## 4 Discussion  
This study investigated the association between the RHR and the HOMA-IR in 6188 participants in the KNHANES who had HOMA-IR and RHR data. The key outcomes indicated a significant association between RHR and HOMA-IR, with a higher RHR being associated with a higher probability of having a HOMA-IR \(\geq\) 2.5 after adjusting for all variables, including the general characteristics, lifestyle habits, and biochemical factors of the participants. After adjusting for the relevant variables, the ORs were 1.277 for 68-71 bpm, 1.599 for 72-79 bpm, and 1.919 for \(\geq\)80 bpm, indicating that an increase in the RHR tends to rise in proportion to an increase in HOMA-IR and, thus, that RHR levels may have a linear relationship with the level of insulin resistance. The RHR has potential for clinical use due to its simplicity, safety, affordability, and high efficiency [18]. Previous studies have explained the relationship between the RHR and T2 DM in terms of biological mechanisms, suggesting that an elevated RHR is driven by the activation of the sympathetic nervous system and represents an imbalance in the autonomic nervous system [19; 20]. Overactivation of the sympathetic nervous system can lead to decreased insulin sensitivity, increasing the risk of T2 DM. There are several studies on such an influence of the RHR on diabetes [21; 22; 23; 24]. Previous studies have reported that insulin resistance tends to increase with increasing RHR, with a significantly higher risk of developing T2 DM in individuals with higher RHR [25] and that insulin resistance mediates the association between the RHR and T2 DM, emphasizing the association of the RHR with T2 DM [9]. This is in line with the findings of the present study suggesting that the RHR may be a useful predictor of insulin resistance and related metabolic diseases. We hypothesized that the RHR may contribute to insulin resistance, and given that the RHR affects T2 DM [26] and insulin resistance is a major contributor to the development of T2 DM, this analysis clarified the extent to which different levels of the RHR affected the relationship with the HOMA-IR. The clinical implications of a linear relationship between the RHR and HOMA-IR suggest that the early detection and management of insulin resistance through the RHR may be crucial in the prevention of and treatment strategies for metabolic diseases. The linear relationship between the RHR and insulin resistance identified in this study is quite interesting. Most importantly, the finding that HOMA-IR levels tended to show a linear increase with increasing RHR suggested that the heart rate could play an important role in the development and progression of metabolic disease beyond just a physical marker, further emphasizing the possibility of the RHR having a direct association with insulin resistance. Although the mechanism has not been fully elucidated, a possible biological explanation is that the RHR is a marker of autonomic nerve activity [27]. Whereas activation of the parasympathetic nerves stimulates insulin secretion from the beta cells of the pancreas, lowering blood sugar levels, activation of the sympathetic nerves suppresses insulin production in the pancreas, resulting in a high fasting blood sugar level. Furthermore, overactivation of the sympathetic nervous system can induce vasoconstriction, which reduces blood flow to the skeletal muscle, thereby impairing glucose uptake [28]. Activation of the sympathetic nervous system also increases lipolytic activity within the white adipose tissue. This process is mediated by the activation of hormone-sensitive lipase (HSL), which catalyzes the breakdown of triglycerides into glycerol and free fatty acids. Glycerol, utilized in the liver for gluconeogenesis, elevates circulating glucose levels [29]. The resultant excess free fatty acids migrate to the peripheral tissues such as the skeletal muscle, where they accumulate as ectopic lipids, thereby impeding insulin signaling pathways and inducing insulin resistance [30].