Publications by authors named "Dianna J Magliano"

194 Publications

Cardiovascular outcomes with sodium-glucose cotransporter-2 inhibitors vs other glucose-lowering drugs in 13 countries across three continents: analysis of CVD-REAL data.

Cardiovasc Diabetol 2021 07 31;20(1):159. Epub 2021 Jul 31.

Cardiovascular, Renal and Metabolism, BioPharmaceuticals Medical, AstraZeneca, Cambridge, CB2 8PA, UK.

Background: Randomized, controlled cardiovascular outcome trials may not be fully representative of the management of patients with type 2 diabetes across different geographic regions. We conducted analyses of data from the multinational CVD-REAL consortium to determine the association between initiation of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and cardiovascular outcomes, including subgroup analyses based on patient characteristics.

Methods: De-identified health records from 13 countries across three continents were used to identify patients newly-initiated on SGLT-2i or other glucose-lowering drugs (oGLDs). Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching for oGLD initiation. In the matched groups hazard ratios (HRs) for hospitalization for heart failure (HHF), all-cause death (ACD), the composite of HHF or ACD, myocardial infarction (MI) and stroke were estimated by country, and pooled using a weighted meta-analysis. Multiple subgroup analyses were conducted across patient demographic and clinical characteristics to examine any heterogeneity in treatment effects.

Results: Following matching, 440,599 new users of SGLT-2i and oGLDs were included in each group. Mean follow-up time was 396 days for SGLT-2i initiation and 406 days for oGLDs initiation. SGLT-2i initiation was associated with a lower risk of HHF (HR: 0.66, 95%CI 0.58-0.75; p < 0.001), ACD (HR: 0.52, 95%CI 0.45-0.60; p < 0.001), the composite of HHF or ACD (HR: 0.60, 95%CI 0.53-0.68; p < 0.001), MI (HR: 0.85, 95%CI 0.78-0.92; p < 0.001), and stroke (HR: 0.78, 95%CI 0.72-0.85; p < 0.001); regardless of patient characteristics, including established cardiovascular disease, or geographic region.

Conclusions: This CVD-REAL study extends the findings from the SGLT-2i clinical trials to the broader setting of an ethnically and geographically diverse population, and across multiple subgroups. Trial registration NCT02993614.
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http://dx.doi.org/10.1186/s12933-021-01345-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325810PMC
July 2021

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

Sci Rep 2021 Jul 19;11(1):14705. Epub 2021 Jul 19.

Department of Clinical Diabetes and Epidemiology, Baker Heart and Diabetes Institute, 99 Commercial Road, Melbourne, VIC, 3004, Australia.

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.
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http://dx.doi.org/10.1038/s41598-021-94099-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290031PMC
July 2021

Associations between fruit intake and risk of diabetes in the AusDiab cohort.

J Clin Endocrinol Metab 2021 Jun 2. Epub 2021 Jun 2.

School of Medical and Health Sciences, Edith Cowan University, Perth, Australia.

Background: Fruit, but not fruit juice, intake is inversely associated with type 2 diabetes mellitus (T2DM). However, questions remain about the mechanisms by which fruits may confer protection. Aims were to examine associations between intake of fruit types and 1) measures of glucose tolerance and insulin sensitivity and 2) diabetes at follow-up.

Methods: Among participants of the Australian Diabetes, Obesity and Lifestyle Study, fruit and fruit juice intake was assessed by food frequency questionnaire at baseline. Associations between fruit and fruit juice intake and 1) fasting plasma glucose, 2-h post-load plasma glucose, HOMA2 of β-cell function (HOMA2-%β), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin levels at baseline and 2) the presence of diabetes at follow-up (5 and 12 years) were assessed using restricted cubic splines in logistic and linear regression models.

Results: This population of 7,675 Australians (45% males) had a mean±SD age of 54±12 years at baseline. Total fruit intakes were inversely associated with serum insulin and HOMA2-%β, and positively associated with HOMA2-%S at baseline. Compared to participants with the lowest intakes (quartile 1), participants with moderate total fruit intakes (quartile 3) had a 36% lower odds of having diabetes at 5 years [OR (95% CI): 0.64 (0.44, 0.92)], after adjusting for dietary and lifestyle confounders. Associations with 12-year outcomes were not statistically significant.

Conclusion: A healthy diet including whole fruits, but not fruit juice, may play a role in mitigating T2DM risk.
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http://dx.doi.org/10.1210/clinem/dgab335DOI Listing
June 2021

Impact of the COVID-19 pandemic and lockdown restrictions on psychosocial and behavioural outcomes among Australian adults with type 2 diabetes: Findings from the PREDICT cohort study.

Diabet Med 2021 09 18;38(9):e14611. Epub 2021 Jun 18.

Baker Heart and Diabetes Institute, Melbourne, Vic., Australia.

Aim: To examine psychosocial and behavioural impacts of the novel coronavirus disease 2019 (COVID-19) pandemic and lockdown restrictions among adults with type 2 diabetes.

Methods: Participants enrolled in the PRogrEssion of DIabetic ComplicaTions (PREDICT) cohort study in Melbourne, Australia (n = 489 with a baseline assessment pre-2020) were invited to complete a phone/online follow-up assessment in mid-2020 (i.e., amidst COVID-19 lockdown restrictions). Repeated assessments that were compared with pre-COVID-19 baseline levels included anxiety symptoms (7-item Generalised Anxiety Disorder scale [GAD-7]), depressive symptoms (8-item Patient Health Questionnaire [PHQ-8]), diabetes distress (Problem Areas in Diabetes scale [PAID]), physical activity/sedentary behaviour, alcohol consumption and diabetes self-management behaviours. Additional once-off measures at follow-up included COVID-19-specific worry, quality of life (QoL), and healthcare appointment changes (telehealth engagement and appointment cancellations/avoidance).

