Chai DJ, Zhu CY, Zhang YM, Rao ZC. Visceral fat area and remnant cholesterol in type 2 diabetes: Nonlinear associations and thresholds. World J Diabetes 2026; 17(5): 117583 [DOI: 10.4239/wjd.v17.i5.117583]
Corresponding Author of This Article
Zi-Chen Rao, MD, Department of Endocrinology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, No. 100 Minjiang Dadao, West District, Quzhou 324000, Zhejiang Province, China. rzc1522@wmu.edu.cn
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Endocrinology & Metabolism
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Observational Study
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May 15, 2026 (publication date) through May 14, 2026
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World Journal of Diabetes
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Chai DJ, Zhu CY, Zhang YM, Rao ZC. Visceral fat area and remnant cholesterol in type 2 diabetes: Nonlinear associations and thresholds. World J Diabetes 2026; 17(5): 117583 [DOI: 10.4239/wjd.v17.i5.117583]
Dong-Jian Chai, Department of Cardiology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou 324000, Zhejiang Province, China
Chun-Yan Zhu, Yi-Ming Zhang, Zi-Chen Rao, Department of Endocrinology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou 324000, Zhejiang Province, China
Author contributions: Chai DJ, Zhang YM and Rao ZC designed the research study, performed the research, analyzed the data, and wrote the manuscript; Zhu CY contributed to investigation, data curation, methodology, supervision, resources and project administration, and reviewed and edited the manuscript; all authors have read and approve the final manuscript.
Institutional review board statement: This study was approved by the Ethics Committee of Quzhou People's Hospital (Approval No. 2022-110).
Informed consent statement: Written informed consent was obtained from all participants.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: The datasets generated and/or analyzed during the current study are not publicly available due to institutional data protection policies but are available from the corresponding author on reasonable request.
Corresponding author: Zi-Chen Rao, MD, Department of Endocrinology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, No. 100 Minjiang Dadao, West District, Quzhou 324000, Zhejiang Province, China. rzc1522@wmu.edu.cn
Received: December 11, 2025 Revised: January 16, 2026 Accepted: March 10, 2026 Published online: May 15, 2026 Processing time: 152 Days and 1.3 Hours
Abstract
BACKGROUND
In people with type 2 diabetes (T2D), both visceral adiposity and remnant cholesterol have been associated with the cardiovascular risk that persists despite standard-of-care management. However, the relationship between visceral fat area (VFA) and remnant cholesterol–based indices, including residual cholesterol (RC) and the less-validated RC-inflammation index (RCII), remains uncertain.
AIM
To examine the associations between VFA and two remnant cholesterol-based indices—RC and RCII—in adults with T2D, and to characterise potential non-linear dose-response patterns, threshold effects, and subgroup differences.
METHODS
This cross-sectional study enrolled 1180 adult patients with T2D. VFA was quantified and categorized into tertiles. RC and RCII were calculated from standard lipid and inflammatory parameters. We applied multivariable linear regression to explore how VFA relates to RC and RCII. VFA was analysed both as a continuous measure and in tertiles, with models adjusted for demographic characteristics, lifestyle behaviours and relevant clinical factors. Smoothing curve fitting and two-piecewise linear regression were applied to explore non-linear and threshold effects. Prespecified subgroup and interaction analyses were also performed.
RESULTS
Across increasing VFA tertiles, body mass index (BMI), waist circumference, triglycerides, C-reactive protein, and the median levels of RC and RCII increased progressively. In fully adjusted models, VFA was positively associated with both RC and RCII. For RC, the β coefficient was 7.59 (95%CI: 0.65-14.53) in participants with VFA in the intermediate tertile and increased to 10.96 (95%CI: 3.50-18.42) in those in the highest tertile, compared with the lowest tertile, with a significant trend across tertiles (P for trend = 0.0036). For RCII, the corresponding β values were 6.74 (95%CI: -2.50 to 15.98) and 12.56 (95%CI: 2.63-22.49), respectively (P for trend = 0.013). In two-piecewise models, RC showed a clear threshold at 126 cm2 (likelihood ratio test P < 0.001), whereas RCII showed only a borderline threshold signal with an inflection at 118 cm2 (likelihood ratio test P = 0.060), which should be considered exploratory. In subgroup analyses, the VFA-RC association appeared stronger in participants with BMI < 28 kg/m2, while subgroup differences for RCII were modest.
