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IntroductionDietary nitrate is potentially beneficial for cardiovascular, cerebrovascular, and nervous systems due to its role as a nitric oxide (NO) precursor. Increased nitrate intake improves cardiovascular health and therefore could protect against dementia, given the cardiovascular-dementia link.ObjectiveTo investigate the association between source-dependent nitrate intake and dementia-related mortality. As individuals with diabetes are at higher risk of dementia, a secondary aim was to investigate if the associations between nitrate and dementia varied by diabetes mellitus (DM) and pre-diabetes status.MethodsThis study involved 9,149 participants aged ≥25 years from the well-characterised Australian Diabetes, Obesity, and Lifestyle (AusDiab) Study followed over a period of 17 years. Intakes of plant-sourced, vegetable-sourced, naturally occurring animal-sourced nitrate, and processed meat (where nitrate is an allowed additive)-sourced nitrate were assessed from a 74-item food frequency questionnaire completed by participants at baseline and nitrate databases were used to estimate nitrate from these different dietary sources. Associations between source-dependent nitrate intake and dementia-related mortality were assessed using multivariable-adjusted Cox proportional hazards models adjusted for demographics, lifestyle, and dietary factors.ResultsOver 17 years of follow-up, 93 (1.0%) dementia-related deaths occurred of 1,237 (13.5%) total deaths. In multivariable-adjusted models, participants with the highest intakes of plant-sourced nitrate (median intake 98 mg/day) had a 57% lower risk of dementia-related mortality [HR (95% CI): 0.43 (0.22, 0.87)] compared to participants with lowest intakes of plant-sourced nitrate (median intake 35 mg/day). A 66% lower risk was also seen for higher intakes of vegetable-sourced nitrate [HR (95% CI): 0.34 (0.17, 0.66)]. No association was observed for animal-sourced nitrate, but the risk was two times higher amongst those who consumed the most processed meat-sourced nitrate intake [HR (95%): 2.10 (1.07, 4.12)]. The highest intake of vegetable-sourced nitrate was associated with a lower risk of dementia-related mortality for those with and without DM and pre-diabetes.ConclusionEncouraging the intake of nitrate-rich vegetables, such as green leafy vegetables and beetroot, may lower the risk of dementia-related mortality, particularly in individuals with (pre-) diabetes who are at a higher dementia risk.

Summary: Background: Metabolic ageing biomarkers may capture the age-related shifts in metabolism, offering a precise representation of an individual’s overall metabolic health. Methods: Utilising comprehensive lipidomic datasets from two large independent population cohorts in Australia (n = 14,833, including 6630 males, 8203 females), we employed different machine learning models, to predict age, and calculated metabolic age scores (mAge). Furthermore, we defined the difference between mAge and age, termed mAgeΔ, which allow us to identify individuals sharing similar age but differing in their metabolic health status. Findings: Upon stratification of the population into quintiles by mAgeΔ, we observed that participants in the top quintile group (Q5) were more likely to have cardiovascular disease (OR = 2.13, 95% CI = 1.62–2.83), had a 2.01-fold increased risk of 12-year incident cardiovascular events (HR = 2.01, 95% CI = 1.45–2.57), and a 1.56-fold increased risk of 17-year all-cause mortality (HR = 1.56, 95% CI = 1.34–1.79), relative to the individuals in the bottom quintile group (Q1). Survival analysis further revealed that men in the Q5 group faced the challenge of reaching a median survival rate due to cardiovascular events more than six years earlier and reaching a median survival rate due to all-cause mortality more than four years earlier than men in the Q1 group. Interpretation: Our findings demonstrate that the mAge score captures age-related metabolic changes, predicts health outcomes, and has the potential to identify individuals at increased risk of metabolic diseases. Funding: The specific funding of this article is provided in the acknowledgements section.

