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To determine rates and predictors of postpartum diabetes screening among Aboriginal and/or Torres Strait Islander and non-Indigenous women with gestational diabetes mellitus (GDM).PANDORA is a prospective longitudinal cohort of women recruited in pregnancy. Postpartum diabetes screening rates at 12 weeks (75-g oral glucose tolerance test (OGTT)) and 6, 12 and 18 months (OGTT, glycated haemoglobin [HbAPostpartum screening rates with an OGTT by 12 weeks and 6 months postpartum were lower among Aboriginal and/or Torres Strait Islander women than non-Indigenous women (18% vs. 30% at 12 weeks, and 23% vs. 37% at 6 months, p 0.001). Aboriginal and/or Torres Strait Islander women were more likely to have completed a 6-month HbAGiven very high rates of type 2 diabetes among Aboriginal and Torres Strait Islander women, early postpartum screening with the most feasible test should be prioritised to detect prediabetes and diabetes for intervention.

Refereed/Peer-reviewed Background: Benefits of breastfeeding on infant growth in children born to mothers with gestational diabetes mellitus (GDM) are uncertain. Objectives: To describe growth trajectories between birth and 14 months according to breastfeeding and maternal hyperglycaemia in pregnancy, and assess associations between breastfeeding and 14 month growth outcomes among children born to mothers with GDM. Subjects/methods: Data on 258 Aboriginal and Torres Strait Islander infants from the PANDORA study born to mothers with normoglycaemia (n = 73), GDM (n = 122), or with pre-existing type 2 diabetes (n = 63) in pregnancy were assessed. Infant weight and BMI growth trajectories according to predominant breastfeeding at 6 months and hyperglycaemia in pregnancy were developed using mixed-effect models and cubic splines. Associations between breastfeeding and 14-month growth outcomes (z-scores: weight-for-age, weight-for-length and BMI) were evaluated using linear regression in a subgroup of infants born to mothers with GDM. Results: Predominantly breastfed infants had lower BMI trajectories compared to those not predominantly breastfed, irrespective of maternal hyperglycaemia in pregnancy status (p

To assess associations of hyperglycemia in pregnancy with the risk of postpartum hemorrhage (PPH) in a prospective cohort of Indigenous and non-Indigenous women, compared with normoglycemia.Data were from 1102 (48% Indigenous) women of the Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) Study. Age-adjusted associations of gestational diabetes mellitus (GDM) or pre-existing type 2 diabetes mellitus (T2DM), obstetric and demographic covariables with PPH (blood loss ≥500 ml) were assessed using logistic regression. Multivariable-adjusted models included Indigenous ethnicity, diabetes type and their interaction.A higher proportion of Indigenous women developed PPH than non-Indigenous women (32% versus 22%; P 0.001). Compared with non-Indigenous women with normoglycemia, risks of PPH for Indigenous women with GDM or T2DM were higher (odds ratio [OR] 1.83, 95% confidence intervals [CI] 1.11-3.02, and OR 1.72, 95% CI 0.99-3.00 after age adjustment, OR 1.84, 95% CI 1.06-3.19, and OR 1.33, 95% CI 0.70-2.54 after adjustment for school education and delivery mode, and OR 1.62, 95% CI 0.95-2.77, and OR 0.99, 95% CI 0.53-1.86 after adjustment for birth weight). Importantly, Indigenous women without hyperglycemia in pregnancy were not at increased risk of PPH.The significantly higher rates of PPH experienced by Indigenous women compared with non-Indigenous women may be explained by a greater effect of GDM among Indigenous women that was only partly accounted for by birth weight.

