Inflammatory burden index predicts arteriogenic erectile dysfunction: a mediation analysis involving the TyG index

Abstract

Introduction

Inflammation and metabolic dysregulation play important roles in the pathophysiology of erectile dysfunction. The inflammatory burden index (IBI), a composite biomarker integrating C-reactive protein (CRP), neutrophils, and lymphocytes, has emerged as a marker of systemic inflammatory load. However, the association between IBI and arteriogenic erectile dysfunction (AED) remains largely unexplored. To investigate the association between IBI and AED and to examine whether insulin resistance (IR), assessed by the triglyceride–glucose (TyG) index, mediates this relationship.

Methods

In this cross-sectional study, men aged 18-65 years were consecutively recruited from the local hospital between April 2023 and November 2025. Erectile function was assessed using the 5-item International Index of Erectile Function (IIEF-5), nocturnal penile tumescence and rigidity monitoring, and penile color Doppler ultrasonography. Multivariable logistic regression models were applied to evaluate the association between IBI and AED. Receiver operating characteristic curves were used to assess the predictive performance of inflammatory markers. Mediation analysis was conducted to explore the potential mediating role of IR using the TyG index.

Results

A total of 211 participants were included (109 AED; 102 controls). Patients with AED exhibited significantly higher inflammatory indices, including CRP, neutrophil-to-lymphocyte ratio (NLR), and IBI. In multivariable analysis, IBI remained independently associated with AED (OR = 1.626, 95% CI, 1.326-1.994, P < .001). Receiver operating characteristic analysis demonstrated that IBI achieved the highest discriminative performance among inflammatory markers (area under the curve [AUC] = 0.736), outperforming CRP and NLR. Mediation analysis revealed a significant indirect effect of TyG (β = −.1885), accounting for 24.08% of the total association between IBI and IIEF-5 scores.

Conclusion

Elevated IBI is independently associated with AED, and IR partially mediates this relationship, suggesting a potential inflammatory–metabolic pathway that may be involved in vascular erectile impairment, although causality cannot be established due to the cross-sectional design.

Introduction

Erectile dysfunction (ED) is defined as the persistent or recurrent inability to achieve or maintain a penile erection sufficient for satisfactory sexual activity.¹ Its prevalence increases substantially with age, with nearly 40% of men over 40 years experiencing some degree of ED.² As a condition often underrecognized and undertreated, ED negatively affects sexual well-being, psychological health, and overall quality of life.^3–5 The pathogenesis of ED is multifactorial, involving cavernous tissue integrity, hormonal balance, vascular regulation, neural pathways, and medication effects. Well-established risk factors include aging, obesity, smoking, depression, hypertension, and diabetes.⁶

In recent years, systemic inflammation has gained increasing attention as a key contributor to ED. Low-grade chronic inflammation impairs endothelial nitric oxide synthesis, promotes oxidative stress, and accelerates vascular remodeling.⁷ Given the small caliber and high sensitivity of penile vasculature, ED may serve as an early clinical indicator of systemic endothelial dysfunction.⁸ This is particularly relevant in arteriogenic erectile dysfunction (AED), a subtype caused by compromised penile arterial inflow, where inflammation is believed to play a central role.⁹ The inflammatory contribution becomes even more prominent in metabolic disorders such as obesity and diabetes, where inflammation and insulin resistance (IR) synergistically impair vascular health.¹⁰

Complete blood count (CBC)–derived inflammatory indices have emerged as convenient and cost-effective tools for assessing systemic inflammation.^11,12 C-reactive protein (CRP) has long been used as a traditional inflammatory biomarker in ED.¹³ Composite indices such as the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and systemic inflammatory response index have shown predictive value across diverse clinical conditions.^14–16 Several studies have also linked these indices to an increased prevalence of ED.^17–19 However, each biomarker has limitations: CRP is a nonspecific acute-phase reactant elevated in various pathological states²⁰; NLR can be altered by stress and medication²¹; and SII excludes acute-phase proteins, potentially reducing its sensitivity to acute inflammatory changes.

