Causes of death among Australians with type 1 or type 2 diabetes, 2002-2019.

AIMS: This population-based study sought to explore in detail the conditions driving the diversification in causes of death among people with diabetes. METHODS: We linked Australians with type 1 or type 2 diabetes of all ages on the National Diabetes Services Scheme to the National Death Index for 2002-2019. We investigated the proportional contributions of different causes of death to total deaths over time across eight categories of causes of death, stratified by sex and diabetes type. The underlying causes of death were classified according to the International Classification of Diseases, Tenth Revision codes. RESULTS: Between 2002 and 2019, there was a shift in the causes of death among Australians with diabetes away from cardiovascular disease. The proportion of deaths attributed to cardiovascular disease declined in both sexes (ptrend <0.001), most substantially among women with type 2 diabetes from 48.2% in 2002 to 30.7% in 2019. Among men with type 2 diabetes, cancer replaced cardiovascular disease as the leading cause of death. The proportion of deaths due to dementia increased overall, from 2% in 2002 to over 7% in 2019, and across all age groups, notably from 1% to 4% in those aged 70-79. The proportion of deaths due to falls and Parkinson's disease also increased. CONCLUSIONS: There has been a shift of causes of death among those with diabetes away from cardiovascular disease. The proportion of deaths due to conditions such as dementia and falls is increasing among those with diabetes, which will require consideration when planning future resource allocation.

The role of combined modifiable lifestyle behaviors in the longitudinal association between stressful life events and allostatic load in Australian adults.

Allostatic load is a model that is used to quantify the physiological damage from exposure to stressors. Stressful life events are chronic stressors that can lead to an elevated allostatic load through the physiological and behavioral stress responses. However, there is limited empirical studies that has tested the proposed behavioural pathway. Our study addresses this gap by examining the mediating role of combined modifiable lifestyle behaviors in the 12-years longitudinal association between stressful life events and allostatic load among participants from the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study cohort. A latent profile analysis was performed to identify latent subgroups with distinct behavioral clusters based on five modifiable lifestyle behaviors (smoking, sedentary behavior, physical activity, alcohol consumption, and diet quality). We then used a sequential mediation model design with path analysis to test the mediating effect of these latent subgroups in the associations between stressful life events and three measures of allostatic load. Indirect effects were estimated using the product of coefficient approach and the statistical significance was determined by the 95% bias-corrected bootstrap confidence intervals with 1000 replications. We identified three latent subgroups: "least healthy lifestyle" (12%; n = 396), "moderately healthy lifestyle" (78.7%; n = 2599), and "most healthy lifestyle" (9.2%; n = 306). Exposure to stressful life events was not associated with the allocation of participants in latent subgroups. Compared to the "moderately healthy lifestyle" subgroups, we found that the "least healthy lifestyle" behavioral cluster was not associated with allostatic load. However, there was a significant inverse association between the "most healthy lifestyle" behavioral cluster and allostatic load. Overall, we did not find significant indirect effects between stressful life events and three measures of allostatic load via the "least healthy lifestyle" and the "most healthy lifestyle" groups. In summary, the combinations of modifiable lifestyle behaviors did not explain the association between stressful life events and allostatic load. More longitudinal studies are needed to replicate our study to confirm this finding.

The future burden of oesophageal and stomach cancers attributable to modifiable behaviours in Australia: a pooled cohort study.

BACKGROUND: We quantified the individual and joint contribution of contemporaneous causal behavioural exposures on the future burden of oesophageal and stomach cancers and their subtypes and assessed whether these burdens differ between population groups in Australia, as such estimates are currently lacking. METHODS: We combined hazard ratios from seven pooled Australian cohorts (N = 367,058) linked to national cancer and death registries with exposure prevalence from the 2017-2018 National Health Survey to estimate Population Attributable Fractions (PAFs) with 95% confidence intervals (CIs), accounting for competing risk of death. RESULTS: Current and past smoking explain 35.2% (95% CI = 11.7-52.4%), current alcohol consumption exceeding three drinks/day 15.7% (95% CI = 0.9-28.4%), and these exposures jointly 41.4% (95% CI = 19.8-57.3%) of oesophageal squamous cell carcinomas in Australia. Current and past smoking contribute 38.2% (95% CI = 9.4-57.9%), obesity 27.0% (95% CI = 0.6-46.4%), and these exposures jointly 54.4% (95% CI = 25.3-72.1%) of oesophageal adenocarcinomas. Overweight and obesity explain 36.1% (95% CI = 9.1-55.1%), current and past smoking 24.2% (95% CI = 4.2-40.0%), and these exposures jointly 51.2% (95% CI = 26.3-67.8%) of stomach cardia cancers. Several population groups had a significantly higher smoking-attributable oesophageal cancer burden, including men and those consuming excessive alcohol. CONCLUSIONS: Smoking is the leading preventable behavioural cause of oesophageal cancers and overweight/obesity of stomach cancers.

