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ObjectivesTo assess the prevalence and incidence of diabetes among Aboriginal peoples in remote communities of the Northern Territory (NT), Australia.DesignRetrospective cohort analysis of linked clinical and administrative data sets from 1 July 2012 to 30 June 2019.SettingRemote health centres using the NT Government Primary Care Information System (51 out of a total of 84 remote health centres in the NT).ParticipantsAll Aboriginal clients residing in remote communities serviced by these health centres (N=21 267).Primary outcome measuresDiabetes diagnoses were established using hospital and primary care coding, biochemistry and prescription data.ResultsDiabetes prevalence across all ages increased from 14.4% (95% CI: 13.9% to 14.9%) to 17.0% (95% CI: 16.5% to 17.5%) over 7 years. Among adults (≥20 years), the 2018/2019 diabetes prevalence was 28.6% (95% CI: 27.8% to 29.4%), being higher in Central Australia (39.5%, 95% CI: 37.8% to 41.1%) compared with the Top End region (24.2%, 95% CI: 23.3% to 25.1%, pConclusionsThe burden of diabetes in the remote Aboriginal population of the NT is among the highest in the world. Strengthened systems of care and public health prevention strategies, developed in partnership with Aboriginal communities, are needed.

BACKGROUND Pancreatitis and diabetes are common among Aboriginal people of Central Australia. The contribution of pancreatitis to the development of Post-Pancreatitis Diabetes-Mellitus (PPDM) is not known. AIMS To describe among Aboriginal and non-Aboriginal people living in Central Australia, (i) the prevalence and aetiology of Acute (AP) and Chronic Pancreatitis (CP) and, (ii) diagnosis of new onset diabetes after pancreatitis. METHODS Retrospective medical record review of patients ≥ 15 years admitted to hospitals in the Central Australia Health Service between 2009 and 2018 with pancreatitis. Prevalence as a proportion of the resident population and aetiology of AP and CP were determined. Diagnosis of new onset diabetes after admission with pancreatitis was assessed. RESULTS Of the 638 patients assessed, 73% were Aboriginal and 48% female. The annual prevalence in 2009 and 2018 for AP was 171 and 203 per 100 000 persons, and for CP was 206 and 114 per 100 000 persons, respectively. Rates were high in Aboriginal people. Alcohol aetiology was most common in Aboriginal people at (66%) and biliary aetiology in non-Aboriginal people (37%). A diagnosis of diabetes after pancreatitis was detected in 125 of 438 (29%) patients who did not have diabetes diagnosis previously recorded, and 20 of the 22 tested for diabetes-associated antibodies were negative, fitting criteria for PPDM. CONCLUSION Prevalence of AP and CP in Central Australia was higher in Aboriginal than non-Aboriginal people. Few patients with diabetes recorded after pancreatitis had appropriate PPDM diagnostic testing. Inter-disciplinary education on the diagnosis of PPDM is required. This article is protected by copyright. All rights reserved.

Objectives To determine demographic and clinical characteristics of youth diagnosed with type 1 (T1D) or type 2 (T2D) diabetes aged ≤15 years from 1999-2019 in Western Australia, and examine time to first diagnosis of diabetes complications. Methods A retrospective cohort study was conducted of patients identified from the population-based, prospective Western Australian Children's Diabetes Database and longitudinal data extracted for available demographic and clinical variables. Patients were followed from diagnosis to transition to adult services, death or 31st December 2019. Cox proportional hazards regression models were used to analyse time to first diagnosis of hypertension, high cholesterol or microalbuminuria, after adjusting for sex, age at diagnosis, time period of diagnosis, haemoglobin A1c and body max index Z-score. Results 2,438 eligible patients were identified (2,209 (91%) T1D: 229 (9%) T2D). The mean age at diagnosis was lower in patients with T1D (8.5(±4.0) vs 12.7(±2.0) years). A higher proportion of patients with T2D were female (58% vs 47%) and of Aboriginal ethnicity (59% vs 2%). The median HbA1c [IQR] at diagnosis was lower (8.9%[6.7,11.5](74mmol/mol[50,102]) vs 11.6%[10.1,13.3](103 mmol/mol[87,122])) and mean body max index Z-score higher (2.05(±0.66) vs 0.37(±0.95)), in patients with T2D compared to T1D. Patients with T2D had a higher risk of hypertension, high cholesterol and microalbuminuria (aHR 3.39(95%CI:2.04,5.63), 2.69(95%CI:1.21,5.98) and 19.79(95%CI:10.99, 35.64) respectively). Conclusion Distinct demographic and clinical characteristics continue to be observed in this contemporary population-based cohort of paediatric patients diagnosed with T1D and T2D. Youth with T2D have significantly higher risk of diabetes complications within five years of diagnosis. This article is protected by copyright. All rights reserved.

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。.

Aboriginal and Torres Strait Islander women have high rates of gestational diabetes (GDM). The Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) study is a prospective longitudinal cohort of women with type 2 diabetes (T2D), GDM or normoglycemia in pregnancy in the Northern Territory, Australia. In this analysis we report progression to prediabetes and T2D at 2.5 years [range 2.1, 3] postpartum in a subgroup of Aboriginal and Europid women with GDM and normoglycemia in pregnancy (n=337). Women with pre-existing T2D were excluded. Data were analysed using Fisher’s exact tests. Among Aboriginal women with GDM we assessed predictions for progression using multivariate logistic regression. Aboriginal women with GDM (n=111) were younger than Europid women with GDM (n=104) (29 years (SD 5.9) vs. 32 (5.6) p Disclosure A. Wood: None. J. Boyle: None. F. Barzi: None. E.L. Barr: None. M.J.I. Hare: None. A. Titmuss: None. E. Death: None. M. Kirkwood: None. A. Simmonds: None. E.M. Moore: None. J. Oats: None. D. McIntyre: Other Relationship; Self; Novo Nordisk A/S. P.Z. Zimmet: None. A.D. Brown: None. J.E. Shaw: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Mylan, Sanofi. Research Support; Self; AstraZeneca. Speaker’s Bureau; Self; Eli Lilly and Company, Mylan. L.J. Maple-Brown: None.

