Serum Resistin and High-sensitivity C-reactive Protein as Independent Predictors of Vascular Complications in Type 2 Diabetes Mellitus: A Cross-sectional Observational Study at a Tertiary Care Center

Abstract

Background:

Serum resistin has been implicated in atherosclerosis and vascular smooth muscle dysfunction through inflammatory pathways, making it a potential biomarker for cardiovascular risk. Comparative data in diabetic patients with acute vascular events are limited. This study evaluates serum resistin and high-sensitivity C-reactive protein (hs-CRP) levels in type 2 diabetes mellitus (T2DM) with acute myocardial infarction (AMI) or acute ischemic stroke (AIS) to explore their association with vascular complications.

Materials and Methods:

A cross-sectional, hospital-based study was conducted among T2DM patients presenting with AMI or AIS. Serum resistin, hs-CRP, glycated hemoglobin (HbA1c), lipid profile, and body mass index (BMI) were evaluated, and their associations with vascular events were statistically analyzed, considering P < 0.05 as statistically significant.

Results:

The mean serum resistin was significantly higher in the diabetes mellitus (DM) with AMI group (23.21 ± 5.65 ng/ml; P < 0.001) compared to controls (13.30 ± 2.94 ng/ml) but not in the DM with AIS group (19.90 ± 5.46 ng/ml; P = 0.215). hs-CRP was significantly elevated in both DM with AMI and AIS groups (3.43 ± 0.70 mg/l and 3.43 ± 1.01 mg/l, respectively) compared to controls (2.43 ± 0.62 mg/l; both P < 0.001). Positive correlations were observed between these biomarkers and conventional risk factors, including HbA1c, BMI, and low-density lipoprotein cholesterol.

Conclusion:

Elevated serum resistin (notably in AMI) and hs-CRP (in both AMI and AIS) in T2DM patients highlight a strong association between inflammation and acute vascular events. These biomarkers may serve as accessible tools for early risk stratification and targeted preventive strategies in high-risk diabetic populations.

INTRODUCTION

In 2025, it is estimated that 589 million people have diabetes, and this number is projected to reach 853 million by 2050. In addition, around 252 million adults remain undiagnosed, highlighting the significant gap in detection. Diabetes was responsible for approximately 3.4 million deaths in 2024 globally.[1]

Coronary artery disease is a major macrovascular complication of diabetes mellitus (DM) and carries high mortality. Evidence suggests that resistin is involved in pathological processes leading to cardiovascular disease (CVD), including inflammation, endothelial dysfunction, thrombosis, angiogenesis, and smooth muscle cell dysfunction.[2] Resistin could also promote the production of pro-inflammatory mediators such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and IL-12, hence aggravating the pro-inflammatory response. Hence, serum resistin is a key mediator to induce macrophage pro-atherosclerotic effect.[2]

Diabetes is a well-established risk factor for stroke, especially ischemic strokes. Of the several stroke subtypes, individuals with diabetes are especially susceptible to cerebral small vessel diseases. Diabetes contributes to stroke through multiple mechanisms, including vascular endothelial dysfunction, premature arterial stiffness, systemic inflammation, and thickening of the capillary basement membrane, all of which promote atherosclerosis, impair cerebral blood flow, and increase the likelihood of ischemic events.[3]

Resistin is a 12.5 kDa cysteine-rich polypeptide derived from adipose tissue.[4] Human resistin directly binds to adenylyl cyclase-associated protein 1 in monocytes and upregulates cyclic AMP concentration, protein kinase A activity, and nuclear factor kappa-light-chain-enhancer of activated B cells-related transcription of inflammatory cytokines.[5] Inflammatory responses stimulated resistin secretion, and resistin could also promote the production of pro-inflammatory mediators such as IL-6, TNF-α, and IL-12. On the other hand, resistin could also affect the functions of vascular cells, activate endothelial cells, upregulate the expression of endothelin-1 (ET-1), adhesion molecules, and chemokines,[6,7] hence aggravating the pro-inflammatory response. Recently, resistin was reported to upregulate the expression of adhesion molecules, such as vascular cell adhesion molecule-1, in cultured endothelial cells.[8]

