Glucose intolerance in patients with chronic liver disease

Focusing on the kinetics of insulin, glucagon and somatostatin

Abstract

Glucose metabolism in patients with chronic liver disease was examined through the kinetics of insulin (IRI), glucagon (IRG) and somatostatin (SRIF) during a 75g oral glucouse tolerance test (OGTT)
The following results were obtained:
1) Chronic liver diseases were frequ ently associated with impaired glucouse tolerance; it was seen in 88% of the liver cirrhosis (LC) group,75% of the chronic active hepatitis (CAH) group and 42% of the chronic inactive hepatitis (CIH) group; parti c u larly,44% of the LC patients exhibited a diabetic-type curve.
2) As to the hormones involved in chronic liver diseas e, delayed overresponse of IRI was observed in all groups, which was most prominently in the LC group. IRG suppress i o n by glucouse administration was reduced in all groups; the LC patients show e d delayed overresponse, and the chronic hepatitis patients a slight overresponse. Of S RIF, delayed overresponse was noted in the LC patients and a slight overresponse i n the chronic hepatitis patients. The increase in SRIF was less than that in IRI or IR G. However, thease three hormones increased with the progression of disease; t h e highest levels were seen in LC, fllowed by CAH and CIH.
3) As to the IRI/IRG (I/G) molar ratio, IRG initially pred ominated in the LC group, but IRI was always high in the CAH and CIH groups. As to the IRI/SRIF (I/S) mo l a r ratio, SRIF was initially predominant in all groups, especially in the LC group. By glucouse tolerability, JIG and I/S molar ratios of the diabetic type were simillar t o those of LC.
4) As to co rreration between each of these hormones and liver function parameters reflecting liver reserve capacity, significant correlations (p<0.01) were obserbed between IRI and Alb., between IRG and ICG-R15, Alb. or E/T, and betwe e n SRIF and ICG-R₁₅, Alb., ChE or BCAA/AAA in the LC group. SRIF correlated with a greater number of parameters than did IRI or IRG.
These resuluts verify that chronic liver disease accom pany hypersomatostatinemia as well as hyperinsulinemia and hyperglucagonemia. Hyperinsulinemia seems attributable to reduced hepatic insulin degradation, excessive secretion of insulin from pancreatic B cells and lowered sensitivity of insulin in the target organs. Hyperglucagonemia seems due to hypersecretion of glucagon from pancreatic A cells and reduced degradation of injured hepatic cells. Hypersomatostatinemia, insofar as can be concluded from the data in this study, is most likely to result from a decrease of degradation of injured hepatic cells, although there is the possibility that it may arise from excessive release of somatostatin from pancreatic D cells or the involvements of hyperinsulinemia and hyperglucagonemia.