Diabetes & Metabolism 36 (2010) 443–449
Original article
Correlation of plasma resistin with obesity and insulin resistance
in type 2 diabetic patients
M.Y. Gharibeh a,∗ , G.M. Al Tawallbeh a , M.M. Abboud b , A. Radaideh c ,
A.A. Alhader d , O.F. Khabour a
a
Department of Medical Laboratory Sciences, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan
b Department of Biochemistry, Muta’ University, Muta’, Jordan
c Princess’ Basma Teaching Hospital, Irbid 22110, Jordan
d Department of Physiology, Jordan University of Science and Technology, Irbid 22110, Jordan
Received 4 March 2010; received in revised form 20 May 2010; accepted 26 May 2010
Available online 23 August 2010
Abstract
Aim. – The aim of this case-control study was to assess the relationship between resistin levels and obesity and insulin resistance in type 2
diabetic patients.
Methods. – The study involved a sample of the Jordanian population that included 140 type 2 diabetic patients and 125 control subjects.
Results. – Serum resistin levels were higher in type 2 diabetic patients compared with the controls (P < 0.01). Markers of adiposity [body mass
index (BMI) and waist circumference (WC)] and insulin resistance, as well as fasting blood glucose, glycated haemoglobin, urea and blood pressure
were considerably higher among the studied diabetics than in the controls. When diabetic patients were subdivided into age-group categories of
10-year intervals, resistin levels significantly increased with increased age, with a significant proportion in the group aged > 60 years (P < 0.01).
Similarly, there was a significant association between plasma resistin and blood urea with growing older in diabetic patients. Pearson’s analysis
revealed positive correlations between plasma resistin and age, urea, creatinine, insulin, BMI, WC, body-fat content and homoeostasis model
assessment (HOMA). Furthermore, plasma resistin concentrations were higher in type 2 diabetic obese patients than in non-diabetic obese subjects
(P < 0.01), whereas no such difference was found between overweight and normal-weight controls.
Conclusion. – These results suggest that variations in resistin concentrations are not directly related to susceptibility to type 2 diabetes. However,
it may be that resistin plays a role in the pathogenesis of obesity and insulin resistance, both of which could, indirectly, contribute to the development
of type 2 diabetes.
© 2010 Elsevier Masson SAS. All rights reserved.
Keywords: Resistin; Type 2 diabetes; Obesity; Insulin resistance; Jordan
Résumé
Corrélation des concentrations plasmatiques de résistine avec l’obésité et l’insulinorésistance chez des diabétique de type 2.
But. – Évaluer les relations entre concentrations plasmatiques de résistine, obésité et insulinorésistance dans le diabète de type 2 (DT2).
Méthodes. – Une étude cas-témoins a été réalisée à partir d’un échantillon de la population jordanienne qui comprenait 140 patients atteints de
DT2 et 125 témoins.
Résultats. – Les concentrations plasmatiques de résistine étaient plus élevées chez les DT2 que celles des témoins (P < 0,01). Les marqueurs
d’adiposité (indice de masse corporelle et tour de taille), d’insulinorésistance, la glycémie à jeun, l’HbA1c , l’urée et la pression artérielle étaient plus
Abbreviations: BMI, Body mass index; DBP, Diastolic blood pressure; FPG, Fasting plasma glucose; HbA1c , Haemoglobin A1c ; HIS, Hepatic insulin
sensitivity; HOMA, Pancreatic ␤-cell secretory capacity; IR, Insulin resistance; LBM, Lean body mass; SBP, Systolic blood pressure; TC, total cholesterol; TR,
Triglycerides.
∗ Corresponding author. Tel.: +962 2 7201000 ext 23772; fax: +962 2 7201087.
E-mail address: younisgh@just.edu.jo (M.Y. Gharibeh).