Summary: Background: Decreased levels of circulating ethanolamine plasmalogens [PE(P)], and a concurrent increase in phosphatidylethanolamine (PE) are consistently reported in various cardiometabolic conditions. Here we devised, a plasmalogen score (Pls Score) that mirrors a metabolic signal that encompasses the levels of PE(P) and PE and captures the natural variation in circulating plasmalogens and perturbations in their metabolism associated with disease, diet, and lifestyle. Methods: We utilised, plasma lipidomes from the Australian Obesity, Diabetes and Lifestyle study (AusDiab; n = 10,339, 55% women) a nationwide cohort, to devise the Pls Score and validated this in the Busselton Health Study (BHS; n = 4,492, 56% women, serum lipidome) and in a placebo-controlled crossover trial involving Shark Liver Oil (SLO) supplementation (n = 10, 100% men). We examined the association of the Pls Score with cardiometabolic risk factors, type 2 diabetes mellitus (T2DM), cardiovascular disease and all-cause mortality (over 17 years). Findings: In a model, adjusted for age, sex and BMI, individuals in the top quintile of the Pls Score (Q5) relative to Q1 had an OR of 0.31 (95% CI 0.21–0.43), 0.39 (95% CI 0.25–0.61) and 0.42 (95% CI 0.30–0.57) for prevalent T2DM, incident T2DM and prevalent cardiovascular disease respectively, and a 34% lower mortality risk (HR = 0.66; 95% CI 0.56–0.78). Significant associations between diet and lifestyle habits and Pls Score exist and these were validated through dietary supplementation of SLO that resulted in a marked change in the Pls Score. Interpretation: The Pls Score as a measure that captures the natural variation in circulating plasmalogens, was not only inversely related to cardiometabolic risk and all-cause mortality but also associate with diet and lifestyle. Our results support the potential utility of the Pls Score as a biomarker for metabolic health and its responsiveness to dietary interventions. Further research is warranted to explore the underlying mechanisms and optimise the practical implementation of the Pls Score in clinical and population settings. Funding: National Health and Medical Research Council (NHMRC grant 233200), National Health and Medical Research Council of Australia (Project grant APP1101320), Health Promotion Foundation of Western Australia, and National Health and Medical Research Council of Australia Senior Research Fellowship (#1042095).

Abstract Recent advancements in plasma lipidomic profiling methodology have significantly increased specificity and accuracy of lipid measurements. This evolution, driven by improved chromatographic and mass spectrometric resolution of newer platforms, has made it challenging to align datasets created at different times, or on different platforms. Here we present a framework for harmonising such plasma lipidomic datasets with different levels of granularity in their lipid measurements. Our method utilises elastic-net prediction models, constructed from high-resolution lipidomics reference datasets, to predict unmeasured lipid species in lower-resolution studies. The approach involves (1) constructing composite lipid measures in the reference dataset that map to less resolved lipids in the target dataset, (2) addressing discrepancies between aligned lipid species, (3) generating prediction models, (4) assessing their transferability into the targe dataset, and (5) evaluating their prediction accuracy. To demonstrate our approach, we used the AusDiab population-based cohort (747 lipid species) as the reference to impute unmeasured lipid species into the LIPID study (342 lipid species). Furthermore, we compared measured and imputed lipids in terms of parameter estimation and predictive performance, and validated imputations in an independent study. Our method for harmonising plasma lipidomic datasets will facilitate model validation and data integration efforts.

BackgroundWith the rapid increase in the prevalence of DM, studies on the awareness, treatment, and control of this condition are essential. Therefore, this study aimed to review the literature and pool the awareness, treatment, and control of diabetes at the global, regional, and national levels.MethodsIn this systematic review and meta-analysis, several databases, including MEDLINE/PubMed, Institute of Scientific Information (ISI), Scopus, and Google Scholar, were searched using appropriate keywords up to June 2022. Observational studies investigating the awareness, treatment, and control of glucose levels among diabetic individuals were included. Awareness, treatment, and control were defined as the proportion of participants who were aware of their diabetes condition, treated pharmacologically, and achieved adequate glucose control, respectively. Two investigators independently conducted the study selection, data extraction, and quality assessment. Heterogeneity among studies was calculated using Chi-square, and a random-effect meta-analysis was used to pool the rates.ResultsA total of 233 studies published between 1985 and 2022 met the inclusion criteria. The included studies had a combined population of 12,537,968. The pooled awareness of DM was 60% (95%CI: 56–63) and ranged from 41% (25–57) in low-income countries to 68% (64–72) in high-income countries, with no significant trend observed over the assessed periods at the global level. The pooled treatment of DM globally was 45% (42–48) and varied from 37% (31–43) in lower-middle-income countries to 53% (47–59) in high-income countries, showing variation over the examined time period. Before 2000, the proportion of adequate DM control was 16% (12–20), which significantly improved and reached 22% (19–25) after 2010. The pooled awareness, treatment, and control of DM were higher in females, high-income countries, and urban areas compared to males, upper and lower-middle-income countries, and rural areas, respectively. The older adults population had higher awareness and treatment rates than the adult population, but their DM control did not differ significantly.ConclusionDespite the high level of awareness and treatment among the diabetic population, treatment success (control) is considerably low, particularly in low-income countries and rural areas. It is crucial to improve awareness, treatment, and control by strengthening the primary care system in all countries.

