Sex differences in risk of incident microvascular and macrovascular complications: a population-based data-linkage study among 25 713 people with diabetes.

BACKGROUND: The global prevalence of diabetes is similar in men and women; however, there is conflicting evidence regarding sex differences in diabetes-related complications. The aim of this study was to investigate sex differences in incident microvascular and macrovascular complications among adults with diabetes. METHODS: This prospective cohort study linked data from the 45 and Up Study, Australia, to administrative health records. The study sample included 25 713 individuals (57% men), aged ≥45 years, with diabetes at baseline. Incident cardiovascular disease (CVD), eye, lower limb, and kidney complications were determined using hospitalisation data and claims for medical services. Multivariable Cox proportional hazards models were used to assess the association between sex and incident complications. RESULTS: Age-adjusted incidence rates per 1000 person years for CVD, eye, lower limb, and kidney complications were 37, 52, 21, and 32, respectively. Men had a greater risk of CVD (adjusted hazard ratio (aHR) 1.51, 95% CI 1.43 to 1.59), lower limb (aHR 1.47, 95% CI 1.38 to 1.57), and kidney complications (aHR 1.55, 95% CI 1.47 to 1.64) than women, and a greater risk of diabetic retinopathy (aHR 1.14, 95% CI 1.03 to 1.26). Over 10 years, 44%, 57%, 25%, and 35% of men experienced a CVD, eye, lower limb, or kidney complication, respectively, compared with 31%, 61%, 18%, and 25% of women. Diabetes duration (<10 years vs ≥10 years) had no substantial effect on sex differences in complications. CONCLUSIONS: Men with diabetes are at greater risk of complications, irrespective of diabetes duration. High rates of complications in both sexes highlight the importance of targeted complication screening and prevention strategies from diagnosis.

Intensive Lifestyle Intervention for Remission of Early Type 2 Diabetes in Primary Care in Australia: DiRECT-Aus.

OBJECTIVE: We aimed to assess whether remission of type 2 diabetes (T2D) could be achieved with a low-energy total diet replacement (TDR) in an Australian primary care setting. RESEARCH DESIGN AND METHODS: Individuals aged 20-65 years with T2D duration up to 6 years, BMI >27.0 kg/m2, and not treated with insulin were prescribed a 13-week low-energy TDR (Optifast; Nestlé Health Science) followed by 8-week structured food reintroduction and 31-week supported weight maintenance. The primary outcome was T2D remission at 12 months. RESULTS: A total of 155 participants comprised the intention-to-treat population. At 12 months, T2D remission was achieved in 86 (56%) participants, with a mean adjusted weight loss of 8.1% (95% CI 7.2-9.1). Two serious adverse events requiring hospitalization related to the study intervention were reported. CONCLUSIONS: At 12 months T2D remission was achieved for one in two Australian adults in a primary care setting.

Sex and age differences in the use of medications for diabetes and cardiovascular risk factors among 25,733 people with diabetes.

AIM: To determine sex and age differences in the use of medications for diabetes and cardiovascular risk factors in people with diabetes in Australia. METHODS: Pharmaceutical claims data of participants in the 45 and Up Study who self-reported having diabetes before 2013, were alive on 1st January 2013 and had at least one medication dispensing record between 1st January 2013 and 31st December 2019 were analysed. Annual sex and age-specific percentages of participants supplied specific medications were estimated for years 2013 to 2019. Percentages were reported for any glucose lowering medications and by drug class, any lipid modifying agents, and any blood pressure lowering medications. RESULTS: Altogether 25,733 participants (45.2% women) with diabetes were included. The percentage of participants who were supplied with glucose lowering medications was consistently lower in women compared to men. In both sexes, the percentage of participants who were supplied with glucose lowering medications was lowest among those aged ≥75 years and this decreased over time. Similar findings were observed for lipid modifying agents and blood pressure lowering medications. The use of sodium glucose co-transporter 2 inhibitors increased substantially in participants aged <75 years since it became available in 2013. However, no sex differences were observed in its use among people with hospital-recorded history of cardiovascular disease. CONCLUSIONS: Practitioners should be aware of possible sex disparities in the pharmacological treatment of diabetes and cardiovascular risk factors in people with diabetes in Australia. There is a possible time lag between reporting of research findings and uptake of sodium glucose co-transporter 2 inhibitors prescribing in individuals with diabetes and high cardiovascular risk in clinical practice, nevertheless, the result observed was consistent with the management guidelines at the time of the study.