1262-3636/$ – see front matter © 2010 Elsevier Masson SAS. All rights reserved.
doi:10.1016/j.diabet.2010.05.003
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M.Y. Gharibeh et al. / Diabetes & Metabolism 36 (2010) 443–449
élevés chez les diabétiques que chez les témoins. Lorsque les patients diabétiques ont été répartis par tranches d’âge de dix ans, les concentrations
plasmatiques de résistine augmentaient selon l’âge avec une proportion significative dans le groupe de plus de 60 ans (P < 0,01). De même, il y avait
une association significative entre la résistine et l’urée selon l’âge. Des corrélations positives entre les concentrations plasmatiques de résistine et
l’âge, l’urée, la créatinine, l’insulinémie, l’indice de masse corporelle, le tour de taille, la masse grasse et le HOMA ont été mises en évidence
grâce au test de Pearson. Les concentrations plasmatiques de résistine étaient plus élevées chez les DT2 obèses que chez les obèses non diabétiques
(P < 0,01), alors qu’il n’y avait pas de différence chez les témoins de poids normal et obèses.
Conclusion. – Ces résultats suggèrent que les variations des concentrations plasmatiques de résistine ne sont pas directement impliquées dans la
susceptibilité au DT2. Ils suggèrent néanmoins que la résistine pourrait jouer un rôle dans la physiopathologie de l’obésité et de l’insulinorésistance,
et contribuer indirectement au développement du DT2.
© 2010 Elsevier Masson SAS. Tous droits réservés.
Mots clés : Résistine ; Obésité ; Diabète de type 2 ; Résistance à l’insuline ; Jordanie
1. Introduction
Type 2 diabetes mellitus is a multistage process that begins
as insulin resistance, characterized by inability of the body to
use its own insulin properly, and ends with exhaustion of the
insulin-producing pancreatic ␤ cells, thereby leading to hyperglycaemia. Several factors are implicated in the development of
type 2 diabetes, including obesity, family history, physical inactivity and inherited factors [1]. However, obesity is considered
the most important risk factor for the disease, as obese individuals are seven times more likely to develop type 2 diabetes than
are normal-weight individuals [2]. In addition, central obesity
is strongly correlated with insulin resistance in type 2 diabetic
patients [3].
Adipose tissue is a highly active endocrine organ that secretes
a range of hormones known as ‘adipocytokines’ [4]. One of these
adipokines is a cysteine-rich protein called ‘resistin’, formed initially in humans as a propeptide consisting of 108 amino acids
prior to losing a signal peptide of 16 amino acids to become
a dimer (92 amino acids) or a hexamer (276 amino acids) connected by disulphide bridges [5]. Although, initially, resistin was
found to be adipose-specific in rodents [6], it was later shown
that, in humans, it is expressed by many other tissues, including preadipocytes, endothelial cells and vascular smooth muscle
cells, and is particularly abundantly expressed in macrophages
[7]. Indeed, Degawa-Yamauchi et al. [8] showed the expression
of resistin in adipose tissue from obese patients.
However, the role of resistin in response to obesity and insulin
resistance in type 2 diabetic patients is still obscure [9]. Several studies have reported increased resistin levels in association
with obesity and insulin resistance in type 2 diabetes [8,10,11],
whereas other studies have failed to detect any change in resistin
levels under such conditions [12,13]. Yet other studies found that
circulating resistin levels are involved in promoting adiposity,
but had no effect on the degree of insulin resistance [14]. These
observations suggest that the role of resistin in the pathogenesis
of diabetes remains controversial.
To clarify this controversy, there is clearly a need for more
data from different ethnic groups, as serum resistin levels might
reflect the impact of genetic or environmental factors on resistin
expression and, thus, be subject to ethnic variations [15].
The prevalence of diabetes in Jordan is 9.8% —
corresponding to that of the world’s population — and is
considered to be relatively high; it also shows a progressively
rising profile [16]. The age-standardized prevalence of diabetes
in Jordan increased from 13.0 to 17.1% over a period of 10
years, and the rate of increase was greatest in those aged ≥ 60
years. Thus, Jordan is not far from being in the increasing
dangerous zone of diabetes in this part of the world.
For this reason, the present study was undertaken to investigate the effects of obesity and insulin-resistance markers in
Jordanians with type 2 diabetes, and to evaluate the relationship
between these markers and plasma levels of resistin.
2. Subjects and methods
2.1. Patients
A total of 140 type 2 diabetic patients were selected according
to the criteria published by the American Diabetes Association
[1]. The present study also included 125 non-diabetic control
subjects, who were age- and gender-matched to the diabetic
patients, but had no history of any pathological conditions. Written informed consent was obtained from all study participants,
and the local institutional review board approved the study.
