Plasma lipoproteins exist as several subpopulations with distinct particle number and size that are not fully reflected in the conventional lipid panel. In this study, we sought to quantify lipoprotein subpopulations in patients with type 2 diabetes mellitus (T2DM) to determine whether specific lipoprotein subpopulations are associated with insulin resistance and inflammation markers. The study included 57 patients with T2DM (age, 61.14 ± 9.99 years; HbA1c, 8.66 ± 1.60%; mean body mass index, 35.15 ± 6.65 kg/m²). Plasma lipoprotein particles number and size were determined by nuclear magnetic resonance spectroscopy. Associations of different lipoprotein subpopulations with lipoprotein insulin resistance (LPIR) score and glycoprotein acetylation (GlycA) were assessed using multi-regression analysis. In stepwise regression analysis, VLDL and HDL large particle number and size showed the strongest associations with LPIR (R² = 0.960; p = 0.0001), whereas the concentrations of the small VLDL and HDL particles were associated with GlycA (R² = 0.190; p = 0.008 and p = 0.049, respectively). In adjusted multi-regression analysis, small and large VLDL particles and all sizes of lipoproteins independently predicted LPIR, whereas only the number of small LDL particles predicted GlycA. Conventional markers HbA1c and Hs-CRP did not exhibit any significant association with lipoprotein subpopulations. Our data suggest that monitoring insulin resistance-induced changes in lipoprotein subpopulations in T2DM might help to identify novel biomarkers that can be useful for effective clinical intervention.

Background: Cardiovascular disease (CVD) is the leading cause of mortality in obese patients with type 2 diabetes mellitus (T2DM). Conventional biomarkers often fail to detect early endothelial dysfunction and oxidative stress. Haptoglobin (Hp), an acute-phase protein with antioxidant and hemoglobin-binding properties, may indicate vascular injury. While plasma Hp (pl-Hp) reflects systemic inflammation, urinary Hp (u-Hp) could signal renal and microvascular damage. We hypothesize that elevated u-Hp and altered pl-Hp levels are associated with increased oxidized LDL and may serve as sensitive indicators of early vascular injury, thereby identifying obese patients with T2DM at higher cardiovascular risk. This study aims to investigate the associations between u-Hp, pl-Hp, and oxidized LDL (ox-LDL) in obese patients with T2DM, and to evaluate the potential role of Hp as an early biomarker of cardiovascular risk in this high-risk population. Methods and Results: The study included 57 patients with T2DM (mean age 61 ± 10 years, HbA1c 8.66 ± 1.60%, and BMI 35.15 ± 6.65 kg/m²). Notably, 95% of the patients had hypertension, 82% had dyslipidemia, and 59% had an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m². Pl-Hp and u-Hp concentrations, as well as ox-LDL levels, were assessed using an enzyme-linked immunosorbent assay (ELISA). Correlations and multivariate regression analyses were employed to investigate the associations between Hp, ox-LDL, and clinical cardiovascular risk factors. Pl-Hp was positively correlated with ox-LDL (r = 0.358, p < 0.006) and negatively correlated with C-reactive protein (CRP) (r = −0.364, p < 0.013), while u-Hp correlated positively with HbA1C and apoB levels (r = 0.298, p < 0.030 and r = 0.310, p < 0.021, respectively). Multivariate analysis indicated that pl-Hp, but not u-Hp, was independently associated with ox-LDL (β = 0.536, p < 0.027) after adjusting for potential confounding factors, including age, gender, BMI, HbA1c, liver enzymes, hs-CRP and creatinine. The Stepwise analysis identified IL-6 as the most significant predictor of cardiovascular disease risk, suggesting its pivotal role in subclinical vascular inflammation among obese individuals with T2DM. Furthermore, the significant positive association between pl-Hp and ox-LDL was stronger in patients with declining renal function as expressed by the estimated glomerular filtration rate (eGFR) (eGFR < 30 mL/min/1.73 m²: β = 2.173, p < 0.031 and eGFR 30–59 mL/min/1.73 m²: β = 1.318, p < 0.002). This association also appeared in early and low-normal ranges of serum albumin: creatinine ratio (s-ACR) (s-ACR < 0.2714 mg/mmol: β = 2.304, p < 0.005 and s-ACR 0.2714–0.3649 mg/mmol: β = 1.000, p < 0.041), suggesting that pl-Hp and ox-LDL rise before overt kidney damage. Elevated IL-6 (≥32.93 pg/mL) further strengthened this link (β = 1.037, p < 0.005), highlighting the role of inflammation in amplifying oxidative stress and acute-phase responses. Conclusions: Taken together, these findings emphasize the interconnected contributions of renal impairment, inflammation, and oxidative stress to vascular injury. While these results need to be confirmed in larger prospective longitudinal studies, monitoring pl-Hp levels in conjunction with inflammatory and kidney function markers could be a sensitive and non-invasive way to identify early CVD risk in high-risk groups, such as obese patients with T2DM.