Results: Among 470 respondents (96%; aged 66 ± 9 years, 69% men), at least 'moderate' worry about COVID-19 infection was reported by 31%, and 29%-73% reported negative impacts on QoL dimensions (greatest for: leisure activities, feelings about the future, emotional well-being). Younger participants reported more negative impacts (p < 0.05). Overall, anxiety/depressive symptoms were similar at follow-up compared with pre-COVID-19, but diabetes distress reduced (p < 0.001). Worse trajectories of anxiety/depressive symptoms were observed among those who reported COVID-19-specific worry or negative QoL impacts (p < 0.05). Physical activity trended lower (~10%), but sitting time, alcohol consumption and glucose-monitoring frequency remained unchanged. 73% of participants used telehealth, but 43% cancelled a healthcare appointment and 39% avoided new appointments despite perceived need.

Conclusions: COVID-19 lockdown restrictions negatively impacted QoL, some behavioural risk factors and healthcare utilisation in adults with type 2 diabetes. However, generalised anxiety and depressive symptoms remained relatively stable.
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http://dx.doi.org/10.1111/dme.14611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237067PMC
September 2021

Projecting the Incidence of Type 2 Diabetes-Related End-Stage Kidney Disease Until 2040: A Comparison Between the Effects of Diabetes Prevention and the Effects of Diabetes Treatment.

Diabetes Care 2021 May 23. Epub 2021 May 23.

Baker Heart and Diabetes Institute, Melbourne, Australia.

Objective: This study sought to examine the effects of two diabetes prevention approaches and of widespread use of sodium-glucose cotransporter 2 inhibitors (SGLT2is) among people with diabetes on the future incidence of diabetes-related end-stage kidney disease (ESKD-D).

Research Design And Methods: We developed a life table model to project the incidence of ESKD-D for type 2 diabetes in Australia until 2040. We projected incident ESKD-D under three separate scenarios: a large-scale lifestyle modification program for diabetes prevention; a population-wide sugar-sweetened beverage tax for diabetes prevention; and widespread use of SGLT2is among people with diabetes.

Results: Assuming current trends, we projected that the annual incidence of ESKD-D will increase from 3.7 per 100,000 of the general population in 2014 to 5.7 by 2040. Incorporating the diabetes prevention approaches, we projected that the annual incidence of ESKD-D will be between 5.2 and 5.5 per 100,000 by 2040. When we modeled scenarios in which 50% and 70% of eligible people with diabetes were prescribed an SGLT2i, the annual incidence of ESKD-D by 2040 was projected to be 4.7 and 4.3 per 100,000, respectively. SGLT2is were projected to reduce the total number of incident ESKD-D cases between 2020 and 2040 by 12-21% compared with current trends, whereas diabetes prevention reduced cases by 1-3%.

Conclusions: It is likely that the number of people developing ESKD-D will increase over the coming decades, although widespread SGLT2i use will be effective at limiting this increase. Diabetes prevention will be crucial to prevent an ever-increasing burden of diabetes complications.
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http://dx.doi.org/10.2337/dc21-0220DOI Listing
May 2021

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

Cancer Epidemiol Biomarkers Prev 2021 Aug 21;30(8):1566-1574. Epub 2021 May 21.

Centre for Big Data Research in Health, University of New South Wales, Sydney, Australia.

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 ( = 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.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0003DOI Listing
August 2021

Fruit and vegetable intake is inversely associated with perceived stress across the adult lifespan.

Clin Nutr 2021 05 15;40(5):2860-2867. Epub 2021 Apr 15.

Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia; Medical School, The University of Western Australia, Perth, Australia; Centre for Kidney Research, Children's Hospital at Westmead, School of Public Health, Sydney Medical School, The University of Sydney, Sydney, NSW, Australia.

Background & Aims: Poor nutritional habits are linked to higher perceived stress, but the relationship between fruit and vegetable (FV) intake and stress is uncertain. The primary aim of this cross-sectional study was to explore the relationship between FV intake and perceived stress in a population-based cohort of men and women aged ≥25 years from the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study. A secondary aim was to investigate the relationship between serum carotenoids, biomarkers of FV intake, and perceived stress.

Methods: In Australian men and women, dietary intake was assessed using a Food Frequency Questionnaire in 1999-2000 (n = 8689). Perceived stress was assessed using a validated Perceived Stress Questionnaire [PSQ index values ranging from 0 (lowest) to 1 (highest)]. Serum carotenoids were measured in a subset of participants (n = 1187) using high-performance liquid chromatography. Multivariable-adjusted linear and logistic regression were performed to investigate the associations between FV intake and perceived stress.

Results: Mean age of participants was 47.4 (SD 14.1) years (49.8% females). Participants with the highest intakes of FV had 10% lower PSQ index values than those with the lowest intake [Q4: 0.27 ± 0.004 vs. Q1: 0.30 ± 0.004 (mean ± SE), p = 0.004]. Similar associations were found for fruits and vegetables, analysed separately. In subgroup analyses higher FV intake was associated with lower perceived stress in the middle-aged adults [≥45-<65 years (p = 0.004)], but not in the younger (<45 years) and older participants (≥65 years). Higher FV intake was also significantly associated with lower perceived stress in men (p = 0.009) and women (p = 0.012), separately. Serum carotenoid levels were inversely associated with perceived stress before, but not after adjusting for age and other confounding factors.

Conclusion: In Australian adults, higher FV intake was associated with lower perceived stress, particularly in the middle-aged adults. These findings support current recommendations that fruit and vegetables are essential for health and well-being.
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http://dx.doi.org/10.1016/j.clnu.2021.03.043DOI Listing
May 2021

Association between Fruit and Vegetable Intakes and Mental Health in the Australian Diabetes Obesity and Lifestyle Cohort.

Nutrients 2021 Apr 24;13(5). Epub 2021 Apr 24.

Institute for Nutrition Research, Edith Cowan University, Perth 6027, Australia.

