Basic HTML Version
24
VOLUME 9 NUMBER 1 • MARCH 2012
RESEARCH ARTICLE
SA JOURNAL OF DIABETES & VASCULAR DISEASE
On multiple regression analysis (Table 3), considering TNF-
α
and
IL-6 as dependent variables, HOMA B, HOMA S and fasting glucose
levels, and WHR showed a significant negative association, and IL-6
showed a significant positive association with TNF-
α
, adjusting for
the confounding factors in the diabetic subjects. HOMA B, HOMA
S, TNF-
α
and fasting glucose levels, and WHR showed a significant
positive association with IL-6, adjusting for the effects of the
confounding factors in the diabetic subjects.
Discussion
Type 2 diabetes mellitus is associated with increased inflammatory
markers. Insulin resistance is a common feature of type 2 diabetes.
It has been shown that inflammatory cytokines such as TNF-
α
and IL-6 have been linked to insulin resistance.
15
The underlying
mechanisms of the development of insulin resistance are not clear,
but a key mechanism by which TNF-
α
was thought to induce insulin
resistance involved serine phosphorylation of the insulin receptor
substrate-1 (IRS-1).
16
TNF-
α
level has been shown to be increased
in patients with type 2 diabetes mellitus. However, whether it
is involved in the development of type 2 diabetes mellitus and
whether elevation of TNF-
α
precedes the onset of type 2 diabetes
mellitus is not clear.
Recently it was shown that inflammation contributes to insulin
resistance in obese and diabetic patients.
17
Inflammatory molecules
such as TNF-
α
and IL-6 may therefore play an important role. It was
found that diabetic patients had elevated levels of TNF-
α
,
18
which
reinforces this hypothesis.
In our study, serum TNF-
α
levels were significantly higher
in the diabetic subjects than in the controls. Other studies have
documented that serum TNF-
α
concentrations were higher in
subjects with impaired glucose tolerance than in those with normal
glucose tolerance.
11,19,20
A Korean study found no elevation in
serum TNF-
α
concentrations in pre-diabetic patients compared
to controls.
21
Spranger
et al
. showed that baseline levels of TNF-
α
were significantly elevated among type 2 diabetes subjects (2.08
pg/ml) compared to controls (1.78 pg/ml,
p
= 0.002).
22
Our study shows similar patterns of association in the type 2
diabetes subjects. Moreover on binary logistic regression analysis,
TNF-
α
was significantly (
β
= 0.102,
p
= 0.039) associated with
diabetes when TNF-
α
and IL-6 were considered as covariates. On
multiple linear regression analysis it was found that levels of HOMA S
(
β
= –0.45,
p
= 0.010), HOMA B (
β
= –0.945,
p
= 0.003) and fasting
glucose (
β
= –0.796,
p
= 0.004), and WHR (
β
= –0.379,
p
= 0.017)
were negatively associated with TNF-
α
in the diabetic subjects.
In our study we found that serum IL-6 levels were significantly
higher in the diabetic subjects compared to controls. In addition,
IL-6 was not significantly associated with diabetes when TNF-
α
and
IL-6 were considered as covariates using binary logistic regression
analysis. With multinominal regression analysis it was shown that
HOMA S (
β
= 0.411,
p
= 0.013), HOMA B (
β
= 0.885,
p
= 0.002)
and fasting glucose (
β
= 0.865,
p
= 0.001) levels, and WHR (
β
= 0.311,
p
= 0.038) were positively associated with IL-6 in the
diabetic subjects.
Other studies have documented that serum IL-6 concentrations
were higher in subjects with impaired glucose tolerance than in
those with normal glucose tolerance,
11,19,20
while a Korean study
found no elevation in serum IL-6 concentrations in pre-diabetic
Koreanwomen compared to controls.
21
A study on Italian Caucasians
has shown that impaired glucose tolerance and type 2 diabetes,
but not impaired fasting glucose levels were associated with
elevated IL-6 levels.
13
This discrepancy was most likely due to racial
differences, environment, geographical condition and nutritional
status.
The major weakness of our study was small sample size. Due to
funding constraints we were limited in the number of patients in
our study.
Conclusion
From our study, it can be concluded that levels of TNF-
α
were
associated with insulin resistance in subjects with type 2 diabetes.
Hyperglycaemia appeared to be a major trigger for the pro-
inflammatory changes in diabetes.
Table 3.
Multiple linear regression analysis of different factors affecting TNF-
α
and IL-6 versus type 2 diabetes subjects.
Group
Factors
Standardised coefficients Unstandardised coefficients
β
SE
β
t p
-value
TNF-
α
vs
type 2 diabetes
(Constant)
1180.937
314.606
3.754
0.001
HOMA B
–2.127
0.618
–0.945
–3.440
0.003
HOMA S
–1.229
0.430
–0.558
–2.861
0.010
IL-6
–3.655
0.528
0.903
6.924
0.001
F_GLU
–32.952
10.150
–0.796
–3.246
0.004
BMI
0.736
3.658
0.062
0.201
0.843
WHR
–755.628
288.776
–0.579
–2.617
0.017
IL-6 vs
type 2 diabetes
(Constant)
–259.714
74.416
–3.490
0.002
HOMA B
0.492
0.141
0.885
3.481
0.002
HOMA S
0.273
0.100
0.711
2.725
0.013
TNF-
α
0.193
0.028
0.903
6.924
0.001
F_GLU
8.838
2.098
0.865
4.212
0.001
BMI
–0.125
0.841
–0.059
–0149
0.883
WHR
153.346
68.821
0.511
2.228
0.038
Standardised coefficient (
β
) was calculated by multiple linear regression analysis using SPSS 11.5.