ISSN 3028-8940 JANUARY-JUNE 2026;3(1):13-29 ORIGINAL ARTICLE https://doi.org/10.36097/rgcs.v3i1.3197 13 San Gregorio de Portoviejo University | Ecuador Glycated hemoglobin correlates with inflammatory markers of cardiovascular risk in patients with type 2 diabetes mellitus La hemoglobina glicada se correlaciona con marcadores inflamatorios de riesgo cardiovascular en pacientes con diabetes mellitus tipo 2 Pablo Aguirre-Villegas 1 , Adriana Pedreáñez 2 * 1 Hospital Provincial General Docente Riobamba, Riobamba, Ecuador. 2 Escuela de Bioanálisis, Facultad de Medicina, Universidad del Zulia. Maracaibo, Venezuela. *Corresponding author Reception: 04-08-2025 Acceptance: 22-10-2025 Publication: 31-01-2026 ABSTRACT Hyperglycemia promotes inflammation and increases cardiovascular risk. This study aimed to analyze the relationship between glycemic control and inflammatory and cardiovascular risk markers in patients with type 2 diabetes (T2DM). A cross-sectional, correlational study was conducted involving 300 adults (240 diabetics classified according to their HbA1c levels and 60 controls). Glucose, HbA1c, lipid profile, fibrinogen, high-sensitivity C-reactive protein (hs- CRP), atherogenix index of plasma (AIP), and erythrocyte sedimentation rate (ESR) were measured. Patients with T2DM had higher levels of fibrinogen, hs-CRP, AIP, and ESR compared to controls and among groups with poorer glycemic control (p<0.001). A significant positive correlation was observed between HbA1c and all biomarkers evaluated (p<0.0001). These findings support the use of HbA1c not only as an indicator of glycemic control but also as an indirect marker of cardiovascular risk in T2DM. Keywords: cardiovascular risk, type 2 diabetes mellitus, HbA1c, inflammation. RESUMEN La hiperglucemia promueve la inflamación e incrementa el riesgo cardiovascular. El objetivo de este estudio fue analizar la relación entre el control glucémico y marcadores inflamatorios y de riesgo cardiovascular en pacientes con diabetes tipo 2 (DM2). Se realizó un estudio transversal y correlacional que incluyó 300 adultos (240 diabéticos clasificados según sus niveles de HbA1c y 60 controles). Se midieron glucemia, HbA1c, perfil lipídico, fibrinógeno, proteína C reactiva ultrasensible (PCR-us), índice aterogénico plasmático (IAP) y velocidad de sedimentación globular (VSG). Los pacientes con DM2 mostraron niveles más altos de fibrinógeno, PCR-us, IAP y VSG en comparación con los controles y entre los grupos con peor control glucémico (p<0,001). Se observó una correlación positiva significativa entre la HbA1c y todos los biomarcadores evaluados (p<0,0001). Estos hallazgos respaldan el uso de la HbA1c no solo como indicador del control glucémico, sino también como marcador indirecto de riesgo cardiovascular en la DM2. Palabras clave: riesgo cardiovascular, diabetes tipo 2, HbA1c, inflamación. Cite as: Aguirre-Villegas, P., & Pedreáñez, A. (2026). Glycated hemoglobin correlates with inflammatory markers of cardiovascular risk in patients with type 2 diabetes mellitus. Revista Gregoriana de Ciencias de la Salud, 3(1), 13-29. https://doi.org/10.36097/rgcs.v3i1.3197 © Author(s) 2026

Glycated hemoglobin correlates with inflammatory markers of cardiovascular risk in patients with type 2 diabetes mellitus Aguirre-Villegas, & Pedreáñez 14 San Gregorio de Portoviejo University | Ecuador INTRODUCTION Atherosclerotic cardiovascular disease (ACD) is the leading cause of morbidity and mortality in patients with diabetes mellitus. It is a chronic, progressive disease that affects the entire arterial body system and often presents as peripheral artery disease of atherosclerotic origin, cerebrovascular disease, and coronary artery disease (American Diabetes Association Professional Practice Committee, 2024). Type 2 diabetes mellitus (T2DM) is linked to early onset of ACD, with dyslipidemia and arterial hypertension being common risk factors in these patients (Liu et al., 2022). Atherosclerosis is a complex chronic inflammatory process that combines alterations in endothelial function, thrombotic activation, increased oxidative stress, and dyslipidemia (Kong et al., 2022). In this context, T2DM represents a metabolic condition in which sustained hyperglycemia perpetuates low-grade systemic inflammation, evidenced by increased proinflammatory cytokines such as IL-6, TNF-α, and C-reactive protein (Rohm et al., 2022). This inflammatory response, together with oxidative stress induced by chronic hyperglycemia (Demir et al., 2021), favors a proatherogenic environment characterized by increased blood viscosity and plasma fibrinogen levels, both recognized risk factors for the development of atherosclerotic cardiovascular disease (Antonova et al., 2022). On the other hand, the atherogenic index of plasma, calculated from the logarithmic ratio between triglycerides and HDL cholesterol, has been proposed as a useful biomarker of atherosclerosis and cardiovascular risk, showing an independent association with adverse cardiovascular events in patients with T2DM (Guo et al., 2025; Ma et al., 2020). At the same time, chronic hyperglycemia promotes the formation of glycosylated hemoglobin (HbA1c), the main indicator of long-term glycemic control and an independent predictor of coronary heart disease and stroke (Mitsios et al., 2018; Aguirre-Villegas & Pedreáñez, 2024). Although several international studies have documented the relationship between hyperglycemia, inflammation, and atherogenic risk, evidence in Latin American populations remains limited. In Ecuador, and particularly in Riobamba, there is little information available that integrates classic inflammatory markers (high-sensitivity C-reactive protein, fibrinogen, and erythrocyte sedimentation rate) and metabolic markers (atherogenic index of plasma) according to