Association of oral health with risk of incident micro and macrovascular complications: A prospective cohort study of 24,862 people with diabetes.

AIMS: To investigate the association between self-reported oral health and incident micro and macrovascular diabetes complications. METHODS: This prospective cohort study linked data from the 45 and Up Study, Australia, to administrative health records. The participants were 24,862 men and women, aged ≥45 years, with diabetes at baseline (2006-2009). The oral health of participants was assessed by questionnaire. Incident diabetes complications were determined using hospitalisation data and claims for medical services up until 2019. Hazard ratios for the association between oral health and incident complications were calculated using multivariable cox proportional hazards models. RESULTS: Almost 60 % of participants had <20 teeth, and 38 % rated their teeth and gums as fair or poor. Compared with those with ≥20 teeth, those with 0 teeth had an increased risk of cardiovascular disease (aHR 1.24, 95 % CI: 1.15, 1.35), lower limb (aHR 1.22, 95 % CI: 1.11, 1.33) and kidney (aHR 1.19, 95 % CI: 1.11, 1.29) complications. Individuals with 1-9 teeth had an increased risk of eye complications (aHR 1.14, 95 % CI: 1.07, 1.22). The associations were generally consistent for poor self-rated teeth and gums. CONCLUSIONS: Self-reported oral health measures may be a marker of elevated risk of complications in people with diabetes.

Oral health status and risk of incident diabetes: A prospective cohort study of 213,389 individuals aged 45 and over.

AIMS: To examine whether simple measures of oral health are associated with incident diabetes. METHODS: This prospective cohort study linked data from the 45 and Up Study, Australia, to administrative health records. The study participants were 213,389 men and women, aged ≥45 years, with no diabetes at baseline. The oral health of participants was assessed by questionnaire. Incident diabetes cases were ascertained based on self-report in follow-up questionnaires, linked data on medical and pharmaceutical claims, and hospitalisation data up until 2019. The association between oral health and incident diabetes were calculated using multivariable cox proportional hazards models. RESULTS: During 2,232,215 person-years of follow-up, 20,487 (9.6%) participants developed diabetes. Compared with those with ≥20 teeth, the adjusted hazard ratio (aHR) for incident diabetes was 1.12 (95% Confidence Interval (CI): 1.08, 1.17) for 10-19 teeth, 1.20 (1.14, 1.26) for 1-9 teeth and 1.15 (1.09, 1.21) for no teeth. Compared with those with excellent/very good teeth and gums, the aHR for incident diabetes was 1.07 (1.03, 1.12) for fair and 1.13 (1.07, 1.20) for poor teeth and gums. CONCLUSIONS: Simple measures of oral health were associated with risk of developing diabetes, demonstrating the potential importance of oral health screening for diabetes prevention.

The burden of type 2 diabetes in Australia during the period 1990-2019: Findings from the global burden of disease study.