Earlier studies have shown that plasma resistin was found a statistically significant elevation in acute coronary syndrome (ACS) compared to the normal and stable angina group.[9] Furthermore, plasma resistin was positively correlated with indicators of inflammation and endothelial activation, such as leukocyte counts, high-sensitivity C-reactive protein (hs-CRP), and ET-1 levels in blood.[10] These findings all suggest that resistin plays a role in the pathogenesis of cardiovascular disease.

However, the relationship between serum resistin levels and ischemic stroke remains unclear. Previous studies have reported conflicting evidence regarding the role of resistin in acute cerebral ischemic events.[11,12] Notably, Yusuf et al. demonstrated no significant association between serum resistin levels and the risk of cardiovascular diseases, including stroke.[12]

C-reactive protein (CRP) is a member of the pentraxin family of proteins. It is an acute-phase reactant synthesized mainly by the liver. CRP has a relatively long half-life of 18–20 h, owing to its stable pentraxin structure. Serum CRP levels are elevated in response to acute infections, inflammatory conditions, and trauma. An association of hs-CRP with risk for CVD has been described in many studies.[,14,15] The Multiple Risk Factor Intervention Trial (MRFIT) showed a strong relationship between levels of hs-CRP and mortality from congenital heart defect in high-risk middle-aged men.[16] A similar association between increasing hs-CRP levels and subsequent rate of myocardial infarction (MI) and stroke was found in an analysis of apparently healthy individuals.[17]

Study objective

1. To assess the significance of serum resistin and hs-CRP as prognostic markers among type 2 DM (T2DM) patients

2. To evaluate the level of association of serum resistin and hs-CRP among T2DM patients along with acute MI (AMI) or acute ischemic stroke (AIS) as complications

3. To assess the short-term outcomes among T2DM patients in correlation with serum resistin and hs-CRP.

MATERIALS AND METHODS

Study design

All patients with T2DM attending a tertiary care teaching hospital with AMI or AIS and meeting the inclusion and exclusion criteria were included in the study group. The study period was 18 months. The study was approved by the institutional ethical committee (JSS/MC/PG/1117/2015-16).

Study subjects

The participants were divided into three groups:

• Group 1: T2DM with AMI 30 in numbers

• Group 2: T2DM with AIS 30 in numbers

• Group 3: DM with and without AMI and AIS – controls 30 in numbers.

Inclusion criteria

1. Age more than 40 years

2. T2DM with AMI

3. T2DM with AIS

4. T2DM without AMI and AIS (age group- and sex-matched patients will be taken as controls).

Exclusion criteria

1. Chronic kidney disease

2. Chronic liver disease

3. Any acute or chronic infection

4. Nondiabetic patients with AMI and AIS.

Methodology

Detailed clinical history and examination were conducted according to the protocol. A sufficient venous sample was collected from one of the veins using a vacutainer, and the sample was then subjected to centrifugation at 1500 rpm for 10 min at 4°C. The serum collected as a result was preserved at − 20°C. Subsequently, all the samples were analyzed for serum resistin (catalog no. GXBH142812) and hs-CRP (catalog no. GXBH141729) using enzyme-linked immunosorbent assay (ELISA) kits from Genxbio Health Sciences Pvt. Ltd. Glycated hemoglobin (HbA1c) levels were assessed by ion-exchange high-performance liquid chromatography. Cardiac biomarkers, troponin T and creatine kinase-MB, were estimated using the ELISA method. Transthoracic two-dimensional echocardiogram (2D ECHO) was performed using a standard 2D view Philips ECHO. The statistical significance of elevated serum resistin and hs-CRP in the study groups compared to the control groups was assessed. In addition, an attempt was made to determine the correlation between individual risk factors such as blood glucose, HbA1c, lipids, body mass index (BMI), and serum resistin.