Revista Gregoriana de Ciencias de la Salud. Bi-annual peer-reviewed publication. ISSN 3028-8940 / January-June 2026;3(1):13-29 San Gregorio de Portoviejo University | Ecuador 15 the degree of glycemic control. This gap limits the characterization of the inflammatory- atherogenic profile in local patients with T2DM and restricts the possibility of using these biomarkers as complementary tools for cardiovascular risk assessment. In this context, the hypothesis was proposed that poor glycemic control, reflected by elevated HbA1c levels, is associated with an increase in inflammatory and atherogenic risk markers. Understanding this relationship could contribute to better cardiovascular risk stratification and optimization of clinical management of T2DM in our population. Therefore, this study aimed to analyze the relationship between glycemic control and inflammatory and cardiovascular risk markers in patients with T2DM. METHODOLOGY An observational, cross-sectional, correlational study was conducted between November 2023 and November 2024. The research included individuals of both sexes, aged between 35 and 65, who were treated at the internal medicine clinic of the Provincial General Teaching Hospital of Riobamba (Ecuador). Intentional non-probabilistic sampling was used, based on patient availability and compliance with inclusion criteria. This type of selection was justified by the hospital nature of the study and the need for comparable groups in terms of glycemic control. However, it is recognized that this strategy limits the extrapolation of the results to the general population, so the findings should be interpreted within the clinical context of the sample studied. People under 18 or over 75 years of age, with other types of diabetes, thyroid disease, acute infection, anemia, pregnancy, autoimmune diseases, or recent treatment with corticosteroids were excluded. No specific control was made of the use of lipid-lowering, antihypertensive, or anti- inflammatory medication, so these factors were not considered in the statistical analysis and are recognized as possible confounding variables in the interpretation of the results. The sample size was estimated using Epi Info™ software, version 7.2.5.0, with a 95% confidence level, 80% power, an expected exposure proportion of 40%, and a minimum detectable relative risk of 1.8, expanded to compensate for possible losses. The total sample included 300 participants, divided as follows: 240 people with a

Glycated hemoglobin correlates with inflammatory markers of cardiovascular risk in patients with type 2 diabetes mellitus Aguirre-Villegas, & Pedreáñez 16 San Gregorio de Portoviejo University | Ecuador confirmed diagnosis of T2DM with at least two years of evolution and 60 healthy controls with no history of metabolic, autoimmune, or inflammatory diseases. Patients with T2DM were classified into three subgroups according to their glycosylated hemoglobin (HbA1c) values: group 1 (HbA1c <7%, n=80), group 2 (HbA1c between 7–9%, n=80), and group 3 (HbA1c >9%, n=80). Each participant underwent a medical history review, physical examination, and anthropometric measurements (weight and height) to calculate body mass index (BMI = weight/height²). Subsequently, venous blood samples were obtained after an 8–12-hour fast. Serum samples were centrifuged at 3000 rpm for 10 minutes and stored at −80°C until analysis. Serum concentrations of glucose, total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and high-sensitivity C-reactive protein were determined using a Cobas C501 analyzer (Roche Diagnostics, USA), following standardized internal quality control procedures. Erythrocyte sedimentation rate was determined using the Wintrobe method. Plasma fibrinogen was quantified using the Von Clauss method from samples collected in sodium citrate tubes and centrifuged at 4°C. The reference values were: glucose (70–110 mg/dL), total cholesterol (<200 mg/dL), triglycerides (<150 mg/dL), HDL-C (>40 mg/dL in men, >50 mg/dL in women), LDL-C (<130 mg/dL), and CRP-us (<3 mg/L). Fibrinogen 200–400 mg/dL (2.0–4.0 g/L). Erythrocyte sedimentation rate ≤10 mm/h in men and ≤15 mm/h in adult women. The atherogenic index of plasma was calculated using the formula AIP = log (TG/HDL- C), with concentrations expressed in mmol/L (Li et al., 2018). HbA1c was determined using a turbidimetric inhibition immunoassay (Tina-quant® HbA1c Gen. 3, Roche), certified by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and the National Glycohemoglobin Standardization Program (NGSP). The study complied with the ethical standards established in the Declaration of Helsinki (Shrestha and Dunn, 2019). All participants signed an informed consent form before inclusion. The protocol was approved by the Bioethics Committee of the Doctorate in Health Sciences at the University of Zulia, Venezuela. Statistical analysis was performed using GraphPad Prism software version 8.0 (San Diego, California, USA). Data were expressed as mean ± standard deviation (SD). Before applying parametric tests, the assumptions of normality were verified using the Shapiro–Wilk test and the