Increasing prevalence of mental health disorders within the Australian population is a serious public health issue. Adequate intake of fruits and vegetables (FV), dietary fibre (DF) and resistant starch (RS) is associated with better mental and physical health. Few longitudinal studies exist exploring the temporal relationship. Using a validated food frequency questionnaire, we examined baseline FV intakes of 5845 Australian adults from the AusDiab study and estimated food group-derived DF and RS using data from the literature. Perceived mental health was assessed at baseline and 5 year follow up using SF-36 mental component summary scores (MCS). We conducted baseline cross-sectional analysis and prospective analysis of baseline dietary intake with perceived mental health at 5 years. Higher baseline FV and FV-derived DF and RS intakes were associated with better 5 year MCS ( < 0.001). A higher FV intake (754 g/d vs. 251 g/d, Q4 vs. Q1) at baseline had 41% lower odds (OR = 0.59: 95% CI 0.46-0.75) of MCS below population average (<47) at 5 year follow up. Findings were similar for FV-derived DF and RS. An inverse association was observed with discretionary food-derived DF and RS. This demonstrates the association between higher intakes of FV and FV-derived DF and RS with better 5 year mental health outcomes. Further RCTs are necessary to understand mechanisms that underlie this association including elucidation of causal effects.
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http://dx.doi.org/10.3390/nu13051447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146262PMC
April 2021

Heterogeneity of Associations between Total and Types of Fish Intake and the Incidence of Type 2 Diabetes: Federated Meta-Analysis of 28 Prospective Studies Including 956,122 Participants.

Nutrients 2021 Apr 7;13(4). Epub 2021 Apr 7.

Postgraduate Program in Epidemiology Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil.

The association between fish consumption and new-onset type 2 diabetes is inconsistent and differs according to geographical location. We examined the association between the total and types of fish consumption and type 2 diabetes using individual participant data from 28 prospective cohort studies from the Americas (6), Europe (15), the Western Pacific (6), and the Eastern Mediterranean (1) comprising 956,122 participants and 48,084 cases of incident type 2 diabetes. Incidence rate ratios (IRRs) for associations of total fish, shellfish, fatty, lean, fried, freshwater, and saltwater fish intake and type 2 diabetes were derived for each study, adjusting for a consistent set of confounders and combined across studies using random-effects meta-analysis. We stratified all analyses by sex due to observed interaction ( = 0.002) on the association between fish and type 2 diabetes. In women, for each 100 g/week higher intake the IRRs (95% CIs) of type 2 diabetes were 1.02 (1.01-1.03, = 61%) for total fish, 1.04 (1.01-1.07, = 46%) for fatty fish, and 1.02 (1.00-1.04, = 33%) for lean fish. In men, all associations were null. In women, we observed variation by geographical location: IRRs for total fish were 1.03 (1.02-1.04, = 0%) in the Americas and null in other regions. In conclusion, we found evidence of a neutral association between total fish intake and type 2 diabetes in men, but there was a modest positive association among women with heterogeneity across studies, which was partly explained by geographical location and types of fish intake. Future research should investigate the role of cooking methods, accompanying foods and environmental pollutants, but meanwhile, existing dietary regional, national, or international guidelines should continue to guide fish consumption within overall healthy dietary patterns.
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http://dx.doi.org/10.3390/nu13041223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068031PMC
April 2021

Predicting Australian Adults at High Risk of Cardiovascular Disease Mortality Using Standard Risk Factors and Machine Learning.

Int J Environ Res Public Health 2021 03 19;18(6). Epub 2021 Mar 19.

Flinders Digital Health Research Centre, College of Nursing & Health Sciences, Flinders University, Adelaide SA 5001, Australia.

Effective cardiovascular disease (CVD) prevention relies on timely identification and intervention for individuals at risk. Conventional formula-based techniques have been demonstrated to over- or under-predict the risk of CVD in the Australian population. This study assessed the ability of machine learning models to predict CVD mortality risk in the Australian population and compare performance with the well-established Framingham model. Data is drawn from three Australian cohort studies: the North West Adelaide Health Study (NWAHS), the Australian Diabetes, Obesity, and Lifestyle study, and the Melbourne Collaborative Cohort Study (MCCS). Four machine learning models for predicting 15-year CVD mortality risk were developed and compared to the 2008 Framingham model. Machine learning models performed significantly better compared to the Framingham model when applied to the three Australian cohorts. Machine learning based models improved prediction by 2.7% to 5.2% across three Australian cohorts. In an aggregated cohort, machine learning models improved prediction by up to 5.1% (area-under-curve (AUC) 0.852, 95% CI 0.837-0.867). Net reclassification improvement (NRI) was up to 26% with machine learning models. Machine learning based models also showed improved performance when stratified by sex and diabetes status. Results suggest a potential for improving CVD risk prediction in the Australian population using machine learning models.
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http://dx.doi.org/10.3390/ijerph18063187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003399PMC
March 2021

Association of habitual intake of fruits and vegetables with depressive symptoms: the AusDiab study.

Eur J Nutr 2021 Oct 29;60(7):3743-3755. Epub 2021 Mar 29.

Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Perth, WA, Australia.

Purpose: To investigate the relationship of habitual FV intake, different types of FV, and vegetable diversity with depressive symptoms.

Methods: Australian men and women (n = 4105) aged > 25 years from the Australian Diabetes, Obesity and Lifestyle Study were included. Dietary intake was assessed using a Food Frequency Questionnaire at baseline, 5 and 12 years. Depressive symptoms were assessed using the validated 10-item Centre for Epidemiology Studies Short Depression Scale at 12 years. Multiple logistic regression models were used to investigate the association between the exposures of interest and depressive symptoms using odds ratios (OR) and 95% confidence intervals (CI) across quartiles of FV intake and vegetable diversity. Analyses were multivariable-adjusted for confounding factors.

Results: At 12 years, 425 (10.4%) participants had "any depressive symptoms". Habitual FV intake was inversely associated with depressive symptoms at 12 years. After adjustment, participants in quartile 2 of FV intake (Q2; median 317 g/day) had a 20% lower odds of having any depressive symptoms (OR [95% CI] 0.80 [0.69, 0.95]) in comparison to those in the lowest quartile of FV intake (Q1; median 223 g/day). Yellow/orange/red and leafy green vegetables were the key vegetable types driving this association. Higher vegetable diversity (4-6 different vegetables/day) was associated with a 24-42% lower odds of having depressive symptoms when compared to < 3 different vegetables/day. The associations remained similar after further adjusting for diet quality.

Conclusion: A FV-rich diet, consisting of a diverse range of vegetables, particularly yellow/orange/red and leafy green vegetables may help to lower depressive symptoms. Promoting such a diet, particularly in men and women with a low FV intake, may have a significant public health impact.
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http://dx.doi.org/10.1007/s00394-021-02532-0DOI Listing
October 2021

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

J Nutr 2021 05;151(5):1222-1230

Institute for Nutrition Research, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.

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.
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http://dx.doi.org/10.1093/jn/nxaa415DOI Listing
May 2021

Heart failure hospitalisation relative to major atherosclerotic events in type 2 diabetes with versus without chronic kidney disease: A meta-analysis of cardiovascular outcomes trials.

Diabetes Metab 2021 Mar 17;47(5):101249. Epub 2021 Mar 17.

Clinical Diabetes and Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Australia.

Aim: We examined whether chronic kidney disease (CKD) modifies the frequency of heart failure hospitalisation (HHF) relative to atherosclerotic major adverse cardiovascular events (MACE; composite of cardiovascular death, myocardial infarction [MI], or stroke) in people with type 2 diabetes.

Methods: Of 16 cardiovascular outcomes trials in type 2 diabetes since 2013, seven reported outcomes stratified by estimated glomerular filtration rate (eGFR) category (<60 vs. ≥60 mL/min/1.73 m), and five by albuminuria status. Placebo-arm incidence rates of HHF, MACE, MI and stroke were extracted for each eGFR and albuminuria subgroup.

Results: CKD coincided with higher rates of all events, but the greatest increase was observed for HHF (2.66 times higher rate in subgroups with reduced eGFR [95% CI 2.23-3.18]; 2.69 times higher in those with albuminuria [95% CI 2.30-3.13]). By contrast, the rate of MACE was 1.78 (1.67-1.91) and 1.80 (1.57-2.07) times higher in those with reduced eGFR and albuminuria, respectively. In people with CKD, HHF occurred at a similar rate to MI (ratio of HHF:MI = 0.92 with eGFR <60, 0.94 with albuminuria), while in those without CKD, MI was significantly more common (HHF:MI = 0.58 with eGFR 60+ and 0.60 with normoalbuminuria). HHF rates exceeded stroke in people with CKD, but these events otherwise occurred at a similar rate. While reduced eGFR was associated with older age, no such differences between people with/without albuminuria explained their different event profile.

Conclusion: CKD is associated with a shift in the profile of cardiovascular events in people with type 2 diabetes, marked by a disproportionate increase in HHF relative to MACE.
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http://dx.doi.org/10.1016/j.diabet.2021.101249DOI Listing
March 2021

Associations of Total Legume, Pulse, and Soy Consumption with Incident Type 2 Diabetes: Federated Meta-Analysis of 27 Studies from Diverse World Regions.

J Nutr 2021 05;151(5):1231-1240

School of Public Health, Physiotherapy & Sports Science, University College Dublin, Dublin, Ireland.

Background: The consumption of legumes is promoted as part of a healthy diet in many countries but associations of total and types of legume consumption with type 2 diabetes (T2D) are not well established. Analyses across diverse populations are lacking despite the availability of unpublished legume consumption data in prospective cohort studies.

Objective: To examine the prospective associations of total and types of legume intake with the risk of incident T2D.

Methods: Meta-analyses of associations between total legume, pulse, and soy consumption and T2D were conducted using a federated approach without physical data-pooling. Prospective cohorts were included if legume exposure and T2D outcome data were available and the cohort investigators agreed to participate. We estimated incidence rate ratios (IRRs) and CIs of associations using individual participant data including ≤42,473 incident cases among 807,785 adults without diabetes in 27 cohorts across the Americas, Eastern Mediterranean, Europe, and Western Pacific. Random-effects meta-analysis was used to combine effect estimates and estimate heterogeneity.

Results: Median total legume intake ranged from 0-140 g/d across cohorts. We observed a weak positive association between total legume consumption and T2D (IRR = 1.02, 95% CI: 1.01 to 1.04) per 20 g/d higher intake, with moderately high heterogeneity (I2 = 74%). Analysis by region showed no evidence of associations in the Americas, Eastern Mediterranean, and Western Pacific. The positive association in Europe (IRR = 1.05, 95% CI: 1.01 to 1.10, I2 = 82%) was mainly driven by studies from Germany, UK, and Sweden. No evidence of associations was observed for the consumption of pulses or soy.

Conclusions: These findings suggest no evidence of an association of legume intakes with T2D in several world regions. The positive association observed in some European studies warrants further investigation relating to overall dietary contexts in which legumes are consumed, including accompanying foods which may be positively associated with T2D.
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http://dx.doi.org/10.1093/jn/nxaa447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112771PMC
May 2021

Trends in the incidence of diagnosed diabetes: a multicountry analysis of aggregate data from 22 million diagnoses in high-income and middle-income settings.

Lancet Diabetes Endocrinol 2021 04 23;9(4):203-211. Epub 2021 Feb 23.

Science Programs Department, Kaiser Permanente Center for Health Research, Portland, OR, USA.

Background: Diabetes prevalence is increasing in most places in the world, but prevalence is affected by both risk of developing diabetes and survival of those with diabetes. Diabetes incidence is a better metric to understand the trends in population risk of diabetes. Using a multicountry analysis, we aimed to ascertain whether the incidence of clinically diagnosed diabetes has changed over time.

Methods: In this multicountry data analysis, we assembled aggregated data describing trends in diagnosed total or type 2 diabetes incidence from 24 population-based data sources in 21 countries or jurisdictions. Data were from administrative sources, health insurance records, registries, and a health survey. We modelled incidence rates with Poisson regression, using age and calendar time (1995-2018) as variables, describing the effects with restricted cubic splines with six knots for age and calendar time.

Findings: Our data included about 22 million diabetes diagnoses from 5 billion person-years of follow-up. Data were from 19 high-income and two middle-income countries or jurisdictions. 23 data sources had data from 2010 onwards, among which 19 had a downward or stable trend, with an annual estimated change in incidence ranging from -1·1% to -10·8%. Among the four data sources with an increasing trend from 2010 onwards, the annual estimated change ranged from 0·9% to 5·6%. The findings were robust to sensitivity analyses excluding data sources in which the data quality was lower and were consistent in analyses stratified by different diabetes definitions.

Interpretation: The incidence of diagnosed diabetes is stabilising or declining in many high-income countries. The reasons for the declines in the incidence of diagnosed diabetes warrant further investigation with appropriate data sources.

Funding: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.
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http://dx.doi.org/10.1016/S2213-8587(20)30402-2DOI Listing
April 2021

Exposure to persistent organic pollutants and the risk of type 2 diabetes: a case-cohort study.

Diabetes Metab 2021 Jan 27;47(5):101234. Epub 2021 Jan 27.

EPI-PHARE Scientific Interest Group in Epidemiology of Health Products, French National Agency for the Safety of Medicines and Health Products and the French National Health Insurance, Saint-Denis, Ile-de-France, France; IRSA, La Riche, France.

Aims: To explore exposure to 22 persistent organic pollutants (POPs) and incident type 2 diabetes in a population-based, prospective cohort.

Methods: This case-cohort study on 753 participants without type 2 diabetes at baseline, was followed-up over nine years, as part of the French D.E.S.I.R. cohort. We measured 22 POPs in fasting serum at baseline. The associations between baseline POP concentrations, pre-adjusted for lipids, BMI, age and sex, with incident type 2 diabetes, were assessed using Prentice-weighted Cox regression models (time scale: age), adjusted for traditional confounding factors. POPs were also modelled summed in functional groups: polychlorinated biphenyls (∑PCB) and organochlorines (∑OC) and also individually, after log-transformation, in adjusted Cox models.

Results: There were 200 incident diabetes cases over nine years. Pre-adjusted POP concentrations were not related to diabetes risk for any of the 22 POPs examined. The fully-adjusted hazard ratios (HRs) per interquartile range of the pre-adjusted POPs, ranged from 0.87 (95% CI: 0.64,1.19) to 1.22 (0.93,1.59,). For dichlorodiphenyldichloroethylene (p, p'-DDE) and dichlorodiphenyltrichloroethane (p, p'-DDT), the HRs were 1.09 (0.83,1.43) and 0.89 (0.70,1.13), respectively. The HRs for PeCB, HCB, β-HCH, γ-HCH, oxychlordane, trans-nonachlor were 0.98 (0.85,1.13), 1.06 (0.84,1.33), 1.22 (0.93,1.59), 1.13 (0.89,1.42), 1.00 (0.76,1.31), 0.86 (0.66,1.13), respectively. HRs for ∑PCB, ∑OC and for individual log-transformed POPs did not differ significantly from one.

Conclusion: We did not observe any relations between exposure to POPs and diabetes in this population-based cohort. These results do not support causal inferences reported in previous studies linking serum POP concentrations and diabetes risk.
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http://dx.doi.org/10.1016/j.diabet.2021.101234DOI Listing
January 2021

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.

Int J Epidemiol 2021 Aug;50(4):1362-1372

Diabetes and Population Health, Baker Heart and Diabetes Institute, Melbourne, Australia.

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.
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http://dx.doi.org/10.1093/ije/dyaa270DOI Listing
August 2021

Productivity Benefits of Preventing Type 2 Diabetes in Australia: A 10-Year Analysis.

Diabetes Care 2021 03 8;44(3):715-721. Epub 2021 Jan 8.

School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia

Objective: Diabetes imposes a heavy burden on both health and productivity. In this study, we sought to estimate the potential productivity gains associated with the prevention of type 2 diabetes over the next 10 years in Australia.

Research Design And Methods: Dynamic life table models were constructed to estimate years of life lived and productivity-adjusted life-years (PALYs) lived by Australians aged 20-69 years over the period from 2020 to 2029. The models distinguished people with and without type 2 diabetes. PALYs were ascribed a financial value equivalent to gross domestic product (GDP) per full-time worker in Australia (∼200,000 Australian dollars [AUD]). The model simulation was first undertaken assuming currently expected trends in the incidence of type 2 diabetes and then repeated assuming hypothetically that the incidence was reduced. The difference between the modeled outputs reflected the impact of new cases of type 2 diabetes on productivity as well as the potential benefits of prevention. An annual 5% discount rate was applied to all outcomes.

Results: Over the next decade, 140 million years of life and 87 million PALYs will be lived by Australians of working age, contributing AUD 18.0 trillion to the country's GDP. A 10% reduction in the incidence of type 2 diabetes would result in a gain of 2,510 PALYs and AUD 532 million in GDP.

Conclusions: This study illustrates the health and economic impact of type 2 diabetes and the gains that could be potentially achieved from the implementation of effective prevention strategies. However, cost-effectiveness evaluations of these prevention strategies are needed.
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http://dx.doi.org/10.2337/dc20-1429DOI Listing
March 2021

Can patterns of medication use explain the increasing incidence of end stage kidney disease among people with diabetes in Australia?

Diabetes Res Clin Pract 2021 Feb 23;172:108635. Epub 2020 Dec 23.

Department of Clinical Diabetes and Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Australia; School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.

Aims: Recently, an increase in the incidence of end-stage kidney disease (ESKD) among people with type 2 diabetes (T2D) aged < 50 years and ≥ 80 years has been observed in Australia. We examined whether patterns of medication use are likely to explain these trends.

Methods: Among National Diabetes Services Scheme registrants, we determined the annual prevalence of dispensed glucose-lowering (GL), blood-pressure-lowering (BPL) and lipid-lowering (LL) agents with ≥3, ≥6 or ≥9 dispensings per year from 2003 to 2013. Relative changes in the prevalence were determined via Poisson regression.

Results: During 2003-2013, the percentage of people with T2D dispensed GL, BPL and LL agents with ≥3, ≥6 or ≥9 dispensings per year increased in all age-groups. From 2003 to 2013, GL, BPL and LL agents use with ≥3 dispensings per year increased by 17%, 8.2%, and 53%, respectively. The use of renin-angiotensin-aldosterone-system-blockers over time also increased but more slowly in those aged <60 years compared to those aged ≥80 years (6% vs 18%, p < 0.001).

Conclusions: Changes in medication use are not likely to explain increasing incidence of ESKD in younger Australians with T2D. Studies are needed to provide insights into the major drivers of the rising incidence of ESKD in this population.
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http://dx.doi.org/10.1016/j.diabres.2020.108635DOI Listing
February 2021

Impact of age at type 2 diabetes mellitus diagnosis on mortality and vascular complications: systematic review and meta-analyses.