CONCLUSION
In adults with T2D, higher VFA was associated, after multivariable adjustment, with higher RC, with a broadly similar but weaker pattern for RCII. The VFA-RC association showed a clear non-linear pattern with a threshold at 126 cm2, whereas the RCII threshold signal at 118 cm2 was borderline and should be considered exploratory.
Core Tip: This cross-sectional study of adults with type 2 diabetes (T2D) quantified visceral fat area (VFA) and examined its associations with residual cholesterol (RC) and the RC-inflammation index (RCII; RC/C-reactive protein). Higher VFA was independently associated with higher RC, and showed a clear non-linear pattern with a threshold at 126 cm2. RCII showed a weaker association and only a borderline threshold signal at 118 cm2, which should be interpreted as exploratory. These findings suggest that quantifying VFA may help contextualize remnant cholesterol-related burden beyond conventional lipid measures in T2D.
Citation: Chai DJ, Zhu CY, Zhang YM, Rao ZC. Visceral fat area and remnant cholesterol in type 2 diabetes: Nonlinear associations and thresholds. World J Diabetes 2026; 17(5): 117583
Type 2 diabetes (T2D) is associated with a substantially increased risk of cardiovascular disease (CVD) even when recommended glucose and lipid targets are achieved[1,2]. A substantial proportion of patients who achieve guideline-based targets for low-density lipoprotein cholesterol (LDL-C) still go on to develop cardiovascular events, implying that considerable cardiovascular risk persists despite LDL-C control[3,4]. Residual cholesterol (RC), which reflects the cholesterol content of triglyceride-rich lipoproteins, has attracted growing attention as a lipid component related to this residual risk[5]. Higher RC levels have been linked to adverse cardiometabolic profiles and higher rates of atherosclerotic events, independent of LDL-C and other conventional lipids[6,7]. In addition, indices that combine RC with inflammatory markers, such as the RC-inflammation index (RCII), have been proposed to reflect remnant cholesterol in the context of systemic inflammation[8,9]. As RCII is not yet widely validated, we treated it as an exploratory, hypothesis-generating biomarker in this study.
Visceral adiposity is another key feature of T2D and is often more strongly related to cardiometabolic abnormalities than general obesity[10,11]. Visceral fat is metabolically active and has been associated with insulin resistance, atherogenic dyslipidaemia and low-grade systemic inflammation[12,13]. Visceral fat area (VFA), measured by imaging or validated bioelectrical impedance devices, provides a quantitative estimate of visceral adiposity[14,15]. Previous studies have indicated that greater visceral fat accumulation is associated with an atherogenic lipid profile, characterised by higher triglyceride levels, lower high-density lipoprotein cholesterol (HDL-C), and increased concentrations of remnant-like particle cholesterol. It is also related to an increased risk of cardiometabolic diseases in various populations[16,17].
Most existing studies have been conducted in general adult or obese populations, using body mass index (BMI) or waist circumference (WC) as crude markers of adiposity and focusing on traditional lipid parameters such as triglycerides (TG), HDL-C or non-HDL-C[18,19]. Studies that specifically examine VFA in relation to RC are relatively limited, and epidemiological data on RCII are even more scarce[20,21]. Furthermore, there is little information on the detailed dose-response relationships and potential threshold effects between VFA and RC indices in patients with T2D[22,23].
In this context, we performed a cross-sectional analysis among adults with T2D who were enrolled in a real-world metabolic management centre. Our aims were twofold: (1) To examine the associations of VFA with RC and RCII in this high-risk population; and (2) To explore potential non-linear patterns and subgroup differences in these associations. By combining quantitative assessment of visceral fat with RC and an inflammation-weighted index (RCII), and integrating non-linear and subgroup analyses, we aimed to provide a more nuanced description of how visceral adiposity is associated with remnant cholesterol-related burden in patients with T2D[24,25].
