Diabetes, Obesity & Metabolism最新文献

Aims: To evaluate the association between longitudinal non-HDL-C exposure and the risks of major adverse cardiovascular events (MACEs) and all-cause mortality in type 2 diabetes patients on lipid-lowering therapy.

Materials and methods: This post hoc analysis of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trial included patients with type 2 diabetes who had non-HDL-C measured at baseline and four subsequent visits over 24 months. Longitudinal exposure was assessed using cumulative load, variability (standard deviation) and trajectory (slope). Outcomes were MACEs and all-cause mortality. Cox proportional hazard models were used to obtain hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Among 4673 participants with a median follow-up of 7.5 years, 695 MACEs and 842 deaths occurred. After adjusting for baseline and mean non-HDL-C levels, the highest quartile of cumulative load (HR, 1.81; 95% CI, 1.41-2.32), variability (HR, 1.27; 95% CI, 1.00-1.60) and the most rapidly increasing slope (HR, 1.26; 95% CI, 1.02-1.56) were each associated with increased risks of MACEs, compared to the lowest quartile. The association with all-cause mortality followed a similar pattern, except for the non-HDL-C slope. Stratified analyses showed that cumulative load and variability were associated with MACEs among participants with baseline non-HDL-C < 130 mg/dL, and with all-cause mortality among those with baseline ≥130 mg/dL. No significant associations with slope were observed within strata of baseline non-HDL-C.

Conclusions: Longitudinal non-HDL-C exposure showed associations with both MACEs and mortality, independent of baseline non-HDL-C, underscoring the need for sustained and stable non-HDL-C control over time.

Aims: Obesity involves both metabolic and neural dysfunction, yet the temporal dynamics of brain connectivity remain unclear. This study applied dynamic functional network connectivity (dFNC) analysis to reveal time-varying brain network patterns in obesity.

Materials and methods: Eighty-three individuals with obesity and 40 normal-weight controls underwent resting-state functional magnetic resonance imaging. After preprocessing and group independent component analysis, dFNC was estimated using a sliding-window approach and clustered into distinct connectivity states. Temporal metrics (fraction time, dwell time and transitions) were compared between groups, and correlations with clinical characteristics were analysed.

Results: Three recurring connectivity states were identified. Compared with controls, individuals with obesity showed enhanced coupling among the default mode, attention and visual networks, with reduced network flexibility-manifested as prolonged dwell time and fewer transitions. Uncontrolled eating correlated positively with time spent in maladaptive states, whereas cognitive restraint was negatively associated with participation in integrative states.

Conclusions: Obesity is characterised by state-dependent reorganisation of large-scale brain networks and diminished temporal flexibility. These dynamic connectivity alterations are closely related to eating behaviour and metabolic characteristics, suggesting that dFNC provides a valuable neuroimaging framework for understanding impaired self-regulation in obesity and for guiding future intervention studies.

Background: The incidence of type 2 diabetes mellitus among young adults has been increasing over the past few decades. There are limited data on contemporary national cardiovascular mortality rates in young adults with diabetes mellitus (DM).

Methods: We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database for patients aged 15 to 44 years from 1999 to 2019 in the primary analysis. A secondary analysis included data from 2020 to 2022 to examine the effect of the COVID-19 pandemic. We analysed patients in whom cardiovascular diseases (CVD) were listed as the main cause of death and DM as a contributing cause of death. In calculating age-adjusted mortality rates (AAMR) per 100 000 individuals, we used CVD mortality in young adults with comorbid diabetes as the numerator and the overall population as the denominator. We determined temporal trends by estimating the average annual percent change (AAPC) using the Joinpoint regression program.

Results: Among 3 309 079 individuals aged 15-44 years who died, 30 978 deaths were due to CVD with comorbid DM listed as a contributing cause. The overall AAMR increased from 1.08 per 100 000 individuals in 1999 to 1.23 per 100 000 individuals in 2019, with an average APC of 0.75 (95% CI, 0.31-1.20). Compared with 1999, the percentage increase in CVD deaths in 2019 among young adults with comorbid DM was +6.2%, whereas a decrease of 19.9% was observed among those without comorbid DM. Males had a higher AAMR than females (1.60 vs. 0.97). Non-Hispanic Black individuals and non-Hispanic American Indian/Alaska Native individuals had the highest AAMRs of 2.99 and 2.89, respectively. The AAMR was higher in rural regions compared to urban areas (1.63 vs. 1.23). The overall AAMR increased markedly from 1.23 in 2019 to 1.60 in 2022, with a similar pattern observed across demographic subgroups.

Conclusion: Our study reveals a rising trend in CVD mortality in young adults with DM as a contributing cause. Males, non-Hispanic Black individuals, and individuals from rural regions had higher AAMR than their counterparts. This warrants the development of specific healthcare policies aimed at these at-risk populations.

Lay summary: Our study shows that cardiovascular disease (CVD) deaths are increasing in young adults with diabetes mellitus listed as a contributing cause.

