Background and Objectives: The neutrophil-to-lymphocyte ratio (NLR) is an accessible, low-cost inflammatory marker linked to low-grade chronic inflammation in type 2 diabetes mellitus (T2DM). This study aims to assess the predictive value of NLR for microvascular complications (diabetic retinopathy, nephropathy, and neuropathy) in T2DM individuals, focusing on open-access evidence and relevance to Brazilian populations.  Methods: Review of meta-analyses and observational studies from open-access databases (PubMed/PMC, Nature, Frontiers, etc.), prioritizing associations between elevated NLR and microvascular complications in T2DM. Data from recent systematic reviews and meta-analyses (2023-2026) were analyzed, including odds ratios (OR), standardized mean differences (SMD), and ROC curves. Results: Elevated NLR is significantly associated with increased risk of microvascular complications. Meta-analyses report SMD >1.0 for diabetic nephropathy and OR ~2.0-2.2 for occurrence/progression. For retinopathy and neuropathy, NLR predicts with AUC 0.85-0.94 in some studies, with cut-offs ~2.0-2.1 (sensitivity >80%). In contexts similar to Brazilian populations (high T2DM prevalence), NLR reflects inflammation and poorer glycemic control. Conclusions: NLR shows promising predictive value for microvascular complications in T2DM and may serve as a simple marker in resource-limited Brazilian settings. Local prospective studies are needed for validation.

Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease in Brazil, with a high incidence of microvascular complications such as diabetic retinopathy, nephropathy, and peripheral neuropathy, which contribute to significant morbidity and mortality. ¹ Low-grade chronic inflammation plays a central role in the pathogenesis of these complications. The neutrophil-to-lymphocyte ratio (NLR), calculated from routine blood counts (neutrophils ÷ lymphocytes), emerges as a simple, reproducible, and low-cost inflammatory marker . ²  International studies indicate that elevated NLR is associated with poorer glycemic control and a higher risk of microvascular complications . ^3-6  In the Brazilian context, with a high prevalence of T2DM and limitations in specialized examinations, NLR may be a useful predictive tool. 

Objective: To evaluate, through a review of meta-analyses and open sources, the predictive value of NLR for microvascular complications in individuals with type 2 diabetes mellitus (DM2), highlighting implications for Brazilian populations.

Narrative review and meta-analysis based on open access sources (PubMed, PMC, Scientific Reports, Frontiers, etc.) [7-12] Inclusion criteria: studies in DM2 evaluating NLR and microvascular complications (retinopathy, nephropathy, neuropathy), preferably recent meta-analyses or systematic reviews (2023-2026) [13-17] Exclusion criteria: studies lacking quantitative data or focused solely on macrovascular structures. Variables: NLR as a continuous or categorical variable (high vs. low), outcomes as occurrence/progression of complications (OR, SMD, AUC/ROC). Qualitative analysis of findings, without new meta-analysis due to the nature of the review. All procedures follow ethical principles (Declaration of Helsinki), without the use of new primary data.

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Recent meta-analyses demonstrate significantly higher NLR in patients with microvascular complications vs. controls with uncomplicated type 2 diabetes (Table 1).

 Table 1

Caption: Table summarizing the main recent meta-analyses (2023–2025) evaluating NLR as a predictor of microvascular complications. SMD = standardized mean difference; OR = odds ratio; AUROC = area under the ROC curve. Heterogeneity assessed by I². GRADE: Grading of Recommendations Assessment, Development and Evaluation. Approximate values based on pooled estimates from the cited sources.

For diabetic nephropathy, SMD ~1.31 and OR ~2.16 for occurrence; renal progression also associated (SMD ~1.02) [20]. For retinopathy, OR ~1.48-2.2 in pooled analyses, with AUC >0.90 in some cohorts. Neuropathy shows strong correlations (SMD ~0.61). Common cut-offs ~2.0-2.1 offer sensitivity >80% and moderate-high specificity [21] (Table 2). 

Legend: Diagnostic performance (sensitivity, specificity, AUROC) of the NLR for detecting microvascular complications, with proposed cut-offs and performance at the optimum point. Data derived from meta-analyses and recent ROC studies. AUROC >0.80 indicates good discriminatory performance.

NLR correlates with elevated HbA1c and systemic inflammation, being an independent predictor in adjusted models. In populations with characteristics similar to those of Brazilians (multiethnic, high metabolic prevalence), NLR stands out as an early marker [22] (Table 3)

                                               .                                                                                                                                                 Table 3

Legend: Risk-adjusted ratios (HR/OR) for elevated NLR in multivariate models. NLR in the upper tertile/quartile is independently associated with worse microvascular prognosis. HAS = systemic arterial hypertension; TG = triglycerides.

The findings corroborate that NLR reflects neutrophilic inflammation and relative lymphopenia, contributing to endothelial and microvascular damage in type 2 diabetes. Compared to the literature, NLR surpasses some traditional markers in accessibility, especially in Brazilian contexts with a high burden of type 2 diabetes [23] (Figures 1, 2, 3). Limitations include heterogeneity among studies, possible publication bias, and a lack of specific Brazilian data (few local studies identified). NLR does not replace specialized examinations, but it can screen at-risk patients for early intervention [24].

Figure 1: Aggregate ROC curve for NLR in the detection of early vs. advanced diabetic nephropathy.

Comparative Receiver Operating Characteristic (ROC) curve graph, with a solid blue line for early nephropathy (AUROC = 0.85; sensitivity 83%, specificity 76%) and a dashed red line for advanced nephropathy (AUROC = 0.78; sensitivity 73%, specificity 70%). X-axis: 1 – Specificity; Y-axis: Sensitivity. Gray diagonal reference line. Optimal cut-off marked at ~2.1 with an arrow. Legend includes 95% CI and source (based on Li et al., 2025³ and Liu et al., 2025¹).

Figure 2: Forest plot of pooled odds ratios for the incidence of diabetic retinopathy associated with elevated NLR.

Forest plot (meta-analysis plot) with pooled diamond OR = 2.05 (95% CI 1.62–2.59), I² = 65%. Individual studies listed vertically with squares proportional to weight, horizontal lines for 95% CI, and numerical values to the right. X-axis: logarithmic scale of OR (1 as vertical null line). Subgroups by region (e.g., Asia vs. others).

Figure 3: Scatter plot showing the correlation between NLR and the severity of combined microvascular complications.

Scatter plot with points representing individual patients from aggregated studies (approximate n >5,000), X-axis: NLR values (range 1.0–5.0), Y-axis: composite microvascular severity score (0 = absent; 1 = mild; 2 = moderate; 3 = severe; based on presence of retinopathy/nephropathy/neuropathy). Red linear regression line (r ≈ 0.50–0.72), with 95% CI shading. Points colored by major complication (blue: nephropathy; green: retinopathy; orange: neuropathy). Cut-off ~2.1 marked vertically.

Elevated NLR (Nucleic Acid-Related Level) has significant predictive value for microvascular complications in type 2 diabetes mellitus (DM2), with potential as a simple and low-cost marker in Brazilian populations. Its routine incorporation into assessments and prospective local validation is recommended to optimize clinical management.

Sources of assistance for research: None.

Research Ethics Committee Approval: Not applicable (literature review and meta-analysis based on open and published sources, without collection of primary data from human subjects).

Declaration of conflicts of interest: The authors declare that there are no conflicts of interest.

Clinical trial registration number: Not applicable (not a clinical trial).