Association Between Pentraxins and Obesity in Prediabetes and Newly Diagnosed Type 2 Diabetes Mellitus Patients

Abstract

Systemic inflammation has an important role in the prognosis and progression of many chronic diseases, including diabetes (T2DM). This retrospective study aimed to evaluate inflammatory status by determining the serum inflammatory biomarkers (PTX3, hs-CRP, TNF-α, and IL-6) and new indices, like the mean corpuscular volume (MCV) to lymphocyte ratio (MCVL) and cumulative inflammatory index (IIC), in a cohort of patients with prediabetes (PreDM) and newly diagnosed T2DM. We also wanted to assess the association with clinical parameters and different obesity-related indices, to identify possible correlations and to evaluate the diagnostic accuracy of the biomarkers using ROC curve analysis. In this study, we included 60 patients diagnosed with T2DM and 30 patients with PreDM. The ELISA method was applied. Elevated PTX3, hs-CRP, TNF-α, and IL-6 levels were found in T2DM patients compared to preDM patients. An independent relationship was found between PTX3, hs-CRP, and different obesity-related indices in patients with preDM and T2DM. The MCVL index exhibited an inverse trend proportional to the rising levels of HbA1c in the T2DM group. Spearman's analysis revealed in the T2DM group that the PTX3 values correlated much better with IIC (rho = 0.445, p-value = 0.014) and MCVL (rho = 0.338, p-value = 0.048). Hs-CRP values expressed moderate-to-weak correlations with IIC and MCVL in both groups. Additionally, ROC analysis showed that the PTX3 (AUC was 0.720; p = 0.003; cut-off value 1888.00 pg/mL, with 67.60% sensitivity and 73.30% specificity) and MCVL index (AUC was 0.677; p = 0.047; cut-off value 39.60, with 63.30% sensitivity and 66.70% specificity) have a good, accurate diagnosis compared with IL-6 (AUC was 0.866; p < 0.0001; cut-off value 40.30 pg/mL, with 100.00% sensitivity and 60.00% specificity). IIC showed 61.70% sensitivity and 60.00% specificity, with an AUC of 0.572, p = 0.027 and a cut-off value of 2.35. PTX3 and MCVL can serve as independent predictor factors in the inflammatory status in preDM and T2DM patients, supporting their potential as biomarkers for T2DM management and future research.

Keywords: IIC; MCVL; cumulative inflammatory index; high-sensitivity C-reactive protein; interleukin 6; mean corpuscular volume-to-lymphocyte ratio; obesity; pentraxin 3; tumor necro-sis factor alpha; type 2 diabetes mellitus.

Figure 1

The PTX3 (a), hs-CRP (b), TNF–α (c), IL–6 (d), PLR (e), AISI (f), MCVL (g), and IIC (h) levels for patients with preDM and T2DM vary in the HbA1c quartiles. When we compared the PreDM group’s levels of inflammatory biomarkers to the HbA1c quartiles, we found statistically significant variations in PTX3 (p = 0.039), and AISI (p = 0.029) values between the Q1 + Q2 and Q3 + Q4 groups. Using the one-way ANOVA test, we found that T2DM patients had statistically significant differences in values among the HbA1c quartiles among PTX3 (p = 0.048), TNF–α (p < 0.0001), PLR (p = 0.013), AISI (p = 0.020), and IIC (p = 0.027); while the MCVL index reached the significance limits (one-way ANOVA test, p = 0.056). The violin plot represents values of the inflammatory biomarkers; horizontal red lines represent median values accompanied by the quartiles represented by horizontal blue lines. PTX3: pentraxin 3; hs–CRP: high–sensitivity C–reactive protein; TNF–α: tumor necrosis factor alpha; IL–6: interleukin 6; PLR: platelet-lymphocyte ratio; AISI: aggregate index of systemic inflammation; MCVL: ratio between the mean corpuscular volume/lymphocytes; IIC: cumulative inflammatory index; *, p ≤ 0.05; **, p < 0.0001; #, reached the significance limit; ns: statistically not significant differences.

Figure 2

Correlations matrix between inflammatory biomarkers and the different obesity-related indices in the PreDM group. The correlation heatmap shows how the measured indicators relate to one another. Strong positive correlations are indicated by bright blue, whereas strong negative correlations are indicated by bright red.

Figure 3

Correlations matrix between inflammatory biomarkers and the different obesity-related indices in the T2DM group. The correlation heatmap shows how the measured indicators relate to one another. Strong positive correlations are indicated by bright blue, whereas strong negative correlations are indicated by bright red.

