A
Plasma fibrinogen level and its association with type 2 diabetes: A Comparative cross-sectional studyAbstract
Background
Diabetes remains a major public health concern in the world amongst non-communicable diseases. It is commonly diagnosed by glycemic level, using various glucose-measuring methods, and the condition of the specimen. In addition, other biochemical markers provide valuable insights into disease progression and complications. Fibrinogen, in particular, serves as an indicator of mild inflammation and atherosclerotic risk. Numerous studies have demonstrated that hemostatic factors, especially elevated fibrinogen levels, may contribute to the development of atherosclerosis and its related complications. These studies also report that fibrinogen concentrations tend to be higher in individuals with diabetes compared to those without the condition.
Aim of the study:
This study aims to investigate the relationship of fibrinogen level with type 2 diabetes, along with other biochemical parameters.
Methods
A comparative cross-sectional study design was employed.
Results
Comparison of fibrinogen level, glycated haemoglobin (HbA1c), Fasting Blood Sugar (FBS), Low-Density Lipoprotein cholesterol (LDL-c), and Total Cholesterol (TC) was significantly higher among diabetics than controls (P < 0.05). The fibrinogen level in microvascular complications was found to be greater than in non-complications and showed a statistically significant difference (357.6 ± 63 vs. 300.3 ± 56.8, p < 0.001)
Conclusion
Our results underline that fibrinogen level is found to be higher in diabetic patients compared to apparently healthy controls and revealed a positive correlation with glycated haemoglobin.
Keywords:
Type 2 diabetes
Fibrinogen
glycated haemoglobin (HbA1c)
A
A
A
Introduction
Diabetes mellitus (DM) is a common metabolic disorder attributed to poor control of blood sugar levels, with chronic hyperglycemia leading to the development and progression of complications associated with DM (1). Type 2 DM is increasingly recognized as an issue related to abnormalities in the innate immune system, with its evolution associated with ongoing low-grade systemic inflammation, oxidative stress, and dysfunction of the endothelium, which together contribute to a hypercoagulable state associated with microvascular and macrovascular complications (2, 3). It poses a significant health challenge for individuals worldwide, affecting both developed and developing countries. Type 2 diabetes mellitus (T2DM) is a primary cause of mortality and morbidity on a global scale(4).
Plasma fibrinogen is a principal protein in the human body, synthesized in the liver, and its primary function is known role in the coagulation or clotting process. It's an important determinant of blood viscosity, platelet aggregation, and thrombus formation (5). The normal reference range of fibrinogen in the blood is 200–400 mg/dl, and the physiologic importance of fibrinogen is demonstrated by the bleeding diathesis related to afibrinogenemia and dysfibrinogenemia (6). Various study suggests that fibrinogen may have a role in the formation of atherosclerotic plaques, including the early stages. Therefore, elevated fibrinogen level in diabetes plays a significant role in the emergence of complications of atherosclerosis(7, 8).
Different investigators are not certain whether hyperfibrinogenemia is a cause or simply a marker of cardiovascular disease. Hence, hyperfibrinogenemia might a result of the chronic inflammation and the buildup of fatty plaques on blood vessel walls that lead to cardiovascular disease. On the other hand, hyperfibrinogenemia may actively increase blood thickness and to form thrombi (9).
Diabetes Mellitus has having significant impact on health both in developed and developing nations. The association between blood hypercoagulability and diabetes mellitus can lead to the rapid progression of atherosclerosis and the onset of microvascular complications related to diabetes. Several studies have shown that hemostatic factor, especially hyperfibrinogenemia, is implicated as a source of atherosclerosis and its complications, and have reported that fibrinogen levels were higher in diabetics than in controls (10, 11).
Additionally, as increasing evidence from epidemiological studies divulges that elevated plasma fibrinogen levels are associated with an increased risk of cardiovascular disorders, including ischemic heart disease, stroke, and others like thromboembolism(12). The rise of cardiovascular morbidity and mortality rates appears to relate to the synergism of hyperglycemia with other cardiovascular risk factors, and individuals with insulin resistance have elevated levels of plasminogen activator inhibitors (especially PAI-1) and fibrinogen, which enhances the coagulation process and impairs fibrinolysis (13). There is a paucity of data and studies on the relation of plasma fibrinogen level in diabetes with complications and in Ethiopia; hence, this study was carried out to fill this gap and to provide updated information
Methods
Aim of the study
To assess the relationship of fibrinogen level with the glycemic status of type 2 diabetes
To determine the correlation of fibrinogen with biochemical parameters
To compare the fibrinogen level between type 2 diabetes and an apparently healthy control group
Study setting
The study was conducted at Durame General Hospital, Durame is a town in Southeastern Ethiopia. Study design and period
An observational comparative cross-sectional study was conducted from June 2023 to March 2024 at Durame General Hospital, Durame, southeastern Ethiopia
Source population
A
For case group: All type 2 diabetic patients attend at Durame General Hospital.