Revista Gregoriana de Ciencias de la Salud. Bi-annual peer-reviewed publication. ISSN 3028-8940 / January-June 2026;3(1):13-29 San Gregorio de Portoviejo University | Ecuador 17 homogeneity of variances using Levene's test. To compare variables between groups, a two-way analysis of variance (ANOVA) was used with Bonferroni's post hoc test for multiple comparisons. Associations between continuous variables were evaluated using Pearson's correlation. A p-value < 0.05 was considered statistically significant. RESULTS AND DISCUSSION The baseline demographic and biochemical characteristics of the participants are shown in Table 1. Patients with T2DM had a significantly higher mean age than controls (p=0.007), with no significant differences in sex distribution between groups (p=0.702). Subjects with diabetes were classified according to their HbA1c levels into three groups: well controlled (<7%), moderately controlled (7–9%), and poorly controlled (>9%). Analysis of variance (ANOVA) revealed a progressive trend toward increased blood glucose, body mass index (BMI), and triglycerides as HbA1c values increased, with statistically significant differences for BMI (p=0.004), blood glucose (p<0.05), and triglycerides (p=0.032). Table 1. Baseline and biochemical characteristics of the studied population Parameters Controls Group 1 <7% Group 2 7-9% Group 3 >9% p value Number 60 80 80 80 – Age (years) 41 ± 6 55 ± 10,9* 56 ± 11,3* 56 ± 12,8* 0.007 Male/female (%) 43/37 44/36 37/43 40/40 0.702 (NS) Blood glucose (mg/dl) 97.4±3.2 120.3±11.2* 177.9±11.3* 264.4±47*ª b <0.05 BMI (kg/m 2 ) 25.6 ± 3.9 27.2 ± 2.1* 26.2 ± 4.3* 28.2 ± 3.3* 0.004 Hematocrit (%) 41.35 ± 3.8 42.03 ± 4.23 42.86 ± 4.24 42.33 ± 4.54 0.384 (NS) Triglycerides (mg/dl) 109.74±35 141.6±62* 155.8±70* 170 ± 59*ª b 0.032 Total cholesterol (mg/dl) 148.1 ± 38 150.8±40 152.4±35 156.9 ± 45 0.679(NS) HDL-C (mg/dl) 44.46 ± 4.8 45.6±6.2 44.9±3.9 43.9 ± 3.2 0.184 (NS) LDL-C (mg/dl) 91.8±4.3 92.48 ± 9.5 95.4±2.3 93.1±3.4 0.487 (NS) Values are expressed as mean ± standard deviation (SD). One-way ANOVA followed by Bonferroni post hoc test. A value of p < 0.05 was considered statistically significant. BMI: body mass index; HDL-C: high-density lipoprotein; LDL-C: low-density lipoprotein. *: significant versus control group. a : significant versus group 1. ᵇ: significant versus group 2. NS: not significant.

Glycated hemoglobin correlates with inflammatory markers of cardiovascular risk in patients with type 2 diabetes mellitus Aguirre-Villegas, & Pedreáñez 18 San Gregorio de Portoviejo University | Ecuador Statistically significant differences were observed in the atherogenic index of plasma when controls were compared with subjects with T2DM. As well as between diabetic patients with different degrees of glycemic control (Figure 1). Control subjects presented a mean atherogenic index of plasma value of (0.34±0.12). The mean values for patients with T2DM were as follows: (group 1: 0.52±0.09; group 2: 0.56±0.11, and group 3: 0.57±0.09). Statistically significant differences were observed between controls and the three groups of subjects with T2DM (p<0.0001) and in diabetic patients between group 1 vs. group 3 (p<0.007). Figure 1. Figure 1. Atherogenic index of plasma in the study groups. Data expressed as mean ± SD; ANOVA with Bonferroni correction; n=60 (controls) and n=80 per T2DM group; p<0.05 was considered significant. Statistical analysis revealed significant differences in fibrinogen, high-sensitivity C- reactive protein, and erythrocyte sedimentation rate concentrations between patients with T2DM and the control group (p<0.001). Likewise, relevant variations were observed between the different subgroups of diabetic patients, as shown in Figures 2, 3, and 4.

