Biomedical Research 2010; 21 (2): 208-213

Assessment of c-reactive protein and fibrinogen levels in type 2

diabetes mellitus

Uma M Iyer and Pallavi Desai

Department of Foods and Nutrition, Faculty of Family and Community Sciences, The Maharaja Sayajirao University of
Baroda, Vadodara -390 002, Gujarat, India

Abstract

Diabetics are more vulnerable to cardiovascular diseases and therefore there is a need to
look for new markers to assess the risk. Aims of the present study are to assess the C-
reactive protein (CRP) and fibrinogen levels in type 2 diabetes mellitus subjects. In a case
control study, stable type 2 diabetics were enrolled from pathology lab and controls were
enrolled from free living population. Anthropometric profile, lipid profile, CRP and fi-
brinogen levels were assessed on 27 stable type 2 diabetics and 30 normal subjects. Students
t test and correlation analysis were done using excel package. The data showed that the
mean CRP and fibrinogen values were 1.7mg/L and 242 mg% in diabetics and 1.16mg/L
and 296mg% in controls. Both CRP and fibrinogen levels were not influenced by elevated
levels of BMI, WC, Total cholesterol and triglyceride levels in controls as well as the diabet-
ics. However, in case of CRP significant correlation was found with Triglyceride (r=0.3, p=
0.05) and TG/H (r=0.4 , p=0.01). No positive correlation existed with fibrinogen values with
any of the lipid indicators monitored. Thus traditional markers of TG and TG/H should be
monitored regularly to assess the risk of CVD.

Key words: T2DM, CRP, Fibrinogen, lipid profile, cardiovascular diseases

Accepted December 07 2009

Introduction atherosclerosis involves inflammation of the vascular en-

dothelium, CRP levels tend to be raised [4]. Several pro-
Diabetes Mellitus (DM) is a chronic disorder resulting spective clinical case control studies in Europeans have
from a number of factors in which an absolute or relative identified CRP as a strong, independent risk factor for
deficiency of insulin or its function occurs. The most CAD[5,6]. With the advent of high sensitive (Hs-CRP)
common and life threatening disorder that besets type 2 assays this risk factor is gaining importance in the field of
diabetic subjects is coronary heart disease (CHD). Irre- CAD and atherosclerosis. Basic research studies have
spective of the ethnic background the risk for CHD revealed that inflammatory markers are high among sub-
among diabetic subjects is greater by a factor of 2 to 4 jects with insulin resistance and diabetes[7]. Inflamma-
compared to non-diabetic subjects [1]. tion is considered to be a part of insulin resistance syn-
The diabetic condition contributes for initiation and pro- drome and this to some extent explains the high risk for
gression of micro and macro vascular complications in CAD among diabetic subjects[8].
diabetics[2]. Of all, cardiovascular complications are the
leading cause of mortality and morbidity in diabetics. Recent studies have identified defects in coagulation and
Framingham heart study (1974) demonstrated a direct the fibrinolytic cascade to play a major role in the patho-
association between diabetes and heart failure [3]. logical mechanisms leading to CAD. These two cascades
consist of activators and inhibitors which regulate clot
As diabetics are at risk of CVD, therefore there is a need formation and vascular potency. Measurements of activa-
to identify markers which would help in prognosis and tors, inactive precursors and inhibitors of this cascade
diagnosis of the disease. C-reactive protein (CRP), an have been considered as indicators of activity of these
acute phase reactant has long been considered as a classic pathways. Fibrinogen is one of the key elements in this
marker for inflammation. Acute inflammation, infection, cascade. Fibrinogen levels have been shown to be associ-
or tissue injury induces a marked increase in CRP. As ated with enhanced platelet aggregation and smooth mus-
208 Biomedical Research Volume 21 Issue 2
Assessment of c-reactive protein…….. diabetes mellitus

