METS-VF outperforms traditional adiposity indices in predicting overactive bladder risk: a NHANES-based cross-sectional study

Abstract

Background

Overactive bladder (OAB) represents a frequent urological disorder with a multifaceted etiology, yet the implication of visceral adiposity in its pathogenesis remains underexplored. Our objective was to evaluate the connection between the metabolic score for visceral fat (METS-VF) and OAB risk in a nationally representative USA population, besides comparing METS-VF predictive utility against conventional adiposity indices.

Methods

This cross-sectional analysis utilized National Health and Nutrition Examination Survey (NHANES) data from 6,366 participants. Multivariable logistic regression (LR) analysis, subgroup analyses, and receiver operating characteristic (ROC) were employed to ascertain the interaction of METS-VF with OAB. Furthermore, ROC analysis was implemented to contrast METS-VF diagnostic capabilities against body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR).

Results

The analysis included 6,366 participants; of them, 4,536 were diagnosed with OAB, showing a significant link between METS-VF and OAB (P<0.001). Notably, OAB prevalence increased progressively across METS-VF quartiles (Q1: 52.20%, Q2: 64.76%, Q3: 74.56%, Q4: 85.19%). After full adjustment for covariates, METS-VF remained significantly related to OAB, revealing a positive association [odds ratio (OR) =1.38, 95% confidence interval (CI): 1.22–1.57]. Subgroup analyses consistently elucidated a significant interconnection between METS-VF and OAB across various demographics. The restricted cubic spline (RCS) analysis results demonstrated a significant non-linear association between METS-VF and OAB (P=0.004). Moreover, METS-VF displayed a superior predictive ability for OAB, unlike conventional indices, including BMI, WC, and WHtR.

Conclusions

The METS-VF, an innovative composite indicator of visceral adiposity and metabolic dysfunction, serves as a robust and reliable predictor of OAB risk among adults in the USA. Its enhanced predictive capacity relative to traditional adiposity metrics highlights its potential application in clinical risk assessment and public health strategies aimed at mitigating visceral obesity-related urological conditions.

Highlight box.

Key findings

• A 6,366-participant National Health and Nutrition Examination Survey (NHANES) cross-sectional study found metabolic score for visceral fat (METS-VF) was positively associated with overactive bladder (OAB) [odds ratio (OR) =1.38, 95% confidence interval (CI): 1.22–1.57], with OAB prevalence rising from 52.20% to 85.19% across METS-VF quartiles.

• A non-linear link was confirmed, with OAB risk accelerating beyond METS-VF =6.1.

• METS-VF outperformed body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) in OAB prediction [area under the curve (AUC): 0.68 vs. 0.58–0.62] and correlated with OAB across all subgroups.

What is known and what is new?

• OAB is prevalent; visceral adiposity drives OAB, while traditional indices poorly reflect visceral fat; METS-VF assesses visceral fat/metabolic health for other diseases.

• Quantified METS-VF-OAB association/threshold; confirmed its utility in identifying OAB risk in metabolically obese normal-weight (MONW) individuals.

What is the implication, and what should change now?

• METS-VF enables precise OAB risk stratification and integrated metabolic-urological care.

• Add METS-VF to clinical screening, intervene in high-score individuals, and conduct prospective studies to verify causality.

Introduction

Overactive bladder (OAB) constitutes a clinically significant and globally prevalent syndrome defined by urinary urgency, frequency, and nocturia, with or without concomitant urge incontinence (1). Epidemiological evidence suggests that OAB affects approximately 10–20% of adults worldwide, particularly in older populations and females (2,3). In addition to its physiological implications, OAB exerts substantial psychosocial impacts, contributing to anxiety, depression, and social withdrawal (4), while increasing the likelihood of falls and fractures in elderly individuals as a result of nocturia-related incidents (5). Its pervasive disruption of daily activities, occupational productivity, and sleep quality underscores its status as a critical public health concern.