Diabetologia 2021 02 14;64(2):275-287. Epub 2020 Dec 14.

School Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia.

Aims/hypothesis: Few studies examine the association between age at diagnosis and subsequent complications from type 2 diabetes. This paper aims to summarise the risk of mortality, macrovascular complications and microvascular complications associated with age at diagnosis of type 2 diabetes.

Methods: Data were sourced from MEDLINE and All EBM (Evidence Based Medicine) databases from inception to July 2018. Observational studies, investigating the effect of age at diabetes diagnosis on macrovascular and microvascular diabetes complications in adults with type 2 diabetes were selected according to pre-specified criteria. Two investigators independently extracted data and evaluated all studies. If data were not reported in a comparable format, data were obtained from authors, presented as minimally adjusted ORs (and 95% CIs) per 1 year increase in age at diabetes diagnosis, adjusted for current age for each outcome of interest. The study protocol was recorded with PROSPERO International Prospective Register of Systematic Reviews (CRD42016043593).

Results: Data from 26 observational studies comprising 1,325,493 individuals from 30 countries were included. Random-effects meta-analyses with inverse variance weighting were used to obtain the pooled ORs. Age at diabetes diagnosis was inversely associated with risk of all-cause mortality and macrovascular and microvascular disease (all p < 0.001). Each 1 year increase in age at diabetes diagnosis was associated with a 4%, 3% and 5% decreased risk of all-cause mortality, macrovascular disease and microvascular disease, respectively, adjusted for current age. The effects were consistent for the individual components of the composite outcomes (all p < 0.001).

Conclusions/interpretation: Younger, rather than older, age at diabetes diagnosis was associated with higher risk of mortality and vascular disease. Early and sustained interventions to delay type 2 diabetes onset and improve blood glucose levels and cardiovascular risk profiles of those already diagnosed are essential to reduce morbidity and mortality. Graphical abstract.
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http://dx.doi.org/10.1007/s00125-020-05319-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801294PMC
February 2021

Seventeen-Year Associations between Diet Quality Defined by the Health Star Rating and Mortality in Australians: The Australian Diabetes, Obesity and Lifestyle Study (AusDiab).

Curr Dev Nutr 2020 Nov 14;4(11):nzaa157. Epub 2020 Oct 14.

The George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.

Background: The Health Star Rating (HSR) is the government-endorsed front-of-pack labeling system in Australia and New Zealand.

Objectives: We aimed to examine prospective associations of a dietary index (DI) based on the HSR, as an indicator of overall diet quality, with all-cause and cardiovascular disease (CVD) mortality.

Methods: We utilized data from the national population-based Australian Diabetes, Obesity and Lifestyle Study. The HSR-DI at baseline (1999-2000) was constructed by ) calculation of the HSR points for individual foods in the baseline FFQ, and ) calculation of the HSR-DI for each participant based on pooled HSR points across foods, weighted by the proportion of energy contributed by each food. Vital status was ascertained by linkage to the Australian National Death Index. Associations of HSR-DI with mortality risk were assessed by Cox proportional hazards regression.

Results: Among 10,025 eligible participants [baseline age: 51.6 ± 14.3 y (mean ± standard deviation)] at entry, higher HSR-DI (healthier) was associated with higher consumption of healthy foods such as fruits, vegetables, and nuts, and lower consumption of discretionary foods such as processed meats and confectionery (-trend < 0.001 for each). During a median follow-up of 16.9 y, 1682 deaths occurred with 507 CVD deaths. In multivariable models adjusted for demographic characteristics, lifestyle factors, and medical conditions, higher HSR-DI was associated with lower risk of all-cause mortality, with a hazard ratio (95% confidence interval) of 0.80 (0.69, 0.94; -trend < 0.001) comparing the fifth with the first HSR-DI quintile. A corresponding inverse association was observed for CVD mortality (0.71; 0.54, 0.94; -trend = 0.008).

Conclusions: Better diet quality as defined by the HSR-DI was associated with lower risk of all-cause and CVD mortality among Australian adults. Our findings support the use of the HSR nutrient profiling algorithm as a valid tool for guiding consumer food choices.
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http://dx.doi.org/10.1093/cdn/nzaa157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649117PMC
November 2020

The association of socioeconomic disadvantage and remoteness with receipt of type 2 diabetes medications in Australia: a nationwide registry study.

Diabetologia 2021 02 20;64(2):349-360. Epub 2020 Oct 20.

Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.

Aims/hypothesis: In recent years, several new medications for the treatment of type 2 diabetes have been released and some evidence indicates sociodemographic disparity in their utilisation. We sought to investigate sociodemographic disparities in receipt of diabetes medications across Australia.

Methods: This study included 1,203,317 people with type 2 diabetes registered on the Australian National Diabetes Services Scheme (NDSS) followed from 2007 to 2015. The NDSS was linked to the Australian pharmaceutical claims database. We investigated trends in diabetes medication dispensing and variation in dispensing by sociodemographic strata.

Results: Compared with individuals in the least disadvantaged areas, those in the most disadvantaged quintile were less likely to receive dipeptidyl peptidase-4 inhibitors (DPP4is), glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is) in the first year of availability (OR [95% CI] for most vs least disadvantaged: 0.78 [0.75, 0.82], 0.65 [0.60, 0.71] and 0.89 [0.84, 0.95], respectively). These disparities dissipated over time for DPP4is and SGLT2is but remained significant for GLP-1RAs. The OR (95% CI) of receiving DPP4is, GLP-1RAs and SGLT2is in the first year of availability for people in remote areas vs major cities was 0.46 (0.39, 0.54), 0.46 (0.35, 0.61) and 0.71 (0.59, 0.84), respectively. These disparities remained significant through to 2015.

Conclusions/interpretation: People with diabetes in more disadvantaged areas are less likely to receive newer diabetes medications, although this effect decreased over time. However, there are considerable and persistent differences in receipt of newer diabetes medications between major cities and remote areas of Australia. Graphical abstract.
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http://dx.doi.org/10.1007/s00125-020-05304-3DOI Listing
February 2021

Changes in prevalence of diabetes over 15 years in a rural Australian population: The Crossroads Studies.