Statistical analysis

Data were organized, tabulated, and analysed using SPSS version 16.0 (SPSS Inc., Chicago, IL, USA) and Microsoft Excel 2010 (Microsoft Corporation, Redmond, WA, USA). Categorical variables were compared using the Chi-square test. Continuous variables were expressed as mean ± standard deviation, and comparisons across the groups (T2DM with AMI, T2DM with AIS, and T2DM without vascular events) were performed using the one-way analysis of variance. Receiver operating characteristic (ROC) curve analysis was employed to assess the predictive ability of serum resistin levels for the occurrence of AMI or AIS in patients with T2DM. P <0.05 was considered statistically significant.

RESULTS

As shown in Table 1, in our study, the mean age in the diabetic group was 61.6 years, diabetics with AMI was 62.57 years, and diabetics with AIS was 61.83 years. Concerning gender, male and female patients were distributed equally in all the subgroups to avoid sex-based bias.

Table 1.

Mean age in diabetes mellitus, diabetes mellitus with acute myocardial infarction, and diabetes mellitus with acute ischemic stroke

Group	Age (years), mean±SD
DM only	61.60±10.48
DM with AMI	62.57±10.06
DM with AIS	61.83±11.07

DM=Diabetes mellitus, SD=Standard deviation, AMI=Acute myocardial infarction, AIS=Acute ischemic stroke

As shown in Table 2, the mean fasting blood sugar (FBS) was highest in the DM + AMI group (274.67 ± 55.05 mg/dl), followed by the DM + AIS group (234.67 ± 57.40 mg/dl) and the control DM group (210.70 ± 70.82 mg/dl). The mean postprandial blood sugar (PPBS) values showed a similar pattern: DM + AMI group (339.07 ± 66.95 mg/dl), DM + AIS group (318.67 ± 69.91 mg/dl), and control DM group (294.73 ± 76.18 mg/dl). HbA1c levels were elevated in both the complication groups – DM + AMI (9.28 ± 1.83%) and DM + AIS (9.69 ± 2.03%) – compared to controls (8.85 ± 1.88%). The mean BMI was also higher in patients with vascular complications (DM + AMI: 24.79 ± 2.99 kg/m²; DM + AIS: 24.52 ± 2.41 kg/m²) than in controls (23.38 ± 2.44 kg/m²).

Table 2.

Variables fasting blood sugar, postprandial blood sugar, glycated hemoglobin, body mass index, and lipid profile in the study group and the control group

	Group
	DM only, mean±SD	DM with AMI, mean±SD	DM with AIS, mean±SD
FBS (mg/dl)	210.70±70.82	274.67±55.05	234.67±57.40
PPBS (mg/dl)	294.73±76.18	339.07±66.95	318.67±69.91
HbA1c (%)	8.85±1.88	9.28±1.83	9.69±2.03
BMI (kg/m2)	23.38±2.44	24.79±2.99	24.52±2.41
Total cholesterol (mg/dl)	176.27±43.82	190.57±50.99	196.03±26.77
HDL (mg/dl)	39.19±9.24	35.32±8.50	38.52±8.21
LDL (mg/dl)	110.71±24.28	115.94±37.96	124.35±25.80
TG (mg/dl)	135.53±35.30	117.30±38.26	145.93±44.19

AMI=Acute myocardial infarction, DM=Diabetes mellitus, SD=Standard deviation, AIS=Acute ischemic stroke, BMI=Body mass index, FBS=Fasting blood sugar, PPBS=Postprandial blood sugar, HbA1c=Glycated hemoglobin, HDL=High-density lipoprotein, LDL=Low-density lipoprotein, TG=Triglyceride

In our study, the mean total cholesterol was significantly elevated in the DM with AMI group (190.57 ± 50.99 mg/dl) and the DM with AIS group (196.03 ± 26.77 mg/dl), compared to the control group (176.27 ± 43.82 mg/dl). In our study, the mean triglyceride in the DM with AIS group was 145.93 ± 44.19 mg/dl, and the mean triglyceride in the control group was 135.53 ± 35.3 mg/dl. In our study, the mean low-density lipoprotein (LDL) in the DM with AMI group was 115.94 ± 37.96 mg/dl, the mean LDL in the DM with AIS group was 124.35 ± 25.80 mg/dl, and the mean LDL in the control group was 110.71 ± 24.28 mg/dl, which was statistically significant (P = 0.0001).

