title: Persistence of anomalies in the growth hormone-releasing hormone-stimulated growth hormone response in diabetic-uremic patients after combined kidney-pancreas transplantation.
abstract: Increased circulating growth hormone (GH) levels and aberrant response to different stimuli characterize both type 1 diabetes mellitus and chronic uremia and are associated with severe retinal, kidney and heart complications. Combined kidney and pancreas transplantation is a therapy that restores the endogenous, closed-loop, insulin secretion in diabetes and cure uremia. To evaluate if combined transplantation can restore a normal secretion and response of GH to growth hormone releasing hormone (GH-RH), we studied four groups of subjects: (1) seven type 1 diabetic patients with end-stage renal failure who had received pancreas and kidney transplantation (KPTx); (2) six diabetic uremic subjects, candidates for combined transplantation (IDDUP); (3) nine patients with chronic uveitis on immunosuppressive therapy comparable to pancreas recipients, six of whom treated only with prednisone (UVEST), while three (4) were treated with both prednisone and cyclosporin (UVESTCY). All subjects underwent a GH-RH test (50 microg intravenously, i.v., at 13:00 h). Serum insulin levels were significantly higher in IDDUP compared to UVEST (P=0.05) both at baseline and post GH-RH stimulus, while were similar to KPTx (P=0.2) and UVESTCY (P=0.7). In contrast, plasma free fatty acids were similar in all groups. In IDDUP baseline plasma glycerol was higher than in KPTx (P=0.04) and UVEST (P=0.02) and similar to UVESTCY (P=0.36); glycerol concentration did not change after GH-RH (P=0.08). Before and after GH-RH, serum GH levels tended to be higher in IDDUP (P=0.5) and KPTx (P=0.2) compared to UVEST and UVESTCY. Our results indicate that: 1) kidney-pancreas transplantation does not normalize the GH response to GH-RH; 2) GH abnormalities are not due either to the chronic immunosuppressive therapy or to the insulin effect on GH release; 3) GH abnormalities are probably secondary to functional and/or organic complications of the hypothalamus and/or pituitary as a sequela of diabetes mellitus.
authors.affiliation: Department of Medicine and Surgery, San Raphael Scientific Institute, University of Milan, Italy.
authors.forename: M E
authors.initials: ME
authors.lastname: Malighetti
authors.forename: C
authors.initials: C
authors.lastname: Berra
authors.forename: A
authors.initials: A
authors.lastname: Secchi
authors.forename: G
authors.initials: G
authors.lastname: Pozza
authors.forename: V
authors.initials: V
authors.lastname: Di Carlo
authors.forename: L
authors.initials: L
authors.lastname: Luzi
mesh_terms: D000328:Adult; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000601:surgery*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation; D012737:Sex Factors; D014511:Uremia / Q000378:metabolism / Q000601:surgery*
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone