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22
VOLUME 9 NUMBER 1 • MARCH 2012
RESEARCH ARTICLE
SA JOURNAL OF DIABETES & VASCULAR DISEASE
Correspondence to: M Hossain
Department of Biochemistry and Molecular Biology, University of Chittagong,
Chittagong, Bangladesh
e-mail: mosarafacme@gmail.com
O Faruque, I Khan, L Ali
Research Division, Bangladesh Institute of Research and Rehabilitation in
Diabetes, Endocrine and Metabolic Disorders (BIRDEM), Dhaka, Bangladesh
G Kabir, D Sikdar
Department of Biochemistry and Molecular Biology, University of Chittagong,
Chittagong, Bangladesh
S Afr J Diabetes Vasc Dis
2012;
9
: 21–24
Association of serum tumour necrosis factor-
α
and
interleukin-6 with insulin secretion and insulin resistance in
subjects with type 2 diabetes in a Bangladeshi population
M HOSSAIN, O FARUQUE, G KABIR, I KHAN, D SIKDAR, L ALI
Abstract
Objective:
Epidemiological evidence suggests that levels
of inflammatory markers, such as tumour necrosis factor-
α
(TNF-
α
) and interleukin-6 (IL-6), can predict the development
of diabetes but the association of these inflammatorymarkers
with the basic pathology of type 2 diabetes is unclear. In the
present study we investigated the association of TNF-
α
and
IL-6 with insulin secretion and insulin sensitivity in subjects
with type 2 diabetes.
Methods:
Thirty-seven subjects with type 2 diabetes were
studied along with 56 age- and body mass index (BMI)-
matched controls. Insulin was measured by ELISA analysis
and TNF-
α
and IL-6 chemiluminescence-based EIA.
Results:
Fasting serum TNF-
α
and IL-6 levels were significantly
higher in subjects with type 2 diabetes (
p
= 0.032) than in
controls. In binary logistic regression analysis, TNF-
α
was
significantly (
p
= 0.026) associated with diabetes when age,
gender and BMI were matched. In linear multiple regression
analysis, it was found that levels of HOMA S (
p
= 0.010),
HOMA B (
p
= 0.003) and fasting glucose (
p
= 0.004), and WHR
(
p
= 0.017) were negatively associated with TNF-
α
in diabetic
subjects. In the same analysis, HOMA S (
p
= 0.013), HOMA B
(
p
= 0.002) and fasting glucose levels (
p
= 0.001), and WHR (
p
=
0.038) were positively associated with IL-6 in diabetic subjects.
The association of TNF-
α
was positive with IL-6 (
p
= 0.001).
Conclusion:
TNF-
α
and IL-6 levels were both associated with
insulin resistance and insulin secretory defects in patients
with type 2 diabetes, and hyperglycaemia seemed to be a
major trigger for pro-inflammatory changes in diabetes.
Keywords:
TNF-
α
, IL-6, cytokines, inflammatory marker
Submitted 21/7/2011, accepted 1/2/2012
Chronic inflammation plays an important role in the pathogenesis
of type 2 diabetes.
1
Recent studies have shown that serum levels
of some inflammatory markers are elevated in patients with type
2 diabetes. Therefore, it has been suggested that long-term
activation of the immune system is involved in the development
of insulin resistance and type 2 diabetes mellitus.
2
Tumour
necrosis factor-
α
(TNF-
α
) and interleukin-6 (IL-6) are two major
pro-inflammatory markers or cytokines and they act primarily
as autocrine and/or paracrine factors. Studies have shown a
relationship between various inflammatory markers, specifically
TNF-
α
, IL-6, C-reactive protein and sialic acid, and the risk of
developing type 2 diabetes.
3-6
TNF-
α
is a pro-inflammatory cytokine secreted by several types
of cells, such as macrophages, monocytes, neutrophils and T cells.
Increased TNF-
α
synthesis has been shown in adipose tissue derived
from obese rodents or human subjects, and TNF-
α
is considered
a contributory factor in obesity-related insulin resistance and
the pathogenesis of type 2 diabetes mellitus.
7
TNF-
α
exerts its
metabolic effects via multiple mechanisms: the down-regulation
of genes that are required for normal insulin action, negative
regulation of PPAR
γ
an important insulin-sensitising nuclear
receptor, the direct effects on insulin signalling, and induction of
elevated free fatty acids via the stimulation of lipolysis.
8
By contrast, IL-6 is a monomer of 184 amino acids, an immune
protein in the haematopoietin family. It is synthesised by T cells,
macrophages and endothelial cells found on a single gene
located at 7p21. It is a major pro-inflammatory cytokine and is
produced by activated leukocytes, adipocytes
and endothelial
cells.
In vivo
infusion of human recombinant
IL-6 has shown it
to induce gluconeogenesis, subsequent hyperglycaemia
and
compensatory hyperinsulinaemia.
9
The role of IL-6 in insulin
resistance is controversial.
10
Adipocytes, skeletal muscle cells
and hepatocytes are involved in peripheral insulin resistance and
glucose homeostasis.
Evidence based on epidemiological studies suggests that
inflammatory markers predict the development of diabetes and
glucose disorders,
3
but the association of these inflammatory
markers with the basic pathology of type 2 diabetes is unclear. In
a recent study it was claimed that TNF-
α
and IL-6 are associated
with insulin resistance in type 2 diabetes.
11
Other studies have
shown that levels of these two inflammatory markers are elevated
in the pre-diabetic, impaired glucose tolerance (IGT) condition.
12,13
In a recent study on Bangladeshi pre-diabetic subjects, it was
shown that TNF-
α
may have a causal relationship with an insulin
secretory defect.
The present study was undertaken to determine the relationship
of TNF-
α
and IL-6 with insulin resistance and insulin secretion
in Bangladeshi subjects with type 2 diabetes, in order to better
understand the mechanism of this deadly disease.