Figure 4

Receiver operating characteristic (ROC) curve for IL-6 (A), PTX3 (B), MCVL (C), TNF-α (D), hs-CRP (E), PLR (F), SII (G), NLR (H), MLR (I), IIC (J), and AISI (K). ROC analysis showed that the PTX3 (AUC was 0.720; p = 0.003; cut-off value 1888.00 pg/mL, with 67.60% sensitivity and the highest specificity of 73.30%) and MCVL index (AUC was 0.677; p = 0.047; cut-off value 39.60, with 63.30% sensitivity and the second highest specificity of 66.70%) had a good accurate diagnosis compared with IL-6 (AUC was 0.866; p < 0.0001; cut-off value 40.30 pg/mL, with 100.00% sensitivity and 60.00% specificity). IIC showed 61.70% sensitivity and 60.00% specificity, with an AUC of 0.572, p = 0.027, and a cut-off value of 2.35. In our study, we found the following results for various hematological indices: PLR demonstrated 73.30% sensitivity and 60.00% specificity (cut-off value of 101); SII exhibited 56.70% sensitivity and 60.00% specificity (cut-off value of 397); NLR showed a sensitivity of 65.00% and a specificity of 60.00% (cut-off value of 1.98); MLR had a sensitivity of 53.30% and a specificity of 56.70% (cut-off value of 0.212); while AISI demonstrated a sensitivity of 56.70% and a specificity of 53.30% (cut-off value of 233). PTX3: pentraxin 3; hs-CRP: high-sensitivity C-reactive protein; TNF-α: tumor necrosis factor alpha; IL-6: interleukin 6; NLR: neutrophil-lymphocyte ratio; MLR: monocyte-lymphocyte ratio; PLR: platelet-lymphocyte ratio; AISI: aggregate index of systemic inflammation; SII: systemic immune-inflammation index; MCVL: ratio between the mean corpuscular volume/lymphocytes; IIC: cumulative inflammatory index.

Figure 4

Receiver operating characteristic (ROC) curve for IL-6 (A), PTX3 (B), MCVL (C), TNF-α (D), hs-CRP (E), PLR (F), SII (G), NLR (H), MLR (I), IIC (J), and AISI (K). ROC analysis showed that the PTX3 (AUC was 0.720; p = 0.003; cut-off value 1888.00 pg/mL, with 67.60% sensitivity and the highest specificity of 73.30%) and MCVL index (AUC was 0.677; p = 0.047; cut-off value 39.60, with 63.30% sensitivity and the second highest specificity of 66.70%) had a good accurate diagnosis compared with IL-6 (AUC was 0.866; p < 0.0001; cut-off value 40.30 pg/mL, with 100.00% sensitivity and 60.00% specificity). IIC showed 61.70% sensitivity and 60.00% specificity, with an AUC of 0.572, p = 0.027, and a cut-off value of 2.35. In our study, we found the following results for various hematological indices: PLR demonstrated 73.30% sensitivity and 60.00% specificity (cut-off value of 101); SII exhibited 56.70% sensitivity and 60.00% specificity (cut-off value of 397); NLR showed a sensitivity of 65.00% and a specificity of 60.00% (cut-off value of 1.98); MLR had a sensitivity of 53.30% and a specificity of 56.70% (cut-off value of 0.212); while AISI demonstrated a sensitivity of 56.70% and a specificity of 53.30% (cut-off value of 233). PTX3: pentraxin 3; hs-CRP: high-sensitivity C-reactive protein; TNF-α: tumor necrosis factor alpha; IL-6: interleukin 6; NLR: neutrophil-lymphocyte ratio; MLR: monocyte-lymphocyte ratio; PLR: platelet-lymphocyte ratio; AISI: aggregate index of systemic inflammation; SII: systemic immune-inflammation index; MCVL: ratio between the mean corpuscular volume/lymphocytes; IIC: cumulative inflammatory index.

Figure 4

Receiver operating characteristic (ROC) curve for IL-6 (A), PTX3 (B), MCVL (C), TNF-α (D), hs-CRP (E), PLR (F), SII (G), NLR (H), MLR (I), IIC (J), and AISI (K). ROC analysis showed that the PTX3 (AUC was 0.720; p = 0.003; cut-off value 1888.00 pg/mL, with 67.60% sensitivity and the highest specificity of 73.30%) and MCVL index (AUC was 0.677; p = 0.047; cut-off value 39.60, with 63.30% sensitivity and the second highest specificity of 66.70%) had a good accurate diagnosis compared with IL-6 (AUC was 0.866; p < 0.0001; cut-off value 40.30 pg/mL, with 100.00% sensitivity and 60.00% specificity). IIC showed 61.70% sensitivity and 60.00% specificity, with an AUC of 0.572, p = 0.027, and a cut-off value of 2.35. In our study, we found the following results for various hematological indices: PLR demonstrated 73.30% sensitivity and 60.00% specificity (cut-off value of 101); SII exhibited 56.70% sensitivity and 60.00% specificity (cut-off value of 397); NLR showed a sensitivity of 65.00% and a specificity of 60.00% (cut-off value of 1.98); MLR had a sensitivity of 53.30% and a specificity of 56.70% (cut-off value of 0.212); while AISI demonstrated a sensitivity of 56.70% and a specificity of 53.30% (cut-off value of 233). PTX3: pentraxin 3; hs-CRP: high-sensitivity C-reactive protein; TNF-α: tumor necrosis factor alpha; IL-6: interleukin 6; NLR: neutrophil-lymphocyte ratio; MLR: monocyte-lymphocyte ratio; PLR: platelet-lymphocyte ratio; AISI: aggregate index of systemic inflammation; SII: systemic immune-inflammation index; MCVL: ratio between the mean corpuscular volume/lymphocytes; IIC: cumulative inflammatory index.