AIMS: To describe morbidity and mortality trends of type 2 diabetes in Australia, from 1990 to 2019, compared with similar sociodemographic index (SDI) countries. METHODS: Australia-specific Global Burden of Diseases data were used to estimate age-standardised, age-specific, and sex-specific rates for prevalence, years lived with disability (YLDs), years of life lost (YLLs), disability-adjusted life years (DALYs), and deaths due to type 2 diabetes between 1990 and 2019. Australian data were compared with 14 similar SDI countries. RESULTS: Type 2 diabetes increased in Australia between 1990 and 2019. The age-standardised prevalence increased from 1,985 [95% Confidence Interval (CI): 1,786.7-2195.3] per 100,000 population, to 3,429 [95% CI 3,053.3-3,853.7]. Cases tripled, from 379,532 [342,465-419,475] to 1,307,261 [1,165,522-1,461,180]. The age-standardised death rates doubled, from 2,098 [1,953-2,203] per 100,000, to 4,122 [3,617-4,512]. DALYs doubled, from 70,348 [59,187-83,500] to 169,763 [129,792-216,150], with increases seen in YLDs and YLLs. Men displayed higher rates. Compared to similar SDI countries, Australia ranked 4th in terms of burden for type 2 diabetes. CONCLUSIONS: The burden of type 2 diabetes in Australia has increased considerably over three decades. There is an urgent need to prioritise resource allocation for prevention programs, screening initiatives to facilitate early detection, and effective and accessible management strategies for the large proportion of the population impacted by type 2 diabetes.

Evaluation of a Continuous Blood Glucose Monitor: A Novel and Non-Invasive Wearable Using Bioimpedance Technology.

BACKGROUND: Frequent blood glucose level (BGL) monitoring is essential for effective diabetes management. Poor compliance is common due to the painful finger pricking or subcutaneous lancet implantation required from existing technologies. There are currently no commercially available non-invasive devices that can effectively measure BGL. In this real-world study, a prototype non-invasive continuous glucose monitoring system (NI-CGM) developed as a wearable ring was used to collect bioimpedance data. The aim was to develop a mathematical model that could use these bioimpedance data to estimate BGL in real time. METHODS: The prototype NI-CGM was worn by 14 adult participants with type 2 diabetes for 14 days in an observational clinical study. Bioimpedance data were collected alongside paired BGL measurements taken with a Food and Drug Administration (FDA)-approved self-monitoring blood glucose (SMBG) meter and an FDA-approved CGM. The SMBG meter data were used to improve CGM accuracy, and CGM data to develop the mathematical model. RESULTS: A gradient boosted model was developed using a randomized 80-20 training-test split of data. The estimated BGL from the model had a Mean Absolute Relative Difference (MARD) of 17.9%, with the Parkes error grid (PEG) analysis showing 99% of values in clinically acceptable zones A and B. CONCLUSIONS: This study demonstrated the reliability of the prototype NI-CGM at collecting bioimpedance data in a real-world scenario. These data were used to train a model that could successfully estimate BGL with a promising MARD and clinically relevant PEG result. These results will enable continued development of the prototype NI-CGM as a wearable ring.

Gambling, fast food and alcohol sponsorship in elite sport - perspectives from Australian sporting fans.

BACKGROUND: Public health bodies in Australia remain concerned about marketing of unhealthy commodities; namely unhealthy food, alcohol and gambling products. Children are particularly susceptible to the influence of unhealthy commodity marketing. This study explored adults' perceptions of unhealthy commodities sponsorship in elite sport and policies to restrict them. METHODS: Four focus groups of 7-8 frequent sport spectators were recruited, including parents and non-parents, and located in inner and outer suburbs of Sydney, Australia. Results were analysed thematically. RESULTS: Participants identified the contradictions of healthy messages of sport and unhealthy commodities, while highlighting the commercial value of sport sponsorship to sporting clubs. There is concern around children's exposure to effective and integrated marketing techniques when viewing sport, which encouraged unhealthy habits. Support for restricting sponsorship related to perceived product harm, with gambling viewed as having the greatest health impact. Participants were supportive of policies that reduced exposure of unhealthy commodities to children, but were concerned about the financial risk to sporting clubs. Governments and sports associations were identified as holding responsibility for enacting changes. CONCLUSION: A number of options were identified for advocates to gain public and political traction to reduce unhealthy commodity sponsorship. There is potential for shifts away from unhealthy sponsorship by both governments and sports associations.

The Australian Obesity Management Algorithm: A simple tool to guide the management of obesity in primary care.