In individuals with type 2 diabetes mellitus (T2DM), elevated levels of both plasma and urinary cystatin C (Cys-C) contribute to increased oxidation, which in turn accelerates the oxidation of low-density lipoprotein (LDL). This process may worsen the development of atherosclerosis and cardiovascular disease by promoting endothelial dysfunction and inflammation. Despite its potential significance, the relationship between Cys-C and oxidized LDL (ox-LDL) in T2DM remains poorly understood. This study investigated the relationship between plasma and urinary Cys-C and ox-LDL levels in T2DM patients. The cohort included 57 patients with T2DM (mean age 61.14 ± 9.99 years; HbA1c 8.66 ± 1.60% and BMI 35.15 ± 6.65 kg/m²). Notably, 95% of the patients had hypertension, 82% had dyslipidemia, 59% had an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m², 14% had coronary artery disease (CAD), and 5% had a history of stroke. Plasma and urinary Cys-C and ox-LDL levels were measured using ELISA. Adipokine and cytokine levels were measured using the multiplex^® MAP Human Adipokine Magnetic Bead Panels. Spearman’s correlation analysis revealed a significant positive correlation of plasma and urinary Cys-C with ox-LDL (r = 0.569, p = 0.0001 and r = 0.485, p = 0.0001, respectively). Multivariable regression analysis indicated that both plasma and urinary Cys-C were independently associated with ox-LDL, after adjusting for confounding factors (β = 0.057, p = 0.0001 and β = 0.486, p = 0.003, respectively). Stepwise linear regression identified TNFα and adiponectin as the strongest predictors of the relationship between urinary Cys-C and ox-LDL (β = 0.382, p = 0.0001; r² = 0.64), while adiponectin alone was the best predictor of the plasma Cys-C and ox-LDL association (β = 0.051, p = 0.005; r² = 0.46). Furthermore, adiponectin partly mediated the relationship between plasma Cys-C and ox-LDL, explaining 18% of the variance in this association. In contrast, TNFα partly mediated the relationship between urinary Cys-C and ox-LDL, accounting for 28% of the variance. This study emphasizes the complex interaction between Cys-C and ox-LDL in T2DM. It highlights the need for additional research involving larger patient cohorts to improve our understanding of the therapeutic potential of plasma and urinary Cys-C in conjunction with ox-LDL for managing complications associated with T2DM.

Atrial natriuretic peptide (ANP) and oxidized low-density lipoprotein (ox-LDL) play essential roles in the development and progression of vascular complications associated with type 2 diabetes mellitus (T2DM), and both are independently linked to cardiovascular diseases (CVD). However, the relationship between ANP and ox-LDL in patients with T2DM remains unclear as previous studies have primarily focused on circulating levels in various diseases. This study investigated the relationship between ANP and ox-LDL levels in obese individuals with T2DM. The cohort included 57 patients with T2DM (mean age 61.14 ± 9.99 years; HbA1c 8.66 ± 1.60%; BMI 35.15 ± 6.65 kg/m²). Notably, 95% of the patients had hypertension, 82% had dyslipidemia, 59% had an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m², 14% had coronary artery disease (CAD), and 5% had a history of stroke. Plasma concentrations of ANP and ox-LDL were measured using ELISA. Adipokines and cytokines levels were measured using the multiplex^® MAP Human Adipokine Magnetic Beads Spearman’s correlation analysis which revealed a negative correlation between ANP and ox-LDL (r = −0.446, p = 0.001) as well as with the ox-LDL/apoB ratio (r = −0.423, p = 0.001) and ox-LDL/LDLc ratio (r = −0.307, p = 0.038). Multivariable regression analysis indicated that ANP was independently associated with ox-LDL (β = −115.736, p = 0.005). Stepwise linear regression further identified TNFα, leptin, and adiponectin as the strongest predictors influencing the relationship between ANP and ox-LDL levels (β = −64.664, p = 0.0311, and r² = 0.546 for the model). However, these factors did not significantly mediate this association. This study emphasizes the need for further exploration of the complex interaction between ANP and ox-LDL in larger patient populations. This could provide valuable insights into potential therapeutic approaches for managing vascular complications in obese individuals with T2DM.