Obesity has been identified as a key risk factor for OAB (6), but emerging evidence highlights that visceral adiposity-rather than total body fat- drives OAB pathophysiology through systemic inflammation and biomechanical stress (7). Traditional adiposity indices, such as body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR), fail to adequately capture visceral adipose tissue (VAT) dynamics. They overlook sex-specific fat distribution, metabolic activity, and interactions with cardiorespiratory fitness (7), limiting their utility in OAB risk stratification. This critical gap necessitates novel biomarkers that integrate anatomical, metabolic, and functional dimensions to enhance predictive accuracy for OAB.The metabolic score for visceral fat (METS-VF) is an innovative composite index designed to accurately evaluate VAT content by integrating age, sex, metabolic score for insulin resistance (METS-IR), and WHtR (8). Unlike conventional indices, METS-VF synthesizes both structural (visceral fat distribution via WHtR) and functional (metabolic dysfunction via METS-IR) parameters, addressing the limitations of single-dimensional anthropometric measures. It has demonstrated robust performance in predicting multiple metabolic and inflammatory conditions, including hypertension (HTN), diabetes mellitus (DM), and osteoarthritis (8-10), validating its applicability across diverse clinical scenarios.

Notably, METS-VF offers distinct clinical advantages over traditional indices (8). First, it accounts for metabolic dysfunction—an overlooked mediator of OAB pathogenesis—by incorporating METS-IR, which reflects insulin resistance (IR) and dyslipidemia linked to bladder tissue inflammation and dysfunction. Second, its integration of sex as a variable addresses the gender-specific differences in fat distribution and OAB susceptibility, a factor ignored by BMI and WC. Despite these strengths, the association between METS-VF and OAB has not been previously explored.

Leveraging the National Health and Nutrition Examination Survey (NHANES), we analyzed 6,366 adults to investigate the METS-VF-OAB association. We postulated that the distinctive amalgamation of visceral fat (VF) and metabolic efficiency represented by METS-VF would surpass traditional indices across a wide range of demographic groups. Our results not only recast OAB as a metabolic-urological condition but also position METS-VF as a groundbreaking biomarker for precision preventive strategies, particularly in high-risk individuals with hidden visceral obesity, regardless of their BMI classification. We present this article in accordance with the STROBE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-643/rc).

Methods

Data source

The NHANES, administered by the USA National Center for Health Statistics, represents a population-based survey designed to determine the USA population’s health and nutritional status (https://www.cdc.gov/nchs/nhanes/), which is released biennially. Through a stratified, multistage probability sampling design, NHANES ensures sample representativeness and generalizable findings for the broader USA population. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Study population

Our analysis included 12 years (2007–2008, 2009–2010, 2011–2012, 2013–2014, 2015–2016, 2017–2018) of NHANES data, comprising 75,059 participants. Missing data were handled via listwise deletion (complete case analysis) for the following critical variables (to ensure data quality and avoid bias from imputation): outcome variable: OAB status (ascertained via questionnaire); exposure variable: METS-VF components (age, sex, METS-IR, WHtR); key covariates: BMI, WC, fasting glucose, fasting triglycerides (TG), high-density lipoprotein cholesterol (HDL-C). After excluding participants with missing values for any of the above variables, a final sample of 6,366 participants was included (see Figure 1 for a detailed flowchart).

Figure 1.

Study flowchart of participant selection for the cross-sectional analysis based on NHANES 2007–2018. Initial sample included 75,059 participants from 6 cycles of NHANES (2007–2008 to 2017–2018). Exclusions were applied for: (I) missing data on OAB status (assessed via OABSS questionnaire); (II) missing key metabolic and anthropometric parameters (BMI, WC, fasting glucose, TG, HDL). A final sample of 6,366 participants was included for the analysis of the association between METS-VF and OAB. BMI, body mass index; HDL, high-density lipoprotein; LDL, low-density lipoprotein; METS-VF, metabolic score for visceral fat; NHANES, National Health and Nutrition Examination Survey; OAB, overactive bladder; OABSS, Overactive Bladder Symptom Score; ROC, receiver operating characteristic; TG, fasting triglycerides; WC, waist circumference; WHtR, waist-to-height ratio.