In Australia's Northern Territory, Indigenous mothers account for 33% of births and have high rates of hyperglycemia in pregnancy. The prevalence of type 2 diabetes (T2D) in pregnancy is up to 10-fold higher in Indigenous than non-Indigenous Australian mothers, and the use of metformin is common. We assessed birth outcomes in relation to metformin use during pregnancy from a clinical register.The study included women with gestational diabetes (GDM), newly diagnosed diabetes in pregnancy (DIP), or pre-existing T2D from 2012 to 2016. Data were analyzed for metformin use in the third trimester. Regression models were adjusted for maternal age, body mass index, parity, and insulin use.Of 1649 pregnancies, 814 (49.4%) were to Indigenous women, of whom 234 (28.7%) had T2D (vs 4.6% non-Indigenous women; P 0.001). Metformin use was high in Indigenous women (84%-90% T2D, 42%-48% GDM/DIP) and increased over time in non-Indigenous women (43%-100% T2D, 14%-35% GDM/DIP). Among Indigenous women with GDM/DIP, there were no significant differences between groups with and without metformin in cesarean section (51% vs 39%; adjusted odds ratio [aOR] 1.25, 95% confidence interval [CI] 0.87-1.81), large for gestational age (24% vs 13%; aOR 1.5, 95% CI 0.9-2.5), or serious neonatal adverse events (9.4% vs 5.9%; aOR 1.32, 95% CI 0.68-2.57). Metformin use was independently associated with earlier gestational age (37.7 vs 38.5 weeks), but the risk did not remain independently higher after exclusion of women managed with medical nutrition therapy alone, and the increase in births37 weeks was not significant on multivariate analysis.We found no clear evidence of any adverse outcomes related to the use of metformin for the treatment of hyperglycemia in pregnancy.摘要: 背景 在澳大利亚北部地区, 原住民母亲的婴儿出生率占33%, 她们妊娠期间出现高血糖的风险很高。原住民母亲在妊娠期间的2型糖尿病(T2D)患病率与非原住民澳大利亚母亲相比较要高10倍, 并且经常使用二甲双胍治疗。我们利用临床登记表数据评估了妊娠期间使用二甲双胍治疗与出生结果之间的关系。 方法 这项研究从2012至2016年纳入了妊娠糖尿病(gestational diabetes, GDM)、妊娠期新诊断糖尿病(newly diagnosed diabetes in pregnancy, DIP)以及既往已经存在T2D的妇女。对妊娠晚期使用二甲双胍的数据进行了分析。根据母亲年龄、体重指数、产次以及胰岛素使用情况校正了回归模型。 结果 在1649名孕妇中有814名(49.4%)为原住民妇女, 其中234名(28.7%)为T2D(非原住民妇女T2D比例为4.6%；P 0.001)。原住民妇女的二甲双胍使用率更高(在T2D中为84%-90%, 在GDM/DIP中为42%-48%), 并且在非原住民妇女中随着时间的推移使用率在上升(在T2D中为43%-100%, 在GDM/DIP中为14%-35%)。在合并GDM/DIP的原住民妇女中, 使用二甲双胍治疗组与不使用二甲双胍治疗组之间的剖宫产率(分别为51%与39%; 校正后的odds ratio [aOR]为1.25, 95%置信区间[CI]为0.87-1.81)、出现大胎龄率(分别为24%与13%；aOR为1.5, 95% CI为0.9-2.5)、新生儿出现严重不良事件率(分别为9.4%与5.9%；aOR为1.32, 95% CI为0.68-2.57)都没有显著性差异。使用二甲双胍治疗与胎龄更小(分别为37.7与38.5周)独立相关, 但是将单独接受药物营养治疗的妇女排除之后, 这种风险没有独立地处于较高的水平, 并且多变量分析显示37周的出生率并没有显著地升高。 结论 我们没有发现任何与妊娠期间高血糖妇女使用二甲双胍治疗出现不良结果相关的明确证据。.