Abstract Obesity is a risk factor for type 2 diabetes and cardiovascular disease. However, a substantial proportion of patients with these conditions have a seemingly normal body mass index (BMI). Conversely, not all obese individuals present with metabolic disorders giving rise to the concept of “metabolically healthy obese”. We use lipidomic-based models for BMI to calculate a metabolic BMI score (mBMI) as a measure of metabolic dysregulation associated with obesity. Using the difference between mBMI and BMI (mBMIΔ), we identify individuals with a similar BMI but differing in their metabolic health and disease risk profiles. Exercise and diet associate with mBMIΔ suggesting the ability to modify mBMI with lifestyle intervention. Our findings show that, the mBMI score captures information on metabolic dysregulation that is independent of the measured BMI and so provides an opportunity to assess metabolic health to identify “at risk” individuals for targeted intervention and monitoring.

Abstract Background There is a dearth of studies on how neighbourhood environmental attributes relate to the metabolic syndrome (MetS) and profiles of MetS components. We examined the associations of interrelated aspects of the neighbourhood environment, including air pollution, with MetS status and profiles of MetS components. Methods We used socio-demographic and MetS-related data from 3681 urban adults who participated in the 3rd wave of the Australian Diabetes, Obesity and Lifestyle Study. Neighbourhood environmental attributes included area socio-economic status (SES), population density, street intersection density, non-commercial land use mix, percentages of commercial land, parkland and blue space. Annual average concentrations of NO2 and PM2.5 were estimated using satellite-based land-use regression models. Latent class analysis (LCA) identified homogenous groups (latent classes) of participants based on MetS components data. Participants were then classified into five metabolic profiles according to their MetS-components latent class and MetS status. Generalised additive mixed models were used to estimate relationships of environmental attributes with MetS status and metabolic profiles. Results LCA yielded three latent classes, one including only participants without MetS (“Lower probability of MetS components” profile). The other two classes/profiles, consisting of participants with and without MetS, were “Medium-to-high probability of high fasting blood glucose, waist circumference and blood pressure” and “Higher probability of MetS components”. Area SES was the only significant predictor of MetS status: participants from high SES areas were less likely to have MetS. Area SES, percentage of commercial land and NO2 were associated with the odds of membership to healthier metabolic profiles without MetS, while annual average concentration of PM2.5 was associated with unhealthier metabolic profiles with MetS. Conclusions This study supports the utility of operationalising MetS as a combination of latent classes of MetS components and MetS status in studies of environmental correlates. Higher socio-economic advantage, good access to commercial services and low air pollution levels appear to independently contribute to different facets of metabolic health. Future research needs to consider conducting longitudinal studies using fine-grained environmental measures that more accurately characterise the neighbourhood environment in relation to behaviours or other mechanisms related to MetS and its components.

Cardiovascular disease (CVD) encompasses a range of disorders affecting the heart and blood vessels, including coronary heart disease and cerebrovascular disease [...]

Abstract Background Adequate dietary protein intake is recommended for older adults to optimise muscle health and function, and support recovery from illness, however, its effect on health-related quality of life (HRQoL) is unclear. The aim of this study was to examine the association between total protein intake and different sources of dietary protein and HRQoL in Australians aged 60 years and older over a 12-year period. Methods This study used data from the Australian Diabetes, Obesity and Lifestyle study (AusDiab), a 12-year population-based prospective study. The sample included 752 (386 females) adults aged 60 years and older. Protein intake was estimated at baseline (1999/2000) from a 74-item Food Frequency Questionnaire, and HRQoL using the 36-item Short-form Health Survey assessed at baseline (1999/2000) and after 12 years (2011/12). The association between protein intake and change in HRQoL was evaluated using multivariate regression analysis adjusted for relevant confounders. The difference in change in HRQoL between participants with total protein intakes of 1.2 g/kg/day were assessed using one-way ANCOVA. Results Total protein intake at baseline was not associated with 12-year changes in physical component summary (PCS) or mental component summary (MCS) scores of HRQoL. Higher animal, red meat and processed animal protein intakes were associated with deteriorations in PCS scores after adjusting for relevant confounders (β = − 0.04; 95% CI: − 0.07, −0.01 ; p = 0.009; β = − 0.05; 95% CI: − 0.08, − 0.01; p = 0.018; β = − 0.17; 95% CI: − 0.31, − 0.02; p = 0.027 respectively). Higher red meat protein intake was associated with deteriorations in MCS scores after adjusting for relevant confounders (β = − 0.04; 95% CI: − 0.08, − 0.01; p = 0.011). There was no difference in 12-year changes in PCS or MCS between participants consuming total protein of 1.2 g/kg/day. Conclusion There was no relationship between total dietary protein intake and HRQoL, but higher protein intakes from animal, red meat and processed animal sources were associated with a deterioration in HRQoL scores over 12 years. Due to the number of associations examined and high drop out of older less healthy participants, further research is required to confirm the associations detected in healthy and less healthy participants, with a view to making protein intake recommendations for older adults.

