The relationship between gestational vitamin D status and offspring autism remains inconsistent, potentially due to genetic differences in vitamin D receptor (VDR) interactions. This exploratory study examined associations between maternal serum vitamin D concentrations, offspring VDR genotypes (BsmI, Fok1, ApaI, TaqI), and autism symptomatology using the Australian Scale for Autism Spectrum Conditions (ASASC) in 192 mother-child pairs at 11-years follow-up. No association was found between gestational vitamin D levels and total ASASC scores, nor between VDR genotype and total ASASC scores. Secondary subscale analyses revealed that higher early vitamin D concentrations were associated with decreased fact-orienting scores in males (β= - 0.05, 95% CI - 0.08, - 0.01, p = 0.02). Additionally, the homozygous recessive TaqI genotype was associated with a 2.5-unit increase in fact-orienting scores compared to the homozygous dominant genotype (β = 2.52, 95% CI 0.36, 4.69, p = 0.02), no significant associations were observed for vitamin D and other ASASC subscales or total scores. Due to the large number of comparisons, no adjustments for multiple testing were made; thus, significant findings should be interpreted with caution. While overall autism traits were unrelated to gestational vitamin D or VDR genotype, preliminary results may suggest modulation of specific autism-related traits by maternal vitamin D levels and offspring genetic variation.

Objective: This study investigated the association between gait speed, handgrip strength, and their combination, and the risk for developing clinically relevant depressive symptoms in community-dwelling older adults. Methods: A secondary analysis was conducted using data from the ASPirin in Reducing Events in the Elderly study. Participants were community-dwelling older adults in Australia and the United States of America followed for a median (interquartile range) of 3.97 (2.26) years. Baseline handgrip strength and gait speed were used as exposure variables, and their combination categories were also explored. Depression was measured using the modified Center for Epidemiological Studies Depression 10-item scale (CES-D 10). Cox regression was used to estimate Adjusted Hazard Ratios (AHR) with 95 % Confidence Intervals (CI) after adjusting for a range of potential confounders. Result: A total of 17,231 participants (55.3 % women) were included in the analysis. Slow gait and weak grip at baseline were associated with the risk of depression (AHR: 1.20; CI: 1.11-1.29 and 1.14; 1.06-1.23, respectively). The combination of the two physical performance measures was associated with a 31 % increase in the risk of depression (1.31; 1.16-1.47) and a significant dose-response association was observed for quintiles of gait and grip with depression. Limitations: Although the CES-D 10 is a validated scale, it is a self-reported tool rather than a clinical diagnosis of depression. Conclusion: Low physical function may be a risk factor for depression in older adults. This highlights the inextricable link between the physical and mental health of older adults, which can inform potential clinical and public health prevention strategies for depression in later life.

Impact microindentation (IMI) measures bone material strength index (BMSi) in vivo. However, its ability to predict fractures is still uncertain. This study aimed to determine the association between BMSi and 10 year fracture probability, as calculated by the FRAX algorithm. BMSi was measured using the OsteoProbe in 388 men (ages 40–90 yr) from the Geelong Osteoporosis Study. The probabilities for a major osteoporotic fracture (MOF) and hip fracture (HF) were calculated using the Australian FRAX tool. Hip (HF) and major osteoporotic (MOF) fracture probabilities were computed with and without the inclusion of femoral neck bone mineral density (BMD). For each participant, four 10 year probability scores were therefore generated: (i) HF-FRAXnoBMD; (ii) HF-FRAXBMD; (iii) MOF-FRAXnoBMD; (iv) MOF-FRAXBMD. BMSi was negatively correlated with age (r = − 0.114, p = 0.025), no associations were detected between BMSi and femoral neck BMD (r = + 0.035, p = 0.507). BMSi was negatively correlated with HF-FRAXnoBMD (r = − 0.135, p = 0.008) and MOF-FRAXnoBMD (r = − 0.153, p = 0.003). These trends held true for HF-FRAXBMD (r = − 0.087, p = 0.094) and MOF-FRAXBMD (r = − 0.111, p = 0.034), but only the latter reached significance. BMSi captures the cumulative effect of clinical risk factors in the FRAX algorithm, suggesting that it could provide additional information that may be useful in predicting risk of fractures. Further studies are warranted to establish its efficacy in predicting fracture risk.

