GH has contra-insulin actions and exogenous GH can reversibly reduce insulin sensitivity in patients treated with GH. It has been recently reported that the exon 3 – deleted (d3) isoform of the GH receptor (GHR) appears to be preventive for type 2 diabetes mellitus in adult subjects (GH&IGF Res 2007;17:392). Aim of this study was to investigate possible influences of the GHR-d3 isoform on glucose metabolism, lipid profile and BMI in children with Prader-Willi syndrome (PWS) treated with GH . We studied 44 PWS subjects (19 male). Mean age was 25.3 (range: 3.0-42.8) years. Of the 44 subjects, 32 had been (n° 9) or were being (n° 23) treated with GH at a mean dose of 0.06 mg/kg/week, while the remaining 12 never received GH therapy, and were therefore used to analyse the sole baseline variables. Patients' genotype at GHR-exon 3 locus was determined by simple multiplex PCR. Height-SDS, BMI-SDS, fasting glucose, insulin, total and HDL-cholesterol, triglycerides, oral glucose tolerance test (OGTT), QUICKI and HOMA-R indexes were regularly evaluated during treatment. Informed written consent was obtained from the subjects and/or their parents where appropriate. The full-length (fl) GHR exon 3 isoform was found in 21 subjects in homozygosity (group fl); d3 was found in 21 subjects in heterozygosity and in 2 in homozygosity (group d3), which corresponds to the common distribution of the exon-3 isoforms in the general population. No differences in the above mentioned parameters were found comparing the two groups at treatment start, during and at the end of treatment. Furthermore, height-SDS and BMI-SDS did not differ between the two groups neither at baseline or during treatment. On the basis of these preliminary data, d3 does not seem to influence glucose and fat metabolism during GH treatment in PWS subjects.
Influence of the Exon 3 – deleted polymorphism of the GH receptor on glucose and lipid metabolism in GH treated subjects with Prader-Willi syndrome: results of a preliminary study / C., Donati; M., Baiocchi; P., Mella; A., Pilotta; A., Crinò; Iughetti, Lorenzo; G., Grugni; A., Salvatoni; F., Buzi. - In: HORMONE RESEARCH. - ISSN 0301-0163. - STAMPA. - 72 (S3):(2009), pp. 105-105. ((Intervento presentato al convegno LWPES/ESPE 8th JOINT MEETING tenutosi a New York nel 9-12 settembre 2009.