Obesity is a complex and multifactorial chronic disease with genetic, environmental, physiological and behavioural determinants that requires long-term care. Obesity is associated with a broad range of complications including type 2 diabetes, cardiovascular disease, dyslipidaemia, metabolic associated fatty liver disease, reproductive hormonal abnormalities, sleep apnoea, depression, osteoarthritis and certain cancers. An algorithm has been developed (with PubMed and Medline searched for all relevant articles from 1 Jan 2000-1 Oct 2021) to (i) assist primary care physicians in treatment decisions for non-pregnant adults with obesity, and (ii) provide a practical clinical tool to guide the implementation of existing guidelines (summarised in Appendix 1) for the treatment of obesity in the Australian primary care setting. MAIN RECOMMENDATIONS AND CHANGES IN MANAGEMENT: Treatment pathways should be determined by a person's anthropometry (body mass index (BMI) and waist circumference (WC)) and the presence and severity of obesity-related complications. A target of 10-15% weight loss is recommended for people with BMI 30-40 kg/m2 or abdominal obesity (WC > 88 cm in females, WC > 102 cm in males) without complications. The treatment focus should be supervised lifestyle interventions that may include a reduced or low energy diet, very low energy diet (VLED) or pharmacotherapy. For people with BMI 30-40 kg/m2 or abdominal obesity and complications, or those with BMI > 40 kg/m2 a weight loss target of 10-15% body weight is recommended, and management should include intensive interventions such as VLED, pharmacotherapy or bariatric surgery, which may be required in combination. A weight loss target of > 15% is recommended for those with BMI > 40 kg/m2 and complications and they should be referred to specialist care. Their treatment should include a VLED with or without pharmacotherapy and bariatric surgery.

Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: a modelling study.

BACKGROUND: Accurate data on type 1 diabetes prevalence, incidence, associated mortality and life expectancy are crucial to inform public health policy, but these data are scarce. We therefore developed a model based on available data to estimate these values for 201 countries for the year 2021 and estimate the projected prevalent cases in 2040. METHODS: We fitted a discrete-time illness-death model (Markov model) to data on type 1 diabetes incidence and type 1 diabetes-associated mortality to produce type 1 diabetes prevalence, incidence, associated mortality and life expectancy in all countries. Type 1 diabetes incidence and mortality data were available from 97 and 37 countries respectively. Diagnosis rates were estimated using data from an expert survey. Mortality was modelled using random-forest regression of published type 1 diabetes mortality data, and life expectancy was calculated accordingly using life tables. Estimates were validated against observed prevalence data for 15 countries. We also estimated missing prevalence (the number of additional people who would be alive with type 1 diabetes if their mortality matched general population rates). FINDINGS: In 2021, there were about 8·4 (95% uncertainty interval 8·1-8·8) million individuals worldwide with type 1 diabetes: of these 1·5 million (18%) were younger than 20 years, 5·4 million (64%) were aged 20-59 years, and 1·6 million (19%) were aged 60 years or older. In that year there were 0·5 million new cases diagnosed (median age of onset 39 years), about 35 000 non-diagnosed individuals died within 12 months of symptomatic onset. One fifth (1·8 million) of individuals with type 1 diabetes were in low-income and lower-middle-income countries. Remaining life expectancy of a 10-year-old diagnosed with type 1 diabetes in 2021 ranged from a mean of 13 years in low-income countries to 65 years in high-income countries. Missing prevalent cases in 2021 were estimated at 3·7 million. In 2040, we predict an increase in prevalent cases to 13·5-17·4 million (60-107% higher than in 2021) with the largest relative increase versus 2021 in low-income and lower-middle-income countries. INTERPRETATION: The burden of type 1 diabetes in 2021 is vast and is expected to increase rapidly, especially in resource-limited countries. Most incident and prevalent cases are adults. The substantial missing prevalence highlights the premature mortality of type 1 diabetes and an opportunity to save and extend lives of people with type 1 diabetes. Our new model, which will be made publicly available as the Type 1 Diabetes Index model, will be an important tool to support health delivery, advocacy, and funding decisions for type 1 diabetes. FUNDING: JDRF International.

