Association Between Liver Fibrosis and Insulin Sensitivity in Chronic HCV
Association Between Liver Fibrosis and Insulin Sensitivity in Chronic HCV
The baseline characteristics of the 83 patients with HCV infection and 20 patients with HBV infection are shown in ( Table 2 ). In HCV patients, there were 56 men (67%) and 27 women (33%), with a mean age of 54 yr. The mean BMI was 23.7 kg/m, and 6 out of the 83 patients were habitual drinkers. The mean level of HCV core protein was 2,068.3 fmol/L. The mean values of HOMA-R, HOMA-β, and Δ-insulin/Δ-glucose 30 were 2.86, 180.4, and 0.86%, respectively. Patients were subdivided into three groups based on the results from OGTT: normal glucose tolerance (NGT): 41 (50%), impaired glucose tolerance (IGT) (2-h plasma glucose 140-200 mg/dL): 21 (25%), and DM (2-h plasma glucose >200 mg/dL): 21 (25%). The staging of fibrosis in these subjects was F1: 17 (20%), F2: 17 (20%), F3: 32 (40%), and F4: 17 (20%), respectively. The classification of necroinflammatory activity in these subjects was A1: 39 (47%), A2: 41 (49%), and A3: 3 (4%), respectively. The grading of steatosis in these subjects was grade 0: 27 (32%), grade 1: 50 (60%), grade 2: 3 (4%), and grade 3: 3 (4%), respectively. In comparison between HCV patients and HBV patients, the HCV patients were older than HBV patients, but there was no significant difference in other factors, including HOMA-R and HOMA-β.
The 83 patients with HCV infection were then divided into two groups, HOMA-R <2.5: 40 patients and HOMA-R ≥2.5: 43 patients; the latter is considered to be the insulin resistance group. The characteristics of each group were subsequently compared ( Table 3 ). There was no significant difference in the level of HCV core protein, BMI, or presence of steatosis. However, there were significant differences in habitual drinkers (P = 0.0148), platelet (P = 0.0182), albumin (P = 0.0006), NGT from OGTT, HOMA-β (P <0.0001), and stage of fibrosis (P = 0.0022). It is noteworthy that 77% of patients with insulin resistance exhibited severe fibrosis (F3 and F4). When 20 patients with HBV infection were divided into two groups, HOMA-R <2.5: 11 patients and HOMA-R ≥ 2.5: 9 patients, there was no significant difference in the characteristics of each group ( Table 4 ).
Univariate and multivariate analyses in 83 patients with HCV infection were performed to identify the independent factors relevant to insulin resistance ( Table 5 ). In the univariate analysis, the following four factors significantly influenced the greater insulin resistance (HOMA-R ≥2.5): albumin (relative risk 0.14, 95% confidence interval [95% CI] 0.04-0.45, P = 0.0010), triglyceride (relative risk 7.05, 95% CI 3.07-16.15, P = 0.0331), not NGT (relative risk 2.18, 95% CI 1.16-6.85, P = 0.0228), and severe fibrosis (F3 and F4) (relative risk 4.95, 95% CI 1.92-12.79, P = 0.0010). However, in the multivariate analysis, severe fibrosis (F3 and F4) was the only independent factor for insulin resistance (relative risk 7.32, 95% CI 1.59-33.73, P = 0.0107).
We examined the differences of the four indices related to β-cell function and insulin sensitivity between the mild fibrosis (F1 and F2) and severe fibrosis (F3 and F4) groups in HCV patients (Fig. 1). Although Δ-insulin/Δ-glucose 30 exhibited no significant change between the mild fibrosis and severe fibrosis groups, there were significant differences in HOMA-β (P = 0.0169), HOMA-R (P = 0.0063), and WBISI (P = 0.0159). When we examined the differences in HOMA-β and HOMA-R between HBV patients with mild fibrosis and those with severe fibrosis, HOMA-R was significantly higher in the severe fibrosis group (Fig. 2).
(Enlarge Image)
Comparison between the mild fibrosis (F1 and F2, N = 34) and severe fibrosis (F3 and F4, N = 49) groups in HCV-infected patients, using the four indices to estimate β-cell function and insulin sensitivity. Data are presented as the mean ± standard error.
(Enlarge Image)
Comparison between the mild fibrosis (F1 and F2, N = 7) and severe fibrosis (F3 and F4, N = 13) groups in HBV-infected patients, using the two indices to estimate β-cell function and insulin sensitivity. Data are presented as the mean ± standard error.
Finally, we analyzed the sequential changes in plasma glucose levels and insulin response during OGTT in the mild fibrosis and severe fibrosis groups in HCV patients (Fig. 3). The peak plasma glucose and the insulin responses occurred at 60 min and at 90 min, respectively, in both groups. The plasma glucose level from 30 to 120 min in the severe fibrosis group was significantly higher than that in the mild fibrosis group (P = 0.0020), whereas there was no significant difference in the insulin level between the two groups.
(Enlarge Image)
Plasma glucose and insulin levels after an oral load of 75 g glucose in HCV-infected patients with mild fibrosis (F1 and F2, N = 34) and severe fibrosis (F3 and F4, N = 49). Data are presented as the mean ± standard error.