Objective: Transportation noise is increasingly recognized as a cardiometabolic stressor, but its relationship with type 2 diabetes mellitus (T2DM) remains poorly defined. We examined whether transportation noise exposure was associated with incident T2DM in a large, diverse U.S. healthcare system cohort.

Methods: We identified adults without baseline T2DM from the Houston Methodist Learning Health System Registry (2016-2023). Transportation noise exposure was assigned at the census block group level using the 2020 U.S. Department of Transportation National Transportation Noise Map. Five noise categories were examined: Road, Rail, Aviation, Road plus Aviation and Total. Cox proportional hazards models estimated associations across predefined categories, Quiet (≤45 dB), Moderate (45-54 dB) and Loud (≥55 dB), and per 10 dB increase, adjusting for demographics, cardiometabolic risk factors, socioeconomic vulnerability and PM₂.₅.

Results: Among 984 658 adults (2.1 million person-years), 39 587 developed T2DM (1.88 per 100 person-years). Loud rail noise (HR 1.14; 95% CI: 1.01-1.29) and loud total noise (HR 1.17; 95% CI: 1.03-1.33) were associated with higher T2DM risk. Continuous models showed similar patterns, with each 10 dB increase in rail noise (HR 1.09; 95% CI: 1.05-1.13) and road noise (HR 1.04; 95% CI: 1.01-1.08) associated with a higher hazard of incident T2DM. Effect sizes were modest but internally consistent and aligned with prior environmental noise studies.

Conclusion: Transportation noise, particularly rail noise, was associated with higher T2DM risk. Given plausible mechanisms involving sleep disruption and stress-related neuroendocrine activation, these findings add to evidence linking environmental noise to metabolic health and motivate further studies to evaluate causality and potential benefits of noise mitigation.

Aims: The precise mechanism of sodium glucose co-transporter 2 (SGLT2) inhibitor on reno-protective effect has been still unclear. In this study, we hypothesised that SGLT2 inhibitor prevents diabetic kidney disease via reduction of hypoxia-induced factors.

Materials and methods: In this multicenter, prospective, randomised, double blinded clinical trial, people with type 2 diabetes and microalbuminuria were randomised equally to empagliflozin (10 mg/day) (n = 40) and placebo (n = 39) and followed 24 weeks. The primary endpoint was change in urinary albumin creatinine ratio (ACR) and urinary liver type fatty acid binding protein (L-FABP) excretion from baseline to 24 weeks. Major secondary outcome was change in serum vascular endothelial growth factor (VEGF), angiopoietin-like proteins 2 (ANGPTL2), angiopoietin-like proteins 4 (ANGPTL4), and adrenomedullin (AM) levels.

Results: Although the reduction of ACR was significantly greater in the empagliflozin group than the placebo group at 4 and 12 weeks, the difference of change at 24 weeks between the two groups was not statistically significant (Empagliflozin group-Placebo group: -0.3643, 95% CI: -0.7571 to 0.0285, p = 0.0686). There was no difference in urinary L-FABP excretion between the empagliflozin and placebo groups. Serum VEGF and ANGPTL2 decreased significantly more in the empagliflozin group, whereas there were no significant differences in AM and ANGPTL4.

Conclusions: These results demonstrated that empagliflozin partially suppressed the hypoxia-induced angiogenic factors overproduction in addition to a declining trend in ACR in the early stage of diabetic kidney disease, which might contribute to the mechanisms of reno-protective effects of this agent (jRCTs051200147).

Aims: The timing of physical activity may influence metabolic health through interactions with circadian rhythms, yet its role in type 2 diabetes mellitus (T2DM) development is unclear. We investigated associations between time-of-day-specific physical activity and incident T2DM, and whether theoretically reallocating activity from morning to later in the day was associated with changes in T2DM risk.

Materials and methods: We included 4615 participants from The Maastricht Study cohort without diabetes (age 59.2 ± 8.6 years; 56.3% women). Device-based physical activity was measured over 7 days using activPAL monitors and classified into light-intensity physical activity (LPA) and moderate-to-vigorous intensity physical activity (MVPA), for morning (06:00-11:59 AM), afternoon (12:00-17:59 PM), evening (18:00-23:59 PM) and night (00:00-05:59 AM). Incident T2DM was assessed during a median 8.2-year follow-up. Cox proportional hazard and isotemporal substitution models were used, adjusted for sociodemographic and lifestyle factors, including diet, employment and sleep duration.

Results: During follow-up, 168 participants (3.6%) developed T2DM. Each additional 10 min/day of afternoon LPA or MVPA was associated with lower T2DM risk (LPA: hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.70-0.97; MVPA: HR 0.85, 95% CI 0.72-1.00). Evening MVPA was also inversely associated with T2DM risk (0.65; 0.45-0.93), whereas night-time MVPA was associated with an increased risk (3.64; 1.30-10.17). No significant associations were found of morning LPA and MVPA or evening and night LPA with T2DM incidence. Substitution analyses indicated that reallocating 10 min of morning LPA to afternoon LPA (HR 0.71; 0.54-0.95) or morning MVPA to evening MVPA (HR: 0.64; 0.43-0.96) was associated with a lower T2DM risk, while no other significant associations were observed.

