Postpartum uptake of diabetes screening tests in women with gestational diabetes: The PANDORA study.

AIMS: 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). METHODS: 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 [HbA1C ] or fasting plasma glucose) were assessed for women with GDM (n = 712). Associations between antenatal factors and screening with any test (OGTT, HbA1C , fasting plasma glucose) by 6 months postpartum were examined using Cox proportional hazards regression. RESULTS: Postpartum 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 HbA1C compared to non-Indigenous women (16% vs. 2%, p < 0.001). Screening by 6 months postpartum with any test was 41% for Aboriginal and/or Torres Strait Islander women and 45% for non-Indigenous women (p = 0.304). Characteristics associated with higher screening rates with any test by 6 months postpartum included, insulin use in pregnancy, first pregnancy, not smoking and lower BMI. CONCLUSIONS: Given 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.

Association between hyperglycaemia in pregnancy and growth of offspring in early childhood: The PANDORA study.

BACKGROUND: Few studies have assessed whether children exposed to in utero hyperglycaemia experience different growth trajectories compared to unexposed children. OBJECTIVES: To assess association of type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) with early childhood weight, length/height and body mass index (BMI) trajectories, and with timing and magnitude of peak BMI in infancy. METHODS: PANDORA is a birth cohort recruited from an Australian hyperglycaemia in pregnancy register, and women with normoglycaemia recruited from the community. Offspring growth measures were obtained from health records over a median follow-up of 3.0 years (interquartile range 1.9-4.0). This analysis included children born to Aboriginal mothers with in utero normoglycaemia (n = 95), GDM (n = 228) or T2D (n = 131). Growth trajectories (weight, length/height and BMI) were estimated using linear mixed models with cubic spline functions of child age. RESULTS: After adjustment for maternal factors (age, BMI, parity, smoking, and socioeconomic measures) and child factors (age, gestational age at birth, and sex), children born to mothers with T2D or GDM had lower weight, length/height and BMI trajectories in infancy than children born to mothers with normoglycaemia, but similar weight and BMI by completion of follow-up. Children exposed to T2D had lower mean peak BMI 17.6 kg/m2 (95% confidence interval [CI] 17.3-18.0) than children exposed to normoglycaemia (18.6 kg/m2 [18.1-18.9]) (p = 0.001). CONCLUSIONS: Maternal hyperglycaemia was associated with differences in early childhood growth trajectories after adjustment for maternal BMI. Exploration of associations between in utero hyperglycaemia exposure and growth trajectories into later childhood is required.

Breastfeeding and infant growth in offspring of mothers with hyperglycaemia in pregnancy: The pregnancy and neonatal diabetes outcomes in remote Australia study.

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 < 0.01 for all groups), and lower weight trajectories among those born to mothers with GDM (p = 0.006). Among offspring of women with GDM, predominant breastfeeding was only associated with lower weight-for-age at 14 months, however adjusting for maternal obesity, smoking, and parity attenuated observed associations. Maternal obesity remained significantly associated with greater infant growth. CONCLUSIONS: Predominant breastfeeding was associated with reduced growth among children born to women with and without hyperglycaemia in pregnancy. However, among children exposed to GDM in utero, maternal obesity largely explained this association.

The ASQ-TRAK: Validating a culturally adapted developmental screening tool for Australian Aboriginal children.

BACKGROUND: Developmental monitoring, performed using culturally relevant tools, is of critical importance for all young children. The ASQ-TRAK is the culturally and linguistically adapted Ages and Stages Questionnaire (ASQ-3), a developmental screening tool, for Australian Aboriginal children. While the ASQ-TRAK has been well received in practice, investigating its psychometric properties will enable professionals to make informed decisions about its use. AIMS: To conduct a rigorous validation study of the ASQ-TRAK by applying Kane's argument-based approach. SUBJECTS: The ASQ-TRAK, Bayley-III and/or BDI-2 were administered cross-sectionally to 336 Australian Aboriginal children aged 2-48 months across ten participating sites in the Northern Territory and South Australia. A sample of staff and caregivers completed feedback surveys about the ASQ-TRAK. RESULTS: ASQ-TRAK domain scores were moderately positively correlated with corresponding domain scores on the Bayley-III or BDI-2. Inter-rater and inter-instrument reliability were high. Sensitivity (83%), specificity (83%) and negative predictive value (99%) were acceptable. Staff and caregivers expressed high levels of satisfaction with the ASQ-TRAK. CONCLUSIONS: Regular developmental screening can provide important information about developmental vulnerability and the need for services. The ASQ-TRAK should be administered by trained Aboriginal community-based workers and the implementation approach carefully planned. Areas for future research include longitudinal follow-up of children, investigating existing norms and cut-off scores, and considering the appropriateness of the ASQ-TRAK with Aboriginal people from different locations. The ASQ-TRAK has the potential to fill an important gap by enabling better access to high-quality developmental monitoring and targeted early intervention.