Aims/hypothesis: Women with gestational diabetes mellitus (GDM) and obesity experience lower rates of breastfeeding. Little is known about breastfeeding among mothers with type 2 diabetes. Australian Indigenous women have a high prevalence of type 2 diabetes in pregnancy. We aimed to evaluate the association of hyperglycaemia, including type 2 diabetes, with breastfeeding outcomes. Methods: Indigenous (n = 495) and non-Indigenous (n = 555) participants of the Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) cohort included women without hyperglycaemia in pregnancy (n = 222), with GDM (n = 684) and with type 2 diabetes (n = 144). The associations of hyperglycaemia in pregnancy and breastfeeding at hospital discharge, 6 weeks and 6 months post-partum were evaluated with logistic regression, after adjustment for maternal obesity, ethnicity, maternal and neonatal characteristics. Results: Indigenous women were more likely to predominantly breastfeed at 6 weeks across all levels of hyperglycaemia. Compared with women with no hyperglycaemia in pregnancy, women with type 2 diabetes had lower odds for exclusive breastfeeding at discharge (adjusted OR for exclusive breastfeeding 0.4 [95% CI 0.2, 0.8] p = 0.006). At 6 weeks and 6 months, the relationship between type 2 diabetes and predominant breastfeeding was not statistically significant (6 weeks 0.7 [0.3, 1.6] p = 0.40, 6 months 0.8 [0.4, 1.6] p = 0.60). Women with gestational diabetes were as likely to achieve predominant breastfeeding at 6 weeks and 6 months as women without hyperglycaemia in pregnancy. Conclusions/interpretation: Indigenous women had high rates of breastfeeding. Women with type 2 diabetes had difficulty establishing exclusive breastfeeding at hospital discharge. Further research is needed to assess the impact on long-term breastfeeding outcomes Refereed/Peer-reviewed

Aims/hypothesis We aimed to assess associations between cord blood metabolic markers and fetal overgrowth, and whether cord markers mediated the impact of maternal adiposity on neonatal anthropometric outcomes among children born to Indigenous and Non-Indigenous Australian women with normal glucose tolerance (NGT), gestational diabetes mellitus (GDM) and pregestational type 2 diabetes mellitus.Methods From the Pregnancy and Neonatal Outcomes in Remote Australia (PANDORA) study, an observational cohort of 1135mother-baby pairs, venous cord blood was available for 645 singleton babies (49% Indigenous Australian) of women with NGT(n = 129),GDM(n = 419) and type 2 diabetes (n = 97). Cord glucose, triacylglycerol, HDL-cholesterol, C-reactive protein (CRP)and C-peptide were measured. Multivariable logistic and linear regression were used to assess the associations between cord blood metabolic markers and the outcomes of birthweight z score, sum of skinfold thickness (SSF), being large for gestational age(LGA) and percentage of body fat. Pathway analysis assessed whether cord markers mediated the associations between maternal and neonatal adiposity. Results Elevated cord C-peptide was significantly associated with increasing birthweight z score (β 0.57 [95% CI 0.42, 0.71]),SSF (β 0.83 [95% CI 0.41, 1.25]), percentage of body fat (β 1.20 [95% CI 0.69, 1.71]) and risk for LGA [OR 3.14 [95% CI 2.11,4.68]), after adjusting for age, ethnicity and diabetes type. Cord triacylglycerol was negatively associated with birthweight z score for Indigenous Australian women only. No associations between cord glucose, HDL-cholesterol and CRP >0.3 mg/l (2.9 nmol/l)with neonatal outcomes were observed. C-peptide mediated 18% (95% CI 13, 36) of the association of maternal BMI with LGAand 11% (95% CI 8, 17) of the association with per cent neonatal fat. Conclusions/interpretation Cord blood C-peptide is an important mediator of the association between maternal and infant adiposity, across the spectrum of maternal glucose tolerance. Refereed/Peer-reviewed

Background: In Australia’s Northern Territory, 33% of babies are born to Indigenous mothers, who experience high rates of hyperglycemia in pregnancy. We aimed to determine the extent to which pregnancy outcomes for Indigenous Australian women are explained by relative frequencies of diabetes type [type 2 diabetes (T2DM) and gestational diabetes (GDM)]. Methods: This prospective birth cohort study examined participants recruited from a hyperglycemia in pregnancy register. Baseline data collected were antenatal and perinatal clinical information, cord blood and neonatal anthropometry. Of 1135 women (48%Indigenous), 900 had diabetes: 175 T2DM, 86 newly diagnosed diabetes in pregnancy(DIP) and 639 had GDM. A group of 235 women without hyperglycemia in pregnancywas also recruited. Results: Diabetes type differed for Indigenous and non-Indigenous women (T2DM, 36 vs5%; DIP, 15 vs 7%; GDM, 49 vs 88%, p < 0.001). Within each diabetes type, Indigenous women were younger and had higher smoking rates. Among women with GDM/DIP,Indigenous women demonstrated poorer birth outcomes than non-Indigenous women:large for gestational age, 19 vs 11%, p ¼ 0002; neonatal fat 11.3 vs 10.2%, p < 0.001. Inthe full cohort, on multivariate regression, T2DM and DIP were independently associated(and Indigenous ethnicity was not) with pregnancy outcomes Conclusions: Higher rates of T2DM among Indigenous women predominantly contribute to absolute poorer pregnancy outcomes among Indigenous women with hyperglycemia.As with Indigenous and minority populations globally, prevention or delay of type 2 diabetes in younger women is vital to improve pregnancy outcomes and possibly to improve the long-term health of their offspring. Refereed/Peer-reviewed

