Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia due to insulin resistance and/or inadequate insulin secretion. Over the past decades, it has become a major global health burden due to its rising prevalence and its role in accelerating cardiovascular and microvascular complications. A growing body of evidence now suggests that low-grade systemic inflammation plays a pivotal role in the pathogenesis and progression of T2DM and its associated complications【1】.

C-reactive protein (CRP), a well-established acute-phase reactant, has emerged as a key marker of systemic inflammation. Elevated CRP levels have been consistently observed in patients with T2DM and are believed to be linked not only to obesity and insulin resistance but also to poor glycemic control and the development of complications such as nephropathy and retinopathy【2】【3】. This inflammatory burden, as reflected by CRP, may contribute to endothelial dysfunction and vascular injury, further compounding the risk for both macrovascular and microvascular complications in diabetes【4】.

Several studies have examined the relationship between CRP and glycemic markers such as HbA1c and glycemic variability, with mixed findings. While some studies reported a significant correlation between high-sensitivity CRP and poor glycemic control, others found CRP levels to be more strongly associated with obesity or the duration of diabetes, rather than glycemia per se【1】【5】. Additionally, the role of CRP in predicting diabetic complications like nephropathy remains under investigation, with some studies suggesting an independent association, particularly in those with poor glycemic control【2】【5】【6】.

Given these observations, the present study aims to evaluate CRP levels in patients with T2DM and assess their association with glycemic control, albuminuria, and diabetes-related complications such as retinopathy, while also exploring the impact of other clinical risk factors such as blood pressure, lipid profile, and obesity. By elucidating these associations, we aim to better understand the inflammatory underpinnings of T2DM and its complications.

Aims and Objectives

Aim

This study aimed to investigate the association of serum C-reactive protein (CRP) levels with glycemic control and diabetes-related complications in patients with type 2 diabetes mellitus (T2DM).

Objectives

1. To compare the serum CRP levels between patients with T2DM and age- and sex-matched non-diabetic controls.
2. To assess the correlation between CRP levels and glycemic control as measured by HbA1c.
3. To evaluate the relationship between CRP levels and microalbuminuria as an early marker of diabetic nephropathy.
4. To determine the prevalence of elevated CRP in association with diabetic retinopathy.
5. To analyze the association of CRP with traditional cardiovascular risk factors such as:

• oBody Mass Index (BMI)
• oBlood Pressure (Systolic/Diastolic)
• oLipid profile (LDL and HDL cholesterol)

6. To identify independent predictors of elevated CRP levels using multivariate logistic regression analysis

Study Design and Setting

This cross-sectional analytical study was conducted at Ahana Hospital, Madurai, from April 2022 to August 2024. The aim was to evaluate the association between serum C-reactive protein (CRP) levels, glycemic control, and diabetic complications in individuals with type 2 diabetes mellitus (T2DM).

Study Population

A total of 100 participants were enrolled, comprising 50 patients diagnosed with T2DM (according to the American Diabetes Association criteria) and 50 age- and sex-matched non-diabetic controls. Controls had fasting plasma glucose levels below 100 mg/dL and no known metabolic or inflammatory conditions.

Inclusion and Exclusion Criteria

Participants were eligible if they were aged 35 to 70 years, had a confirmed diagnosis of T2DM for at least six months, and provided written informed consent. Exclusion criteria included the presence of acute infections, chronic inflammatory diseases, cardiovascular events within the past six months, stage 3 or higher chronic kidney disease, liver dysfunction, autoimmune disorders, malignancy, or current use of anti-inflammatory or immunosuppressive medications.

Ethical Considerations

The study protocol was reviewed and approved by the Institutional Ethics Committee of Ahana Hospital, Madurai. Written informed consent was obtained from all study participants.

Clinical and Biochemical Assessment

All participants underwent a comprehensive evaluation. Anthropometric measurements included height and weight, used to calculate body mass index (BMI, kg/m²). Blood pressure was measured in the sitting position using a calibrated sphygmomanometer. Fundus photography was performed to assess for diabetic retinopathy.

