c-peptide and Hypertension--Portal

A 73-year-old woman had previously been diagnosed with CREST syndrome, PBC and diabetes. Hepatic fibrosis was not evident, in spite of the transudative ascites and active esophageal varices. ACA were positive, whereas AMA and anti-gp210 antibodies were negative. She showed low urinary excretion of C-peptide and was weakly positive for anti-GAD antibody. She was diagnosed with a form of PBC that progresses via portal hypertension rather than liver failure and with SPIDDM. Her HLA type did not contain risk allele for IDDM or PBC. SPIDDM should be considered when patients with PBC with portal hypertension-type progression develop diabetes.

Topics: Aged; C-Peptide; CREST Syndrome; Diabetes Mellitus, Type 1; Disease Progression; Female; Histocompatibility Testing; Humans; Hypertension, Portal; Liver Cirrhosis, Biliary; Polyendocrinopathies, Autoimmune

Hyperglucagonemia has been described to be associated with insulin resistance in patients with liver cirrhosis. Portosystemic shunts may be involved in the etiology of hyperglucagonemia. To test this hypothesis we investigated fasting peripheral plasma glucagon levels before and after portal decompression by transjugular intrahepatic portosystemic shunting (TIPS).. Glucagon, insulin, plasma glucose, HbA1c, and C-peptide were determined in peripheral venous samples from 21 non-diabetic (ND)- and 15 diabetic patients (D; 3 treated with insulin, 3 with sulfonylurea, 9 with diet alone) with liver cirrhosis, showing comparable clinical features (gender, age, BMI, creatinine, Child-Pugh-score, complications, and etiology of liver cirrhosis) before, 3 and 9 months after elective TIPS implantation. Insulin resistance was calculated as R (HOMA) according to the homeostasis model assessment (HOMA).. Glucagon levels before TIPS were elevated in patients with diabetes compared to patients without diabetes (D: 145.4 +/- 52.1 pg/ml vs. ND: 97.3 +/- 49.8 pg/ml; p = 0.057). 3 and 9 months after TIPS implantation glucagon levels increased significantly in ND (188.9 +/- 80.3 pg/ml and 187.2 +/- 87.6 pg/ml) but not in D (169.6 +/- 62.4 pg/ml and 171.9 +/- 58.4 pg/ml). While plasma glucose, HbA1c, and C-peptide were significantly higher in D than in ND, they did not change significantly 3 and 9 months after TIPS implantation. Insulin was increased in D before TIPS (D: 31.6 +/- 15.9 mU/l vs. ND: 14.8 +/- 7.1 mU/l; p = 0.0001). 3 and 9 months after TIPS insulin significantly increased in ND (26.6 +/- 14.7 mU/l and 23.2 +/- 10.9 mU/l vs. 14.8 +/- 7.1 mU/l before TIPS) but not in D. In ND R (HOMA) also increased from 3.5 +/- 2 mU x mmol/l(2) to 5.7 +/- 3.3 mU x mmol/l(2) after 3 and 5.4 +/- 2.6 mU x mmol/l(2) after 9 months. BMI, liver and kidney function did not change with time.. In non-diabetic cirrhotic patients TIPS implantation is followed by an increase of glucagon. However, this does not result in a worsening of glycemic control, probably because of a simultaneous increase of insulin.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Diabetes Complications; Female; Glucagon; Glycated Hemoglobin; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Portasystemic Shunt, Transjugular Intrahepatic

Patients with cirrhosis of the liver suffer from hyperinsulinaemia and a certain degree of insulin resistance. More frequently than in the rest of the population they have diabetes. Transjugular intrahepatic portosystemic shunts (TIPS) as a therapeutic method in complications of portal hypertension lead to rapid haemodynamic changes in the liver. The objective of the submitted work was to assess whether TIPS has an impact on insulinaemia and whether it influences insulin resistance in patients with cirrhosis of the liver.. The authors evaluated a group of 22 patients with cirrhosis of the liver (10 diabetics and 12 subjects without diabetes) indicated for TIPS. They investigated the insulin and C-peptide concentration in blood obtained by catheterization from the hepatic and portal vein before and after TIPS and in the peripheral blood before TIPS, 1 hour, 1 day, 1 week and 1 month after TIPS. The insulin resistance was examined by the method of the hyperinsulin euglycaemic clamp (HEC) before TIPS, 1 day, 1 week, and 1 month after TIPS. The levels of C-peptide and insulin were assessed by the IRMA method. The blood sugar level in HEC was measured by means of a Hemocue apparatus. The results were evaluated by the non-parametric Wilcoxon test for two dependent samples.. Both groups (diabetics and non-diabetics) were comparable as to age, sex, etiology of liver cirrhosis and indication for TIPS. After introduction of TIPS a change of insulin clearance occurred (p = 0.01) and a change of the insulin level in the hepatic vein immediately after TIPS (p = 0.02). Insulin clearance before TIPS was 37-90% (median 54%) and after TIPS it declined to 0-79% (median 38%) (p = 0.01). Already 1 hour after the operation the authors observed a rise of the insulin level in peripheral blood as compared with baseline values (p = 0.002). Statistically significant hyperinsulinaemia persisted one month after TIPS (p = 0.005). Values of C-peptide did not change significantly in time, neither in the hepatic vein nor in the peripheral blood. On examination of IR no statistically significant changes occurred after TIPS. On evaluation of different groups of diabetics and non-diabetics the IR was more marked in patients with DM (mean M = 1.7 mg/kg/min.) than in patients without DM (3.7 mg/kg/min.) (p = 0.03). The authors did not record significant changes of IR in time in different groups. Compensation of DM was not influenced by TIPS. The fasting blood sugar levels before TIPS and 1 month after TIPS were comparable.. After TIPS a rise of the insulin level in peripheral blood occurred due to the reduced insulin clearance in the liver. Despite hyperinsulinaemia which persisted for one month after the operation, the insulin resistance did not deteriorate. Compensation of diabetes was not affected by TIPS.