Aims: Preconception care may decrease adverse pregnancy outcomes associated with pre-existing diabetes mellitus. Aboriginal Australians are at high risk of type 2 diabetes mellitus (T2DM), with earlier onset. We explored practitioner views on preconception care delivery for women with T2DM in the Northern Territory, where 31% of births are to Aboriginal women. Methods: Mixed-methods study including cross-sectional survey of 156 health practitioners and 11 semi-structured interviews. Results: Practitioners reported low attendance for preconception care however, 51% provided counselling on an opportunistic basis. Rural/remote practitioners were most likely to find counselling feasible. The majority (69%) utilised appropriate guidelines and addressed lifestyle modifications including smoking (81%), weight management (79%), and change medications appropriately such as ceasing ACE inhibitors (69%). Fewer (40%) prescribed the recommended dose of folate (5 mg) or felt comfortable recommending delaying pregnancy to achieve optimal preconception glucose control (42%). Themes identified as barriers to care included the complexity of care setting and infrequent preconception consultations. There was a focus on motivation of women to make informed choices about conception, including birth spacing, timing and contraception. Preconception care enablers included cross-cultural communication, a multi-disciplinary care team and strong client-based relationships. Conclusions: Health practitioners are keen to provide preconception counselling and reported knowledge of evidence-based guidelines. Improvements are needed in recommending high dose folate and optimising glucose control. Cross-cultural communication and team-based care were reported as fundamental to successful preconception care in women with T2DM. Continued education and policy changes are required to support practitioners in opportunities to enhance pregnancy planning. Refereed/Peer-reviewed

Background: Australian Indigenous women experience high rates of social disadvantage and type 2 diabetes (T2D) in pregnancy, but it is not known how social factors and maternal behaviours impact neonatal adiposity in offspring of women with hyperglycaemia in pregnancy.Methods: Participants were Indigenous (n = 404) and Europid (n = 240) women with gestational diabetes mellitus (GDM) or T2D in pregnancy and their offspring in the Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) study. Social, economic factors, and maternal behaviours were measured in pregnancy and six neonatal anthropometric outcomes were examined after birth.Results: On univariate analysis, maternal education < 12 years (p = 0.03), unemployment(p = 0.001), welfare income vs no welfare income (p = 0.001), lower area based socioeconomic score (p < 0.001), and fast food intake > 2 times/week (p = 0.002) were associated with increased sum of skinfolds (SSF) in offspring. Smoking was significantly associated witha reduction in anthropometric measures, except SSF. In multivariable models adjusted for ethnicity, BMI and hyperglycaemia, social and economic factors were no longer significant predictors of neonatal outcomes. Smoking was independently associated with a reduction inlength, head circumference and fat free mass. Frequent fast food intake remained independently associated with SSF (b-coefficient 1.08 mm, p = 0.02).Conclusion: In women with hyperglycaemia in pregnancy, social factors were associated with neonatal adiposity, particularly skinfold measures. Promoting smoking cessation and limited intake of energy-dense, nutrient-poor foods in pregnancy are important to improve neonatal adiposity and lean mass outcomes. Addressing inequities in social and economic factors are likely to be important, particularly for Indigenous women or women experiencing social disadvantage. Refereed/Peer-reviewed