The rupture of an abdominal aortic aneurysm (AAA) causes about 200,000 deaths worldwide each year. However, there are currently no effective drug therapies to prevent AAA formation or, when present, to decrease progression and rupture, highlighting an urgent need for more research in this field. Increased vascular inflammation and enhanced apoptosis of vascular smooth muscle cells (VSMCs) are implicated in AAA formation. Here, we investigated whether hydralazine, which has anti-inflammatory and anti-apoptotic properties, inhibited AAA formation and pathological hallmarks. In cultured VSMCs, hydralazine (100 μM) inhibited the increase in inflammatory gene expression and apoptosis induced by acrolein and hydrogen peroxide, two oxidants that may play a role in AAA pathogenesis. The anti-apoptotic effect of hydralazine was associated with a decrease in caspase 8 gene expression. In a mouse model of AAA induced by subcutaneous angiotensin II infusion (1 µg/kg body weight/min) for 28 days in apolipoprotein E-deficient mice, hydralazine treatment (24 mg/kg/day) significantly decreased AAA incidence from 80% to 20% and suprarenal aortic diameter by 32% from 2.26 mm to 1.53 mm. Hydralazine treatment also significantly increased the survival rate from 60% to 100%. In conclusion, hydralazine inhibited AAA formation and rupture in a mouse model, which was associated with its anti-inflammatory and anti-apoptotic properties.

Abstract Metabolic Associated Fatty Liver Disease (MAFLD) is the most common cause of liver disease in Australia, but prevalence data are limited. We aimed to describe the frequency of alanine aminotransferase (ALT) elevation, and MAFLD within a large prospective Australian cohort. Cross-sectional analysis of the 2012 survey of the Australian Diabetes, Obesity and Lifestyle (AusDiab) study which included 4747 Australian adults (aged 34–97 yrs) was performed. Frequency of ALT elevation (men ≥ 40 IU/L, women ≥ 30 IU/L) and MAFLD (Fatty Liver Index (FLI) > 60 alongside metabolic risk factors) was determined and risk of advanced fibrosis stratified using the BARD score. Elevated ALT was found in 13% of the cohort, including 22% of people with diabetes, 18% with obesity, and 17% with the metabolic syndrome. 37% of the cohort had MAFLD, and those with MAFLD were more likely to be older (OR 1.01 per 1 year (95% CI 1.00–1.02)), male (OR 1.37 (95% CI 1.17–1.59)), have ALT elevation (OR 3.21 (95% CI 2.59–3.99)), diabetes (OR 3.39 (95% CI 2.61–4.39)), lower HDL-C (OR 0.15 per 1 mmol/L (95% CI 0.12–0.19)), higher diastolic blood pressure (OR 1.05 per 10 mmHg (95% CI 1.05–1.06)), a sedentary lifestyle (OR 1.99 (95% CI 1.59–2.50)) and less likely to have tertiary education (OR 0.81 (95% CI 0.7–0.94) compared to those without MAFLD. Of those with MAFLD, 61% had a BARD score suggesting risk of advanced fibrosis and 22% had an elevated ALT. Over 10% of this Australian cohort had elevated ALT, and 37% had MAFLD, with many at risk for advanced fibrosis.

Abstract 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

Abstract 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 20 years compared to those diagnosed at 50–59 or those with duration of diabetes

BackgroundAlthough 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.MethodsData 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.ResultsThe 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.ConclusionsData 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.

Background and AimsHigher total fruit and vegetable (FV) intakes have been associated with lower perceived stress. However, the relationship of FV intake with domains of perceived stress is unclear. The aim of this cross-sectional study was to explore the relationship between consumption of FV and four perceived stress domains (worries, tension, lack of joy and demands) in a population-based cohort of Australian adults.MethodsParticipants (n = 8,640) were men and women aged ≥25 years from the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study. Dietary intake was assessed using a 74-item validated Food Frequency Questionnaire. Perceived stress domains were determined using a validated 20-item version of the Perceived Stress Questionnaire, with higher scores representing higher perceived stress. Cut-offs for high perceived stress domains were obtained from the highest quartiles of each domain for each sex. Multivariable-adjusted logistic regression was performed to investigate cross-sectional associations.ResultsThe mean age of participants (50.1% females) was 47.8 (SD 15) years. Those with higher intakes of FV, combined and separately, had a significantly lower odds (16–36%) for higher worries, tension and lack of joy, independent of other lifestyle factors.ConclusionIn Australian adults, higher consumption of FV was associated with lower odds of worries, tension and lack of joy. Following the dietary guidelines for the recommended intake of FV may help improve feelings of worries, tension and lack of joy, which are linked to mental health problems.