Feasibility of once weekly exenatide-LAR and enhanced diabetes care in Indigenous Australians with type 2 diabetes (Long-acting-Once-Weekly-Exenatide laR-SUGAR, 'Lower SUGAR' study).

BACKGROUND: Diabetes is 3-4 times more prevalent in Indigenous Australians with blood glucose levels often above target range. Once weekly formulations of exenatide(exenatide-LAR) have demonstrated significantly greater improvements in glycaemic management with no increased risk of hypoglycaemia and with reductions in bodyweight but have not been studied in Indigenous Australians. AIMS: To assess the feasibility and metabolic effects of once weekly supervised injection of exenatide-LAR in addition to standard care in Indigenous Australians with type 2 diabetes. METHODS: Two communities in Central Australia with longstanding specialist clinical outreach services were allocated by random coin toss to receive once-weekly exenatide-LAR injection with weekly nurse review and adjustment of medication for 20 weeks (community with exenatide-LAR) or to weekly nurse review in addition to standard care over 20 weeks (community without exenatide-LAR). The primary outcome was the feasibility of an intensive diabetes management model of care with and without weekly supervised exenatide-LAR. Secondary outcomes included change in HbA1c. RESULTS: Thirteen participants from the community with exenatide-LAR and nine participants from the community without exenatide-LAR were analysed. Eighty-five percent of individuals in the community with exenatide-LAR and 67% in the community without exenatide-LAR attended more than half of clinic visits. Median difference in the change in HbA1c from baseline to final visit, adjusted for baseline HbA1c, between the community with exenatide-LAR and the community without exenatide-LAR was -3.1%, 95% CI (-5.80%, -0.38%; P = 0.03). CONCLUSIONS: Weekly exenatide-LAR combined with weekly nurse review demonstrated greater improvements in HbA1c, highlighting its potential for use in remote communities.

Social and economic factors, maternal behaviours in pregnancy and neonatal adiposity in the PANDORA cohort.

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 socio-economic 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 with a 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 in length, head circumference and fat free mass. Frequent fast food intake remained independently associated with SSF (ß-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.

Maternal body mass index, excess gestational weight gain, and diabetes are positively associated with neonatal adiposity in the Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) study.

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.

High Baseline Levels of Tumor Necrosis Factor Receptor 1 Are Associated With Progression of Kidney Disease in Indigenous Australians With Diabetes: The eGFR Follow-up Study.

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 <60 mL/min/1.73 m2, progression to renal replacement therapy, or renal death) for increasing sTNFR1. 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.

Comparison of creatinine and cystatin C based eGFR in the estimation of glomerular filtration rate in Indigenous Australians: The eGFR Study.

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 4h. 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<0.001) and eGFRcysC+cr (10.3; 8.8-11.5, p<0.001) compared to eGFRcr (5.4; 3.0-7.2). Accuracy was lower for eGFRcysC (80.3%; 76.7-83.5, p<0.001) but not for eGFRcysC+cr (91.9; 89.3-94.0, p=0.29) compared to eGFRcr (90.0; 87.2-92.4). Precision was comparable for all equations. The performance of eGFRcysC deteriorated across increasing levels of c-reactive protein. CONCLUSION: Cystatin C based eGFR equations may not perform well in populations with high levels of chronic inflammation. CKD-EPI eGFR based on serum creatinine remains the preferred equation in Indigenous Australians.