BACKGROUND:With the increasing global burden of type 2 diabetes, prevention strategies that target prediabetes, a state of hyperglycaemia that puts individuals at high risk of type 2 diabetes, are required. We aimed to estimate global rates of transition from prediabetes to normoglycaemia or type 2 diabetes, stratified by age, sex, and race and ethnicity. We also aimed to quantify the effect of modifiable and non-modifiable risk factors on these transitions. METHODS:In this pooled analysis of individual-level data, we included original data from 19 prospective cohort studies conducted in Asia (Iran and Japan), Australia, Europe (Spain and Sweden), North America (USA and Mexico), and South America (Venezuela). We applied discrete-time hidden Markov models to estimate rates and ratios of prediabetes transitions to type 2 diabetes and normoglycaemia specific to age, sex, and race and ethnicity. We used Fine-Gray competing risk models to derive cohort-specific subhazard ratios (SHRs) for potential risk factors influencing these transitions. We subsequently pooled these SHRs using a random-effects meta-analysis. In subgroup analyses stratified by age, sex, race and ethnicity, and recruitment period, we used multivariate Cox models to investigate the degree of heterogeneity between studies. FINDINGS:76 092 participants (39 842 [52·3%] women and 36 250 [47·6%] men; mean age 51·1 years [SD 12·7]) with available data on glycaemic status from at least one follow-up visit were included in the analysis, of whom 56 837 (74·7%) had normoglycaemia and 19 255 (25·3%) had prediabetes. Median follow-up was 9·8 years (IQR 5·8-12·5). Within 10 years, individuals with prediabetes had a 12·5% probability of progressing to type 2 diabetes, whereas the probability of reverting to normoglycaemia was 36·1%. However, in the highest fasting plasma glucose quartile, the probability of progression increased to 16·1% and reversion decreased to 13·4%. Male sex, older age (≥55 years), and Latinx populations were associated with an increased risk of transitioning to type 2 diabetes. Risk factors that significantly reduced prediabetes reversion to normoglycaemia were overweight (SHR 0·88 [95% CI 0·76-0·99]), obesity (0·66 [0·52-0·81]), elevated waist-to-height ratio (0·82 [0·70-0·95]), elevated waist-to-hip ratio (0·79 [0·68-0·91]), and reduced HDL concentration (0·72 [0·59-0·84]). INTERPRETATION:Our findings highlight that reversion to normoglycaemia was more common than progression to type 2 diabetes among individuals with prediabetes, and that these transitions were strongly influenced by modifiable risk factors. The increased risk of progression with advancing age and among men underscores the importance of early identification and targeted interventions in population groups at high risk of type 2 diabetes. Furthermore, the elevated progression risk in individuals with higher fasting plasma glucose concentrations at baseline reinforces the need for timely detection and intervention during this crucial clinical window. FUNDING:Deakin University Postgraduate Research Scholarship.