cle cell proliferation. Furthermore, there is a strong asso- dominal obesity as compared to the Normals representing
ciation of fibrinogen with blood viscosity and thrombus the Control group (Table 1).
formation and circulating levels of fibrinogen have been
known to have a strong and consistent relationship with Table 2 depicts the FBS and HbA1c levels of the subjects.
CAD[9] The mean FBS in the experimental group was 135 mg/dl
while that in case of control subjects it was 86 mg/dl. The
Thus CRP and Fibrinogen levels were estimated in type 2 HbA1c levels were estimated only for diabetic subjects.
diabetic subjects and compared with controls to assess The mean HbA1c levels which is an indicator of meta-
CVD risk. bolic control of sugar over the past 3 months was 7.98 %
which was higher than the cut off value of 7 indicating
that majority of the diabetic subjects had poor glycemic
Materials and Methods control. All the subjects had HbA1C >7 and nearly 44.4%
of the subjects had HbA1C levels ≥ 8. The HbA1c levels
For this, a prospective case control study was conducted were found to be higher for males than females (8.07 %
wherein 27 stable T2DM subjects who were regularly Vs 7.87 %). The mean HbA1c values indicated poor
monitoring their blood sugar and who gave consent for metabolic control among the diabetics.
the study were enrolled from the pathology lab over a
period of one month. Based on medical records only sta- Aberrations in lipid profile were more in diabetic subjects
ble diabetics were enrolled i.e whose blood sugar did not than control group (Table 3 & 4). Further, dyslipidemia
fluctuate widely and were on same medication for past with regard to TC and atherogenic lipoprotein was higher
one year were enrolled for the study. Thirty controls (non in diabetic female subjects than male diabetic subjects.
diabetics) residing near the pathological laboratory having Thus this data highlights that dyslipidemia is a common
similar baseline characteristics as diabetics such as age feature in diabetes which should be monitored to avert
and lifestyle factors (sedentary activity pattern, non coronary event.
smokers, non tobacco chewers and non-alcoholics were
enrolled Table 5 shows the CRP levels of the diabetic and control
. subjects. The mean CRP levels in T2DM subjects was
Out of the 27 diabetics, 15 were males and 12 were fe- 1.70 mg/l, while that in case of control group subjects, it
males. The control group consisted of 11 males and 19 was 1.16 mg/l. In case of diabetic group, CRP levels were
female subjects. The study was approved by the departm- comparable between the two genders (1.73 mg/l Vs 1.66
ental board of ethics committee. Data was then collected mg/l). In the control group, the female subjects had a
for all the subjects on anthropometry, FBS, HbA1c, lipid higher level of CRP as compared to male subjects (1.44
profile and inflammatory markers such as CRP and Fi- mg/l Vs 0.67 mg/l) but this difference was not statistically
brinogen. All the biochemical estimations were done on significant.
fasting samples. FBS and lipid profile were estimated
using enzymatic kit supplied by CHEMA. Ion exchange
resin method (ACCUREX) was used to estimate the gly- Table 6 shows the CRP values in relation to various vari-
cosylated hemoglobin (GHb). C-Reactive Protein (Latex) ables. In general the values of CRP were higher in dia-
High Sensitive Assay method was used to estimate C - betic subjects having these risk factors than the control
reactive protein (Roche/Hitachi cobas c system). Turbox group subjects having the same risk factors. However the
Fibrinogen Orion Diagnostica was used to estimate Fi- differences were not significant. Similar trend was noticed
brinogen levels (Orion Diagnostica Turbox Fibrinogen). when CRP was studied in relation to the lipid variables
(Table 7).
Statistical analysis
Correlation analysis was done (Table 8) between CRP
All the data was entered on excel and analysis was done and variables such as WC, BMI, FBS, TC, TG, LDL and
using excel package. Students t test and correlation analy- TG/H.
sis were done to find out significant differences between
the two groups. All tests were considered significant at Fibrinogen was another indicator used to assess the
p<0.05 level atherogenic risk. Table 9 shows the mean fibrinogen val-
ues for T2DM and control subjects. The mean levels in
the T2DM group were 242.31 mg% as against 296.20
Results and Discussion
mg% in case of control subjects. No significant correla-
Baseline Parameters and comparison of groups tion (Table 10) could be established between fibrinogen
The anthropometric profile of the study subjects showed and other variables such as waist circumference, BMI and
that the diabetic subjects were overweight and had ab- lipid profile. Thus in the present study Fibrinogen levels
remained unaltered in relation to a number of variables.
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 Iyer/ Desai