Background In-utero exposures likely influence the onset and severity of obesity in youth. With increasing rates of type 2 diabetes mellitus (T2DM) and maternal adiposity in pregnancy globally, it is important to assess the impact of these factors on neonatal adipose measures. Objectives To evaluate the contribution of maternal ethnicity, body mass index (BMI), gestational weight gain, and hyperglycaemia to neonatal adiposity. Methods Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) is a longitudinal cohort study of Australian mother and neonate pairs. In this analysis, Indigenous (n = 519) and Europid (n = 358) women were included, of whom 644 had hyperglycaemia (type 2 diabetes [T2DM], diabetes in pregnancy [DIP], or gestational diabetes [GDM]). Associations between maternal ethnicity, hyperglycaemia, BMI and gestational weight gain, and the neonatal outcomes of length, head circumference, sum of skinfolds, total body fat, and percentage body fat were examined. Models were adjusted for maternal age, smoking status, parity, education, neonatal gender, and gestational age. Results Among those with hyperglycaemia in pregnancy, Indigenous women had a higher proportion of T2DM and DIP (36%, 13%) compared with Europid women (4%, 3%). In multivariate analysis, maternal T2DM (compared with no hyperglycaemia), BMI during pregnancy, and excess compared with appropriate gestational weight gain, were significantly associated with greater neonatal measures. DIP was associated with greater sum of skinfolds, total body fat, and percentage body fat. Indigenous ethnicity was associated with greater sum of skinfolds. Conclusions Maternal BMI, excess gestational weight gain, and hyperglycaemia operated as independent factors influencing neonatal adiposity. Interventions addressing these factors are needed to reduce neonatal adiposity.

Diabetes in pregnancy (DIP) is a common complication of pregnancy and its global prevalence is increasing, due to increase in both obesity rates and childbearing age. This is of concern as DIP is associated with worse perinatal outcomes for both mother and baby. There are also long-term outcomes for the offspring including increased risk of obesity and diabetes in their adolescence and adulthood. This review highlights the methodological challenges in estimating the global prevalence of gestational diabetes and its trends and population groups that are at risk of DIP. In addition the review discusses the increasing burden of type 2 diabetes in pregnancy and its complications, the importance of pre-conception counselling in women with pre-existing diabetes, and the challenges in management of this condition.

Aims To assess outcomes of women in the Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) cohort with gestational diabetes mellitus (GDM) managed by lifestyle modification compared with women without hyperglycaemia in pregnancy. Methods Indigenous (n = 97) and Europid (n = 113) women managed by lifestyle modification were compared to women without hyperglycaemia (n = 235). Multivariate linear and logistic regressions assessed whether GDM-lifestyle women had poorer outcomes compared to women without hyperglycaemia. Results Women with GDM-lifestyle had higher body mass index and lower gestational weight gain than women without hyperglycaemia. On univariate analysis, gestational age at delivery was lower and induction rates were higher in women with GDM-lifestyle than without hyperglycaemia. On multivariable regression, GDM-lifestyle was associated with lower gestational age at delivery (by 0.73 weeks), lower birthweight z-score (by 0.26, p = 0.007), lower likelihood of large for gestational age (LGA) [OR (95% CI): 0.55 (0.28, 1.02), p = 0.059], and greater likelihood of labour induction [2.34 (1.49, 3.66), p Conclusion Women with GDM managed by lifestyle modification had higher induction rates and their offspring had lower birthweight z-scores, with a trend to lower LGA than those without hyperglycaemia in pregnancy. Further studies are indicated to explore reasons for higher induction rates.

Introduction Thyrotoxic patients presenting for surgery should ideally be biochemically and clinically euthyroid. This is conventionally achieved through the use of anti-thyroid drugs, beta-blocker therapy and iodine. However, there are some circumstances where anti-thyroid drugs may not be a viable option. The implications of this scenario are not widely reported in the literature. This clinical review looks at the evidence on the safety of beta-blocker therapy without the use of anti-thyroid drugs in the preparation of the thyrotoxic patient for surgery. We also highlight key points in the pathophysiology of thyrotoxicosis and the management goals of these patients. Conclusion In circumstances where the use of anti-thyroid drugs is not possible in the preoperative management of patients for thyroid or non-thyroid surgery, the use of beta-blockers has been shown to be safe and effective. Safety can be increased by using iodine with or without corticosteroids up to the day of surgery in the rapid preoperative preparation of a severely thyrotoxic patient.