BACKGROUND:With Australia's aging population, the incidence of falls is expected to rise. The proportion of adults aged ≥65 years is projected to increase from 15 % in 2017 to 22 % by 2057, highlighting the growing need for effective fall prevention measures. Therefore, this study aimed to assess fall trends and determinants using repeated follow-up data from a population-based study. METHODS:This study utilized data from the Geelong Osteoporosis Study (GOS) to analyse fall trends in men and women. Men's data were collected at baseline (2001-2006; n = 1533), 5 years (2006-2011; n = 968), and 15 years (2016-2021; n = 627), while women's data were from 6 years (2001-2003; n = 1014), 10 years (2004-2008; n = 1098), and 15 years (2011-2014; n = 844). Falls data, self-reported for the past 12 months, were age-standardised to the Australian population. Data included self-reported prior fractures, medications, comorbidities, alcohol use, and smoking, along with measured anthropometrics, muscle strength, biochemical tests, and imaging. A multivariable Generalised Estimating Equation model identified fall determinants, reporting adjusted odds ratios (AORs) and 95 % confidence intervals. RESULTS:In men, the age-adjusted prevalence of falls declined over time, while in women, it initially dropped by 4.2 % before a slight 0.6 % increase. After adjusting for confounders, each additional year of age raised the fall risk by 1 % (AOR = 1.01, 95 % CI: 1.00-1.02). Women had a 52 % higher likelihood of falling than men (AOR = 1.52, 95 % CI: 1.22-1.88). Diabetes increased the risk by 69 % (AOR = 1.69, 95 % CI: 1.23-2.31), while a 1 N/kg increase in hip flexion strength lowered the risk by 3 % (AOR = 0.97, 95 % CI: 0.95-0.99). CONCLUSION:Men experienced a steady decrease in fall prevalence over time, whereas women displayed a more intricate trend, with falls initially declining before subsequently rising, following a polynomial pattern. The key predictors of falls included age, sex, diabetes and hip flexion strength. Policies should prioritize tailored fall prevention, strength training, and diabetes care integration.

Introduction:Bipolar disorder is associated with several physical conditions and possibly increased pain, although research outside hospital settings is limited. We compared perceived pain among population-based women with and without bipolar disorder. Method:This study examined 113 women with bipolar disorder (59 euthymic, 54 symptomatic in past month) and 316 age-matched women without bipolar disorder drawn from studies located in the same region of south-eastern Australia. Mental disorders were confirmed by clinical interview (SCID-I/NP). Pain during the past week was determined by numeric rating scale (0-10, 10 = pain as severe as I can imagine) and deemed present if ≥5. Demographic, lifestyle, and health information was obtained via questionnaire. Odds ratios (OR) with 95% confidence intervals for the likelihood of pain were estimated using marginal binary logistic regression models, adjusting for potential confounders. Results:Women with bipolar disorder who were euthymic at the appointment were at increased odds of headache [adjOR 3.4, 95% CI (1.4, 7.9)], back pain [2.6 (1.3, 5.4)], overall pain(s) [5.7 (2.9, 11.4)], pain at ≥3 sites [2.3 (1.0, 5.2)] and were in pain ≥50% time spent awake [2.3 (1.1, 5.1)] compared to women without bipolar disorder. The pattern of association was similar but stronger for women symptomatic in the past month; headache [6.0 (2.6, 13.9)], back pain [4.2 (2.0, 8.5)], overall pain(s) [7.2 (3.4, 15.4)], pain at ≥3 sites [5.1 (2.3, 11.1)] and ≥50% time in pain [4.5 (2.2, 9.3)]. Daily activity interference from pain did not differ between groups (all p > 0.05). Conclusion:Women with bipolar disorder are more likely to report pain regardless of phase. Assessment and management of pain is necessary to reduce associated burden.