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

© 2020. Introduction: This study sought to determine change in chronic condition risk factors in a remote Indigenous community following a 3-year period of community-led health promotion initiatives. Methods: Data were compared between two cross-sectional surveys of Indigenous Australian community residents before and after health promotion activities, and longitudinal analysis of participants present at both surveys using multilevel mixed-effects regression. Results: At baseline, 294 (53% women; mean age 35 years) participated and 218 attended the second survey (56% women, mean age 40 years), and 87 attended both. Body composition, blood pressure and urinary albumin-to-creatinine ratio remained stable between baseline and follow-up. After adjusting for age and sex, haemoglobin A1c significantly increased (from 57 to 63 mmol/mol (7.5% to 8.1%), p=0.021) for those with diabetes. Increases were also observed for total cholesterol (from 4.4 to 4.6 mmol/L, p=0.006) and triglycerides (from 1.5 to 1.6 mmol/L, p=0.019), and high-density lipoprotein cholesterol levels improved (from 0.98 to 1.02 mmol/L, p=0.018). Self-reported smoking prevalence was high but stable between baseline (57%) and follow-up (56%). Similar results were observed in the longitudinal analysis to the cross-sectional survey comparison. Conclusion: Community-led health promotion initiatives may have had some benefits on chronic condition risk factors, including stabilisation of body composition, in this remote Indigenous community. Given that less favourable trends were observed for diabetes and total cholesterol over a short time period and smoking prevalence remained high, policy initiatives that address social and economic disadvantage are needed alongside community-led health promotion initiatives.

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: Hyperglycaemia in pregnancy contributes to adverse outcomes for women and their children. The postpartum period is an opportune time to support women to reduce cardiometabolic and diabetes risk in subsequent pregnancies. Aims: To identify strengths and gaps in current care for Aboriginal women after a pregnancy complicated by hyperglycaemia. Methods: A retrospective review of the 12 month postpartum care provided by primary health centres in remote Australia in 2013&ndash, 2014 identified 195 women who experienced hyperglycaemia in pregnancy (gestational diabetes (GDM) (n = 147), type 2 diabetes (T2D) (n = 39), and unclear diabetes status (n = 9)). Results: Only 80 women (54%) with GDM had postpartum glycaemic checks. Of these, 32 women were diagnosed with prediabetes (n = 24) or diabetes (n = 8). Compared to women with GDM, women with T2D were more likely to have their weight measured (75% vs. 52%, p &lt, 0.01), and smoking status documented as &ldquo, discussed&rdquo, (65% vs. 34%, p &lt, 0.01). Most women (97%) accessed the health centre at least once in the 12 month postpartum period but, during these visits, only 52% of women had service provision, either structured or opportunistic, related to diabetes. Conclusion: High rates of dysglycaemia among women screened for T2D after GDM in the 12 month postpartum period highlight the need for increased screening and early intervention to prevent the development of T2D and its complications. Whilst a clear strength was high postpartum attendance, many women did not attend health services for diabetes screening or management.

Background: The postpartum period is a critical time to improve health outcomes for Aboriginal women, particularly for those who have chronic conditions. Aims: To assess enhanced support methods (for women following diabetes in pregnancy (DIP)) to improve completion rates of recommended postpartum health checks. Materials and Methods: Fifty-three Aboriginal women in the Northern Territory (NT) were contacted in the postpartum period to encourage medical check-ups.Messages were delivered through phone (call or text messages) or other methods (Facebook or email). The primary outcome was postpartum blood glucose testing (oral glucose tolerance testing (OGTT), random or fasting glucose and HbA1c). Results: Establishing contact with women was difficult. Of 137 messages sent to52 women, 22 responded (42%). Phone was the most common contact method with successful contact made from 16 of 119 (13%) attempts. Rates of postpartum OGTT completion were higher in the group successfully contacted (32% vs 7%). However, for any postpartum glucose testing (including OGTT and HbA1c) rates were 25 of 42 (60%) and neither success in making contact nor the contact method was associated with higher rates. Conclusions: The small sample size limits our conclusions; however, results highlight that engaging remote women postpartum is difficult. While rates of postpartum OGTT completion differed according to successful contacts, rates of any postpartum blood glucose testing did not. Further research is needed to explore feasible intervention methods to improve postpartum screening after a pregnancy complicated by diabetes. Refereed/Peer-reviewed

Background Risk factors for estimated glomerular filtration rate (eGFR) decline beyond albuminuria are not fully understood in Indigenous Australians who have a 6-fold risk of end-stage kidney disease. We assessed associations between cardio-metabolic risk factors and eGFR decline according to baseline albuminuria status to identify potential treatment targets. Methods The eGFR Follow-up study is a longitudinal cohort of 520 Indigenous Australians. Linear mixed regression was used to estimate associations between baseline cardio-metabolic risk factors and annual Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR change (ml/min/1.73 m2/year), among those classified with baseline normoalbuminuria (uACR

Being able to estimate kidney decline accurately is particularly important in Indigenous Australians, a population at increased risk of developing chronic kidney disease and end stage kidney disease. The aim of this analysis was to explore the trend of decline in estimated glomerular filtration rate (eGFR) over a four year period using multiple local creatinine measures, compared with estimates derived using centrally-measured enzymatic creatinine and with estimates derived using only two local measures. Method: The eGFR study comprised a cohort of over 600 Aboriginal Australian participants recruited from over twenty sites in urban, regional and remote Australia across five strata of health, diabetes and kidney function. Trajectories of eGFR were explored on 385 participants with at least three local creatinine records using graphical methods that compared the linear trends fitted using linear mixed models with non-linear trends fitted using fractional polynomial equations. Temporal changes of local creatinine were also characterized using group-based modelling. Analyses were stratified by eGFR ( < 60; 60-89; 90-119 and ≥120ml/min/1.73m 2 ) and albuminuria categories ( < 3mg/mmol; 3-30mg/mmol; > 30mg/mmol). Results: Mean age of the participants was 48years, 64% were female and the median follow-up was 3years. Decline of eGFR was accurately estimated using simple linear regression models and locally measured creatinine was as good as centrally measured creatinine at predicting kidney decline in people with an eGFR < 60 and an eGFR 60-90ml/min/1.73m 2 with albuminuria. Analyses showed that one baseline and one follow-up locally measured creatinine may be sufficient to estimate short term (up to four years) kidney function decline. The greatest yearly decline was estimated in those with eGFR 60-90 and macro-albuminuria: -6.21 (-8.20, -4.23) ml/min/1.73m 2 . Conclusion: Short term estimates of kidney function decline can be reliably derived using an easy to implement and simple to interpret linear mixed effect model. Locally measured creatinine did not differ to centrally measured creatinine, thus is an accurate cost-efficient and timely means to monitoring kidney function progression. Refereed/Peer-reviewed

OBJECTIVE To examine the association between soluble tumor necrosis factor receptor 1 (sTNFR1) levels and kidney disease progression in Indigenous Australians at high risk of kidney disease. RESEARCH DESIGN AND METHODS This longitudinal observational study examined participants aged ≥18 years recruited from >20 sites across diabetes and/or kidney function strata. Baseline measures included sTNFR1, serum creatinine, urine albumin-to-creatinine ratio (uACR), HbA1c, C-reactive protein (CRP), waist-to-hip ratio, systolic blood pressure, and medical history. Linear regression was used to estimate annual change in estimated glomerular filtration rate (eGFR) for increasing sTNFR1, and Cox proportional hazards were used to estimate the hazard ratio (HR) and 95% CI for developing a combined renal outcome (first of a ≥30% decline in eGFR with a follow-up eGFR RESULTS Over a median of 3 years, participants with diabetes (n = 194) in the highest compared with the lowest quartile of sTNFR1 experienced significantly greater eGFR decline (−4.22 mL/min/1.73 m2/year [95% CI −7.06 to −1.38]; P = 0.004), independent of baseline age, sex, eGFR, and uACR. The adjusted HR (95% CI) for participants with diabetes per doubling of sTNFR1 for the combined renal outcome (n = 32) was 3.8 (1.1–12.8; P = 0.03). No association between sTNFR1 and either renal outcome was observed for those without diabetes (n = 259). CONCLUSIONS sTNFR1 is associated with greater kidney disease progression independent of albuminuria and eGFR in Indigenous Australians with diabetes. Further research is required to assess whether TNFR1 operates independently of other metabolic factors associated with kidney disease progression.

