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1.
Low myocardial glucose uptake in Turner syndrome is unaffected by growth hormone: a randomized, placebo-controlled FDG-PET study.
Trolle, C, Hjerrild, B, Mortensen, KH, Knorr, S, Søndergaard, HM, Christiansen, JS, Gravholt, CH
Clinical endocrinology. 2015;(1):133-40
Abstract
BACKGROUND An unfavourable cardiovascular and metabolic phenotype causes threefold excess mortality in Turner syndrome (TS), and perturbed cardiac substrate metabolism is increasingly recognized as a common component of cardiovascular and metabolic diseases. We therefore hypothesized that myocardial glucose uptake (MGU) is reduced in TS and that growth hormone (GH) treatment improves MGU. To this end, this controlled trial elucidates MGU in TS and the impact of 6 months of growth hormone treatment on MGU. METHODS AND RESULTS Women with TS (n = 9) were examined at baseline, sequentially treated with either Norditropin(®) SimpleXx or placebo and re-examined after 6 months. MGU and myocardial blood flow (MBF) were measured using 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) during a hyperinsulinaemic euglycaemic clamp (at baseline and 6 months). Blood pressure measurement, blood sampling, echocardiography and dual energy X-ray absorptiometry scan were also performed. Age-matched female controls (n = 9) were examined once. Baseline MGU was reduced in TS (0.24 ± 0.08 vs. 0.36 ± 0.13 μmol/g/min in controls; P = 0.036) despite similar insulin sensitivity (whole body glucose uptake (M-value): 9.69 ± 1.86 vs. 9.86 ± 2.58 mg/(min*kg) in controls; P = 0.9). Six months of GH carried no impact on MGU (0.25 ± 0.08 vs. 0.26 ± 0.12 μmol/g/min in the placebo group; P = 0.8). Plasma glucose, low-density cholesterol and triglycerides increased, while M-value and exercise capacity decreased during 6 months of GH treatment. CONCLUSION MGU is reduced in TS despite normal insulin sensitivity. GH treatment does not alter MGU despite decreased whole body insulin sensitivity. A perturbed cardiac glucose uptake appears to be a feature of TS.
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2.
Diabetes-ameliorating effects of fermented red ginseng and causal effects on hormonal interactions: testing the hypothesis by multiple group path analysis.
Lee, KJ, Lee, SY, Ji, GE
Journal of medicinal food. 2013;(5):383-95
Abstract
Although diagnostic criteria for metabolic syndrome (MtS) vary among various health professionals and organizations, blood glucose dysregulation and insulin resistance are common to all definitions. Red ginseng is beneficial for glucose regulation and insulin sensitivity but the mechanism is not yet elucidated. Ginsenosides Rh1 and Rg3 act as ligands of the estrogen receptor, and Rh2 and compound K act as ligands of the glucocorticoid receptors, which may influence the diabetes markers. The objective of this study was to test the hypothesis that there are significant causal relationships among diabetes-related markers and several hormones, and assess whether or not the consumption of fermented red ginseng (FRG) influences these causal relationships by multiple group path analysis and conventional statistical analyses. The 93 postmenopausal women were randomly divided into two groups for a double-blind trial. FRG powder and placebo were provided for 2 weeks. The data were analyzed by multiple group path analysis and the mean between groups were compared. The model's goodness of fit was excellent, with a root mean square error of approximation of 0.00, and comparative fit index of 1.00. The FRG group exhibited significantly increased levels of dehydroepiandrosterone sulfate (DHEAS), growth hormone (GH), and estradiol (E2), and they exhibited decreased levels of glycosylated hemoglobin (HbA1c), insulin, and homeostatic model assessment of insulin resistance. With regard to the hypothesis, the blood glucose lowering effects of FRG were due to the negative effects of aldosterone and increased GH, which was associated with DHEAS and E2. Even though the differences of variables between both groups were small, the total effects of these variables may indicate beneficial changes for the prevention of diabetes in healthy postmenopausal women.
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3.
Effect of oxandrolone on glucose metabolism in growth hormone-treated girls with Turner syndrome.