Longitudinal cohort studies across the lifespan suggest an association between ultra-processed food (UPF) and depression. However, the effect of UPF on depression and mental health in older adults has not been determined. Therefore, this study investigated the effect of UPF on depressive symptoms and mental health in community-dwelling older adults. A pragmatic target trial was designed and emulated using the ASPirin in Reducing Events in the Elderly longitudinal data. Participants were community-dwelling older adults (≥ 70 years) in Australia. We specified and emulated the protocol of a two-arm randomised pragmatic clinical trial using the level of UPF consumption as the intervention. Greater than or equal to 4 servings of UPF per day was considered the intervention, with less than 4 servings per day the control. Dietary consumption was assessed using a mail-based diet screening questionnaire, and the level of food processing was classified based on the NOVA classification. The study outcomes were depressive symptoms, defined as a score of ≥ 8 on the Center for Epidemiological Studies Depression 10-item scale, and general mental health, defined by the mental component summary score of the Short Form-12. We applied inverse probability treatment weighting to balance confounders. Marginal structural models were employed to estimate the population-level average effect of intervention using generalised estimated equations. A total of 11,192 participants (3415 intervention and 7777 control) were eligible for the emulation. High UPF consumption at time zero was associated with an increased risk of depressive symptoms at follow-ups (RR: 1.10; CI: 1.04–1.18). The finding was consistent with sensitivity analyses; after excluding participants on antidepressants at time zero, the risk of depressive symptoms in the intervention group was increased by 11

Objective: This study assessed the individual and combined associations of slow gait speed, weak grip strength, and depressive symptoms with the risk of serious falls in an aging population. Methods: This study used data from the Aspirin in Reducing Events in the Elderly (ASPREE) trial, which collected adjudicated events on serious falls from Australian community-dwelling older adults (≥70 years). Cox proportional hazard models were employed to estimate adjusted hazard ratios (AHR). Results: Of 16,357 participants, 1505 (9.2 %) had serious falls over the median (IQR) follow-up of 4.4 (3.3–5.5) years. Slow gait, weak grip, and depressive symptoms at baseline were associated with serious falls (AHR = 1.38, 95 %CI: 1.22–1.56; AHR = 1.22, 95 %CI: 1.07–1.38, and AHR=1.28, 95 %CI:1.10–1.50, respectively). Combined slow gait, weak grip, and depressive symptoms were associated with a more than two-fold increase in the risk of serious falls (AHR=2.15, 95 %CI: 1.56–2.97). The presence of slow gait and weak grip were associated with a 66 % increase in the risk of serious falls (AHR=1.66, 95 %CI:1.40–1.97). Depressive symptoms worsened the risk of falls among individuals with chronic conditions such as diabetes. Conclusion: Combined gait speed, grip strength, and depressive symptoms have a strong association with serious falls in an aging population. Therefore, incorporating strength and mobility training interventions to improve physical functions and addressing depression through timely diagnosis and effective treatment may help to prevent the risk of falls among older adults.

The relationship between rheumatoid arthritis (RA) and fracture risk was estimated in an international meta-analysis of individual-level data from 29 prospective cohorts. RA was associated with an increased fracture risk in men and women, and these data will be used to update FRAX®. RA is a well-documented risk factor for subsequent fracture that is incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between rheumatoid arthritis and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD) with a view to updating FRAX. The resource comprised 1,909,896 men and women, aged 20–116 years, from 29 prospective cohorts in which the prevalence of RA was 3

BACKGROUND:There is developing evidence of excess mortality among people with mental disorders. This protocol presents the methodology to undertake a systematic review to definitively examine the current evidence on the risk of all-cause and cause-specific mortality in people with mental disorders (mood, anxiety, substance use, eating, personality and psychotic disorders) compared with populations without mental disorders in broadly representative studies of general populations worldwide. In addition, we seek to understand whether the excess mortality has increased further over time, and if the COVID-19 pandemic exacerbated the excess mortality in people with mental disorders. METHODS:A systematic review of cohort studies will be conducted. The search strategy to yield peer-reviewed (in Medline Complete, CINAHL Complete, Embase and APA PsycInfo) and published grey literature will be developed in consultation with a liaison librarian. A preliminary scope of peer-reviewed literature in Medline Complete using the EBSCOhost platform was conducted on 20 November 2023. Epidemiological cohort or case-control studies will be eligible if they examine (1) diagnoses of mental disorders (according to the Diagnostic and Statistical Manual of Mental Disorders and the International Classification of Diseases classification systems) and (2) risk of all-cause and/or cause-specific mortality. A critical appraisal of the included studies will be undertaken. A synthesis of the findings will include the characteristics of the included studies, critical appraisal and a summary of the key findings in texts and visually in tables. Where appropriate, meta-analyses and subgroup analyses will be performed. ETHICS AND DISSEMINATION:This study is exempt from ethics approval, as it does not include identifiable human data. The outcomes of the proposed review will be shared in national/international conferences, published in a peer-reviewed journal and disseminated to new and existing networks. PROSPERO REGISTRATION NUMBER:CRD42023477494.