2.2. Quantification of body fat
Lean body mass (LBM) was calculated as follows: in
men, LBM (kg) = 0.32810 × weight (kg) + 0.33929 × height
(cm) − 29.5336; in women, LBM (kg) = 0.29569 × weight
(kg) + 0.41893 × height (cm) − 43.2933 [17].
2.3. Pancreatic β-cell secretion, insulin resistance and
hepatic insulin sensitivity
Pancreatic ␤-cell secretory capacity was estimated by the
␤-cell index [index of ␤-cell secretory force, homoeostasis
model assessment (HOMA) ␤-cell index] using the formula
proposed by Hosker et al. [18]. The rate of insulin resistance
was evaluated by the HOMA devised by Matthews et al. [19]
and calculated using the formula described by Bonora et al.
[20]. Insulin resistance (IR) was expressed as: IR = fasting serum
insulin (␮U/mL) × fasting plasma glucose (mmol/L)/22.5. Hepatic insulin sensitivity (HIS) was assessed using the following
formula: HIS = k/[FPG (mg/dL) × fasting insulin (␮U/mL)],
wherein k = 22.5 × 18 = 405.
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M.Y. Gharibeh et al. / Diabetes & Metabolism 36 (2010) 443–449
Table 1
Means ± SEM of various parameters in type 2 diabetics and controls.
Parameter
Age (years)
Body mass index (kg/m2 )
Waist circumference (cm)
Waist-to-hip ratio
Fasting blood glucose (mmol/L)
HbA1c (%)
Total cholesterol (mmol/L)
Triglycerides (mmol/L)
HDL (mmol/L)
LDL (mmol/L)
Urea (mmol/L)
Creatinine (␮mol/L)
Insulin (␮U/mL)
Resistin (ng/mL)
Systolic blood pressure (mmHg)
Diastolic blood pressure (mmHg)
Lean body mass (kg)
Body fat (kg)
HOMA (␤-cell index)
Insulin resistance
Hepatic insulin sensitivity
Group
P
Control (n = 125)
Diabetic (n = 140)
51.81
29.84
98.09
0.906
5.50
5.94
4.87
1.90
0.97
3.26
4.91
72.0
10.38
6.34
131.7
86.9
52.79
30.61
2.17
2.55
0.60
54.36
30.89
103.90
0.937
10.10
7.70
5.08
2.70
0.90
3.27
5.78
78.6
11.94
7.82
138.6
91.6
52.32
32.20
1.47
5.46
0.30
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
1.04
0.43
1.03
0.005
0.05
0.06
0.09
0.11
0.02
0.08
0.16
1.9
0.56
0.17
1.5
1.1
0.69
0.80
0.11
0.14
0.05
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
0.88
0.47
1.04
0.005
0.32
0.14
0.13
0.21
0.02
0.08
0.21
3.4
0.60
0.29
1.2
1.1
0.62
0.91
0.08
0.37
0.02
0.061
0.109
0.0001*
< 0.0001*
< 0.0001*
< 0.0001*
0.209
0.001*
0.035*
0.901
0.001*
0.105
0.061
< 0.0001*
0.0004*
0.003*
0.614
0.199
< 0.0001*
< 0.0001*
< 0.0001*
Lean body mass (kg) = 0.32810 × weight (kg) + 0.33929 × height (cm) − 29.5336.
HOMA = 20 × FI/(FPG – 3.5), where FI (␮U/mL) = fasting insulin and FPG (mg/dL) = fasting plasma glucose.
Insulin resistance = fasting serum insulin (␮U/mL) × FPG (mmol/L)/22.5.
Hepatic insulin sensitivity = k/[FPG (mg/dL) × FI (␮U/mL)], where k = 22.5 × 18 = 405.
* Statistically significant difference.
2.4. Biochemical assays
3. Results
Blood samples were obtained in the morning after an
overnight fast. A commercially available ELISA kit (BioVender Laboratory Medicine Inc., Brno, Czech Republic) was used
to measure human resistin in plasma according to the manufacturer’s instructions. The assay is based on the detection of
circulatory homodimeric resistin by rabbit polyclonal antihuman resistin antibody. Human insulin was measured with an
insulin kit (Roche Diagnostics, Indianapolis, IN, USA) using
a cobas immunoassay analyzer (Roche Diagnostics). Glucose,
glycosylated haemoglobin (HbA1c ), urea, creatinine, cholesterol, triglycerides and high-density lipoprotein (HDL) were
measured in plasma by standard methods using the Roche Chemistry Analyzer and Roche kits (Roche Diagnostics). All samples
were assayed in duplicate, and the mean of the paired results
was determined.
