal survey data on demographics, behavioral risks, and HIV care were collected from participants at baseline, before service delivery, and at 6-month follow-up. Unadjusted and adjusted generalized linear mixed models were used to assess the intervention effects on HIV care utilization and study retention. Participants were majority black (75.5%), cisgender male (55.1%), and heterosexual (55.4%). No significant intervention effect was observed on HIV care utilization, although both groups improved significantly over time [adjusted odds ratio (AOR): 2.09, 95% confidence interval (CI): 1.30-3.37]. Intervention participants were more likely to be retained in the study (AOR: 1.50, 95% CI: 1.03-2.20). Community intervention did not affect HIV care utilization more than standard of care, but intervention participants were more likely to be retained in the study, suggesting that such approaches support relationship building in ways that can facilitate follow-up of socially vulnerable PLWH. More research is needed to understand how such community efforts can support better HIV care utilization in these populations

Active NF-E2-related Factor (Nrf2) Contributes to Keep Endothelial NO Synthase (eNOS) in the Coupled State: ROLE OF REACTIVE OXYGEN SPECIES (ROS), eNOS, AND HEME OXYGENASE (HO-1) LEVELS*

The aim of our study was to examine in detail the impact of NF-E2-related factor (Nrf2) activation on endothelial cell function with focus on redox homeostasis and the endothelial nitric oxide synthase (eNOS) system. We administered 2-cyano-3,12-dioxooleana-1,9-dien-28-oic imidazolide (CDDO-IM), a known activator of Nrf2, to primary human umbilical vein endothelial cells. Activation of Nrf2 by CDDO-IM increased the amount of bioavailable nitric oxide (NO), a major contributor to vascular homeostasis, in naive and stressed cells. Concomitantly, intracellular reactive oxygen species were dose-and time-dependently reduced. In apparent contrast to elevated NO levels, eNOS protein expression was transiently decreased in an Nrf2-dependent manner. Employing pharmacological inhibitors as well as a small interfering RNA approach, we identified de novo protein synthesis of heme oxygenase 1 (HO-1) and its enzymatic activity as cause for the observed reduction of eNOS. We hypothesize that under redox stress, when the availability of tetrahydrobiopterin, a pivotal stoichiometric cofactor for eNOS, is limited, activation of Nrf2 leads (a) to transient reduction of eNOS protein levels and (b) to an antioxidant defense in human umbilical vein endothelial cells. Both activities ensure that a stoichiometric ratio of eNOS and tetrahydrobiopterin is sustained and that the risk of eNOS uncoupling is reduced. Our study is the first to provide a causal link between Nrf2 activation and eNOS expression and NO levels, respectively