Table 1. Clinical Profile of the Control and Diabetic Subjects (Mean ± SD)

T2DM Control ‘t’ ‘t’

(T2DM Vs Ctrl) (T2DM Vs Ctrl)
Male Female Male Female Male Female
(15) (12) (11) (19)
Age (year) 52±5.9 53 ± 5.3 54±5.09 52 ± 5.9 - -
Weight(Kg) 71.2±9.5 68.4±8.8 70.9 ±7.4 62.4±9.4 0.07 1.79
Height (m) 167.1±6.8 154.6±4.7 166.4±4.4 153.8±5.03 0.33 0.46
WC (cm) 85.2 ± 7.2 93.9±10.8 85.2±10.3 83.3 ± 8.8 0.00016 2.84(p<0.05)
BMI 28.5±13.0 28.5±2.4 25.6 ± 1.8 26.3 ± 3.3 0.87 2.13(p<0.05)

Table 2. FBS & HbA1c of the Diabetic and Control Subjects (Mean ± SD)

T2DM Control

Male Female Total Male Female Total

n=15 n=12 n=27 n=11 n=19 n=30

FBS (mg/dl) 138±21.99 130±30.73 135±26.02 86±11.56 86 ± 8.25 86.±9.40
HbA1c (%) 8.07± 0.75 7.87 ± 0.98 7.98 ±0.85 - - -

Table 3. Lipid Profile of Diabetic and Control Subjects (Mean ± SD, mg/dl)

T2DM Control
Variable Male Female Male Female
TC 170 ± 29 219 ± 49 192 ± 21 182 ± 25
HDL-C 42 ± 10 46 ± 10 41 ± 6 49 ± 9
LDL-C 96 ± 27 135 ± 41 122 ±18 109 ±18
VLDL-C 33 ± 19 37 ± 12 29 ± 9 24 ± 8
L/H 2.3 ± 0.6 3.0 ± 1.05 3.05 ± 0.54 2.3 ± 0.54
TC/H 4.2 ± 1.08 4.7 ± 1.32 4.8 ± 0.71 3.8 ± 0.68
TC/L 1.8 ± 0.37 1.6 ± 0.18 1.6 ± 0.10 1.7 ± 0.12
TG 163 ± 95 187 ± 59 148 ± 47 121 ± 41
TG/H 4.5 ± 3.9 4.2 ± 1.6 3.7 ± 1.4 2.6 ± 1.01

Table 4. ‘t’ test between Diabetic and Control Subjects

Variable T2DM Vs Ctrl T2DM Vs Ctrl T2DM Ctrl

(M) (F) (M Vs F) (M Vs F)
TC 2.3 (p<0.05) 2.4 (p<0.02) 3.04 (p<0.005) 1.23
HDL-C 0.51 0.67 1.11 2.98
LDL-C 2.94 (0.005) 2.14 2.88 (p< 0.01) 1.94
VLDL-C 0.55 3.37 (0.002) 0.78 1.54
L/H 3.38(p<0.002) 2.20 (p<0.05) 2.09 3.71
TC/H 1.7 2.29 (p<0.05) 1.17 3.77(p<0.001)
TC/L 2.59(p<0.02) 0.59 1.80 2.44* (p<0.02)
TG 0.55 3.37 (p<0.002) 0.31 2.42
TG/H 0.69 3.10(p<0.005) 0.78 1.54

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Assessment of c-reactive protein…….. diabetes mellitus

Table 5. CRP Levels of the Diabetic and Control Subjects (Mean ± SD)

n CRP (mg/L)

T2DM
Male 15 1.73 ± 1.90
Female 12 1.66 ± 1.34
Total 27 1.70 ± 1.65
Control
Male 11 0.67 ± 0.50
Female 19 1.44 ± 1.14
Total 30 1.16 ± 1.02

Table 6. CRP Values in Relation to Various Variables (Mean ± SD)

