Insulin Resistance in Cirrhosis: Evidence for a Post‐receptor Defect

Abstract

Receptor and post-receptor abnormalities of insulin action and their possible role in the insulin resistance of cirrhosis were examined in eight biopsy-proven cirrhotic subjects and eight age-weight matched healthy volunteers. To this end, oral glucose tolerance tests (OGTT), insulin dose response curves and insulin binding to circulating monocytes were determined for each subject. The dose-response curves for the cirrhotic subjects were significantly shifted to the right compared to the control subjects, indicating the presence of insulin insensitivity (ED50 223 +/- 30 versus 64 +/- 8 mU/l respectively; P less than 0.001). The magnitude of the right shift of the insulin-dose response curves correlated significantly (P less than 0.001) with the OGTT 2 h insulin levels (r = 0.74) and the insulin areas under the OGTT curves (r = 0.86). In contrast, insulin responsiveness was marginally elevated in the cirrhotic group (maximal glucose disposal 680 +/- 47 versus 574 +/- 21 ml/m2/min; P less than 0.05). Insulin binding to circulating monocytes was normal in the cirrhotic subjects. It is concluded that the insulin resistance of cirrhosis is due to a post-receptor defect in insulin action which reduces insulin sensitivity but not insulin responsiveness.

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.…”

Metabolic and hemodynamic responses of bivascularly perfused rat liver to nerve stimulation, noradrenaline, acetylcholine and glucagon in thioacetamide-induced micronodular cirrhosis

“…Hepatic glucose production seems to be slightly reduced (1 1). Increases in peripheral insulin, glucagon, catecholamines and glucocorticoids have been attributed to augmented secretion, diminished hepatic extraction and portosystemic shunting (9,(12)(13)(14)(15)(16). The prominent hemodynamic alterations in human cirrhosis such as portal hypertension and portosystemic shunting are often accompanied by a hyperdynamic state with increased cardiac output and decreased peripheral vascular resistance (6).…”

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.…”