METS-VF evaluation

The METS-VF index is a composite marker that estimates VF and associated metabolic status by integrating age, gender, WHtR, and METS-IR information, calculated as follows:

$$\begin{array}{l}METS\text{-}VF=4.466+0.011{\left(\text{ln}\left(METS\text{-}IR\right)\right)}^3+3.329{\left(\text{ln}\left(WHtR\right)\right)}^3\\ +0.319\left(gender\right)+0.594\left(\text{ln}\left(age\right)\right)\end{array}$$ [1]

where “gender” is coded where “male” =1 and “female” =0.

METS-IR is derived from:

$$METS\text{-}IR=\text{ln}\left(\left(2\times GLU\right)+TG\right)\times BMI/\left(\text{ln}\left(HDL\text{-}C\right)\right)$$ [2]

BMI is derived from:

$$BMI=Weight\left(kg\right)/height{\left(m\right)}^2$$ [3]

WHtR is derived from:

$$WHtR=WC\left(cm\right)/HT\left(cm\right)$$ [4]

Assessment of OAB

OAB is characterized by an excessive voiding reflex, leading to urgent urinary incontinence (UUI) and nocturia (11). OAB-related data were collected via structured questionnaire surveys administered by trained personnel via personal interviews. The presence of UUI was ascertained by asking: “During the past 12 months, have you leaked or lost control of even a small amount of urine when you felt the urge or pressure to urinate and were unable to reach the toilet in time?” The UUI severity was determined based on participants’ responses. Nocturia prevalence and severity were evaluated with the questions: “How often does this occur?” and “In the past 30 days, how many times per night did you typically awaken to urinate, from the moment you retired for the night until the time you arose in the morning?”, respectively. Moreover, OAB was assessed via the OAB Symptom Score (OABSS; Table S1), with a score ≥3 indicating that the participant has OAB (12).

Covariate assessment

This study considered a range of covariates identified from existing literature, including age, sex, race, education level, marital status, alcohol consumption, smoking history, HTN, DM, low-density lipoprotein (LDL), and total cholesterol (TC), based on their established or potential associations with OAB or metabolic health. Data were extracted from the NHANES modules of demographic, clinical examination, and questionnaire.

Statistical analysis

Herein, NHANES sampling weights were incorporated to produce nationally representative estimates. Continuous variables are summarized using weighted means and standard errors, while categorical variables are described using weighted frequencies and proportions. Multivariable logistic regression (LR) models were deployed to assess odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to ascertain the interconnection between METS-VF and OAB presence.

Three LR models were constructed to define the link between METS-VF and OAB. Model 1 was unadjusted; model 2 was adjusted for age, sex, and race; and model 3 was further adjusted for education level, marital status, alcohol consumption, smoking history, HTN, DM, LDL, and TC. To account for potential non-linear relations, smooth curve fitting was performed. In cases of observed non-linearity, segmented regression models were applied to estimate threshold effects within specified intervals. A two-step recursive algorithm was employed to identify the optimal breakpoint (K) that best partitioned the data by maximizing model likelihood. Subgroup stratification and interaction analyses were conducted based on gender, race, education, age, BMI, DM, HTN, smoking status, and alcohol consumption. All analyses incorporated the appropriate sampling weights in accordance with the NHANES 2007–2018 documentation “Demographic Variables and Sample Weights”. As the study included laboratory examination components, the mobile examination center weight “WTMEC2YR” was applied to ensure nationally representative estimates.

Analyses were performed through the Empower program (v2.0) and R Studio (v4.4.1), using a two-sided P<0.05 as the threshold for statistical significance.