Diabetes Res Clin Pract 2020 Dec 8;170:108492. Epub 2020 Oct 8.

Department of Rural Health, University of Melbourne, Australia.

Aims: Secular trends in diabetes prevalence vary globally. We compared the prevalence of diabetes in two surveys 15 years apart in rural Australia.

Method: Two cross-sectional household surveys and clinics (biomedical assessments including oral glucose tolerance tests (OGTTs)) in 2001-2003 (Crossroads) and 2016-2018 (Crossroads-II).

Setting: Four rural Victorian towns.

Participants: Residents of randomly selected households (Crossroads (n = 5258), Crossroads-II (n = 2649)) with nested clinic assessments for randomly selected participants (n = 1048 and 736 respectively). Response rate 61%.

Main Outcome Measures: Self-reported diagnosed diabetes, screening history, and diabetes defined by OGTT.

Results: The age standardised prevalence of diagnosed diabetes increased from 5.0(4.4-5.7)% to 7.7(6.7-8.6)%, with crude prevalence increasing overall (5.4 to 10.4% p < 0.001), in the smaller towns (5.4 to 11.1% p = 0.001) and, the regional centre (4.1 to 7.3% p < 0.001). Screening for diabetes over the previous two years increased (rural towns 49.8 to 63.8%; regional centre 44.9 to 63.6%; both p < 0.001). The proportion of undiagnosed diabetes was 23.2% in 2003 and 13.7% in 2018. The age and sex adjusted change in total diabetes was (1.15(0.84-1.59)). Central obesity (adjusted odd ratio 1.28(1.00-1.64)) but not overall obesity (adjusted odd ratio 1.17(0.95-1.46)) increased over time.

Conclusions: Over 15 years, the crude prevalence of diagnosed diabetes increased while the age and sex adjusted total diabetes prevalence did not change significantly. The epidemic may be slowing in some settings.
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http://dx.doi.org/10.1016/j.diabres.2020.108492DOI Listing
December 2020

Educating junior doctors and pharmacists to reduce discharge prescribing of opioids for surgical patients: a cluster randomised controlled trial.

Med J Aust 2020 11 10;213(9):417-423. Epub 2020 Oct 10.

Alfred Health, Melbourne, VIC.

Objectives: To evaluate whether educating junior doctors and hospital pharmacists about analgesic prescribing improved discharge prescribing of opioids for opioid-naïve patients after surgical admissions.

Design: Cluster randomised controlled trial, undertaken during the first half of 2019.

Setting: The Alfred Hospital, a major Melbourne teaching hospital with 13 surgical units.

Participants: Opioid-naïve patients discharged from surgical units after a stay of at least 24 hours.

Intervention: Surgical units were randomised to the intervention or control arms. Interns, residents, and clinical pharmacists assigned to intervention arm units attended education sessions, presented by the hospital analgesic stewardship pharmacist, about appropriate analgesic prescribing for patients in hospital surgical units.

Main Outcome Measures: The patients prescribed slow release opioids on discharge from hospital during the baseline (1 February - 30 April 2018) and post-intervention periods (17 February - 30 April 2019).

Results: During the baseline period, 1369 intervention unit and 1014 control unit admissions were included in our analysis; during the evaluation period, 973 intervention unit and 706 control unit episodes were included. After adjusting for age, length of stay, pain score, acute pain service involvement, and use of immediate release opioids prior to admission, patients in the intervention group were prescribed slow release opioids at discharge less frequently than patients in the control group (adjusted odds ratio [aOR], 0.52; 95% CI, 0.35-0.77) and were more frequently discharged without any prescribed opioids following the intervention (aOR, 1.69; 95% CI, 1.24-2.30). Providing de-escalation plans was more frequent for intervention than control group patients prescribed slow release opioids on discharge post-intervention (OR, 2.36; 95% CI, 1.25-4.45).

Conclusions: Specific education for clinicians and pharmacists about appropriate analgesic prescribing for surgical patients is effective in reducing prescribing of opioids at discharge.

Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12618000876291 (prospective).
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http://dx.doi.org/10.5694/mja2.50812DOI Listing
November 2020

High-coverage plasma lipidomics reveals novel sex-specific lipidomic fingerprints of age and BMI: Evidence from two large population cohort studies.

PLoS Biol 2020 09 28;18(9):e3000870. Epub 2020 Sep 28.

Baker Heart and Diabetes Institute, Melbourne, Australia.

Obesity and related metabolic diseases show clear sex-related differences. The growing burden of these diseases calls for better understanding of the age- and sex-related metabolic consequences. High-throughput lipidomic analyses of population-based cohorts offer an opportunity to identify disease-risk-associated biomarkers and to improve our understanding of lipid metabolism and biology at a population level. Here, we comprehensively examined the relationship between lipid classes/subclasses and molecular species with age, sex, and body mass index (BMI). Furthermore, we evaluated sex specificity in the association of the plasma lipidome with age and BMI. Some 747 targeted lipid measures, representing 706 molecular lipid species across 36 classes/subclasses, were measured using a high-performance liquid chromatography coupled mass spectrometer on a total of 10,339 participants from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), with 563 lipid species being validated externally on 4,207 participants of the Busselton Health Study (BHS). Heat maps were constructed to visualise the relative differences in lipidomic profile between men and women. Multivariable linear regression analyses, including sex-interaction terms, were performed to assess the associations of lipid species with cardiometabolic phenotypes. Associations with age and sex were found for 472 (66.9%) and 583 (82.6%) lipid species, respectively. We further demonstrated that age-associated lipidomic fingerprints differed by sex. Specific classes of ether-phospholipids and lysophospholipids (calculated as the sum composition of the species within the class) were inversely associated with age in men only. In analyses with women alone, higher triacylglycerol and lower lysoalkylphosphatidylcholine species were observed among postmenopausal women compared with premenopausal women. We also identified sex-specific associations of lipid species with obesity. Lysophospholipids were negatively associated with BMI in both sexes (with a larger effect size in men), whilst acylcarnitine species showed opposing associations based on sex (positive association in women and negative association in men). Finally, by utilising specific lipid ratios as a proxy for enzymatic activity, we identified stearoyl CoA desaturase (SCD-1), fatty acid desaturase 3 (FADS3), and plasmanylethanolamine Δ1-desaturase activities, as well as the sphingolipid metabolic pathway, as constituent perturbations of cardiometabolic phenotypes. Our analyses elucidate the effect of age and sex on lipid metabolism by offering a comprehensive view of the lipidomic profiles associated with common cardiometabolic risk factors. These findings have implications for age- and sex-dependent lipid metabolism in health and disease and suggest the need for sex stratification during lipid biomarker discovery, establishing biological reference intervals for assessment of disease risk.
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http://dx.doi.org/10.1371/journal.pbio.3000870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7544135PMC
September 2020

Incidence of Hospitalization for Heart Failure Relative to Major Atherosclerotic Events in Type 2 Diabetes: A Meta-analysis of Cardiovascular Outcomes Trials.