To overcome these constraints, the Inflammatory Burden Index (IBI)—a composite marker integrating CRP and NLR—has recently been proposed. Inflammatory Burden Index was initially developed in a multicenter study involving 6359 patients with various types of cancer to assess inflammatory burden and predict cancer prognosis. The results confirmed that IBI is a feasible biomarker for cancer prognosis.²² Elevated IBI has been associated with increased cardiovascular risk,²³ and one prior analysis using National Health and Nutrition Examination Survey (NHANES) data suggested a link between IBI and ED.²⁴ However, whether IBI is associated specifically with AED has not yet been thoroughly examined. Parallel to inflammation, IR is another fundamental determinant of endothelial dysfunction and impaired erectile physiology.²⁵ Insulin resistance reduces nitric oxide availability, induces endothelial apoptosis, and disrupts microvascular perfusion.²⁶ The triglyceride-glucose (TyG) index, derived from fasting triglyceride and glucose levels, is now recognized as a reliable surrogate marker for IR with strong predictive value for cardiometabolic diseases.²⁷ Prior studies have reported associations between higher TyG levels, endothelial dysfunction, and greater ED severity,²⁸ suggesting that metabolic dysregulation may serve as a pathway linking inflammation and AED.

Despite these findings, it remains unclear whether IR mediates the relationship between systemic inflammatory burden and AED. No study to date has jointly evaluated the association between IBI and AED while examining the potential mediating role of TyG-defined IR. Clarifying this interaction is clinically important, as it may refine early risk stratification and identify modifiable therapeutic targets. Accordingly, we asked the following research question: Is a higher IBI associated with an increased likelihood of AED, and to what extent is this association statistically mediated by IR as reflected by the TyG index? Using clinical data and robust statistical models—including multivariable regression and mediation analysis—we aimed to examine the association between inflammatory burden and AED and to explore potential inflammatory–metabolic pathways.

Methods

Study participants

Participants were consecutively recruited between April 2023 and November 2025, and all data were completed and locked before statistical analysis. We consecutively enrolled men aged 18-65 years who presented with ED to the andrology or urology outpatient clinics of the local hospital. Erectile function was evaluated using the 5-item International Index of Erectile Function (IIEF-5).²⁹ Erectile dysfunction was defined as an IIEF-5 score ≤21, in accordance with established clinical criteria. Eligible participants were required to report regular sexual activity with a stable heterosexual partner (≥1 intercourse per week) for at least 6 months.

Participants were excluded if they had a history of pelvic or perineal surgery and pelvic radiation; known endocrine disorders such as hypothyroidism, hyperthyroidism, androgen deficiency, or hyperprolactinemia; chronic inflammatory or autoimmune diseases (eg, rheumatoid arthritis or osteoarthritis); neurological disorders; alcohol abuse; or current use of medications known to affect sexual function (including antipsychotics, antidepressants, or phosphodiesterase type 5 inhibitors). To minimize confounding related to inflammation, lipid metabolism, or hormonal status, men receiving anti-inflammatory therapy, lipid-lowering agents (such as statins or fibrates), or androgen-modulating treatments (including testosterone replacement or anti-androgens) were also excluded.

A control group was recruited from the health examination centers of the same institutions, applying identical inclusion and exclusion criteria. Controls had no symptoms suggestive of ED and an IIEF-5 score ≥21 at enrollment. The study protocol was approved by the institutional ethics committees of all participating centers, and written informed consent was obtained from each participant prior to inclusion.

Hematologic and biochemical assessment

After completing a standardized clinical evaluation conducted by experienced andrologists, all participants underwent venous blood sampling between 07:00 and 09:00 following an overnight fast of at least 8 h. Hematologic and biochemical measurements were performed in the clinical laboratories of the participating centers using uniform protocols and rigorous quality-control procedures.

Complete blood count were obtained using an automated hematology analyzer (Sysmex XN-9000, Sysmex Corporation, Kobe, Japan), from which neutrophil and lymphocyte counts were extracted. Serum total cholesterol (TC) and triglycerides (TG) were measured enzymatically, and fasting blood glucose (FBG) was assessed using the glucose oxidase method. C-reactive protein and total testosterone (TT) levels were quantified by chemiluminescent immunoassay.

The IBI was calculated as: IBI = CRP (mg/l) × neutrophils/lymphocytes. Triglyceride-glucose, used as a surrogate of IR, was computed according to the formula: TyG index = ln [Fasting TG (mg/dl) × FBG (mg/dl)]/2. All assays were performed by trained laboratory personnel who were blinded to participants’ clinical information. Internal calibration and external quality assurance were routinely implemented to ensure the accuracy and reliability of the measurements.