Background: Studies have shown that among people with diabetes, those with non-albuminuric chronic kidney disease (CKD) have a slower rate of reduction in renal function than do those with normal renal function. This suggests the presence of protective factors, the identification of which may open up targets for intervention. The aim of this study was to identify protective clinical factors and nonclinical biomarkers that contribute to the association between non-albuminuric CKD and the low rate of progression of CKD. Methods: We tested for significant associations of several clinical factors and 33 nonclinical biomarkers with (1) normoalbuminuria and (2) a low rate of CKD progression among participants with diabetes and CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study in the United States. Factors significantly associated with both normoalbuminuria and a low rate of CKD progression were assessed in linear regression to estimate their potential contributions to the association between non-albuminuric CKD and rate of CKD progression. Results: Systolic blood pressure (SBP), glycated A1c (HbA1c), estimated glomerular filtration rate (eGFR) and six biomarkers [β-trace protein (BTP), kidney injury molecule (KIM-1), fibrinogen, fractalkine, brain natriuretic peptide (BNP) and high-sensitivity troponin-T (hsTnT)] were associated with both normoalbuminuria and a low rate of eGFR decline. The univariate β-coefficient for normoalbuminuria was 0.93 [95% confidence interval (CI): 0.82, 1.05]. When all associated factors and biomarkers were included, the regression coefficient decreased to 0.54 (95% CI: 0.40, 0.67). The factors that contributed to the association between non-albuminuric CKD and low rate of eGFR were lower levels of SBP, HbA1c, BTP, KIM-1, hsTnT, BNP, fibrinogen and fractalkine. Conclusion: Lower levels of SBP and biomarkers that have pro-inflammatory and vascular modulating features may explain up to 40% of the association between non-albuminuric CKD and low rate of CKD progression. Further investigation of these biomarkers may lead to therapeutic interventions.

Aim: To investigate the incidence of, and factors associated with addition and switching of glucose-lowering medications within 12-months of initiating metformin or a sulfonylurea for type 2 diabetes (T2D).Methods: We identified 109,573 individuals aged 18–99 years who initiated metformin or a sulfonylurea between July 2013 and April 2015 using Australian National Diabetes Service Scheme (NDSS) data linked with national dispensing data. Cox proportional hazards regression was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CI) for factors associated with time to addition to or switch from metformin or sulfonylurea over a 12-months follow-up.Results: Treatment addition or switching occurred in 18% and 4% of individuals who initiated metformin and in 28% and 13% of individuals who initiated sulfonylureas. Median time to addition was 104 days for metformin and 82 days for sulfonylureas. Median time to switching was 63 days for metformin and 52 days for sulfonylureas. Congestive heart failure, nicotine dependence, end stage renal disease and dispensing of systemic corticosteroids were associated with higher likelihood of treatment additions and switching in individuals initiating metformin. Antipsychotic dispensing was associated with a higher likelihood of treatment addition in individuals initiating sulfonylureas. Women initiating metformin were less likely to receive treatment additions but more likely to switch treatment than men.Conclusion: Nearly one quarter of Australians who initiate treatment for T2D with metformin or sulfonylureas switch or receive additional treatment within 12-months, with those who initiate sulfonylureas more likely to switch or receive additional treatment than those who initiate metformin.

Abstract Background The economic burden of type 2 diabetes has not been adequately investigated in many low- and lower middle-income countries, including Bangladesh. The aim of this study was to estimate the cost-of-illness of type 2 diabetes and to find its determinants in Bangladesh. Methods A cross-sectional study was conducted in 2017 to recruit 1253 participants with type 2 diabetes from six diabetes hospitals, providing primary to tertiary health care services, located in the northern and central regions of Bangladesh. A structured questionnaire was used for face-to-face interviewing to collect non-clinical data. Patients’ medical records were reviewed for clinical data and hospital records were reviewed for hospitalisation data. Cost was calculated from the patient’s perspective using a bottom-up methodology. The direct costs for each patient and indirect costs for each patient and their attendants were calculated. The micro-costing approach was used to calculate direct cost and the human capital approach was used to calculate indirect cost. Median regression analysis was performed to identify the determinants of average annual cost. Results Among the participants, 54% were male. The mean (±SD) age was 55.1 ± 12.5 years and duration of diabetes was 10.7 ± 7.7 years. The average annual cost was US$864.7 per patient. Medicine cost accounted for 60.7% of the direct cost followed by a hospitalisation cost of 27.7%. The average annual cost for patients with hospitalisation was 4.2 times higher compared to those without hospitalisation. Being females, use of insulin, longer duration of diabetes, and presence of diabetes complications were significantly related to the average annual cost per patient. Conclusions The cost of diabetes care is considerably high in Bangladesh, and it is primarily driven by the medicine and hospitalisation costs. Optimisation of diabetes management by positive lifestyle changes is urgently required for prevention of comorbidities and complications, which in turn will reduce the cost.