Diabetics Controls t value

- -
Normal 0.62 ±0.59 (3)
Ow 0.82 ± 0.28 (3) 0.88 ±0.55 (8) 0.22
Ob 1.92 ± 1.81 (21) 1.35 ±1.18 (19) 1.18
WC (M>90cm, F>80cm) 1.65 ± 1.24 (16) 1.59 ±1.24 (14) 0.12
WC (M<90cm, F<80cm) 1.75 ± 2.05 (13) 0.88 ±0.64 (12) 1.46
HbA1c ≥ 8 1.07 ± 0.62 (12) - -
HbA1c < 8 2.20 ± 2.03 (15) - -
TG/H ≥ 3 1.79 ± 1.87 (16) 1.36 ±1.10 (15) 0.78
TG/H < 3 1.57 ± 1.32 (11) 0.95 ±0.92 (15) 1.33

Values in parentheses indicate number of subjects

Table 7. CRP Values in Relation to Lipid Profile and HbA1c Levels (Mean + SD)

CRP (mg/L)

mg/dl n T2DM n Control

TC>180 15 1.78 ± 1.22 18 0.92 ± 0.77

TC<180 12 1.60 ± 2.12 12 1.51 ± 1.26
TG>150 15 1.95 ± 1.99 8 0.99 ± 0.92
TG<150 12 1.38 ± 1.07 22 1.21 ± 1.07
LDL>100 17 1.56 ± 1.23 6 1.12 ± 0.99
LDL<100 10 1.94 ± 2.24 24 1.29 ± 1.22
TG/H>3 16 1.79 ± 1.87 15 1.36 ± 1.10
TG/H<3 11 1.57 ± 1.32 15 0.95 ± 0.92
(%)
HbA1c>8 12 1.07 ± 0.65 - -
HbA1c<8 15 2.20 ± 2.03 - -

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 Iyer/ Desai

Table 8. Correlation Analysis in Relation to CRP than control group (OR 33.25, CI 95% 5.4-263.8). This
highlights the fact that in order to characterize the risk of
Variables ‘r’ cardiovascular events, CRP should be added to the list of
WC-CRP 0.24 screening tests for diabetic subjects. Secondly, high CRP
BMI-CRP 0.07 levels may also identify high risk subjects who would be
FBS-CRP 0.23 “missed” by just measuring cholesterol and triglyceride
levels.
TC-CRP 0.14
TG-CRP 0.30 (p<0.02)
Interpretations and implications
LDL-CRP 0.25
TG/H-CRP 0.40 (p< 0.00162) In view of these observations we recommend that the tra-
ditional markers be monitored regularly for assessing the
CVD risk. Diabetics or healthy population having dyslip-
idemia with regard to triglyceridemia (TG>150 mg/dl)
Table 9. Fibrinogen Levels of the Subjects &/or having elevated levels of small dense lipoproteins
(TG/H>3) may be encouraged to assess CRP levels to
monitor the risk of CVD or diabetes. This strategy may
T2DM Control help to identify and monitor high risk diabetic subjects for
Fibrinogen 242.22 ± 40.36 296.20 ± 30.57 any cardiovascular event thereby reducing the economic
(mg%) burden and improving the quality of life.

Future research directions

Table 10. Correlation Analysis in Relation There is a need to validate the results on large sample size
to Fibrinogen and on diabetic subjects with coronary heart diseases.

Acknowledgements:
Variables ‘r’
Part of the data forms the dissertation work of Ms Pallavi
WC-Fibrinogen 0.16 Desai for her PhD work submitted to The M S University
BMI-Fibrinogen 0.25 of Baroda, Baroda
TC-Fibrinogen 0.12
TG-Fibrinogen 0.08
LDL-Fibrinogen 0.19 References
TG/H-Fibrinogen 0.04
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Correspondence
Uma M Iyer
Department of Foods and Nutrition
Faculty of Family and Community Sciences
The Maharaja Sayajirao University of Baroda
Vadodara -390 002, Gujarat, India
E-mail: umamsufn@hotmail.com
Phone: 098240-56921

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