MATERIALS AND METHODS
Study population
In this cross-sectional study conducted at the metabolic management centre of the Department of Endocrinology, the Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, we consecutively enrolled adult patients with T2D who underwent standardized evaluation between December 2022 and June 2025. T2D was defined in accordance with the 2023 criteria of the American Diabetes Association (ADA). Participants were eligible if they met all of the following conditions: (1) Age ≥ 18 years; (2) A confirmed diagnosis of T2D according to the 2023 ADA criteria; and (3) Completion of the baseline metabolic management centre evaluation with available measurements of VFA, fasting lipid profile and C-reactive protein (CRP).
We excluded patients with acute diabetic complications at the time of evaluation (such as diabetic ketoacidosis or hyperosmolar hyperglycaemic crisis) or with type 1 diabetes, gestational diabetes, or other specific forms of diabetes. We also excluded those with known severe hepatic or renal insufficiency (including decompensated cirrhosis, end-stage renal disease or maintenance dialysis); clinically evident acute infection or other acute inflammatory diseases; active cancer, cachexia, or other serious systemic illnesses that could markedly influence lipid or inflammatory profiles; pregnancy or lactation; missing data on VFA, key lipid parameters, CRP or other major covariates required for the analyses; and CRP values > 10 mg/L or extremely elevated TG (≥ 11.3 mmol/L), in order to minimise the impact of acute inflammation and marked hypertriglyceridaemia on RC measures.
In total, 1180 adults with T2D met the eligibility criteria and were retained for the final analysis. The study protocol complied with the principles of the Declaration of Helsinki and was reviewed and approved by the Ethics Committee of Quzhou People’s Hospital, Quzhou Affiliated Hospital of Wenzhou Medical University (Approval No. 2022-110). All participants gave written informed consent before enrolment and data collection.
Measurements
At baseline, trained nurses collected demographic data (age and sex), medical history, and information on smoking and drinking habits using a standardized questionnaire.
Body weight and height were measured with participants wearing light clothing and no shoes. BMI was calculated as body weight in kilograms divided by the square of height in metres (kg/m2). WC was assessed using a flexible tape placed midway between the lowest rib and the iliac crest, after a normal, relaxed expiration. In the metabolic management centre, VFA and subcutaneous fat area (SFA) were measured with a multifrequency bioelectrical impedance body composition analyser, in accordance with the manufacturer’s instructions.
Blood pressure was recorded on the right arm with the participant in a seated position, after resting for at least 5 minutes, using an automated blood pressure monitor. Two measurements were obtained 1-2 minutes apart, and the average values of systolic blood pressure and diastolic blood pressure were used in the analyses. Fasting venous blood samples were drawn in the morning after participants had abstained from food for at least 8 hours overnight. Glycated haemoglobin (HbA1c) levels were analysed by high-performance liquid chromatography. Serum biochemical indices, including lipids, uric acid, liver enzymes and creatinine, were measured on automated analysers using standard enzymatic methods. White blood cell (WBC) count, 25-hydroxyvitamin D [25(OH)D] and CRP were determined on automated biochemical or immunoassay platforms under routine internal and external quality control. Estimated glomerular filtration rate (eGFR) was derived from serum creatinine, age and sex according to the Chronic Kidney Disease Epidemiology Consortium equation.
Free triiodothyronine (FT3), free thyroxine and thyroid-stimulating hormone were assessed in the hospital laboratory using a chemiluminescence immunoassay.
RC and RCII were calculated from standard lipids and CRP [RC = total cholesterol (TC) - LDL-C - HDL-C; RCII = RC/CRP]. RCII was included to place remnant cholesterol in the context of systemic inflammation and was considered a hypothesis-generating biomarker given its limited validation.