For control group: All apparently healthy clients who visited Durame General Hospital
and for medical and master health check-ups.
Study population
Case-group: Type two diabetic patients, both newly diagnosed and those on treatment, who attended the hospital during the study period, and were willing to take part in the study.
Control-group: Apparently healthy clients who visited the hospital during the study period and were willing to take part in the study. Those were medical and master health check-ups
Eligibility criteria
Inclusion criteria
Case group: Type 2 diabetic subjects of adult age groups giving consent.
Control group: Apparently healthy subjects of adults who are matched to case groups and willing to participate in the study.
Exclusion criteria
Patients who take oral anti-coagulant, anti-platelet, and fibrinolytic drug therapy
Pregnancy
Women use oral contraceptives
Patients who had a recent history of surgery
Patients had a history of chronic illness
History of hypercoagulability, thromboembolism, inherited coagulation disorders, and cancer.
Study variables
Dependent variable
Fibrinogen level
Independent variable
Age
sex
Marital state
Residence
Duration of illness
Duration of treatment
Measurement and Data Collection
Sample size determination
The sample size was calculated based on the previously studied mean and standard deviation of cases and controls by using a comparative study calculation formula (14).
372.30 ± 123.78 case group and 323.60 ± 73.16 Controls
(𝑍𝛼/2. 𝑍𝛽)2 2(SD)2 /d2
where 𝑍𝛼/2 is the critical value for the significance level of 95%
𝑍𝛽 is the critical value for the desired power (0.84 for 80% power)
d = effect size (mean difference)
n = (1.96 + 0.84)2. 2(124)2÷ (49)2
n = 101
With a 10% non-response rate, the total sample size is 112 in each group
Fibrinogen measurement: A blood sample was drawn, and it was mixed with sodium citrate (3.2%) solution in the ratio of 9:1, and plasma was separated from the tube and stored in plastic tubes; plasma fibrinogen level was measured by the Clauss method as per the prescribed guidelines. Platelet-poor plasma was prepared from the sample in the citrated tube after centrifuging at 1500g for 15 minutes to analyze the fibrinogen level by a coagulation analyzer (Ares linear, Spain).
HA1c estimation
is based on the fluorescence immunoassay technology, specifically the sandwich immuno–detection method. Whole blood is added to the mixture of hemolysis buffer and detection buffer, which results in hemolysis of red blood cells. Such that by mixing the detector buffer with the blood specimen in a test tube, the fluorescence–labelled detector anti-HbA1c antibody in the buffer binds to the HbA1c antigen in the blood specimen.
Lipid profiles
Total cholesterol, triglycerides, High-Density Lipoprotein (HDL), and Low-Density Lipoprotein (LDL) were determined using the enzymatic principle of the test methods, and the Siemens X200 dimension chemistry analyzer was used.
Data collection procedure
The data was collected after informed consent was obtained from participants for the procedure. Then, clinical history was collected without breaching the confidentiality of the patient, and the clinical information was obtained from the chronic outpatient department. Socio-demographic data were collected through a self-administered questionnaire for those who can read and a face-to-face interview for those who cannot read. The respondent reads the questions and fills in the answers by him/herself in the presence of the interviewer's assistance.
Data Quality Assurance
The data was collected by the principal investigator, with the assistance of highly skilled staff in the working area. Laboratory tests were done with stringent adherence to Standard Operating Procedure (SOP). The patient sample was collected by an experienced phlebotomist and transported to the analysis section. Samples were properly labelled with the corresponding patient's ID number. Adequate sample volume was collected for analysis, and the sample shipment processed was monitored prudently to prevent hemolysis. The sample was platelet-poor plasma, and the impact of anticoagulant proportionality was considered. Pre-tested standardized questionnaire was used for comprehensiveness, effectiveness, reliability, and validity.
Data analysis and interpretation
The Data were coded, entered, and edited via Microsoft Excel and transferred to SPSS version 27 for analysis. Basic descriptive analysis, mean, and standard deviation as appropriate, were done.
Distribution was tested analytically and graphically. The most common analytical test to check data for a normal distribution, the Kolmogorov-Smirnov test, was used. Data was checked for
completeness, discerned, and entered into SPSS version 27. Student t-test, one-way analysis of variance (ANOVA) were used for the analyses. A p-value of < 0.05 was considered significant.
