Individuals with type 2 diabetes mellitus (T2DM) are at substantially increased risk of infections, yet effective strategies for infection prevention remain limited. Although adherence to healthy lifestyles has been associated with lower infection risk in the general population, whether these benefits extend to individuals with T2DM remains unclear. Moreover, the association between the American Heart Association’s Life’s Essential 8 (LE8) metrics and infection risk has not been investigated. Therefore, this study aimed to evaluate associations between multidimensional lifestyle factors, Life’s Essential 8 (LE8) scores, and infection incidence rate in T2DM, and to explore underlying pathways using multi-omics mediation analysis.
This prospective cohort included 12,885 UK Biobank participants with T2DM (mean age 60.1 years; 30.6% female), followed for a median of 13.1 years. Exposures were adherence to a healthy lifestyle (smoking, BMI, diet, physical activity, sleep, alcohol) and LE8 score (
n
= 9,164). The primary outcome was total incident infections, with pneumonia, gastroenteritis, and sepsis as secondary outcomes, ascertained from hospitalization and death registries. Multivariable negative binomial regression estimated associations as incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Mediation analyses were conducted using nuclear magnetic resonance metabolomics (
n
= 8,971; 325 biomarkers) and Olink proteomics (
n
= 1,078; 2,920 proteins), with candidate mediators identified via false-discovery-rate-controlled screening and effects estimated using bootstrap methods..
Ideal lifestyle adherence was associated with a 44% lower infection incidence rate (IRR 0.56, 95% CI 0.46–0.68), with similar reductions for pneumonia and sepsis. Key protective factors included never smoking, healthy BMI, adequate sleep, and physical activity. LE8 scores showed dose-dependent associations, with each 5-point increase linked to an 11% lower risk (IRR 0.89, 95% CI 0.87–0.91). Mediation analysis highlighted lipid and fatty acid metabolism, including degree of unsaturation, HDL-related lipids, and GlycA. Proteomic mediators, including TRAIL-R2 and Galectin-9, implicated inflammation and innate immunity.
Maintaining an ideal lifestyle and higher LE8 scores was associated with lower infection incidence rate in T2DM, partly mediated by lipid metabolism and immune-inflammatory pathways.
Ming-Ming Li, Hao-Jun Zhai, Xiao-Qiu Dai et al.· BMC Medicine· 0 citations
Background: Combining immune checkpoint inhibitors (ICIs) with chemotherapy has become a major clinical research focus. Patients with extensive-stage small-cell lung cancer (ES-SCLC) have been treated with different first-line ICI combinations in randomized controlled trials (RCTs), but the optimal combination strategy has not yet been determined. Our aim was to evaluate this strategy through a systematic review and meta-analysis. Methods: Articles published from inception to October 20, 2024 were systematically searched in PubMed, Cochrane CENTRAL, Embase, and MEDLINE. Candidates were RCTs using ICI treatments as first-line treatment for ES-SCLC. According to PRISMA guidelines, 3 independent investigators extracted data. Hazard/odds ratios (HRs/ORs) with their 95% confidence intervals (CIs) and adverse event (AEs) were extracted. ICI combinations were compared for overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and AEs. A random-effects model and Bayesian network meta-analysis were used. PROSPERO: CRD42023388838. Results: The meta-analysis included 8 RCTs with 3910 patients. Overall, ICI-chemotherapy provided superior OS (HR, 0.78; 95% CI, 0.72 to 0.86), PFS (HR, 0.73; 95% CI, 0.64 to 0.82), ORR (OR, 1.20; 95% CI, 1.01 to 1.42) and DCR (OR, 2.64; 95% CI, 1.32 to 5.24) compared with chemotherapy alone. A higher risk of any grade irAEs (OR, 3.88; 95% CI, 2.09 to 7.18) and grade ≥ 3 irAEs (OR, 5.54; 95% CI, 2.38 to 12.88) was associated with ICI addition. ICI-chemotherapy combinations did not differ significantly in OS, PFS, ORR, DCR, or safety. In the Bayesian ranking analysis, the PD-1 inhibitor–based regimens Serplu-EP and Nivo-EP achieved the highest efficacy rankings; Serplu-EP ranked first for both OS and PFS, followed by Nivo-EP. Efficacy and safety were effectively balanced in Serplu-EP and Adebre-EP. Similar results were shown in subgroup analyses. Conclusion: First-line ICI-chemotherapy combinations improved survival outcomes but increased the risk of irAEs, with no significant differences in efficacy or safety among ICI-chemotherapy combinations. Among the evaluated regimens, the PD-1 inhibitor–based Serplu-EP and Nivo-EP achieved the highest efficacy rankings, whereas Serplu-EP and Adebre-EP appeared to provide the most favorable efficacy-safety balance. Further head-to-head trials are warranted to confirm the optimal first-line ICI strategy for ES-SCLC.
Xiao-Qi Ye, Haoru Meng, Qiuyan Guo et al.· Medicine· 0 citations
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