Original article 27
Serum visfatin in type 2 diabetes mellitus
Samiha A. Abd Raboa, Nagwa A. Mohammedb, Somayh S. Eissaa,
Abeer A. Alia, Sahar M. Ismaila and Reham S. Gadc
a
Department of Internal Medicine, Faculty of Medicine
for Girls, Al-Azhar University, bDepartment of Clinical
and Chemical Pathology, National Research Center
and cDepartment of Internal Medicine, Matareya
Teaching Hospital, Cairo, Egypt
Correspondence to Somayh S. Eissa,
131 Saker Quriesh, New Maadi, Cairo, Egypt
Tel: +00201113754668;
e-mail: meedo_69@windowslive.com
Received 6 November 2012
Accepted 27 November 2012
Egyptian Journal of Internal Medicine
2013, 25:27–32
Introduction
Obesity is commonly associated with insulin resistance and hyperinsulinemia and is
the most important risk factor for type 2 diabetes. Visfatin is an adipokine that exerts
insulin-mimetic effects that stimulate muscle and adipocyte glucose transport
and inhibit hepatocyte glucose production.
Purpose
The aim of this study was to assess levels of visfatin and its relationship to obesity and
insulin resistance in type 2 diabetes mellitus.
Patients and methods
This study included 40 patients with type 2 diabetes as the patient group: 20 of them
were obese (BMIZ30) and 20 were not (BMIo25). Forty apparently healthy
individuals matched for age and sex were included as the control group: 20 of them
were obese (BMIZ30) and the other 20 were not (BMIo25). All patients and controls
underwent history taking, physical examination including determination of BMI, and the
following laboratory investigations: determination of levels of fasting blood glucose, 2 h
postprandial blood glucose, serum cholesterol, triglycerides, fasting insulin, and fasting
visfatin; kidney and liver function tests and calculation of homeostasis model of
assessment-insulin resistance (HOMA-IR) were also performed. Neither the patients
nor controls suffered from any chronic disease other than diabetes.
Results
The results of this study revealed a highly significant increase in the fasting serum
insulin level, HOMA-IR, and fasting serum visfatin level among diabetic patients
(26.10 ± 6.04 mIU/ml, 12.18 ± 5.24, 36.70 ± 6.86 ng/ml, respectively) when compared
with controls (12.10 ± 3.45 mIU/ml, 2.42 ± 0.79, 13.63 ± 3.98 ng/ml, respectively;
Po0.01). Fasting insulin levels, HOMA-IR, and visfatin levels were significantly higher
in obese diabetic patients (31.13 ± 4.34 mIU/ml, 14.71 ± 6.22, 42.36 ± 4.11 ng/ml,
respectively) than in obese controls (14.31 ± 3.11 mIU/ml, 2.89 ± 0.77,
16.72 ± 3.16 ng/ml, respectively; Po0.01). Visfatin levels were higher in nonobese
diabetic patients than in nonobese controls. Moreover, visfatin levels were higher
in obese diabetic patients (31.04 ± 3.49 ng/ml) than in nonobese diabetic patients
(10.54 ± 1.53 ng/ml; Po0.01). The present study revealed a highly significant positive
correlation between levels of visfatin and fasting insulin in both obese and nonobese
diabetic patients. Although there was a significant positive correlation between visfatin
levels and HOMA-IR, there was no significant correlation between visfatin levels and
BMI in obese diabetic patients.
Conclusion
Visfatin levels are increased in patients with type 2 diabetes regardless the degree
of adiposity.
Keywords:
insulin resistance, obesity, type 2 diabetes mellitus, visfatin
Egypt J Intern Med 25:27–32
& 2013 The Egyptian Society of Internal Medicine
1110-7782
Introduction
The prevalence of obesity is increasing in most societies,
even among young adults and children. Obesity is the
single most important risk factor for the development of
type 2 diabetes mellitus (type 2 DM) [1].
Adipose tissue produces several proteins (adipokines)
such as leptin, adiponectin, and resistin that modulate
insulin sensitivity and play an important role in the
pathogenesis of insulin resistance and diabetes [2].