Ethical consideration
All the study procedures and issues were reviewed and approved by the Ethics Committee of
Addis Ababa University College of Health Science, Department of Medical Laboratory Sciences,
Department of Research, and Ethics Committee (DREC/728/23). A support letter was written to
A
Durame General Hospital to get permission to start the study. Informed, and written consent wasattained from each of the participants at the time of enrollment for the study, and the risk of harm,
confidentiality, anonymity, and conflict of interest were considered and maintained. Hence, all these ethical issues were managed.
Result
Sociodemographic characteristics
A total of 224 study participants were recruited for this study, and the gender composition was 111(49.5%) males and 113 (50.5%) females. The mean age of the diabetic group with age range of 48.6 ± 8.6 years, which was a little bit higher than that of the control group (47.6 ± 8.2) years with age range of 30–65 years, and didn’t show a statistically significant difference. The highest number of patients, 42 (37.5%), belonged to the 41–50 year age group. The lowest number of patients was found in the > 61 years age group (Table 1).
Variables | Diabetics | Non-diabetics | P value | |||
|---|---|---|---|---|---|---|
Frequency | Percentage | Frequency | Percentage | |||
Age | 0.23 | |||||
30–40 | 22 | 19.6% | 21 | 18.8 | ||
41–50 | 42 | 37.5% | 56 | 50 | ||
51–60 | 37 | 33% | 23 | 20.5 | ||
> 61 | 11 | 9.8% | 12 | 10.7 | ||
Gender | Male | 59 | 52 | 46.4 | 0.35 | |
Females | 53 | 60 | 53.6 | |||
Marital status | Married | 97 | 86.6% | 105 | 93.8% | 0.07 |
Unmarried | 9 | 8% | 5 | 4.5% | ||
Divorced /widowed | 6 | 5.4% | 2 | 1.8% | ||
Residence | Urban | 81 | 72.3% | 82 | 73.2% | 0.88 |
Rural | 31 | 27.7% | 30 | 26.8% | ||
Educational status | No formal education | 32 | 28.6 | 40 | 35.7% | 0.43 |
Elementary | 40 | 35.7% | 35 | 31.3% | ||
Secondary | 25 | 22.3% | 21 | 18.8% | ||
College and above | 15 | 13.4% | 16 | 14.3% | ||
Occupation | Employed | 21 | 18.8% | 26 | 23.2% | 0.27 |
Self employed | 49 | 43.8% | 51 | 45.5% | ||
others | 42 | 37.5% | 35 | 31.3% | ||
Blood pressure and BMI characteristics of diabetics and controls.
The clinical data of the diastolic, systolic blood pressure, and Body Mass Index (BMI) showed statistical differences between diabetics and controls (Table 2).
Variables | Cases | Controls | t value | ||
|---|---|---|---|---|---|
BMI (kg/m2) | 23.4 ± 2.8 | 22.3 ± 2.6 | 2.1 | P = 0.03 | |
DBP | 81.6 ± 5.7 | 79.7 ± 7.2 | 3.0 | P = 0.036 | |
SBP | 124.5 ± 8.9 | 116.9 ± 9 | 6.2 | P < 0.001 |
Comparison of fibrinogen, glucose, and lipid parameters in diabetic and apparently healthy controls
The mean value differences of fibrinogen, glucose level, and lipid profiles, with the exceptions of Triglyceride (TG) and High-Density Lipoproteins (HDL), show statistically significant differences between type 2 diabetes and apparently healthy controls (Table 3).
Variables | Diabetic patients (mean ± SD) | Apparently healthy Control (mean ± SD) | t value | P value |
|---|---|---|---|---|
Fibrinogen | 315.1 ± 63.4 | 292.1 ± 62.8 | 2.7 | P = 0.007 |
FBS | 132.4 ± 38.8 | 96.1 ± 16.2 | 9.1 | P < 0.001 |
PPG | 202.5 ± 42.8 | 136.4 ± 21.5 | 14.5 | P < 0.001 |
Hba1c | 7.2 ± 1.4 | 5.8 ± 0.96 | 8.7 | P < 0.001 |
TC | 178.4 ± 30.4 | 166.1 ± 30.2 | 3.0 | P = 0.03 |
TG | 139.8 ± 24 | 134.6 ± 19.8 | 1.7 | P = 0.082 |
LDL | 125.2 ± 20.4 | 117.5 ± 18.2 | 2.9 | P = 0.03 |
HDL | 62.3 ± 12.5 | 62.4 ± 15.7 | -0.24 | P = 0.097 |
Data are expressed as mean values ± standard deviation (SD). The inter-group variability is determined by the independent Student’s t-test; the significance level the P < 0.05.
HbA1c = glycated hemoglobin; FBS = Fasting blood Sugar; PPG = Postprandial glucose; TC = Total cholesterol; TG = Triglyceride; LDL = Low-Density Lipoprotein; HDL = High-Density Lipoprotein.
Plasma fibrinogen levels with age distribution
Based on age group categories, plasma fibrinogen mean value disparity didn’t reveal a statistically significant difference (Table 4).
Age distribution | Number | Df | F | P value | |
|---|---|---|---|---|---|
30–40 | 22 | 320.5 ± 51.3 | 3 | 0.24 | 0.87 |
41–50 | 42 | 316 ± 64.3 | |||
51–60 | 37 | 308.6 ± 72.1 | |||
> 61 | 11 | 322.8 ± 56 |
ANOVA was used, P < 0.05
Gender wise distribution of plasma fibrinogen, glucose level, and lipid parameters of type 2 diabetes
The mean value of Triglyceride (TG) and Total Cholesterol (TC) in males and females was (144.4 ± 24.5), (P = 0.03), (134.6 ± 22.7), (P = 0.04), respectively, and it revealed a statistically significant difference. Mean of fibrinogen in females (321.2 ± 59.3) was higher compared to males (309.6 ± 66.9, p = 0.34 (Table 5).
Variables | Male | Females | P value |
|---|---|---|---|
FBS | 136.3 ± 41.4 | 128.1 ± 35.6 | 0.27 |
PPG | 198.9 ± 45.6 | 206 ± 39.6 | 0.38 |
HbA1C | 7.3 ± 1.5 | 7.1 ± 1.3 | 0.64 |
Fibrinogen | 309.6 ± 66.9 | 321.2 ± 59.3 | 0.34 |
TG | 144.4 ± 24.5 | 134.6 ± 22.7 | 0.03 |
TC | 184 ± 32.2 | 172.2 ± 27.2 | 0.04 |
LDL | 126.5 ± 19.9 | 123.8 ± 21.1 | 0.49 |
HDL | 63.3 ± 11.6 | 61.2 ± 13.3 | 0.38 |
Data are expressed as mean values ± standard deviation (SD). The inter–group variability is determined by the independent Student’s t-Test; significance level of P < 0.05
A
Fibrinogen and lipid profiles in HbA1c Outcome of poor and good glycemic control.In accordance with good and poor HbA1c cut-off values, glycemic control of the mean value of fibrinogen level (p = 0.02) and Low-Density Lipoprotein cholesterol (LDL-c) (P < 0.001) demonstrates statistically significant changes (Table 6 ).
Variables | HbA1c cut-off value < 6.5 | (Mean ± SD) | P value |
|---|---|---|---|
≥ 6.5 | |||
Fibrinogen | < 6.5 | 300.9 ± 62.5 | 0.02 |
≥ 6.5 | 328.3 ± 61.9 | ||
TC | < 6.5 | 177.6 ± 31.6 | 0.147 |
≥ 6.5 | 179.2 ± 29.4 | ||
TG | < 6.5 | 136.4 ± 22.8 | 0.79 |
≥ 6.5 | 142.9 ± 24.8 | ||
LDL | < 6.5 | 117.4 ± 19.2 | P < 0.001 |
≥ 6.5 | 132.6 ± 18.8 | ||
HDL | < 6.5 | 63.6 ± 10.8 | 0.28 |
≥ 6.5 | 61.1 ± 13.7 |
Data are expressed as mean values ± standard deviation (SD). The independent Student’s t-test determines the variability of the group; the significance level of the p-value is P < 0.05
A
Fig. 1
Bar chart of fibrinogen in good vs poor glycemic status
Simple Pearson correlations of fibrinogen with glycemic level and lipid profiles.
The current study of the correlation between fibrinogen with glycemic status and lipid profiles demonstrated a positive correlation between HbA1c, Fasting Blood Sugar levels (FBS), LDL-c, and triglyceride levels in relation to plasma fibrinogen levels. In contrast, no correlation was found with HDL levels. Therefore, with poor glycemic control, a higher level of fibrinogen was found (r = 0.2, p = 0.011) (Table 7).
Variable | Hb1c | FBS | TC | TG | LDL | HDL | Duration of disease | Duration of treatment |
|---|---|---|---|---|---|---|---|---|
r | 0.24 | 0.28 | -0.12 | 0.26 | 0.25 | -0.19 | 0.007 | 0.06 |
P Value | 0.011 | 0.03 | 0.19 | 0.007 | 0.009 | 0.038 | 0.91 | 0.5 |
Statistical analysis was done by Pearson's rank correlation coefficient (r), significance level is p < 0.005
R2 = 0.058
A
Figure 2: A scattered diagram showed the correlation between mean HbA1C and plasma fibrinogenComparison of fibrinogen, glycemic status, and lipid profiles in complicated vs non-complicated type 2 diabetes.
