Calcineurin inhibitor effects on glucose metabolism and endothelial function following renal transplantation.
BACKGROUND
Calcineurin inhibitors (CNI) are involved in the development of post-transplant diabetes mellitus (PTDM). Changes in insulin secretion and sensitivity contribute to the development of PTDM and are associated with endothelial function.


METHODS
In a pre-defined substudy of a previously published randomized trial in renal transplant recipients we compared the effect of CNI treatment (n = 23) with complete CNI-avoidance (n = 21) on insulin secretion and sensitivity (oral glucose tolerance test) as well as endothelial function (laser Doppler flowmetry), 10 wk and 12 months following transplantation.


RESULTS
Insulin sensitivity differed 10 wk post-transplant and was significantly better after 12 months in patients never treated with CNI drugs [0.091 (0.050) vs. 0.083 (0.036) micromol/kg/min/pmol/L, p = 0.043]. Insulin secretion tended to be higher in CNI treated patients at both time points (p = 0.068). Endothelial function was not significantly different at week 10 [540 (205) vs. 227 (565) arbitary units x minutes, p = 0.35] or month 12 [510 (620) vs. 243 (242), p = 0.33].


CONCLUSIONS
Findings in the present study indicate that long-term CNI treatment negatively affects glucose metabolism and this may contribute to the increased risk for premature cardiovascular disease in CNI treated renal transplant recipients. Further studies to elucidate this hypothesis are, however, needed.
Asberg
Anders
A
Laboratory for Renal Physiology, Medical Department, Rikshospitalet Medical Center, Oslo, Norway. anders.asberg@farmasi.uio.no
Midtvedt
Karsten
K
Voytovich
Monica H
MH
Line
Pål-Dag
PD
Narverud
Janicke
J
Reisaeter
Anna V
AV
Mørkrid
Lars
L
Jenssen
Trond
T
Hartmann
Anders
A
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D065095:Calcineurin Inhibitors; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000139:chemically induced*; D042783:Endothelial Cells / Q000187:drug effects*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D016030:Kidney Transplantation; D017078:Laser-Doppler Flowmetry; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000098:blood supply; D013995:Time
D001786:Blood Glucose; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D007328:Insulin