Abstract Background Diabetes is one of the world’s most prevalent and serious non-communicable diseases (NCDs). It is a leading cause of death, disability and financial loss; moreover, it is identified as a major threat to global development. The chronic nature of diabetes and its related complications make it a costly disease. Estimating the total cost of an illness is a useful aid to national and international health policy decision making. The aim of this systematic review is to summarise the impact of the cost-of-illness of type 2 diabetes mellitus in low and lower-middle income countries, and to identify methodological gaps in measuring the cost-of-illness of type 2 diabetes mellitus. Methods This systematic review considers studies that reported the cost-of-illness of type 2 diabetes in subjects aged 18 years and above in low and lower-middle income countries. The search engines MEDLINE, EMBASE, CINAHL, PSYCINFO and COCHRANE were used form date of their inception to September 2018. Two authors independently identified the eligible studies. Costs reported in the included studies were converted to US dollars in relation to the dates mentioned in the studies. Results The systematic search identified eight eligible studies conducted in low and lower-middle income countries. There was a considerable variation in the costs and method used in these studies. The annual average cost (both direct and indirect) per person for treating type 2 diabetes mellitus ranged from USD29.91 to USD237.38, direct costs ranged from USD106.53 to USD293.79, and indirect costs ranged from USD1.92 to USD73.4 per person per year. Hospitalization cost was the major contributor of direct costs followed by drug costs. Conclusion Type 2 diabetes mellitus imposes a considerable economic burden which most directly affects the patients in low and lower-middle income countries. There is enormous scope for adding research-based evidence that is methodologically sound to gain a more accurate estimation of cost and to facilitate comparison between studies.

Traffic-related air pollution (TRAP) is associated with lower cognitive function and diabetes in older adults, but little is known about whether diabetes status moderates the impact of TRAP on older adult cognitive function. We analysed cross-sectional data from 4141 adults who participated in the Australian Diabetes, Obesity and Lifestyle (AusDiab) study in 2011–2012. TRAP exposure was estimated using major and minor road density within multiple residential buffers. Cognitive function was assessed with validated psychometric scales, including: California Verbal Learning Test (memory) and Symbol–Digit Modalities Test (processing speed). Diabetes status was measured using oral glucose tolerance tests. We observed positive associations of some total road density measures with memory but not processing speed. Minor road density was not associated with cognitive function, while major road density showed positive associations with memory and processing speed among larger buffers. Within a 300 m buffer, the relationship between TRAP and memory tended to be positive in controls (β = 0.005; p = 0.062), but negative in people with diabetes (β = −0.013; p = 0.026) and negatively associated with processing speed in people with diabetes only (β = −0.047; p = 0.059). Increased TRAP exposure may be positively associated with cognitive function among urban-dwelling people, but this benefit may not extend to those with diabetes.

In this paper, we assess the cost-effectiveness of 1 g daily of carnosine (an over the counter supplement) in addition to standard care for the management of type 2 diabetes and compare it to standard care alone. Dynamic multistate life table models were constructed in order to estimate both clinical outcomes and costs of Australians aged 18 years and above with and without type 2 diabetes over a ten-year period, 2020 to 2029. The dynamic nature of the model allowed for population change over time (migration and deaths) and accounted for the development of new cases of diabetes. The three health states were ‘Alive without type 2 diabetes’, ‘Alive with type 2 diabetes’ and ‘Dead’. Transition probabilities, costs, and utilities were obtained from published sources. The main outcome of interest was the incremental cost-effectiveness ratio (ICER) in terms of cost per year of life saved (YoLS) and cost per quality-adjusted life year (QALY) gained. Over the ten-year period, the addition of carnosine to standard care treatment resulted in ICERs (discounted) of AUD 34,836 per YoLS and AUD 43,270 per QALY gained. Assuming the commonly accepted willingness to pay threshold of AUD 50,000 per QALY gained, supplemental dietary carnosine may be a cost-effective treatment option for people with type 2 diabetes in Australia.

Abstract Background The aim of this study was to assess inadequate glycaemic control and its associated factors among people with type 2 diabetes in Saudi Arabia. Methods A cross-sectional study design was used. Adults with type 2 diabetes attending diabetes centres in Riyadh, Hofuf and Jeddah cities were interviewed and their anthropometrics were measured. Their medical records were also reviewed to collect information related to recent lab tests, medications, and documented comorbidities. Multivariable logistic regression were used for data analysis. Results A total of 1111 participants were recruited in the study. Mean age was 57.6 (±11.1) years, 65.2% of the participants were females, and mean HbA1c was 8.5 ± 1.9%. About three-fourths of participants had inadequate glycaemic control (≥ 7%). Multivariable analysis showed that age ≤ 60 years, longer duration of diabetes, living in a remote location, low household income, low intake of fruits and vegetable, low level of physical activity, lack of knowledge about haemoglobin A1c, high waist-hip ratio, low adherence to medication, and using injectable medications were independent risk factors for inadequate glycaemic control. Conclusions Inadequate glycaemic control is prevalent among people with type 2 diabetes in Saudi Arabia. In order to improve glycaemic control diabetes management plan should aim at controlling the modifiable risk factors which include low intake of fruits and vegetable, low level of physical activity, lack of knowledge about haemoglobin A1c, high waist-hip ratio, and low adherence to medications.

