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مقاله پژوهشي 1393/07/01
مقاله پژوهشي
مقاله پژوهشي

RESEARCH ARTICLE Open Access
Relationship between beta-globin gene carrier
state and insulin resistance
Adele Bahar1, Zahra Kashi1*, Mehrnoush Sohrab2, Mehrnoush Kosaryan1,3 and Ghasem Janbabai4
Abstract
Objective: To assess the relationship between being beta globin gene carrier and developing insulin resistance.
Methods: This study was conducted on 164 subjects including 82 healthy ones and 82 patients with beta
thalassemia minor (microcytosis (MCV Fasting blood glucose (FBS) values of 100–125 mg/dl were considered as impaired fasting glucose, and above
125 mg/dl as diabetes mellitus. Two hours After 75 gram glucose load(GTT), blood sugar level of 140–199 mg/dl
was considered as impaired glucose tolerance and above 199 mg/dl as diabetes mellitus. Insulin resistance was
diagnosed based on homeostasis model assessment method (HOMA).
Results: According to FBS and BS2hPG values, the percentages of diabetes mellitus, pre diabetes, and normal
glucose tolerance in case group was 8.5%, 9.8% and 81.7%, respectively. There was no case of diabetes mellitus in
control group and 6.1% of this group were pre diabetic and 93.9% of them had normal glucose tolerance test
(P = 0.02). Relative risk for diabetes mellitus and insulin resistance in the cases with minor thalassemia was
2 (95% CI: 1.8-2.5) and 2.02 (95% CI: 1.7-2.4), respectively.
Conclusion: The risk of developing diabetes and insulin resistance in patients with thalassemia minor is two times
greater than the general population. Considering the high serum levels of CRP in these cases, the inflammation
noted in liver cells could be considered as the underlying cause of insulin resistance, impaired glucose tolerance
and diabetes in these patients.
Keywords: Thalassemia minor, Insulin resistance, Impaired glucose tolerance, Diabetes mellitus, HOMA
Introduction
Insulin resistance is a common problem in patients with
different types of hemoglobinopathies including beta
thalassemia major. Excessive iron deposition in the pancreas
and liver of patients suffering from thalassemia
major as well as insulin resistance has been described
[1]. It is believed that the increase in iron overload may
damage the pancreatic β cells [2]. Increased iron turnover,
similarly, may damage liver, contributing to oxidative
stress and insulin resistance [3]. The reported
prevalence of impaired glucose tolerance and diabetes
mellitus in thalassemia major is up to 24% and 26%
respectively and it is believed that insulin resistance
can be occurred in these patients before the onset of
glucose intolerance or diabetes mellitus [4]. Insulin
resistance in beta thalassemia minor (carrier state) has
been demonstrated as well [4].
Considering high number of complications associated
with insulin resistance and impaired glucose metabolism,
the present study was designed to evaluate the prevalence
of these metabolic disorders in patients with beta
thalassemia minor.
Materials and methods
After being approved by the Ethical Board of Mazandaran
University of Medical Sciences, Sari, Iran this study
was conducted on 82 individuals with beta thalassemia
minor and 82 healthy subjects as control group[according
to P1=6% (prevalence of IGT in normal population),
P2=14% (prevalence of IGT in beta thalassemia minor),
d2=10% , Z1-β ,Z1- α/2=1.96]. The diagnosis of beta thalassemia
minor was based on the detection of hemoglobin
(Hgb) A2 > 3.5% by column chromatography (Spain bio
* Correspondence: kashi_zahra@yahoo.com
1Diabetes Research Center, Mazandaran University of Medical Sciences, Sari,
Iran
Full list of author information is available at the end of the article
© 2012 Bahar et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Bahar et al. Journal of Diabetes & Metabolic Disorders 2012, 11:22
http://www.jdmdonline.com/content/11/1/22
system Co.) and hemoglobin electrophoresis using HPLC
(High-performance liquid chromatography) and cellulose
acetate gel.
Subjects in the two groups were matched in terms of
body mass index (BMI) and family history of diabetes
mellitus. Age range was from 20 to 60 years of age.
Blood pressure values were normal (having diastolic
blood pressure < 80 mmHg and systolic blood pressure <
120 mmHg) [5].
Exclusion criteria consisted of history of kidney, liver
and heart disease, history of diabetes, receiving medications
which affect carbohydrate metabolism (such as
corticostroids,cyclosporin,closapin) and waist circumference
(WC) more than 102 cm in men and more than
88 cm in women [6].