Assessment of AED

All patients diagnosed with ED underwent nocturnal penile tumescence and rigidity (NPTR) monitoring using the RigiScan™ device (GOTOP, United States) for 2 consecutive nights under standardized sleep conditions, avoiding behaviors that could interfere with nocturnal erections. Nocturnal penile tumescence and rigidity parameters included baseline and tip rigidity, penile tumescence, number of erectile episodes, and the duration of the longest event. Nocturnal penile tumescence and rigidity was considered normal if either of the following criteria was met: (1) at least 3 erectile episodes lasting ≥10 min with tip rigidity ≥70% during a single night; or (2) an increase in penile circumference of ≥3 cm at the base or ≥2 cm at the tip. Recordings not fulfilling these criteria were classified as abnormal.³⁰

Participants with abnormal NPTR findings subsequently underwent penile hemodynamic assessment via color duplex Doppler ultrasonography (CDDU). After intra-cavernosal injection of 20 μg alprostadil (Caverject®, Pfizer, NY, United States), CDDU was performed using an Aixplorer™ ultrasound system (Supersonic Imagine, Aix-en-Provence, France) by experienced radiologists. Peak systolic velocity (PSV) and end-diastolic velocity (EDV) of both cavernosal arteries were measured at baseline and then at 5-min intervals up to 25 min post-injection. Arteriogenic erectile dysfunction was diagnosed when both cavernosal arteries demonstrated a PSV < 30 cm/s and EDV < 5 cm/s, indicating impaired penile arterial inflow.^31,32

Statistical analysis

Statistical analyses were performed using SPSS (version 26.0, SPSS Inc., Chicago, IL, United States). Two-tailed P < .05 was considered statistically significant. Data distribution was assessed by the Shapiro–Wilk test. Normally distributed variables are expressed as mean ± SD and compared using the independent-samples t test, whereas skewed variables are presented as median (IQR) and compared using the Mann–Whitney U test. Categorical variables were analyzed using the chi-square test. Multivariate logistic regression analysis was used to identify independent factors associated with AED. Results are reported as ORs with 95% CIs. In addition, IBI was categorized into quartiles based on its distribution, and multivariable logistic regression was used to assess the association across quartiles, with Q1 as the reference. A trend test was performed using the quartile variable as an ordinal term. Multicollinearity among covariates was assessed using variance inflation factors, with values <5 considered acceptable. In the multivariable logistic regression analysis, composite indices were not entered together with their individual components in the same model in order to avoid overadjustment and potential collinearity. The adequacy of the sample size was evaluated using the events-per-variable (EPV) principle. In the present study, 109 AED events and 10 covariates yielded an EPV of approximately 10.9, which meets the recommended threshold (≥10) for logistic regression models. Diagnostic performance of CRP, NLR, and IBI for AED was assessed through receiver operating characteristic curve analysis. Area under the curves (AUCs) and 95% CIs were calculated, and optimal cut-off values were determined using the Youden index. Comparisons between AUCs were performed using DeLong’s test.

To examine whether IR mediated the association between inflammatory burden and erectile function, mediation analysis was conducted with IBI as the exposure, TyG as the mediator, and IIEF-5 as the outcome. A multiple mediation analysis was conducted using the SPSS PROCESS macro (Model 4) developed by Hayes. Models were adjusted for age, BMI, smoking status, cardiovascular disease (CVD), diabetes mellitus (DM), TC, and TT. Indirect, direct, and total effects were estimated using bootstrapping (5000 samples), and mediation was considered significant when the 95% CI of the indirect effect did not cross zero. Mediation analysis was conducted to explore potential statistical mediation pathways, and these analyses were considered exploratory given the cross-sectional design.

Results

Baseline characteristics

A total of 211 men were enrolled, including 109 with AED and 102 controls. As shown in Table 1, age (36.05 ± 6.79 vs. 34.49 ± 6.31 years, P = .087) and BMI (24.06 ± 2.35 vs. 23.61 ± 1.60 kg/m², P = .109) were similar between groups, as were smoking status and exercise habits. Compared with controls, AED patients showed a less favorable metabolic profile, with higher TC (153.59 ± 22.98 vs. 143.79 ± 23.72 mg/dl, P = .007) and TG (133.05 ± 41.19 vs. 115.55 ± 30.57 mg/dl, P = .001). Inflammatory markers were notably elevated in the AED group, including CRP (1.50 vs. 1.09 mg/l, P < .001), NLR (2.48 ± 0.98 vs. 1.92 ± 0.77, P < .001), and IBI (3.29 [IQR 2.96] vs. 1.89 [IQR 1.53], P < .001). Total testosterone was slightly lower in AED patients but without statistical significance (17.23 ± 3.99 vs. 17.99 ± 4.09 nmol/L, P = .171). Cardiovascular disease was more common in the AED group (33.03% vs. 19.61%, P = .027), while DM prevalence was similar. In summary, men with AED exhibited higher lipid levels and a markedly increased inflammatory burden compared with controls.

