Hypertension and sarcopenia are major global public health problems among the aging society. This study aims to explore the causal associations and mediating effects of insulin resistance (IR) between hypertension and sarcopenia.

A bidirectional two-step Mendelian randomization (MR) was applied to determine the causal mediating role of IR in the pathway between hypertension and four sarcopenia related traits (right and left handgrip strength/HGS, Appendicular lean mass/ALM, and Usual walking pace/UWP) by using single nucleotide polymorphisms as instrumental variables to predict insulin, body mass index (BMI), fasting blood glucose (FBG), glycosylated hemoglobin a1c (HbA1c) and triglycerides (TG) genetically.

The IVW analysis indicated that there was a suggestive causality between hypertension and a reduced risk of UWP (OR = 0.952, 95% CI 0.913–0.991, P = 0.018), with triglycerides mediating a moderate proportion of this effect (6.985–13.666%).No significant causal associations were found between hypertension and right HGS, left HGS, or ALW (all P > 0.05). Each 1-standard deviation decrease in genetically determined right HGS (OR 0.963, 95% CI 0.935–0.992, P = 0.013) increased the suggestive risk of hypertension, each 1-standard deviation decrease in genetically determined left HGS (OR 0.958, 95% CI 0.930–0.986, P = 0.004), and ALM (OR 0.977, 95% CI 0.969–0.986, P = 0.000) also increased the risk of hypertension. No significant causal association was found between UWP and hypertension (P > 0.05). Compared with other indicators, insulin, strongly associated with the link between right HGS, left HGS, ALM and hypertension, has gained the notably total proportion mediated effect accounted from 11.378 to 21.297%. Furthermore, we systematically summarized the pathogenesis between hypertension and sarcopenia.

The study indicates the causality between hypertension and sarcopenia, potentially mediated by insulin resistance (BMI, insulin, FBG, HbA1c, and TG). It provides crucial evidence for the genetic association between hypertension and sarcopenia, while also offering insights for managing both conditions, particularly in terms of blood glucose, lipid, and weight control.