Menke, LA, Sas, TC, Stijnen, T, Zandwijken, GR, de Muinck Keizer-Schrama, SM, Otten, BJ, Wit, JM
Hormone research in paediatrics. 2011;(2):115-22
Abstract
BACKGROUND The weak androgen oxandrolone (Ox) may increase height but may also affect glucose metabolism in girls with Turner syndrome (TS). METHODS In a randomized, placebo-controlled, double-blind study, we assessed the effect of Ox at a dosage of either 0.06 or 0.03 mg/kg/day on glucose metabolism in 133 growth hormone (GH)-treated girls with TS. Patients were treated with GH (1.33 mg/m(2)/day) from baseline, combined with placebo (Pl) or Ox from the age of 8, and estrogens from the age of 12. Oral glucose tolerance tests (OGTT) were performed, and HbA1c levels were measured before, during, and after discontinuing Ox/Pl therapy. RESULTS Insulin sensitivity, assessed by the whole-body insulin sensitivity index (WBISI) decreased during GH+Ox/Pl (p = 0.003) without significant differences between the dosage groups. Values returned to pre-treatment levels after discontinuing GH+Ox/Pl. On GH+Ox, fasting glucose was less frequently impaired (Ox 0.03, p = 0.001; Ox 0.06, p = 0.02) and HbA1c levels decreased more (p = 0.03 and p = 0.001, respectively) than on GH+Pl. CONCLUSIONS We conclude that in GH-treated girls with TS, Ox at a dosage of 0.03 or 0.06 mg/kg/day does not significantly affect insulin sensitivity. Insulin sensitivity decreases during GH therapy, to return to a pre-treatment level after discontinuing therapy.
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4.
The effects of protein ingestion on GH concentrations in visceral obesity.
van Vught, AJ, Nieuwenhuizen, AG, Veldhorst, MA, Brummer, RJ, Westerterp-Plantenga, MS
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2010;(10):740-5
Abstract
Growth hormone (GH), a hormone originating from the anterior pituitary gland, is an important regulator of metabolism and body composition. Low GH secretion is associated with features of the metabolic syndrome, in particular increased visceral body fat and decreased lean body mass. It has been shown that GH release can be promoted by ingestion of protein, in particular gelatin protein. The question remains; is the GH-promoting effect of gelatin protein also present in a population with blunted GH response, such as visceral obesity? 8 lean women (age: 23+/-3 years, BMI: 21.6+/-2.0 kg/m (2)) and 8 visceral obese women (age: 28+/-7 years, BMI: 33.8+/-5.5 kg/m (2)) were compared with regard to their 5-h GH response after oral ingestion of gelatin protein (0.6 g protein per kg bodyweight), placebo (water), or injection of growth hormone releasing hormone (GHRH) (1 mu/kg body weight), in a randomized crossover design. GH response after placebo, gelatin protein, or GHRH was higher in lean subjects than in visceral obese subjects (p<0.05). Ingestion of gelatin protein increased GH response compared with placebo in both visceral obese (182.1+/-81.6 microg/l.5 h vs. 28.4+/-29.8 microg/l.5 h) and lean (631.7+/-144.2 microg/l.5 h vs. 241.0+/-196.8 microg/l.5 h) subjects (p<0.05). GH response after ingestion of gelatin protein in visceral obese did not differ from that in lean, placebo-treated subjects (p=0.45). GH concentrations after GHRH injection correlated significantly with GH concentrations after gelatin ingestion (AUC; r=0.71, p<0.01, Peak; r=0.81, p<0.01). Further research is needed to investigate if gelatin protein is able to improve metabolic abnormalities in hyposomatotropism in the long term or to investigate the relevance of protein as diagnostic tool in hyposomatotropism.
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5.
Cardiovascular and metabolic risk profile and acylation-stimulating protein levels in children with Prader-Willi syndrome and effects of growth hormone treatment.