Table 1.

Demographic and clinical characteristics of men with and without AED.

	AED (n = 109)	Control (n = 102)	P
Age (years)	36.05 ± 6.79	34.49 ± 6.31	.087a
BMI (kg/m2)	24.06 ± 2.35	23.61 ± 1.60	.109a
Personal history
Smoking, n (%)	41 (37.61)	32 (31.37)	.341b
Regular exercise, n (%)	32 (29.36)	31 (30.69)	.870b
Hematologic parameters
FBG (mg/dl)c	94.14 (12.60)	90.99 (12.47)	.217d
TC (mg/dl)	153.59 ± 22.98	143.79 ± 23.72	.007 a
TG (mg/dl)	133.05 ± 41.19	115.55 ± 30.57	.001 a
TT (nmol/l)	17.23 ± 3.99	17.99 ± 4.09	.171a
CRP (mg/l)c	1.50(0.91)	1.09 (0.82)	<.001 d
NLR	2.48 ± 0.98	1.92 ± 0.77	<.001 a
IBIc	3.29 (2.96)	1.89 (1.53)	<.001 d
CVD, n (%)	36 (33.03)	20 (19.61)	.027 b
DM, n (%)	18 (16.51)	13 (12.75)	.440b

Values are percentages or mean ± SD unless noted otherwise. Bold indicates P < .05.

Abbreviations: AED, arteriogenic erectile dysfunction; BMI, body mass index; CRP, C-reactive protein; CVD, cardiovascular disease; DM, diabetes mellitus; ED, erectile dysfunction; FBG, fasting blood glucose; IBI, Inflammatory Burden Index; NLR, neutrophil-to-lymphocyte ratio; TC, total cholesterol; TG, triglyceride; TT, total testosterone.

^aIndependent sample t tests.

^bChi-square test.

^cValues are presented as median with interquartile range. Regular exercise: Twice a week, at least 30 min each time.

^dMann–Whitney U test was used.

Multivariable logistic regression analysis

The multivariable logistic regression model identified several independent predictors of AED. As shown in Table 2, multivariable logistic regression analysis showed that IBI was independently associated with AED (OR = 1.626, 95% CI, 1.326-1.994, P < .001). When IBI was further categorized into quartiles, a clear dose–response relationship was observed. Compared with the lowest quartile (Q1), the odds of AED increased progressively across higher quartiles, reaching statistical significance in Q3 (OR = 3.215, 95% CI, 1.512-6.838, P = .002) and Q4 (OR = 7.964, 95% CI, 3.214-19.741, P < .001). A significant trend across quartiles was also identified (P for trend <.001), supporting a graded association between inflammatory burden and AED. Among metabolic parameters, TG were also independently associated with AED (OR = 1.010, 95% CI, 1.001-1.019, P = .038), whereas TC and FBG were not significant predictors after adjustment. Regarding clinical factors, age showed a modest but significant association with AED (OR = 1.055, 95% CI, 1.003-1.109, P = .036), and CVD remained independently correlated with increased AED risk (OR = 1.329, 95% CI, 1.085-2.999, P = .030). Body mass index, smoking status, DM, and TT levels were not significantly associated with AED in the adjusted model.

Table 2.

Multivariate logistic regression analysis for AED (AED vs. control).

Variable	Multivariate logistic regression
	OR	95% CI	P
Age	1.055	1.003-1.109	.036
BMI	1.071	0.903-1.272	.431
Smoking	1.284	0.664-2.482	.457
CVD	1.329	1.085-2.999	.030
DM	1.290	0.649-2.896	.311
FBG	1.027	0.993-1.062	.125
TC	1.009	0.996-1.023	.180
TG	1.010	1.001-1.019	.038
TT	0.942	0.868-1.024	.160
IBI	1.626	1.326-1.994	<.001
IBI (quartiles)
Q1 (<1.625)	Reference	Reference
Q2 (1.625-2.471)	1.482	0.702-3.120	.302
Q3 (2.471-3.978)	3.215	1.512-6.838	.002
Q4 (>3.978)	7.964	3.214-19.741	<.001
	P for trend		<.001

Multivariate logistic regression model included age, BMI, smoking status, CVD, DM, FBG, TC, TG, TT, and IBI. Bold indicates P < .05.