Revista Gregoriana de Ciencias de la Salud. Bi-annual peer-reviewed publication. ISSN 3028-8940 / January-June 2026;3(1):13-29 San Gregorio de Portoviejo University | Ecuador 19 Figure 2. Plasma fibrinogen concentrations in the different groups studied. Data expressed as mean ± SD; ANOVA with Bonferroni correction; n=60 (controls) and n=80 per T2DM group. Figure 3. Serum high-sensitivity C-reactive protein concentrations in the different groups studied. Data expressed as mean ± SD; ANOVA with Bonferroni correction; n=60 (controls) and n=80 per T2DM group.

Glycated hemoglobin correlates with inflammatory markers of cardiovascular risk in patients with type 2 diabetes mellitus Aguirre-Villegas, & Pedreáñez 20 San Gregorio de Portoviejo University | Ecuador Figure 4. Values of erythrocyte sedimentation rate in the different groups studied. Data expressed as mean ± SD; ANOVA with Bonferroni correction; n=60 (controls) and n=80 per T2DM group. Taking into account that a highly significant difference was found in the blood concentrations of the inflammatory markers studied, as well as in the atherogenic index of plasma in patients with T2DM. Correlations were performed to evaluate the association between the variables mentioned and HbA1c levels. Significant positive correlations were observed between the levels of the aforementioned variables with the HbA1c percentages in the subjects studied (high-sensitivity C-reactive protein: r=0.3535, p<0.0001; plasma atherogenic index: r=0.5048, p<0.0001; Fibrinogen: r=0.8063, p<0.0001; erythrocyte sedimentation rate: r=0.8072, p<0.0001) (Figure 5).

Revista Gregoriana de Ciencias de la Salud. Bi-annual peer-reviewed publication. ISSN 3028-8940 / January-June 2026;3(1):13-29 San Gregorio de Portoviejo University | Ecuador 21 Figure 5. Correlations between HbA1c and inflammatory and cardiovascular risk biomarkers (Pearson analysis). Each point represents a subject with T2DM (n=240). A p < 0.05 (adjusted using Bonferroni correction for multiple comparisons) was considered significant. A) HbA1c vs hs-CRP; B) HbA1c vs AIP; C) HbA1c vs fibrinogen; D) HbA1c vs ESR. Pearson correlation. HbA1c: glycated hemoglobin; hs-CRP: high-sensitivity C-reactive protein. Table 2 summarizes the average values of inflammatory biomarkers (fibrinogen, high- sensitivity C-reactive protein, erythrocyte sedimentation rate) and the atherogenic index of plasma in the different study groups, as well as their correlations with HbA1c levels in patients with T2DM. A progressive increase in all markers is observed as glycemic control worsens. Pearson's correlation shows significant positive associations between HbA1c and each of the biomarkers, indicating that higher levels of glycosylated hemoglobin are related to a more pronounced inflammatory state and a higher atherogenic risk. Statistical analysis was performed using ANOVA followed by Bonferroni correction for multiple comparisons; values of p < 0.05 were considered significant.

Glycated hemoglobin correlates with inflammatory markers of cardiovascular risk in patients with type 2 diabetes mellitus Aguirre-Villegas, & Pedreáñez 22 San Gregorio de Portoviejo University | Ecuador Table 2. Inflammatory biomarkers and correlation coefficients with HbA1c Biomarker Control Group 1 Group 2 Group 3 r with HbA1c p Fibrinogen (mg/dL) 280±42 345±51 389±59 425±64 0.8063 <0.0001 hs-CRP (mg/L) 1.8±0.5 3.4±0.9 4.1±1.1 4.8±1.2 0.3535 <0.0001 ESR (mm/h) 8.5±2.4 13.7±3.1 16.9±3.8 19.4±4.2 0.8072 <0.0001 AIP (log TG/HDL-c) 0.34±0.12 0.52±0.09 0.56±0.11 0.57±0.09 0.5048 <0.0001 All analyses include the 240 patients with type 2 diabetes mellitus (n= 80 per group). Values are expressed as mean ± standard deviation. The p-values indicate statistical significance when p ≤ 0.05. r: Pearson's correlation coefficient between HbA1c and inflammatory and cardiovascular risk biomarkers. HbA1c: glycated hemoglobin; hs-CRP: high-sensitivity C-reactive protein; ESR: erythrocyte sedimentation rate; AIP: atherogenic index plasma. This study evaluated plasma levels of fibrinogen, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, and atherogenic index of plasma in subjects with T2DM who had different degrees of glycemic control. Patients with poor control (HbA1c > 9%) of these parameters showed significantly higher levels than well-controlled and healthy individuals. HbA1c correlated strongly and positively with all of these biomarkers, indicating a direct relationship between inadequate glycemic control and the intensity of inflammatory and atherogenic activity. The increase in high-sensitivity C-reactive protein is consistent with previous studies, in which low-grade systemic inflammation is a central feature of T2DM (Yang et al., 2021; Zhou et al., 2024). This protein, synthesized by hepatocytes under the stimulation of IL-6 and IL-1β, is a sensitive marker of cardiovascular risk and mortality in diabetic patients (Tian et al., 2019; Reddy et al., 2024). Given that the subjects did not have active infections or inflammatory processes at the time of sampling, the elevated high-sensitivity C-reactive protein values can be attributed to metabolic inflammation induced by chronic hyperglycemia, reinforcing its usefulness as a complementary indicator of glycemic control and cardiovascular risk. On the other hand, the mean fibrinogen concentration was significantly higher in patients with T2DM and was closely associated with HbA1c levels (r = 0.8063; p < 0.0001). This finding is consistent with studies linking increased fibrinogen to macrovascular and microvascular complications (Hamidullah et al., 2024; Khanam et al., 2024). Elevated fibrinogen reflects an increase in its hepatic production stimulated by proinflammatory cytokines (de Oliveira et al., 2021). In addition, glycosylated fibrinogen, which is more abundant in T2DM, forms more rigid clots that are resistant to fibrinolysis, increasing cardiovascular risk (Li et al., 2021; Pereira et al.,