1110-7782 & 2013 The Egyptian Society of Internal Medicine
However, the mechanisms by which fat tissue induces
insulin resistance and the role of adipokines in the
pathogenesis of type 2 DM have not been established [3].
Visfatin is an adipokine (protein) expressed mainly by
the visceral adipose tissues (hence the name); it has
insulin-like action and its plasma concentration is closely
related to the amount of visceral fats. Visfatin can be
detected in visceral adipose tissues and to a much lower
extent in subcutaneous adipose tissues [4]. It is also
DOI: 10.7123/01.EJIM.0000425961.54125.23
Copyright © The Egyptian Society of Internal Medicine. Unauthorized reproduction of this article is prohibited.
28 Egyptian Journal of Internal Medicine
highly expressed in human liver, muscles, and macrophages [5].
Visfatin is produced by many tissues and cells, including
adipose tissue, white blood cells, macrophages, and
colonic and mammary epithelial cells; it is also present
synovial fluid and plasma [6].
Visfatin is involved in regulation of the cell cycle [6]. It is
secreted by activated lymphocytes and is upregulated in
neutrophils and monocytes after exposure to inflammatory stimuli; it also promotes the growth of B-cell
precursors and is therefore known as pre-B-cell colonyenhancing factor [7].
Visfatin induces the production of cytokines such as
interleukin-6 and tumor necrosis factor-a in human
leukocytes. Its plasma level increases during chronic
inflammatory conditions such as psoriasis, arthritis, and
obesity [6].
Visfatin is a nuclear as well as a cytoplasmic protein.
It increases the lifespan of aging human vascular smooth
muscle cells [8].
Visfatin enhances neovascularization in the chorioallantoic membrane and stimulates migration and invasion of
the endothelial cells and tube development in the human
umbilical vein [9].
Visfatin exhibits insulin-mimetic properties, causing a
glucose lowering effect. It increases glucose uptake and
lipogenesis and decreases glucose production by hepatocytes. Visfatin improves insulin sensitivity, resulting in
decreased glucose and insulin levels. The insulin sensitizing
effect of visfatin appears to be additive to the effect of
insulin. Visfatin and insulin do not compete to bind to the
insulin receptors, indicating that the two proteins are
recognized by different regions of the receptors [10].
Visfatin may be used as promising predictor for obesity,
insulin resistance, diabetes status, metabolic syndrome, and
cardiovascular disease [11]. Elevation of visfatin levels in
type 2 DM is independent of obesity and insulin resistance
and is mainly determined by levels of fasting glucose and
triglycerides [12].
The aim of this study was to assess levels of visfatin and
its relationship with obesity and insulin resistance in type
2 DM.
selected from the Department of Internal Medicine, AlAzhar University and Matareya Teaching Hospitals.
All patients and controls were subjected to medical
history taking, complete physical examination including
determination of BMI (the weight in kilograms divided
by the square of the height in meters), and laboratory
investigations: determination of levels of FBG, 2 h PBG,
serum cholesterol and triglycerides; liver function tests
and kidney function tests were also performed.
About 3 ml of fasting (12 h) venous blood was withdrawn
from each study participant and left to clot. Thereafter,
the serum was separated by centrifugation and the FBG
level was immediately determined using a Hitachi auto
analyzer (Hitachi 736; Hitachi, Japan). The remaining
serum was stored at – 201C for determination of the
following parameters: serum levels of cholesterol, triglyceride, insulin, and visfatin.
Two hours after a meal, 2 ml of blood was withdrawn from
each study participant and aliquoted into a tube containing fluoride for determination of PBG.
Determination of FBG, PBG, serum cholesterol, and
serum triglyceride levels was carried out on a Hitachi auto
analyzer (Hitachi 736; Hitachi)using colorimetric techniques. The level of fasting serum insulin was measured
using a radioimmunoassay kit supplied by BioSource
Europe (Nivelles, Belgium) [13].
Insulin sensitivity was assessed using a homeostasis
model of assessment-insulin resistance (HOMA-IR),
which uses the formula [(fasting insulin (mIU/ml) FBG
(mg/dl)]/405 [13].
The level of serum visfatin was determined using a competitive enzyme immunoassay kit (Phoenix Pharmaceutical Inc.,
California, USA) [14].