Systemic inflammation is associated with depression. Certain oral bacterial species contribute to inflammation; however their potential association with mental disorders remains unclear. This study investigated the associations between oral microbiota pathogens and depressive and anxiety symptoms. Data came from 436 men from the Geelong Osteoporosis Study. Oral microbiota was characterized using 16S rRNA sequencing, and an oral pathogen composite was created comprising Porphyromonas gingivalis, Treponema denticola, Fusobacterium nucleatum, and Prevotella nigrescens species relative abundances. Binary variables were created representing elevated depressive and anxiety symptoms using the Hospital Anxiety and Depression Scale. Logistic regression was used to investigate associations between oral pathogens and elevated depressive/anxiety symptoms. Models were adjusted for confounders: age, socioeconomic status, diet, smoking, alcohol, exercise, obesity, and hypertension. We report a modest (nonsignificant) association between the pathogen composite and elevated depressive (OR 1.35 [95% CI 0.974, 1.87]) but not anxiety symptoms. Moreover, some of the comprising species were significantly associated with elevated depressive symptoms, including P. nigrescens (1.61 [1.21, 2.13]). Our exploratory analyses revealed that several other taxa were significantly associated with depression and anxiety symptoms. The findings suggest that specific oral bacteria may contribute to symptoms of depression, warranting further research through larger and longitudinal investigations.

AIMS:Fractures during childhood and adolescence are common as peak bone mass has not yet been accrued. Previous studies have reported that offspring are at higher risk of a fragility fracture if one or both parents have experienced a fracture, however, it is not known if this association holds true for fractures experienced in early life, and if so, whether there are differential risk profiles across the sexes. Therefore, this study aimed to determine the associations between maternal and paternal fracture history and offspring fracture risk in early life. METHODS:At baseline, Geelong Osteoporosis Study participants self-reported fracture history for themselves and their parents. This analysis included personal fracture data relating to birth until 20 years of age and parental fracture for 1336 female and 1174 male participants who provided complete data, including age and site of fracture. Multivariable logistic regression models were used to assess the odds of participant fracture in childhood or adolescence in association with paternal and/or maternal fracture. RESULTS:In total, 141 (12.2 %) female and 323 (25.7 %) male participants reported at least one fracture by age 20 years. For females, there were 247 maternal and 211 paternal parents with fractures and in males, 233 maternal and 189 paternal fractures. A maternal fracture was associated with an increased odds of early life fracture in female participants (OR 1.86; 95 % CI 1.17-2.95) but not male participants (OR 1.16; 95 % CI 0.81-1.65), while a paternal fracture was associated with an increased odds of early life fracture in males (OR 1.47; 95 % CI 1.01-2.14) but not females (OR 1.61; 95 % CI 0.98-2.64). CONCLUSION:Parental fracture history appears to have sex-specific associations with offspring early life fracture risk. Whereby maternal fracture history is associated with an increased risk of early life fracture in females, while paternal fracture history is associated with early life fracture risk in males.

