title: Temporal changes in insulin sensitivity following the development of acute liver failure secondary to acetaminophen.
abstract: Insulin resistance in chronic liver disease (CLD) is well documented. This study investigated whether similar changes occur in acute liver failure (ALF). Patients with ALF (n = 10) were recruited within 72 hours of their peak prothrombin time (range 42-120 seconds). All patients were ventilated for encephalopathy (grade III-IV). Peripheral and endogenous insulin sensitivity were assessed by a hyperinsulinemic euglycemic clamp (Human Actrapid 1.5 mU/min/kg) with an infusion of D-[6,6-(2)H(2)] glucose. The clamp was performed on day 0 and then on day 7 and day 14. During the insulin infusion, the mean total peripheral glucose uptake (area under the curve [AUC]) was 1,422 (SD, 1,253), 2,244 (SD, 1,392), and 4,500 (SD, 1,120) micromol/kg on days 0, 7, and 14, respectively. Significant changes occurred from day 0 to 14 (day 14-day 0: 3,078 [95% CI, 1,798 to 4,359]; P =.001) and day 7 to 14 (day 14-day 7: 2,256 [95% CI, 923 to 3,589]; P =.001). No significant difference in endogenous glucose production was demonstrated over time. Mean peripheral insulin sensitivity altered over time, increasing from 0.09 (SD, 0.09) micromol/kg/min/mU/L on day 0 to 0.24 (SD, 0.16) on day 7 and 0.5 (SD, 0.1) on day 14. Significant changes occurred between days 0, 7, and 14 (day 7-day 0: 0.15 [95% CI, 0.04 to 0.26], P =.006; day 14-day 0: 0.4 [95% CI, 0.28 to 0.5], P =.001; day 14-day 7: 0.2 [95% CI, 0.12 to 0.38], P =.001). This study demonstrates that in ALF, impaired peripheral uptake of glucose occurs, peripheral insulin sensitivity being restored at 2 weeks in subjects who survived.
authors: Institute of Liver Studies, Kings College Hospital, London, UK. slaneys@madasafish.com
authors: S J
authors: SJ
authors: Clark
authors: F
authors: F
authors: Shojaee-Moradie
authors: P
authors: P
authors: Croos
authors: P T
authors: PT
authors: Seed
authors: A M
authors: AM
authors: Umpleby
authors: J A
authors: JA
authors: Wendon
authors: J
authors: J
authors: Miell
mesh_terms: D000082:Acetaminophen / Q000506:poisoning*; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D017809:Fatal Outcome; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007700:Kinetics; D017114:Liver Failure, Acute / Q000139:chemically induced* / Q000503:physiopathology*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000139:chemically induced
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D000082:Acetaminophen; D007334:Insulin-Like Growth Factor I; D005934:Glucagon