Statistical analysis
We assessed the associations between VFA and RC indices (RC and RCII) using the following statistical methods. Continuous variables showed non-normal distributions and were therefore expressed as median (interquartile range), while categorical variables were described as n (%). We compared baseline characteristics across VFA tertiles using the Kruskal-Wallis test for continuous variables and the χ2 test for categorical variables, applying Fisher’s exact test when expected cell counts were small. The primary outcomes were RC and RCII, analysed as continuous variables. Findings involving RCII were interpreted cautiously because of its limited validation. The main exposure was VFA, which was treated both as a continuous variable and as tertiles (T1-T3), with T1 serving as the reference group. Associations between VFA and RC/RCII were assessed using linear regression models. Three models were constructed. The non-adjusted model included no covariates. Model 1 included adjustment for age and sex only. Covariates in model 2 were prespecified according to clinical relevance and their potential to confound the associations, and comprised markers of glycaemic control (HbA1c), thyroid function (FT3), renal function (eGFR) and liver function [alanine aminotransferase (ALT)], as well as age, sex, smoking status and drinking status. We summarised the associations using regression coefficients (β) together with their 95%CIs. Linear trends across VFA tertiles were assessed by entering the tertiles as an ordinal variable in the models.
To assess whether the relationships between VFA and RC/RCII were non-linear, we fitted smoothing curves using generalized additive models with penalized splines, while controlling for the covariates included in model 2. If the smoothed relationships suggested deviation from linearity, we then fitted two-piecewise (segmented) linear regression models to evaluate potential threshold effects. The optimal inflection point of VFA was determined using a recursive algorithm that searched over a series of candidate values to maximize model likelihood. We used a likelihood ratio test to compare the two-piecewise regression model with a single linear model.
We performed prespecified subgroup analyses to examine whether the associations between VFA and RC/RCII varied across subgroups defined by age, sex, obesity status, current smoking, current drinking and glycaemic control (HbA1c < 7.0% vs ≥ 7.0%). For each subgroup analysis, an interaction term between VFA and the stratifying variable was added to the fully adjusted model, and interaction P values were derived from the interaction (cross-product) terms in the models.
Analyses were restricted to participants with complete data. Statistical significance was defined as a two-sided P value less than 0.05. Data processing and modelling were performed with EmpowerStats (www.empowerstats.com) and R (version 4.2.2).
RESULTS
Baseline characteristics across VFA tertiles
Clinical and demographic features of the 1180 adults with T2D across VFA tertiles are summarized in Table 1. Median VFA increased from 63.0 cm2 in T1 to 92.0 cm2 in T2 and 130.0 cm2 in T3. Patients in the higher VFA tertiles were more frequently men and showed a higher prevalence of current smoking and drinking. RC increased steadily with VFA, with median values of 15.85 (2.71-26.30), 17.79 (6.96-30.16) and 22.43 (10.44-42.92) in T1-T3, respectively (P for trend < 0.001). RCII showed a similar graded pattern, rising from 0.92 (0.00-3.42) in T1 to 2.03 (0.00-6.75) in T2 and 4.05 (0.00-12.65) in T3 (P for trend < 0.001). TG increased and HDL-C decreased across VFA tertiles, whereas TC and LDL-C remained broadly comparable. Higher VFA was also associated with higher blood pressure, serum uric acid, liver enzymes (aspartate aminotransferase and ALT), markers of low-grade inflammation (CRP and WBC), and greater overall and abdominal adiposity (BMI, WC and SFA), while serum 25(OH)D levels declined modestly. Thyroid hormones remained within the euthyroid range, with only slightly higher FT3 in the highest VFA tertile. Based on these differences, we further evaluated the associations of VFA with RC and RCII using multivariable linear regression models (Table 2).
Table 1 Baseline characteristics of the study population across visceral fat area tertiles.