Diabetes Care 2020 10;43(10):2614-2623

Clinical Diabetes and Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.

Background: Emerging evidence points to heart failure as being a common first presentation of cardiovascular (CV) disease in type 2 diabetes.

Purpose: The purpose of this study was to determine whether hospitalization for heart failure (HHF) occurs more or less frequently than major adverse CV events (MACE) in people with type 2 diabetes.

Data Sources: Placebo arms of CV outcomes trials in type 2 diabetes were included.

Study Selection: Sixteen CV outcomes trials were selected, including five dipeptidyl peptidase 4 inhibitor trials, seven glucagon-like peptide 1 receptor agonist trials, and four sodium-glucose cotransporter 2 inhibitor trials.

Data Extraction: We extracted incidence rates of HHF, myocardial infarction (MI), stroke, and the composite outcomes of CV death or HHF and MACE (CV death, nonfatal MI, or nonfatal stroke).

Data Synthesis: In two trials enriched with people with chronic kidney disease, HHF was more common than both MI and stroke. Among the remaining 14 trials, HHF was less frequent than MI in 13 (93%), with this difference being significant in 8 (57%); however, HHF surpassed stroke in all but 1 study (93%; significant in 7 studies [50%]). Heterogeneity among trials was moderate/high ( >50%) and partly explained by HHF/MI correlating with age and previous MI history ( < 0.05). In seven trials that reported events stratified by presence/absence of preexisting CV disease, ratios of HHF/MI and HHF/stroke were similar between groups.

Limitations: Enrichment of trial populations with those at high risk of CV events limits generalizability.

Conclusions: Although less frequent than MI, HHF is a common event in type 2 diabetes, both in those with and those without prior CV disease.
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http://dx.doi.org/10.2337/dc20-0654DOI Listing
October 2020

Addressing Gender Equity in Senior Leadership Roles in Translational Science.

ACS Pharmacol Transl Sci 2020 Aug 15;3(4):773-779. Epub 2020 Jul 15.

Baker Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.

Inequities for women exist across many leverage points of an academic career in science, technology, engineering, mathematics, and medicine (STEMM) disciplines, ranging from poorer success rates at promotion, reduced grant success, and a lower likelihood of invited conference presentations, to a propensity to undertake the lion's share of academic service roles. Moreover, an almost intractable salary gap exists, along with a stark under-representation of women in senior scientific leadership roles, widespread throughout the United States, United Kingdom, Europe, and Australia. Numerous factors have been put forward as contributors to this disparity, including the notions that these inequities are a result of a pipeline issue and that women are less qualified or have less experience than men, implicit bias, a lack of flexibility in the work place, a lack of role models, the use of biased measures of success for promotion, and the lack of equitable parental leave programs. In this viewpoint, we address factors shown to contribute to the lack of women in leadership roles. Specifically, we look at systemic barriers, parental and carer leave, and domestic barriers, and we present solutions to address these barriers across an individual's professional and personal life. For women to achieve equity in senior scientific leadership roles, we believe that barriers across all facets of life need to be addressed and that the important contributions that women make and have made to STEMM need to be recognized.
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http://dx.doi.org/10.1021/acsptsci.0c00056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432663PMC
August 2020

A systematic review of trends in all-cause mortality among people with diabetes.

Diabetologia 2020 09 6;63(9):1718-1735. Epub 2020 Jul 6.

Baker Heart and Diabetes Institute, 75 Commercial Road, Melbourne, VIC, 3004, Australia.

Aims/hypothesis: We examined all-cause mortality trends in people with diabetes and compared them with trends among people without diabetes.

Methods: MEDLINE, EMBASE and CINAHL databases were searched for observational studies published from 1980 to 2019 reporting all-cause mortality rates across ≥2 time periods in people with diabetes. Mortality trends were examined by ethnicity, age and sex within comparable calendar periods.

Results: Of 30,295 abstracts screened, 35 studies were included, providing data on 69 separate ethnic-specific or sex-specific populations with diabetes since 1970. Overall, 43% (3/7), 53% (10/19) and 74% (32/43) of the populations studied had decreasing trends in all-cause mortality rates in people with diabetes in 1970-1989, 1990-1999 and 2000-2016, respectively. In 1990-1999 and 2000-2016, mortality rates declined in 75% (9/12) and 78% (28/36) of predominantly Europid populations, and in 14% (1/7) and 57% (4/7) of non-Europid populations, respectively. In 2000-2016, mortality rates declined in 33% (4/12), 65% (11/17), 88% (7/8) and 76% (16/21) of populations aged <40, 40-54, 55-69 and ≥70 years, respectively. Among the 33 populations with separate mortality data for those with and without diabetes, 60% (6/10) of the populations with diabetes in 1990-1999 and 58% (11/19) in 2000-2016 had an annual reduction in mortality rates that was similar to or greater than in those without diabetes.

Conclusions/interpretation: All-cause mortality has declined in the majority of predominantly Europid populations with diabetes since 2000, and the magnitude of annual mortality reduction matched or exceeded that observed in people without diabetes in nearly 60% of populations. Patterns of diabetes mortality remain uncertain in younger age groups and non-Europid populations.

Registration: PROSPERO registration ID CRD42019095974. Graphical abstract.
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http://dx.doi.org/10.1007/s00125-020-05199-0DOI Listing
September 2020
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