Temporal changes in insulin sensitivity following the development of acute liver failure secondary to acetaminophen

TY - JOUR

T1 - Temporal changes in insulin sensitivity following the development of acute liver failure secondary to acetaminophen

AU - Clark, S J

AU - Shojaee-Moradie, F

AU - Croos, P

AU - Seed, P T

AU - Umpleby, A M

AU - Wendon, J A

AU - Miell, J

PY - 2001

Y1 - 2001

N2 - 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-H-2(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 up-take (area under the curve [AUC]) was 1,422 (SD, 1,253), 2,244 (SD, 1,392), and 4,500 (SD, 1,120) mu mol/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) mu mol/kg/min/mU/L on day 0 to 0.24 (SD, 0.16) on day 7 and 0.5 (SD, 0.1) on day 1.4. 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.

AB - 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-H-2(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 up-take (area under the curve [AUC]) was 1,422 (SD, 1,253), 2,244 (SD, 1,392), and 4,500 (SD, 1,120) mu mol/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) mu mol/kg/min/mU/L on day 0 to 0.24 (SD, 0.16) on day 7 and 0.5 (SD, 0.1) on day 1.4. 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.

UR - http://www.scopus.com/inward/record.url?scp=0034955988&partnerID=8YFLogxK

U2 - 10.1053/jhep.2001.25514

DO - 10.1053/jhep.2001.25514

M3 - Article

SN - 1527-3350

VL - 34

SP - 109

EP - 115

JO - Hepatology

JF - Hepatology

IS - 1

ER -