This pilot study was initiated to evaluate factors controlling glucose tolerance in patients with hepatitis C virus-induced liver disease before and after therapy with recombinant interferon-alpha ...(r-INF-alpha). Fifteen patients with histologically and serologically proven hepatitis C infection underwent oral and frequently sampled intravenous glucose tolerance tests (FSIGTT) before and after four months of therapy (6 x 106 U r-INF-alpha, subcutaneously, three times a week). Glucose, insulin and C-peptide data from FSIGTT were analysed using the minimal modeling technique to determine insulin sensitivity, glucose effectiveness and first and second phase insulin secretion. According to the WHO criteria 13 patients, had normal glucose tolerance; diabetes mellitus was diagnosed in 2 patients. In the morning following the last r-INF-alpha injection four months later, insulin sensitivity improved significantly in hepatitis C virus-infected patients with normal glucose tolerance (2.17 +/- 0.37 vs. 6.18 +/- 0.94 10(-4) min(-1) per microU/ml, p < 0.001) and with diabetes mellitus (0.86 to 2.61; 0.46 to 1.06 10(-4) min(-1) per microU/ml). This effect was independent of the extent of fibrosis, virus load before treatment and therapy response. First phase insulin secretion increased in non-diabetic (139.2 +/- 17.1 vs. 200.0 +/- 32.7, p < 0.05) and diabetic patients with HCV infection (55.24 to 118.5; 84.23 to 261.1). Moreover, free fatty acid concentrations in all HCV-infected patients were significantly reduced (0.48 +/- 0.01 vs 0.21 +/- 0.03 mmol/l, p < 0.01). Therapy with recombinant interferon-alpha is associated with an amelioration of glucose tolerance in non-diabetic and diabetic HCV-infected patients.
To examine whether factors controlling glucose tolerance, i.e., insulin sensitivity (SI) and first‐(φ1) and second‐phase insulin secretion (φ2), are impaired in after orthotopic liver transplantation ...(OLT), they were assesssed in patients that had undergone OLT for cirrhosis (n = 10) with cyclosporin A and low‐dose steroid therapy (5 mg prednisone per day) and were compared with those of healthy matched control subjects (n = 10). These factors were determined by means of computer‐based analysis of frequently sampled intravenous glucose tolerance tests (FSIGTT). Glucose and insulin profiles (posthepatic insulin) did not differ between both groups, whereas C‐peptide levels (prehepatic insulin) were elevated in the transplant group after the FSIGTT, indicating an increased hepatic insulin degradation. SI and φ1 did not differ between both groups. φ2, however, was significantly enhanced (23.94 ± 2.63 vs 13.88 ± 1.25 min‐1, p < 0.05). These results indicate that cyclosporine and low‐dose steroid therapy do not impair SI and φ1. However, enhanced φ2 compensates the increased hepatic insulin clearance.
To evaluate the impact of acute and chronic liver disease and single immunosuppression (cyclosporine A CSA or FK506) on insulin sensitivity and glucose effectiveness in liver-grafted patients, we ...performed a frequently sampled intravenous glucose tolerance test (FSIGTT) in nondiabetic patients after orthotopic liver transplantation (OLT) with acute liver failure (ALF group, n = 9, with CSA therapy), in patients after OLT with chronic liver disease (CSA group, n = 8; FK506 group, n = 8), and in 9 healthy control subjects. Insulin sensitivity and glucose effectiveness were determined by analyzing glucose and insulin data from the FSIGTT with Bergman's minimal model technique for glucose. The intravenous glucose tolerance index (K
G ie, the slope of the regression of the logarithm of blood glucose concentration) was not different between the ALF group (2.17 ± 0.16 min
−1) and controls (2.29 ± 0.13 min
−1), but was lower (
P < .05) in both groups with chronic liver disease (CSA group, 1.46 ± 0.1; FK506 group, 1.61 ± 0.11 min
−1) compared with the ALF group (
P < .05). A positive relation for the K
G and glucose effectiveness was found in all liver-grafted patients and controls. Insulin sensitivity was not different between all liver-grafted patients and controls. The body mass index (BMI) was the overall determinant of insulin sensitivity in all groups. Single immunosuppressive therapy does not impair insulin sensitivity in liver-grafted patients. The lower glucose effectiveness in liver-grafted patients with chronic liver disease but not in patients after ALF points to a defect in the regulation of glucose-mediated glucose uptake in peripheral tissue.
To examine whether factors controlling glucose tolerance, i.e., insulin sensitivity (SI) and first-(phi1) and second-phase insulin secretion (phi2), are impaired in after orthotopic liver ...transplantation (OLT), they were assesssed in patients that had undergone OLT for cirrhosis (n = 10) with cyclosporin A and low-dose steroid therapy (5 mg prednisone per day) and were compared with those of healthy matched control subjects (n = 10). These factors were determined by means of computer-based analysis of frequently sampled intravenous glucose tolerance tests (FSIGTT). Glucose and insulin profiles (posthepatic insulin) did not differ between both groups, whereas C-peptide levels (prehepatic insulin) were elevated in the transplant group after the FSIGTT, indicating an increased hepatic insulin degradation. SI and (phi1 did not differ between both groups. phi2, however, was significantly enhanced (23.94 +/- 2.63 vs 13.88 +/- 1.25 min(-1), P < 0.05). These results indicate that cyclosporine and low-dose steroid therapy do not impair SI and phi1. However, enhanced phi2 compensates the increased hepatic insulin clearance.
Pseudoketogenesis in hepatectomized dogs Des Rosiers, C; Montgomery, J A; Garneau, M ...
The American journal of physiology,
03/1990, Letnik:
258, Številka:
3 Pt 1
Journal Article
Recenzirano
Overestimation of ketone body turnover in vivo, measured by tracer kinetics, could occur if specific activity or molar percent enrichment is diluted in extrahepatic tissues by label exchange via ...reversal of 3-oxoacid-CoA transferase, a process we call pseudoketogenesis. To test this hypothesis, euglycemic hepatectomized dogs were injected with a bolus of acetoacetate (0.8 mmol/kg), 32% enriched in 3,4-13C2acetoacetate. Concentrations and labeling patterns of blood acetoacetate and R-3-hydroxybutyrate were measured by selected ion-monitoring gas chromatography-mass spectrometry. During the 60 min after bolus injection of 3,4-13C2acetoacetate, the molar percent enrichment of blood 3,4-13C2acetoacetate decreased to 73 +/- 3% (n = 5) in controls and to 11.5 +/- 0.8% (n = 3) during infusion of dichloroacetate, an activator of pyruvate dehydrogenase. The enrichment of R-3-hydroxy-3,4-13C2butyrate followed closely that of 3,4-13C2acetoacetate. These dilutions occurred despite a net uptake of ketone bodies. Concomitantly, 10.6 +/- 2.2 (n = 5) and 6.0 +/- 2.9% (n = 3) of 13Cacetoacetate molecules were labeled on all four carbons in control and dichloroacetate-treated dogs, respectively. This uniformly labeled acetoacetate arises from partial equilibration between 3,4-13C2acetoacetate and 1,2-13C2acetyl-CoA via the reactions catalyzed by 3-oxoacid-CoA transferase and acetoacetyl-CoA thiolase. Our data demonstrate the reversibility of the 3-oxoacid-CoA transferase in intact extrahepatic tissues and support the concept of pseudoketogenesis. This phenomenon has been quantitated by kinetic analysis of the data.
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