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OR07-6 EFFECTS OF GH-TREATMENT ON INTIMA MEDIA THICKNESS (IMT) AND CARDIOVASCULAR RISK-FACTORS IN MEN WITH ABDOMINAL OBESITY AND IMPAIRED GLUCOSE TOLERANCE. A 12-MONTH PLACEBO-CONTROLLED STUDY
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Growth Hormone & IGF Research 16 (2006) Suppl B
evaluated by DEXA. Serum IGF-I, IGFBP-3 and lipid levels were determined centrally. QoL was evaluated by SF-36 score. Results: The primary endpoint was a change in truncal fat. For all patients combined, truncal fat was decreased from baseline in the GH group compared with the placebo (−16.1% vs +1.7%, P < 0.0001). There was a gender difference in change of truncal fat after GH treatment (men −22.7% vs. women −8.4%, P < 0.001), whereas there was no difference between the CO GHD and the AO GHD group. An increase in lean body mass (LBM) was also found for total body, trunk, arms and legs. Serum total cholesterol and LDL-cholesterol levels were decreased in the GH group compared with the placebo (P < 0.01 and <0.05, respectively). An increase in both serum IGF-I and IGFBP-3 levels was seen over the 24 weeks treatment with GH. There was no statistical change in QoL. The most common adverse events were related to fluid retention. Oedema and joint pain were more frequent in the GH than in the placebo (13.3 vs 1.7%, 20 vs 5%). Conclusion: GH treatment significantly decreased truncal fat and serum cholesterol levels in adult Japanese GHD patients. The change in truncal fat was much greater in men than in women. The GH treatment was well accepted with some adverse events mainly caused by fluid retention. OR07-5 BASELINE CHARACTERISTICS AND THE EFFECTS OF TWO-YEAR GROWTH HORMONE (GH) REPLACEMENT THERAPY IN ELDERLY PATIENTS WITH ADULT ONSET GH DEFICIENCY ˚ Celina Franco, Gudmundur Johannsson, Bengt-Ake Bengtsson, Johan Svensson ° . Department of Endocrinology, Sahlgrenska University Hospital, Sweden Background: The effects of GH replacement in elderly GH deficient (GHD) adults are not well known. Design and patients: In this prospective, single-centre, open-label study, baseline characteristics and the effects of 2-year GH replacement on serum insulin-like growth factor-I (IGF-I) concentration, body composition, bone mass, and metabolic indexes were determined in 24 GHD adults above 65 years of age and in 24 younger GHD patients (mean age 37; range 27−46 years). All patients had adult onset disease and both groups were comparable in terms of number of anterior pituitary hormonal deficiencies, gender, body mass index (BMI), and waist: hip ratio. Duration of hypopituitarism was, however, longer in the elderly patients. Results: The mean maintenance dose of GH was 0.31 (SEM 0.03) mg/day in the elderly GHD patients, which was lower than the dose of 0.44 (0.04) mg/day in the younger patients. The less marked response to GH replacement in IGF-I SD score, total body fat and extracellular water in the elderly patients lost significance when the differences in the dose of GH were accounted for in the statistical analyses. In spite of the lower dose in the elderly GHD group, these patients had a more marked reduction in waist: hip ratio and serum low density lipoprotein-cholesterol (LDL-C) level, and these between-group differences remained also after correction for duration of hypopituitarism. There was no difference at baseline or in responsiveness in lean mass, bone mineral density and glucose homeostasis. Conclusion: This study identifies elderly GHD adults as a GH sensitive group in whom a low dose of GH can improve body composition and serum lipid profile without any significant impairment of glucose metabolism. GH replacement should therefore be considered in elderly GHD adults.