Diabetic patients showed significantly (P < 0.05) higher
levels of resistin, fasting blood glucose (FBG), HbA1c , triglycerides, HDL and urea in comparison to control subjects (Table 1).
Also, diabetic patients had higher values of waist circumference (WC), waist-to-hip ratio (WHR), systolic and diastolic
blood pressure, HOMA ␤-cell index, IR and HIS. Some parameters, such as BMI, total cholesterol, creatinine and insulin,
were markedly increased in the diabetic group, although the
increase was not statistically significantly different from that
in the controls. No differences were detected in levels of lowdensity lipoprotein (LDL), LBM and body fat (BF) between the
two groups. However, proportions of serum resistin were almost
14% higher in the diabetics than in the controls.
On comparing male and female type 2 diabetic patients with
their corresponding healthy controls (Table 2), WC and systolic
blood pressure values were significantly different in women,
but not in men. However, no statistically significant gender differences were detected in any other parameters, such as resistin,
WHR, FBG, HbA1c , triglycerides, urea, diastolic blood pressure,
HOMA, IR and HIS (Table 2).
Patients with type 2 diabetes and their matching controls
were further subdivided into four age groups of 10-year intervals (Table 3). Below the age of 40 years, the diabetes group
showed no significant differences in serum levels of resistin
compared with the healthy control group. However, as the age
of the diabetics increased, resistin levels also began to increase
2.5. Statistical analysis
Data were expressed as means ± SEM. Analyses that
involved two variables were carried out by Student’s t test,
while multiple comparisons were performed using ANOVA
followed by post-hoc tests. The SPSS 15.0 statistical software package (SPSS Inc., Chicago, IL, USA) was used for all
statistical evaluations. P values < 0.05 were considered significant.
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M.Y. Gharibeh et al. / Diabetes & Metabolism 36 (2010) 443–449
Table 2
Effect of gender on various clinical parameters in type 2 diabetic patients and controls.
Parameter
Age (years)
Body mass index (kg/m2 )
Waist circumference (cm)
Waist-to-hip ratio
FBG (mmol/L)
HbA1c (%)
TC (mmol/L)
TG (mmol/L)
HDL (mmol/L)
LDL (mmol/L)
Urea (mmol/L)
Creatinine (␮mol/L)
Insulin (␮U/mL)
Resistin (ng/mL)
SBP (mmHg)
DBP (mmHg)
Lean body mass (kg)
Body fat (kg)
HOMA (␤-cell index)
Insulin resistance
HIS
Male
Female
Controls (n = 61)
Diabetics (n = 63)
P
Controls (n = 64)
Diabetics (n = 77)
P
50.3
28.5
98.6
0.93
5.49
5.84
4.83
2.14
0.87
3.24
5.10
81.9
10.8
6.34
132.8
86.7
58.0
28.7
2.26
2.67
0.54
54.1
29.06
102.5
0.96
10.71
7.82
5.12
3.16
0.86
3.21
6.00
85.6
11.92
7.55
137.3
91.4
56.37
28.74
1.37
5.89
0.30
0.061
0.491
0.051
0.004*
< 0.0001*
< 0.0001*
0.291
0.039*
0.737
0.865
0.021*
0.518
0.386
0.005*
0.107
0.040*
0.141
0.959
< 0.0001*
< 0.0001*
< 0.0001*
53.1
31.1
97.5
0.87
5.52
6.03
4.91
1.67
1.07
3.28
4.74
62.5
9.93
6.34
130.6
87.1
47.8
32.5
2.08
2.45
0.65
54.5
32.39
105.1
0.91
9.59
7.60
5.05
2.32
0.94
3.33
5.60
72.9
11.96
8.04
139.7
91.8
49.01
35.02
1.55
5.10
0.31
0.471
0.186
0.0007*
< 0.0001*
< 0.0001*
< 0.0001*
0.497
0.0007*
0.014*
0.777
0.026*
0.064
0.075
0.002*
0.001*
0.045*
0.225
0.153
0.006*
< 0.0001*
0.0009*
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
1.4
0.52
1.3
0.01
0.06
0.08
0.11
0.17
0.03
0.10
0.18
2.6
0.86
0.19
1.9
1.6
0.73
1.09
0.17
0.22
0.04
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
1.4
0.51
1.3
0.01
0.53
0.24
0.25
0.45
0.02
0.13
0.33
4.9
0.88
0.32
1.9
1.5
0.74
1.10
0.10
0.59
0.03
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
1.4
0.65
1.5
0.01
0.07
0.09
0.13
0.13
0.03
0.12
0.25
2.1
0.72
0.23
2.2
1.7
0.72
1.14
0.15
0.18
0.10
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
±
1.1
0.71
1.5
0.01
0.38
0.17
0.13
0.12
0.03
0.11
0.27
4.7
0.83
0.46
1.6
1.5
0.690
1.31
0.11
0.47
0.02
Data are expressed as means ± SEM.