Statistical data were analyzed using Microsoft Excel 2003
and SPPS version 10 (SPSS Inc., Chicago, Illinois, USA).
Quantitative data were described in terms of range
of minimum and maximum and mean and standard
deviation. Comparative statistical analysis was carried out
using Student’s-t test and the Spearman correlation
coefficient.
A P-value of more than 0.05 was considered nonsignificant.
Patients and methods
A P-value of less than 0.05 was considered significant.
This study included 40 patients with type 2 DM
[diagnosed on the basis of a fasting blood glucose
(FBG) level of Z126 mg/dl and 2 h postprandial blood
glucose (PBG) level of >140 mg/dl]. Twenty of them
were obese diabetic patients (BMIZ30 kg/m2); 17
women and three men with ages ranging from 35 to 70
years, with a mean age of 55.60 ± 9.27 years. The other 20
patients were nonobese (BMIo25 kg/m2). Forty healthy
individuals were also included as controls; 20 of them
were obese: 12 women and eight men matched for age,
and the other 20 were nonobese. All patients were
A P-value of less than 0.01 was considered highly significant.
Results
There was an insignificant increase in the BMI and a
highly significant increase in the levels of FBG, PBG,
cholesterol, triglycerides, fasting insulin and visfatin as
well as in HOMA-IR of all diabetic patients compared
with all nondiabetic controls (Table 1).
Copyright © The Egyptian Society of Internal Medicine. Unauthorized reproduction of this article is prohibited.
Visfatin in type 2 DM Abd Rabo et al. 29
There was a highly significant increase in the levels of
FBG, PBG, cholesterol, triglycerides, fasting insulin, and
visfatin and in HOMA-IR in obese diabetic patients
compared with obese controls (Table 2).
Table 3 The studied parameters in nonobese diabetic patients
compared with nonobese controls
There was an insignificant increase in the BMI and levels
of cholesterol and triglycerides, whereas there was a
highly significant increase in the levels of FBG, PBG,
fasting insulin, and visfatin as well as in HOMA-IR in
nonobese diabetic patients compared with nonobese
controls (Table 3).
Parameters
There was an insignificant increase in the levels of FBG
and PBG, whereas there was a highly significant increase
in the BMI, serum levels of cholesterol, triglycerides,
fasting insulin, and visfatin, and in HOMA-IR of obese
diabetic patients compared with nonobese diabetic
patients (Table 4).
In the obese diabetic patients (Table 5), there was no
significant correlation between serum levels of visfatin
and BMI (Fig. 1), levels of FBG, PBG, serum cholesterol,
and triglycerides, whereas there was a significant positive
correlation between serum levels of visfatin and fasting insulin levels (Po0.01; Fig. 2) and HOMA-IR
(Po0.05; Fig. 3).
In the nonobese diabetic patients, there was insignificant
correlation between serum visfatin levels and BMI (Fig. 4),
HOMA-IR (Fig. 5), and serum levels of FBG, PBG,
cholesterol, and triglycerides (Table 6), whereas there was
a highly significant correlation between levels of visfatin
and fasting insulin levels (Po0.01; Table 6; Fig. 6).
Table 1 The studied parameters in all diabetic patients
compared with controls
Parameters
BMI (kg/m2)
FBG (mg/dl)
PBG (mg/dl)
Serum cholesterol (mg/dl)
Serum triglycerides (mg/dl)
Fasting insulin (mIU/ml)
HOMA-IR
Serum visfatin (ng/ml)
All diabetic
patients
(mean ± SD)
All controls
(mean ± SD)
Nonobese
diabetic
patients
(mean ± SD)
2
BMI (kg/m )
FBG (mg/dl)
PBG (mg/dl)
Serum cholesterol (mg/dl)
Serum triglycerides (mg/dl)
Fasting insulin (mIU/ml)
HOMA-IR
Serum visfatin (ng/ml)
Nonobese
controls
(mean ± SD)
P-value
23.27 ± 1.01
23.24 ± 1.21 40.05
184.60 ± 35.52 80.85 ± 9.35 o0.01
239.45 ± 43,81 104.00 ± 9.90 o0.01
186.45 ± 42.91 166.95 ± 41.77 40.05
116.20 ± 33.92 97.85 ± 28.91 40.05
21.08 ± 1.69
9.90 ± 2.14 o0.01
9.65 ± 2.09
1.96 ± 0.49 o0.01
31.04 ± 3.49 10.54 ± 1.53 o0.01
HOMA-IR, homeostasis model of assessment-insulin resistance;
FBG, fasting blood glucose; PBG, postprandial blood glucose.