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 of biomarkers and risk scores with subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus.

BACKGROUND: Subclinical LV dysfunction (LVD) identifies heart failure (HF) risk in type 2 diabetes mellitus (T2DM). We sought the extent to which clinical scores (ARIC-HF, WATCH-DM), natriuretic peptides (NTpBNP) and troponin (hs-TnT) were associated with subclinical LV dysfunction (LVD). These associations could inform the ability of these tests to identify which patients should undergo echocardiography. METHODS: Participants with T2DM were prospectively recruited from three community-based populations. ARIC-HF risk at 4 years and WATCH-DM scores were calculated from clinical data. NTpBNP and hs-TnT were measured using an electro-chemiluminescence assay. All underwent a comprehensive echocardiogram. We calculated the sensitivity and specificity of clinical scores and biomarkers to identify abnormal global longitudinal strain (GLS ≥ -16%)), diastolic function (E/e' ≥ 14 or e' < 8 cm/s), left atrial volume index (LAV > 34 ml/m2) and LV hypertrophy (LV mass index > 88 g/m2 (F) > 102 g/m2(M)). RESULTS: Of 804 participants (median age 69 years [inter-quartile range (IQR) 65-73], 36% female), clinical scores suggested significant HF risk (median ARIC-HF 8% [IQR 4-12]; WATCH-DM 10 points [IQR 8-12]), and the median NTpBNP was 50 pg/mL [IQR 25-101] and hs-TnT 9.6 pg/mL [IQR 6.8-13.6]. Abnormal GLS was present in 126 (17%), elevated E/e' in 114 (15%), impaired e' in 629 (78%), increased LAV in 351 (44%) and LV hypertrophy in 113 (14%). After adjustments for age, body-mass index, and renal function, each standard deviation increase in NTpBNP was associated with a GLS increase of 0.32 (p < 0.001) and hs-TnT increase by 0.26 (p < 0.001). Similar trends were observed with ARIC-HF (standardised ß = 0.22, p < 0.001) and WATCH-DM (standardised ß = 0.22, p < 0.001) in univariable analyses. However, none of the risk assessment tools provided satisfactory discrimination for abnormal GLS (AUC 63%), diastolic indices (e' AUC 54-61%) or LV mass (AUC 59-67%). At a sensitivity of 90%, there was an unacceptably low (< 50%) specificity. CONCLUSION: Although risk assessment based on clinical scores or biomarkers would be desirable to stratify HF risk in people with T2DM, they show a weak relationship with subclinical LVD.

Associations between data-driven lifestyle profiles and cognitive function in the AusDiab study.