Out of the total number of diabetes cases, 25.9% (29) exhibited microvascular complications. The fibrinogen level was (357.6 ± 63 vs. 300.3 ± 56.8, p < 0.001), and HbA1c levels (7.8 ± 1.4 vs. 7.0 ± 1.4, p = 0.01) showed statistically significant differences (Table 8 ).
Variables | Type 2 diabetes with microvascular complications | Type 2 diabetes without microvascular complications | P value |
|---|---|---|---|
Fibrinogen | 357.6 ± 63 | 300.3 ± 56.8 | P < 0.001 |
HbA1c | 7.8 ± 1.4 | 7.0 ± 1.4 | 0.01 |
FBS | 144.2 ± 43.8 | 128.3 ± 36.3 | 0.057 |
TG | 142.7 ± 24.6 | 138.7 ± 23.9 | 0.45 |
TC | 173.6 ± 28.8 | 180.1 ± 30.9 | 0.32 |
LDL | 129.3 ± 19.7 | 123.8 ± 20.6 | 0.22 |
HDL | 55.2 ± 12.3 | 56. ± 13.7 | 0.76 |
An independent samples t-test was used: P < 0.05: Statistically significant
The values are shown as mean ± Standard error of the mean.
Relationship of Fibrinogen level with microvascular complications
Although the average fibrinogen levels are elevated in the complicated group compared to the non-complicated group, the mean differences observed among microvascular complications did not show a statistically significant difference (p = 0.89) (Table 9).
Microvascular complications | Mean ± SD | F value | P value |
|---|---|---|---|
Retinopathy | 11 (364 ± 45.5) | 0.144 | 0.89 |
Nephropathy | 13 (356.9 ± 76.6) | ||
Neuropathy | 3 (345.2 ± 68.3) | ||
Total | 29 (357.6 ± 63) |
ANOVA was used, with statistical significance set at p < 0.005
A
Fig. 3
Mean plot of fibrinogen with relation to microvascular complications.
Diagnostic value of fibrinogen in type 2 diabetes
To evaluate the diagnostic value of fibrinogen in differentiating between diabetic and healthy individuals, the figure shows the ROC curve comparing patients and healthy controls. The test indicated that the area under the curve (AUC) was [ 0.61 ± 0.38(SE), 95% CI (0.53–0.68), P = 0.007]. The sensitivity and specificity at a cutoff value of 307.25 mg/dL were 0.60 and 0.40, respectively, indicating moderate discrimination (Fig. 4).
Fig. 4
Receiver operating characteristic (ROC) curve for fibrinogen in the context of discrimination of diabetic patients from apparently healthy controls, and it has poor or limited clinical/practical utility in this finding.
Discussion
The present study was conducted to evaluate the plasma fibrinogen in patients with type 2 DM, and to study its correlation with certain parameters such as age, gender, duration of diabetes, lipid profile, glycosylated hemoglobin (HbA1c), and microvascular complications. In our study, 112 patients with type 2 DM were studied compared to 112 non-diabetic participants as a control, and the report showed, diabetics had higher fibrinogen levels than controls, with a mean value of diabetics 315.1 ± 63.4 and a mean value of controls 292.1 ± 62.8 (p = 0.07), and HbA1c. A study by Asharaf H. et al. agrees with our finding fibrinogen levels were higher in diabetics than in controls. Mean of fibrinogen level was 331.48 ± 63.5 among diabetes group, and mean fibrinogen level was 246.19 ± 18.2 in the non-diabetes group (p < 0.001), and the average of hemoglobin A1c among type 2 diabetes cases and in non-diabetes cases was found to be 9.40 ± 1.1 and 6.12 ± 0.5, respectively (p < 0.01)(15) Similarly, fibrinogen levels are elevated in type II diabetes mellitus patients(16). However, a study conducted by K.N. et al. revealed that the level of fibrinogen didn’t show a significant difference between cases and controls(17).
In our study, we found that the mean fibrinogen level was slightly higher in males(337.73mg/dl) than in females (320.44 mg/dl), ( p > 0.05), indicating that the changes in male and female mean value of fibrinogen levels were not significant. A similar finding was demonstrated in the study, that the males had a mean fibrinogen level of 342 ± 156 mg/dl, and females had a mean fibrinogen of 301 ± 110 mg/dl, which was lower, but not statistically significant(18).
The current study of plasma fibrinogen based on gender differences of diabetics is in line with the study conducted by Soliman GZ. Although female patients showed a higher plasma level of fibrinogen (4.19 ± 2.3 mg/dL) than male patients (3.82 ± 1.29 mg/dL), this difference was not statistically significant (P = 0.496)(19). Similarly, a study by Jain et al., in line with our report, did not find any association between fibrinogen and sex (9).
