|Year : 2018 | Volume
| Issue : 3 | Page : 928-934
Evaluation of pentraxin-3 level in patients with diabetic retinopathy
Mohamed Zakarya Nouh1, Ahmed Sonbol2, Mohammed Mogahed3
1 Department of Internal Medicine, Faculty of Medicine, Menoufia University, Al Minufiyah, Egypt
2 Department of Clinical Pathology, Faculty of Medicine, Menoufia University, Al Minufiyah, Egypt
3 Department of Internal Medicine, Ministry of Health, Cairo, Egypt
|Date of Submission||21-Feb-2017|
|Date of Acceptance||18-Apr-2017|
|Date of Web Publication||31-Dec-2018|
Department of Internal Medicine, Ministry of Health, Cairo
Source of Support: None, Conflict of Interest: None
The aim of this study was to evaluate serum pentraxin-3 (PTX3) levels as an indicator of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).
DR is responsible for 10.2% of worldwide visual loss. Pentraxin-3 is an acute phase protein secreted by different types of cells and correlates with the disease activity.
Patients and methods
A total of 80 individuals were included in the study. They were divided into three groups. Group 1 included 30, type 2 diabetic patients without retinopathy, group 2 included 30, type 2 diabetic patients with retinopathy, and group 3 included 20 apparently healthy individuals. Group 2 was subdivided into 20 patients with nonproliferative and 10 patients with proliferative DR. Serum glycated hemoglobin, C-reactive protein (CRP), lipid profile, liver function tests, renal function tests, serum PTX3 level, and fundus examination were measured in all the patients.
Serum PTX3 was significantly elevated in T2DM with retinopathy than T2DM without retinopathy and control group. There is no statistical difference between proliferative and nonproliferative DR regarding PTX3. Serum PTX3 was significantly positively correlated with age and high-sensitivity CRP in the proliferative DR group and cholesterol, low-density lipoprotein and high-sensitivity CRP in the proliferative DR group.
PTX3 levels were significantly higher in T2DM with retinopathy than those without retinopathy and control group, and positively correlated with inflammatory marker. Thus, it might be used in the prognosis of DR.
Keywords: diabetes mellitus, diabetic retinopathy, pentraxin-3, prognosis
|How to cite this article:|
Nouh MZ, Sonbol A, Mogahed M. Evaluation of pentraxin-3 level in patients with diabetic retinopathy. Menoufia Med J 2018;31:928-34
|How to cite this URL:|
Nouh MZ, Sonbol A, Mogahed M. Evaluation of pentraxin-3 level in patients with diabetic retinopathy. Menoufia Med J [serial online] 2018 [cited 2019 Jun 19];31:928-34. Available from: http://www.mmj.eg.net/text.asp?2018/31/3/928/248721
| Introduction|| |
Diabetes mellitus (DM) is an epidemic disease that accounts for high rate of morbidity and mortality. This is due to the high rate of occurrence of complications that lead to health burden both for patients and countries. Death from cardiovascular complications affects nearly 50% of type 2 diabetes mellitus (T2DM) patients.
Diabetic complications include both microvascular and macrovascular. Retinopathy, nephropathy, and neuropathy are microvascular complications.
DM microvascular complications are caused by systemic inflammatory reaction,. The relationship between increased plasma concentration of acute phase biomarkers such as C-reactive protein (CRP) and T2DM has been reported by several studies,.
Singh et al. stated that diabetic retinopathy (DR) is a microangiopathy affecting all of the small retinal vessels, such as arterioles, capillaries, and venules. DR is characterized by increased vascular permeability, ocular hemorrhages, and lipid exudate. DR is responsible for a higher percentage of patients with visual loss. Recently, DR is classified as either nonproliferative or proliferative.
Pentraxin-3 (PTX3) is an acute phase reactant released by peripheral tissues in response to endothelial dysfunction. PTX3 promotes restenosis, inhibits angiogenesis, and increases the formation of advanced atherosclerotic lesions, typically by inhibiting the fibroblast growth factor (FGF2) reaction of angiogenesis,. Recently, PTX3 has been shown to be a sensitive biomarker of localized inflammatory reactions and innate immunity in cardiovascular and renal diseases,,.
Elevated levels of plasma CRP and short pentraxin are more frequently observed in both DM and DR patients,.
There are very few studies on PTX3 in DR, so the aim of our study was to determine the PTX3 level in T2DM patients with retinopathy and use it as a diagnostic and prognostic tool among those patients.
| Patients and Methods|| |
This study was carried out at the Internal Medicine Department, Menoufia University Hospitals and Ahmed Maher Teaching Hospital. We divided the patients into three groups: group 1 included 30 T2DM patients without retinopathy (16 men and 14 women); group 2 included 30 T2DM patients with retinopathy (17 men and 13 women); and group 3 included 20 apparently healthy volunteers as a control (10 men and 10 women). Group 2 is subdivided into 20 patients with nonproliferative diabetic retinopathy (NPDR) and 10 patients with proliferative diabetic retinopathy (PDR).