Venous blood samples were collected after an overnight fast. Laboratory tests included fasting plasma glucose, glycated hemoglobin (HbA1c, measured by high-performance liquid chromatography), and lipid profile (total cholesterol, HDL, LDL, and triglycerides). High-sensitivity C-reactive protein (hs-CRP) was measured by immunoturbidimetry. Microalbuminuria was assessed using the albumin-to-creatinine ratio from an early morning spot urine sample, expressed in mg/g.

Definitions

Poor glycemic control was defined as HbA1c >7%, in accordance with American Diabetes Association guidelines. Microalbuminuria was defined as an albumin-to-creatinine ratio between 30 and 300 mg/g, indicating early diabetic nephropathy. Dyslipidemia was defined by LDL cholesterol levels >130 mg/dL and/or HDL cholesterol <40 mg/dL in men or <50 mg/dL in women. Elevated CRP was defined as hs-CRP ≥3 mg/L, consistent with AHA/CDC guidelines for increased cardiovascular risk. Hypertension was defined as systolic blood pressure ≥140 mmHg and/or diastolic pressure ≥90 mmHg, or current use of antihypertensive therapy. Overweight was defined as BMI between 25.0 and 29.9 kg/m², while obesity was defined as BMI ≥30.0 kg/m².

Statistical Analysis

Data were analyzed using SPSS Version 26.0. Continuous variables were expressed as mean ± standard deviation (SD) and compared using independent t-test or Mann–Whitney U test, based on data distribution.

Categorical variables were analyzed using the chi-square test. Pearson or Spearman correlation coefficients were calculated to assess relationships between CRP and clinical variables. A binary logistic regression model was used to identify independent predictors of elevated CRP.

A p-value <0.05 was considered statistically significant.

1 Baseline Characteristics of Study Population

A total of 100 participants were enrolled, comprising 50 patients with type 2 diabetes mellitus and 50 age- and sex-matched non-diabetic controls. The baseline clinical and biochemical characteristics of both groups are summarized in Table 1.

Patients with diabetes exhibited significantly higher mean BMI (27.39 ± 4.11 kg/m²) compared to controls (24.65 ± 2.45 kg/m²; p < 0.001). Similarly, both systolic (139.27 ± 13.21 vs. 128.65 ± 11.93 mmHg; p < 0.001) and diastolic blood pressure (85.55 ± 11.07 vs. 78.52 ± 7.29 mmHg; p < 0.001) were significantly elevated in the diabetic group.

Lipid profile comparison revealed higher LDL cholesterol in diabetics (131.19 ± 27.78 mg/dL) versus controls (109.82 ± 22.83 mg/dL; p < 0.001) and lower HDL cholesterol (41.08 ± 8.89 vs. 49.95 ± 6.80 mg/dL; p < 0.001). Inflammatory burden was notably greater in diabetics, as reflected by CRP levels (5.05 ± 1.87 vs. 2.13 ± 0.76 mg/L; p < 0.001).

Glycemic control markers confirmed poor control in diabetics, with a mean HbA1c of 8.05% compared to 5.73% in controls (p < 0.001). Microalbuminuria, an early renal complication, was markedly elevated among diabetics (167.71 ± 104.67 mg/g vs. 18.06 ± 7.06 mg/g; p < 0.001). Additionally, 23 diabetic participants had evidence of retinopathy, while none was reported among controls (p < 0.001 by chi-square analysis).

Table 1. Clinical and Biochemical Parameters of Study Participants (n = 100)

2. Comparison of CRP Levels Between Diabetics and Controls

The mean CRP level among diabetic patients was significantly elevated at 5.05 ± 1.87 mg/L, compared to 2.13 ± 0.76 mg/L in non-diabetic controls (p < 0.001). This indicates a substantially higher inflammatory burden in individuals with type 2 diabetes mellitus.