Conversely, a study by Kamath SD, et al. the mean fibrinogen level in male and female diabetics was 450.95 ± 25 mg/dl and 438.26 ± 32.15 mg/dl, respectively. Thus, the level was higher in males than in females, and this difference was significant (p < 0.01)(20). There are various possible mechanisms for hyperfibrinogenemia in diabetics. the fact that a procoagulant state often exists in people with diabetes signifies an increased risk of cardiovascular conditions (10).
Our study supports that an increase in glycosylated hemoglobin was found to be increase in plasma fibrinogen levels and is statistically significant. Mean of fibrinogen levels in diabetic patients with HbA1c ≥ 6.5 (476.27 ± 202.04) is higher compared to those with HbA1C < 6.5 (373.23 ± 178.11), with a statistically significant difference (p = 0.039). Hyperglycemia in diabetes contributes to hyperfibrinogenemia and activates the coagulation cascade. This could be due to glycosylated fibrinogen is less susceptible to plasmin degradation, relative insulin deficiency in diabetes results in differential protein synthesis, a decrease in albumin synthesis, and an increase in fibrinogen (21, 22).
In diabetic microangiopathy, certain phenomena have been proposed to explain elevated fibrinogen levels in patients with diabetes mellitus. Increased fibrinogen is considered to be associated with low-grade inflammation, increased activation of platelets, leukocytes, and the presence of heterotypic aggregations(23). Furthermore, levels of cytokines like Interleukin-6 are elevated in diabetes, which is thought to trigger liver cells to produce larger amounts of fibrinogen, indicating an important link between inflammation and increased blood clotting(24). Insulin resistance is considered another important risk factor that leads to escalated fibrinogen hepatic production in patients with T2DM(25). The rise in fibrinogen levels could be a consequence of inflammation driven by the underlying disease process, potentially increasing the risk of developing type 2 diabetes. However, additional evidence supports the idea that higher plasma fibrinogen levels might have a direct impact (26).
In accordance with the study conducted by Mohan G. et al. (2017), which aligns with the current study, and shows plasma fibrinogen level was higher in diabetic patients compared to controls, and it is also exceeded in diabetic patients with microvascular complications (293.43 ± 51.09 mg/dl) compared to those without microvascular complications (238.90 ± 44.1, p < 0.001) (27).
In the current study, HbA1c level indicated a positive correlation with fibrinogen levels ( r = 0.24, p = 0.011), and similarly, Abdelmonem M. et al. (2023) found a significant positive correlation between fibrinogen and HbA1c in the fair control group (r = 0.424, p = 0.003) and the poor control group (r = 0.369, P < 0.001)(28). Moreover, the mean HbA1c in T2DM cases correlated significantly with fibrinogen level. Similar results were observed by Bemde AS. And Gupta RK et al, (10, 29). On the contrary, Desai KP. et al. report that fibrinogen level did not reveal a significant correlation with HbA1c ( r = 0.58, p = 0.083) (17). Thus, it might be possible that the study, diabetic patients with controlled HbA1c levels, and this could have caused a lack of significant positive correlation between fibrinogen and HbA1c levels.
A study by Jain K. et al., and Desai, V. A. et al. (2020) supports our study and showed a positive correlation between serum cholesterol levels, LDL levels, and triglyceride levels, with plasma fibrinogen levels, and an inverse relation with HDL levels(30, 31). Unlikely the current report, Razak M.K. and Sultan A.A. found that triglyceride and High-Density Lipoprotein (HDL) showed significant differences between type 2 diabetes and controls(32).
Conclusion
The present study found that the average plasma fibrinogen level was higher in individuals with type 2 diabetes compared to controls and was greater in those with complications versus those without. Spearman's correlation analysis revealed significant positive associations between fibrinogen levels and glycosylated hemoglobin (HbA1c), fasting glucose, serum cholesterol, and low-density lipoprotein (LDL-c) in type 2 diabetic patients. Thus, plasma fibrinogen measurement may serve as a marker for cardiovascular disease and inflammation in type 2 diabetes.
Limitations
The study was observational, cross-sectional, and conducted on a small scale. To gain a clear understanding of the association, larger, multicenter studies are necessary. Although the study provided valuable information, it had some limitations. The sample size was relatively small and came from a single center, which may restrict the applicability of the findings. Additionally, inflammatory markers such as interleukin and CRP levels were not measured, which could have offered further insight into fibrinogen's involvement in systemic inflammation in diabetes.
