Elevated Serum Tumor Necrosis Factor Alpha and Ferritin May Contribute
to the Insulin Resistance Found in HCV Positive Egyptian Patients
M. Elsammak; W. Refai; A. Elsawaf; I. Abdel-Fattah; E. Abd Elatti; A.
Ghazalf
Abstract and Introduction
Abstract
Objective: There is evidence of an increased incidence of insulin
resistance and diabetes mellitus (DM) in patients with hepatitis C
virus (HCV) infection. Several mechanisms have been proposed, including
inadequate insulin secretion or interference with signaling within the
insulin receptor. We assessed serum tumor necrosis factor alpha (TNFa)
and ferritin levels as potential mediators of insulin resistance in HCV
positive Egyptian patients.
Patients and Results: Patients ( n = 27) with HCV infection, patients (
n = 23) with hepatitis C and DM (HCV + DM), patients ( n = 22) with DM,
and sex- and age-matched controls ( n = 18) were included in this
study. The degree of insulin resistance (HOMA index) was significantly
higher in the HCV, HCV + DM and DM groups compared to the controls. The
mean ± SD of the HOMA index was 4.53 ± 2.84, 6.1 ± 2.36, 3.69 ± 2.2
and 1.32 ± 0.49, in HCV, HCV + DM, DM and controls, respectively.
Serum TNFa levels were significantly higher in the HCV, HCV + DM groups
compared with the healthy controls and DM patients ( p < 0.001). The
median (range) values of TNFa in HCV, HCV + DM, DM patients and
controls subjects were 25.5 (0.43-124.0), 19.8 (0.51-139), 0.85
(0-10.5) and 0.32 (0-5.8)pg/mL, respectively. There was a significant
positive correlation between the HCV load and both HOMA index and TNFa
level. HCV and HCV + DM patients also had significantly higher serum
ferritin levels compared with healthy controls and patients with DM.
The mean ± SD of serum ferritin in HCV, HCV + DM, DM patients and
controls subjects was 258.1 ± 116.2, 285.8 ± 124.3, 86.9 ± 41.8 and
159.9 ± 76.9ng/mL, respectively.
Conclusion: Patients with HCV infection had a significantly higher
level of TNFa and ferritin which may explain their insulin resistance.
HOMA index and serum TNFa levels correlated positively with the HCV
load.
Introduction
Evidence showing a higher prevalence of diabetes mellitus (DM) in
patients with chronic hepatitis C virus (HCV) infection has been
accumulating.[1-3] The underlying mechanisms explaining the connection
between HCV and insulin resistance and the onset of type 2 DM are still
unclear. Several mechanisms have been proposed, including insulin
resistance and inadequate insulin secretion.[4-6] Other reports
suggested that insulin resistance may just be a consequence of
steatosis. Hepatic steatosis is recognized as a component of the
metabolic syndrome and precedes the onset of type 2 DM.[7-9] It has
been suggested that the connection between hepatitis C and DM could be
secondary to the ability of HCV to induce hepatic steatosis.[7,8]
Another possible explanation is a direct effect of HCV proteins on
insulin-signaling pathways.[10-12]
Tumor necrosis factor alpha (TNFa) induces serine phosphorylation of
IRS-1 (insulin receptor substrate-1) and thus inhibits its tyrosine
phosphorylation and signaling activity.[12] Defects in the insulin
receptor and IRS-1 are present in insulin resistance and type 2 DM.[13]
Furthermore, the proinflammatory cytokine, TNFa, has the ability to
inhibit insulin-stimulated glucose uptake.[13]
Other factors that could play a role in the development of insulin
resistance and subsequent DM include obesity and high iron level.
Cross-sectional studies suggested that there is a positive correlation
between body iron stores and disease severity in HCV.[14] Furthermore,
the relationship between iron overload and the development of DM is
well established.[15,16]
To date, few data are available about the relationship between the HCV
load, serum levels of TNFa and ferritin and the development of insulin
resistance. We aimed to investigate the status of insulin resistance in
Egyptian patients with HCV infection, patients with HCV + DM (HCV + DM)
and its relationship to TNFa and ferritin levels and virus load in
comparison with age- and sex-matched healthy controls and another
control group with DM but without HCV infection.
--------------------------------------------------------------------------------
M. Elsammak ,a W. Refai ,b A. Elsawaf ,c I. Abdel-Fattah ,d E. Abd
Elatti e and A. Ghazalf f
aDepartment of Chemical Pathology, Medical Research Institute,
Alexandria University, Egypt
bDepartment of Gastroenterology, Medical Research Institute, Alexandria
University, Egypt
cDepartment of Physiology, Medical Research Institute, Alexandria
University,Egypt
dInternal Medicine Department, Alexandria Student University Hospital,
Egypt
eDepartment of Internal Medicine, Menofeya University, Egypt
fDepartment of Microbiology, Medical Research Institute, Alexandria
University, Egypt
Curr Med Res Opin. 2005; 21 (4): 527-533. ©2005 Librapharm Limited
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