3. Glycemic Control and Albumin Excretion

Among the 50 patients with type 2 diabetes mellitus, 31 individuals (62%) exhibited poor glycemic control, defined as an HbA1c level ≥ 7%. The remaining 19 patients (38%) had HbA1c levels < 7%. Microalbuminuria was present in 25 patients (50%), indicating a high prevalence of early diabetic nephropathy. These findings underscore the substantial burden of inadequate glycemic control and renal involvement in the diabetic population.

Table 2. Distribution of Glycemic Control and Microalbuminuria Among Diabetic Participants (n = 50)

4. Correlation Analysis

To investigate associations between systemic inflammation and key diabetic parameters, Pearson’s correlation analysis was conducted.

A strong positive correlation was observed between CRP and HbA1c (r = 0.829, p < 0.0001), indicating that higher CRP levels are significantly associated with poorer glycemic control. CRP also showed a moderate correlation with microalbuminuria (r = 0.461, p = 0.0007), suggesting a possible inflammatory link to early nephropathy. The correlation between CRP and duration of diabetes was weak and statistically insignificant (r = 0.202, p = 0.1595).

Table 3. Correlation of CRP with Diabetic Parameters

5. Association of CRP with Risk Factors

CRP levels were analyzed across several clinical and metabolic subgroups. Individuals with BMI >30 kg/m² exhibited the highest mean CRP (6.1 ± 1.2 mg/L), followed by those in the BMI 25–30 group (4.8 ± 1.0 mg/L), while those with BMI <25 had the lowest mean CRP (3.2 ± 0.7 mg/L). Diabetic patients with hypertension also showed elevated CRP levels (5.7 ± 1.3 mg/L) compared to normotensive participants (4.1 ± 1.0 mg/L).

CRP was substantially higher in individuals with retinopathy (6.2 ± 1.4 mg/L) than those without (3.9 ± 1.1 mg/L). Stratification by lipid parameters showed that subjects with LDL ≥130 mg/dL had a higher mean CRP (5.4 ± 1.2 mg/L) than those with LDL <130 mg/dL (3.6 ± 0.9 mg/L). Similarly, those with HDL <40 mg/dL had a higher CRP (5.9 ± 1.3 mg/L) than participants with HDL ≥40 mg/dL (4.2 ± 0.8 mg/L).

6. Multivariate Regression Analysis

To determine the independent predictors of elevated CRP levels (defined as ≥3 mg/L, consistent with the definitions section), a multivariate logistic regression analysis was performed using variables that were significant in univariate analysis.

After adjustment, elevated HbA1c, microalbuminuria, and LDL cholesterol levels were found to be significantly associated with increased odds of elevated CRP. Specifically:

• For each 1% increase in HbA1c, the odds of elevated CRP increased by approximately 2.14 times (OR: 2.14; 95% CI: 1.41–3.26; p < 0.001).
• Presence of microalbuminuria increased the odds of elevated CRP by 3.78 times (OR: 3.78; 95% CI: 1.71–8.33; p = 0.001).
• LDL cholesterol >130 mg/dL was also a significant predictor (OR: 2.21; 95% CI: 1.05–4.64; p = 0.036).
• Systolic blood pressure, for each 10-mmHg increase, was associated with modestly increased odds (OR: 1.32; 95% CI: 1.01–1.74; p = 0.045).
• BMI >25 kg/m² showed borderline significance (OR: 1.71; 95% CI: 0.95–3.08; p = 0.074).

Table 4. Multivariate Logistic Regression Identifying Predictors of Elevated CRP (≥3 mg/L) in Type 2 Diabetes Mellitus

This study provides comprehensive evidence supporting the role of C-reactive protein (CRP) as an inflammatory biomarker linked to poor glycemic control and early diabetic complications. The significantly elevated CRP levels in type 2 diabetic patients compared to non-diabetic controls (5.05 ± 1.87 mg/L vs. 2.13 ± 0.76 mg/L; p < 0.001) align with findings by Sasidharan et al. and Habib et al., who demonstrated higher CRP in diabetic cohorts and correlated it with worsening metabolic parameters and insulin resistance【7,8】.