Abbreviations: AED, arteriogenic erectile dysfunction; BMI, body mass index; CVD, cardiovascular disease; DM, diabetes mellitus; FBG, fasting blood glucose; IBI, inflammatory burden index; TC, total cholesterol; TG, triglyceride; TT, total testosterone

Overall, these results demonstrate that IBI is a robust and independent predictor of AED, outperforming conventional inflammatory and metabolic markers. This aligns with Figure 1, where IBI showed the largest effect size among all included variables.

Figure 1.

Multivariable logistic regression analysis for predictors of AED. Abbreviations: AED, arteriogenic erectile dysfunction; BMI, body mass index; CVD, cardiovascular disease; DM, diabetes mellitus; FBG, fasting blood glucose; IBI, inflammatory burden index; TC, total cholesterol; TG, triglycerides; TT, total testosterone.

Diagnostic performance and mediation findings

As shown in Table 3 and Figure 2, IBI demonstrated moderate discriminative ability for identifying AED (AUC = 0.736, 95% CI, 0.669-0.803). Neutrophil-to-lymphocyte ratio showed moderate accuracy (AUC = 0.679, 95% CI, 0.606-0.751), while CRP exhibited a lower discriminative value (AUC = 0.654, 95% CI, 0.580-0.728). These findings indicate that IBI outperforms conventional inflammatory markers in distinguishing AED from controls.

Table 3.

Diagnostic performance for identifying AED.

Indicator	Optimal cut-off	Specificity	Sensitivity	AUC (95%CI)	P  value
CRP, mg/l	1.253	0.647	0.642	0.654 (0.580-0.728)	<.001
NLR	2.052	0.615	0.696	0.679 (0.606-0.751)	<.001
IBI	2.479	0.706	0.679	0.736 (0.669-0.803)	<.001

Abbreviations: AED, arteriogenic erectile dysfunction; AUC, area under the curve; CI, confidence interval; CRP, C-reactive protein; IBI, inflammatory burden index; NLR, neutrophil-to-lymphocyte ratio.

Figure 2.

Receiver operating characteristic curve analysis of inflammatory biomarkers for identifying AED. (A) C-reactive protein; (B) NLR; (C) IBI. Abbreviations: AED, arteriogenic erectile dysfunction; CRP, C-reactive protein; IBI, inflammatory burden index; NLR, neutrophil-to-lymphocyte ratio; ROC, receiver operating characteristic.

Mediation analysis further revealed that IBI had a significant total effect on IIEF-5 scores (β = −.7829, 95% CI, −1.1544 to −0.4113), and the direct effect remained significant after adjustment (β = −.5944, 95% CI, −0.9733 to −0.2302) (Table 4). A significant indirect effect via the TyG index (β = −.1885, 95% CI, −0.3336 to −0.0634) accounted for 24.08% of the association (Figure 3). This suggests that IR may statistically account for part of the association between inflammatory burden and erectile function.

Table 4.

Serial multiple mediation test (TyG).

	Effect	BootSE	BootLLCI	BootULCI	Proportion mediated
Total effect	−0.7829	0.1884	−1.1544	−0.4113	—
Direct effect	−0.5944	0.1883	−0.9733	−0.2302	75.92%
Total indirect effect: IBI → IR (TyG) → IIEF-5	−0.1885	0.0702	−0.3336	−0.0634	24.08%

Adjusted for age, BMI, smoking status, CVD, DM, TC, and TT. This table shows the mediation analysis of IBI and TyG on erectile function.

Abbreviations: BMI, body mass index; CVD, cardiovascular disease; DM, diabetes mellitus; IBI, Inflammatory Burden Index; IIEF-5, International index of erectile dysfunction-5; LLCI, lower limit of confidence interval; TC, total cholesterol; TT, total testosterone; TyG, triglyceride-glucose index; ULCI, upper limit of confidence interval.

Figure 3.

