c-peptide and Hepatitis--Chronic

We report a patient with Addison's disease whose clinical features became worse during interferon therapy for chronically active hepatitis C. A 47-year-old male was admitted because somnolence developed during a 4 week treatment with interferon-alpha-2a (IFN: 900 x 104U/day). Serum Na level was 113mEq/l and plasma osmolarity was lowered to 238mOsm/kg on admission. Plasma ACTH level was high, while serum cortisol, urinary 17-OHCS and 17-KS excretion were far below the normal levels. On admission, serum prolactin, insulin levels and urinary CPR excretion increased. Normalization of serum Na level by NaCl administration attenuated hyperinsulinemia associated with the reduction of increased CPR excretion. It was supposed that IFN administration might increase cortisol consumption and worsen hypoadrenocortinism in a patient with Addison's disease. In addition, the present case raised the possibility that hyposmolarity may induce a hyperinsulinemic state in humans.

Topics: Addison Disease; C-Peptide; Hepatitis C; Hepatitis, Chronic; Humans; Hyponatremia; Insulin; Insulin Secretion; Interferon alpha-2; Interferon-alpha; Male; Middle Aged; Osmolar Concentration; Recombinant Proteins; Water-Electrolyte Imbalance

One hundred consecutive patients with nonautoimmune chronic active hepatitis (51% HBsAg-positive), 50 patients with cirrhosis (38% HBsAg-positive), 25 patients with chronic persistent hepatitis, and 118 patients with hepatoma who were seen at this hospital were reviewed to determine the prevalence and characteristics of glucose intolerance and diabetes in these conditions. Diabetes (fasting serum glucose greater than 7.8 mmol/L, 140 mg/dl on two separate occasions) was present in 8% of patients with chronic persistent hepatitis and mild chronic active hepatitis, 44% of patients with severe chronic active hepatitis, 40% of patients with cirrhosis, and 15% of patients with hepatoma, compared with 7% of all other patients aged 35 yr or over, undergoing liver biopsy. Compared with this high prevalence of diabetes in liver disease, only 3% of diabetic patients referred to the hospital diabetic clinic had chronic hepatitis or cirrhosis. Glucose tolerance was similar in chronic active hepatitis and cirrhosis and was characterized initially by basal hyperinsulinemia, normal basal glucose levels but elevated serum glucose following glucose loading, and evidence of insulin resistance. We suggest that the high prevalence of diabetes in chronic active hepatitis and cirrhosis in Saudi Arabia is due to the insulin resistance of chronic liver disease acting over many years in a population with a high genetic predisposition to diabetes.

Topics: Adrenal Cortex Hormones; C-Peptide; Carcinoma, Hepatocellular; Diabetes Complications; Diabetes Mellitus; Female; Glucose Tolerance Test; Hepatitis, Chronic; Humans; Infant; Insulin; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged

Insulin and C-peptide in venous blood were determined during oral glucose tolerance testing in 59 non-manifest diabetics with histologically established chronic liver disease (fatty degeneration, chronic aggressive hepatitis, cirrhosis). Glucose tolerance was pathologic in 60-80% of patients. When compared to a control group patients with chronic liver disease showed significantly increased values of blood glucose (after glucose intake), of insulin and of C-peptide (fasting and after glucose intake). The C-peptide/insulin ratio, a measure of hepatic insulin degradation, was significantly decreased after glucose uptake. There were no significant differences of blood sugar, insulin and C-peptide among the various liver diseases. In chronic aggressive hepatitis and in cirrhosis the C-peptide/insulin ratio was partly significantly lower than in fatty degeneration. From the increased C-peptide values increased insulin secretion in chronic liver diseases can be deducted. In addition, the decreased C-peptide/insulin ratios show an impairment of insulin degradation in liver cirrhosis and other chronic hepatic diseases. However, in fatty liver degeneration this is clearly less pronounced than in more serious liver diseases.

Topics: C-Peptide; Chronic Disease; Fatty Liver; Female; Glucose Tolerance Test; Hepatitis, Chronic; Humans; Insulin; Liver Cirrhosis; Liver Diseases; Male; Middle Aged

Exaggerated insulin response to oral glucose was demonstrated in peripheral blood of patients with chronic hepatic diseases. High peripheral insulin levels may be the result of pancreatic hypersecretion or decreased hepatic removal of insulin. The simultaneous assay of insulin and C-Peptide concentrations in peripheral blood enables the determination of both beta-cell activity and hepatic fractional insulin extraction. We have measured peripheral insulin and C-Peptide levels during OGTT in a group of subjects with chronic active hepatitis (CAH). These subjects showed glucose levels and incremental areas significantly higher than controls, but still in the upper range of normality. Insulin response to oral glucose was significantly greater in CAH patients than in controls, whereas C-Peptide levels and areas were quite similar in the two groups. The C-Peptide to insulin molar ratios before and after glucose, and the relations between C-Peptide and insulin incremental areas were lower in CAH patients than in controls. We conclude that the peripheral hyperinsulinemia observed in subjects with CAH is due to diminished insulin removal by the diseased liver rather than pancreatic hypersecretion.

Topics: Adult; Blood Glucose; C-Peptide; Glucose Tolerance Test; Hepatitis, Chronic; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Islets of Langerhans; Liver; Male; Middle Aged