BACKGROUND: Mounting evidence highlights the importance of combined modifiable lifestyle factors in reducing risk of cognitive decline and dementia. Several a priori additive scoring approaches have been established; however, limited research has employed advanced data-driven approaches to explore this association. This study aimed to examine the association between data-driven lifestyle profiles and cognitive function in community-dwelling Australian adults. METHODS: A cross-sectional study of 4561 Australian adults (55.3% female, mean age 60.9 ± 11.3 years) was conducted. Questionnaires were used to collect self-reported data on diet, physical activity, sedentary time, smoking status, and alcohol consumption. Cognitive testing was undertaken to assess memory, processing speed, and vocabulary and verbal knowledge. Latent Profile Analysis (LPA) was conducted to identify subgroups characterised by similar patterns of lifestyle behaviours. The resultant subgroups, or profiles, were then used to further explore associations with cognitive function using linear regression models and an automatic Bolck, Croon & Hagenaars (BCH) approach. RESULTS: Three profiles were identified: (1) "Inactive, poor diet" (76.3%); (2) "Moderate activity, non-smokers" (18.7%); and (3) "Highly active, unhealthy drinkers" (5.0%). Profile 2 "Moderate activity, non-smokers" exhibited better processing speed than Profile 1 "Inactive, poor diet". There was also some evidence to suggest Profile 3 "Highly active, unhealthy drinkers" exhibited poorer vocabulary and verbal knowledge compared to Profile 1 and poorer processing speed and memory scores compared to Profile 2. CONCLUSION: In this population of community-dwelling Australian adults, a sub-group characterised by moderate activity levels and higher rates of non-smoking had better cognitive function compared to two other identified sub-groups. This study demonstrates how LPA can be used to highlight sub-groups of a population that may be at increased risk of dementia and benefit most from lifestyle-based multidomain intervention strategies.

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.

The burden and risks of emerging complications of diabetes mellitus.

The traditional complications of diabetes mellitus are well known and continue to pose a considerable burden on millions of people living with diabetes mellitus. However, advances in the management of diabetes mellitus and, consequently, longer life expectancies, have resulted in the emergence of evidence of the existence of a different set of lesser-acknowledged diabetes mellitus complications. With declining mortality from vascular disease, which once accounted for more than 50% of deaths amongst people with diabetes mellitus, cancer and dementia now comprise the leading causes of death in people with diabetes mellitus in some countries or regions. Additionally, studies have demonstrated notable links between diabetes mellitus and a broad range of comorbidities, including cognitive decline, functional disability, affective disorders, obstructive sleep apnoea and liver disease, and have refined our understanding of the association between diabetes mellitus and infection. However, no published review currently synthesizes this evidence to provide an in-depth discussion of the burden and risks of these emerging complications. This Review summarizes information from systematic reviews and major cohort studies regarding emerging complications of type 1 and type 2 diabetes mellitus to identify and quantify associations, highlight gaps and discrepancies in the evidence, and consider implications for the future management of diabetes mellitus.

Real-World Application of Insulin Pump Therapy Among Patients With Type 1 Diabetes in China: A Cross-Sectional Study.

Background: Although insulin pump therapy is an important treatment modality for patients with type 1 diabetes, rates of pump use appear to vary broadly internationally. This study aimed to investigate the application of insulin pump therapy among patients with type 1 diabetes in China. Methods: Data were collected from the Type 1 Diabetes Mellitus in China: Coverage, Costs and Care Study (3C Study). A total of 779 participants from this cross-sectional study were included. Multivariable logistic regression was used for data analysis. Results: The median (interquartile range) age at diagnosis of diabetes was 17 (10-28) years and the duration of diabetes was 4 (1-8) years. Among 779 patients, only 89 patients (11.4%) used an insulin pump to control blood glucose. A statistically significant difference was found in HbA1c favoring insulin pump therapy (8.3 ± 1.7% vs. 9.2 ± 2.6%) without obvious differences for severe hypoglycaemia. There were higher proportions of patients with no smoking, frequent daily intake of fruits and vegetables, and adequate self-blood glucose monitoring among patients with insulin pump therapy as compared to those using multiple daily insulin injections. Logistic regression analysis showed that younger age at diagnosis, longer duration of diabetes, higher education level of family members, and higher household income were associated with the use of an insulin pump. Conclusions: Data from 3C Study demonstrated that only a minority of patients with type 1 diabetes in China utilize insulin pump therapy. Insulin pump therapy was associated with better blood glucose control and self-management. Patients with younger age at diagnosis and longer duration of diabetes, and patients with better socioeconomic status were more likely to use an insulin pump.

Trends in all-cause mortality among people with diagnosed diabetes in high-income settings: a multicountry analysis of aggregate data.

