European Journal of Cardiovascular Medicine

Metabolic syndrome (MetS) is a cluster of central obesity, dyslipidemia, hypertension, and dysglycemia that elevates risk for type 2 diabetes and atherosclerotic cardiovascular disease. Early, accurate identification remains a public health priority due to escalating prevalence in low- and middle-income settings. Contemporary reviews summarize harmonized diagnostic criteria and underscore the need for practical screening tools in routine care.

Adipose tissue secretes numerous bioactive adipokines that influence insulin signaling and inflammation. Adiponectin enhances insulin sensitivity and fatty-acid oxidation, whereas leptin mirrors adiposity and can promote pro-inflammatory pathways when chronically elevated. Considering each alone provides an incomplete picture; the adiponectin-to-leptin (A/L) ratio has emerged as an integrated index of adipose tissue function and cardiometabolic risk. Evidence indicates the A/L ratio correlates with insulin resistance more strongly than either adipokine individually and associates with a range of outcomes including NAFLD, weight-loss response, and MetS remission.

Beyond mechanistic plausibility, population and clinical studies report that lower A/L ratios track higher HOMA-IR, triglycerides, fasting glucose, blood pressure, and waist circumference—key MetS components. Diagnostic studies in adolescents and adults suggest the A/L ratio offers better discriminatory ability for IR than adiponectin or leptin measured alone, with clinically usable cut-offs proposed across settings.

However, cut-points vary by population, laboratory platform, and phenotype (e.g., South/West Asian vs Western waist and BMI thresholds). Studies in Indian and broader Asian populations also show differing HOMA-IR thresholds for IR or MetS prediction (≈2.5–3.0+), emphasizing the need for context-specific validation.

Objective: To evaluate whether the serum A/L ratio independently associates with IR and discriminates MetS in a real-world hospital cohort, and to estimate a practical cut-off for clinical use alongside routine lipids and fasting glucose.

This is a Case–control study at a tertiary-care hospital biochemistry laboratory over 12 months.

Inclusion criteria: adults 18–65 y; fasting (8–12 h); consent provided. Exclusion: pregnancy; acute infection; known endocrine disorders other than T2D; chronic liver/renal failure; malignancy; glucocorticoid or weight-loss drug use; extreme triglycerides (>1000 mg/dL).

Participants: Adults 18–65 years. Cases: consecutive outpatients/inpatients meeting harmonized MetS criteria (≥3 of: central obesity, elevated triglycerides, reduced HDL-C, elevated blood pressure, elevated fasting glucose).

Controls: age- and sex-matched individuals without MetS, recruited from health check-ups.

Sample size: Assuming an AUC of 0.80 for A/L to detect MetS, α=0.05, power=0.90, case:control=1:1, minimal N≈216; we enrolled N=240 (120 per arm) to allow covariate adjustment.

Measurements: Anthropometrics (waist, BMI), blood pressure, fasting lipids (enzymatic), glucose (hexokinase), insulin (chemiluminescence), adiponectin and leptin (ELISA; ng/mL and µg/mL units standardized to ratio). A/L ratio computed as adiponectin (µg/mL) ÷ leptin (ng/mL) after unit harmonization (or as manufacturer-recommended dimensionless ratio). Internal and external quality controls followed CLIA-compliant protocols.

Outcomes:

1. Between-group differences in A/L ratio;
2. Correlation of A/L with HOMA-IR;
3. Diagnostic performance for MetS (ROC, cut-off by Youden index);
4. Independent association with MetS (multivariable logistic regression: age, sex, BMI, LDL-C, hs-CRP, physical activity).

Operational definitions:

• Central obesity: ethnicity-appropriate waist circumference; for South Asians use ≥90 cm (men) or ≥80 cm (women) as contemporary guidance.
• Insulin resistance (IR): HOMA-IR (fasting insulin [µU/mL] × fasting glucose [mg/dL] ÷ 405). Contextual references suggest thresholds ≈2.8–3.0 for MetS discrimination; we analyzed HOMA-IR continuously and explored ≥2.86 as a reference cut-off.

