Fung, JJ

Furukawa, H

Jain, A

Mieles, L

Starzl, TE

Susuki, M

Todo, S

PubMed

D-Scholarship@Pitt

~ t J() 7 L i f , Oral Glucose Tolerance Test in Liver Recipients Treated With FK 506 L. Mieles, S. Todo, J.J. Fung, A. Jain, H. Furukawa, M. Susuki, and T.E. Starzl I NITIAL human trials with FK 506 conducted at the University of Pittsburgh have demonstrated a remark-able immunosuppressive effect of the drug on liver. kid-ney, and pancreatic transplants. 1-3 It is expected that the drug may be used more extensively in the field of trans-plantation over the next few years. Since some of the early experiments suggested that FK 506 might be diabeto-genic.4 oral glucose tolerance tests were performed in 12 liver transplant recipients who received FK 506, searching for possible derangements in glucose metabolism. MATERIALS AND METHODS The 12 patients whose immunosuppression consisted of FK 506 and low doses of prednisone were all adult individuals with no acute illness. no previous history of diabetes mellitus, and normal fasting blood sugar levels before transplantation. Table I shows the age, sex, steroid dose, and time after transplant of these 12 patients. The test was conducted in the following fashion: after a 100hour fast, a sample was obtained, and 75 g of glucose was administered orally. Samples for venous serum sugar levels were obtained at 30 minutes and I, 2, 3, 4, and 5 hours. Simultaneous insulin levels were done at fasting and at hourly intervals for 5 hours. The glucose determinations were made using the Kodak Ektachem Colorimetric method (Eastman Kodak Company, Rochester, NY), while the insulin measurements were done by the radioim-munoassay method (1251 Insulin Radioimmunoassay Kit, Cam-bridge Medical Diagnostics). The results of this test are shown in Figs I and 2. RESULTS None of the patients were on insulin therapy. The fasting blood sugar levels were normal in II patients and abnormal in one (patient no. 4). Their mean values were 99 ± 18 (SD) mg/dl (Table I). In six patients, the oral glucose tolerance test was considered normal (patients no. 2. 3, 6, 9, to. and 12). In two patients (nos. 4 and 5). the results were consistent with incipient diabetes mellitus. while in the remaining four patients (nos. I, 7, 8, and II). although not entirely normal (a 2-hour sample <200 and> 140 mg/dl with intermediate values of <200 mg/dl), the tests could not be classified as being indicative of diabetes or of impaired glucose tolerance tests. The fasting insulin levels were <20 Io'U/ml in all patients, with mean peak insulin levels of 42 ± 28 ~r/ml (Table I). The insulin curves are shown in Fig 2, and most follow a normal pattern. Again. patient no. 4 presented with the lowest peak insulin levels and a flat insulin curve. This patient had a family history of diabetes mellitus and a DR4 on human leukocyte antigen typing, which suggested that heredity was a major contrib-utor to this patient's abnormal glucose tolerance test. Although asymptomatic, the patient has continued to have mildly elevated fasting blood sugar levels. The other patient with a diabetic-type curve (patient no. 5) has From the Department of Surgery, UniverSity Health Center of Pittsburgh, University of Pittsburgh; and the Veterans Administra-tion Medical Center, Pittsburgh, PA. Supported by research grants from the Veterans Administration and Project Grant No. DK 29961 from the National Institutes of Health, Bethesda, MD. Address reprint requests to T.E. Starzl, MD, PhD, Department of Surgery,3601 Fifth Avenue, Falk Clinic 5C, Pittsburgh, PA 15213. 9 1990 by Appleton & Lange 0041-1345/90/$3.001 +0 Table 1. Features of the 12 Liver Transplant Recipients Tested Prednisone Fasting Blood Peak Insulin Patient Age Days After Dose Sugar Level Level No. (yr) Sex Transplant (mgld) (mgldl) /LU1ml) 41 F 25 5 82 30 2 31 M 15 10 95 42 3 18 M 25 5 100 66 4 38 M 19 10 154 22 5 42 M 23 0 99 41 6 39 M 34 5 90 23 7 49 M 24 0 85 35 8 28 M 21 20 115 26 9 55 M 35 10 103 37 10 36 F 24 10 99 128 11 33 F 27 5 97 34 12 36 M 49 5 80 27 Mean :t SD 37 ± 9 27 :t 9 7±5 99 ± 18 48 ± 28 Transplantation Proceedings, Vol 22, No 1, Suppl 1 (February), 1990: pp 41-43 41 42 MIELES. TODO. FUNG ET AL 400 ~----------------------------------------------~ 350 I-300 I-"0 en 250 l-E 100 50 l-0 I I 0 30 60 90 120 150 180 Minutes remained asymptomatic, with nonnal fasting blood sugar levels. This last patient has been completely weaned from steroids. DR typing for this patient was not available. DISCUSSION Posttransplant hyperglycemia is a well-recognized hazard of organ transplantation. The reason may be multifactorial. although drug toxicity may playa major role, since most standard immunosuppressive regimens contain prednisone and/or CyA, which are known to be diabetogenic in 140 130 120 110 100 90 Insulin 80 uU/ml 70 60 50 40 30 20 10 0 0 30 60 90 120 150 180 Minutes Fig 1. Oral glucose toler-I ance test in 12 liver trans-210 240 270 300 plant recipients receiving FK 506. humans. 5-8 Since similar effects had been ascribed to FK 506 in experimental animals.4 we were prompted to per-fonn the present study. A significant diabetogenic effect of FK 506 on liver transplant recipients, at least during the first weeks following transplantation, was not found to be different than in patients under conventional immunosup-pression. Longer-tenn studies are needed to detennine whether the minimal abnormalities seen in some of these patients will eventually disappear or whether they will evolve into a diabetic state. 210 240 270 300 Fig 2. Corresponding insulin curve in the 12 liver transplant recipients receiving FK 506. .-JI __ iDii~~ ORAL GLUCOSE TOLERANCE TEST .. ~KK;KKD" r ~~D " ~·KDu;D . ;: .... ! :i" REFERENCES I. Stanl TE. Todo S. Fung J. et aI: Lancet 2:1000. 1989 2. Todo S: Transplant Proc <this issue) 3. Fung J, Todo S, Jain A. et aI: Transplant Proc (this issue) 4. Collier D St J, Caine R. Thiru S. et aI: Transplant Proc 19:3975. 1987 43 5. Starzl TE: Experience in Renal Transplantation. WB Saun-ders Company. Philadelphia. PA. 1964. pp 117. 161.221 6. Ruiz JO. Simmons RL. Callender CO. et al: Surgery 73:759. 1973 7. Roth M, Milgrom M. Esquenai V, et al: Transplantation 47:278. 1989 8. Ost L. Tyden G. Fehrman I: Transplantation 46:370. 1989 

Oral glucose tolerance test in liver recipients treated with FK 506

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Oral glucose tolerance test in liver recipients treated with FK 506

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