Results

Baseline characteristics

This study enrolled 6,366 participants, with a weighted prevalence of OAB of 71.25% (Table 1). Unlike non-OAB participants, OAB patients exhibited significantly increased BMI, WC, WHtR, and METS-VF, which were 29.53±26.84, 101.16±16.45, 0.60±0.10, and 6.70±0.60, respectively (P<0.001). The OAB group displayed significantly higher proportions of females, widowed/divorced/separated individuals, and those with obesity (BMI ≥30 kg/m²), elevated fasting glucose, hypertriglyceridemia, alcohol consumption, smoking, HTN, and DM (P<0.05). To further explore these associations, METS-VF was stratified into quartiles (Table S2). With increasing METS-VF quartiles, there was a progressive rise in the proportions of older adults, widowed/divorced/separated individuals, HTN, DM, obesity, elevated fasting glucose, hypertriglyceridemia, and OAB. These trends aligned with the findings from Table 1, reinforcing the robustness of the observed correlations.

Table 1. Baseline characteristics of 6,366 participants stratified by OAB status.

Variables	Non-OAB (n=1,830)	OAB (n=4,536)	P value
Age (years)	41.42±15.48	53.01±16.96	<0.001
Gender			<0.001
Male	1,069 (58.42)	2,287 (50.42)
Female	761 (41.58)	2,249 (49.58)
Race			<0.001
Mexican American	326 (17.81)	681 (15.01)
Other Hispanic	224 (12.24)	484 (10.67)
Non-Hispanic White	793 (43.33)	2,039 (44.95)
Non-Hispanic Black	265 (14.48)	955 (21.05)
Other races	222 (12.13)	377 (8.31)
Marital status			<0.001
Married/living with partner	1,103 (60.27)	2,717 (59.90)
Widowed/divorced/separated	259 (14.15)	1,154 (25.44)
Never married	468 (25.57)	665 (14.66)
Education level			<0.001
Less than high school	339 (18.52)	1,105 (24.36)
High school	366 (20.00)	1,076 (23.72)
Above high school	1,125 (61.48)	2,355 (51.92)
History of heavy drinking (4–5 drinks/day)			<0.001
Yes	264 (14.43)	818 (18.03)
No	1,566 (85.57)	3,718 (81.97)
Smoked at least 100 cigarettes in life			<0.001
Yes	847 (46.28)	2,360 (52.03)
No	983 (53.72)	2,176 (47.97)
High blood pressure			<0.001
Yes	388 (21.20)	1,922 (42.37)
No	1,442 (78.80)	2,614 (57.63)
Diabetes			<0.001
Yes	131 (7.16)	837 (18.45)
No	1,699 (92.84)	3,699 (81.55)
Weight (kg)	79.83±20.43	83.11±21.42	<0.001
Height (cm)	169.33±9.70	167.52±9.97	<0.001
BMI (kg/m2)			<0.001
<25	655 (35.79)	1,208 (26.63)
25–30	657 (35.90)	1,511 (33.31)
>30	518 (28.31)	1,817 (40.06)
WC (cm)	95.45±15.53	101.16±16.45	<0.001
Fasting glucose (mg/dL)	102.66±22.37	112.09±38.58	<0.001
Total cholesterol (mg/dL)	190.48±40.31	191.92±41.35	0.20
Triglyceride (mg/dL)	113.65±66.08	119.30±66.07	0.002
HDL (mg/dL)	53.57±16.34	54.32±16.35	0.10
LDL (mg/dL)	114.17±35.42	113.75±35.96	0.67
WHtR	0.56±0.09	0.60±0.10	<0.001
METS-VF	6.31±0.68	6.70±0.60	<0.001

Continuous variables are expressed as weighted mean ± standard deviation and categorical variables as weighted percentage (%). Baseline characteristics of the study population were determined according to the presence or absence of OAB. BMI, body mass index; HDL, high-density lipoprotein; LDL, low-density lipoprotein; METS-VF, metabolically associated visceral fat index; OAB, overactive bladder; WC, waist circumference; WHtR, waist-to-height ratio.