Associations of VFA with RC and RCII are presented in Table 2. VFA showed a clear positive association with RC. When VFA was entered as a continuous predictor, higher VFA was associated with higher RC after adjustment for all covariates (β = 0.09, 95%CI: 0.01-0.17, P = 0.033), and estimates were of similar size in the crude and age- and sex-adjusted models. When VFA was categorised into tertiles, RC was lowest in T1 and highest in T3. In models that accounted for all covariates, RC in the highest VFA tertile was about 11 units greater than in the lowest tertile (β = 10.96, 95%CI: 3.50-18.42, P = 0.004), with T2 showing intermediate values, and a clear linear trend across tertiles (P for trend = 0.0036). For RCII, the pattern was broadly similar. When VFA was entered as a continuous exposure, higher VFA was associated with higher RCII in both the unadjusted model and the model adjusted for age and sex, with β values of 0.09 (95%CI: 0.04-0.15; P = 0.0018) and 0.08 (95%CI: 0.02-0.14; P = 0.0057), respectively. After further adjustment for all covariates, the association became weaker and was no longer statistically significant (β = 0.10; 95%CI: -0.01 to 0.21; P = 0.078). In the tertile analysis, RCII levels in T2 and T3 were higher than in T1, with fully adjusted β coefficients of 6.74 (95%CI: -2.50 to 15.98; P = 0.154) and 12.56 (95%CI: 2.63-22.49; P = 0.013), respectively. Despite the non-significant difference between T2 and T1, there was an overall positive linear trend in RCII across increasing VFA tertiles (P for trend = 0.013).
Non-linear and threshold effects of VFA on RC indices
We explored the dose-response patterns between VFA and RC/RCII using spline-based smoothing techniques (Figure 1 and Table 3). For RC, the smoothing spline curve showed a non-linear association with VFA. RC increased with VFA and showed a turning point at 126 cm2, followed by a slight decline at higher VFA levels. In the two-piecewise linear regression model, the inflection point for VFA was estimated at 126 cm2. When VFA was < 126 cm2, each increment in VFA was associated with higher RC (β = 0.24, 95%CI: 0.12-0.35; P < 0.0001). In contrast, at VFA ≥ 126 cm2, RC decreased with increasing VFA (β = -0.22, 95%CI: -0.42 to -0.02; P = 0.028). For RCII, the smoothing spline suggested a non-linear association, with an estimated VFA inflection point at 118 cm2. Below this level, higher VFA was associated with higher RCII (β = 0.22, 95%CI: 0.05-0.39; P = 0.011), whereas at VFA ≥ 118 cm2 the association was weak and non-significant (β = -0.10, 95%CI: -0.33 to 0.14; P = 0.41). The difference in slopes across the threshold was of borderline significance (Δβ = -0.32, 95%CI: -0.66 to 0.02; P = 0.062), and the likelihood ratio test only marginally favoured the two-piecewise model over a single linear model (P = 0.060). Overall, support for a segmented (two-piecewise) association for RCII was limited and was interpreted as exploratory.
Figure 1 The dose-response patterns between visceral fat area and residual cholesterol/residual cholesterol-inflammation index using spline-based smoothing techniques.
A: Smoothing spline curve for the association between visceral fat area (VFA) and residual cholesterol (RC); B: Smoothing spline curve for the association between VFA and the RC to C-reactive protein ratio (RC-inflammation index). The red line represents the fitted smoothing spline and the blue dotted lines represent the 95%CIs. Vertical ticks along the X-axis indicate the distribution of VFA. Models were adjusted for age, sex, current smoking, current drinking, glycated haemoglobin, free triiodothyronine, estimated glomerular filtration rate and alanine aminotransferase. RCII: Residual cholesterol-inflammation index.
Table 3 Threshold effects of visceral fat area on residual cholesterol and the residual cholesterol to C-reactive protein ratio based on two-piecewise linear regression models.
Subgroup analyses of the associations of VFA with RC and RCII are presented in Table 4. For RC, the positive association with VFA was generally similar across strata of age, sex, current smoking, current drinking and HbA1c, and none of the corresponding interaction terms was statistically significant. BMI modified the association between VFA and RC. Among participants with BMI < 28 kg/m2, higher VFA was clearly associated with higher RC, whereas in those with BMI ≥ 28 kg/m2, the association between VFA and RC was not apparent. There was a statistically significant interaction between VFA and BMI category. For RCII, the associations with VFA across subgroups were generally in the same direction as those observed for RC, but the effect sizes were smaller, and no statistically significant interactions were detected in any subgroup.