This study explores the potential of DNA complexes prepared with methylated collagen (MC) and unmodified native collagen (NC) to deliver genes into cells. The physicochemical properties and transfection abilities of these two types of complexes are studied in parallel. MC was prepared by methylation of the carboxyl groups of collagen, rendering the collagen net positively charged at neutral pH. NC/DNA complexes were prepared at pH approximately 3, but aggregated rapidly at neutral pH. These complexes did not confer significant protection to DNA due to its poor stability in serum. MC carried a positive charge at neutral pH and formed complexes with DNA in PBS; therefore MC improved DNA binding ability and the stability of the complexes at physiological conditions. MC/DNA complexes were smaller and more stable than NC/DNA complexes in PBS, and sustained released of DNA from MC/DNA complexes was observed for up to 3 weeks in PBS at 37 degrees C. In contrast, NC/DNA complexes released almost all the DNA within 6h under the same condition. In vitro gene transfection experiments revealed that MC mediated a higher gene expression than NC, although the level of gene expression was still much lower than that achieved with polyethyleneimine/DNA complexes. In contrast to in vitro results, NC/DNA complexes yielded a 3.8-fold higher gene expression than naked DNA and MC/DNA complexes (P < 0.05) at week 2 following intramuscular injection at a DNA dose of 3 microg per muscle and a weight ratio of 1. Higher weight ratios resulted in significant decrease of transfection efficiency, particularly for MC/DNA complexes. The results suggested that gene delivery via the intramuscular route followed a different mechanism that demands a different set of physiochemical properties of the carrier from other parental routes. The potential of these collagen-based gene carriers for other administration routes remain to be further investigated.

Potassium levels are regularly used as a prognostic factor to cease resuscitation in significant hypothermia. In this case report, we highlight how survival is still possible with extreme hyperkalaemia in severe hypothermia. We present a case of a 65-year-old Caucasian man who presented with metformin associated lactic acidosis. On presentation he had potassium of 9.1 mmol/l and a temperature of 31.5 °C. Cardiopulmonary resuscitation was commenced when he went into asystolic arrest. This presentation would commonly make attempts at resuscitation futile with a 100% death rate. However, with appropriate management this patient's condition improved and survival was possible. We provide evidence that survival is possible in profound hyperkalaemia and hypothermia. Effective cardiopulmonary resuscitation with early haemofiltration can be successful.

Background: Diabetes in pregnancy carries an increased risk of adverse pregnancy outcomes for both the mother and foetus, but it also provides an excellent early opportunity for intervention in the life course for both mother and baby. In the context of the escalating epidemic of chronic diseases among Indigenous Australians, it is vital that this risk is reduced as early as possible in the life course of the individual. The aims of the PANDORA Study are to: (i) accurately assess rates of diabetes in pregnancy in the Northern Territory (NT) of Australia, where 38% of babies are born to Indigenous mothers; (ii) assess demographic, clinical, biochemical, anthropometric, socioeconomic and early life development factors that may contribute to key maternal and neonatal birth outcomes associated with diabetes in pregnancy; and (iii) monitor relevant post-partum clinical outcomes for both the mothers and their babies. Methods/Design: Eligible participants are all NT women with diabetes in pregnancy aged 16 years and over. Information collected includes: standard antenatal clinical information, diagnosis and management of diabetes in pregnancy, socio-economic status, standard clinical birth information (delivery, gestational age, birth weight, adverse antenatal and birth outcomes). Cord blood is collected at the time of delivery and detailed neonatal anthropometric measurements performed within 72 hours of birth. Information will also be collected regarding maternal postpartum glucose tolerance and cardio-metabolic risk factor status, breastfeeding and growth of the baby up to 2 years post-partum in the first instance. Discussion: This study will accurately document rates and outcomes of diabetes in pregnancy in the NT of Australia, including the high-risk Indigenous Australian population. The results of this study should contribute to policy and clinical guidelines with the goal of reducing the future risk of obesity and diabetes in both mothers and their offspring. Refereed/Peer-reviewed