Background:Achieving survival free from physical disability or neurocognitive impairment, known as disability-free survival (DFS), is a key public health goal. This study aimed to (1) determine the long-term interactive effects of depression and cardiometabolic diseases (CMDs) on DFS, and (2) explore any associated antidepressant treatment effect on improvements in DFS among older adults. Methods:We used data from the ASPREE trial and its observational follow-ups (2010-2019), involving community-dwelling adults aged ≥ 70 years (≥65 for U.S. minorities). Time-updated Cox models were used to estimate the combined effect of depression and CMDs (type 2 diabetes, dyslipidemia, hypertension, chronic kidney disease, metabolic-associated steatotic liver disease, and major adverse cardiovascular events) as well as cardiometabolic multimorbidity (≥2 CMDs) on DFS. To evaluate the improvement in DFS associated with antidepressant treatment in individuals with depression, we estimated the number needed to treat (NNT) to achieve a one-year increase in DFS through antidepressant therapy. Findings:18,739 participants (mean [SD] age, 75.1 [4.6] years; 56.0% female) were included, with a median follow-up of seven years; individuals with both depression and CMDs demonstrated a significantly lower DFS compared to those without either condition. In individuals with depressive symptoms, antidepressant use was associated with a median increase in DFS of 2.95 years (95% CI, 2.12-3.04), with an estimated NNT of 8.05 (95% CI, 5.63-14.86) associated with a one-year increase in DFS. Interpretation:Integrating depression treatment into chronic disease management, when appropriate, is associated with an improvement in DFS among older adults. Funding:Deakin University Postgraduate Research Scholarship.

Polypharmacy is common in older adults and may be associated with poor outcomes. However, methods used to define polypharmacy are rarely reported precisely, with potential implications for polypharmacy exposure estimates. The aim was to investigate prevalence estimates according to different methods in an Australian population-based sample of older adults. This cross-sectional study included 735 adults aged ≥ 60 years participating in the Geelong Osteoporosis Study. Current prescription, non-prescription and complementary and alternative medicines were self-reported. Counting methods included the number of active ingredients and unique products. Polypharmacy and hyperpolypharmacy were determined using ≥ 5 and ≥ 10 medicine cut points respectively. Prevalence was estimated using ingredient- and product-level counts according to criteria defined by medicine schedule and type (i.e. scheduled prescription, non-prescription). Non-parametric testing measured differences between counting methods, univariate logistic regressions investigated disagreement between total counts and polypharmacy exposure. Polypharmacy prevalence (scheduled prescription medicines) was 30.3

To assess the association between a one-year fall history and QoL domains and compare QoL between single and recurrent fallers in older Australians. Recurrent falls were affected all QoL domains, while single falls were linked mainly to physical and psychological health. Compared to single fallers, those with recurrent falls experienced greater declines in social and environmental QoL domains. Falls, particularly recurrent ones, diminish QoL in older Australians, highlighting the need for targeted prevention efforts and offering valuable guidance for promoting healthy ageing. Older adults are at increased risk of falls, which can substantially impact their quality of life (QoL). While few global studies have explored this association, comprehensive research in Australia remains limited. This study aimed to assess the association between a one-year fall history and QoL domains and compare QoL between single and recurrent fallers in older Australians. Participants (n = 530, age ≥ 65 yr) were drawn from the 15-year assessment wave of the Geelong Osteoporosis Study. QoL was assessed using the World Health Organization Quality of Life-BREF (WHOQOL-BREF), a 26-item questionnaire covering four domains: physical, psychological, social, and environmental health. Falls within the previous 12 months were self-reported. Tobit regression was used to analyse associations between falls and QoL. Post-estimation linear combination tests were used to assess whether the associations differed between single and recurrent falls. The participants had a mean age of 75.4 ± 7.2 years, and 266 (50.2