As shown in Graph 1, the mean serum resistin levels were highest in the DM + AMI group (23.21 ± 5.65 ng/ml, P < 0.001 vs. controls), followed by the DM + AIS group (19.90 ± 5.46 ng/ml, P = 0.215 vs. controls), while the control DM group recorded the lowest levels (13.30 ± 2.94 ng/ml).

Graph 1.

Mean serum resistin in study subjects. DM = Diabetes mellitus, SD = Standard deviation, AMI = Acute myocardial infarction, AIS = Acute ischemic stroke

As shown in Graph 2, the mean hs-CRP levels were elevated in both the DM + AMI group (3.43 ± 0.70 mg/l) and the DM + AIS group (3.43 ± 1.01 mg/l) compared to the control DM group (2.43 ± 0.62 mg/l). This increase in the case groups was statistically significant (P < 0.001), highlighting a strong inflammatory component in diabetic patients with vascular complications.

Graph 2.

Mean high-sensitivity C-reactive protein in study subjects. hs-CRP = High-sensitivity C-reactive protein, DM = Diabetes mellitus, SD = Standard deviation, AMI = Acute myocardial infarction, AIS = Acute ischemic stroke

As shown in Graph 3, serum resistin demonstrated a strong ability to discriminate AMI cases among patients with T2DM, with an area under the curve (AUC) of 0.802 (standard error [SE] =0.050, 95% confidence interval [CI]: 0.703–0.902, P < 0.0001), indicating excellent predictive power. Similarly, hs-CRP also showed significant discriminative capacity for AMI, with an AUC of 0.713 (SE = 0.057, 95% CI: 0.602–0.824, P < 0.001), suggesting that it is a useful complementary biomarker.

Graph 3.

Area under the curve for diabetes mellitus with acute myocardial infarction and acute ischemic stroke groups. AMI = Acute myocardial infarction, AIS = Acute ischemic stroke, ROC curve = Receiver operating characteristic curve, hs-CRP = High-sensitivity C-reactive protein

As shown in Graph 3, hs-CRP demonstrated a modest but statistically significant ability to discriminate AIS in patients with T2DM, with an AUC of 0.629 (SE = 0.061, 95% CI: 0.508–0.749, P = 0.048). In contrast, serum resistin showed only limited discriminative capacity for AIS, with an AUC of 0.581 (SE = 0.061, 95% CI: 0.461–0.700, P = 0.215), which was not statistically significant.

As shown in Table 3, in the present study, serum resistin levels showed a statistically significant positive correlation with LDL cholesterol, FBS, and BMI, indicating that higher resistin levels are associated with worsening of these conventional cardiovascular risk factors. Similarly, hs-CRP levels also demonstrated a positive correlation with these parameters, although these associations did not reach statistical significance.

Table 3.

Pearson’s correlation of elevated serum resistin levels with other variables

Pearson’s correlation	hs-CRP (P)	Serum resistin (P)
FBS (mg/dl)
r	0.153	0.303
P	0.150	0.004
n	90	90
PPBS (mg/dl)
r	0.117	0.173
P	0.271	0.103
n	90	90
HbA1c (%)
r	0.374	0.195
P	0.095	0.066
n	90	90
BMI (kg/m2)
r	0.191	0.263
P	0.072	0.012
n	90	90
Total cholesterol (mg/dl)
r	0.117	0.125
P	0.272	0.240
n	90	90
HDL (mg/dl)
r	−0.179	−0.140
P	0.091	0.187
n	90	90
LDL (mg/dl)
r	0.402	0.973
P	0.089	0.004
n	90	90
TG (mg/dl)
r	−0.073	−0.001
P	0.493	0.996
n	90	90