All patients underwent full history taking and clinical examination was performed. Blood pressure measurements were taken using sphygmomanometer as a mean on three times at different occasions in sitting position: diastolic pressure (DP), systolic pressure (SP) measured, and mean arterial pressure = DP + 1/3(SP − DP), (normally 70–110 mmHg). Also, BMI was calculated as the weight in kilograms divided by the square of the height in meters (kg/m2).
Patients with the following criteria were excluded: patients with a history of hypertension, patients with any form of chronic infection or current or past history of receiving any immune modulating drugs, patients with malignancy, renal impairment, intravenous drug abusers, patients with severe eye disease, and retinal detachment.
The protocol for this study followed the ethical standards and approved by the ethical committee of our institution and all patients gave informed consent to participate in this study.
Blood samples for hematological and biochemical measurements were obtained from the forearm after overnight fasting. Serum glycated hemoglobin (HA1C), CRP, liver function tests, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and renal function tests (urea, creatinine) were measured by standard methods in the routine clinical laboratory.
Serum PTX3 levels were determined by an enzyme-linked immunoassay using PTX3 ELISA kits from Shanghai Sunred Biological Technology Company (Shanghai, China), according to the manufacturer's instructions.
Fundus examination was carried out by slit lamp biomicroscope and indirect ophthalmoscopy, fundus color photograph centered on the macula and fundus fluorescein angiography wherever indicated.
Data were analyzed using the Program for Social Science, version 20.0 for windows (SPSS Inc., Chicago, Illinois, USA) and MedCalc 13 for windows (MedCalc Software BVBA, Ostend, Belgium). Data were analyzed using statistical quantitative data and were expressed as mean ± SD. Qualitative data were expressed as frequency and percentage. The following statistical tests were used as appropriate: χ2-test, Student's t-test. Correlations between variables were done using Spearman's rank correlation coefficient (r). Values of P less than 0.05 were taken as statistically significant.
| Results|| |
Sixty diabetic patients were included in our study. They were divided into two groups; group 1 diabetic without retinopathy (30 patients), group 2 included 30 T2DM patients with retinopathy (17 men and 13 women); group 3 included 20 apparently healthy volunteers as a control (10 men and 10 women); besides group 2 was subdivided into NPDR (20 patients) and PDR (10 patients). Mean age of the groups were 55.03 ± 7.44,58 ± 6.68 and 66 ± 5.14 years, respectively, and the female: male ratios were 14: 16, 8: 12, and 5: 5, respectively [Table 1].
|Table 1: Comparison between studied groups according to demographic and clinical data|
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HA1C was highly significant in diabetes with normal fundus and retinopathy groups than in the control group (P = 0.000), whereas there was no significant difference between retinopathy group and diabetes with normal fundus group (P = 0.914) [Table 1].
As regards PTX3 and high-sensitivity C-reactive protein (hsCRP) levels, there were highly significant increase in NPDR group than in diabetes with normal fundus group (P = 0.000); there was also significant difference between PDR and diabetes with normal fundus group (P = 0.001 and 0.002, respectively) and no significant difference between PDR and NPDR (P = 0.891 and 0.981v) [Table 2] and [Figure 1] and [Figure 2].
|Table 2: Comparison between diabetes without retinopathy group and retinopathy subgroups (nonproliferative diabetic retinopathy and proliferative diabetic retinopathy) according to demographic and clinical data|
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|Figure 1: Comparison between log PTX3 and log hsCRP in the studied groups. DM, diabetes mellitus; log hsCRP, log-transformed value of high-sensitivity C-reactive protein; PTX3, Pentraxin-3.|
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|Figure 2: Comparison between levels of log hsCRP and log PTX3 in the patient group. DM, diabetes mellitus; log hsCRP, log-transformed value of high-sensitivity C-reactive protein; NPDR, nonproliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy; PTX3, Pentraxin-3.|
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In diabetes with normal fundus group PTX3 was positively correlated with hsCRP and age, significant with systolic blood pressure and not significant with duration, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, cholesterol, diastolic blood pressure, LDL, HDL, and HA1C [Table 3].
|Table 3: Correlation between log Pentraxin-3 and other measured laboratory parameters|
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In NPDR group, PTX3 did not correlate with duration, blood pressure, AST, ALT, creatinine, cholesterol, blood pressure, LDL, HDL, and HA1C. However, PTX3 is highly significant with age, with significant correlation with hsCRP [Table 3].