BACKGROUND: Population-level trends in mortality among people with diabetes are inadequately described. We aimed to examine the magnitude and trends in excess all-cause mortality in people with diabetes. METHODS: In this retrospective, multicountry analysis, we collected aggregate data from 19 data sources in 16 high-income countries or jurisdictions (in six data sources in Asia, eight in Europe, one from Australia, and four from North America) for the period from Jan 1, 1995, to Dec 31, 2016, (or a subset of this period) on all-cause mortality in people with diagnosed total or type 2 diabetes. We collected data from administrative sources, health insurance records, registries, and a health survey. We estimated excess mortality using the standardised mortality ratio (SMR). FINDINGS: In our dataset, there were approximately 21 million deaths during 0·5 billion person-years of follow-up among people with diagnosed diabetes. 17 of 19 data sources showed decreases in the age-standardised and sex-standardised mortality in people with diabetes, among which the annual percentage change in mortality ranged from -0·5% (95% CI -0·7 to -0·3) in Hungary to -4·2% (-4·3 to -4·1) in Hong Kong. The largest decreases in mortality were observed in east and southeast Asia, with a change of -4·2% (95% CI -4·3 to -4·1) in Hong Kong, -4·0% (-4·8 to -3·2) in South Korea, -3·5% (-4·0 to -3·0) in Taiwan, and -3·6% (-4·2 to -2·9) in Singapore. The annual estimated change in SMR between people with and without diabetes ranged from -3·0% (95% CI -3·0 to -2·9; US Medicare) to 1·6% (1·4 to 1·7; Lombardy, Italy). Among the 17 data sources with decreasing mortality among people with diabetes, we found a significant SMR increase in five data sources, no significant SMR change in four data sources, and a significant SMR decrease in eight data sources. INTERPRETATION: All-cause mortality in diabetes has decreased in most of the high-income countries we assessed. In eight of 19 data sources analysed, mortality decreased more rapidly in people with diabetes than in those without diabetes. Further longevity gains will require continued improvement in prevention and management of diabetes. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

Thyroid cancers potentially preventable by reducing overweight and obesity in Australia: A pooled cohort study.

Thyroid cancer incidence and the prevalence of overweight and obesity are increasing, but the future thyroid cancer burden attributable to contemporary levels of overweight and obesity has not been evaluated before. We quantified this burden in Australia, and assessed whether the overweight/obesity-attributable burden differed by sex or other population subgroupings. We estimated the strength of the associations of overweight and obesity with thyroid cancer with adjusted proportional hazards models using pooled data from seven Australian cohorts (N = 367 058) with 431 thyroid cancer cases ascertained from linked national cancer registry data during a maximum 22-year follow-up. We combined these estimates with nationally representative 2017 to 2018 estimates of overweight and obesity prevalence to estimate population attributable fractions (PAFs) of future thyroid cancers attributable to overweight and obesity, accounting for competing risk of death, and compared PAFs for population subgroups. Contemporary levels of overweight and obesity explain 18.6% (95% confidence interval [CI] = 5.2%-30.2%), and obesity alone 13.7% (95% CI: 5.2%-21.4%), of the future thyroid cancer burden. The obesity-attributable thyroid cancer burden is 21.4% (95% CI: 2.8%-36.5%) for men and 10.1% (95% CI: 0.8%-18.6%) for women. Were the currently obese overweight instead, 9.9% (95% CI: 1.0%-18.1%) of thyroid cancers could be avoided. The relative overweight/obesity-attributable burden is higher for those consuming on average more than two alcoholic drinks per day (63.4%) and for those who are not married/co-habiting (33.2%). In conclusion, avoiding excess weight, especially obesity, should be a priority for thyroid cancer prevention. Further studies, with findings stratified by tumour size, may reveal the potential role of overdiagnosis in our results.

Nineteen-Year Associations between Three Diet Quality Indices and All-Cause and Cardiovascular Disease Mortality: The Australian Diabetes, Obesity, and Lifestyle Study.

