Key result
High adipose tissue insulin resistance (Adipo-IR) was associated with a higher risk of cardiac mortality compared with low Adipo-IR (HR 1.20; 95% CI 1.05-1.38) over 15.6 years.
Why the study?
Insulin resistance is a fundamental pathophysiology of cardiovascular disease, prompting this investigation into the association of adipose tissue insulin resistance with cardiac and cerebrovascular mortality compared with hepatic and skeletal muscle insulin resistance.
Is high adipose tissue insulin resistance associated with increased cardiac and cerebrovascular mortality compared with low adipose tissue insulin resistance or hepatic and skeletal muscle insulin resistance?
Cohort (n=12,306)
Is high adipose tissue insulin resistance associated with increased cardiac and cerebrovascular mortality compared with low adipose tissue insulin resistance or hepatic and skeletal muscle insulin resistance?
Insulin resistance specifically in adipose tissue (Adipo-IR) is independently associated with an increased risk of long-term cardiac mortality, even after adjusting for glycemic status, unlike hepatic or skeletal muscle insulin resistance.
Adipo-IR may refine cardiac mortality risk stratification beyond glycemia; extends tissue-specific IR observations but leaves causal and therapeutic implications open.
OBJECTIVE: Insulin resistance is a fundamental pathophysiology of cardiovascular disease. This study aimed to investigate the association of adipose tissue insulin resistance with cardiac and cerebrovascular mortality in comparison with hepatic and skeletal muscle insulin resistance. METHODS: This retrospective cohort study enrolled 12 306 participants (mean age, 64.5 years; female, 49.9%) who underwent a general health checkup in Hiroshima City between January 1982 and March 2003. Based on the median values of adipose insulin resistance index (Adipo-IR), homeostasis model assessment of insulin resistance (HOMA-IR), and Matsuda index, participants were divided into high and low insulin resistance groups in adipose tissue, liver, and skeletal muscle, respectively. RESULTS: Over a median 15.6-year follow-up period, 1001 cardiac and 629 cerebrovascular deaths occurred. Multivariate Cox proportional hazards regression analysis revealed that the hazard ratio (HR) for cardiac mortality was higher in the high Adipo-IR group than in the low Adipo-IR group (1.20 [95% confidence interval, 1.05-1.38]), whereas the HR for cerebrovascular mortality did not differ. In the stratified analyses, a significantly increased HR for cardiac mortality was observed in participants without antihypertensive or antihyperlipidemic medications in the high Adipo-IR group. HOMA-IR and the Matsuda index were also associated with cardiac mortality; however, these associations were not significant after adjusting for glycemic status. CONCLUSION: The association between insulin resistance in various tissues and cardiac mortality has been clarified. An increased risk of cardiac mortality was associated with insulin resistance in adipose tissue, independent of glycemic status.
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Sasaki et al. (2026) conducted a cohort in Insulin resistance and cardiovascular mortality risk (n=12,306). High adipose tissue insulin resistance (Adipo-IR) vs. Low adipose tissue insulin resistance (Adipo-IR) and hepatic/skeletal muscle insulin resistance (HOMA-IR, Matsuda index) was evaluated on Cardiac mortality (HR 1.20, 95% CI 1.05-1.38). High adipose tissue insulin resistance (Adipo-IR) was associated with a higher risk of cardiac mortality compared with low Adipo-IR (HR 1.20; 95% CI 1.05-1.38) over 15.6 years.
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