The effects of maintenance doses of FK506 versus Cyclosporin A on glucose and lipid metabolism after orthotopic liver transplantation

Background Posttransplant diabetes mellitus (PTDM) has gained widespread at tention due to the micro and macro-vascular complications that increase the morbidity and mortality of patients receiving solid organs. The higher inc idence of PTDM has been mainly attributed to the immunosuppressive therapy. Therefore, this study compares the metabolic side effects of low dose main tenance therapy of FK-506 and Cyclosporin A (CsA) in 14 patients 1 year aft er ortho-topic liver transplant and analyzes possible factors that contribu te Ire, the development of PTDM. Methods. Two groups (n=7) differing in their immunosuppressive regimen, (FK 506 or CsA) were matched to eight control subjects and compared to each oth er. The effects of in vivo insulin action were assessed by means of the eug lycemic hyperinsulinemic clamp technique. Arginine stimulation tests sat no rmo- (5.5 mM and hyperglycemic (15 mM) levels were performed and the acute insulin, C-peptide, and glucagon response (2-5 min) to arginine were determ ined. Results. Insulin sensitivity (total glucose disposal) was statistically low er in patients treated with FK-506 and CsA (5.05+/-0.47 and 5.05+/-0.42 mg/ kg/min) as compared to controls (6.62+/-0.38 mg/kg/min) (P<0.02), with a si gnificantly higher nonoxidative glucose disposal for the control group (P<0 .01), and lower free fatty acid levels (P<0.05). Absolute values for acute insulin response were higher but not significantly differene for the transp lanted groups. The lower percentage of? increase of insulin release after a rginine stimulation observed in the FM-506 and CsA groups as compared with controls (754%+/-100, 644%+/-102 vs. 1191%+/-174) (P<0.03 and 0.02), respec tively), suggests a reduced beta cell secretory reserve in both treated gro ups. Also, the acute glucagon response to arginine during hyperglycemia dec lined less in the FK-506 (28%)and CsA groups (29%) compared with controls ( 48%) (P<0.05) indicating a defect in the pancreatic beta cell-alpha cell ax is. Conclusions. There are no major metabolic differences on low maintenance do ses between FK-506 and CsA. Both immunosuppressant agents contribute to the development of PTDM at different levels.