The baseline characteristics of the 83 patients with HCV infection and 20 patients with HBV infection are shown in ( Table 2 ). In HCV patients, there were 56 men (67%) and 27 women (33%), with a mean age of 54 yr. The mean BMI was 23.7 kg/m, and 6 out of the 83 patients were habitual drinkers. The mean level of HCV core protein was 2,068.3 fmol/L. The mean values of HOMA-R, HOMA-β, and Δ-insulin/Δ-glucose 30 were 2.86, 180.4, and 0.86%, respectively. Patients were subdivided into three groups based on the results from OGTT: normal glucose tolerance (NGT): 41 (50%), impaired glucose tolerance (IGT) (2-h plasma glucose 140-200 mg/dL): 21 (25%), and DM (2-h plasma glucose >200 mg/dL): 21 (25%). The staging of fibrosis in these subjects was F1: 17 (20%), F2: 17 (20%), F3: 32 (40%), and F4: 17 (20%), respectively. The classification of necroinflammatory activity in these subjects was A1: 39 (47%), A2: 41 (49%), and A3: 3 (4%), respectively. The grading of steatosis in these subjects was grade 0: 27 (32%), grade 1: 50 (60%), grade 2: 3 (4%), and grade 3: 3 (4%), respectively. In comparison between HCV patients and HBV patients, the HCV patients were older than HBV patients, but there was no significant difference in other factors, including HOMA-R and HOMA-β.
The 83 patients with HCV infection were then divided into two groups, HOMA-R <2.5: 40 patients and HOMA-R ≥2.5: 43 patients; the latter is considered to be the insulin resistance group. The characteristics of each group were subsequently compared ( Table 3 ). There was no significant difference in the level of HCV core protein, BMI, or presence of steatosis. However, there were significant differences in habitual drinkers (P = 0.0148), platelet (P = 0.0182), albumin (P = 0.0006), NGT from OGTT, HOMA-β (P <0.0001), and stage of fibrosis (P = 0.0022). It is noteworthy that 77% of patients with insulin resistance exhibited severe fibrosis (F3 and F4). When 20 patients with HBV infection were divided into two groups, HOMA-R <2.5: 11 patients and HOMA-R ≥ 2.5: 9 patients, there was no significant difference in the characteristics of each group ( Table 4 ).
Univariate and multivariate analyses in 83 patients with HCV infection were performed to identify the independent factors relevant to insulin resistance ( Table 5 ). In the univariate analysis, the following four factors significantly influenced the greater insulin resistance (HOMA-R ≥2.5): albumin (relative risk 0.14, 95% confidence interval [95% CI] 0.04-0.45, P = 0.0010), triglyceride (relative risk 7.05, 95% CI 3.07-16.15, P = 0.0331), not NGT (relative risk 2.18, 95% CI 1.16-6.85, P = 0.0228), and severe fibrosis (F3 and F4) (relative risk 4.95, 95% CI 1.92-12.79, P = 0.0010). However, in the multivariate analysis, severe fibrosis (F3 and F4) was the only independent factor for insulin resistance (relative risk 7.32, 95% CI 1.59-33.73, P = 0.0107).
We examined the differences of the four indices related to β-cell function and insulin sensitivity between the mild fibrosis (F1 and F2) and severe fibrosis (F3 and F4) groups in HCV patients (Fig. 1). Although Δ-insulin/Δ-glucose 30 exhibited no significant change between the mild fibrosis and severe fibrosis groups, there were significant differences in HOMA-β (P = 0.0169), HOMA-R (P = 0.0063), and WBISI (P = 0.0159). When we examined the differences in HOMA-β and HOMA-R between HBV patients with mild fibrosis and those with severe fibrosis, HOMA-R was significantly higher in the severe fibrosis group (Fig. 2).
(Enlarge Image)
Comparison between the mild fibrosis (F1 and F2, N = 34) and severe fibrosis (F3 and F4, N = 49) groups in HCV-infected patients, using the four indices to estimate β-cell function and insulin sensitivity. Data are presented as the mean ± standard error.
(Enlarge Image)
Comparison between the mild fibrosis (F1 and F2, N = 7) and severe fibrosis (F3 and F4, N = 13) groups in HBV-infected patients, using the two indices to estimate β-cell function and insulin sensitivity. Data are presented as the mean ± standard error.
Finally, we analyzed the sequential changes in plasma glucose levels and insulin response during OGTT in the mild fibrosis and severe fibrosis groups in HCV patients (Fig. 3). The peak plasma glucose and the insulin responses occurred at 60 min and at 90 min, respectively, in both groups. The plasma glucose level from 30 to 120 min in the severe fibrosis group was significantly higher than that in the mild fibrosis group (P = 0.0020), whereas there was no significant difference in the insulin level between the two groups.
(Enlarge Image)
Plasma glucose and insulin levels after an oral load of 75 g glucose in HCV-infected patients with mild fibrosis (F1 and F2, N = 34) and severe fibrosis (F3 and F4, N = 49). Data are presented as the mean ± standard error.
Source...