Anthropometric measurements including weight and
height were obtained with light clothing and without
shoes by trained technicians following international
guidelines. The height (to the nearest 0.1 cm) and weight
(to the nearest 0.1 kg) were measured using a stediometer
and a digital scale (Micro life ws80, Switzerland),
respectively. The BMI was calculated as the body weight
divided by the height squared (Kg/m2). WC was measured
using a non-elastic flexible anthropometric tape
(to the nearest 0.1 cm) in the standing position. The tape
was applied horizontally midway between the lowest rib
margin and the iliac crest.
A fasting blood sample (FBS) was taken from all the
participants. Serum FBS was analyzed by enzymatic
calorimetric method using glucose kit of Parsazmoon
Co, Iran. AST (Aspartate aminotransferase) and ALT
(Alanine aminotransferase) were measured by calorimetric
method using Biosystem kit, Spain and Hitachi917,
Germany. High sensitive C-reactive protein (hs-CRP)
was measured by imminotorbidometry assay by Pars
Azmoon kit, England, using Hitachi917 machine Germany.
ELISA test with Hitachi auto analizer using Monobind kit,
USA was used to assess serum insulin levels. A standard
oral glucose tolerance test (OGTT) was performed in all
subjects.
Individuals with abnormal FBS (FBS ≥100) and/or
abnormal OGTT (blood sugar 2 hours post-prandial
(BS 2hpp) ≥140) were re-tested. FBS values below
100 mg/dl were considered as normal, 100–125 mg/dl
as impaired fasting glucose, and above 125 as diabetes.
BS 2hpp below 140 mg/dl was considered as normal,
140–199 mg/dl as impaired glucose tolerance and above
199 as diabetes [7].
Insulin resistance was calculated using HOMA-IR
(homeostasis model assessment method) [8].
HOMAIR ¼ Fasting plasma insulin mIU=L
 Fasting Plasma Glucose mmol=l22:5
Considering HOMA-IR values, the studied population
was divided into three groups:
1. (Insulin Sensitive) HOMA-IR < 2.24
2. (Intermediate) 2.24 ≤ HOMA-IR ≤ 3.59
3. (Insulin Resistance) HOMA-IR > 3.59
The student t-test and chi-squared test were used to
compare demographic data between the two groups.
Relative Risk was measured to test the risk of diabetes
and insulin resistance in two groups. P value less than
0.05 was considered statistically significant.
Results
In patient group, 53 cases (64.6%) were female and 29
(35.4%) were male. In control group 38 subjects (46.3%)
were male and 44 (53.7%) were female (P = 0.1). Other
demographic data are outlined in Table 1: According to
FBS and BS2hPG values, the percentages of cases with
diabetes mellitus, impaired fasting glucose, and normal
glucose tolerance were 8
.5%, 9.8% and 81.7%, respectively.
There was no case of diabetes mellitus in control
group and 6.1% of subjects had impaired fasting glucose
and 93.9% of them were normal glucose tolerance test.
(P = 0.02).
According to FBS and BS2hPG values, the percentages
of cases with diabetes mellitus, impaired fasting glucose,
and impaired glucose tolerance were 7.3%, 11% and
81.7%, respectively. There was no case of diabetes mellitus
in control group and 7.3% of subjects had impaired
fasting glucose or impaired glucose tolerance. (P = 0.02).
AST and hs-CRP values were also similarly higher
among the cases (Table 2). There was, however, no significant
difference between mean ALT, fasting insulin
and HOMA-IR levels between the two groups .Fasting
insulin level was 6.5± 5.3 and 5.9±2.0 in case and control
group respectively.
Table 1 Demographic findings of the subjects with beta
thalassemia minor regarding demographic data, Sari,
Iran, 2010
Controls Cases P value
(N = 82) (N= 82)
Mean ± SD Mean ± SD
Age (year) 39.5±8.7 39.7±8.8 0.8
Weight(kg) 67.4±8.5 66.4±8.4 0.4
Height(meter) 170.1±7.7 169.3±7.5 0.5
BMI(kg/m2) 22.9±1.4 22.7±1.4 0.4
Systolic blood pressure(mmHg) 109±4.9 110±4.9 0.6
Diastolic blood pressure(mmHg) 67±4.9 68±5.4 0.8
Waist(cm) Male 83±2 83±2.2 0.8
Female 77±1.3 76±1.8 0.8
Bahar et al. Journal of Diabetes & Metabolic Disorders 2012, 11:22 Page 2 of 4
http://www.jdmdonline.com/content/11/1/22
Relative risk of developing diabetes mellitus (based on
FBS and BS2hPG values) and insulin resistance(based on
HOMA-IR) in patients with beta thalassemia minor
were 2 (CI 95%: 1.8-2.5) and 2.025 (CI 95%: 1.7-2.4)
respectively.