Low serum bilirubin concentrations are reported to be strongly associated with cardio-metabolic disease, but this relationship has not been reported among Indigenous Australian people who are known to be at high risk for diabetes and chronic kidney disease (CKD). Hypothesis: serum bilirubin will be negatively associated with markers of chronic disease, including CKD and anaemia among Indigenous Australians. Method: A cross-sectional analysis of 594 adult Aboriginal and Torres Strait Islander (TSI) people in good health or with diabetes and markers of CKD. Measures included urine albumin: creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), haemoglobin (Hb) and glycated haemoglobin (HbA1c). Diabetes was defined by medical history, medications or HbA1c. ≥. 6.5% or ≥. 48. mmol/mol. Anaemia was defined as Hb. < . 130. g/L or < . 120. g/L in males and females respectively. A multivariate regression analysis examining factors independently associated with log-bilirubin was performed. Results: Participants mean (SD) age was 45.1 (14.5) years, and included 62.5% females, 71.7% Aboriginal, 41.1% with diabetes, 16.7% with anaemia, 41% with ACR > 3mg/mmol and 18.2% with eGFR < 60mL/min/1.73m 2 . Median bilirubin concentration was lower in females than males (6 v 8μmol/L, p < 0.001) and in Aboriginal than TSI participants (6 v 9.5μmol/L, p < 0.001). Six factors explained 35% of the variance of log-bilirubin; Hb and cholesterol (both positively related) and ACR, triglycerides, Aboriginal ethnicity and female gender (all inversely related). Conclusion: Serum bilirubin concentrations were positively associated with Hb and total cholesterol, and inversely associated with ACR. Further research to determine reasons explaining lower bilirubin concentrations among Aboriginal compared with TSI participants are needed. Refereed/Peer-reviewed

Aims: To determine among First Nations and Europid pregnant women the cumulative incidence and predictors of postpartum type 2 diabetes and prediabetes and describe postpartum cardiovascular disease (CVD) risk profiles. Methods: PANDORA is a prospective longitudinal cohort of women recruited in pregnancy. Ethnic-specific rates of postpartum type 2 diabetes and prediabetes were reported for women with diabetes in pregnancy (DIP), gestational diabetes (GDM) or normoglycaemia in pregnancy over a short follow-up of 2.5 years (n = 325). Pregnancy characteristics and CVD risk profiles according to glycaemic status, and factors associated with postpartum diabetes/prediabetes were examined in First Nations women. Results: The cumulative incidence of postpartum type 2 diabetes among women with DIP or GDM were higher for First Nations women (48%, 13/27, women with DIP, 13%, 11/82, GDM), compared to Europid women (nil DIP or GDM p < 0.001). Characteristics associated with type 2 diabetes/prediabetes among First Nations women with GDM/DIP included, older age, multiparity, family history of diabetes, higher glucose values, insulin use and body mass index (BMI). Conclusions: First Nations women experience a high incidence of postpartum type 2 diabetes after GDM/DIP, highlighting the need for culturally responsive policies at an individual and systems level, to prevent diabetes and its complications. 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

ObjectiveTo assess the performance of cardiovascular disease (CVD) risk equations in Indigenous Australians.MethodsWe conducted an individual participant meta-analysis using longitudinal data of 3618 Indigenous Australians (55% women) aged 30–74 years without CVD from population-based cohorts of the Cardiovascular Risk in IndigenouS People(CRISP) consortium. Predicted risk was calculated using: 1991 and 2008 Framingham Heart Study (FHS), the Pooled Cohorts (PC), GloboRisk and the Central Australian Rural Practitioners Association (CARPA) modification of the FHS equation. Calibration, discrimination and diagnostic accuracy were evaluated. Risks were calculated with and without the use of clinical criteria to identify high-risk individuals.ResultsWhen applied without clinical criteria, all equations, except the CARPA-adjusted FHS, underestimated CVD risk (range of percentage difference between observed and predicted CVD risks: −55% to −14%), with underestimation greater in women (−63% to −13%) than men (−47% to −18%) and in younger age groups. Discrimination ranged from 0.66 to 0.72. The CARPA-adjusted FHS equation showed good calibration but overestimated risk in younger people, those without diabetes and those not at high clinical risk. When clinical criteria were used with risk equations, the CARPA-adjusted FHS algorithm scored 64% of those who had CVD events as high risk; corresponding figures for the 1991-FHS were 58% and were 87% for the PC equation for non-Hispanic whites. However, specificity fell.ConclusionThe CARPA-adjusted FHS CVD risk equation and clinical criteria performed the best, achieving higher combined sensitivity and specificity than other equations. However, future research should investigate whether modifications to this algorithm combination might lead to improved risk prediction.

Refereed/Peer-reviewed

Background: Glomerular hyperfiltration is not able to be detected in clinical practice. We assessed whether hyperfiltration is associated with albuminuria progression among Indigenous Australians at high risk of diabetes and kidney disease to determine its role in kidney disease progression. Methods: Longitudinal observational study of Indigenous Australians aged ≥18 years recruited from >20 sites, across diabetes and/or kidney function strata. At baseline, iohexol clearance was used to measure glomerular filtration rate (mGFR) and hyperfiltration was defined as (i) a mGFR of ≥125 mL/min/1.73 m 2 , and (ii) an age-adjusted definition, with the top 10% of the mGFR for each 10 year age group at baseline. Baseline and follow-up urine albumin-to-creatinine ratio (uACR) was collected, and linear regression was used to assess the associations of hyperfiltration and uACR at follow up. Results: 407 individuals (33% men, mean age 47 years) were followed-up for a median of 3 years. At baseline, 234 had normoalbuminuria and 173 had albuminuria. Among participants with normoalbuminuria, those with mGFR ≥125 mL/min/1.73 m 2 had 32% higher uACR at follow-up (p = 0.08), and those with age-adjusted hyperfiltration had 60% higher uACR (p = 0.037) compared to those who had normofiltration. These associations were independent of uACR at baseline, but attenuated by HbA 1c . Associations were stronger among those without than those with albuminuria at baseline. Conclusions: Although not available for assessment in current clinical practice, hyperfiltration may represent a marker of subsequent albuminuria progression among individuals who have not yet developed albuminuria. Refereed/Peer-reviewed

