Insulin Resistance and Hyperinsulinemia in Patients with Chronic Liver Disease and Hepatocellular Carcinoma

ObjectivesTo investigate the role of insulin resistance (IR) and insulin plasma levels (IRI) in patients with chronic liver disease (CLD) and hepatocellular carcinoma (HCC).MethodsWe recruited the following patients: 125 with HCC, 128 with liver cirrhosis (LC) and 133 with chronic hepatitis C (CHC). IR was assessed by the HOMA-IR method. To define IR and hyperinsulinemia we selected as a cut-off level, the value of the 80th percentile for HOMA-IR (2.72) and IRI (11.18) in 113 healthy subjects.ResultsThe mean levels of HOMA-IR and IRI increase progressively among CHC (2.7 ± 2.9 and 11.5 ± 10.5, respectively), LC (5.4 ± 4.5 and 17.6 ± 11.2) and HCC (6.4 ± 9.8 and 18.2 ± 18.8). In the upper quintiles for HOMA-IR and IRI, the frequency of patients in the LC and HCC groups was twice as much in CHC cases. HCC with DM2 have the greatest percentage above the 80th percentile of HOMA-IR, their quintiles distribution is inverted and HOMA-IR mean values are significantly higher in comparison with HCC without DM2 cases.DiscussionOur study shows that the association between IR and CLD begins in the early stages of liver fibrosis. DM2 increases HOMA-IR and IRI mean levels in HCC patients and these metabolic factors could play a major role in the link between diabetes mellitus and hepatocarcinoma

Clustering of risk factors in hypertensive insulin-dependent diabetics with high sodium-lithium countertransport

Clustering of risk factors in hypertensive insulin-dependent diabetics with high sodium-lithium countertransport. Diabetic nephropathy is more common in patients with a positive family history of hypertension and with elevated red blood cell sodium-lithium countertransport, a marker of risk for essential hypertension. To evaluate whether there is a relationship between this cation transport system and indicators of risk of renal and cardiovascular complications in diabetic patients before the development of clinical proteinuria, we studied 31 type 1 (insulin-dependent) diabetic patients with arterial hypertension, without clinical proteinuria and 12 normotensive normoalbuminuric diabetic patients. Sodium-lithium countertransport activity was significantly higher in hypertensive patients (0.43 ± 0.03 mmol/1 RBC x hr) than in normotensive patients (0.23 ± 0.03; P < 0.001). To better explore the nature of the association between this transport system and arterial hypertension, hypertensive patients were divided in two groups, with high (>0.41 mmol/1 RBC x hr) or normal (<0.41) sodium-lithium countertransport activity. The two groups of hypertensive diabetics were similar in age, sex, body mass index and blood pressure levels. Hypertensive patients with elevated rates of sodium-lithium counter-transport compared with those with normal sodium-lithium counter-transport activity showed elevated glomerular filtration rate (130 ± 4 ml/min/1.73 m2 vs. 122 ± 3; P < 0.05), albumin excretion rate (median 26 /Lcg/min vs. 11; P < 0.001), higher fractional proximal sodium reabsorption (74 ± 1.2% vs. 71.6 ± 0.9; P < 0.01), exchangeable sodium pool (2937 ± 62 mmol/1.73 m2 vs. 2767 ± 56; P < 0.01), larger kidney volume (317 ± 7 ml/1.73 m2 vs. 270 ± 8; P < 0.05) and left ventricular mass index (122 ± 4 g/m2 vs. 107 ± 5; P < 0.05). Hypertensive patients with normal sodium-lithium countertransport activity had renal parameters similar to normotensive diabetic patients, except higher left ventricular mass index and kidney volume. Hypertensive diabetic patients with elevated sodium-lithium countertransport activity also had higher levels of plasma triglycerides, lower plasma HDL-cholesterol and impaired insulin sensitivity (assessed by euglyce-mic insulin-glucose clamp) compared with the other two groups. In conclusion, renal, cardiac and metabolic abnormalities are prominent in hypertensive type 1 (insulin-dependent) diabetic patients with higher sodium-lithium countertransport

Alcohol and HCV Chronic Infection Are Risk Cofactors of Type 2 Diabetes Mellitus for Hepatocellular Carcinoma in Italy

Type 2 diabetes mellitus (DM2) has been associated with hepatocellular carcinoma (HCC) development. To study this relationship, we enrolled 465 HCC patients compared with 618 Cirrhotic cases and 490 Controls. The prevalence of DM2 is significantly higher in HCC patients with an Odds Ratio of 3.12 versus Controls. In HCC cases with alcohol abuse, the frequency of DM2 is the highest. In our HCC patients, when HCV infection is associated with alcohol abuse, the liver cancer develops earlier. In addition, multivariate analysis shows that alcohol consumption is an independent risk factor for HCC more relevant than HCV infection

Glycated hemoglobin and antidiabetic strategies as risk factors for hepatocellular carcinoma

AIM: To evaluate the relationship between glycemic control [assessed by glycated hemoglobin (HbA1c)], antidiabetic therapies and the risk of hepatocellular carcinoma (HCC)

Association between hepatocellular carcinoma and type 2 diabetes mellitus in Italy: Potential role of insulin

AIM: To investigate the relationships between Type 2 diabetes mellitus (DM2) and the risk of hepatocellular carcinoma (HCC)

Insulin Resistance and Hyperinsulinemia in Patients with Chronic Liver Disease and Hepatocellular Carcinoma

Objectives To investigate the role of insulin resistance (IR) and insulin plasma levels (IRI) in patients with chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Methods We recruited the following patients: 125 with HCC, 128 with liver cirrhosis (LC) and 133 with chronic hepatitis C (CHC). IR was assessed by the HOMA-IR method. To define IR and hyperinsulinemia we selected as a cut-off level, the value of the 80th percentile for HOMA-IR (2.72) and IRI (11.18) in 113 healthy subjects. Results The mean levels of HOMA-IR and IRI increase progressively among CHC (2.7 ± 2.9 and 11.5 ± 10.5, respectively), LC (5.4 ± 4.5 and 17.6 ± 11.2) and HCC (6.4 ± 9.8 and 18.2 ± 18.8). In the upper quintiles for HOMA-IR and IRI, the frequency of patients in the LC and HCC groups was twice as much in CHC cases. HCC with DM2 have the greatest percentage above the 80th percentile of HOMA-IR, their quintiles distribution is inverted and HOMA-IR mean values are significantly higher in comparison with HCC without DM2 cases. Discussion Our study shows that the association between IR and CLD begins in the early stages of liver fibrosis. DM2 increases HOMA-IR and IRI mean levels in HCC patients and these metabolic factors could play a major role in the link between diabetes mellitus and hepatocarcinoma

Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease

AIM: To explore the association between hepatocellular carcinoma (HCC) and type 2 diabetes mellitus, describe the temporal relations between the onset of diabetes and the development of HCC and evaluate the possible effects of antidiabetic therapy on HCC risk