Connection between METS-VF and OAB

Multivariable LR analyses showcased a significant positive connection between METS-VF and OAB across the three models (Table 2). Within Model 3, each one-unit increment in METS-VF was related to a 38% higher OAB odds (OR =1.38, 95% CI: 1.22–1.57). When stratified into quartiles, METS-VF showed a dose-response relationship with OAB risk: the highest quartile individuals exhibited 88% greater OAB odds than the lowest quartile individuals (OR =1.88, 95% CI: 1.49–2.39). These connections remained significant after controlling for demographic and metabolic confounders.

Table 2. Multivariable logistic regression analysis of the association between METS-VF and OAB.

METS-VF	Model 1			Model 2			Model 3
	OR (95% CI)	P value		OR (95% CI)	P value		OR (95% CI)	P value
Continuous	2.50 (2.29–2.72)	<0.0001		1.49 (1.32–1.67)	<0.0001		1.38 (1.22–1.57)	<0.0001
Q1	Reference			Reference			Reference
Q2	1.64 (1.42–1.89)	<0.0001		1.20 (1.03–1.41)	0.02		1.17 (1.00–1.37)	0.047
Q3	3.09 (2.65–3.61)	<0.0001		1.78 (1.49–2.12)	<0.0001		1.64 (1.37–1.97)	<0.0001
Q4	5.65 (4.74–6.73)	<0.0001		2.27 (1.81–2.84)	<0.0001		1.88 (1.49–2.39)	<0.0001
P for trend	3.11 (2.80–3.45)	<0.0001		1.70 (1.48–1.95)	<0.0001		1.54 (1.33–1.78)	<0.0001

Model 1: no covariates were adjusted; model 2: adjusted for age, gender, and race; model 3: adjusted for age, gender, race, education level, marital status, history of heavy drinking (4–5 drinks/day), smoked at least 100 cigarettes in life, high blood pressure, diabetes, LDL, and TC. CI, confidence interval; LDL, low-density lipoprotein; METS-VF, metabolically associated visceral fat index; OAB, overactive bladder; OR, odds ratio; TC, total cholesterol.

Smooth curve fitting and threshold effect

Smooth curve fitting analysis manifested a non-linear interconnection between METS-VF and OAB risk (P=0.004 for log-likelihood ratio test), with an inflection point identified at a METS-VF value of 6.1 (Figure 2, Table 3). In fully adjusted models, participants with METS-VF ≤6.1 showed no significant increase in OAB risk (β=1.08, 95% CI: 0.88–1.33, P=0.45). Beyond the identified threshold, each unit increase in METS-VF was associated with a 0.76-unit rise in OAB risk (P<0.001). Altogether, the relation between METS-VF and OAB risk intensifies nonlinearly, with a significant acceleration in risk escalation beyond the inflection point of 6.1.

Figure 2.

Smooth curve fitting of the association between METS-VF and OAB risk. Solid red line: smooth curve fit of the association between METS-VF and OAB risk; blue dashed lines: 95% CI of the smooth curve; Black horizontal bar (bottom): distribution of METS-VF values across the study sample. CI, confidence interval; METS-VF, metabolic score for visceral fat; OAB, overactive bladder; OR, odds ratio.

Table 3. Threshold effect analysis of METS-VF and OAB.

OAB	β (95% CI)	P value
METS-VF
Model I	1.38 (1.22–1.57)	<0.0001
Model II
Inflection point	6.1
<6.1	1.08 (0.88–1.33)	0.45
>6.1	1.76 (1.44–2.16)	<0.0001
Log-likelihood ratio rest		0.004

Age, gender, race, education level, marital status, history of heavy drinking (4–5 drinks/day), smoked at least 100 cigarettes in life, high blood pressure, diabetes, LDL, TC were all adjusted for model I: univariable linear regression; model II: two-part regression model. CI, confidence interval; LDL, low-density lipoprotein; METS-VF, metabolically associated visceral fat index; OAB, overactive bladder; TC, total cholesterol.