Diabetes in pregnancy is not only associated with increased risk of pregnancy complications and subsequent maternal metabolic disease, but also increases the risk of long-term metabolic disease in the offspring. At the interface between genetic and environmental factors, epigenetic variation established in utero represents a plausible link between the in utero environment and later disease susceptibility. The identification of an epigenetic fingerprint of diabetes in pregnancy linked to the metabolic health of the offspring might provide novel biomarkers for the identification of offspring most at risk, before the onset of metabolic dysfunction, for targeted monitoring and intervention. In this Personal View, we (1) highlight the scale of the problem of diabetes in pregnancy, (2) summarise evidence for the variation in offspring epigenetic profiles following exposure to diabetes in utero, and (3) outline potential future approaches to further understand the mechanisms by which exposure to maternal metabolic dysfunction in pregnancy is transmitted through generations.

Background: To test the feasibility of benchmarking the care of women with pregnancies complicated by hyperglycaemia. Methods: A retrospective audit of volunteer diabetes services in Australia and New Zealand involving singleton pregnancies resulting in live births between 2014 and 2020. Ranges are shown and compared across services. Results: The audit included 10,144 pregnancies (gestational diabetes mellitus (GDM) = 8696, type 1 diabetes (T1D) = 435, type 2 diabetes (T2D) = 1013) from 11 diabetes services. Among women with GDM, diet alone was used in 39.4% (ranging among centres from 28.8–57.3%), metformin alone in 18.8% (0.4–43.7%), and metformin and insulin in 10.1% (1.5–23.4%), when compared between sites, all p &lt, 0.001. Birth was by elective caesarean in 12.1% (3.6–23.7%) or emergency caesarean in 9.5% (3.5–21.2%) (all p &lt, 0.001). Preterm births (&lt, 37 weeks) ranged from 3.7% to 9.4% (p &lt, 0.05), large for gestational age 10.3–26.7% (p &lt, 0.001), admission to special care nursery 16.7–25.0% (p &lt, 0.001), and neonatal hypoglycaemia (&lt, 2.6 mmol/L) 6.0–27.0% (p &lt, 0.001). Many women with T1D and T2D had limited pregnancy planning including first trimester hyperglycaemia (HbA1c &gt, 6.5% (48 mmol/mol)), 78.4% and 54.6%, respectively (p &lt, 0.001). Conclusion: Management of maternal hyperglycaemia and pregnancy outcomes varied significantly. The maintenance and extension of this benchmarking service provides opportunities to identify policy and clinical approaches to improve pregnancy outcomes among women with hyperglycaemia in pregnancy.

The higher serum adiponectin concentrations observed in females are often attributed to differences in adiposity or sex hormones. There is little data describing adiponectin in Indigenous Australians, and no studies examining its association with cardio-metabolic disease risk markers and chronic kidney disease (CKD). Aim To describe the relationship of serum adiponectin with cardio-metabolic disease risk markers and kidney function in a community-based sample of Indigenous Australian adults, with particular reference to sex-specific differences. Methods A cross-sectional analysis of a community-based volunteer sample of 548 Indigenous Australian adults (62% female), stratified into five cardio-metabolic risk groups ranging from good health (strata-1) to high cardio-metabolic risk and low measured glomerular filtration rate (mGFR

Background: Early-life risk factors, including maternal hyperglycaemia and birthweight, are thought to contribute to the high burden of cardiometabolic disease experienced by Indigenous populations. We examined rates of pre-existing diabetes in pregnancy, gestational diabetes mellitus (GDM) and extremes of birthweight over three decades in the Northern Territory (NT) of Australia. Methods: We performed a retrospective cohort analysis of the NT Perinatal Data Collection from 1987 to 2016, including all births >20 weeks gestation, stratified by maternal Aboriginal identification. Key outcomes were annual rates of pre-existing diabetes, GDM, small-for-gestational-age, large-for-gestational-age, low birthweight (4000 g). Logistic regression was used to assess trends and interactions. Findings: 109 349 babies were born to 64 877 mothers, 36% of whom identified as Aboriginal ethnicity. Among Aboriginal women, rates of GDM and pre-existing diabetes, respectively, were 3 · 4% and 0 · 6% in 1987 and rose to 13% and 5 · 7% in 2016 (both trends p

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.

ObjectiveWomen with a history of gestational diabetes mellitus (GDM) have an elevated risk of ultimately developing pre-diabetes and diabetes later in life. They also have an increased prevalence of fatty liver, but recent studies have reported conflicting findings on whether hepatic fat affects their risk of pre-diabetes/diabetes. Thus, we sought to evaluate the associations of liver fat with glucose homeostasis and determinants thereof in women with and without recent gestational dysglycemia.MethodsTwo hundred and fifty-seven women underwent an antepartum oral glucose tolerance test (OGTT), which diagnosed 97 with GDM, 40 with gestational impaired glucose tolerance (GIGT), and 120 with normal glucose tolerance (NGT). At a mean of 4.8 years post partum, they underwent an OGTT (which revealed that 52 had progressed to pre-diabetes/diabetes) and hepatic ultrasound, on which liver fat was graded as none (n=164), mild (n=66), or moderate (n=27).ResultsLiver fat was more prevalent in women with previous GDM than in those with GIGT or NGT (p=0.009) and in women with current pre-diabetes/diabetes than in those without (p=0.0003). As the severity of liver fat increased, there was a progressive worsening of insulin sensitivity and beta-cell function, coupled with rising fasting and 2-hour glucose (all pConclusionThe higher prevalence of liver fat in women with previous GDM is associated with their increased risk of pre-diabetes/diabetes.

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.