BACKGROUND: Examining a variety of diet quality methodologies will inform best practice use of diet quality indices for assessing all-cause and cardiovascular disease (CVD) mortality. OBJECTIVES: To examine the association between 3 diet quality indices (Australian Dietary Guideline Index, DGI; Dietary Inflammatory Index, DII; Mediterranean-DASH (Dietary Approaches to Stop Hypertension) Intervention for Neurodegenerative Delay, MIND) and risk of all-cause mortality, CVD mortality, and nonfatal CVD events ≤19 y later. METHODS: Data on 10,009 adults (mean age 51.8 y; 52% female) from the Australian Diabetes, Obesity, and Lifestyle study were used. An FFQ was used to calculate DGI, DII, and MIND at baseline. Cox proportional hazard models were used to estimate HRs and 95% CI of all-cause mortality, CVD mortality, and nonfatal CVD events (stroke; myocardial infarction) according to 1 SD increase in diet quality, adjusted for age, sex, education, smoking, physical activity, energy intake, history of stroke or heart attack, and diabetes and hypertension status. RESULTS: Deaths due to all-cause (n = 1955) and CVD (n = 520), and nonfatal CVD events (n = 264) were identified during mean follow-ups of 17.7, 17.4, and 9.6 y, respectively. For all-cause mortality, HRs associated with higher DGI, DII, and MIND were 0.94 (95% CI: 0.89, 0.99), 1.08 (95% CI: 1.02, 1.15), and 0.93 (95% CI: 0.89, 0.98), respectively. For CVD mortality, HRs associated with higher DGI, DII, and MIND were 0.93 (95% CI: 0.85, 0.99), 1.10 (95% CI: 1.00, 1.24), and 0.90 (95% CI: 0.82, 0.98), respectively. There was limited evidence of associations between diet quality and nonfatal CVD events. CONCLUSIONS: A better quality diet predicted lower risk of all-cause and CVD mortality in Australian adults, whereas a more inflammatory diet predicted higher mortality risk. These findings highlight the applicability of following Australian dietary guidelines, a Mediterranean-style diet, and a low-inflammatory diet for the reduction of all-cause and CVD mortality risk.

Excess all-cause and cause-specific mortality for people with diabetes and end-stage kidney disease.

AIMS: Excess mortality is high in the setting of diabetes and end-stage kidney disease (ESKD), but the effects of ESKD beyond diabetes itself remains incompletely understood. We examined excess mortality in people with diabetes with versus without ESKD, and variation by age, sex and diabetes type. METHODS: This study included 63,599 people with type 1 (aged 20-69 years; 56% men) and 1,172,160 people with type 2 diabetes (aged 30+ years; 54% men), from the Australian National Diabetes Services Scheme. Initiation of renal replacement therapy and mortality outcomes were obtained via linkage to the Australia and New Zealand Dialysis and Transplant Registry and the National Death Index, respectively. Excess mortality was measured by calculating the mortality rate ratio (MRR) for people with versus without ESKD via indirect standardisation. RESULTS: A total of 9027 people developed ESKD during 8,601,522 person-years of follow-up. Among people with type 1 diabetes, the MRR was 34.9 (95%CI: 16.6-73.1) in men and 41.5 (20.8-83.1) in women aged 20-29 years and was 5.6 (4.5-7.0) and 7.4 (5.5-10.1) in men and women aged 60-69 years, respectively. In type 2 diabetes, MRRs were 16.6 (8.6-31.8) and 35.8 (17.0-75.2) at age 30-39 years and were 2.8 (2.6-3.1) and 3.6 (3.2-4.1) at age 80+ years in men and women, respectively. Excess cause-specific mortality was highest for peripheral artery disease, cardiac arrest, and infections, and lowest for cancer. CONCLUSIONS: Among people with diabetes, excess mortality in ESKD is much higher at younger ages and is higher for women compared with men.

Rate of decline in kidney function and known age-of-onset or duration of type 2 diabetes.

The association between rate of kidney function decline and age-of-onset or duration of diabetes has not been well investigated. We aimed to examine whether rates of estimated glomerular filtration rate (eGFR) decline differ by age-of-onset or duration in people with type 2 diabetes. Using the Action to Control Cardiovascular Risk in Diabetes study which included those with HbA1c ≥ 7.5% and who were at high risk of cardiovascular events,, rates of eGFR decline were calculated and were compared among groups defined by the known age-of-onset (0-39, 40-49, 50-59, 60-69 and > 70 years) and 5-year diabetes duration intervals. Changes in renal function were evaluated using median of 6 (interquartile range 3-10) eGFR measurements per person. eGFR decline was the slowest in those with known age-at-diagnosis of 50-59 years or those with duration of diabetes < 5 years. The rates of eGFR decline were significantly greater in those with known age-of-onset < 40 years or those with duration of diabetes > 20 years compared to those diagnosed at 50-59 or those with duration of diabetes < 5 years (- 1.98 vs - 1.61 mL/min/year; - 1.82 vs - 1.52 mL/min/year; respectively (p < 0.001). Those with youngest age-of-onset or longer duration of diabetes had more rapid declines in eGFR compared to those diagnosed at middle age or those with shorter duration of diabetes.