Table 4 The studied parameters in obese diabetic patients
compared with nonobese diabetic patients
Parameters
Obese diabetic
patients
(mean ± SD)
Nonobese
diabetic
patients
(mean ± SD)
P-value
BMI (kg/m2)
FBG (mg/dl)
PBG (mg/dl)
Serum cholesterol (mg/dl)
Serum triglycerides (mg/dl)
Fasting insulin (mIU/ml)
HOMA-IR
Serum visfatin (ng/ml)
35.79 ± 3.72
188.40 ± 68.62
245.55 ± 76.43
229.00 ± 53.40
159.50 ± 31.24
31.13 ± 4.34
14.71 ± 6.22
42.36 ± 4.11
23.27 ± 1.01
184.60 ± 35.52
239.45 ± 43,81
186.45 ± 42.91
116.20 ± 33.92
21.08 ± 1.69
9.65 ± 2.09
31.04 ± 3.49
o0.01
40.05
40.05
o0.01
o0.01
o0.01
o0.01
o0.01
HOMA-IR, homeostasis model of assessment-insulin resistance;
FBG, fasting blood glucose; PBG, postprandial blood glucose.
Table 5 Correlation between the studied parameters and
visfatin levels in obese diabetic patients
Serum visfatin
Pvalue
29.37 ± 6.88
27.29 ± 4.47 40.05
186.50 ± 53.97 81.33 ± 10.27 o0.01
247.00 ± 61.96 107.33 ± 10.66 o0.01
207.98 ± 52.34 168.00 ± 41.09 o0.01
137.85 ± 38.94 95.08 ± 24.12 o0.01
26.10 ± 6.04
12.10 ± 3.45 o0.01
12.18 ± 5.24
2.42 ± 0.79 o0.01
36.70 ± 6.86
13.63 ± 3.98 o0.01
Parameters
2
BMI (kg/m )
FBG (mg/dl)
PBG (mg/dl)
Serum cholesterol (mg/dl)
Serum triglycerides (mg/dl)
Fasting insulin (mIU/ml)
HOMA-IR
R
P
Significance
0.336
0.260
0.227
0.008
0.367
0.981
0.516
40.05
40.05
40.05
40.05
40.05
o0.01
o0.05
Not significant
Not significant
Not significant
Not significant
Not significant
Highly significant
Significant
HOMA-IR, homeostasis model of assessment-insulin resistance;
FBG, fasting blood glucose; PBG, postprandial blood glucose.
HOMA-IR, homeostasis model of assessment-insulin resistance;
FBG, fasting blood glucose; PBG, postprandial blood glucose.
Table 2 The studied parameters in obese diabetic patients
compared with obese controls
Figure 1
Parameters
Obese diabetic
patients
Obese controls
(mean ± SD)
(mean ± SD)
FBG (mg/dl)
PBG (mg/dl)
Serum cholesterol (mg/dl)
Serum triglycerides (mg/dl)
Fasting insulin (mIU/ml)
HOMA-IR
Serum visfatin (ng/ml)
188.40 ± 68.62 81.80 ± 11.35 o0.01
245.55 ± 76.43 110.50 ± 10.62 o0.01
229.00 ± 53.40 169.05 ± 41.45 o0.01
159.50 ± 31.24 92.30 ± 18.51 o0.01
31.13 ± 4.34
14.31 ± 3.11 o0.01
14.71 ± 6.22
2.89 ± 0.77 o0.01
42.36 ± 4.11
16.72 ± 3.16 o0.01
Correlation between serum visfatin and BMI among obese diabetics
50
Pvalue
HOMA-IR, homeostasis model of assessment-insulin resistance;
FBG, fasting blood glucose; PBG, postprandial blood glucose.