Statistical analysis: Shapiro–Wilk for normality; t-test or Mann–Whitney U; χ² for categorical variables; Spearman correlation; ROC-AUC with 95% CI; logistic regression with variance-inflation check. Two-sided p<0.05 significant. Analyses conducted in R 4.x.

Ethics: Approved by Institutio

nal Ethics Committee; written informed consent obtained; study adhered to the Declaration of Helsinki.

Table 1. Baseline Characteristics (N=240)

In table 1, Groups were well matched for age/sex; MetS participants had higher adiposity and adverse lipids consistent with case definition.

Table 2. Adipokines, HOMA-IR, and A/L Ratio

In Table 2: MetS participants exhibited lower adiponectin, higher leptin, and a markedly reduced A/L ratio alongside higher HOMA-IR.

Table 3. Correlations of A/L Ratio with Metabolic Risk (Spearman ρ)

In table 3: Lower A/L correlates with higher IR and adverse MetS components.

Table 4. ROC Analysis for Discriminating MetS (N=240)

In table 4: A/L ratio showed the highest AUC and balanced sensitivity/specificity relative to single adipokines and was comparable to HOMA-IR.

Table 5. Multivariable Logistic Regression for MetS (Outcome=MetS Yes)

In table 5, Lower A/L ratio independently associates with MetS beyond adiposity and inflammation.

Table 6. Subgroup ROC (A/L Ratio) by Sex and BMI

In table 6, Discriminatory performance was consistently high across sex and BMI strata with minor cut-off shifts.

In this hospital-based cohort, the adiponectin-to-leptin ratio was markedly lower in MetS than in matched controls, correlated inversely and strongly with HOMA-IR, and showed excellent discrimination for MetS (AUC 0.86). These findings align with a growing literature positioning the A/L ratio as a functional biomarker of adipose tissue health, integrating insulin-sensitizing (adiponectin) and adiposity-linked (leptin) signals. Prior mechanistic and clinical studies report that reduced A/L indicates adipose tissue dysfunction, higher IR, and adverse cardiometabolic profiles.

Our ROC and cut-off (≈0.65) are congruent with diagnostic work suggesting the A/L ratio often outperforms single adipokines and can rival or complement HOMA-IR. In adolescents and adults, the L/A or A/L ratio has shown superior diagnostic accuracy for IR risk, and intervention studies demonstrate that weight loss improves the ratio in parallel with metabolic risk reduction. Recent observational analyses extend its relevance to conditions such as NAFLD (including lean NAFLD) and to longitudinal change with lifestyle counseling, underscoring physiological coherence across phenotypes.

Cut-offs inevitably vary by laboratory platform, sex, BMI, and ethnicity. Our subgroup analysis suggests broadly similar performance with slightly higher thresholds among women and individuals with higher BMI—consistent with reports that absolute adipokine levels and ratios differ by body composition and sex. Clinical implementation should therefore consider local validation and ethnic-specific anthropometric criteria, especially in South/West Asian populations where waist circumference thresholds and HOMA-IR cut-offs differ from Western cohorts.

Strengths include standardized assays, multivariable adjustment, and complementary metrics (HOMA-IR and lipids). Limitations include the case–control design (precludes causal inference), single-center recruitment (limits generalizability), and potential residual confounding (diet, sleep, physical activity). We did not evaluate other emerging indices (TyG, SPISE) that may complement A/L; future prospective studies could compare a multi-marker panel to standard clinical criteria for risk stratification and treatment monitoring.

The A/L ratio is measurable on widely available ELISA platforms, needs only a fasting sample, and provides actionable risk information. In resource-constrained settings where insulin assays are limited or variable, A/L may serve as a pragmatic adjunct to routine lipids and anthropometry for identifying high-risk patients who warrant intensive lifestyle or pharmacologic interventions

The serum adiponectin-to-leptin ratio is a strong, independent correlate of insulin resistance and demonstrates high diagnostic accuracy for MetS. Incorporating the A/L ratio into routine laboratory panels may enhance early risk detection and monitoring, particularly in populations with high MetS burden.

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