Aim: To assess the relationships of diabetes and albuminuria with all-cause mortality and cardiovascular disease outcomes in a population without prior cardiovascular disease using data from the Darwin Region Urban Indigenous Diabetes (DRUID) study. Methods: We conducted a prospective cohort study of 706 participants (aged 15–81 years, 68% women) without prior cardiovascular disease who underwent a 75-g oral glucose tolerance test. Deaths and fatal or non-fatal cardiovascular disease were determined over 7 years, and hazard ratios with 95% CIs and population attributable risks were estimated for baseline glycaemia and albuminuria. Results: Compared with normoglycaemia and after adjustment for age, sex, hypertension, dyslipidaemia and smoking, known diabetes was associated with an adjusted hazard ratio of 4.8 (95% CI 1.5–14.7) for all-cause mortality and 5.6 (95% CI 2.1–15.2) for cardiovascular disease. Compared with normoalbuminuria, the respective adjusted risks for macroalbuminuria were 10.9 (95% CI 3.7–32.1) and 3.9 (95% CI 1.4–10.8). The Adjusted all-cause mortality and cardiovascular disease estimated population attributable risks for diabetes were 27% and 32%, and for albuminuria they were 32% and 21%, respectively. Conclusions: In our study population, the burden of mortality and cardiovascular disease was largely driven by diabetes and albuminuria. This finding on the influence of diabetes and albuminuria is consistent with reports in other high-risk Indigenous populations and should be better reflected in risk scores and intervention programmes. Refereed/Peer-reviewed

Background: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation that combines creatinine and cystatin C is superior to equations that include either measure alone in estimating glomerular filtration rate (GFR). However, whether cystatin C can provide any additional benefits in estimating GFR for Indigenous Australians, a population at high risk of end-stage kidney disease (ESKD) is unknown. Methods: Using a cross-sectional analysis from the eGFR Study of 654 Indigenous Australians at high risk of ESKD, eGFR was calculated using the CKD-EPI equations for serum creatinine (eGFRcr), cystatin C (eGFRcysC) and combined creatinine and cystatin C (eGFRcysC + cr). Reference GFR (mGFR) was determined using a non-isotopic iohexol plasma disappearance technique over 4. h. Performance of each equation to mGFR was assessed by calculating bias, % bias, precision and accuracy for the total population, and according to age, sex, kidney disease, diabetes, obesity and c-reactive protein. Results: Data were available for 542 participants (38% men, mean [sd] age 45 [14] years). Bias was significantly greater for eGFRcysC (15.0mL/min/1.73m2; 95% CI 13.3-16.4, p

Background/Objectives: To describe the development of a single-frequency bioimpedance prediction equation for fat-free mass (FFM) suitable for adult Aboriginal and Torres Strait Islander peoples with and without diabetes or indicators of chronic kidney disease (CKD). Subjects/Methods: FFM was measured by whole-body dual-energy X-ray absorptiometry in 147 adult Indigenous Australians. Height, weight, body circumference and resistance were also measured. Adults with and without diabetes and indicators of CKD were examined. A random split sample with internal cross-validation approach was used to predict and subsequently validate FFM using resistance, height, weight, age and gender against measured FFM. Results: Among 147 adults with a median body mass index of 31 kg/m2, the final model of FFM was FFM (kg)=0.432 (height, cm2/resistance, ohm)-0.086 (age, years)+0.269 (weight, kg)-6.422 (if female)+16.429. Adjusted R2 was 0.94 and the root mean square error was 3.33 kg. The concordance was high (rc =0.97) between measured and predicted FFM across a wide range of FFM (31-85 kg). Conclusions: In the context of the high burden of diabetes and CKD among adult Indigenous Australians, this new equation for FFM was both accurate and precise and based on easily acquired variables (height, weight, age, gender and resistance) among a heterogeneous adult cohort. Refereed/Peer-reviewed

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.

Aims In the Diabetes Control and Complications Trial, mean updated HbA(1c) accounted for most of the differential risk of microvascular complications between intensive and conventional insulin therapy. We hypothesized, however, that a more precise measure of chronic hyperglycaemic exposure may be the incremental area-under-the-HbA(1c)-curve above the Diabetes Control and Complications Trial-standardized normal range for HbA(1c) (iAUC(HbA1c>norm)). Methods Using the Principal Diabetes Control and Complications Trial data set, we compared the following three measures of chronic glycaemic exposure for their capacity to predict retinopathy, nephropathy and neuropathy during the Diabetes Control and Complications Trial: mean updated HbA(1c), iAUC(HbA1c>norm), and total area-under-the-HbA(1c)-curve (tAUC(HbA1c)). For each outcome, models using each of these three glycaemic measures were compared in the following three ways: hazard or odds ratio, χ(2) statistic, and Akaike information criterion. Results The three glycaemic measures did not differ in their prediction of neuropathy. iAUC(HbA1c>norm) was modestly superior to mean updated HbA(1c) for predicting nephropathy (χ(2) P = 0.017, Akaike P = 0.032). In contrast, for predicting retinopathy, both iAUC(HbA1c>norm) (χ(2) P = 0.0005, Akaike P = 0.0005) and tAUC(HbA1c) (χ(2) P = 0.004, Akaike P = 0.004) were significantly better than mean updated HbA(1c). Varying its HbA(1c) threshold incrementally between 37 and 53 mmol/mol (5.5-7.0%), inclusive, did not improve the prediction of retinopathy by iAUC(HbA1c>threshold) beyond that of tAUC(HbA1c,) consistent with the concept of a continuous relationship between glycaemia and retinopathy, with no glycaemic threshold. Conclusions Both iAUC(HbA1c>norm) and tAUC(HbA1c) were superior to mean updated HbA(1c) for predicting retinopathy. Optimal assessment of chronic glycaemic exposure as a determinant of retinopathic risk may require consideration of both the degree of hyperglycaemia and its duration.

To describe the detailed associations of albuminuria among a contemporary cohort of Aboriginal and Torres Strait Islander people to inform strategies for chronic kidney disease prevention and management. A cross-sectional analysis of Indigenous participants of the eGFR Study. Clinical, biochemical and anthropometric measures were collected (including body-circumferences, blood pressure (BP); triglycerides, HbA1c, liver function tests, creatinine; urine- microscopic-haem, albumin: creatinine ratio (ACR), prescriptions- angiotensin converting enzyme inhibitor or angiotensin receptor II antagonist (ACEI/ARB). Albuminuria and diabetes were defined by an ACR>3.0 mg/mmol, and HbA1c≥48 mmol/mol or prior history respectively. Waist: hip ratio (WHR), and estimated glomerular filtration rate (eGFR) were calculated. ACR was non-normally distributed; a logarithmic transformation was applied (in base 2), with each unit increase in log2-albuminuria representing a doubling of ACR. 591 participants were assessed (71% Aboriginal, 61.6% female, mean age 45.1 years, BMI 30.2 kg/m2 , WHR 0.94, eGFR 99.2 ml/min/1.73m2 ). The overall prevalence of albuminuria, diabetes, microscopic-haem and ACEI/ARB use was 41.5%, 41.5%, 17.8% and 34.7% respectively; 69.3% of adults with albuminuria and diabetes received an ACEI/ARB. Using multivariable linear regression modelling, the potentially modifiable factors independently associated with log2-albuminuria were microscopic-haem, diabetes, WHR, systolic BP, alkaline phosphatase (all positive) and eGFR (inverse). Albuminuria is associated with diabetes, central obesity and haematuria. High ACEI/ARB prescribing for adults with diabetes and albuminuria was observed. Further understanding of the links between fat deposition, haematuria and albuminuria is required.