Abstract Background To analyse trends over the period 1991–2013 in systolic blood pressure (SBP), diastolic blood pressure (DBP) and the prevalence of hypertension in adults aged 25–64 years in Samoa; and to assess the contribution of rising obesity levels to period trends. Methods Unit record data from seven population-based surveys (n = 10,881) conducted between 1991 and 2013 were included for analysis. Surveys were adjusted to the nearest previous census to improve national representativeness. Hypertension was defined as SBP ≥140 mmHg and/or DBP ≥90 mmHg and/or on medication for hypertension. Obesity was measured by body mass index (BMI). Poisson, linear and meta-regression were used to assess period trends. Results Over 1991–2013 mean SBP and DBP (mmHg), and the prevalence of hypertension (%) increased in both sexes. Increases in hypertension were: from 18.3 to 33.9% (p

Abstract Background High quality, contemporary data regarding patterns of chronic disease is essential for planning by health services, policy makers and local governments, but surprisingly scarce, including in rural Australia. This dearth of data occurs despite the recognition that rural Australians live with high rates of ill health, poor health behaviours and restricted access to health services. Crossroads-II is set in the Goulburn Valley, a rural region of Victoria, Australia 100–300 km north of metropolitan Melbourne. It is primarily an irrigated agricultural area. The aim of the study is to identify changes in the prevalence of key chronic health conditions including the extent of undiagnosed and undermanaged disease, and association with access to care, over a 15 year period. Methods/design This study is a 15 year follow up from the 2000–2003 Crossroads-I study (2376 households participated). Crossroads-II includes a similar face to face household survey of 3600 randomly selected households across four towns of sizes 6300 to 49,800 (50% sampled in the larger town with the remainder sampled equally from the three smaller towns). Self-reported health, health behaviour and health service usage information is verified and supplemented in a nested sub-study of 900 randomly selected adult participants in ‘clinics’ involving a range of additional questionnaires and biophysical measurements. The study is expected to run from October 2016 to December 2018. Discussion Besides providing epidemiological and health service utilisation information relating to different diseases and their risk factors in towns of different sizes, the results will be used to develop a composite measure of health service access. The importance of access to health services will be investigated by assessing the correlation of this measure with rates of undiagnosed and undermanaged disease at the mesh block level. Results will be shared with partner organisations to inform service planning and interventions to improve health outcomes for local people.

Lipid metabolism is tightly linked to adiposity. Comprehensive lipidomic profiling offers new insights into the dysregulation of lipid metabolism in relation to weight gain. Here, we investigated the relationship of the human plasma lipidome and changes in waist circumference (WC) and body mass index (BMI). Adults (2653 men and 3196 women), 25–95 years old who attended the baseline survey of the Australian Diabetes, Obesity and Lifestyle Study (AusDiab) and the 5-year follow-up were enrolled. A targeted lipidomic approach was used to quantify 706 distinct molecular lipid species in the plasma samples. Multiple linear regression models were used to examine the relationship between the baseline lipidomic profile and changes in WC and BMI. Metabolic scores for change in WC were generated using a ridge regression model. Alkyl-diacylglycerol such as TG(O-50:2) [NL-18:1] displayed the strongest association with change in WC (β-coefficient = 0.125 cm increment per SD increment in baseline lipid level, p = 2.78 × 10−11. Many lipid species containing linoleate (18:2) fatty acids were negatively associated with both WC and BMI gain. Compared to traditional models, multivariate models containing lipid species identify individuals at a greater risk of gaining WC: top quintile relative to bottom quintile (odds ratio, 95% CI = 5.4, 3.8–6.6 for women and 2.3, 1.7–3.0 for men). Our findings define metabolic profiles that characterize individuals at risk of weight gain or WC increase and provide important insight into the biological role of lipids in obesity.

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 (p = 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, I2 = 61%) for total fish, 1.04 (1.01–1.07, I2 = 46%) for fatty fish, and 1.02 (1.00–1.04, I2 = 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, I2 = 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.