Mediation analysis of the association between IBI and erectile function. Mediation model illustrating the indirect effect of IR, assessed by the TyG index, on the association between IBI and erectile function measured by the IIEF-5. Abbreviations: IBI, inflammatory burden index; IIEF-5, international index of erectile function-5; IR, insulin resistance; TyG, triglyceride–glucose.

Discussion

In this study, we examined the association between systemic inflammatory burden and AED and further evaluated whether IR, assessed using the TyG index, contributed to this relationship. Several key observations emerged. First, patients with AED exhibited higher levels of inflammatory markers, and the IBI showed a stronger association with AED than traditional single-parameter indicators. Second, IBI demonstrated superior discriminative ability for identifying AED compared with CRP and NLR. Third, our mediation findings suggest that IR, as reflected by the TyG index, may statistically account for part of the observed association between systemic inflammatory burden and erectile function. However, given the cross-sectional design, these findings should be interpreted as associations rather than evidence of causal pathways.

The present findings align with and expand upon existing evidence linking systemic inflammation to ED. The IBI, which integrates CRP, neutrophil, and lymphocyte parameters, provides a more comprehensive assessment of inflammatory status than individual biomarkers.³³ C-reactive protein is a well-established acute-phase protein widely used as an indicator of systemic inflammation in ED,^13,34,35 while neutrophils and lymphocytes contribute to endothelial injury, vascular dysregulation, and subsequent tissue remodeling.¹⁹ Prior studies have demonstrated associations between ED and single inflammatory markers such as NLR, which has been linked to increased ED prevalence and vascular risk.^17,19,36 In contrast, our results show that IBI offers stronger discriminatory performance, likely due to its multidimensional approach that captures both acute-phase responses and immune-cell dynamics, reflecting overall inflammatory burden more accurately than isolated markers. A recent NHANES analysis also reported a positive association between IBI and ED.²⁴ However, that study has important limitations. Erectile dysfunction was assessed using a single self-reported question, which may underestimate prevalence and does not differentiate etiological subtypes. Moreover, NHANES does not capture information on the use of erectile function–improving medications, such as Phosphodiesterase type 5 (PDE5) inhibitors, making it difficult to exclude pharmacological influences. Compared with that population-based analysis, our study provides more refined clinical insights by focusing specifically on AED, objectively confirmed through NPTR monitoring and duplex Doppler ultrasonography. Additionally, by incorporating the TyG index, we were able to evaluate the potential contribution of IR—an aspect not investigated in the NHANES study. These methodological differences enhance the precision of phenotype classification and offer more mechanistic insight into the inflammation–metabolic profile associated with AED.

The association between IBI and AED may be partly understood through the established relationship between systemic inflammation and endothelial impairment.³⁷ Chronic low-grade inflammation has been shown to reduce nitric oxide bioavailability, promote oxidative stress, and induce endothelial apoptosis and vascular remodeling,^38,39 all of which can compromise penile arterial inflow. Given the small caliber of penile arteries, these changes may disproportionately affect erectile hemodynamics, providing a plausible explanation for the stronger inflammatory profile observed in AED.⁴⁰ Our mediation results further suggest that IR, reflected by the TyG index, contributes to this association. Insulin resistance is a recognized risk factor for ED and is thought to impair endothelium-dependent vasodilation through disrupted PI3K/Akt signaling and increased metabolic stress.⁴¹ Importantly, inflammation is also considered a driver of IR, as pro-inflammatory cytokines can interfere with insulin receptor pathways.⁴² Thus, part of the observed relationship between IBI and erectile function may reflect an inflammation-induced metabolic pathway, while the remaining portion is consistent with inflammation-related vascular impairment independent of IR. Although these mechanisms cannot be confirmed due to the observational design, the pattern of our findings aligns with prior literature linking inflammation, IR, and endothelial dysfunction.

Clinically, these findings suggest that IBI may serve as a potential indicator associated with a higher likelihood of AED. Given its moderate discriminative ability, IBI may be considered as an adjunctive marker in the initial assessment of men with erectile symptoms, particularly in settings where specialized vascular testing is not readily available. However, its performance alone is insufficient for clinical diagnosis, and it should not be used as a standalone diagnostic tool. The partial mediation by TyG highlights a potential link between inflammatory burden, metabolic status, and erectile function. Given that both IBI and TyG are derived from simple and widely available laboratory tests, they may provide additional information to support risk assessment when interpreted alongside other clinical parameters. This combined approach may help identify individuals who could benefit from further vascular evaluation or targeted management of systemic inflammation and metabolic dysfunction. Nevertheless, these findings should be interpreted with caution. Due to the cross-sectional design, the temporal sequence required to establish mediation cannot be confirmed, and the observed indirect effect reflects statistical mediation rather than a definitive causal or biological pathway.