Objectives Diabetes mellitus and periodontal disease are highly prevalent among Indigenous Australian adults. Untreated periodontitis impacts glycaemic control in people with diabetes. The aim of this study was to report on the effect of periodontal therapy on glycaemic control among people with obesity. Methods This subgroup analysis is limited to 62 participants with diabetes from the original 273 Aboriginal Australian adults enrolled into the PerioCardio study. Intervention participants received full-mouth non-surgical periodontal scaling during a single, untimed session while controls were untreated. Endpoints of interest included change in glycated haemoglobin (HbA1c), C-reactive protein (CRP) and periodontal status at 3 months post-intervention. Results There were more females randomized to the treatment group (n = 17) than control (n = 10) while the control group had a higher overall body mass index (BMI) [mean (SD)] 33.1 (9.7 kg m−2) versus 29.9 (6.0 kg m−2). A greater proportion of males were followed up at 3 months compared to females, P = 0.05. Periodontal therapy did not significantly reduce HbA1c: ancova difference in means 0.22 mmol mol−1 (95% CI −6.25 to 6.69), CRP: ancova difference in means 0.64 (95% CI −1.08, 2.37) or periodontal status at 3 months. Conclusions Non-surgical periodontal therapy did not significantly reduce glycated haemoglobin in participants with type 2 diabetes. Reasons are likely to be multifactorial and may be influenced by persistent periodontal inflammation at the follow-up appointments. Alternatively, the BMI of study participants may impact glycaemic control via alternative mechanisms involving the interplay between inflammation and adiposity meaning HbA1c may not be amenable to periodontal therapy in these individuals.

Type 2 diabetes mellitus (T2DM), cardiovascular disease, and chronic kidney disease are significant contributors to the 17-year disparity in life expectancy between Indigenous and non-Indigenous Australians. These three conditions are prevalent from a young age in Indigenous Australians and clearly contribute to their premature mortality. Risk factors that both exacerbate and promote these conditions include central obesity, dyslipidemia, cigarette smoking, albuminuria, inflammation, and poor socio-economic status. Although rates of screening for T2DM are higher in Indigenous Australians than in non-Indigenous Australians, gaps in clinical management of both T2DM and cardiovascular disease exist. To enhance survival and quality of life, prevention strategies are required at a population level and from a young age in Indigenous Australians.

Rates of type 2 diabetes are higher among Indigenous than non-Indigenous Australian children and adolescents. Presentation may be incidental, part of obesity investigation, symptomatic (polyuria and polydipsia) or in ketoacidosis. Investigation should include assessment of fasting insulin, c-peptide and autoantibodies, as well as assessment of diabetes complications and co-morbidities. Management is a challenge, particularly in a resource-limited setting. Management should involve the whole family and, in some cases, extended family, and community, local health-care providers are key, and a multidisciplinary team approach is essential. The primary initial intervention involves life-style change, but medications (oral and insulin) are frequently necessary. Screening of high-risk individuals is recommended. Waist circumference is a key component of risk assessment. Prevention strategies targeting children and adolescents from this high-risk population are urgently required.

Summary Objective To investigate whether cardiovascular risk factors can explain the higher carotid intima–media thickness (CIMT) in Indigenous compared with European Australians. Design Cross-sectional study in three subgroups. Patients Non-diabetic urban European (n = 86), urban Indigenous (n = 69), and remote Indigenous (n = 60) Australians aged 25–64 years. Measurements CIMT, age, sex, anthropometry, blood pressure, smoking status, fasting glucose and insulin, haemoglobin (Hb)A1c, homocysteine, C-reactive protein (CRP), lipids, urinary albumin and creatinine. Results CIMT and levels of risk factors, except fasting glucose and total cholesterol, worsened across the three groups. Logn fasting insulin [β = 0·022, 95% confidence interval (CI) 0–0·0439], age (β = 0·006, 95% CI 0·004–0·007), gender (female β = –0·005 vs. male, 95% CI –0·084 to –0·026), mean arterial pressure (MAP) (β = 0·001, 95% CI 0·001–0·002) and ethnicity/location [urban Indigenous (β = 0·027, 95% CI –0·010 to 0·064 vs. European); remote Indigenous (β = 0·083, 95% CI 0·042–0·123 vs. European)] explained 41% of variance in CIMT. Significant interactions were seen for ethnicity/location with age (P = 0·014) and MAP (P = 0·018). Age was consistently associated with CIMT across the three populations, and was associated with larger increments in CIMT for the Indigenous subgroups (β = 0·007, 95% CI 0·005–0·009 urban; β = 0·007, 95% CI 0·004–0·010 remote) compared with Europeans (β = 0·003, 95% CI 0·002–0·006) in models including age, sex and MAP. MAP was only associated with CIMT in the remote Indigenous subgroup. Conclusion After adjusting for selected risk factors, CIMT in remote Indigenous participants was still higher than in Europeans. The slope of the association between age and CIMT steepened from urban Europeans to remote Indigenous.

Observational studies and nonrandomized trials support an association between periodontal disease and atherosclerotic vascular disease. Both diseases occur frequently in Aboriginal Australians. We hypothesized that nonsurgical periodontal therapy would improve measures of arterial function and structure that are subclinical indicators of atherosclerotic vascular disease. This parallel-group, randomized, open label clinical trial enrolled 273 Aboriginal Australians aged ≥18 years with periodontitis. Intervention participants received full-mouth periodontal scaling during a single visit, whereas controls received no treatment. Prespecified primary end points measured 12-month change in carotid intima-media thickness, an indicator of arterial structure, and 3- and 12-month change in pulse wave velocity, an indicator of arterial function. ANCOVA used complete case data to evaluate treatment group differences. End points could be calculated for 169 participants with follow-up data at 3 months and 168 participants at 12 months. Intima-media thickness decreased significantly after 12 months in the intervention group (mean reduction=−0.023 [95% confidence interval {CI}, −0.038 to −0.008] mm) but not in the control group (mean increase=0.002 [95% CI, −0.017 to 0.022] mm). The difference in intima-media thickness change between treatment groups was statistically significant (−0.026 [95% CI, −0.048 to −0.003] mm; P =0.03). In contrast, there were no significant differences between treatment groups in pulse wave velocity at 3 months (mean difference, 0.06 [95% CI, −0.17 to 0.29] m/s; P =0.594) or 12 months (mean difference, 0.21 [95% CI, −0.01 to 0.43] m/s; P =0.062). Periodontal therapy reduced subclinical arterial thickness but not function in Aboriginal Australians with periodontal disease, suggesting periodontal disease and atherosclerosis are significantly associated.