FBG: fasting blood glucose; TC: total cholesterol; TG: triglycerides; HDL/LDL: high-/low-density lipoprotein; SBP/DBP: systolic/diastolic blood pressure; HIS:
hepatic insulin sensitivity.
* Statistically significant difference.
significantly compared with the controls. The most significant
resistin increase was observed in patients aged > 60 years. Also,
a particular increase in blood urea and HOMA was observed
in the diabetic patients as their age increased to > 50 years. In
fact, all of the investigated diabetic age groups exhibited significant increases in levels of FBG, HbA1c , HOMA, IR and HIS
compared with the healthy controls.
Patients with type 2 diabetes were also divided into three
groups according to BMI: normal weight; overweight; and
obese. Serum resistin levels in the diabetics were significantly
increased (P < 0.001) in those who were obese compared with
the controls (Table 4), whereas no statistically significant differences were detected in either the overweight or normal-weight
diabetic patients.
Resistin plasma levels in the diabetics were strongly associated with age (r = 0.16, P < 0.05), urea (r = 0.44, P < 0.001)
and creatinine (r = 0.46, P < 0.0001). Positive correlations were
also observed between resistin and obesity markers such as BMI
(r = 0.19, P < 0.05), BF (r = 0.19, P < 0.05) and WC (r = 0.22,
P < 0.01). Similarly, positive correlations were found between
resistin and parameters of IR rate such as insulin (r = 0.19,
P < 0.05) and HOMA (r = 0.24, P < 0.005). In contrast, plasma
Table 3
Effect of age on various parameters in type 2 diabetic patients and their matched controls.
Parameter
< 40 years
Controls (n = 16)
Diabetics (n = 10)
40–49 years
Controls (n = 36)
Diabetics (n = 37)
50–59 years
Controls (n = 37)
Diabetics (n = 49)
> 60 years
Controls (n = 36)
Diabetics (n = 44)
FBG (mmol/L)
HbA1c (%)
Urea (mmol/L)
Resistin (ng/mL)
WC (cm)
WHR
SBP (mmHg)
DBP (mmHg)
HOMA (␤-cell)
HOMA (IR)
HIS
< 0.001*
< 0.05*
NS
NS
< 0.01*
NS
NS
< 0.05*
NS
< 0.01*
< 0.01*
< 0.001*
< 0.001*
NS
0.049*
NS
< 0.05*
< 0.01*
NS
NS
< 0.001*
< 0.01*
< 0.001*
< 0.001*
< 0.01*
0.024*
NS
< 0.05*
< 0.01*
< 0.01*
< 0.001*
< 0.01*
< 0.05*
< 0.001*
< 0.001*
< 0.05*
0.001*
< 0.05*
NS
NS
NS
< 0.01*
< 0.01*
< 0.01*
NS: not significant; FBG: fasting blood glucose; WC: waist circumference; WHR: waist-to-hip ratio; SBP/DBP: systolic/diastolic blood pressure; HOMA: homoeostatic model assessment; IR: insulin resistance; HIS: hepatic insulin sensitivity.
* Statistically significant difference.
