Glucosamine is a commonly used supplement, but concerns persist regarding its use in individuals with diabetes. This study aimed to examine the association of habitual glucosamine use with risks of all-cause and cause-specific mortality among individuals with type 2 diabetes, and to explore the potential mediating role of blood biomarkers in these associations. We included 19125 participants with type 2 diabetes from the UK Biobank who provided self-reported information on glucosamine use at baseline. Cox proportional hazards models were used to estimate the associations, with results presented as hazard ratios (HRs) and its 95% confidence intervals (CIs). Mediation analyses were conducted to estimate the extent to which selected blood biomarkers may be involved in these associations. Over a median follow-up of 13.5 years, 3045 deaths were recorded, including 1095 cancer deaths and 741 cardiovascular deaths. In multivariable-adjusted analyses, glucosamine use was associated with lower risks of all-cause, cancer, and cardiovascular mortality, with HRs (95% CIs) of 0.77 (0.68, 0.86), 0.82 (0.68, 0.99), and 0.73 (0.57, 0.94), respectively. These associations were generally consistent across several subgroups, including diabetes-related factors, demographic characteristics, lifestyle, medication use and health conditions. Furthermore, blood biomarkers (such as cystatin C, alkaline phosphatase, and C-reactive protein) explained 13.61% (95% CI, 8.26, 34.14) of the association between glucosamine use and all-cause mortality. Our findings suggest that glucosamine use was inversely associated with mortality in individuals with type 2 diabetes, with several blood biomarkers partly explaining this association; however, clinical trials are needed to confirm these findings.
Mengyang Xia, Rui Li, Yuxiang Wang et al.· The Innovation Nutrition· 0 citations
BACKGROUND
Peripheral artery disease (PAD) risk varies substantially across glycemic states, but glycemic status-specific proteomic features of PAD remain poorly characterized. This study aimed to provide comprehensive proteomic insights into PAD risk across the glycemic spectrum.
METHODS
We included 43,875 UK Biobank participants, categorized into normoglycemia, prediabetes, and type 2 diabetes (T2D). Associations between 2920 plasma proteins and PAD were assessed using Cox regression models. PAD-related proteins underwent pathway enrichment and protein-protein interaction (PPI) analyses, and protein predictors were selected via least absolute shrinkage and selection operator models. The differential expression-sliding window analysis identified proteomic changes across the glycemic continuum.
RESULTS
We identified 558 proteins associated with PAD risks, and those proteins were predominantly involved in pathways related to immune system regulation, inflammatory processes, and vascular remodeling. Two major PPI networks were identified, centered on tumor necrosis factor in normoglycemic participants and T-cell surface glycoprotein CD4 in those with T2D. The integration of protein predictors or derived protein risk scores into the clinical model significantly improved PAD prediction performance, achieving a maximum C-index of 0.834. Two proteomic peaks were revealed at glycated hemoglobin levels of 37 and 42 mmol/mol (5.5% and 6.0%), at which 11 and 4 proteins, respectively, showed potential causal associations with PAD.
CONCLUSION
This study revealed glycemic state-specific proteomic features of PAD risk. These findings suggest the involvement of innate immunity in normoglycemia, and adaptive immune dysregulation with chronic inflammation in T2D. Integrating proteomic data also improved PAD risk prediction. Further validation is warranted.
Hancheng Yu, Jijuan Zhang, Frank Qian et al.· Metabolism: Clinical and Exp...· 0 citations