脾虚样代谢-功能表型的构建及其与功能状态和长期健康结局的关联:基于UK Biobank前瞻性队列研究OA

Objective To construct a spleen deficiency-like metabolic-functional phenotype(SD-MFP)and examine its associations with muscle-limb function,fatigue,digestive symptoms,and chronic disease outcomes,thereby evaluating its construct and predictive validity.Methods A total of 375925 participants from the UK Biobank were included.Outcome-specific Cox models estimated the associations of SD-MFP with incident type 2 diabetes,cardiovascular disease,and all-cause mortality,with adjustment for age,sex,ethnicity,Townsend deprivation index,smoking,alcohol use,physical activity,and BMI.Stratified 10-fold cross-validation with locked out-of-fold predictions was used for exploratory descriptions of the 10-year Harrell C-index,inverse-probability-of-censoring-weighted Brier score,calibration,and decision curves.Results Each 1-standard-deviation increase in SD-MFP was associated with a 0.79 kg decrease in handgrip strength.Higher SD-MFP was also associated with increased odds of low handgrip strength,slow walking pace,fatigue,and digestive symptoms,with odds ratios of 1.33,1.46,1.22,and 1.09,respectively.In longitudinal analyses,higher SD-MFP was associated with increased risks of incident type 2 diabetes,cardiovascular disease,and all-cause mortality,with hazard ratios of 2.02,1.22,and 1.38,respectively.In out-of-fold internal validation,the Harrell C-indices of the extended models including SD-MFP were 0.834,0.717,and 0.747 for incident type 2 diabetes,cardiovascular disease,and all-cause mortality,respectively,compared with 0.791,0.711,and 0.735 for the corresponding base models.Conclusion Higher SD-MFP was associated with impaired muscle-limb function,fatigue,digestive symptoms,and elevated risks of type 2 diabetes,cardiovascular disease,and all-cause mortality.This study provides indirect population-level evidence supporting the traditional concepts of"the spleen as the foundation of acquired constitution","the spleen governing muscles and limbs",and the heart-spleen relationship theory of"disease of the child organ affecting the mother organ".SD-MFP can be applied for population stratification,risk identification and exploration of intervention targets.However,SD-MFP should be interpreted as a proxy phenotype rather than a clinical diagnosis of spleen deficiency syndrome,and its clinical application requires further validation in populations with traditional Chinese medicine syndrome differentiation.