Definition and Classification of Diabetes and Prediabetes and Emerging Data on Phenotypes.

Diabetes diagnosis has important implications for individuals. Diagnostic criteria for fasting and 2-hour plasma glucose and HbA1c are universally agreed. Intermediate hyperglycemia/prediabetes is a risk factor for diabetes and cardiovascular disease. Because risk is a continuum, determining cut-point is problematic and reflected in significant differences in recommended fasting glucose and HbA1c criteria. Many types of diabetes are recognized. Diabetes classification systems are limited by a lack of understanding of etiopathogenetic pathways leading to diminished ß-cell function. The World Health Organization classification system is designed to assist clinical care decisions. Newly recognized phenotypic clusters of diabetes might inform future classification systems.

Polygenic risk scores predict diabetes complications and their response to intensive blood pressure and glucose control.

AIMS/HYPOTHESIS: Type 2 diabetes increases the risk of cardiovascular and renal complications, but early risk prediction could lead to timely intervention and better outcomes. Genetic information can be used to enable early detection of risk. METHODS: We developed a multi-polygenic risk score (multiPRS) that combines ten weighted PRSs (10 wPRS) composed of 598 SNPs associated with main risk factors and outcomes of type 2 diabetes, derived from summary statistics data of genome-wide association studies. The 10 wPRS, first principal component of ethnicity, sex, age at onset and diabetes duration were included into one logistic regression model to predict micro- and macrovascular outcomes in 4098 participants in the ADVANCE study and 17,604 individuals with type 2 diabetes in the UK Biobank study. RESULTS: The model showed a similar predictive performance for cardiovascular and renal complications in different cohorts. It identified the top 30% of ADVANCE participants with a mean of 3.1-fold increased risk of major micro- and macrovascular events (p = 6.3 × 10-21 and p = 9.6 × 10-31, respectively) and a 4.4-fold (p = 6.8 × 10-33) higher risk of cardiovascular death. While in ADVANCE overall, combined intensive blood pressure and glucose control decreased cardiovascular death by 24%, the model identified a high-risk group in whom it decreased the mortality rate by 47%, and a low-risk group in whom it had no discernible effect. High-risk individuals had the greatest absolute risk reduction with a number needed to treat of 12 to prevent one cardiovascular death over 5 years. CONCLUSIONS/INTERPRETATION: This novel multiPRS model stratified individuals with type 2 diabetes according to risk of complications and helped to target earlier those who would receive greater benefit from intensive therapy.

Incorporating fatty liver disease in multidisciplinary care and novel clinical trial designs for patients with metabolic diseases.

With the global epidemics of obesity and associated conditions, including type 2 diabetes, metabolic dysfunction-associated fatty liver disease, chronic kidney disease, hypertension, stroke, cardiovascular disease, osteoporosis, cancer, and cognitive changes, the prevalence of multimorbidity is rapidly increasing worldwide. In this Review, a panel of international experts from across the spectrum of metabolic diseases come together to identify the challenges and provide perspectives on building a framework for a virtual primary care-driven, patient-centred, multidisciplinary model to deliver holistic care for patients with metabolic dysfunction-associated fatty liver disease and associated metabolic diseases. We focus on clinical care and innovative trial design for metabolic dysfunction-associated fatty liver disease and associated metabolic diseases. This work represents a call to action to promote collaboration and partnerships between stakeholders for improving the lives of people with, or at risk of, metabolic dysfunction-associated fatty liver disease and associated metabolic diseases.

Race/ethnicity and challenges for optimal insulin therapy.