Discussion
In line with previous studies, our findings revealed that
the relative risk of developing diabetes mellitus and insulin
resistance in patients with beta thalassemia minor is
two times higher than the general population. Tang et al.
reported that thalassemia minor patients with normal
glucose tolerance have higher fasting insulin levels and
insulin resistance (HOMA-IR) than the healthy controls
matched for age, gender and BMI [4]. In another study
Alhezmy et al. reported that 6 percent of thalassemia
major patients and only 2 percent of the kids with thalassemia
minor or no hemoglobinopathy were diagnosed
with diabetes mellitus. The prevalence of impaired glucose
tolerance was, similarly, higher in patients with
thalassemia major compared to those suffering from
thalassemia minor and healthy subjects. In this study,
subjects were not matched in terms of BMI and family
history of diabetes; both of which play an important role
in the development of diabetes and insulin resistance [9].
Corroborating previous studies, our research reported
significantly higher CRP levels in thalassemia minor
patients [4]. This finding can explain the higher prevalence
of insulin resistance in these patients [10]. Mean
AST and ALT levels were also higher in this group of
patients [11]. The correlation between ALT levels and
insulin resistance has been reported in other studies
[12-15]. Berget et al. while studying a group of adolescents,
pointed out that any increase in ALT levels, even
when it is within the normal range, lowers the sensitivity
of the cells to insulin, contributing to impaired
glucose tolerance and increased levels of free fatty
acids and triglycerides [11]. In another study in Native
American adults (Pima Indians), ALT was reported as a
predictor of type II diabetes [15]. Considering the higher
serum levels of liver enzymes and hs-CRP in thalassemia
minor patients, the inflammation of liver cells could be
accounted for the underlying cause of insulin resistance
and impaired glucose tolerance in these patients [4]. In
other words, liver inflammation and increased oxidative
stress secondary to microcytic erythrocytes hemolysis is
the main reason contributing to higher prevalence of
diabetes in thalassemia minor patients. According to
this concept Noetzli et al. in their study showed that
Pancreatic iron overload and diabetes mellitus (DM) are
common in thalassemia major patients and iron deposition
in pancreas is the strongest predictor of beta cell
toxicity and total body iron burden, age, and body
habitus also influence glucose regulation too [16].
The certain limitation of our study was that serum
level of ferritin a marker of liver inflammation was not
measured though we measured the CRP another marker
of inflammation.
Conclusion
The present study revealed that similar to thalassemia
major sufferers, the prevalence of insulin resistance and
diabetes is higher in patients with thalassemia minor
than the general population. Considering the high prevalence
of thalassemia minor in our country and the fact
that impaired glucose metabolism is associated with
multiple complications, it is recommended to screen
thalassemia minor patients for glucose tolerance at a
younger age. Further studies are also required to detect
other mechanisms contributing to insulin resistance in
these patients.
Competing interests
We have no competing interests.
Authors’ contributions
AB: ES-FG, ZK: ES-FG, MS: ES-FG, MK: FG, GJ: FG. All authors read and
approved the final manuscript.
Acknowledgements
This study was Dr Mehrnoosh Sohrab postgraduate thesis and was
supported by a grant from Mazandaran University of Medical Sciences.
Funding
Diabetes Research Center, Mazandaran University of Medical Sciences, Sari,
Iran.
Author details
1Diabetes Research Center, Mazandaran University of Medical Sciences, Sari,
Iran. 2Deparment of internal medicine, Imam Khomeini hospital, Razi street,
Sari, Iran. 3Thalassemia Research Center, Mazandaran University of Medical
Sciences, Sari, Iran. 4Cancer center, Mazandaran University of Medical
Sciences, Sari, Iran.
Received: 13 July 2012 Accepted: 10 November 2012
Published: 19 November 2012
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doi:10.1186/2251-6581-11-22
Cite this article as: Bahar et al.: Relationship between beta-globin gene
carrier state and insulin resistance. Journal of Diabetes & Metabolic
Disorders 2012 11:22.
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