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 (p < 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 (

The impact of statin treatment on the abnormal plasma lipidome of mixed dyslipidemic patients with metabolic syndrome (MetS), a group at increased risk of developing diabetes, was evaluated. Insulin-resistant hypertriglyceridemic hypertensive obese males (n = 12) displaying MetS were treated with pitavastatin (4 mg/day) for 180 days; healthy normolipidemic age-matched nonobese males (n = 12) acted as controls. Statin treatment substantially normalized triglyceride (−41%), remnant cholesterol (−55%), and LDL-cholesterol (−39%), with minor effect on HDL-cholesterol (+4%). Lipidomic analysis, normalized to nonHDL-cholesterol in order to probe statin-induced differences in molecular composition independently of reduction in plasma cholesterol, revealed increment in 132 of 138 lipid species that were subnormal at baseline and significantly shifted toward the control group on statin treatment. Increment in alkyl- and alkenylphospholipids (plasmalogens) was prominent, and consistent with significant statin-induced increase in plasma polyunsaturated fatty acid levels. Comparison of the statin-mediated lipidomic changes in MetS with the abnormal plasma lipidomic profile characteristic of prediabetes and T2D in the Australian Diabetes, Obesity, and Lifestyle Study and San Antonio Family Heart Study cohorts by hypergeometric analysis revealed a significant shift toward the lipid profile of controls, indicative of a marked trend toward a normolipidemic phenotype. Pitavastatin attenuated the abnormal plasma lipidome of MetS patients typical of prediabetes and T2D.

The aim of this systematic review is to assess patient-related factors affecting glycaemic control among people with type 2 diabetes in the Arabian Gulf Council countries. MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL databases were searched from their date of inception to May 2016. Two researchers independently identified eligible studies and assessed the risk of bias. A total of 13 studies met the inclusion criteria. One study was population based, six recruited participants from multiple centres, and the remaining were single centred. The majority of the studies were of low to moderate quality. Factors associated with poor glycaemic control include longer duration of diabetes, low level of education, poor compliance to diet and medication, poor attitude towards the disease, poor self-management behaviour, anxiety, depression, renal impairment, hypertension, and dyslipidaemia. Healthcare providers should be aware of these factors and provide appropriate education and care especially for those who have poor glycaemic control. Innovative educational programs should be implemented in the healthcare systems to improve patient compliance and practices. A variation in the results of the included studies was observed, and some potentially important risk factors such as dietary habits, physical activity, family support, and cognitive function were not adequately addressed. Further research is needed in this area.

Lipid-lowering therapy (LLT) should be accompanied by dietary guidance for cardiovascular risk reduction; however, current evidence suggests sub-optimal dietary behaviors in those on LLT. We examined the associations between the dietary intake of key food groups (vegetables, fruit, cereal, protein, and dairy) and LLT use in Australian adults using quantile regression. We used data from the Australian Diabetes, Obesity and Lifestyle Study (AusDiab), a prospective population-based study of adults aged ≥25 years, conducted over 5 years (1999−2005). Measurements included a 121-item food frequency questionnaire and LLT use. LLT use was categorized as: LLT users (n = 446), commenced LLT (n = 565), ceased LLT (n = 71), and non-users (n = 4813). Less than 1% of the cohort met recommended intakes of all food groups at the baseline and follow up. The median daily dietary intake at the follow up among LLT users was 2.2 serves of vegetables, 1.4 serves of fruit, 2.8 serves of cereal, 2.0 serves of protein, and 1.4 serves of dairy. Adjusted analysis showed no differences across the quantiles of intake of key food groups in LLT users and commenced LLT compared to non-users. The LLT medication status is not associated with any difference in meeting recommended intakes of key foods.

Abstract Objective: To project prevalence of normal weight, overweight and obesity by educational attainment, assuming a continuation of the observed individual weight change in the 5‐year follow‐up of the national population survey, the Australian Diabetes, Obesity and Lifestyle study (AusDiab; 2000–2005). Methods: Age‐specific transition probabilities between BMI categories, estimated using logistic regression, were entered into education‐level‐specific, incidence‐based, multi‐state life tables. Assuming a continuation of the weight change observed in AusDiab, these life tables estimate the prevalence of normal weight, overweight and obesity for Australian adults with low (secondary), medium (diploma) and high (degree) levels of education between 2005 and 2025. Results: The prevalence of obesity among individuals with secondary level educational attainment is estimated to increase from 23% in 2000 to 44% in 2025. Among individuals with a degree qualification or higher, it will increase from 14% to 30%. If all current educational inequalities in weight change could be eliminated, the projected difference in the prevalence of obesity by 2025 between the highest and lowest educated categories would only be reduced by half (to a 6 percentage point difference from 14 percentage points). Conclusion: We predict that almost half of Australian adults with low educational status will be obese by 2025. Current trends in obesity have the potential to drive an increase in the absolute difference in obesity prevalence between educational categories in future years. Implications: Unless obesity prevention and management strategies focus specifically on narrowing social inequalities in obesity, inequalities in health are likely to widen.