In the PDR group, PTX3 did not correlate with age, duration, blood pressure, AST, ALT, creatinine, cholesterol, blood pressure, HDL, and HA1C). In contrast, PTX3 was significant with (log hsCRP, cholesterol, LDL) [Table 3] and [Figure 3].
|Figure 3: Correlation between log hsCRP and log PTX3 in diabetes with retinopathy. log hsCRP, log-transformed value of high-sensitivity C-reactive protein; PTX3, Pentraxin-3.|
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The cutoff point for PTX3 was 1150 pg/ml that has sensitivity 93.3% and specificity 72%, and cutoff point of CRP was 760 pg/ml has sensitivity 93.3% and specificity 68%. Combined use of PTX3 and CRP decrease sensitivity to 76.7%, but increase specificity to 90% [Figure 4].
|Figure 4: Receiver operating characteristic curve for detection of the best cutoff point of serum PTX3 and hsCRP in diabetic retinopathy. log hsCRP, log-transformed value of high-sensitivity C-reactive protein; PTX3, Pentraxin-3.|
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| Discussion|| |
The most common microvascular complication of DM is DR that leads to preventable visual loss in diabetic patients,. The percentage of DR in T2DM after a duration of 20 years is estimated at about 60%. The increased incidence of DR is due to many factors such as poor glycemic control and long duration of diabetes, associated hypertension, hyperlipidemia, nephropathy, pregnancy, and anemia.
Many factors have involved in the pathogenesis of DR such as chronic hyperglycemia, increased polyol and protein kinase C pathway activity,, increased vascular endothelial growth factor, production of advanced glycation end products, chronic oxidative damage, increased activation of the renin angiotensin system, and chronic inflammation and leukostasis.
PTX3 is a 200 amino acid protein that is secreted from the endothelium, macrophages, myeloid cells, dendritic cells, and many other cells in response to cytokines and endotoxins such as bacterial products, interleukin-1, and tumor necrosis factor.
PTX3 plays many biological roles such as in the regulation of inflammatory reaction, innate immunity, and female fertility. The expression of PTX3 is increased in acute coronary syndromes, and it is a predictor of poor outcome in congestive heart failure patients. PTX3 is also increased in many other diseases such as sleep apnea syndrome, pulmonary infection, rheumatoid arthritis, progressive systemic sclerosis, and in other rheumatologic diseases.
Both PTX3 and CRP are acute phase reactants known to be involved in inflammation, endothelial dysfunction, and atherosclerosis,,,,. As they are increased in DM, they can be used as prognostic factors for vascular complications such as DR,,.
In our study, plasma levels of PTX3 and CRP were significantly higher in both NPDR and PDR than in diabetes with normal fundus group and with normal individuals, whereas there was no significant difference between both groups of diabetic retinopathy. This reflects that DR in T2DM is an inflammatory process associated with increase inflammatory reactants.
PTX3 and CRP, in our study as well as in the study by Zhou et al. and Yang et al., showed significant increase in their levels with the development and progression of DR, with a cutoff value of 1150 pg/ml and sensitivity 93.3% and specificity 72% for PTX3, and with a cutoff value of 760 pg/ml and sensitivity 93.3% and specificity 68% for CRP. The combined use of PTX3 and CRP decreases the sensitivity to 76.7%, but increases specificity to 90%.
Similar results regarding elevated PTX3 and CRP in DR were documented by Yang et al. and Woo et al.,, who reported that the retinal pigment epithelium and vascular tissues can express PTX3 locally reflecting that it can be used as a biomarker of vascular inflammation. Yang et al. stated that PTX3 levels are associated with the development and progression of DR in Korean patients with T2DM. This was a case–control study which recruited 163 individuals – 92 diabetic patients with DR, 30 diabetics without DR, and 41 healthy controls whose plasma levels of PTX3 and hsCRP were measured and compared. The proportion of higher-degree retinal complications increased in direct correlation with log PTX3 levels with a P trend less than 0.001 whereas a similar analysis based on log hsCRP values had a P trend of 0.006. On the basis of the PTX3 and hsCRP levels selected based on receiver operating curves, the diagnostic sensitivity of PTX3 for DR was 53.3% and the sensitivity was 91.7% while for hsCRP it was 51.1 and 70.8%, respectively. The authors therefore suggested that PTX3 may be a more accurate predictor of DR development than hsCRP. The presence of elevated PTX3 levels from early disease and its progressive elevation with increasing disease severity seem to suggest it has potential as a screening marker.
Nowak et al. reported similar results regarding CRP whereas other studies such as that of Cai et al. and Nguyen et al., did not show significant association between CRP and DR. Few studies have reported lower serum levels of CRP in T2DM with DR compared with those without DR as in Lim et al. and Tsunoda et al.. Yang et al. assumed that this discrepancy could be due to differences in the sites of inflammation and production of inflammatory cytokines or the effects of confounding factors such as drugs or liver disease.
Possible explanations of this association are that DM microangiopathy is associated with endothelial dysfunction and neutrophil adhering to the damaged endothelium and inducing local vascular and tissue injury. This leukocyte–endothelial interaction produces PTX3 that is believed to be involved in innate immunity and tissue remodeling.. This supports the hypothesis that T2DM may be a manifestation of ongoing cytokine-mediated acute-phase response, initiated by the innate immune system.
| Conclusion|| |
PTX3 as well as CRP are acute phase reactants that can be used as markers of progression of retinopathy in T2DM and they are increased with disease duration. Moreover, poor glycemic control was significantly associated with higher incidence and severity of diabetic retinopathy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3]