Abbreviations
BMI Body Mass Index
DSB Diastolic Blood Pressure
SBP Systolic Blood Pressure
DM Diabetes Mellitus
FBS Fasting Blood Sugar
HbA1c Glycated haemoglobin
HDL-c High-Density Lipoprotein Cholesterol
LDL-c Low-Density Lipoprotein Cholesterol
PAI Plasminogen Activator Inhibitors
T2DM Type 2 Diabetes Mellitus
TC Total Cholesterol
TG Triglyceride
Correspondence: Yazal Abay
Email: yazalabay12@gmail.com
A
Author Contribution
Yazal Abay1: Conceptualization, data collection, formal analysis, methodology, and writing-original draft.Birku Gashaw2: Data collection, formal analysis, investigation, and methodology.Bisrat Fikadu2: Data curation and visualizationDerso Wale3: Writing, review, and editing.Abate Atimut4: methodology and data analysisAbera Abreham5: Data collection, formal analysis, and supervisionAbush Getaneh5: Overall supervision and editing.All authors have read and agreed to the published version of the manuscript.
Birku Gashaw2: Data collection, formal analysis, investigation, and methodology.
Bisrat Fikadu2: Data curation and visualization
Derso Wale3: Writing, review, and editing.
Abate Atimut4: methodology and data analysis
Abera Abreham5: Data collection, formal analysis, and supervision
Abush Getaneh5: Overall supervision and editing.
A
All authors have read and agreed to the published version of the manuscript.Affiliation:
1.
1. Department of Medical Laboratory Science, Hematology and Immunohematology, College of Health Science, Wolkite University, Ethiopia
2.
2. Department of Medical Laboratory Science, Clinical Chemistry, College of Health Science, Wolkite University, Ethiopia
3.
3. Department of Medical Laboratory Science, Medical Microbiology, College of Health Science, Wolkite University, Ethiopia
4.
4. Department of Medical Laboratory Science, Medical Parasitology, College of Health Science, Wolkite University, Ethiopia
5.
5. Department of Medical Laboratory Science, Clinical Chemistry, College of Health Science, Dilla University, Ethiopia
A
Funding:
No funding was available
A
Data Availability
Data is available upon contacting the corresponding author for further information when needed, with a reasonable request. The main sheet of the data is available with the corresponding author and will be made available to the editor on demand.
Declarations
Ethics approval and consent to participate
A
The Ethics Committee of the Department of Medical Laboratory, Addis Ababa University, approved. A
All participants provided informed consent at the baseline assessment.Consent for publication:
Not Applicable.
Competing interests:
The authors declare no competing interests.
Reference
1.
Maritim A, Sanders A, Watkins J. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol. 2003;17(1):24–38.
2.
Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27(5):1047–53.
3.
Sarangi R, Padhi S, Mahapatra S, Bhumika N. Serum nitric oxide metabolites and high sensitivity C-reactive protein are important biomarkers in non obese, Indian type 2 diabetic males. Int J Diabetes Developing Ctries. 2012;32(3):163–8.
4.
Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge A, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138:271–81.
5.
Abdulrahaman Y, Dallatu M. Evaluation of prothrombin time and activated partial thromboplastin in patients with diabetes mellitus. Nigerian J basic Appl Sci. 2012;20(1):60–3.
6.
Yang S-H, Du Y, Zhang Y, Li X-L, Li S, Xu R-X, et al. Serum fibrinogen and cardiovascular events in Chinese patients with type 2 diabetes and stable coronary artery disease: a prospective observational study. BMJ open. 2017;7(6):e015041.
7.
Davalos D, Akassoglou K, editors. Fibrinogen as a key regulator of inflammation in disease. Seminars in immunopathology. Springer; 2012.
8.
Lu PP, Liu JT, Liu N, Guo F, Ji YY, Pang X. Pro-inflammatory effect of fibrinogen and FDP on vascular smooth muscle cells by IL-6, TNF-α and iNOS. Life Sci. 2011;88(19–20):839–45.
9.
Jain A, Gupta H, Narayan S. Hyperfibrinogenemia in patients of diabetes mellitus in relation to glycemic control and urinary albumin excretion rate. J Assoc Phys India. 2001;49:227–30.
10.
Gupta P, Bhambani P, Narang S. Study of plasma fibrinogen level and its relation to glycemic control in type-2 diabetes mellitus patients attending diabetes clinic at a tertiary care teaching hospital in Madhya Pradesh, India. Int J Res Med Sci. 2016;4(9):3748–54.
11.
Le DSN, Miles R, Savage PJ, Cornell E, Tracy RP, Knowler WC, et al. The association of plasma fibrinogen concentration with diabetic microvascular complications in young adults with early-onset of type 2 diabetes. Diabetes Res Clin Pract. 2008;82(3):317–23.
