Hyperinsulinaemia and Insulin Resistance of Cirrhosis: The Importance of Insulin Hypersecretion

Abstract

The mechanism for the hyperinsulinaemia in cirrhosis was investigated using two different approaches. In the first study, the metabolic clearance rate of insulin was measured at steady state in 13 cirrhotic and 13 weight-matched control subjects. With comparable insulin infusion rates (1.00 +/- 0.19 versus 1.07 +/- 0.15 mU/kg/min), steady-state plasma insulin concentrations (104 +/- 25 versus 87 +/- 12 microU/ml; P greater than 0.5) and MCRIRI (13.6 +/- 1.6 versus 15.4 +/- 2.0 ml/kg/min; P greater than 0.5) were similar. In the second study, fasting and oral glucose stimulated C-peptide/insulin ratios were compared in 16 cirrhotic and 18 weight matched control subjects. Although fasting glucose levels were significantly higher in the cirrhotic groups, all values were in the normal range (5.5 +/- 0.3 versus 4.8 +/- 0.1 mmol/l, P less than 0.02). However, fasting insulin (0.171 +/- 0.02 versus 0.068 +/- 0.004 nmol/l) and C-peptide (1.02 +/- 0.13 versus 0.42 +/- 0.02 nmol/l) were strikingly higher (P less than 0.001) in cirrhotic subjects. On the other hand, fasting C-peptide/insulin ratios were not statistically different in the two groups (6.18 +/- 0.52 versus 6.77 +/- 0.46; P greater than 0.3). This suggests that beta cell hypersecretion was the principal cause of the fasting hyperinsulinaemia, rather than decreased insulin hepatic extraction. Following the glucose load in 13 of the control and seven of the cirrhotic group, the C-peptide/insulin ratio fell in both groups but was significantly lower in the cirrhotic compared to control subjects at 30, 60 and 120 min, consistent with possible impairment of hepatic insulin extraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of diabetes mellitus in Japanese patients infected chronically with hepatitis C virus

“…Indeed, these characteristics are indistinguishable from those typically associated with cirrhosis, as well as obesity. [3][4][5]22,23 Another possible explanation is that -cell responsiveness is impaired in patients with HCV, possibly because of direct viral effects on -cell function. 7 Thus, for a given degree of liver dysfunction and, presumably, insulin resistance, diabetes would be more likely to occur in patients with HCV.…”

“…1 Progression to non-insulin-dependent diabetes mellitus (NIDDM; type II DM) in cirrhotic patients is suggested to be a consequence of a number of varied mechanisms that include hyperinsulinemia, insulin resistance, a stress response related to established cirrhosis, and reduced hepatic uptake of glucose. [2][3][4][5] Hepatitis C virus (HCV) infection is one of the most important causes of cirrhosis worldwide. There is now emerging epidemiological data to suggest that HCV infection may also contribute to the development of DM.…”

Der hepatogene Diabetes – aktueller Stand der Diagnostik und Therapie

“…Ein wesentlicher auslösender Faktor der Hyperinsulinämie ist die reaktive Insulin-Hypersekretion des Pankreas, um die periphere Insulinresistenz, z. B. der Muskulatur, sowie die gestörte hepatische Glukoseutilisation mit der daraus resultierenden Hyperglykämie zu kompensieren [67]. Außerdem scheint bei einer Zirrhose die Degradationsleistung der Leber für Insulin bei Existenz von portosystemischen Shunts sowie der gestör-ten Hepatozytenfunktion vermindert zu sein [4].…”

Further evidence for an association between non-insulin-dependent diabetes mellitus and chronic hepatitis C virus infection

“…[2][3][4] In addition, a number of disorders of the liver are associated with pancreatic disease including hemochromatosis and alcoholic liver disease.…”