Background: Low levels of serum 25-hydroxy vitamin D (25(OH)D), have been associated with development of type 2 diabetes and cardiovascular disease (CVD); however there are limited data on serum 25(OH)D in Indigenous Australians, a population at high risk for both diabetes and CVD. We aimed to assess levels of serum 25(OH)D in Aboriginal and Torres Strait Islander Australians and to explore relationships between 25(OH)D and cardio-metabolic risk factors and diabetes. Conclusion: The percentage of 25(OH)D levels 72 nmol/L, respectively) after adjusting for known cardio-metabolic risk factors. Refereed/Peer-reviewed

Background: The aim of this study was to describe the caries experience and severity of periodontal disease in a convenience sample of Indigenous Australians living in the Northern Territory. Methods: Data were gathered via self-reported questionnaire and dental examination by calibrated examiners. Socio-demographic characteristics were compared with data from the 2011 Australian census while prevalence of periodontal disease and dental caries was compared against weighted estimates from the National Survey of Adult Oral Health 2004-2006. In each comparison, non-overlapping 95% confidence intervals inferred a significant difference. Within-study comparisons were assessed via chi-square, t-tests and analysis of variance for differences among study participants. Results: A total of 312 Indigenous Australian participants provided completed data (average age 39.5 ± 10.5 years, 174 males). Of these, 87.5% were confirmed periodontitis cases; 3.5 times that of national-level estimates. The experience of untreated caries was five times that of national estimates (mean decayed 3.0 versus 0.6). Periodontitis case status was positively associated with older age, male gender and presence of diabetes Conclusions: Periodontal disease and untreated caries were significantly more prevalent in this sample of Indigenous Australians compared to the general Australian population. The prevalence of periodontal disease was markedly higher than that previously described for Indigenous Australians. Refereed/Peer-reviewed

The burden of type 2 diabetes mellitus (T2DM) among Indigenous children and adolescents is much greater than in non-Indigenous young people and appears to be rising, although data on epidemiology and complications are limited. Young Indigenous people living in remote areas appear to be at excess risk of T2DM. Most young Indigenous people with T2DM are asymptomatic at diagnosis and typically have a family history of T2DM, are overweight or obese and may have signs of hyperinsulinism such as acanthosis nigricans. Onset is usually during early adolescence. Barriers to addressing T2DM in young Indigenous people living in rural and remote settings relate to health service access, demographics, socioeconomic factors, cultural factors, and limited resources at individual and health service levels. We recommend screening for T2DM for any Aboriginal or Torres Strait Islander person aged > 10 years (or past the onset of puberty) who is overweight or obese, has a positive family history of diabetes, has signs of insulin resistance, has dyslipidaemia, has received psychotropic therapy, or has been exposed to diabetes in utero. Individualised management plans should include identification of risk factors, complications, behavioural factors and treatment targets, and should take into account psychosocial factors which may influence health care interaction, treatment success and clinical outcomes. Preventive strategies, including lifestyle modification, need to play a dominant role in tackling T2DM in young Indigenous people. Refereed/Peer-reviewed

Indigenous populations of Australia and Canada experience disproportionately high rates of chronic disease. We hypothesized that despite the common outcome of increased diabetes prevalence, differences in cardiometabolic risk profile may exist between these populations.We compared community-based data on cardiometabolic risks in Aboriginal Australians (n=297 without, 45 with diabetes), and Aboriginal Canadians (n=409 without, 87 with diabetes).Despite strikingly lower weight (62 vs 83 kg, p0.0001) and body mass index (BMI, 22 vs 29 kg/m(2), p0.0001), Aboriginal Australians without diabetes had similar waist-hip ratio (WHR, 0.91 vs 0.91, p=0.732), lower HDL-cholesterol (0.97 vs 1.25 mmol/L, p0.0001) and higher HbA1c (5.4 vs 5.2%, p0.0001) than Aboriginal Canadians without diabetes. Waist was the obesity measure most strongly related to diabetes or cardiometabolic risk in Australians while BMI performed similarly to other obesity measures only in Canadians. Multiple regression of HbA1c revealed age and fasting glucose as independent predictors in each study group, with the addition of WHR in Aboriginal Australians.The notable finding was that waist or WHR are preferred obesity measures to appropriately reflect cardiometabolic risk in Aboriginal Australians, who although leaner by BMI criteria, displayed a similarly adverse risk profile to Aboriginal Canadians. Waist or WHR should be routinely included in clinical assessment in these high-risk populations.

Background Indigenous populations of Australia and Canada experience disproportionately high rates of chronic disease. Our goal was to compare cardiovascular (CVD) risk profile and diabetes complications from three recent comprehensive studies of diabetes complications in different Indigenous populations in Australia and Canada. Methods We compared participants from three recent studies: remote Indigenous Australians (2002-2003, n = 37 known diabetes), urban Indigenous Australians (2003-2005, n = 99 known diabetes), and remote Aboriginal Canadians (2001-2002, n = 188 known diabetes). Results The three groups were similar for HbA1c, systolic BP, diabetes duration. Although leaner by body-mass-index criteria, remote Indigenous Australians displayed a more adverse CVD risk profile with respect to: waist-hip-ratio (1.03, 0.99, 0.94, remote Indigenous Australians, urban Indigenous Australians, remote Canadians, p < 0.001); HDL-cholesterol (0.82, 0.96, 1.17 mmol/L, p < 0.001); urine albumin-creatinine-ratio (10.3, 2.4, 4.5 mg/mmol); and C-reactive protein. With respect to diabetes complications, microalbuminuria (50%, 25%, 41%, p = 0.001) was more common among both remote groups than urban Indigenous Australians, but there were no differences for peripheral neuropathy, retinopathy or peripheral vascular disease. Conclusions Although there are many similarities in diabetes phenotype in Indigenous populations, this comparison demonstrates that CVD risk profiles and diabetes complications may differ among groups. Irrespective, management and intervention strategies are required from a young age in Indigenous populations and need to be designed in consultation with communities and tailored to community and individual needs.

Background Previous studies reported high C-reactive protein (CRP) levels in Indigenous Australians, which may contribute to their high risk of cardiovascular disease. We compared CRP levels in Indigenous Australians and the general population, accounting for obesity and other risk factors. Methods Cross-sectional study of CRP and risk factors (weight, height, waist and hip circumferences, blood pressure, lipids, blood glucose, and smoking status) in population-based samples from the Diabetes and Related conditions in Urban Indigenous people in the Darwin region (DRUID) study, and the Australian Diabetes, Obesity and Lifestyle study (AusDiab) follow-up. Results CRP concentrations were higher in women than men and in DRUID than AusDiab. After multivariate adjustment, including waist circumference, the odds of high CRP (>3.0 mg/L) in DRUID relative to AusDiab were no longer statistically significant, but elevated CRP was still more likely in women than men. After adjusting for BMI (instead of waist circumference) the odds for elevated CRP in DRUID participants were still higher relative to AusDiab participants among women, but not men. Lower HDL cholesterol, impaired glucose tolerance (IGT), and higher diastolic blood pressure were associated with having a high CRP in both men and women, while current smoking was associated with high CRP in men but not women. Conclusions High concentrations of CRP in Indigenous participants were largely explained by other risk factors, in particular abdominal obesity. Irrespective of its independence as a risk factor, or its aetiological association with coronary heart disease (CHD), the high CRP levels in urban Indigenous women are likely to reflect increased vascular and metabolic risk. The significance of elevated CRP in Indigenous Australians should be investigated in future longitudinal studies.