Abstracts, 3rd Int. Congress of GRS & IGF Society OR07-6 EFFECTS OF GH-TREATMENT ON INTIMA MEDIA THICKNESS (IMT) AND CARDIOVASCULAR RISK-FACTORS IN MEN WITH ABDOMINAL OBESITY AND IMPAIRED GLUCOSE TOLERANCE. A 12-MONTH PLACEBO-CONTROLLED STUDY Gudmundur Johannsson1 , Anna Ekfjorden1 ° , Jozsef Koranyi1 , ˚ Bengtsson1 . 1 Department Lars L¨onn2 , Kenneth Caidahl3 , Bengt-Ake of Endocrinology, Sahlgrenska University Hospital; 2 Sahlgrenska University Hospital, Department of Clinical Radiology, G¨oteborg, Sweden, 3 Sahlgrenska University Hospital, Department of Diagnostic Physiology, G¨oteborg, Sweden Background: Abdominal obesity is associated with blunted GH secretion and increased risk of type 2 diabetes. Previous data suggest that GH may have beneficial effects on the adverse metabolic profile associated with central adiposity in men and women. Administration of GH is, however, hampered by the potential risk of impairing glucose tolerance. Objective: To study the effects of GH treatment on IMT, visceral adipose tissue (VAT), glucose metabolism, blood pressure and high sensitive (hs)CRP in men with abdominal obesity and impaired glucose-tolerance. Study design: Forty men aged 40−65 year with BMI > 25, waist hip ratio > 0.95, impaired fasting glucose or impaired glucose tolerance were randomized after a 3-month run-in-period to two parallel treatment groups with GH and placebo for 12 months. IMT of the carotid artery was measured with ultrasound and VAT was measured using CT. Glucose metabolism was evaluated by oral glucose load, serum insulin, HbA1c, and C-peptide. In addition hsCRP and blood pressure were measured. All measurements took place at baseline and after 12 months. Results: Twelve months of GH treatment did not significantly change IMT as compared with placebo (p = 0.4). The average change in the GH treated was +13% and in the placebo treated +11%. VAT decreased by 4 % in the GH treated with no change in the placebo group (p < 0.01). CRP and diastolic blood pressure (DBP) decreased in the GH treated as compared with placebo (p < 0.05). The mean decrease in DBP was on average 3 mmHg and hsCRP decreased from 2.5 to 2.2 mg/L. Glucose metabolism did not change significantly by the GH treatment. Conclusions: GH treatment reduced VAT, DBP and hsCRP, as compared with placebo, whereas no significantly changes were detected on IMT. This is in contrast to some open-labelled trials of IMT in adult GHD reported in the literature. Although GH was administered to a group with impaired glucose tolerance, no deleterious effect on glucose metabolism was observed.
IGFBP physiology/signaling OR08-1 UNRAVELING THE BIOLOGICAL ACTIONS OF IGFBPS: NEW PARADIGM BEYOND OUR IMAGINATION Youngman Oh ° . Department of Pathology, MCV Campus, Virginia Commonwealth University, USA Constitutive activation of NF-kB is held responsible for both the highly malignant phenotype and the chemoresistance of human cancer. In comparison to normal tissue, a high proportion of cancerous tissues are characterized by a strong nuclear staining in many cancers that has been directly associated with advanced clinical stage and negative patient outcomes. The elevated NF-kB activity significantly contributes to tumorigenicity by induction of specific genes involved in cell survival, angiogenesis, invasion, metastasis and chemoresistance. We have recently identified the growth-inhibitory signaling of IGFBP-3 through an authentic IGFBP-3 receptor in cancer cells. Intriguingly, our studies demonstrate that restoration of IGFBP-3
Growth Hormone & IGF Research 16 (2006) Suppl B
evaluated by DEXA. Serum IGF-I, IGFBP-3 and lipid levels were determined centrally. QoL was evaluated by SF-36 score. Results: The primary endpoint was a change in truncal fat. For all patients combined, truncal fat was decreased from baseline in the GH group compared with the placebo (−16.1% vs +1.7%, P < 0.0001). There was a gender difference in change of truncal fat after GH treatment (men −22.7% vs. women −8.4%, P < 0.001), whereas there was no difference between the CO GHD and the AO GHD group. An increase in lean body mass (LBM) was also found for total body, trunk, arms and legs. Serum total cholesterol and LDL-cholesterol levels were decreased in the GH group compared with the placebo (P < 0.01 and <0.05, respectively). An increase in both serum IGF-I and IGFBP-3 levels was seen over the 24 weeks treatment with GH. There was no statistical change in QoL. The most common adverse events were related to fluid retention. Oedema and joint pain were more frequent in the GH than in the placebo (13.3 vs 1.7%, 20 vs 5%). Conclusion: GH treatment significantly decreased truncal fat and serum cholesterol levels in adult Japanese GHD patients. The change in truncal fat was much greater in men than in women. The GH treatment was well accepted with some adverse events mainly caused by fluid retention. OR07-5 BASELINE CHARACTERISTICS AND THE EFFECTS OF TWO-YEAR GROWTH HORMONE (GH) REPLACEMENT THERAPY IN ELDERLY PATIENTS WITH ADULT ONSET GH DEFICIENCY ˚ Celina Franco, Gudmundur Johannsson, Bengt-Ake Bengtsson, Johan Svensson ° . Department of Endocrinology, Sahlgrenska University Hospital, Sweden Background: The effects of GH replacement in elderly GH deficient (GHD) adults are not well known. Design and patients: In this prospective, single-centre, open-label study, baseline characteristics and the effects of 2-year GH replacement on serum insulin-like growth factor-I (IGF-I) concentration, body composition, bone mass, and metabolic indexes were determined in 24 GHD adults above 65 years of age and in 24 younger GHD patients (mean age 37; range 27−46 years). All patients had adult onset disease and both groups were comparable in terms of number of anterior pituitary hormonal deficiencies, gender, body mass index (BMI), and waist: hip ratio. Duration of hypopituitarism was, however, longer in the elderly patients. Results: The mean maintenance dose of GH was 0.31 (SEM 0.03) mg/day in the elderly GHD patients, which was lower than the dose of 0.44 (0.04) mg/day in the younger patients. The less marked response to GH replacement in IGF-I SD score, total body fat and extracellular water in the elderly patients lost significance when the differences in the dose of GH were accounted for in the statistical analyses. In spite of the lower dose in the elderly GHD group, these patients had a more marked reduction in waist: hip ratio and serum low density lipoprotein-cholesterol (LDL-C) level, and these between-group differences remained also after correction for duration of hypopituitarism. There was no difference at baseline or in responsiveness in lean mass, bone mineral density and glucose homeostasis. Conclusion: This study identifies elderly GHD adults as a GH sensitive group in whom a low dose of GH can improve body composition and serum lipid profile without any significant impairment of glucose metabolism. GH replacement should therefore be considered in elderly GHD adults.