12.
Soma P, Pretorius E. Interplay between ultrastructural findings and atherothrombotic complications in type 2 diabetes mellitus. Cardiovasc Diabetol. 2015;14(1):96.
13.
Manjiri R, Naik SM. Plasma Fibrinogen Levels in Deranged Lipids of T2DM. Int J Curr Med Appl Sci. 2020;26(1):0–5.
14.
Ghongade PV, Atram MA, Shivkumar VB. A study of correlation of plasma fibrinogen levels with glycemic status in type 2 Diabetes Mellitus patients. J Pathol Nepal. 2020;10(2):1746–50.
15.
Ashraf H, Rani K, Bai K, Bhatti U, Rustam M. Association of Serum Fibrinogen with Hemoglobin A1c among Type 2 Diabetic patients and non-diabetics. P J M H S 2021;15(1).
16.
Festa A, D’Agostino R Jr, Tracy RP, Haffner SM. Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes. 2002;51(4):1131–7.
17.
Desai KP, Roopakala M, Silvia CWD, Kumar KP. Evaluation of plasma fibrinogen levels in type 2 diabetes mellitus. Int J Diabetes Developing Ctries. 2012;32(4):209–13.
18.
Bembde AS. A study of plasma fibrinogen level in type-2 diabetes mellitus and its relation to glycemic control. Indian J Hematol Blood Transfus. 2012;28(2):105–8.
19.
Soliman GZ. Abnormalities in plasma concentration of lipids and fibrinogen of Egyptian microalbuminuric NIDDM type 2 diabetic patients. Egypt J Hosp Med. 2005;21(1):66–81.
20.
Kamath SD, Prasanna US, Srivastava S, Sunder A. The Study of Relationship between Plasma Fibrinogen Level and the Macrovascular Complications in Type 2 Diabetes Mellitus patients in a Tertiary Health Care Centre in Eastern India. 2024.
21.
De Feo P, Gaisano MG, Haymond MW. Differential effects of insulin deficiency on albumin and fibrinogen synthesis in humans. J Clin Investig. 1991;88(3):833–40.
22.
Bruno G, Cavallo-Perin P, Bargero G, Borra M, D'Errico N, Pagano G. Association of fibrinogen with glycemic control and albumin excretion rate in patients with non-insulin-dependent diabetes mellitus. Ann Intern Med. 1996;125(8):653–7.
23.
Yeom E, Byeon H, Lee SJ. Effect of diabetic duration on hemorheological properties and platelet aggregation in streptozotocin-induced diabetic rats. Sci Rep. 2016;6(1):21913.
24.
Carty C, Heagerty P, Heckbert S, Jarvik G, Lange L, Cushman M, et al. Fibrinogen and IL6 Gene Variants and IL-6 Levels in Relation to Plasma Fibrinogen Concentration and Cardiovascular Disease Risk in the Cardiovascular Health Study. Ann Hum Genet. 2010;74(1):1.
25.
Barazzoni R, Kiwanuka E, Zanetti M, Cristini M, Vettore M, Tessari P. Insulin acutely increases fibrinogen production in individuals with type 2 diabetes but not in individuals without diabetes. Diabetes. 2003;52(7):1851–6.
26.
Machlus KR, Cardenas JC, Church FC, Wolberg AS. Causal relationship between hyperfibrinogenemia, thrombosis, and resistance to thrombolysis in mice. Blood J Am Soc Hematol. 2011;117(18):4953–63.
27.
Mohan G, Kaur R, Aggarwal A, Singh P. To study levels of serum fibrinogen in type 2 diabetes mellitus and its association with diabetic microvascular complications. Int J Adv Med. 2017;4(1):10–4.
28.
Abdelmonem M, Abdulla S, Wasim H, Elawamy H. The correlation between Plasma Fibrinogen Levels and Glycemic Status in type 2 Diabetes Mellitus. Am J Clin Pathol. 2023;160(Supplement1):S19–20.
29.
Gupta R, Dhawale S. Association between serum fibrinogen level in type-2 diabetes mellitus patient with or without microvascular complication. IJAR. 2015;1(9):555–61.
30.
Jain SK. Correlation of fibrinogen level with lipid profile in type 2 diabetes mellitus: An observational study.
31.
Desai VA, Chandrakala, Takalkar AA. Correlation of fibrinogen level with lipid profile in type 2 diabetes mellitus. Int J Adv Med. 2020;7(5):849–52.
32.
Razak MKA, Sultan AA. The importance of measurement of plasma fibrinogen level among patients with type 2 diabetes mellitus. Diabetes Metabolic Syndrome: Clin Res Reviews. 2019;13(2):1151–8.