Background: Premature cardiovascular disease (CDV) is highly prevalent in urban Indigenous Australians. We studied arterial structure and function in 144 volunteers aged 15–66 years to assess the role of dyslipidaemia and other traditional vascular risk factors on cardiovascular risk in young and older urban Indigenous Australians. Methods: We assessed carotid intima-media thickness (CIMT) by high-resolution B-mode ultrasound imaging of the common carotid artery and peripheral wave reflection using applanation tonometry to obtain the aortic augmentation index (AI) in Indigenous Australian participants of the Darwin Region Urban Indigenous Diabetes (DRUID) study. Results: Participants aged 15–24 years demonstrated fewer cardiovascular risk factors than the older group (25–66 years) and predictors of CIMT and AI differed between younger and older groups. CIMT was higher in the older group (0.67 mm vs. 0.61 mm, p = 0.004) and in those with diabetes (0.81 mm vs. 0.67 mm, p < 0.001). AI was higher in the older group (24% vs. 0%, p < 0.001), but was not affected by diabetes status. On multivariate regression analysis, low HDL-cholesterol was the only independent predictor of CIMT in the younger group; triglycerides, heart rate (inverse) and height (inverse) were independent predictors of AI in the same group. Conclusion: Dyslipidaemia (low HDL-cholesterol or elevated triglycerides) is independently associated with non-invasive measures of cardiovascular disease in a relatively healthy and young subgroup of this high-risk population. We propose that triglycerides and low HDL-cholesterol may represent the most useful commonly measured clinical indicators of cardiovascular risk in young, urban Indigenous Australians. Refereed/Peer-reviewed

Introduction Little is known about the burden of diabetes and related conditions among urban Indigenous Australians. The DRUID study was established to address this important information gap. Subjects Eligible participants were Aboriginal and Torres Strait Islander adult volunteers aged 15 years and over who had lived in a defined region in and around Darwin, NT for at least 6 months. Materials and methods Participants underwent a health examination based on the AusDiab protocol, including blood and urine collection, clinical and anthropometric measurements and questionnaires, in 2003–2005. Results Among 861 participants included in the analysis (approximately 14% of the target population), diabetes and other cardiovascular risk factors were common and increased with age. Almost one-third of those aged ≥35 years (31.7%) and over half of those ≥55 years (52.4%) had diabetes. Of 48 participants with newly diagnosed diabetes, half would not have been diagnosed without OGTT. Cardiovascular risk factors were common even among young people without diabetes—45% had ≥2 risk factors and only 18% had none. Conclusions This study indicates a very high burden of current disease and high risk of future disease, even among young people. Both primary prevention and better management of known risk factors and existing disease are urgently required.

Summary Objective Indigenous Australians have rates of cardiovascular (CVD) mortality some seven to 10-fold higher than non-Indigenous Australians aged 25–64 years. We aimed to evaluate the impact of type 2 diabetes and components of the metabolic syndrome on carotid intima-media thickness (CIMT) as a marker of cardiovascular risk in Indigenous Australians living in remote and urban environments and in Australians of European ancestry. Design, patients and measurements CIMT was measured by high-resolution B-mode ultrasound imaging of the common carotid artery in 119 remote Indigenous, 144 urban Indigenous and 122 urban European Australians with and without diabetes. Results In nondiabetic participants, CIMT was lowest in Europeans (mean (SD) 0·64 mm (0·10)), higher in urban Indigenous Australians (0·67 mm (0·12)) and highest in remote Indigenous Australians (0·73 mm (0·15), P

OBJECTIVE To determine the influence of central obesity and type 2 diabetes on peripheral wave reflection in Indigenous Australians. DESIGN AND METHODS A cross-sectional study of remote Indigenous Australians with (n = 43) and without (n = 54) type 2 diabetes of similar age (47 years) and sex; using anthropometric and bioelectrical impedance measures of obesity and applanation tonometry to determine the aortic augmentation index (AI) as an index of peripheral wave reflection. RESULTS Indices of obesity were significantly higher in the diabetic than non-diabetic participants [body mass index (BMI): 27.3 versus 24.6 kg/m, P = 0.018; waist circumference: women 101 versus 94 cm, P = 0.008, men 102 versus 91 cm, P = 0.039]. AI was negatively related to obesity: BMI (r = -0.35, P = 0.0003), weight (r = -0.44, P < 0.0005), waist circumference (r = -0.34, P = 0.0003) and fat mass (r = -0.35, P < 0.0005). There was no significant difference in AI between the groups with and without diabetes. On multiple regression analysis, 66% of the variance in AI was explained with the following significant predictors: age, heart rate, male gender, fat mass and mean arterial pressure. Similar results were obtained when weight, waist circumference or BMI were substituted for fat mass. CONCLUSION When compared with Indigenous Australians without diabetes, those with type 2 diabetes do not have greater aortic pressure augmentation from peripheral wave reflection. However, obesity, irrespective of the index used, was related to lower peripheral wave reflection in both those with and without type 2 diabetes.

Prevalence of complications of type 2 diabetes in a remote Australian Indigenous community was measured as part of a population survey of risk factors for diabetes and cardiovascular disease. Information was obtained from history, clinical examination, blood sample and medical records. Forty-three diabetic participants (six newly diagnosed) were assessed from a sample of 339 (12% diabetes prevalence); mean age 50 (range 31–67), duration of diabetes 5.6 (0–15) years, 40% male. Risk factors/complications: 70% with BMI≥25, 50% cigarette smokers, HbA1c 8.5 (S.D. 2.9)%, cholesterol 4.8 (0.8) mmol/l, triglycerides 2.7 (1.6) mmol/l, HDL 0.83 (0.2) mmol/l; 60% had albuminuria (micro 38%, macro 22%), 47% were hypertensive, 7% (n=2) had retinopathy, 24% had peripheral neuropathy, none had peripheral vascular disease, 14% had documented coronary vascular and one participant cerebrovascular disease. Of 37 with previously diagnosed diabetes: 43% were on aspirin, 65% on metformin, 80% with albuminuria on ACE inhibitors. Four additional diabetic participants (not studied) were receiving renal dialysis elsewhere. The results demonstrate on the one hand, very high indices of cardiovascular risk (smoking, hypertension, dyslipidaemia and albuminuria) and on the other, good quality primary health care providing good detection and follow up management of type 2 diabetic patients.