OBJECTIVES:Although cardiovascular disease (CVD) is responsible for a large global burden of disease, a large proportion of CVD incidence can be prevented through health literacy (ie, the skills and resources of an individual to access, understand, and use information to make decisions and act on one's own health and health care). We reviewed and synthesized peer-reviewed literature on health literacy and primary prevention of CVD. METHODS:We followed methods from the review's previously published protocol, which outlined a search strategy conducted on August 16, 2024, for 6 databases, linking concepts of health literacy and CVD risk and its associated knowledge, attitudes, or practices. One reviewer screened and extracted all articles, and a second reviewer screened a randomly selected 10% of articles at each stage to examine interrater agreement. We used the Office of Health Assessment and Translation Risk of Bias Tool to assess the potential risk of bias. RESULTS:Of 35 studies in the synthesis, 26 (74%) were cross-sectional and 21 (60%) measured functional health literacy only. Twenty-three articles investigated health literacy as an exposure variable, 20 of which reported significant results. Eight articles examined the administration of health literacy interventions to populations at risk of CVD, and 4 presented health literacy profiles of populations at risk of CVD. Each study demonstrated at least 1 area of potential risk of bias but was deemed low risk of bias overall. CONCLUSIONS:Several studies in this review found an association between health literacy and CVD risk. More longitudinal studies, as well as studies that measure health literacy more deeply than simply reading and comprehending health texts, are needed to better understand the extent of this relationship.

BACKGROUND:Sarcopenia is an age-related skeletal muscle disorder associated with deleterious health outcomes. Few studies have examined associations between sarcopenia and quality of life (QoL). Therefore, the purpose of this study was to determine whether sarcopenia is independently associated with specific domains of QoL. METHODS:This cross-sectional study examined associations between sarcopenia and domains of QoL in a population-based sample of 682 adults aged 60-96 years. Sarcopenia was defined according to the revised European Working Group on Sarcopenia in Older People algorithm. Appendicular lean mass was assessed using dual-energy Xray absorptiometry, handgrip strength by dynamometry, and physical performance using the Timed UupandGo test. The World Health Organisation's abbreviated QoL tool was used to assess QoL across four domains: physical health, psychological, social relationships and environment. Multivariable logistic regression was used to investigate associations between sarcopenia and poor QoL. RESULTS:After adjusting for potential covariates, sarcopenia (either probable or confirmed) was associated with an increased likelihood for poor physical health-related QoL [OR 2.77 (95% CI 1.31-5.88)] and poor psychological-related QoL [OR 2.69 (95% CI 1.41-5.15)]. No associations were detected between sarcopenia and the social relationships or environment domains. CONCLUSIONS:These findings highlight the importance of maintaining skeletal muscle health in older age. Interventions to prevent or manage sarcopenia among older adults may contribute to better QoL for this population and warrant further investigation.

Aims/hypothesisWe aimed to investigate the association between reversion to normoglycaemia among individuals with prediabetes (fasting plasma glucose 5.6-6.9 mmol/l in the absence of other criteria for type 2 diabetes) and the subsequent risk of type 2 diabetes, and to examine whether concurrent favourable cardiometabolic risk factor profiles modify this association.MethodsWe used individual-level data from prospective cohorts in the USA, Australia and Asia. Participants with prediabetes at baseline, with at least two follow-ups (n=8191) at median intervals of 2.9 years (IQR 2.3-9.0) and 3.1 years (IQR 2.6-3.6), were classified into restoration of normoglycaemia and persistent prediabetes groups based on the glucose status at the first follow-up (normoglycaemia or prediabetes). Type 2 diabetes occurrence was assessed at subsequent follow-ups. Hierarchical mixed-effects proportional hazards Weibull models estimated type 2 diabetes risk, adjusting for age, sex and cardiometabolic risk factors. A subgroup analysis evaluated the combined association of normoglycaemia restoration and normal cardiometabolic risk factor levels on subsequent type 2 diabetes risk.ResultsIn individuals with prediabetes, normoglycaemia restoration compared with persistent prediabetes was associated with a 51% lower risk of developing type 2 diabetes. Even lower risks were observed among individuals with concurrent favourable cardiometabolic profiles, including non-smokers (HR 0.20, 95% CI 0.10, 0.31), and those with normal BMI (0.16, 95% CI 0.06, 0.27), waist circumference (0.22, 95% CI 0.12, 0.33), waist-to-height ratio (0.15, 95% CI 0.03, 0.26), WHR (0.17, 95% CI 0.05, 0.28), and systolic (0.20, 95% CI 0.11, 0.30) and diastolic (0.25, 95% CI 0.12, 0.38) blood pressure, triacylglycerol (0.24, 95% CI 0.13, 0.35) and HDL-cholesterol levels (0.21, 95% CI 0.13, 0.29). Weight loss combined with normoglycaemia restoration was also associated with lower type 2 diabetes risk (0.18, 95% CI 0.07, 0.30) compared with weight gain and persistent prediabetes.Conclusions/interpretationOur results suggest that prioritising normoglycaemia restoration during the prediabetes stage in clinical guidelines may contribute to reducing the risk of type 2 diabetes, particularly when accompanied by favourable cardiometabolic health profiles.

