RESUMO
Tacrolimus (Tac) has a narrow therapeutic range. Dosing is generally targeted at Tac trough levels (C 0), notwithstanding conflicting reports on the correlation between Tac C 0 and systemic exposure measured by the area-under-the-concentration-over-time curve (AUC). The Tac dose required to meet the target C 0 varies highly among patients. We hypothesized that patients requiring a relatively high Tac dose for a certain C 0 may show a higher AUC. Methods: We retrospectively analyzed data from 53 patients in which a 24-h Tac AUC24 estimation was performed at our center. Patients were divided into those taking a low (≤0.15 mg/kg) or high (>0.15 mg/kg) once-daily Tac dose. Multiple linear regression models were used to investigate if the association between C 0 and AUC24 changes according to dose level. Results: Despite the large difference in mean Tac dose between the low- and high-dose group (7 versus 17 mg/d), C 0 levels were similar. However, the mean AUC24 was substantially higher in the high-dose group (320 ± 96 h·µg/L versus 255 ± 81 h·µg/L, P < 0.001). This difference remained significant after adjusting for age and race. For a same C 0, every 0.01 mg/kg increase in Tac dose resulted in an AUC24 increase of 3.59 h·µg/L. Conclusions: This study challenges the general belief that C 0 levels are sufficiently reliable to estimate systemic drug exposure. We demonstrated that patients requiring a relatively high Tac dose to attain therapeutic C 0 levels have higher drug exposure and could therefore potentially be overdosed.
RESUMO
BACKGROUND/OBJECTIVES: To study the importance and clinical usefulness of the 1-h plasma glucose (1hPG) in a Caucasian obese population with regard to the presence of prediabetes, diabetes, and metabolic syndrome (MetS). SUBJECTS/METHODS: We conducted a cross-sectional study of 2439 overweight or obese subjects. All received an oral glucose tolerance test (OGTT) using the American Diabetes Association criteria. ROC-curves were used to compare the sensitivity and (1-specificity) of 1hPG versus FPG and 2hPG to diagnose prediabetes and diabetes. RESULTS: Of 2439 patients (72.1% female) (age 43 ± 13 years, BMI 37.9 (34.6-41.6) kg/m2), 1262 (51.7%) had a 1hPG ≥ 155 mg/dL. The prevalence of prediabetes was 33.8% and of diabetes 9.8%. In these 240 diabetic patients, only 1.6% (four patients) did not show a 1hPG ≥ 155 mg/dL. Subjects with 1hPG ≥ 155 mg/dL were more insulin resistant (p < 0.001), had a higher waist (p < 0.001), visceral adipose tissue (VAT) (p < 0.001), systolic blood pressure (p < 0.001), microalbuminuria (p < 0.001), PAI-1 (p < 0.001), and worse lipid profile (p < 0.001) than subjects with 1hPG < 155 mg/dL. MetS was present in 64.1% of subjects with 1hPG ≥ 155 mg/dL versus 42.5% of subjects with 1hPG < 155 mg/dL (p < 0.001). In the group with 1hPG ≥ 155 mg/dL 32.6% had a normal glucose tolerance (NGT), 48.9% had prediabetes, and 18.5% was diagnosed with T2DM compared to 81.7% NGT, 17.7% prediabetes, and 0.6% T2DM in subjects with 1hPG < 155 mg/dL (p < 0.001). Among NGT subjects, 30.0% had a 1hPG ≥ 155 mg/dL and showed higher HOMA-IR (p = 0.008), VAT (p < 0.001), blood pressure (p < 0.001), and worse lipid profile (p = 0.001). Compared to 1hPG < 155 mg/dL, the sensitivity and specificity of 1hPG ≥ 155 mg/dL of prediabetes were 74.8% and 60.0% and for diabetes 97.1% and 53.2%, respectively. CONCLUSIONS: This study supports the role of 1hPG value as a valuable tool in the detection of obese subjects at high risk for T2DM and MetS.
