Table 1.
Placebo | Tacrolimus | Ciclosporin | P | |
---|---|---|---|---|
Fasting values | ||||
Plasma glucose (mmol l−1) | 5.29 ± 0.12 | 5.19 ± 0.14 | 5.22 ± 0.07 | 0.82 |
Serum insulin pmol l−1 | 40.55 ± 5.5 | 40.85 ± 8.9 | 37.75 ± 4.6 | 0.55 |
Serum C-peptide (pmol l−1) | 480.7 ± 63.4 | 573.3 ± 94 | 472.5 ± 37.8 | 0.53 |
Serum FFA (mmol l−1) | 0.27 ± 0.03 | 0.42 ± 0.08 | 0.33 ± 0.05 | 0.18 |
Plasma glucagon (pg ml−1) | 28.5 ± 5.7 | 38 ± 12.2 | 35.6 ± 8 | 0.65 |
Insulin sensitivity | ||||
M (mg kg−1 min−1) | 9.9 ± 08 | 11.2 ± 0.4 | 12.4 ± 0.8 | <0.005* |
Insulin clearance | ||||
MCRINS (l min−1) | 1.72 (1.44–3.33) | 1.58 (1.41–2.74) | 1.52 (1.37–2.03) | 0.28 |
Insulin secretion | ||||
AUCins(120,130min) first phase (pmol l−1 min) | 2209 ± 228 | 2197 ± 167 | 2125 ± 114 | 0.84 |
AUCins(120,165 min) (pmol l−1 min) | 5614 ± 717 | 4833 ± 335 | 4689 ± 307 | 0.32 |
AUCC-peptide(120,130 min) first phase (pmol l−1 min) | 18186 ± 1991 | 19119 ± 1557 | 17153 ± 1171 | 0.19 |
Regularity analysis | ||||
Spectral density | 10.27 (3.11–12.49) | 10.07 (7.61–11.68) | 11.53 (7.21–12.01) | 0.6 |
Autocorrelation coefficient | 0.54 (−0.1–0.75) | 0.52 (0.29–0.70) | 0.51 (0.26–0.72) | 0.99 |
Deconvolution analysis | ||||
Secretory burst mass (pmol l−1 pulse−1) | 33.35 ± 5.1 | 38.9 ± 6 | 34.68 ± 4.4 | 0.33 |
Secretory burst amplitude (pmol l−1 min−1) | 13.3 ± 2.1 | 15.5 ± 2.4 | 13.8 ± 1.7 | 0.33 |
Basal secretion (pmol l−1 min−1) | 2.7 ± 0.52 | 2.56 ± 0.71 | 2 ± 0.58 | 0.53 |
Pulse fraction | 0.55 ± 0.08 | 0.64 ± 0.07 | 0.66 ± 0.08 | 0.17 |
Substrate metabolism | ||||
Glucose oxidation (mg kg−1 min−1) | 2.95 ± 0.19 | 3.47 ± 0.23 | 4.11 ± 0.99 | 0.48 |
Lipid oxidation (mg kg−1 min−1) | −0.09 (−0.67–0.31) | −0.23 (−0.44–0.11) | −0.17 (−0.44–0.02) | 0.38 |
Energy expenditure (kcal 24 h–1) | 1971 ± 63 | 1940 ± 58 | 1998 ± 62 | 0.41 |
RQ (ratio O2 : CO2) | 0.94 ± 0.01 | 0.96 ± 0.01 | 0.95 ± 0.008 | 0.31 |
Counter-regulatory response | ||||
Serum FFA (mmol l−1) (t = 255–285 min) | 0.0349 ± 0.003 | 0.0321 ± 0.003 | 0.0343 ± .003 | 0.56 |
Plasma glucagon (pg ml−1) (t = 255–285 min) | 17.25 ± 2.9 | 20.15 ± 5 | 17.85 ± 3 | 0.81 |
Inflammatory markers | ||||
Serum adiponectin (mg l−1) (t = 285 min) | 8.33 ± 1.12 | 8.58 ± 1.13 | 7.96 ± 1.05 | 0.18 |
Serum hsCRP (mg l−1) (t = 285 min) | 0.22 (0.03–3.45) | 0.115 (0.02–3.14) | 0.285 (0.02–2.11) | 0.03** |
Pharmacokinetics | ||||
Drug concentration (µg l−1) | 12.8 ± 0.5 | 486.9 ± 23.5 |
Data are means ± SEM and medians with (range).
P = 0.038 CsA vs. Tac, P < 0.0001 CsA vs. placebo, P = 0.047 Tac vs. placebo.
P = 0.016 CsA vs. Tac, P = 0.02 Tac vs. placebo.