Our nationwide cross-sectional study examines the relevance of the TyG index to shifts in the hearing threshold among adult populations residing in the U.S. After correcting for confounding variables such as sex, age, race, educational level, BMI, smoking status, noise exposure, diabetes, hypertension, HDL cholesterol, C-reactive CRP, insulin, TCL, and glycated hemoglobin, the TyG index correlates with SF and HF PTAs in a nonlinear fashion, either positively or negatively (as depicted in Table 2 and Fig. 4). As per our awareness, this study represents the inaugural cross-sectional investigation into such relationship among U.S. adults. The findings intimate the TyG index to be a potential predictive biomarker for auditory threshold modifications.
In recent years, the incidence of metabolic disorders has escalated dramatically, posing not only significant risks to patient health but also imposing a weighty burden on socio-economic infrastructure. As a result, contemporary medical research has pivoted towards a more in-depth investigation of metabolic diseases from various standpoints. Insulin resistance (IR), a primary manifestation of numerous metabolic disorders (obesity, impaired glucose tolerance, metabolic syndrome, diabetes, etc.), is implicated in oxidative stress and inflammation [14]. Diminished insulin sensitivity results in decreased insulin-mediated glucose uptake, leading to increases in plasma glucose and TGs. Presently, the TyG index is deemed a dependable and economical surrogate biomarker for IR [15]. It has proven to be more efficacious than the HOMA-IR [16]. Numerous recent studies have established that an elevated TyG index reports elevated risks of diabetes, hypertension, and non-alcoholic fatty liver disease, and it is capable of predicting the onset of cardiovascular diseases [17,18]. Nevertheless, the correlation between the TyG index and hearing threshold fluctuations has not been well explored.
The pathophysiological underpinnings of HL are multifaceted, encompassing oxidative stress, inflammatory processes, systemic diseases, and genetic predispositions [19,20]. Previous studies have verified the association between HL and inflammatory diseases (diabetes and cardiovascular disease) [21]. Additionally, research has indicated a significant correlation between heightened serum triglyceride levels and auditory function [22]. Given that the IR can reflect the metabolic and inflammatory pathophysiological processes present at the time of sample collection, and the TyG index can reliably indicate IR indicator, our study endeavors to build the direct correlation between the TyG index and hearing thresholds. This will further allow us to probe the impact of insulin resistance and, potentially, metabolic diseases on the hearing threshold.
In this investigation, the TyG index is non-linearly related to both SF and HF PTAs. A bifurcated piecewise linear regression model assisted in identifying an inflection point at 8.35 and 8.57 for SF and HF PTAs, respectively. Prior to the inflection point, a negative correlation existed between the TyG index and both SF and HF PTAs. Conversely, a positive correlation emerged when the TyG index exceeded the inflection point. In a univariate analysis, we discovered significant associations between diabetes, insulin, and HBA1c and LF, SF and HF PTA hearing thresholds, a finding generally in alignment with previous investigations involving U.S. adults. For instance, in 2010, Bainbridge et al., selected 1,058 adult participants from the NHANES database for statistical analysis, and found a correlation between diabetes and the incidence of low, medium, and high-frequency HL [23]. Further, in 2017, Paul D Loprinzi et al. studied the relationship between biomarkers for cardiovascular disease and hearing sensitivity with the NHANES database and ascertained a positive correlation between human insulin levels and HF PTA [24]. In a 2019 study, Braffett BH et al. recruited 1,150 participants for a hearing study in the Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) and observed in follow-ups the relevance of higher HBA1c level to HL in speech and high frequencies [25].
The strong relevance of a high TyG index to increased SF and HF PTAs might be attributable to the fact that any disruption to the insulin system can trigger complications in any bodily system. Insulin receptors, glucose transporters, and insulin signaling components exist within sensory receptors, cochlear supporting cells, stria vasorum, and spiral ligament, which implies that auditory and balance functions can be easily impacted by impaired glucose utilization [26–31]. Furthermore, hyperglycemia resulting from insulin resistance can instigate a range of functional pathologies, including mitochondrial DNA damage [32,33]. Affected mitochondria can disrupt oxidative phosphorylation and ATP production, consequently leading to dysfunction in organ systems with high energy demands, such as the kidneys and the inner ear stria vascularis [34,35].
Obviously, a lower TyG index (< 8.35 corresponding to speech-frequency PTA and < 8.57 corresponding to high-frequency PTA) alters the relevance of the TyG index to hearing thresholds. When the TyG index is below the associated inflection point threshold, an elevated TyG index corresponds to diminished speech-frequency and high-frequency PTAs, indicating superior auditory acuity. Intriguingly, there is evidence to suggest that exceedingly low TG or FPG levels may have detrimental health impacts. According to a systematic investigation together with and a meta-analysis conducted recently, low FPG (< 4.0 mmol/L) reported elevated future risk of the all-cause mortality, the total stroke and the ischemic stroke, and primary cardiovascular diseases in people who do not have baseline diabetes or cardiovascular disease [36]. It is hypothesize that these findings are possibly attributable to cellular dy speech-frequencyunction. Pancreatic cells, which can remarkably help to regulate and maintain glucose, amino, and lipid homeostasis [37], may manifest hypoglycemia as a sign of dy speech-frequencyunction, and potentially a pivotal factor in diabetes pathogenesis [38]. Besides, in a prospective cohort analysis covering a large scale, low serum TG levels might heighten the hemorrhagic stroke risk in females [39], which could also predict the cardiogenic death in heart failure patients [39]. The TyG index exhibits a non-linear relationship with the hearing threshold, which implies that inappropriate TyG index level is possibly a potential target for intervention to forestall the development of speech-frequency and high-frequency HL. In our study, particularly low and high TyG would augment speech-frequency and high-frequency PTAs, thus escalating the risk of HL [40,41]. These results indicate the necessity for maintaining the TyG index at an optimal level, emphasizing that a TyG index that is either too high or too low can be deleterious.
This study offers many strengths. The data came from NHANES, which is methodologically standardized and robust. Participants who had abnormal otoscopy results, subpar tympanogram quality, or tympanogram compliance ≤ 0.3 ml were excluded to circumvent the analysis of data pertaining to conductive or mixed HL.
Despite these advantages, our study also has some limitations. As NHANES is a cross-sectional study, the findings of this study have not yet undergone validation. Data characterizing noise exposure were drawn from a pre-test hearing questionnaire administered 24 hours before the hearing test, which may not accurately capture participants' noise exposure history. Some potential confounding factors were not controlled for in the model.