Conclusions: Later-day physical activity, particularly in the afternoon, was associated with a lower incidence of T2DM, independent of intensity. This highlights the potential relevance of activity timing in relation to T2DM incidence.

Aims: As type 2 diabetes (T2D) continues to rise globally and remains a major driver of cardiovascular disease, its remission has emerged as a therapeutic target. Current evidence supports bariatric surgery and low-calorie diets with meal replacements. No clinical trial to date has evaluated plant-based dietary alternatives as an intensive lifestyle intervention (ILI) strategy, despite the emphasis on plant-based diets in current clinical practice guidelines for diabetes and cardiovascular disease. The REmission of diabetes using a PlAnt-based weight loss InteRvention (REPAIR) trial will assess whether a 52-week plant-based ILI targeting ≥15% weight loss is effective for diabetes remission in a multi-ethnic Canadian population.

Materials and methods: The REPAIR trial is a prospective, randomised, 2-arm, open-label, blinded-endpoint efficacy trial. Participants will include 160 adults with early T2D (<6 years) and living with obesity. They will be randomised to standard of care or a 2-phase ILI targeting ≥15% weight loss consisting of a 12-week weight loss phase on a plant-based total diet meal replacement, followed by a 40-week weight loss maintenance phase on a plant-based dietary pattern combined with a 16-week structured exercise program, and a 52-week (19-session) sustainable behaviour change curriculum. The primary outcome is diabetes remission (HbA1c <6.5% without glucose-lowering medication for ≥3 months) and the key secondary outcome is the proportion achieving ≥15% weight loss at 52 weeks.

Conclusions: This trial will provide high-quality clinical evidence on the use of plant-based ILIs to address the epidemics of obesity and diabetes to inform public health policies and programs in Canada and beyond.

Aims: Patients with type 2 diabetes mellitus (T2DM) have a significantly increased risk of cognitive impairment, and the protective effects of traditional hypoglycaemic drugs on cognitive function remain unclear. This study systematically evaluated the neuroprotective effects of GLP-1 receptor agonists (GLP-1RAs) based on randomized controlled trial (RCT) evidence, aiming to provide key evidence-based insights for optimizing diabetes management strategies.

Materials and methods: A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, and ClinicalTrials.gov databases to identify studies investigating the impact of GLP-1RAs on cognitive function in T2DM patients, with the search timeframe extending up to July 2025. The analysis focused on RCTs comparing the effects of GLP-1RAs versus placebo (or conventional therapy) on neurocognitive function in T2DM patients.

Results: Based on the inclusion criteria, 18 RCTs involving 11 114 participants were included in the primary meta-analysis. Pooled results demonstrated that, compared to the placebo group, GLP-1RA treatment significantly increased Mini-Mental State Examination (MMSE) scores by a weighted mean difference (WMD) of 1.33 (95% CI: 0.67-1.99; I² = 82%) and Montreal Cognitive Assessment (MoCA) scores by a WMD of 1.70 (95% CI: 0.83-2.56; I² = 96%). The effect size on MMSE was significantly greater with long-term GLP-1RA use (≥24 weeks) compared to short-term use (<24 weeks) (mean difference = 3.74; t = 6.52, df = 269, p < 0.0001; Cohen's d = 0.79). Sensitivity analyses yielded results closely aligned with the primary analysis, indicating robust stability. Jadad scale assessment confirmed that all included studies achieved a score ≥3.

Conclusions: Current evidence indicates that GLP-1 RA-based therapy may improve cognitive function in patients with type 2 diabetes mellitus compared with placebo. Furthermore, long-term administration or early initiation of GLP-1 RA treatment may offer greater cognitive benefits.

Aim: To assess the application of current waist-to-height ratio (WHtR) and waist circumference (WC) evaluation criteria and identify preferred recommendations for public health practise.

Materials and methods: Data were from three waves of the Chinese National Survey on Students Constitution and Health (CNSSCH) conducted in 2010, 2014 and 2019; abdominal obesity was classified using four WHtR and WC standards. Age- and sex-specific WHtR and WC percentile curves were generated using the LMS method. Prevalence of central adiposity by WHtR/WC and general obesity by BMI were compared. Predictive performance of the criteria was validated using an independent dataset with cardiometabolic risk factors.

Results: WHtR percentile curves showed a relatively flat trend with age in both sexes compared to WC curves. Abdominal obesity prevalence increased significantly from 2010 to 2019 across all criteria: international cut-off (0.46) (21.26%-27.66%), Chinese WC cut-offs (13.77%-19.64%), international WHtR cut-off (0.50) (9.12%-13.01%) and international WC cut-offs (7.95%-11.95%). All abdominal obesity criteria identified substantially more cases than BMI-based general obesity in 2019 (8.14%). The Chinese WC cut-offs showed superior predictive performance compared to the other three standards for cardiometabolic outcomes.

Conclusions: The Chinese WC cut-offs and international cut-off (0.50) are optimal for childhood abdominal obesity screening in China due to their public health applicability. Standardized global criteria are urgently needed to enhance research comparability.