Resting heart rate, physiological stress and disadvantage in Aboriginal and Torres Strait Islander Australians: analysis from a cross-sectional study.

BACKGROUND: Lower socioeconomic status has been linked to long-term stress, which can manifest in individuals as physiological stress. The aim was to explore the relationship between low socioeconomic status and physiological stress in Aboriginal and Torres Strait Islander Australians. METHODS: Using data from the eGFR Study (a cross-sectional study of 634 Indigenous Australians in urban and remote areas of northern and central Australia), we examined associations between resting heart rate and demographic, socioeconomic, and biomedical factors. An elevated resting heart rate has been proposed as a measure of sustained stress activation and was used as a marker of physiological stress. Relationships were assessed between heart rate and the above variables using univariate and multiple regression analyses. RESULTS: We reported a mean resting heart rate of 74 beats/min in the cohort (mean age 45 years). On multiple regression analysis, higher heart rate was found to be independently associated with Aboriginal ethnicity, being a current smoker, having only primary level schooling, higher HbA1c and higher diastolic blood pressure (model R(2) 0.25). CONCLUSIONS: Elevated resting heart rate was associated with lower socioeconomic status and poorer health profile in Aboriginal and Torres Strait Islander Australians. Higher resting heart rate may be an indicator of stress and disadvantage in this population at high risk of chronic diseases.

Effect of periodontal therapy on arterial structure and function among aboriginal australians: a randomized, controlled trial.

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.

Associations between periodontal disease and cardiovascular surrogate measures among Indigenous Australians.

BACKGROUND/OBJECTIVES: Inflammation is a key pathogenetic factor in atherogenesis. Periodontitis is a chronic inflammatory source which can have systemic impacts. Indigenous Australians have a higher prevalence of periodontal disease and experience cardiovascular disease earlier than non-Indigenous Australians. The aim was to describe the association between severity of periodontal inflammatory disease and measures of arterial structure and function. METHODS: Periodontal disease in a convenience sample of Indigenous Australians was assessed clinically; for those with periodontal disease, the extent of periodontal pockets ≥ 4 mm was stratified into quartiles. Vascular health was measured non-invasively via carotid-dorsalis pedis pulse-wave velocity (PWV), and via B-mode ultrasound of the common carotid intima-media (IMT). Non-fasting blood samples were collected for lipid and inflammatory marker evaluation. Linear regression models were constructed to determine the associations between extent of periodontal pocketing and vascular health, adjusting for traditional cardiovascular common risk factors. RESULTS: 273 Indigenous Australian adults were recruited and complete data was available for 269 participants (154 males), median age 39 years. Arterial stiffness (PWV) significantly increased with increasing extent of periodontal pocketing (p trend=0.001). By contrast, carotid IMT did not differ across quartiles. CONCLUSIONS: Periodontal pocketing was associated with central arterial stiffness, a marker of presymptomatic arterial dysfunction, in Indigenous Australian adults with periodontal disease.

Effects of full-mouth scaling on the periodontal health of Indigenous Australians: a randomized controlled trial.

BACKGROUND: Simplified periodontal therapy might be a pragmatic strategy for public health programmes targeting Indigenous Australian adults. The objective of this randomized controlled trial was to evaluate oral health effects of single-visit, non-surgical periodontal therapy compared to no treatment. METHODS: This parallel-group, randomized, open label clinical trial enrolled 273 Indigenous Australians aged ≥18 years with periodontitis. Intervention participants received full-mouth periodontal scaling and root planing during a single visit while the control group received no treatment. Endpoints were summary variables derived from clinical assessments of probing depth, clinical attachment loss, plaque, calculus and gingival bleeding before treatment and 3 months later. RESULTS: Endpoints could be calculated for 169 participants with follow-up data. Compared to the control group, there were statistically significant reductions in extent of shallow pockets: PD ≥4 mm (mean difference -2.86, [95% CI -5.01 to -0.71], p = 0.009) and gingival bleeding (mean difference -0.25, [95% CI -0.43 to -0.08], p = 0.005) but not deeper pockets PD ≥5 mm (mean difference -0.48, [95% CI -1.78 to 0.82], p = 0.468) or plaque scores. CONCLUSIONS: Periodontal therapy produced improvements in shallow periodontal pockets and measures of gingival bleeding in these Indigenous Australians.