“r” denotes Pearson’s correlation coefficient, n represents the number of samples for each variable, and P indicates the significance of the statistical analysis (P<0.05 is considered statistically significant). BMI=Body mass index, FBS=Fasting blood sugar, PPBS=Postprandial blood sugar, HbA1c=Glycated hemoglobin, HDL=High-density lipoprotein, LDL=Low-density lipoprotein, TG=Triglyceride, hs-CRP=High-sensitivity C-reactive protein

As shown in Table 4, in the present study, hs-CRP levels in the DM with AMI group were higher among patients who deceased (3.84 mg/L) compared to those who survived (3.39 mg/L). In the DM with AIS group, hs-CRP levels were lower in the single deceased patient (3.07 mg/L) compared to survivors (3.44 mg/L); however, no meaningful conclusion can be drawn due to the extremely small sample size in this subgroup.

Table 4.

Short-term mortality in relation to high-sensitivity C-reactive protein and serum resistin

Group
	DM + AMI		DM + AIS
	n	Mean±SD	n	Mean±SD
hs-CRP
Alive	27	3.39±0.71	29	3.44±1.02
Death	03	3.84±0.36	01	3.07±1.01
Serum resistin
Alive	27	23.16±5.64	29	19.81±5.55
Death	03	23.69±3.33	01	22.27±0.86

Similarly, serum resistin levels in the DM with AMI group were slightly higher in deceased patients (23.69 ng/mL) compared to survivors (23.16 ng/mL). In the DM with AIS group, deceased patients had higher serum resistin levels (22.27 ng/mL) compared to survivors (19.81 ng/mL). These findings suggest a possible trend toward higher inflammatory biomarker levels being associated with mortality, although the small number of deaths limits definitive interpretation.

DISCUSSION

In our study, serum resistin levels were significantly elevated in patients with T2DM who experienced AMI, with a 1.75-fold increase compared to the control group (P < 0.001). This finding is consistent with previous studies by Wang et al.[9] and Solovey A et al.,[10] who also reported a strong association between elevated resistin and acute coronary events. Chu et al.[18,19] demonstrated that plasma resistin levels in patients with ACS were up to 2.8 times higher than in controls, while Hesham Hibrahim et al.[20] observed markedly elevated levels in Egyptian patients with both T2DM and ST-elevation myocardial infarction. Moreover, Del Cristo Rodríguez Pérez et al.[21] linked elevated resistin to increased all-cause and cardiovascular mortality. Mechanistically, the resistin promotes systemic inflammation and endothelial dysfunction – key drivers of atherosclerosis – thereby plausibly contributing to the heightened AMI risk in T2DM patients.

In contrast, serum resistin levels in T2DM patients presenting with AIS were also higher than in controls but did not reach statistical significance (P=0.215). Nevertheless, this trend aligns with findings Yusuf S et al.[14] Lee et al.[22] reported significantly higher median Resistin levels in ischemic stroke patients compared to controls (35.7 [interquartile range (IQR): 13.0–70.5] ng/mL vs. 10.0 [IQR: 5.4–16.5] ng/mL; P < 0.001), and cross sectional studies have shown a direct relationship between Resistin and carotid intima–media thickness – a surrogate marker for atherosclerosis.[23] Given its pro inflammatory and pro atherogenic actions, Resistin may contribute to cerebrovascular events by accelerating vascular injury and plaque instability, even if statistical significance is not always demonstrable in smaller cohorts.

hs-CRP levels were also significantly elevated in both AMI and AIS groups compared to controls (P < 0.001), reflecting an inflammatory milieu. This finding is in agreement with Rao VS, Kadarinarasimhiah et al.,[24] who observed a significant increase in hs-CRP in AMI patients compared to controls. Furthermore, in a prospective cohort study by Rao et al.,[25] involving 1021 subjects (772 with established coronary artery disease and the remainder as controls), hs-CRP emerged as an independent predictor of recurrent coronary events. These results suggest that hs-CRP is not only a sensitive marker of inflammation but also a potential prognostic indicator, likely contributing to the development and progression of atherosclerosis.

