ECE2013 Poster Presentations Pituitary – Clinical (<emphasis role="italic">Generously supported by IPSEN</emphasis>) (127 abstracts)
Metabolic impact of IGF(CA)19 gene polymorphism on the response to GH therapy in adult GH-deficient (GHD) patients
Claudia Giavoli 1, , Eriselda Profka 1, , Elisa Sala 1, , Marcello Filopanti 1, , Silvia Bergamaschi 1, , Emanuele Ferrante 1, , Maura Arosio 1, , Bruno Ambrosi 1, , Anna Spada 1, & Paolo Beck-Peccoz 1,
1Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy; 2Endocrinology and Diabetology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; 3Unit of Endocrinology, Ospedale San Giuseppe Multimedica, Milan, Italy; 4Endocrinology and Diabetology Unit, Department of Medical and Surgical Sciences, IRCCS Policlinico San Donato, San Donato Milanese, Italy.
A highly polymorphic microsatellite in the IGF-I gene promoter composed of variable cytosine–adenine (CA) repeats (n=10–24) has been linked to IGF-I levels, risk of diabetes and cardiovascular diseases with conflicting results. Aim of this study was to investigate the impact of this polymorphism on the response to rhGH (mean dose 0.34±0.14 mg/day) in adult GH-deficient (GHD) patients after 1 (n=98) and 5 (n=50) years. Different genotypes were studied by microsatellite method, according to the most frequent 192 bp allele (19 CA repeats) subjects were divided into three groups: homozygous (192/192, n=38), heterozygous (192/X, n=44) and non-carriers (X/X, n=16). Allelic distribution was similar in the subgroup followed for 5 years. The genotype did not influence neither the phenotype of patients at baseline (including IGF-I levels), nor their response to rhGH in terms of decrease in BF% and increase in IGF-I levels. Conversely, after 1 year, there was a significant worsening of insulin sensitivity, documented by increase in fasting glucose levels and HOMA-IR (from 81±8 to 86±8 mg/dl and from 1.7±1.0 to 2.4±1.6 respectively, P<0.001), as well as a significant improvement in lipid profile shown by reduction in total and LDL-cholesterol (from 215±42 to 192±39 and from 138±38 to 111±34 mg/dl respectively, P<0.001) only in homozygous. During long-term treatment, HOMA-IR restored to basal values in all patients, though fasting glucose levels remained higher than at baseline in homozygous. The decrease in total and LDL-cholesterol was significant both in homozygous and in heterozygous, but not in non-carriers. No difference among groups was observed in rhGH dose throughout study. In conclusion, the presence of the wild-type allele in the IGF-I gene promoter might increase sensitivity to metabolic changes induced by rhGH, either negative or positive. In the long-term, beneficial effects (i.e. persistent BF% reduction) may overcome the negative impact on glucose metabolism regardless IGF-I genotype, while positive effects on lipid profile manifest in patients carrying at least one 192 bp allele.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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