In our study, the strength of association between CRP and glycemic control was notable. A robust positive correlation was observed between CRP and HbA1c (r = 0.829, p < 0.0001), indicating that systemic inflammation escalates with deteriorating glycemic regulation. This supports mechanisms described by Tang et al. and Elimam et al., where chronic hyperglycemia induces oxidative stress, endothelial dysfunction, and systemic inflammatory cascades【9,10】.

Renal involvement was also evident. Microalbuminuria was present in 50% of diabetic patients (mean 167.71 mg/g) and showed a moderate positive correlation with CRP (r = 0.461, p = 0.0007). Choudhary and Rodríguez-Morán have similarly reported CRP’s role in the pathogenesis of diabetic nephropathy, suggesting that it may predict early microvascular renal complications【12,13】.

Multivariate logistic regression further supported this inflammatory-metabolic interplay. HbA1c (OR: 2.14, 95% CI: 1.41–3.26; p < 0.001), microalbuminuria (OR: 3.78, 95% CI: 1.71–8.33; p = 0.001), and LDL cholesterol >130 mg/dL (OR: 2.21, 95% CI: 1.05–4.64; p = 0.036) were independently associated with elevated CRP (defined as ≥3 mg/L). These findings echo those of Mojiminiyi et al. and reinforce the clinical utility of CRP as a cardiovascular risk stratifier in diabetes【14】.

Subgroup analysis revealed elevated CRP levels in diabetics with retinopathy (mean: 6.2 ± 1.4 mg/L) compared to those without retinopathy (3.9 ± 1.1 mg/L). This finding is consistent with studies by Jabeen et al. and Stanimirovic et al., who emphasized CRP's contribution to microvascular pathogenesis and retinal ischemia【15,16】.

Dyslipidemia also played a role. Patients with LDL ≥130 mg/dL had higher CRP levels (5.4 ± 1.2 mg/L) than those with lower LDL (3.6 ± 0.9 mg/L). Similarly, HDL <40 mg/dL was associated with higher CRP (5.9 ± 1.3 mg/L), reflecting the intertwined nature of lipid abnormalities and inflammation.

Obesity, assessed via BMI, was another critical contributor. Participants with BMI >25 kg/m² showed significantly higher CRP levels (mean: 5.51 mg/L) than those with normal BMI (3.97 mg/L). These results are consistent with Al-Hamodi et al., who reported close associations between CRP, adiposity, and chronic subclinical inflammation mediated by adipokines【17】.

Broadly, our results are aligned with population-based studies like that of Phosat et al., which demonstrated associations between elevated inflammatory markers (CRP, IL-6, TNF-α), glycemic load, and type 2 diabetes prevalence【18】. Together, these findings support the potential utility of CRP as both a diagnostic and prognostic marker in diabetes care.

This study demonstrated a clear association between elevated C-reactive protein (CRP) levels and markers of poor glycemic control and diabetic complications among patients with type 2 diabetes mellitus. Diabetics exhibited significantly higher CRP levels than non-diabetic controls. Furthermore, CRP levels positively correlated with HbA1c and microalbuminuria, suggesting a role for systemic inflammation in both glycemic dysregulation and early renal involvement. The presence of higher CRP concentrations among patients with retinopathy, dyslipidemia, and elevated BMI further reinforces the potential of CRP as a composite biomarker reflecting the inflammatory milieu underlying diabetic pathophysiology. Multivariate regression analysis identified HbA1c and microalbuminuria as independent predictors of elevated CRP levels, underscoring the intertwined relationship between inflammation, glycemic burden, and end-organ damage. These findings suggest that integrating CRP into clinical monitoring may provide additional prognostic insight, potentially guiding early therapeutic strategies to mitigate the inflammatory risks associated with type 2 diabetes.

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