ROC curve analysis in our study revealed that serum resistin demonstrated a strong discriminatory capacity for AMI (AUC: 0.802, 95% CI: 0.703–0.902; P < 0.0001), while hs-CRP also showed good predictive ability (AUC: 0.713, 95% CI: 0.602–0.824; P < 0.001). For AIS, hs-CRP had a modest but statistically significant discriminatory capacity (AUC: 0.629, 95% CI: 0.508–0.749; P = 0.048), whereas resistin’s performance was weaker and nonsignificant (AUC: 0.581, 95% CI: 0.461–0.700; P = 0.215).

Correlation analysis demonstrated a statistically significant positive association between serum resistin levels and LDL cholesterol, fasting blood glucose, and BMI. hs-CRP levels also correlated positively with these parameters, though not significantly. These findings reinforce the interplay between metabolic dysregulation, inflammation, and cardiovascular risk.

Glycemic control markers (fasting and PPBSs and HbA1c) and lipid parameters (total cholesterol and triglycerides) were consistently elevated in the study group compared to controls. BMI was also higher in cases, reflecting the clustering of obesity, dyslipidemia, and hyperglycemia – all factors that may amplify the inflammatory burden and atherogenic potential of elevated resistin and hs-CRP.

Finally, mortality analysis revealed that among AMI patients, both serum resistin and hs-CRP levels were higher in those who died compared to survivors. In AIS patients, resistin levels were also higher in nonsurvivors, though hs-CRP was paradoxically lower, possibly due to the limited number of deaths in this subgroup. While not definitive, these trends suggest that elevated inflammatory biomarkers may portend poorer outcomes in acute vascular events.

In summary, our findings add to the growing body of evidence implicating resistin as both a biomarker and potential mediator of cardiovascular and cerebrovascular disease in T2DM. The combined elevation of resistin and hs-CRP underscores the intertwined roles of inflammation and metabolic dysregulation in atherothrombotic events. Larger, longitudinal studies are warranted to confirm causality, refine predictive models, and evaluate whether targeting resistin-mediated pathways could reduce vascular risk in high-risk diabetic populations.

Limitations

This study has several limitations. Serum resistin was measured without fasting standardization, although postprandial increases have been reported. Isoform-specific resistin variations were not assessed. The cross-sectional, single-center design with a single postevent measurement precludes causal inference – elevated resistin may be a marker rather than a cause of ischemic events. Furthermore, the absence of serial measurements and follow-up limits our understanding of temporal changes. The modest sample size restricts generalizability, underscoring the need for larger, prospective, multicentric studies with standardized protocols to validate these findings.

CONCLUSION

Our study demonstrates that elevated serum resistin and hs-CRP levels in DM are strongly linked to AMI and AIS, with robust correlations to established risk factors such as HbA1c, BMI, and LDL-cholesterol. Importantly, we observed a higher mortality trend in diabetics with AMI and AIS compared to diabetics without vascular events, underscoring their potential prognostic value. These results position serum resistin and hs-CRP as promising, accessible biomarkers of systemic vascular inflammation that may aid in early risk stratification. Given the scarcity of Indian data in this domain, our findings warrant urgent validation through large-scale, multicenter prospective studies to establish their role in predicting acute ischemic events and guiding preventive strategies.

Conflicts of interest

We declare that this manuscript is original, has not been published before, and is not currently being considered for publication elsewhere. We confirm that the manuscript has been read and approved by all named authors and that there are no other people who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. We understand that the corresponding author is the sole contact for the editorial process. He/she is responsible for communicating with the other authors about progress, submissions of revisions and final approval of proofs.

Funding Statement

Nil.