Abstracts, 3rd Int. Congress of GRS & IGF Society OR07-6 EFFECTS OF GH-TREATMENT ON INTIMA MEDIA THICKNESS (IMT) AND CARDIOVASCULAR RISK-FACTORS IN MEN WITH ABDOMINAL OBESITY AND IMPAIRED GLUCOSE TOLERANCE. A 12-MONTH PLACEBO-CONTROLLED STUDY Gudmundur Johannsson1 , Anna Ekfjorden1 ° , Jozsef Koranyi1 , ˚ Bengtsson1 . 1 Department Lars L¨onn2 , Kenneth Caidahl3 , Bengt-Ake of Endocrinology, Sahlgrenska University Hospital; 2 Sahlgrenska University Hospital, Department of Clinical Radiology, G¨oteborg, Sweden, 3 Sahlgrenska University Hospital, Department of Diagnostic Physiology, G¨oteborg, Sweden Background: Abdominal obesity is associated with blunted GH secretion and increased risk of type 2 diabetes. Previous data suggest that GH may have beneficial effects on the adverse metabolic profile associated with central adiposity in men and women. Administration of GH is, however, hampered by the potential risk of impairing glucose tolerance. Objective: To study the effects of GH treatment on IMT, visceral adipose tissue (VAT), glucose metabolism, blood pressure and high sensitive (hs)CRP in men with abdominal obesity and impaired glucose-tolerance. Study design: Forty men aged 40−65 year with BMI > 25, waist hip ratio > 0.95, impaired fasting glucose or impaired glucose tolerance were randomized after a 3-month run-in-period to two parallel treatment groups with GH and placebo for 12 months. IMT of the carotid artery was measured with ultrasound and VAT was measured using CT. Glucose metabolism was evaluated by oral glucose load, serum insulin, HbA1c, and C-peptide. In addition hsCRP and blood pressure were measured. All measurements took place at baseline and after 12 months. Results: Twelve months of GH treatment did not significantly change IMT as compared with placebo (p = 0.4). The average change in the GH treated was +13% and in the placebo treated +11%. VAT decreased by 4 % in the GH treated with no change in the placebo group (p < 0.01). CRP and diastolic blood pressure (DBP) decreased in the GH treated as compared with placebo (p < 0.05). The mean decrease in DBP was on average 3 mmHg and hsCRP decreased from 2.5 to 2.2 mg/L. Glucose metabolism did not change significantly by the GH treatment. Conclusions: GH treatment reduced VAT, DBP and hsCRP, as compared with placebo, whereas no significantly changes were detected on IMT. This is in contrast to some open-labelled trials of IMT in adult GHD reported in the literature. Although GH was administered to a group with impaired glucose tolerance, no deleterious effect on glucose metabolism was observed.
IGFBP physiology/signaling OR08-1 UNRAVELING THE BIOLOGICAL ACTIONS OF IGFBPS: NEW PARADIGM BEYOND OUR IMAGINATION Youngman Oh ° . Department of Pathology, MCV Campus, Virginia Commonwealth University, USA Constitutive activation of NF-kB is held responsible for both the highly malignant phenotype and the chemoresistance of human cancer. In comparison to normal tissue, a high proportion of cancerous tissues are characterized by a strong nuclear staining in many cancers that has been directly associated with advanced clinical stage and negative patient outcomes. The elevated NF-kB activity significantly contributes to tumorigenicity by induction of specific genes involved in cell survival, angiogenesis, invasion, metastasis and chemoresistance. We have recently identified the growth-inhibitory signaling of IGFBP-3 through an authentic IGFBP-3 receptor in cancer cells. Intriguingly, our studies demonstrate that restoration of IGFBP-3