Type 2 diabetes in young Indigenous Australians in rural and remote areas: diagnosis, screening, management and prevention.

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.

High rates of albuminuria but not of low eGFR in urban indigenous Australians: the DRUID study.

BACKGROUND: Indigenous Australians have an incidence of end stage kidney disease 8-10 times higher than non-Indigenous Australians. The majority of research studies concerning Indigenous Australians have been performed in rural or remote regions, whilst the majority of Indigenous Australians actually live in urban settings. We studied prevalence and factors associated with markers of kidney disease in an urban Indigenous Australian cohort, and compared results with those for the general Australian population. METHODS: 860 Indigenous adult participants of the Darwin Region Urban Indigenous Diabetes (DRUID) Study were assessed for albuminuria (urine albumin-creatinine ratio≥2.5 mg/mmol males, ≥3.5 mg/mmol females) and low eGFR (estimated glomular filtration rate < 60 mls/min/1.73 m(2)). Associations between risk factors and kidney disease markers were explored. Comparison was made with the AusDiab cohort (n = 8,936 aged 25-64 years), representative of the general Australian adult population. RESULTS: A high prevalence of albuminuria (14.8%) was found in DRUID, whilst prevalence of low eGFR was 2.4%. Older age, higher HbA1c, hypertension, higher C-reactive protein and current smoking were independently associated with albuminuria on multiple regression. Low eGFR was independently associated with older age, hypertension, albuminuria and higher triglycerides. Compared to AusDiab participants, DRUID participants had a 3-fold higher adjusted risk of albuminuria but not of low eGFR. CONCLUSIONS: Given the significant excess of ESKD observed in Indigenous versus non-Indigenous Australians, these findings could suggest either: albuminuria may be a better prognostic marker of kidney disease than low eGFR; that eGFR equations may be inaccurate in the Indigenous population; a less marked differential between Indigenous and non-Indigenous Australians for ESKD rates in urban compared to remote regions; or that differences in the pathophysiology of chronic kidney disease exist between Indigenous and non-Indigenous populations.

Fibrinogen and associated risk factors in a high-risk population: urban Indigenous Australians, the DRUID Study.

BACKGROUND: Epidemiological evidence suggests that fibrinogen and CRP are associated with coronary heart disease risk. High CRP in Indigenous Australians has been reported in previous studies including our 'Diabetes and Related diseases in Urban Indigenous population in Darwin region' (DRUID) Study. We studied levels of fibrinogen and its cross-sectional relationship with traditional and non-traditional cardiovascular risk factors in an urban Indigenous Australian cohort. METHODS: Fibrinogen data were available from 287 males and 628 females (aged ≥ 15 years) from the DRUID study. Analysis was performed for associations with the following risk factors: diabetes, HbA1c, age, BMI, waist circumference, waist-hip ratio, total cholesterol, triglyceride, HDL cholesterol, C-reactive protein, homocysteine, blood pressure, heart rate, urine ACR, smoking status, alcohol abstinence. RESULTS: Fibrinogen generally increased with age in both genders; levels by age group were higher than those previously reported in other populations, including Native Americans. Fibrinogen was higher in those with than without diabetes (4.24 vs 3.56 g/L, p < 0.001). After adjusting for age and sex, the following were significantly associated with fibrinogen: BMI, waist, waist-hip ratio, systolic blood pressure, heart rate, fasting triglycerides, HDL cholesterol, HbA1c, CRP, ACR and alcohol abstinence. On multivariate regression (age and sex-adjusted) CRP and HbA1c were significant independent predictors of fibrinogen, explaining 27% of its variance; CRP alone explained 25% of fibrinogen variance. On factor analysis, both CRP and fibrinogen clustered with obesity in women (this factor explained 20% of variance); but in men, CRP clustered with obesity (factor explained 18% of variance) whilst fibrinogen clustered with HbA1c and urine ACR (factor explained 13% of variance). CONCLUSIONS: Fibrinogen is associated with traditional and non-traditional cardiovascular risk factors in this urban Indigenous cohort and may be a useful biomarker of CVD in this high-risk population. The apparent different associations of fibrinogen with cardiovascular disease risk markers in men and women should be explored further.