Subgroup analysis

Consistently, subgroup analyses (Figure 3) displayed a significant positive link across all subgroups within Model 3 (P<0.0001). Notably, the strength of the correlation was more significant in specific subgroups: ≥50 years (OR =1.93, 95% CI: 1.59–2.34), female (OR =2.67, 95% CI: 2.33–3.05), other Hispanic individuals (OR =3.45, 95% CI: 2.54–4.68), participants with education levels above high school (OR =2.81, 95% CI: 2.49–3.16), widowed/divorced/separated participants (OR =2.65, 95% CI: 2.08–3.36), participants who do not consume alcohol (OR =2.60, 95% CI: 2.37–2.86), nor smoke (OR =2.61, 95% CI: 2.31–2.86), individuals without HTN (OR =2.16, 95% CI: 1.95–2.40), those with DM (OR =2.60, 95% CI: 1.78–3.79), and those with BMI ≥30 kg/m² (OR =6.77, 95% CI: 5.02–9.13).

Figure 3.

Subgroup analysis of METS-VF and OAB association. Subgroups were stratified by age (<50, ≥50 years), sex (male, female), BMI categories (<25, 25–30, >30 kg/m²), DM (yes/no), and HTN (yes/no). Adjusted ORs and 95% CIs are presented for each subgroup. BMI, body mass index; CI, confidence interval; DM, diabetes mellitus; HTN, hypertension; METS-VF, metabolic score for visceral fat; OAB, overactive bladder; OR, odds ratio.

Receiver operating characteristic (ROC) analysis

The ROC analysis outcomes showcased that METS-VF exhibited a significantly superior diagnostic ability for OAB relative to BMI, WC, and WHtR. Specifically, the AUCs for METS-VF, BMI, WC, and WHtR were 0.68, 0.58, 0.60, and 0.62, respectively (Figure 4, Table 4). Collectively, METS-VF exhibits superior discriminatory performance and predictive precision for OAB risk relative to conventional adiposity metrics (BMI, WC, and WHtR).

Figure 4.

ROC curve analysis comparing the performance of METS-VF and conventional adiposity indices in predicting OAB. ROC curves for four predictive indices: METS-VF, BMI, WC, and WHtR. Statistical comparison of AUCs was performed using the DeLong test. AUC, area under the curve; BMI, body mass index; METS-VF, metabolic score for visceral fat; OAB, overactive bladder; ROC, receiver operating characteristic; WC, waist circumference; WHtR, waist-to-height ratio.

Table 4. ROC curve parameters for adiposity indices predicting OAB.

Test	AUC (95% CI)	Best threshold	Specificity	Sensitivity
BMI	0.5804 (0.5650–0.5958)	28.9950	0.6623	0.4612
WC	0.6033 (0.5881–0.6185)	94.2500	0.5131	0.6424
WHtR	0.6235 (0.6085–0.6386)	0.5868	0.6563	0.5370
METS-VF	0.6799 (0.6657–0.6941)	6.7821	0.7546	0.5295

AUC, area under the curve; BMI, body mass index; CI, confidence interval; METS-VF, metabolically associated visceral fat index; OAB, overactive bladder; ROC, receiver operating characteristic; WC, waist circumference; WHtR, waist-to-height ratio.

Discussion

Based on nationally representative data from the NHANES, this study is the first to systematically explore the association between the METS-VF and the risk of OAB. Its core findings provide critical supplements for clinical practice and epidemiological risk stratification. First, multivariable LR analysis showed that after full adjustment for demographic factors, lifestyle variables, and comorbidities (e.g., HTN, DM), each 1-unit increase in METS-VF was significantly associated with a 38% higher risk of OAB (OR =1.38, 95% CI: 1.22–1.57). Moreover, this association exhibited a clear dose-response relationship across METS-VF quartiles (Q4 vs. Q1: OR =1.88, 95% CI: 1.49–2.39). More importantly, restricted cubic spline (RCS) analysis identified an inflection point at METS-VF =6.1; when METS-VF exceeded this threshold, the risk of OAB increased nonlinearly and accelerated (β=0.76, P<0.001). This threshold can provide a quantitative reference for the early identification of high-risk populations in clinical settings—for instance, patients with METS-VF approaching or exceeding 6.1 require enhanced monitoring of OAB symptoms, even if their BMI falls within the normal range. Notably, METS-VF demonstrated superior predictive capabilities for OAB, unlike traditional metrics: BMI, WC, and WHtR.