Gestational diabetes is associated with postpartum hemorrhage in Indigenous Australian women in the PANDORA study: A prospective cohort.

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

Erectile function in men with type 2 diabetes treated with dulaglutide: an exploratory analysis of the REWIND placebo-controlled randomised trial.

BACKGROUND: Diabetes is a major risk factor for erectile dysfunction, however, the effect of GLP-1 receptor agonists on erectile dysfunction is unknown. We aimed to assess the incidence, prevalence, and progression of erectile dysfunction in men treated with dulaglutide compared with placebo, and to determine whether dulaglutide's effect on erectile dysfunction was consistent with its effect on other diabetes-related outcomes. METHODS: The Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial was a double-blind, placebo-controlled randomised trial of the effect of dulaglutide on cardiovascular outcomes. REWIND was done at 371 sites in 24 countries. Men and women aged older than 50 years with type 2 diabetes, who had either a previous cardiovascular event or cardiovascular risk factors, were randomly assigned (1:1) to receive either dulaglutide or placebo. Participating men were offered the opportunity to complete the standardised International Index of Erectile Function (IIEF) questionnaire at baseline, 2 years, 5 years, and study end. We did an exploratory analysis, in which we included participants who completed a baseline and at least 1 follow-up IIEF questionnaire. The primary outcome for these analyses was the first occurrence of moderate or severe erectile dysfunction following randomisation, assessed by the erectile function subscores on IIEF. This analysis was part of the REWIND trial, which is registered with ClinicalTrials.gov, NCT01394952. FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 3725 (70·1%) of 5312 male participants with a mean age of 65·5 years (SD 6·4 years) were analysed, of whom 1487 (39·9%) had a history of cardiovascular disease, and 2104 (56·5%) had moderate or severe erectile dysfunction at baseline. The incidence of erectile dysfunction following randomisation was 21·3 per 100 person-years in the dulaglutide group and 22·0 per 100 person-years in the placebo group (HR 0·92, 95% CI 0·85-0·99, p=0·021). Men in the dulaglutide group also had a lesser fall in erectile function subscore compared with the placebo group, with a least square mean difference of 0·61 (95% CI 0·18-1·05, p=0·006). INTERPRETATION: Long-term use of dulaglutide might reduce the incidence of moderate or severe erectile dysfunction in men with type 2 diabetes. FUNDING: Eli Lilly and Company.

The Future Burden of Head and Neck Cancers Attributable to Modifiable Behaviors in Australia: A Pooled Cohort Study.

BACKGROUND: Estimates of future burden of cancer attributable to current modifiable causal exposures can guide cancer prevention. We quantified future head and neck cancer burden in Australia attributable to individual and joint causal exposures, and assessed whether these burdens differ between population subgroups. METHODS: We estimated the strength of the associations between exposures and head and neck cancer using adjusted proportional hazards models from pooled data from seven Australian cohorts (N = 367,058) linked to national cancer and death registries and estimated exposure prevalence from the 2017 to 2018 Australian National Health Survey. We calculated population attributable fractions (PAF) with 95% confidence intervals (CI), accounting for competing risk of death, and compared PAFs for population subgroups. RESULTS: Contemporary levels of current and former smoking contribute 30.6% (95% CI, 22.7%-37.8%), alcohol consumption exceeding two standard drinks per day 12.9% (95% CI, 7.6%-17.9%), and these exposures jointly 38.5% (95% CI, 31.1%-45.0%) to the future head and neck cancer burden. Alcohol-attributable burden is triple and smoking-attributable burden is double for men compared with women. Smoking-attributable burden is also at least double for those consuming more than two alcoholic drinks daily or doing less than 150 minutes of moderate or 75 minutes of vigorous activity weekly, and for those aged under 65 years, unmarried, with low or intermediate educational attainment or lower socioeconomic status, compared with their counterparts. CONCLUSIONS: Two-fifths of head and neck cancers in Australia are preventable by investment in tobacco and alcohol control. IMPACT: Targeting men and other identified high-burden subgroups can help to reduce head and neck cancer burden disparities.