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M.Y. Gharibeh et al. / Diabetes & Metabolism 36 (2010) 443–449
Table 4
Comparison of serum resistin levels in type 2 diabetics and controls according to body mass index (BMI).
Resistin
P
Normal weight (BMI ≤ 24.99 kg/m2 )
Overweight (BMI 25–29.99 kg/m2 )
Obese (BMI ≥ 30 kg/m2 )
Controls (n = 28)
Diabetics (n = 20)
Controls (n = 46)
Diabetics (n = 49)
Controls (n = 51)
Diabetics (n = 71)
6.7 ± 0.3
0.511
7.1 ± 0.5
6.3 ± 0.3
0.113
7.2 ± 0.5
6.3 ± 0.3
0.0006*
8.5 ± 0.5
Data are presented as means ± SEM.
* Statistically significant difference.
resistin levels showed no significant correlation with FBG,
HbA1c , total cholesterol, triglycerides, HDL, LDL, systolic and
diastolic blood pressure, LBM, WHR and IR.
4. Discussion
The present study data revealed significantly higher levels
of plasma resistin in type 2 diabetic patients compared with
healthy control subjects, with an overall difference in levels of
around 14% in the two tested groups. This finding is consistent
with several other studies linking resistin and type 2 diabetes
[12,21,22], but contradicts other reports that failed to detect any
considerable levels of resistin in such patients [5,23]. In the
present study, our Jordanian diabetics were also characterized
by high WC, WHR and HOMA (␤-cell index) values, as well as
an increase in plasma levels of glucose, HbA1c and triglycerides,
with a decrease in plasma HDL.
Analysis of the gender effect showed that male diabetic
patients had no significant differences in systolic blood pressure,
WC and HDL values in comparison to the male controls. On
the other hand, changes in female diabetic patients’ parameters,
including resistin, were consistent with the parameters seen in
the whole Jordanian diabetic group. Indeed, several studies have
suggested significant gender differences in plasma concentrations of resistin [10,23,24], although other reports [12,25] — in
agreement with our present study — could not verify such a
finding.
However, growing older appears to be a major factor in determining levels of serum resistin in type 2 diabetics. Patients who
were ≤ 40 years of age had similar levels of plasma resistin as
their corresponding controls. However, patients aged > 60 years
had a highly significant increase in resistin values compared with
their corresponding controls. This observation may be explained
by the development of obesity and IR with ageing [26]. The
importance of the age factor on levels of plasma resistin in diabetic patients may have been overlooked in the past, and could
partly explain some of the controversial data regarding plasma
resistin levels in such patients [5,13,23].
The present study also demonstrated a significant relationship
between diabetics’ age and IR as expressed by HOMA, IR and
HIS markers. Similarly, the observed association of resistin with
serum insulin and HOMA values shown by Pearson’s analysis
confirms the role of resistin in IR (Table 5). This finding of a link
between plasma resistin and IR in Jordanian type 2 diabetics is
contrary to previous reports of other diabetic ethnic groups, such
as the Japanese [12] and Pima Indians of Arizona [27]. However, such differences are probably due to ethnic variations or to
technical discrepancies that may require further investigations
involving a wider range of different ethnic groups and the use
of standardized assessment methodology.
The data from Pearson’s analysis also showed positive correlations between circulating resistin and obesity markers as
conveyed by BMI, WC and BF values (Table 5). The latter observation was further substantiated by the detection of a positive
correlation between serum resistin and obese — but not overweight or normal-weight — type 2 diabetic patients. This finding
is in agreement with a study of resistin levels in Saudi diabetics
by Al-Harithy and Al-Ghamdy [28] that showed no correlation
in lean subjects, but a highly significant correlation with BMI,
WHR and WC in diabetic women. However, our present finding
contradicts another Saudi report by Al-Daghri et al. [29] that
failed to find a positive correlation between resistin levels and
BMI in diabetic Saudi patients.
An increase in human obesity can raise serum resistin
levels [8,30] and is directly correlated with IR [10,31], while
medical treatment resulted in declines in both serum resistin and
obesity [32]. Lazar [7] proposed that communication between
adipocytes and macrophages might lead to hyperresistinaemia,
as human resistin is mainly expressed in macrophages. In
addition, there is genetic evidence to support a relationship
Table 5
Pearson’s analysis of correlation of resistin with various parameters in type 2
diabetics.
