THE EFFECT OF FK506 GLYCEMIC RESPONSE AS ASSESSED BY THE HYPERGLYCEMIC CLAMP TECHNIQUE

We studied seven nondiabetic subjects with the autoimmune diseases pso riasis, multiple sclerosis, and primary biliary sclerosis who were to receive FK506 as experimental immunotherapy. All subjects underwent tw o standard oral glucose tolerance tests and two 180-min hyperglycemic clamps immediately before and 10 weeks after starting FK506. There was no significant difference in weight or HbA1c pre- vs, post-FK506 trea tment, FK506 levels were therapeutic and nontoxic (0.1-1 ng/ml) for al l subjects studied, Repeated measures analysis of variance for interac tion between time and treatment was performed on insulin (after outlie r removed) and glucose values from the OGTT, There was neither time-by -treatment interaction, nor a treatment effect (P>0.1), There were no significant differences in pre- vs, post-FK506 treatment values of pla sma glucose during the hyperglycemic clamp mean acute insulin response to glucose (AIRG) 164+/-38 pmol/L vs. 148+/-46 pmol/L (P>0.1); mean i ncremental area under the insulin curve (IAUC) during the first 10 min of the study, 473+/-109 pmol/L vs. 443+/-146 pmol/L (P>0.1); total ar ea under the insulin curve (TAUC) during the first 10 min of the study , 786+/-152 pmol/L vs, 781+/-18 pmol/L (P>0.1); mean glucose infusion rate (GIR) 37.7+/-5.0 mu mol/kg/min vs. 33.8+/-4.4 mu mol/kg/min (P>0. 1); or mean insulin sensitivity index (ISI), 3.05+/-0.4 vs, 3.13+/-0.5 (P>0.1), Mean steady-state insulin secretion (SSI) was significantly lower 244+/-43 pmol/L vs. 200+/-25.2 pmol/L (P=0.03), Peak first-phase insulin secretion values of 321+/-62 pmol/L vs, 263+/-57 pmol/L appro ached significance (P=0.07), No patient progressed to diabetes during the study. FK506 decreased steady-state insulin secretion during the l ast 60 min of the clamp, regardless of initial glucose tolerance, Insu lin sensitivity and glucose infusion rate did not change in the group as a whole with FK506 treatment.