In this cross-sectional analysis of adults with T2D, higher VFA was positively associated with RC, while RCII, treated as a hypothesis-generating biomarker, showed a broadly similar direction. These patterns were evident when VFA was treated as a continuous variable and across higher VFA tertiles, and they persisted after adjustment for multiple covariates. The associations were more robust for RC, whereas those for RCII were weaker but directionally consistent and should be interpreted cautiously. Smoothing curve fitting and two-piecewise linear regression suggested a non-linear pattern between VFA and RC, with a threshold at 126 cm2. A weaker, borderline threshold signal was also observed for RCII at 118 cm2; this finding should be considered exploratory and requires further validation. Taken together, these findings suggest that visceral adiposity is closely associated with remnant cholesterol-related burden in adults with T2D, with a clear non-linear pattern for RC and a weaker, exploratory pattern for RCII. Conceptually, RCII combines remnant cholesterol with CRP to describe remnant lipid burden in the context of systemic inflammation; however, it still requires further validation.
Many clinical and epidemiological studies have linked visceral adiposity to atherogenic lipid profiles and adverse cardiovascular outcomes[26]. In general adult and obese populations, greater visceral adipose tissue (VAT) or VFA has been associated with higher TG, lower HDL-C, higher non-HDL-C and a more adverse cardiometabolic phenotype[27-29]. In obesity and fatty liver cohorts, VAT/VFA has also shown positive associations with remnant-like particle cholesterol and other remnant-related markers, suggesting that visceral fat accumulation often coincides with enrichment of triglyceride-rich lipoproteins[30,31]. Cross-sectional analyses from NHANES further reported positive associations between computed tomography (CT)-measured VAT and remnant cholesterol in United States adults[21]. In addition to cross-sectional evidence, several prospective cohort studies have reported that elevated remnant cholesterol is linked to a higher risk of developing CVD, as well as increased all-cause and cardiovascular mortality, including in individuals with T2D. These relationships persist even after controlling for LDL-C and other traditional risk factors[32-34]. Consistently, a retrospective study in patients with acute ischemic stroke reported that the atherogenic index of plasma [log(TG/HDL-C)] was associated with 1-month mortality, supporting the prognostic relevance of lipid-derived indices for vascular outcomes[35]. Overall, prior work[23,36] indicates that visceral adiposity is linked to atherogenic lipid disturbances and that RC is an independent lipid component associated with residual cardiovascular risk, whereas epidemiological evidence on composite indices such as the RCII remains limited.
Several biological pathways may underlie the observed relationships between VFA, RC and RCII. VAT is highly lipolytic and drains into the portal circulation[37]; experimental and human studies show that[38,39] visceral depots release larger amounts of free fatty acids into the portal vein than subcutaneous depots, exposing the liver to a higher lipid flux. This portal load may be related to higher hepatic production of very-low-density lipoproteins, enrichment of triglyceride-rich remnant particles with cholesterol, and reduced remnant clearance, which could contribute to higher RC concentrations[40]. In parallel, visceral fat acts as an endocrine and immune organ. Prior studies report higher expression of cytokines such as interleukin-6 and tumour necrosis factor-α in visceral depots, which may be associated with low-grade inflammation and higher CRP[41]. Remnant lipoproteins can be taken up by arterial wall macrophages and may contribute to foam-cell formation and atherosclerotic lesion development[42]. Together, these pathways offer a biologically plausible context for the positive associations between VFA, RC, and RCII observed in our study.
In this T2D cohort, the associations between VFA and RC indices showed clear non-linear features. Smoothing curves and two-piecewise linear models indicated that RC increased more steeply across lower to moderate VFA levels and then plateaued and slightly declined beyond 126 cm2. RCII showed a similar but weaker pattern, and its threshold signal at 118 cm2 was borderline and exploratory and should not be overinterpreted. These findings are broadly consistent with an NHANES analysis in United States adults, where CT-measured VAT was positively and non-linearly related to remnant cholesterol, with rapid increases at lower VAT ranges and a flatter slope at higher VAT values[21]. A plausible explanation is that the shift from low to moderate VFA indicates a transition to a visceral fat-dominant phenotype. This transition may be accompanied by greater portal free fatty acid delivery to the liver, higher production of triglyceride-rich lipoproteins, and low-grade inflammation. Together, these changes may result in marked increases in RC and, to a lesser extent, RCII[41]. When visceral fat accumulation becomes very high, the pathways involved in VLDL secretion and remnant lipoprotein clearance may already be close to saturation. In addition, some patients at this stage are more likely to receive intensive lifestyle interventions and lipid-lowering therapy. As a result, further increases in VFA may be associated with only a modest additional change in RC-related indices. The weaker non-linearity observed for RCII is also plausible, because CRP is affected by many determinants other than visceral fat, which adds variability and may blur any clear threshold pattern.