Parameter
Pearson r
R squared
P (two-tailed)
Age
Fasting blood glucose
HbA1c
Cholesterol
Triglycerides
HDL
LDL
Urea
Creatinine
Insulin
Body mass index
Waist-to-hip ratio
Waist circumference
Systolic blood pressure
Diastolic blood pressure
Lean body mass (kg)
Body fat (kg)
Homoeostatic model assessment
Insulin resistance
0.1677
−0.1328
−0.01842
−0.06133
0.02444
−0.00739
−0.1102
0.4468
0.4686
0.1928
0.1932
0.1336
0.2215
0.05648
0.04291
0.08809
0.1915
0.2389
0.08505
0.02811
0.01763
0.0003394
0.003761
0.0005974
0.00005463
0.01214
0.1996
0.2196
0.03717
0.03668
0.01784
0.04905
0.003189
0.001842
0.007761
0.03668
0.05706
0.007233
0.0477*
0.1178
0.8290
0.4717
0.7744
0.9309
0.1949
< 0.0001**
< 0.0001**
0.0225*
0.0234*
0.1156
0.0085*
0.5075
0.6147
0.3007
0.0234*
0.0045*
0.3178
r: correlation coefficient;
* Statistically significant correlation.
** Highly statistically significant correlation.
448
M.Y. Gharibeh et al. / Diabetes & Metabolism 36 (2010) 443–449
between human resistin protein and obesity or IR [33]. Overall,
these data favour a possible link between human plasma resistin
levels, obesity, IR and type 2 diabetes, despite being clearly
inconsistent with other observations [12,13,23].
The present study data also revealed a significant increase in
blood urea in diabetics compared with non-diabetics, especially
when these patients were older in age (> 50 years). This finding
was clearly demonstrated by Pearson’s analysis, which showed
a positive correlation between resistin and old age and urea, as
well as creatinine, in type 2 diabetic patients. Altogether, they
support earlier reports of an association of high plasma resistin
with a decrease in glomerular filtration rate [34] and progressive
impairment of renal function, as well as chronic kidney disease
[35]. Moreover, it signifies the potential role of resistin as a
biomarker for renal complications in type 2 diabetes.
There was a significant increase in blood pressure in diabetics, and hypertension remains a high-risk factor even for
older, non-diabetic, subjects, which makes any comparison of
the blood pressure effect in relation to age parameters somewhat meaningless. This may partly explain the failure to obtain
a relationship between systolic and diastolic blood pressure values with increasing age in Jordanian diabetics, or any significant
correlation between blood pressure and plasma resistin levels in
such patients. Evidently, resistin possesses a proinflammatory
action in humans, allowing it to play an important role as a
vasoactive factor that directly affects endothelial function and
vascular homoeostasis [36]. This particular property of resistin
may be linked to the risks of nephropathy and atherosclerosis
that are encountered as common complications of type 2 diabetes
[6,37].
The lack of association between serum resistin and blood
glucose or HbA1c in diabetic patients is consistent with previous
data [6]. Taken together, this suggests an indirect role of resistin
on the development of type 2 diabetes most likely by aggravating
the inherent incompetence of insulin metabolism.
Several studies have shown that the production of other
adipokines, such as leptin and adiponectin, is altered in type
2 diabetes and might be involved in IR pathophysiology [38].
In addition, certain variations in leptin and adiponectin genes
have been implicated in successful ageing (ageing without agerelated diseases) in the Jordanian population [39]. However, the
contribution of these adipokines to the development of obesity
and IR in type 2 diabetes was not investigated in the present
study, although it will be the subject of future research.
In conclusion, the present findings suggest that resistin may
be implicated in the pathogenic mechanisms through which
increased adiposity leads to the development of IR and type 2
diabetes in the Jordanian population. Furthermore, resistin could
serve as a biomarker for renal and other vascular complications
associated with type 2 diabetes, particularly in older-aged
patients.
Conflict of interest statement
The authors do not have any conflict of interests to declare
regarding the present study.
Acknowledgments
This research was supported by the Deanship of Research
at Jordan University of Science and Technology (grant no.
63/2009). The authors also wish to thank Mr Mohammad Alzubi
for his technical help during the study.
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