AIMS:To determine the prevalence of the novel diabetes subgroups in a population-based study, and investigate clinical characteristics and mortality in these subgroups compared to participants without diabetes. METHODS:Men from the Geelong Osteoporosis study (n = 895) were categorised according to diabetes status. Men with diabetes (n = 105) were categorised into the severe auto-immune diabetes (SAID) subgroup based on islet antibody seropositivity. The remaining men were then classified into the other subgroups using k-means clustering. ANOVA and chi-squared tests were used to determine differences in demographics, lifestyle factors and comorbidities between the novel diabetes subgroups and normoglycaemia (n = 790). Cox proportional hazard models were used to compare mortality over a median of 11.8 years (IQR 9.7-11.3). A p-value< 0.05 was considered significant, models were adjusted for age, physical activity, and systolic blood pressure. RESULTS:Compared to men with normoglycaemia, mean blood pressure and cardiovascular comorbidities were higher in the mild obesity-related diabetes (MOD), mild age-related diabetes (MARD), and severe insulin-resistant diabetes (SIRD) subgroups. The MARD subgroup was associated with higher mortality in unadjusted models (HR 5.5, 95 %CI 3.6-8.4); although this was attenuated after adjustment. In unadjusted models, mortality was not different in the SIRD subgroup, however, after adjustment this subgroup had higher mortality (HR 2.0; 95 %CI 1.0-3.9). CONCLUSIONS:These data may influence choice of antihyperglycaemic medication and management of cardiovascular risk factors in men with type 2 diabetes particularly in the SIRD subgroup which is associated with cardiovascular-related comorbidities, and mortality.

Post-menopausal bone loss has been well described, however fewer studies have focussed on changes around the time of menopause. This study describes bone mineral density (BMD) loss following recent menopause, stratified by hormone replacement therapy (HT) use. Women (n = 287) who self-reported recent menopause (≥ 12 months to < 5 yr since last menstrual period) for at least one assessment phase of the Geelong Osteoporosis Study were included. BMD was measured using Lunar DPX-L and GE-Prodigy machines. Time since menopause was calculated for each participant at each assessment phase and divided into three categories: < 5 yr, 5-10 yr and ≥ 10 yr. BMD loss was expressed as: (i) cumulative loss over time, (ii) absolute value per year and (iii) percentage loss per year. Proportions of women with normal BMD, osteopenia and osteoporosis were also calculated. Cumulative BMD loss was lower among HT users than non-users at all sites and time categories, except the femoral neck. Compared to the other time categories, HT non-users had a greater rate of BMD loss (expressed as an absolute value or percentage per year) during the first five years postmenopause at the ultra-distal forearm and lumbar spine. No differences were observed between the time categories for HT users. The proportions of women with osteopenia and osteoporosis increased across each of the time categories, but patterns differed by skeletal site, being more pronounced for the femoral neck and mid-forearm sites. Rates of bone loss were greater at the lumbar spine and ultra-distal forearm during the first five years following menopause.