OAB represents a prevalent urological condition impairing quality of life and leading to significant economic burdens and elevated healthcare expenditures (13). Societal pressures and lifestyle changes have contributed to the rising incidence of OAB over time. While OAB symptom presentation may differ between genders due to anatomical and pathophysiological distinctions, shared underlying mechanisms in bladder pathophysiology likely exist. Disruptions in bladder function across both sexes may stem from structural and functional alterations in vascular perfusion, epithelial integrity, neuronal signaling, smooth muscle dynamics, and connective tissue remodeling, collectively contributing to OAB symptomatology (14-17). Notably, clinical assessments using lower urinary tract symptom questionnaires reveal comparable symptom profiles in elderly females and age-matched males, suggesting overlapping age-related pathogenic pathways (18).

In their systematic review, Hsu et al. reported growing evidence linking OAB to metabolic syndrome (METS) (19). Patients having METS are facing an escalated risk of developing OAB due to several interrelated pathophysiological mechanisms, including heightened sympathetic nervous system activity, oxidative stress, chronic low-grade inflammation, and endothelial dysfunction, alongside bladder wall ischemic injury at the storage phase. Additional contributing factors include reduced bladder as well as bladder neck perfusion, elevated non-esterified fatty acid levels, and diminished nitric oxide bioavailability (19,20). These metabolic disturbances can lead to structural and functional alterations in the bladder wall—such as disruptions in smooth muscle function or neural signaling—that may precipitate OAB symptoms. IR, a critical element of METS, is significantly influenced by obesity. Uzun et al. elucidated markedly elevated serum insulin concentrations in OAB patients relative to controls (21). The homeostasis model assessment of insulin resistance (HOMA-IR) index, a widely used index for quantifying IR, was significantly higher in the OAB group than in the control (22). Additionally, HDL levels were significantly reduced in females diagnosed with OAB (21). In a comparative analysis of various obesity metrics, METS-VF emerged as the most effective indicator of VF (23). Moreover, METS-VF exhibited enhanced sensitivity compared to BMI in predicting a range of systemic diseases (8-10). Our findings further support the utility of METS-VF, showing that it possesses robust predictive and evaluative performance in relation to OAB risk.

The identified connection between increased METS-VF and OAB risk (OR =1.38) is consistent with evolving evidence that links VAT to lower urinary tract dysfunction (24). In contrast to subcutaneous fat, VAT displays significant endocrine functionality, releasing IL-6 and TNF-α pro-inflammatory cytokines and adipokines (e.g., leptin and resistin) that may directly influence bladder sensory pathways (25-29). Experimental research utilizing rodent models has illustrated that the intravesical administration of IL-6 activates TRPV1 channels on bladder afferent nerves, thereby lowering the threshold for detrusor overactivity—a defining characteristic of OAB pathophysiology (30). Furthermore, leptin receptors are prominently expressed in human detrusor smooth muscle cells, with increased serum leptin levels correlating with heightened bladder contractility in vitro (28). These molecular interactions imply that mediators derived from VAT could potentially disrupt bladder neuromodulation through neuroimmune crosstalk.

Obesity may impose biomechanical influences on the anatomy of the pelvis. An increase in intra-abdominal pressure (IAP) resulting from VAT accumulation can alter the geometry of the bladder neck (7,31). This alteration is supported by urodynamic investigations indicating elevated post-void residual volumes in obese individuals (27). Our subgroup analysis, which identified a more robust connection between METS-VF and OAB in women (OR =2.67 for urgency incontinence), reinforces this hypothesis, particularly considering the gender-specific vulnerability to pelvic floor disorders. Importantly, METS-VF encompasses both metabolic dysfunction (assessed through metabolic equivalents of exercise) and VF accumulation (calculated as the cube of WC), thereby effectively capturing these multifactorial interactions compared to static anthropometric indicators, such as BMI or waist-to-hip ratio.

