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. 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. 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]). 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. Deakin University Postgraduate Research Scholarship.

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. 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. 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. Integrating depression treatment into chronic disease management, when appropriate, is associated with an improvement in DFS among older adults. 10.13039/501100001778 Deakin University Postgraduate Research Scholarship.

Background/Objectives: Evidence suggests a J-shaped association between alcohol consumption and depression, but it remains unclear whether this reflects a true causal effect, reverse causation, or methodological bias. This uncertainty is particularly relevant in older adults, who are at increased risk for both depression and alcohol-related harms. This study aimed to examine the association between varying levels of alcohol consumption and depression risk in community-dwelling older adults. Methods: We analyzed 16,563 community-dwelling older adults (mean age 75.1 ± 4.6 years) from the ASPirin in Reducing Events in the Elderly (ASPREE) trial. Alcohol intake, reported at baseline and follow-up, was categorized as abstinent, occasional, moderate, or above-guideline. Both intention-to-treat (classified by baseline alcohol consumption, regardless of later changes) and per-protocol (using annual time-updated alcohol consumption ) analyses were performed. To address confounding, informative censoring, and selection bias, we applied marginal structural models with inverse probability weighting. Results: In per-protocol analyses, abstainers (OR 1.17), occasional drinkers (OR 1.11), and above-guideline drinkers (OR 1.15) were significantly associated with a higher risk of depression compared with moderate drinkers, consistent with a J-shaped association. Sensitivity analyses excluding former drinkers and those with baseline depressive symptoms showed similar results. The association remained robust after adjusting for social isolation, social support, social interactions, physical activity, pain, sleep duration, sleep difficulties, and sleep medication use (n = 14,892; Australian sub-sample), and did not differ by sex. Conclusions: Moderate alcohol consumption was associated with the lowest depression risk, confirming a J-shaped relationship after comprehensive confounder adjustment.