RESUMO
BACKGROUND: Glucocorticoid (GC)-induced hyperglycemia is a frequent adverse effect in hospitalized patients. Guidelines recommend insulin treatment to a target range of 6-10 mmol/L (108-180 mg/dl), but efficacies of particular regimes have not been well-studied. METHODS: In this retrospective cohort study, hospitalized patients receiving GCs at the medical ward were analyzed by treatment (basal-bolus vs. bolus-only vs. pre-mixed insulin) and compared to a non-insulin-therapy reference group. Coefficients of glucose variation (CV), percentage of glucose readings in range (4-10 mmol/L (72-180 mg/dl)) and hypoglycemia (< 4 mmol/L (< 72 mg/dl)) were evaluated. RESULTS: Of 2424 hospitalized patients receiving systemic GCs, 875 (36%) developed GC-induced hyperglycemia. 427 patients (17%) had a previous diagnosis of diabetes. Adjusted relative risk ratios (RRR) for the top tertile of CV (> 29%) were 1.47 (95% Cl 1.01-2.15) for bolus-only insulin, 4.77 (95% CI 2.67-8.51) for basal-bolus insulin, and 4.98 (95% CI 2.02-12.31) for premixed insulin, respectively. Adjusted RRR for percentages of glucose readings in range were 0.98 (95% Cl 0.97-0.99) for basal-bolus insulin, 0.99 (95% Cl 0.98-1.00) for premixed insulin, and 1.01 (95% Cl 1.00-1.01) for bolus-only insulin, respectively. Adjusted RRR for hypoglycemia was 13.17 (95% Cl 4.35-39.90) for basal-bolus insulin, 8.92 (95% Cl 2.60-30.63) for premixed insulin, and 2.99 (95% Cl 1.01-8.87) for bolus-only insulin, respectively. CONCLUSIONS: Current guidelines recommend a basal-bolus regimen for treatment of GC-induced hyperglycemia, but we found similar outcomes with pre-mixed and bolus-only insulin regimens. As GC-induced hyperglycemia is a frequent issue in hospitalized patients, it might be reasonable to prospectively study the ideal regimen.
Assuntos
Glicemia/efeitos dos fármacos , Glucocorticoides/farmacologia , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Idoso , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND & AIMS: Approximately 50% of patients with chronic hepatitis C (CHC) have a sustained virologic response to treatment with pegylated interferon (pegIFN)-α and ribavirin. Nonresponse to treatment is associated with constitutively increased expression of IFN-stimulated genes (ISGs) in the liver. Treatment of patients with acute hepatitis C (AHC) is more effective, with sustained virologic response rates greater than 90%. We investigated mechanisms of the different responses of patients with CHC and AHC to pegIFN-α therapy. METHODS: We analyzed IFN signaling and ISG expression in liver samples from patients with AHC, patients with CHC, and individuals without hepatitis C (controls) using microarray, immunohistochemical, and protein analyses. Findings were compared with those from primary human hepatocytes stimulated with IFN-α or IFN-γ, as reference sets. RESULTS: Expression levels of hundreds of genes, primarily those regulated by IFN-γ, were altered in liver samples from patients with AHC compared with controls. Expression of IFN-γ-stimulated genes was induced in liver samples from patients with AHC, whereas expression of IFN-α-stimulated genes was induced in samples from patients with CHC. In an expression analysis of negative regulators of IFN-α signaling, we did not observe differences in expression of suppresor of cytokine signaling 1 or SOCS3 between liver samples from patients with AHC and those with CHC. However, USP18 (another negative regulator of IFN-α signaling), was up-regulated in liver samples of patients with CHC that did not respond to therapy, but not in AHC. CONCLUSIONS: Differences in expression of ISGs might account for the greater response of patients with AHC, compared with those with CHC, to treatment with pegIFN-α and ribavirin. Specifically, USP18 is up-regulated in liver samples of patients with CHC that did not respond to therapy, but not in patients with AHC.