Tumor necrosis factor–α–induced insulin resistance may mediate the hepatitis C virus–diabetes association

H Knobler, T Zhornicky, A Sandler… - Official journal of the …, 2003 - journals.lww.com
H Knobler, T Zhornicky, A Sandler, N Haran, Y Ashur, A Schattner
Official journal of the American College of Gastroenterology| ACG, 2003journals.lww.com
OBJECTIVES: Among patients infected with hepatitis C virus (HCV), 13–33% develop type 2
diabetes mellitus (DM). The mechanism for this remains unclear. Because tumor necrosis
factor–α (TNF-α) has been identified as a mediator of insulin resistance and is induced by
HCV, we examined TNF-α and proinflammatory cytokines in noncirrhotic patients with
chronic hepatitis C, both with and without diabetes. METHODS: HCV-infected patients with
type 2 DM (n= 23) were compared with age-and sex-matched patients with chronic hepatitis …
Abstract
OBJECTIVES:
Among patients infected with hepatitis C virus (HCV), 13–33% develop type 2 diabetes mellitus (DM). The mechanism for this remains unclear. Because tumor necrosis factor–α (TNF-α) has been identified as a mediator of insulin resistance and is induced by HCV, we examined TNF-α and proinflammatory cytokines in noncirrhotic patients with chronic hepatitis C, both with and without diabetes.
METHODS:
HCV-infected patients with type 2 DM (n= 23) were compared with age-and sex-matched patients with chronic hepatitis C and without DM (n= 28), patients with DM and without HCV (n= 31), and healthy controls (n= 21). Serum levels of TNF-α, interleukin-1β (IL-1β), interleukin-6 (IL-6), and soluble TNF receptors (sTNFR) 1 (p55) and 2 (p75) were determined by ELISA.
RESULTS:
Detectable serum TNF was found in 74% of the HCV/DM patients, versus 64% of the nondiabetic HCV group and≤ 10% in the other groups. Mean sTNFR1 in the HCV/DM group was 1931 pg/ml (95% CI= 1449–2413), compared with 1289 pg/ml (95% CI= 1101–1476) in nondiabetic HCV patients, with similar values in the other two groups (p= 0.001). The mean sTNFR2 level in the HCV/DM patients was 3326 pg/ml (95% CI= 2924–3727) compared with 2367 pg/ml (95% CI= 1951–2784) in the nondiabetic HCV patients, and similar results in the other groups (p< 0.0001). Serum IL-1β, IL-6, and C-reactive protein were not significantly different between HCV patients with or without DM.
CONCLUSIONS:
Excessive TNF-α response characterizes HCV-infected patients who develop DM. STNFR may be a marker for the development of DM in chronic hepatitis C.
Lippincott Williams & Wilkins