Revista Gregoriana de Ciencias de la Salud. Bi-annual peer-reviewed publication. ISSN 3028-8940 / January-June 2026;3(1):13-29 San Gregorio de Portoviejo University | Ecuador 23 2016; Perween et al., 2019; Nencini et al., 2024). Furthermore, the ability of glycosylated fibrinogen to interact with RAGE receptors activates proinflammatory pathways such as NF-κB, promoting the progression of atherosclerosis (Wieczór et al., 2019; de Vries et al., 2020; Sulimai et al., 2022; Wolberg, 2023; Nencini et al., 2024). This study also detected a significant increase in triglyceride concentrations in patients with T2DM. Previous research has reported that dyslipidemia is a cardiovascular risk factor and a promoter of inflammatory responses that favor the formation of atherosclerotic lesions within the vascular wall (Viigimaa et al., 2020; Kane et al., 2021). An increase in triglyceride concentration accompanied by a reduction in HDL-C levels, commonly defined as atherogenic dyslipidemia, has been observed in approximately 41% of patients with diabetes (Núñez-Cortés & Pedro-Botet, 2021). In this context, the plasma atherogenic index, calculated as the logarithm of the triglyceride/HDL-C ratio (in mmol/L), has been described as a key biomarker for assessing atherosclerosis and is closely related to the development of cardiovascular complications. It reflects the esterification degree of plasma ApoB lipoproteins, providing information on the balance between protective and atherogenic lipoproteins (Yin et al., 2023). Hypertriglyceridemia and low HDL-C levels are easily measurable, low-cost markers that are independent of coronary heart disease. The plasma atherogenic index integrates these two parameters into a single biomarker. An increase in this parameter has been associated with adverse cardiovascular events in patients with T2DM (Ma et al., 2020) and may indicate a more severe metabolic form of the disease (Li et al., 2018). In addition, a recent systematic review and meta- analysis showed that people with high PAI values are more likely to develop atherosclerotic cardiovascular disease (Ulloque-Badaracco et al., 2022). Erythrocyte sedimentation rate also increased significantly in patients with T2DM, correlating with HbA1c (R = 0.8072; p < 0.0001), in agreement with other authors (Li et al., 2015). Hyperglycemia promotes hemoglobin glycation and alters erythrocyte elasticity, reducing their deformability and affecting microcirculation (Lee et al., 2019; Obeagu, 2024). The erythrocytes of diabetic patients are less flexible and more fragile, contributing to the development of microangiopathy and coronary heart disease (Agrawal et al., 2016; Wang et al., 2021).

Glycated hemoglobin correlates with inflammatory markers of cardiovascular risk in patients with type 2 diabetes mellitus Aguirre-Villegas, & Pedreáñez 24 San Gregorio de Portoviejo University | Ecuador Limitations of the study included non-probabilistic sampling, moderate sample size, and lack of control over variables such as the use of lipid-lowering or anti-inflammatory drugs. However, the findings highlight the clinical utility of combining HbA1c with fibrinogen, high- sensitivity C-reactive protein, and plasma atherogenic index for better cardiovascular risk stratification. In the Ecuadorian context, where T2DM and cardiovascular diseases are leading causes of morbidity and mortality, the incorporation of these accessible biomarkers could strengthen comprehensive assessment and preventive strategies in clinical practice. CONCLUSIONS Poorer glycemic control was significantly associated with higher concentrations of these parameters, demonstrating a positive and direct correlation between HbA1c and systemic inflammation and atherogenic risk. These findings suggest that HbA1c, in addition to reflecting metabolic control, could be used as an indirect marker of inflammatory status and cardiovascular risk in T2DM. The joint evaluation of HbA1c with biomarkers such as fibrinogen, high-sensitivity C-reactive protein, and atherogenic index of plasma could improve risk stratification and guide more personalized therapeutic strategies aimed at reducing macro- and microvascular complications. Future research should expand on these results through multicenter longitudinal studies evaluating the predictive utility of these biomarkers and their response to therapeutic intervention. Furthermore, their integration into clinical metabolic monitoring programs could help optimize glycemic control and reduce cardiovascular burden in patients with T2DM. ACKNOWLEDGMENTS The authors express their gratitude to the patients who participated in this research. The Provincial Teaching Hospital of Riobamba supported this study. No additional funding was received from commercial, public, or non-profit sources. CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest. AUTHOR CONTRIBUTIONS Conceptualization: Pablo Aguirre and Adriana Pedreáñez. Data curation: Pablo Aguirre and Adriana Pedreáñez. Formal analysis: Pablo Aguirre and Adriana Pedreáñez.