Several limitations should be acknowledged when interpreting our findings. First, although the study included objective assessments of erectile function through NPTR monitoring and CDDU, its cross-sectional design precludes any inference regarding causality, and the observed associations should not be interpreted as directional or mechanistic relationships. Second, the recruitment strategy, with cases enrolled from andrology/urology clinics and controls from health examination centers, may introduce selection bias. Although consistent inclusion and exclusion criteria and standardized ED assessment were applied, residual differences between groups cannot be entirely excluded. Third, although IBI and TyG provide practical and accessible measures of systemic inflammation and IR, they remain surrogate indices and may not fully capture the complexity of inflammatory or metabolic pathways. Fourth, medication use was carefully screened; however, undetected use of agents influencing vascular or metabolic status cannot be entirely ruled out. In addition, although we adjusted for several important covariates, including demographic and metabolic factors, residual confounding cannot be excluded. Some potentially relevant factors were not comprehensively assessed, including psychological conditions (eg, anxiety and depression), specific medication use, detailed lifestyle behaviors (such as physical activity, dietary patterns, and sleep quality), and the full spectrum of metabolic syndrome components. These variables may independently influence both inflammatory burden and erectile function, thereby potentially affecting the observed associations. Moreover, no internal or external validation, calibration assessment, or decision curve analysis was performed, which may limit the evaluation of its clinical utility. Finally, mediation analysis can only describe statistical pathways rather than physiological mechanisms, and the proportion mediated should be interpreted with caution. Future longitudinal and interventional studies are required to clarify the temporal sequence and causal relationships among inflammation, IR, and AED.

Conclusion

In this clinical study, higher levels of the IBI were associated with a greater likelihood of AED, and IBI demonstrated superior discriminative performance compared with traditional inflammatory markers. Mediation analysis further indicated that IR, reflected by the TyG index, accounted for part of this association, suggesting an interplay between inflammatory and metabolic pathways in vascular erectile impairment. Given that both IBI and TyG are derived from routine laboratory tests, these findings support their potential use as practical markers for risk stratification and preliminary evaluation in men with erectile symptoms. Further longitudinal and mechanistic studies are needed to confirm these associations and clarify their implications for clinical management.

Author contributions

X.D.: Conceptualization, Methodology, Writing—Original Draft, Funding Acquisition, Data Curation, Formal Analysis, Visualization, Investigation, Validation, Writing—Review & Editing. P.G.: Conceptualization, Methodology, Writing—Original Draft, Funding Acquisition. H.W.: Conceptualization, Methodology, Writing—Original Draft, Funding Acquisition. D.L.: Conceptualization, Methodology, Writing—Original Draft, Funding Acquisition, Project Administration, Resources, Supervision. H.J.: Conceptualization, Methodology, Writing—Original Draft, Funding Acquisition, Investigation, Validation, Writing—Review & Editing, Project Administration, Resources, Supervision. X.Z.: Conceptualization, Methodology, Writing—Original Draft, Funding Acquisition, Investigation, Validation, Writing—Review & Editing, Project Administration, Resources, Supervision. J.G.: Data Curation, Formal Analysis, Visualization. Y.Z.: Data Curation, Formal Analysis, Visualization. D.P.: Data Curation, Formal Analysis, Visualization. C.L.: Data Curation, Formal Analysis, Visualization. All authors have read and agreed to the published version of the manuscript. Drs. Xianming Dou, Pan Gao, and Herui Wang contributed equally to this manuscript.

Funding

This work was supported by grants from the Major Project of Anhui Provincial Education Department (Natural Science Category) (2025AHGXZK20069, 2025AHGXZK20070), the National Natural Science Foundation of China (No. 82371635), and the National Natural Science Foundation of China (No. 82071637).

Conflicts of interest

The authors declare no competing interests.

Data availability

The data are currently not publicly available due to participant privacy, but, if necessary, they are available from the corresponding author upon reasonable request.

Ethics approval and consent to participate

This study was performed in line with the principles of the Declaration of Helsinki. The study was approved by the Ethics Committee of the First Affiliated Hospital of Anhui Medical University. All study participants submitted written informed consent.