Causal Links Between Type 2 Diabetes and Hypertension and TCM Intervention Prediction:a Comorbidity Perspective
LIU Yuhan
YANG Kongming
ZHANG Xixu
YIN Yuanping
Abstract：Objective To investigate the causal relationship between type 2 diabetes mellitus(T2DM)and hypertension using Mendelian randomization(MR),and to predict potential Chinese herbal medicines(CHMs)that may regulate both T2DM and hypertension.Methods Summary data from genome-wide association studies(GWAS)on T2DM and hypertension were obtained from public databases.MR analysis was performed using the TwoSampleMR package in R,with the inverse variance weighted(IVW)method as the primary approach for assessing genetic causal effects.Functional enrichment analysis of instrumental variable-proximal genes was conducted to explore relevant signaling pathways.The Coremine database was used to predict CHMs with potential regulatory effects on these genes,and information on their properties,flavors,meridian tropisms,and efficacy was summarized.Results MR analysis revealed that T2DM was associated with an increased risk of hypertension.Instrumental variable-proximal genes were mainly enriched in signaling pathways such as phosphatidylinositol-3-hydroxykinase(PI3K)/protein kinase B(Akt),rat sarcoma(Ras),mitogen-activated protein kinase(MAPK),and endocrine resistance.CHMs were predominantly warm in property,supplemented by cold and neutral properties;bitter in flavor,complemented by sweet and pungent flavors;primarily associated with the liver meridian,followed by the lung,spleen,stomach,and kidney meridians.Their main efficacy was clearing heat,followed by tonifying deficiency,and also included activating blood circulation,regulating qi,dispelling wind-dampness,resolving phlegm and relieving cough and asthma,and promoting diuresis and draining dampness.Representative CHMs with these high-frequency characteristics included Salviae Miltiorrhizae Radix et Rhizoma(Danshen),Ginseng Radix et Rhizoma(Renshen),Coptidis Rhizoma(Huanglian),Scutellariae Radix(Huangqin),Curcumae Radix(Yujin),Curcumae Longae Rhizoma(Jianghuang),and Astragali Radix(Huangqi).Conclusion This MR analysis suggests that T2DM may increase the risk of hypertension,potentially mediated through signaling pathways such as PI3K/Akt,MAPK,and Ras.Potential regulatory CHMs mainly include heat-clearing herbs,tonifying herbs,phlegm-resolving and cough-relieving herbs,and qi-regulating herbs,providing a reference for the prevention and treatment of diabetes complicated with hypertension using traditional Chinese medicine.
Keywords：type 2 diabetes mellitushypertensionmendelian randomizationgenetic causal effectgenetic correlationDanshenRenshenHuanglian
Publication Date：2026-01-20
Online Publishing Date：2026-07-17(First online date of this platform, not the publication date of the document)
Pages：12( 32-43 )