Revista Gregoriana de Ciencias de la Salud. Bi-annual peer-reviewed publication. ISSN 3028-8940 / January-June 2026;3(1):13-29 San Gregorio de Portoviejo University | Ecuador 25 Investigation: Pablo Aguirre and Adriana Pedreáñez. Methodology: Pablo Aguirre and Adriana Pedreáñez. Writing – original draft: Pablo Aguirre and Adriana Pedreáñez. Writing – review & editing: Pablo Aguirre and Adriana Pedreáñez. REFERENCES Agrawal, R., Smart, T., Nobre-Cardoso, J., Richards, C., Bhatnagar, R., Tufail, A., Shima, D., H Jones, P., & Pavesio, C. (2016). Assessment of red blood cell deformability in type 2 diabetes mellitus and diabetic retinopathy by dual optical tweezers stretching technique. Scientific Reports, 6, 15873. https://doi.org/10.1038/srep15873 Aguirre-Villegas, P., & Pedreañez, A. (2024). Could glycated hemoglobin be considered a marker of inflammation in patients with diabetes mellitus? International Journal of Medical and Surgical Sciences, 11(2), 1-13. https://doi.org/10.32457/ijmss.v11i2.2619 American Diabetes Association Professional Practice Committee (2024). 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2024. Diabetes Care, 47(Suppl 1), S179-S218. https://doi.org/10.2337/dc24-S010 Antonova, N., Velcheva, I., & Paskova, V. (2022). Hemorheological and microvascular disturbances in patients with type 2 diabetes mellitus. Clinical Hemorheology and Microcirculation, 81(4), 325–341. https://doi.org/10.3233/CH-221393 de Oliveira Dos Santos, A. R., de Oliveira Zanuso, B., Miola, V. F. B., Barbalho, S. M., Santos Bueno, P. C., Flato, U. A. P., Detregiachi, C. R. P., Buchaim, D. V., Buchaim, R. L., Tofano, R. J., Mendes, C. G., Tofano, V. A. C., & Dos Santos Haber, J. F. (2021). Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions. International Journal of Molecular Sciences, 22(5), 2639. https://doi.org/10.3390/ijms22052639 de Vries, J. J., Snoek, C. J. M., Rijken, D. C., & de Maat, M. P. M. (2020). Effects of Post- Translational Modifications of Fibrinogen on Clot Formation, Clot Structure, and Fibrinolysis: A Systematic Review. Arteriosclerosis, Thrombosis, and Vascular Biology, 40(3), 554-569. https://doi.org/10.1161/ATVBAHA.119.313626 Demir, S., Nawroth, P. P., Herzig, S., & Ekim Üstünel, B. (2021). Emerging Targets in Type 2 Diabetes and Diabetic Complications. Advanced Science, 8(18), e2100275. https://doi.org/10.1002/advs.202100275

Glycated hemoglobin correlates with inflammatory markers of cardiovascular risk in patients with type 2 diabetes mellitus Aguirre-Villegas, & Pedreáñez 26 San Gregorio de Portoviejo University | Ecuador Guo, Y., Wang, F., Ma, S., Mao, Z., Zhao, S., Sui, L., Jiao, C., Lu, R., Zhu, X., & Pan, X. (2025). Relationship between atherogenic index of plasma and length of stay in critically ill patients with atherosclerotic cardiovascular disease: a retrospective cohort study and predictive modeling based on machine learning. Cardiovascular Diabetology, 24(95). https://doi.org/10.1186/s12933-025-02654-3 Hamidullah, Ahmad, I., Ashraf, Ali, M., Hussain, M., & Zakirullah (2024). Correlation between plasma fibrinogen levels and microvascular complications in type 2 diabetes. Journal of the Pakistan Medical Association, 74(8), 1441-1448. https://doi.org/10.47391/JPMA.10403 Kane, J. P., Pullinger, C. R., Goldfine, I. D., & Malloy, M. J. (2021). Dyslipidemia and diabetes mellitus: Role of lipoprotein species and interrelated pathways of lipid metabolism in diabetes mellitus. Current Opinion in Pharmacology, 61, 21-27. https://doi.org/10.1016/j.coph.2021.08.013 Khanam, A., Alouffi, S., Alyahyawi, A. R., Husain, A., Khan, S., Alharazi, T., Akasha, R., Khan, H., Shahab, U., & Ahmad, S. (2024). Generation of autoantibodies against glycated fibrinogen: Role in diabetic nephropathy and retinopathy. Analytical Biochemistry, 685, 115393. https://doi.org/10.1016/j.ab.2023.115393 Kong, P., Cui, Z. Y., Huang, X. F., Zhang, D. D., Guo, R. J., & Han, M. (2022). Inflammation and atherosclerosis: signaling pathways and therapeutic intervention. Signal Transduction and Targeted Therapy, 7(131). https://doi.org/10.1038/s41392-022-00955-7 Lee, H., Na, W., Lee, S. B., Ahn, C. W., Moon, J. S., Won, K. C., & Shin, S. (2019). Potential Diagnostic Hemorheological Indexes for Chronic Kidney Disease in Patients With Type 2 Diabetes. Frontiers in Physiology, 10, 1062. https://doi.org/10.3389/fphys.2019.01062 Li, Q., Li, L., & Li, Y. (2015). Enhanced RBC Aggregation in Type 2 Diabetes Patients. Journal of Clinical Laboratory Analysis, 29, 387-389. https://doi.org/10.1002/jcla.21784 Li, X., Weber, N. C., Cohn, D. M., Hollmann, M. W., DeVries, J. H., Hermanides, J., & Preckel, B. (2021). Effects of Hyperglycemia and Diabetes Mellitus on Coagulation and Hemostasis. Journal of Clinical Medicine, 10(11), 2419. https://doi.org/10.3390/jcm10112419