Dietary Nitrate Intake Is Positively Associated with Muscle Function in Men and Women Independent of Physical Activity Levels.

BACKGROUND: Nitrate supplements can improve vascular and muscle function. Whether higher habitual dietary nitrate is associated with better muscle function remains underexplored. OBJECTIVE: The aim was to examine whether habitual dietary nitrate intake is associated with better muscle function in a prospective cohort of men and women, and whether the relation was dependent on levels of physical activity. METHODS: The sample (n = 3759) was drawn from the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab) (56% female; mean ± SD baseline age: 48.6 ± 11.1 y). Habitual dietary intake was assessed over 12 y by obtaining an average [of at least 2 time points, e.g., baseline (2000/2001) and 2004/2005 and/or 2011/2012] from a food-frequency questionnaire. Nitrate intake was calculated from a validated nitrate database and other published literature. Muscle function was quantified by knee extension strength (KES) and the 8-ft-timed-up-and-go (8ft-TUG) test performed in 2011/2012. Physical activity was assessed by questionnaire. Generalized linear models and logistic regression were used to analyze the data. RESULTS: Median (IQR) total nitrate intake was 65 (52-83) mg/d, with ∼81% derived from vegetables. Individuals in the highest tertile of nitrate intake (median intake: 91 mg/d) had 2.6 kg stronger KES (11%) and 0.24 s faster 8ft-TUG (4%) compared with individuals in the lowest tertile of nitrate intake (median intake: 47 mg/d; both P < 0.05). Similarly, individuals in the highest tertile of nitrate intake had lower odds for weak KES (adjusted OR: 0.69; 95% CI: 0.47, 0.73) and slow 8ft-TUG (adjusted OR: 0.63; 95% CI: 0.50, 0.78) compared with those in the lowest tertile. Physical activity did not influence the relationship between nitrate intake and muscle function (KES; P-interaction = 0.86; 8ft-TUG; P-interaction = 0.99). CONCLUSIONS: Higher habitual dietary nitrate intake, predominantly from vegetables, could be an effective way to promote lower-limb muscle strength and physical function in men and women.

Declining mortality in older people with type 2 diabetes masks rising excess risks at younger ages: a population-based study of all-cause and cause-specific mortality over 13 years.

BACKGROUND: Excess mortality in people with vs without type 2 diabetes (T2DM) has fallen, but it is unclear whether men/women at all ages have benefited and which causes of death have driven these trends. METHODS: All-cause and cause-specific mortality rates and excess mortality [by mortality rate ratios (MRRs) relative to the non-diabetic general population] were examined in 1 268 018 Australians with T2DM registered on the National Diabetes Services Scheme (2002-2014). RESULTS: Age-standardized mortality decreased in men (-2.2%/year; Ptrend < 0.001) and women with T2DM (-1.3%/year; Ptrend < 0.001) throughout 2002-14, which translated to declines in the MRRs (from 1.51 to 1.45 in men; 1.59 to 1.46 in women; Ptrend < 0.05 for both). Declining mortality rates in T2DM were observed in men aged 40+ years and women aged 60+ years (Ptrends <0.001), but not at younger ages. However, the only age group in which excess mortality declined relative to those without diabetes was 80+ years (Ptrends < 0.05); driven by reductions in excess cancer-related deaths in men and cardiovascular disease (CVD) in women. Among age groups <80 years, CVD and cancer MRRs remained similar or increased over time, despite falls in both CVD and cancer mortality rates. MRRs for non-CVD/non-cancer-related deaths increased in 60-79 year-olds, but were otherwise unchanged. CONCLUSIONS: Declining excess mortality attributable to T2DM from 2002-14 was driven entirely by reductions in those aged 80+ years. Declines in total mortality among those with T2DM were apparent in more age groups, but often to a lesser extent than in the general population, thereby serving to increase the excess risk associated with T2DM.