Study Protocol--accurate assessment of kidney function in Indigenous Australians: aims and methods of the eGFR study.

BACKGROUND: There is an overwhelming burden of cardiovascular disease, type 2 diabetes and chronic kidney disease among Indigenous Australians. In this high risk population, it is vital that we are able to measure accurately kidney function. Glomerular filtration rate is the best overall marker of kidney function. However, differences in body build and body composition between Indigenous and non-Indigenous Australians suggest that creatinine-based estimates of glomerular filtration rate derived for European populations may not be appropriate for Indigenous Australians. The burden of kidney disease is borne disproportionately by Indigenous Australians in central and northern Australia, and there is significant heterogeneity in body build and composition within and amongst these groups. This heterogeneity might differentially affect the accuracy of estimation of glomerular filtration rate between different Indigenous groups. By assessing kidney function in Indigenous Australians from Northern Queensland, Northern Territory and Western Australia, we aim to determine a validated and practical measure of glomerular filtration rate suitable for use in all Indigenous Australians. METHODS/DESIGN: A cross-sectional study of Indigenous Australian adults (target n = 600, 50% male) across 4 sites: Top End, Northern Territory; Central Australia; Far North Queensland and Western Australia. The reference measure of glomerular filtration rate was the plasma disappearance rate of iohexol over 4 hours. We will compare the accuracy of the following glomerular filtration rate measures with the reference measure: Modification of Diet in Renal Disease 4-variable formula, Chronic Kidney Disease Epidemiology Collaboration equation, Cockcroft-Gault formula and cystatin C- derived estimates. Detailed assessment of body build and composition was performed using anthropometric measurements, skinfold thicknesses, bioelectrical impedance and a sub-study used dual-energy X-ray absorptiometry. A questionnaire was performed for socio-economic status and medical history. DISCUSSION: We have successfully managed several operational challenges within this multi-centre complex clinical research project performed across remote North, Western and Central Australia. It seems unlikely that a single correction factor (similar to that for African-Americans) to the equation for estimated glomerular filtration rate will prove appropriate or practical for Indigenous Australians. However, it may be that a modification of the equation in Indigenous Australians would be to include a measure of fat-free mass.

Increased arterial stiffness in remote Indigenous Australians with high risk of cardiovascular disease.

OBJECTIVE: To assess central and peripheral arterial stiffness in Indigenous and European Australians with and without type 2 diabetes using applanation tonometry to obtain the augmentation index (AI) and pulse wave velocity (PWV). METHODS: AI was assessed in 162 Indigenous Australians (60 with type 2 diabetes) participating in a population-based study and 121 Australians of European ancestry (38 with diabetes) of similar age and sex. PWV was assessed in a subgroup: n = 62 indigenous, n = 118 European participants. RESULTS: The indigenous group had higher AI than the European group [mean (SD) 32 (12) versus 24 (12)%, P < 0.0001] and carotid-femoral PWV [8.4 (1.8) versus 7.1 (2.2) ms(-1), P < 0.0001]. There were no significant differences between groups regarding blood pressure and total cholesterol; however, indigenous individuals had higher fasting glucose, insulin, haemoglobin A1c, triglycerides, waist circumference (despite lower body mass index), and a higher prevalence of cigarette smoking. Fifty-five per cent of the variance in AI was explained on multiple regression analysis by age, sex, indigenous participant, heart rate, mean arterial pressure, height, triglycerides and waist circumference. Age, indigenous participant, heart rate, mean arterial pressure and antihypertensive medication explained 56% of the variance in PWV. Variables of the metabolic syndrome and smoking, C-reactive protein (CRP), homocysteine and heart rate clustered with indigenous status on factor analysis. CONCLUSIONS: Indigenous Australians have higher indices of peripheral and central arterial stiffness than European Australians of similar age and sex. Factor analysis revealed that metabolic syndrome variables, smoking, CRP, homocysteine and heart rate clustered with 'indigenous participant' and may explain increased arterial stiffness in this group.