Revista Gregoriana de Ciencias de la Salud. Bi-annual peer-reviewed publication. ISSN 3028-8940 / January-June 2026;3(1):13-29 San Gregorio de Portoviejo University | Ecuador 27 Li, Z., Huang, Q., Sun, L., Bao, T., & Dai, Z. (2018). Atherogenic Index in Type 2 Diabetes and Its Relationship with Chronic Microvascular Complications. International Journal of Endocrinology, 2018, 1765835. https://doi.org/10.1155/2018/1765835 Liu, R., Li, L., Shao, C., Cai, H., & Wang, Z. (2022). The Impact of Diabetes on Vascular Disease: Progress from the Perspective of Epidemics and Treatments. Journal of Diabetes Research, 2022, 1531289. https://doi.org/10.1155/2022/1531289 Ma, X., Sun, Y., Cheng, Y., Shen, H., Gao, F., Qi, J., Yang, L., Wang, Z., Shi, D., Liu, Y., Liu, X., & Zhou, Y. (2020). Prognostic impact of the atherogenic index of plasma in type 2 diabetes mellitus patients with acute coronary syndrome undergoing percutaneous coronary intervention. Lipids in Health and Disease, 19, 240. https://doi.org/10.1186/s12944-020-01418-0 Mitsios, J. P., Ekinci, E. I., Mitsios, G. P., Churilov, L., & Thijs, V. (2018). Relationship Between Glycated Hemoglobin and Stroke Risk: A Systematic Review and Meta-Analysis. Journal of the American Heart Association, 7(11), e007858. https://doi.org/10.1161/JAHA.117.007858 Nencini, F., Bettiol, A., Argento, F. R., Borghi, S., Giurranna, E., Emmi, G., Prisco, D., Taddei, N., Fiorillo, C., & Becatti, M. (2024). Post-translational modifications of fibrinogen: implications for clotting, fibrin structure and degradation. Molecular Biomedicine, 5, 45. https://doi.org/10.1186/s43556-024-00214-x Núñez-Cortés, J. M., & Pedro-Botet, J. (2021). Atherogenic dyslipemia: the other pandemic, associated with diabesity. Dislipemia aterogénica: la otra pandemia, asociada a la diabesidad. Clínica e Investigación en Arteriosclerosis, 33(1), 30-32. https://doi.org/10.1016/j.arteri.2020.12.001 Obeagu, E. I. (2024). Red blood cells as biomarkers and mediators in complications of diabetes mellitus: A review. Medicine, 103(8), e37265. https://doi.org/10.1097/MD.0000000000037265 Pereira, C., Sant’Ana, L. M., das Graças, M., Pires, L., Braga, K., & Fernandes, A. P. (2016). Diabetes mellitus: The linkage between oxidative stress, inflammation, hypercoagulability and vascular complications. Journal of Diabetes and its Complications, 30(4), 738-745. https://doi.org/10.1016/j.jdiacomp.2015.12.018