In our stratified analyses, the overall pattern that higher VFA was associated with higher RC remained broadly similar across most clinical subgroups, but appeared more evident in participants with BMI < 28 kg/m2, whereas little association was seen at higher BMI. This supports the idea that, in individuals who are not overtly obese, an increase in VFA may better capture a shift toward a visceral fat-dominant phenotype that is more closely linked to remnant cholesterol, while in those with higher BMI the effect of visceral fat may be partly obscured by the larger overall fat mass. For RCII, subgroup differences were modest, which may relate to variability in CRP and is consistent with its hypothesis-generating nature. Overall, these findings suggest that VFA may be particularly informative for RC burden among individuals who are not overtly obese, whereas its incremental value beyond general adiposity may be attenuated at higher BMI levels.
Our results suggest that, among patients with T2D, visceral adiposity is closely linked to RC-related burden beyond traditional lipids and general adiposity measures. Even at moderate VFA levels, RC was already higher, and RCII showed a broadly similar direction, indicating that individuals who are not overtly obese by BMI may still have higher RC-related indices when visceral fat is increased. This supports the potential value of incorporating visceral fat assessment, where available, into routine risk evaluation to help identify T2D patients with a more adverse remnant lipid profile. Clinically, our findings support closer attention to visceral adiposity and markers of triglyceride-rich lipoproteins and remnant cholesterol in individuals with increased VFA. However, prospective and interventional studies are still required to clarify whether targeting these pathways can translate into improved clinical outcomes.
This study has notable strengths as well as important limitations. The study was carried out in a real-world metabolic management centre and specifically included adults with T2D, a group in whom residual cardiovascular risk is particularly important. VFA was quantified rather than inferred from BMI or WC, and both RC and a combined RCII were evaluated, with multivariable, non-linear, threshold and subgroup analyses providing a relatively detailed description of how visceral adiposity relates to remnant cholesterol-related indices. However, the cross-sectional, single-centre design in Chinese adults with T2D limits causal inference and generalisability to other settings and ethnic groups. Visceral fat was assessed by validated bioelectrical impedance rather than CT or magnetic resonance imaging (MRI) so the absolute VFA values and the estimated thresholds may not be directly comparable to those obtained by CT/MRI. In addition, information on lipid- and glucose-lowering medications, diet, physical activity and other potential confounders was not available, including statins/fibrates and contemporary glucose-lowering agents such as GLP-1 receptor agonists and SGLT2 inhibitors; these therapies may influence lipids, inflammation and adiposity, and could have affected the observed associations, particularly for RC. In addition, RC and CRP were assessed only once, which may not adequately reflect long-term exposure or temporal variability. Finally, RCII is not yet widely validated, and findings involving RCII should be viewed as hypothesis-generating and require further validation.
CONCLUSION
In adults with T2D, higher VFA was associated with higher RC and, to a lesser extent, RCII. The VFA-RC association showed a clear non-linear pattern with a threshold at 126 cm2, whereas the RCII-related threshold signal at 118 cm2 was borderline and should be interpreted as exploratory. These findings suggest that quantifying visceral adiposity may help contextualize remnant cholesterol-related burden beyond conventional lipid measures in this population.
ACKNOWLEDGEMENTS
We thank Zheng-Ping Zhu for his valuable support and constructive input during the preparation of this manuscript.
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P-Reviewer: Liu CW, MD, Chief Physician, Researcher, China; Pappachan JM, MD, Professor, Senior Researcher, United Kingdom; Tatar S, Associate Professor, Türkiye; Tung TH, PhD, Associate Professor, China S-Editor: Lin C L-Editor: A P-Editor: Zhao S