BMI
40
30
20
10
0
0
10
20
30
S visfatin
40
50
60
Nonsignificant positive correlation between visfatin levels and BMI
among obese diabetic patients.
Copyright © The Egyptian Society of Internal Medicine. Unauthorized reproduction of this article is prohibited.
30
Egyptian Journal of Internal Medicine
Figure 2
Figure 5
Correlation between serum visfatin and HOMA-IR among non obese diabetics
HOMA IR
F Insulin
Correlation between serum visfatin and fasting insulin among obese diabetics
40
35
30
25
20
15
10
5
0
0
10
20
30
S visfatin
40
50
60
16
14
12
10
8
6
4
2
0
0
Highly significant positive correlation between levels of visfatin and
fasting insulin among obese diabetic patients.
5
10
15
20
25
30
35
40
S visfatin
Nonsignificant positive correlation between visfatin levels and HOMAIR among nonobese diabetic patients. HOMA-IR, homeostasis model
of assessment-insulin resistance.
Figure 3
Table 6 Correlation between the studied parameters and
visfatin levels in nonobese diabetic patients
Correlation between serum visfatin and HOMA-IR among obese diabetics
30
HOMA IR
25
Serum visfatin
20
15
Parameters
10
2
5
0
0
10
20
30
S visfatin
40
50
60
Significant positive correlation between visfatin level and HOMA-IR
among obese diabetic patients. HOMA-IR, homeostasis model of
assessment-insulin resistance.
BMI(kg/m )
FBG (mg/dl)
PBG(mg/dl)
Serum cholesterol(mg/dl)
Serum triglycerides(mg/dl)
Fasting insulin(mIU/ml)
HOMA-IR
R
P
Significance
– 0.284
0.120
– 0.170
– 0.031
0.097
0.942
0.423
40.05
40.05
40.05
40.05
40.05
o0.01
40.05
Not significant
Not significant
Not significant
Not significant
Not significant
Highly significant
Not significant
HOMA-IR, homeostasis model of assessment-insulin resistance; FBG,
fasting blood glucose; PBG, postprandial blood glucose.
Figure 6
Correlation between serum visfatin and BMI among non obese diabetics
25.5
25
24.5
24
23.5
23
22.5
22
21.5
21
Correlation between serum visfatin and fasting insulin among non obese diabetics
25
20
F insulin
BMI
Figure 4
0
5
10
15
20
S visfatin
25
30
35
15
10
40
5
0
0
Nonsignificant positive correlation between visfatin levels and BMI
among nonobese diabetic patients.
Visfatin levels (Fig. 7), fasting insulin levels (Fig. 8), and
HOMA-IR (Fig. 9) were high in the obese and nonobese
diabetic patients, and they were higher in the obese
controls than in nonobese controls.
5
10
15
20
S visfatin
25
30
35
40
Highly significant positive correlation between levels of visfatin and
fasting insulin among nonobese diabetic patients.
Figure 7
S.Visfatin
45
42.36
40
35
Discussion
In the present study, fasting insulin levels and HOMA-IR
showed a highly significant increase in all diabetic
patients compared with healthy controls. This result is
similar to those of the studies carried out by Chen
et al. [3] and Varma et al. [15], who reported that the
precise etiology of insulin resistance is unknown; however, many studies have suggested that lipotoxicity or
ectopic fat accumulation may be responsible for insulin
resistance.
31.04
30
25
20
16.72
15
10.54
10
5
0
Obese diabetics
Non obese
diabetics
Obese controls
Non obese
controls
Visfatin levels in the studied groups.
Copyright © The Egyptian Society of Internal Medicine. Unauthorized reproduction of this article is prohibited.
Visfatin in type 2 DM Abd Rabo et al. 31
resistance and hyperinsulinemia in diabetic patients as a
compensatory mechanism because visfatin has insulin
like action on the insulin receptors but on site different
than that on which the insulin acts [21].
Figure 8
F.Insulin
35
31.13
30
25
21.08
20
14.31
15
9.9
10
5
0
Obese diabetics
Non obese
diabetics
Obese controls
Non obese
controls
Fasting insulin levels in the studied groups.
