Transient epigenomic changes during pregnancy and early postpartum in women with and without type 2 diabetes.

AIM: To investigate epigenomic changes in pregnancy and early postpartum in women with and without type 2 diabetes. METHODS: Dimethylation of histones H3K4, H3K9, H3K27, H3K36 and H3K79 was measured in white blood cells of women at 30 weeks pregnancy, at 8-10 and 20 weeks postpartum and in never-pregnant women. RESULTS: Dimethylation levels of all five histones were different between women in pregnancy and early postpartum compared with never-pregnant women and were different between women with and without type 2 diabetes. CONCLUSION: Histone methylation changes are transient in pregnancy and early postpartum and may represent normal physiological responses to hormones. Different epigenomic profiles in women with type 2 diabetes mellitus may correlate with hormonal responses, leading to high risk pregnancy outcomes.

Mothers after Gestational Diabetes in Australia (MAGDA): A Randomised Controlled Trial of a Postnatal Diabetes Prevention Program.

BACKGROUND: Gestational diabetes mellitus (GDM) is an increasingly prevalent risk factor for type 2 diabetes. We evaluated the effectiveness of a group-based lifestyle modification program in mothers with prior GDM within their first postnatal year. METHODS AND FINDINGS: In this study, 573 women were randomised to either the intervention (n = 284) or usual care (n = 289). At baseline, 10% had impaired glucose tolerance and 2% impaired fasting glucose. The diabetes prevention intervention comprised one individual session, five group sessions, and two telephone sessions. Primary outcomes were changes in diabetes risk factors (weight, waist circumference, and fasting blood glucose), and secondary outcomes included achievement of lifestyle modification goals and changes in depression score and cardiovascular disease risk factors. The mean changes (intention-to-treat [ITT] analysis) over 12 mo were as follows: -0.23 kg body weight in intervention group (95% CI -0.89, 0.43) compared with +0.72 kg in usual care group (95% CI 0.09, 1.35) (change difference -0.95 kg, 95% CI -1.87, -0.04; group by treatment interaction p = 0.04); -2.24 cm waist measurement in intervention group (95% CI -3.01, -1.42) compared with -1.74 cm in usual care group (95% CI -2.52, -0.96) (change difference -0.50 cm, 95% CI -1.63, 0.63; group by treatment interaction p = 0.389); and +0.18 mmol/l fasting blood glucose in intervention group (95% CI 0.11, 0.24) compared with +0.22 mmol/l in usual care group (95% CI 0.16, 0.29) (change difference -0.05 mmol/l, 95% CI -0.14, 0.05; group by treatment interaction p = 0.331). Only 10% of women attended all sessions, 53% attended one individual and at least one group session, and 34% attended no sessions. Loss to follow-up was 27% and 21% for the intervention and control groups, respectively, primarily due to subsequent pregnancies. Study limitations include low exposure to the full intervention and glucose metabolism profiles being near normal at baseline. CONCLUSIONS: Although a 1-kg weight difference has the potential to be significant for reducing diabetes risk, the level of engagement during the first postnatal year was low. Further research is needed to improve engagement, including participant involvement in study design; it is potentially more effective to implement annual diabetes screening until women develop prediabetes before offering an intervention. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12610000338066.

Epigenetic Markers to Predict Conversion From Gestational Diabetes to Type 2 Diabetes.

CONTEXT: Lifestyle factors mediate epigenetic changes that can cause chronic diseases. Although animal and laboratory studies link epigenetic changes to diabetes, epigenetic information in women with gestational diabetes (GDM) and type 2 diabetes is lacking. OBJECTIVE: This study sought to measure epigenetic markers across pregnancy and early postpartum and identify markers that could be used as predictors for conversion from GDM to type 2 diabetes. DESIGN: Global histone H3 dimethylation was measured in white blood cells at three time points: 30 wk gestation, 8-10 wk postpartum, and 20 wk postpartum, from four groups of women with and without diabetes. SETTING AND PARTICIPANTS: A total of 39 participants (six to nine in each group) were recruited including: nondiabetic women; women with GDM who developed postpartum type 2 diabetes; women with GDM without postpartum type 2 diabetes; and women with type 2 diabetes. MAIN OUTCOME MEASURE: Percentages of dimethylation of H3 histones relative to total H3 histone methylation were compared between diabetic/nondiabetic groups using appropriate comparative statistics. RESULTS: H3K27 dimethylation was 50-60% lower at 8-10 and 20 wk postpartum in women with GDM who developed type 2 diabetes, compared with nondiabetic women. H3K4 dimethylation was 75% lower at 8-10 wk postpartum in women with GDM who subsequently developed type 2 diabetes compared with women who had GDM who did not. CONCLUSIONS: The percentage of dimethylation of histones H3K27 and H3K4 varied with diabetic state and has the potential as a predictive tool to identify women who will convert from GDM to type 2 diabetes.

Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) post-natal intervention: an update to the study protocol for a randomized controlled trial.

BACKGROUND: The Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) is a randomized controlled trial (RCT) that aims to assess the effectiveness of a structured diabetes prevention intervention for women who had gestational diabetes. METHODS/DESIGN: The original protocol was published in Trials (http://www.trialsjournal.com/content/14/1/339). This update reports on an additional exclusion criterion and change in first eligibility screening to provide greater clarity. The new exclusion criterion "surgical or medical intervention to treat obesity" has been added to the original protocol. The risks of developing diabetes will be affected by any medical or surgical intervention as its impact on obesity will alter the outcomes being assessed by MAGDA-DPP. The screening procedures have also been updated to reflect the current recruitment operation. The first eligibility screening is now taking place either during or after pregnancy, depending on recruitment strategy. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ANZCTRN 12610000338066.

Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) post-natal intervention: study protocol for a randomized controlled trial.

BACKGROUND: Gestational diabetes mellitus (GDM) is defined as glucose intolerance with its onset or first recognition during pregnancy. Post-GDM women have a life-time risk exceeding 70% of developing type 2 diabetes mellitus (T2DM). Lifestyle modifications reduce the incidence of T2DM by up to 58% for high-risk individuals. METHODS/DESIGN: The Mothers After Gestational Diabetes in Australia Diabetes Prevention Program (MAGDA-DPP) is a randomized controlled trial aiming to assess the effectiveness of a structured diabetes prevention intervention for post-GDM women. This trial has an intervention group participating in a diabetes prevention program (DPP), and a control group receiving usual care from their general practitioners during the same time period. The 12-month intervention comprises an individual session followed by five group sessions at two-week intervals, and two follow-up telephone calls. A total of 574 women will be recruited, with 287 in each arm. The women will undergo blood tests, anthropometric measurements, and self-reported health status, diet, physical activity, quality of life, depression, risk perception and healthcare service usage, at baseline and 12 months. At completion, primary outcome (changes in diabetes risk) and secondary outcome (changes in psychosocial and quality of life measurements and in cardiovascular disease risk factors) will be assessed in both groups. DISCUSSION: This study aims to show whether MAGDA-DPP leads to a reduction in diabetes risk for post-GDM women. The characteristics that predict intervention completion and improvement in clinical and behavioral measures will be useful for further development of DPPs for this population. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ANZCTRN 12610000338066.

Anaphylaxis - identification, management and prevention.

OBJECTIVE: This article summarises current knowledge regarding the identification, management and prevention of anaphylaxis, highlighting risk minimisation strategies relevant to general practitioners. DISCUSSION: The most common causes of anaphylaxis are medication, food and insect venom. Medications are the most common cause of anaphylaxis in older adults, particularly antibiotics, anaesthetic drugs, nonsteroidal anti-inflammatory drugs and opiates. Food allergy is the most common cause of anaphylaxis in children, but rarely results in death. Anaphylaxis is a medical emergency requiring immediate treatment with adrenaline, as well as ongoing management. Important steps for long-term risk minimisation include avoidance of triggers, prescription of an adrenaline autoinjector, maintenance of a personalised emergency action plan for anaphylaxis, education for patients and families and regular review to optimise management.

Can scientists and policy makers work together?

This paper addresses a fundamental question in evidence based policy making--can scientists and policy makers work together? It first provides a scenario outlining the different mentalities and imperatives of scientists and policy makers, and then discusses various issues and solutions relating to whether and how scientists and policy makers can work together. Scientists and policy makers have different goals, attitudes toward information, languages, perception of time, and career paths. Important issues affecting their working together include lack of mutual trust and respect, different views on the production and use of evidence, different accountabilities, and whether there should be a link between science and policy. The suggested solutions include providing new incentives to encourage scientists and policy makers to work together, using knowledge brokers (translational scientists), making organisational changes, defining research in a broader sense, re-defining the starting point for knowledge transfer, expanding the accountability horizon, and finally, acknowledging the complexity of policy making. It is hoped that further discussion and debate on the partnership idea, the need for incentives, recognising the incompatibility problems, the role of civil society, and other related themes will lead to new opportunities for further advancing evidence based policy and practice.

Congestive cardiac failure: urban and rural perspectives in Victoria.

OBJECTIVE: Effective and timely care for congestive cardiac failure (CCF) should reduce the risks of hospitalisation. The purpose of this study is to describe variations in rates of hospital admissions for CCF in Victoria as an indicator of the adequacy of primary care services. Detailed analyses identify trends in hospitalisations, urban/rural differentials and variations by the Primary Care Partnerships (PCP). SETTING: Acute care hospitals in Victoria. DESIGN: Routine analyses of age and sex standardised admission rates of CCF in Victoria using the Victorian Admitted Episodes Dataset from 1993-1994 to 2000-2001. SUBJECTS: All patients admitted to acute care hospitals in Victoria with the principal diagnosis of CCF between 1993-1994 and 2000-2001. RESULTS: There were 8359 admissions for CCF in Victoria with an average of 7.37 bed days in 2000-2001. There was a significantly higher admission rate for CCF in rural areas compared to metropolitan in 2000/200--(2.53/1000 (2.44-2.62) and 1.80/1000 (1.75-1.85))--respectively. Small area analyses identified 17 PCP (14 of which were rural) with significantly higher admission rate ratios of CCF compared to Victoria. CONCLUSION: Small area analyses of CCF have identified significant gaps in the management of CCF in the community. This may be a reflection of deficit in primary care availability, accessibility, or appropriateness. Detailed studies may be needed to determine the relative importance of these factors in Victoria for targeting specific interventions at the PCP level.

A public health model of the social determinants of health.

As we move forward in the new century, epidemiologists and public health practitioners are faced with the challenge of reviewing the current direction of epidemiology and its links with public health. While the history of epidemiology has been a successful and productive one, there is a danger that modern epidemiology is becoming too narrow in its scope, concerned primarily with the analysis of risk factors in individuals, while ignoring sociological and ecological perspectives of health. We argue that a theoretical framework to guide the practice of epidemiology is needed which encompasses a role for social determinants of health while simultaneously also acknowledging the importance of behaviour and biology, and the inter-connectedness of all these factors. This paper presents a public health model of social determinants of health, which provides a framework for testing the causal pathways linking social determinant variables with health care system attributes, disease inducing behaviours and health outcomes. This approach provides an improved opportunity to identify and evaluate evidence-based public health interventions, and facilitates stronger links between modern epidemiology and public health practice.