A pivotal discovery is the continued presence of METS-VF and OAB associations in individuals classified as normal weight (BMI of 18.5–24.9 kg/m²; OR =2.32), which challenges the traditional dependence on BMI for obesity identification. Approximately 30% of individuals classified as normal weight exhibited obesity-related metabolic abnormalities, including IR, elevated TG levels, blood pressure, atherogenic lipids, and adverse inflammatory markers—collectively termed the “metabolically obese normal-weight” (MONW) phenotype (32,33), likely to represent individuals with ectopic fat accumulation, a condition increasingly associated with cardiometabolic complications (34). Our findings indicate that individuals with MONW, who are frequently overlooked in clinical settings, may represent a high-risk demographic for OAB. This observation aligns with cross-sectional studies indicating that VF area, as quantified by computed tomography, is a predictor of incident OAB independent of BMI (27).

The enhanced predictive capability of METS-VF compared to conventional metrics (AUC =0.68 versus 0.58–0.62 for BMI, WC, and WHtR) arises from its innovative formulation, which is a composite measure that integrates VF content, metabolic efficacy, and sex-specific adipose distribution. This equation concurrently quantifies three essential dimensions: (I) anatomical fat distribution (as indicated by the waist³ component, representing VAT volume); (II) gender-specific fat allocation (the coefficient corresponding to male sex); and (III) dynamic metabolic capability (the METS component, which inversely weighs physical activity). This multidimensional approach permits METS-VF to identify individuals with discordant metabolic and morphological characteristics, such as those exhibiting a moderate BMI but inadequate cardiorespiratory fitness, who may face an elevated risk of OAB despite appearing “metabolically healthy” by traditional standards.

Although our findings are biologically plausible, several limitations warrant cautious interpretation. First, the cross-sectional design cannot establish a causal relationship: although there is a significant association between METS-VF and OAB, it is impossible to determine whether elevated METS-VF precedes OAB onset or whether OAB-related lifestyles (e.g., reduced physical activity) lead to visceral fat accumulation. For example, OAB patients may reduce exercise due to frequent nocturia, thereby increasing visceral fat; this reverse causality requires further verification by prospective cohort studies. Second, although we accounted for significant confounding variables (including DM and HTN), unmeasured variables—such as dietary sodium intake (a recognized bladder irritant) and levels of sex hormones (which modulate adipose tissue inflammation)—may partially confound the observed associations. Third, METS-VF was derived from regression equations rather than direct imaging of VAT (e.g., MRI), although its strong correlation with CT-measured VAT (AUC =0.78) supports its biological relevance (35). Additionally, OAB diagnosis relies on self-reported questionnaire data (OABSS ≥3), which carries risks of potential bias and misclassification: on the one hand, patients may underestimate symptoms such as nocturia and urgency due to privacy concerns (recall bias); on the other hand, the questionnaire does not distinguish between OAB subtypes (e.g., dry vs. wet OAB) and does not incorporate objective indicators such as urodynamic testing, which may lead to misclassification of some patients with asymptomatic detrusor overactivity or symptomatic non-OAB lower urinary tract symptoms. Although previous studies have shown high concordance between OAB questionnaires and objective measures (36), such misclassification may still slightly weaken the association between METS-VF and OAB in large-scale population studies. Future studies should integrate urinary biomarkers (e.g., nerve growth factor, ATP) to improve diagnostic accuracy.

Conclusions

This study establishes METS-VF as a multidimensional biomarker that robustly predicts OAB risk, transcending the limitations of traditional obesity metrics. By elucidating the interplay between visceral adiposity, metabolic dysfunction, and bladder pathophysiology, our findings advocate for a paradigm shift in OAB prevention—from isolated urologic management to integrated metabolic-urologic care. Future research should validate these associations longitudinally and explore mechanistically targeted therapies to disrupt the adiposity-OAB axis.

Supplementary

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Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.