Topics: Adult; Aged; C-Peptide; Diabetes Complications; Diabetes Mellitus; Female; Humans; Hypertension, Portal; Insulin; Insulin Resistance; Liver Cirrhosis; Male; Middle Aged; Portasystemic Shunt, Transjugular Intrahepatic

To assess if spontaneous portosystemic shunting from collaterals contributes to the hyperinsulinemia of cirrhosis, 12 patients with alcoholic cirrhosis underwent a 5-hour oral glucose tolerance test 1 day before and 10 days after an elective side-to-side portacaval shunt. The glucose, insulin, and C peptide responses to oral glucose post-shunt were exaggerated but comparable to preoperative values. Compared with preoperative values, the fasting molar ratio of C peptide to insulin postoperatively had increased 40% (6.0 +/- 1.2 versus 8.4 +/- 0.7), indicating improved hepatic function. These results suggest that extrahepatic portosystemic shunting secondary to spontaneous splanchnic collaterals plays little or no role in the hyperinsulinemia of cirrhosis. It appears that decreased hepatic degradation of insulin in these patients is secondary to hepatocellular dysfunction rather than a result of shunting of portal blood around the liver.

Topics: Adult; C-Peptide; Female; Glucose; Glucose Tolerance Test; Humans; Hypertension, Portal; Insulin; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Portacaval Shunt, Surgical; Portal System; Venous Pressure

The possible contribution of hepatocellular damage and portal-systemic shunting to hyperinsulinism in cirrhosis was studied in 23 cirrhotics, 8 of whom had a surgical portacaval shunt, and 16 controls by measuring insulin and the connecting peptide (C-peptide) concentrations in simultaneous samples of peripheral arterial and hepatic venous blood. The fractional hepatic insulin extraction (0.48 +/- 0.06, mean +/- SE) was normal in cirrhosis. The hepatic insulin elimination rate was directly related to arterial insulin levels (r = 0.91, P less than 0.001) even at very high circulating levels. Extrahepatic insulin metabolism was measured across the kidney and lower limb. There were no significant differences between cirrhotics and control subjects in relation to renal (0.25 +/- 0.05 vs. 0.23 +/- 0.04) and lower limb insulin extraction (0.14 +/- 0.07 vs. 0.19 +/- 0.04). While in the control group hepatic venous insulin (0.143 +/- 0.018 pmol/ml) markedly exceeded the peripheral insulin concentration (0.083 +/- 0.009 pmol/ml, P less than 0.01), the contrary was found in cirrhotics with end-to-side portacaval shunt in whom all the pancreatic venous effluent is shunted to the systemic circulation (hepatic venous insulin, 0.130 +/- 0.028 pmol/ml; peripheral, 0.234 +/- 0.037 pmol/ml; P less than 0.01). Portal-hypertensive cirrhotics without a surgical portacaval shunt also had hepatic venous insulin levels (0.132 +/- 0.029 pmol/ml) below peripheral arterial insulin concentrations (0.205 +/- 0.041 pmol/ml, P less than 0.01). The study suggests that hyperinsulinism in cirrhosis is not the result of an intrinsic defect of hepatic insulin metabolism but of the spontaneous shunting of portal blood to the systemic circulation.

Topics: C-Peptide; Humans; Hyperinsulinism; Hypertension, Portal; Insulin; Kidney; Liver; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Portal System; Portasystemic Shunt, Surgical

To elucidate the relative contribution of parenchymal liver damage and spontaneous portal-systemic shunting to the reduction of peripheral insulin degradation rate and the decrease in plasma concentrations of three branched chain amino acids (valine, leucine, and isoleucine), plasma insulin, C-peptide, and amino acid concentrations were measured during oral glucose tolerance tests in 17 patients with liver cirrhosis, 10 with idiopathic portal hypertension, 5 hospitalized controls, and normal subjects. None of the patients had evidence of hepatic encephalopathy. Patients with idiopathic portal hypertension had histologically minimum hepatic fibrosis in spite of the existence of extensive exophageal varices. The molar ratio between plasma concentrations of C-peptide and insulin was significantly decreased in patients with cirrhosis, but not in those with idiopathic portal hypertension. In both patients with cirrhosis and idiopathic portal hypertension, the three branched chain amino acid levels were significantly decreased and the molar ratio between the concentrations of the three branched chain amino acids and two aromatic amino acids (tyrosine and phenylalanine) were markedly reduced. These results suggest that spontaneous portal-systemic shunting does not primarily contribute to the reduced degradation of insulin, but has a close relationship with the decrease in branched chain amino acid levels and in the molar ratio of plasma amino acids. In addition, the present data indicate that decreased branched chain amino acid levels in patients with cirrhosis is not merely ascribed to hyperinsulinemia and that the decrease in the molar ratio of plasma amino acids is not specific to the presence of hepatic encephalopathy.

Topics: Adult; Aged; Amino Acids; Amino Acids, Branched-Chain; C-Peptide; Female; Glucose Tolerance Test; Humans; Hypertension, Portal; Insulin; Liver Cirrhosis; Male; Middle Aged; Phenylalanine; Portal System; Tyrosine