Glycated hemoglobin correlates with inflammatory markers of cardiovascular risk in patients with type 2 diabetes mellitus Aguirre-Villegas, & Pedreáñez 28 San Gregorio de Portoviejo University | Ecuador Perween, S., Abidi, M., Faizy, A. F., & Moinuddin (2019). Post-translational modifications on glycated plasma fibrinogen: A physicochemical insight. International Journal of Biological Macromolecules, 126, 1201-1212. https://doi.org/10.1016/j.ijbiomac.2019.01.018 Reddy, K. S. S., Varadaraj, P., Nallusamy, G., & SenthilNathan, S. (2024). Correlation Between Hemoglobin A1c (HbA1c) and High-Sensitivity C-Reactive Protein (hs-CRP) in Myocardial Infarction Patients and Their Six-Month Mortality Follow-Up. Cureus, 16(8), e67070. https://doi.org/10.7759/cureus.67070 Rohm, T. V., Meier, D. T., Olefsky, J. M., & Donath, M. Y. (2022). Inflammation in obesity, diabetes, and related disorders. Immunity, 55(1), 31-55. https://doi.org/10.1016/j.immuni.2021.12.013 Shrestha, B., & Dunn, L. (2019). The Declaration of Helsinki on Medical Research involving Human Subjects: A Review of Seventh Revision. Journal of Nepal Health Research Council, 17(45), 548-552. https://scispace.com/papers/the-declaration-of-helsinki-on- medical-research-involving-yq85cdd235 Sulimai, N. H., Brown, J., & Lominadze, D. (2022). Fibrinogen, Fibrinogen-like 1 and Fibrinogen- like 2 Proteins, and Their Effects. Biomedicines, 10(7), 1712. https://doi.org/10.3390/biomedicines10071712 Tian, R., Tian, M., Wang, L., Qian, H., Zhang, S., Pang, H., Liu, Z., Fang, L., & Shen, Z. (2019). C-reactive protein for predicting cardiovascular and all-cause mortality in type 2 diabetic patients: A meta-analysis. Cytokine, 117, 59-64. https://doi.org/10.1016/j.cyto.2019.02.005 Ulloque-Badaracco, J. R., Hernandez-Bustamante, E. A., Alarcon-Braga, E. A., Mosquera-Rojas, M. D., Campos-Aspajo, A., Salazar-Valdivia, F. E., Valdez-Cornejo, V. A., Benites- Zapata, V. A., Herrera-Añazco, P., Valenzuela-Rodríguez, G., & Hernandez, A. V. (2022). Atherogenic index of plasma and coronary artery disease: A systematic review. Open Medicine, 17(1), 1915-1926. https://doi.org/10.1515/med-2022-0590 Viigimaa, M., Sachinidis, A., Toumpourleka, M., Koutsampasopoulos, K., Alliksoo, S., & Titma, T. (2020). Macrovascular Complications of Type 2 Diabetes Mellitus. Current Vascular Pharmacology, 18(2), 110-116. https://doi.org/10.2174/1570161117666190405165151

Revista Gregoriana de Ciencias de la Salud. Bi-annual peer-reviewed publication. ISSN 3028-8940 / January-June 2026;3(1):13-29 San Gregorio de Portoviejo University | Ecuador 29 Wang, Y., Yang, P., Yan, Z., Liu, Z., Ma, Q., Zhang, Z., Wang, Y., & Su, Y. (2021). The Relationship between Erythrocytes and Diabetes Mellitus. Journal of Diabetes Research, 2021, 6656062. https://doi.org/10.1155/2021/6656062 Wieczór, R., Wieczór, A. M., Kulwas, A., & Rość, D. (2019). Type 2 Diabetes and Cardiovascular Factors Contrasted with Fibrinolysis Disorders in the Blood of Patients with Peripheral Arterial Disease. Medicina, 55(7), 395. https://doi.org/10.3390/medicina55070395 Wolberg, A. S. (2023). Fibrinogen and fibrin: synthesis, structure, and function in health and disease. Journal of thrombosis and haemostasis. Journal of Thrombosis and Haemostasis, 21(11), 3005-3015. https://doi.org/10.1016/j.jtha.2023.08.014 Yang, X., Tao, S., Peng, J., Zhao, J., Li, S., Wu, N., Wen, Y., Xue, Q., Yang, C. X., & Pan, X. F. (2021). High-sensitivity C-reactive protein and risk of type 2 diabetes: A nationwide cohort study and updated meta-analysis. Diabetes/Metabolism Research and Reviews, 37(8), e3446. https://doi.org/10.1002/dmrr.3446 Yin, B., Wu, Z., Xia, Y., Xiao, S., Chen, L., & Li, Y. (2023). Non-linear association of atherogenic index of plasma with insulin resistance and type 2 diabetes: a cross-sectional study. Cardiovascular Diabetology, 22, 157. https://doi.org/10.1186/s12933-023-01886-5 Zhou, H. H., Tang, Y. L., Xu, T. H., & Cheng, B. (2024). C-reactive protein: structure, function, regulation, and role in clinical diseases. Frontiers in Immunology, 15, 1425168. https://doi.org/10.3389/fimmu.2024.1425168 Disclaimer / Editor's Note: All publications' statements, opinions, and data are solely those of the individual authors and contributors, not Revista Gregoriana de Ciencias de la Salud or the editors. Revista Gregoriana de Ciencias de la Salud and/or the editors disclaim all responsibility for any injury to persons or property resulting from any ideas, methods, instructions, or products referred to in the content.