AIMS: We aimed to review insulin dosing recommendations, insulin regulation and its determinants, glycaemic response to carbohydrates, and the efficacy and safety of insulin therapy in different races/ethnicities. METHODS: We searched for articles in PubMed and Google Scholar databases up to 31 March 2021, with the following keywords: "ethnicity", "diabetes", "insulin", "history of insulin", "insulin therapy", "food/rice", "carbohydrate intake", "insulin resistance", "BMI", "insulin dosing", "insulin sensitivity", "insulin response", "glycaemic index", "glycaemic response", "efficacy and safety", with interposition of the Boolean operator "AND".In addition, we reviewed the reference lists of the articles found. RESULTS: The differential effect of race/ethnicity has not yet been considered in current insulin therapy guidelines. Nevertheless, body size and composition, body mass index, fat distribution, diet, storage, and energy expenditure vary significantly across populations. Further, insulin sensitivity, insulin response, and glycaemicresponse to carbohydrates differ by ethnicity. These disparities may lead to different insulin requirements, adversely impacting the efficacy and safety of insulin therapy among ethnic groups. CONCLUSIONS: Race/ethnicity affects glucose metabolism and insulin regulation.Until now, international guidelines addressing racial/ethnic-specific clinical recommendations are limited. Comprehensive updated insulin therapy guidelines by ethnicity are urgently needed.

Implications for farmers of measures to reduce sugars consumption.

OBJECTIVE: To estimate the impact of reduced consumption of free sugars in line with World Health Organization recommendations, on sugar farmers globally. METHODS: Using multiregion input-output analysis, we estimated the proportional impact on production volumes of a 1% reduction in free sugars consumption by the public. We extracted data on sugar production from the Food and Agriculture Organization of the United Nations database for the top 15 sugar-cane- and beet-producing countries globally, and created a custom multiregion input-output database to assess the proportions of production going to human consumption, drawing on household expenditure surveys and national input-output databases (data valid for years 2000-2015). We also considered the impact on production volumes in relation to countries' gross domestic product. FINDINGS: A high proportion of current sugar production from these countries goes to human consumption, and would thus be impacted by reduced consumption of sugars. The largest impacts on cane sugar production, and thus on farmers, would likely occur in Brazil, China, India and Thailand and on beet production in Belarus, Germany, Russian Federation and United States of America. CONCLUSION: A global opportunity exists for public health leadership to bring together the health, economic, environmental and agriculture sectors to collaborate and build capacity for promotion of alternative livelihoods for sugar farmers. Lessons regarding strategy and the importance of political economy factors can be learnt from tobacco control measures. Further research to quantify the impact of reductions in sugars consumption would provide useful insights for designing policies to complement and strengthen efforts to improve diets and health.

Effectiveness of dietetic intervention for people with type 2 diabetes: A meta-analysis.

BACKGROUND: Diet is central to treatment of type 2 diabetes. This review aimed to compare the effectiveness of nutrition therapy delivered by dietitians to nutrition advice delivered by other healthcare professionals in adults with type 2 diabetes on metabolic parameters. METHODS: Cochrane CENTRAL, CINAHL, EMBASE, MEDLINE and PsychINFO were searched for randomised controlled trials of three months duration or longer, published from 1st January 2008 to 18th June 2019. Relevant data were extracted from studies with additional author information. Random-effects meta-analysis assessed mean changes in HbA1c and other clinical parameters. PROSPERO registration number: CRD42019130528. RESULTS: Of 2477 records identified, fourteen studies, involving 3338 participants, were eligible for qualitative synthesis and meta-analysis. The mean changes [95% CI] at follow-up in HbA1c, BMI, weight, LDL cholesterol, systolic and diastolic blood pressure were -0·47 [-0·92, -0·02] %, -0·38 [-0·63, -0·13] kg/m2, -1·49 [-2·14, -0·84] kg, -0·15 [-0·33, 0·04] mmol/L, -0·75 [-2·45, 0·96] mm Hg and -1·17 [-4·52, 2·17] mm Hg respectively in favour of the intervention group. The quality of evidence was limited due to heterogeneity, risk of bias, publication bias and indirectness. CONCLUSIONS: Nutrition therapy provided by dietitians was associated with better clinical parameters of type 2 diabetes, including clinically significant improved glycaemic control, across diverse multiethnic patient groups from all six inhabited continents. This conclusion should be reflected in clinical guidelines.