In our study, the obese diabetic patients showed a
nonsignificant positive correlation between visfatin levels
and BMI. This is in agreement with the results of Chen
et al. [3] Pangono et al. [22], and Dogru et al. [23], who
found no correlation between visfatin levels and BMI.
Moreover, Abdullah and Barakat [19] found that visfatin
levels were increased in obese patients with type 2 DM,
regardless of BMI. These findings may indicate that
elevation of visfatin levels in patients with type 2 DM is
independent of obesity and insulin resistance, which is in
agreement with the results of Esteghamati et al. [12].
In contrast to the study carried out by Berndt et al. [24],
Curat et al. [5], Gursoy et al. [25], and Salah et al. [21]
found a significant positive correlation between visfatin
levels and BMI.
Figure 9
HOMA-IR
16
In our results, obese diabetic patients showed a
significant positive correlation between serum visfatin
levels and HOMA-IR; this is in agreement with the
results of Sandeep et al. [18], who found a strong
correlation between serum visfatin levels and HOMA-IR.
14.71
14
12
9.65
10
8
6
4
2.89
1.96
2
0
Obese diabetics
Non obese
diabetics
Obese controls
Non obese
controls
Homeostasis model of assessment-insulin resistance in the studied
groups.
In the present study, fasting insulin levels were higher in
obese diabetic patients than in obese controls. This is in
agreement with the results of Zahorska et al. [16].
In the present study, serum visfatin levels showed a highly
significant increase in all diabetic patients when compared
with healthy controls. Similar findings were reported by
Hammarsted et al. [17], Sandeep et al. [18], Abdullah and
Barakat [19], Rosa et al. [20], and Shelbaya et al. [21].
According to our results, visfatin levels were higher in
obese diabetic patients than in obese controls. This is in
agreement with the results of Miao et al. [3], who
suggested that elevated visfatin levels in patients with
type 2 DM may be because of an impairment in visfatin
signaling in target tissues or dysregulation of its
biosynthesis in response to hyperglycemia, hyperinsulinemia, or adipocytokines in the condition of diabetes.
Moreover, serum visfatin levels were higher in obese
diabetic patients than in nonobese diabetic patients. This
is in agreement with the study carried out by Adghate [6],
who reported that there may be a direct relationship
between levels of visfatin and obesity.
In the present study, visfatin levels were also significantly
higher in nonobese diabetic patients than in nonobese
controls. This is similar to the results of Shelbaya
et al. [21]. This may be explained by increased insulin
The mechanism by which hyperglycemia induces increase in circulating visfatin levels is not clear, but it may
be due to oxidative stress, increased apoptosis, or
destruction of B lymphocytes [6].
Finding a significant positive correlation between serum
levels of visfatin and fasting insulin in diabetic patients
(obese and nonobese) and HOMA-IR in obese diabetic
patients and between a higher level of serum visfatin and
fasting serum insulin level and HOMA-IR in nonobese
diabetic patients compared with nonobese healthy
controls makes us suggest that elevation in levels of
circulating visfatin is a compensatory mechanism for the
decreased insulin sensitivity in patients with type 2 DM.
This is in agreement with the results of Rosa et al. [20],
who suggested that increased visfatin levels may be a part
of the pathophysiology of diabetes. Visfatin exhibits
insulin-mimetic properties, such as increasing glucose
uptake and lipogenesis and decreasing hepatic glucose
production. It also improves insulin sensitivity, resulting
in decreased glucose and insulin levels. The insulin
sensitizing effect of visfatin appears to be additive to the
effect of insulin [10].
In contrast, Takebayashi et al. [26] found no correlation
between diabetes and levels of visfatin.
Visfatin may be used as promising predictor for obesity,
insulin resistance, diabetes status, metabolic syndrome,
and cardiovascular disease [11].
Conclusion
Visfatin levels are increased in patients with type 2 DM
regardless the degree of adiposity as a compensatory
Copyright © The Egyptian Society of Internal Medicine. Unauthorized reproduction of this article is prohibited.
32 Egyptian Journal of Internal Medicine
mechanism for the increased insulin resistance and
insufficient insulin action that may represent a new
target in the treatment of type 2 diabetes in the future.
Acknowledgements
Conflicts of interest
There are no conflicts of interest.
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