Insulin resistance derived from zinc deficiency in non-diabetic patients with chronic hepatitis C

Abstract

Abstract. chronic hepatitis c virus (hcV) infection frequently evokes metabolic abnormalities including insulin resistance. a decrease in serum zinc (Zn) levels is often observed in association with hepatic fibrosis. Zn also plays important roles in insulin secretion. however, little is known about the relationship between Zn deficiency and insulin resistance in patients with hcV-related chronic liver disease. the main purpose of this study was to examine the contribution of Zn deficiency to insulin resistance in patients with chronic hepatitis c (ch-c). Forty-eight non-diabetic patients with ch-c were enrolled. Serum alanine aminotransferase (alt), ferritin and Zn levels were examined in the enrolled patients with ch-c. insulin resistance was determined by the homeostasis model for assessment of insulin resistance (HOMA-IR). Zn deficiency was defined as serum Zn levels <65 µg/dl. Seven out of the 48 (15%) patients with CH-C fulfilled the criteria for Zn deficiency. Serum Zn levels were inversely correlated with serum ferritin levels (r=-0.364, p=0.0140). The values of HOMA-IR were positively linked to serum ferritin levels (r=0.299, p=0.0484). The mean value of HOMA-IR in the Zn deficiency group was significantly higher than that in the normal-range Zn group (3.76±0.66 vs. 2.08±1.35, p=0.0019). Serum ALT levels were also closely associated with serum ferritin levels (r=0.727, p<0.001). These findings were independent of HCV genotypes or loads of hcV-rna. Our data suggest that iron overload in patients with CH-C derives from Zn deficiency and thereby causes insulin resistance. IntroductionZinc (Zn) is an essential trace element that serves as the active center of approximately 300 enzymes and participates in physiological functions including immune function, neurosensory function, protein metabolism, wound healing and sexual function (1,2). Zn plays important roles as a growth co-factor, an immunomodulator and a cytoprotectant with antioxidant, antiapoptotic and anti-inflammatory effects (3,4). Therefore, Zn depletion results in numerous types of symptoms including taste disorder, hyperkeratotic skin change, wound healing disturbance and testicular dysfunction.Zn deficiency is also frequently observed in patients with chronic liver diseases (cld), including chronic hepatitis and liver cirrhosis (5-8). Serum Zn levels inversely correlate with the severity of hepatic fibrosis (7). Zn depletion in patients with liver cirrhosis is closely related to the progression of hepatic encephalopathy. Zn deficiency usually leads to a decrease in the activity of ornitine transcarbamylase, a key Zn-containing enzyme for the urea cycle. this consequently causes the accumulation of ammonia and seems to account for the pathogenesis of hepatic encephalopathy (9). Zn administration has favorable effects on the inhibition of hepatic fibrosis, activating collagenase, which belongs to a zinc-metallo-enzyme, and/or diminishing prolyl hydroxylase, which contributes to collagen synthesis (10). Zn supplementation also relieves hepatic ence...

Status of Essential Trace Minerals and Oxidative Stress in Viral Hepatitis C Patients with Nonalcoholic Fatty Liver Disease

“…The presence of NAFLD in the subjects with IR implies further oxidative stress and inflammation 43. The plasma concentrations of Zn ( r = -0.38, p = 0.04) and Se ( r = -0.54, p = 0.00) inversely correlated with HOMA-IR values in HCV patients, which agrees with the results of other studies 8,9. In the present study, plasma mineral concentrations also correlated with HOMA-IR and HDL values in the HCV-NAFLD patient group.…”

Evolution of ferritin levels in hepatitis C patients treated with antivirals

“…In contrast, the pretherapy-only factors (sex, HOMA-IR, hemoglobulin and IFNL3-rs12979860 genotype) and posttherapy-only factors (TC and anti-HCV therapy) suggested potential links, direct or indirect, between HCV infection and ferritin levels. Consistently, higher hepatic iron concentrations were observed in male CHC patients 29 ; the connection between HOMA-IR and ferritin levels in CHC patients has been reported 30 and may correlate with the grade of hepatic iron deposition 31,32 ; the negative association between hemoglobin and ferritin levels among CHC patients seemed to reflect the links between fibrosis (portal hypertension subsequent to hepatic fibrosis might lead to variceal bleeding with anemia and then low hemoglobin levels) and ferritin levels, as elevated serum ferritin levels are independently associated with advanced liver fibrosis in CHC patients 12 . Of note, it is a novel finding that the IFNL3-rs12979860 CC genotype was negatively associated with baseline ferritin levels, which echoes previous studies revealing that baseline ferritin levels were independently associated with poor response to interferon-based therapy 12,33,34 ; the association might occur through advanced hepatic fibrosis 12,35 , hepatic steatosis 12,36,37 or high necroinflammatory activity 35 .…”

Associations between Zinc Deficiency and Metabolic Abnormalities in Patients with Chronic Liver Disease

“…Zn deficiency seems to be associated with the pathogenesis of type 2 diabetes mellitus (DM), supporting the notion that Zn deficiency may result in the exacerbation of insulin resistance. Zn deficiency may derive from hyperzincuria in patients with type 2 DM [ 61 ].…”