de Lind van Wijngaarden, RF, Cianflone, K, Gao, Y, Leunissen, RW, Hokken-Koelega, AC
The Journal of clinical endocrinology and metabolism. 2010;(4):1758-66
Abstract
CONTEXT Reports on the cardiovascular and metabolic risk profile in children with Prader-Willi syndrome (PWS) and the effects of GH treatment are scarce. Acylation-stimulating protein (ASP) stimulates glucose uptake and triglyceride storage in adipose tissue. OBJECTIVES The aim was to study the metabolic and cardiovascular risk profile and ASP levels and to investigate the effects of GH treatment. DESIGN We conducted a randomized controlled GH trial. Infants and prepubertal children were assigned to receive GH (1 mg/m(2) . d) or to serve as controls for 12 and 24 months, respectively. PATIENTS Eighty-five children with PWS (mean +/- sd age of 4.9 +/- 3.0 yr) participated in the study. MAIN OUTCOME MEASURES We measured fat percentage (fat%) with dual-energy x-ray absorptiometry, blood pressure, fasting insulin and glucose levels, serum lipids, and ASP levels. RESULTS Mean +/- SD fat% was 28.4 +/- 6.2 in infants and 36.9 +/- 8.5 in prepubertal children. Fat% sd score (SDS) was above 2 SDS in 95% of prepubertal children. In addition, 63% of infants and 73% of prepubertal children demonstrated at least one cardiovascular risk factor, defined as hypertension or dyslipidemia. The metabolic syndrome was demonstrated in 5% of all children. Mean +/- sd baseline ASP was 107 +/- 45 nmol/liter (normal < 58 nmol/liter) and correlated with fat mass and TG levels. GH improved fat%SDS and the HDLc/LDLc ratio (P < 0.0001 and P = 0.04). GH had no effect on mean ASP levels in this population. CONCLUSIONS Many children with PWS had dyslipidemia and high ASP levels. GH improved fat% and high-density lipoprotein cholesterol/low-density lipoprotein cholesterol, but not ASP. High ASP levels may prevent complete normalization of fat%SDS during GH treatment but may contribute in keeping glucose and insulin levels within normal range.
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6.
Long-term follow-up of GH-treated girls with Turner syndrome: metabolic consequences.
Bannink, EM, van der Palen, RL, Mulder, PG, de Muinck Keizer-Schrama, SM
Hormone research. 2009;(6):343-9
Abstract
AIMS: To investigate the metabolic consequences of long-term GH treatment in young women with Turner syndrome (TS), several years after GH discontinuation. METHODS Follow-up study of a randomized GH dose-response trial, with 3 GH dosages (1.3, 2.0, and 2.7 mg/m(2)/day). Thirty-nine TS patients (20.0 +/- 2.1 years) participated 4.8 +/- 1.9 years after GH discontinuation. Mean GH treatment duration was 8.7 +/- 2.0 years. Fasting glucose, insulin, and serum lipids were measured. RESULTS Several years after GH discontinuation, insulin sensitivity remained lower, while beta-cell function and fasting insulin levels remained higher than before treatment. Only BMI influenced beta-cell function. Serum total cholesterol (TC), low-density lipoprotein and high-density lipoprotein (HDL) had further increased compared to 6 months after GH, resulting in higher TC, but also higher HDL levels compared to controls. The atherogenic index remained constant, but lower than controls. CONCLUSIONS Besides height, GH therapy in girls with TS has additional beneficial effects on serum lipids. Nearly 5 years after discontinuation of GH therapy the favorable effect of GH was still noticeable. The GH-induced decrease in insulin sensitivity, however, remained unchanged, possibly due to having TS.
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7.
Evidence for distinct effects of GH and IGF-I in the metabolic syndrome.
Maison, P, Balkau, B, Souberbielle, JC, Cunin, P, Vol, S, Macquin-Mavier, I, Eschwège, E, ,
Diabetic medicine : a journal of the British Diabetic Association. 2007;(9):1012-8
Abstract
AIMS: The metabolic syndrome is a cluster of cardiovascular risk factors which include central obesity, dyslipidaemia, glucose intolerance and hypertension. These risk factors are common in patients with growth hormone (GH) deficiency, suggesting a role for the somatotropic axis in the development of metabolic syndrome. METHODS We used factor analysis to investigate the relationships linking serum levels of GH and insulin-like growth factor I (IGF-I) to metabolic syndrome variables (high-density lipoprotein cholesterol, triglycerides, fasting glucose, blood pressure and waist circumference). We studied 359 men and 388 women from the Data from an Epidemiological Study on the Insulin Resistance syndrome (DESIR). Their age range was 30-64 years. RESULTS Three independent latent factors explained 61% of the total variance in women and four factors explained 73% in men. In both men and women, IGF-I showed a strong positive correlation with the lipid factor and a negative correlation with the obesity/glucose factor. In women, GH showed a strong negative correlation with the obesity/glucose factor but not the lipid factor. In men, GH was unrelated to the lipid and obesity/glucose factors. The blood pressure factor was not related to GH or IGF-I. In contrast with IGF-I, GH was significantly lower in women with metabolic syndrome (1575 +/- 449 pg/ml) than in the other women (2121 +/- 520 pg/ml, P = 0.002). No significant difference was observed in men for GH or IGF-I. CONCLUSION Our results support a link between the somatotropic axis and several features of the metabolic syndrome, and suggest distinct effects of GH and IGF-I on these parameters.
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8.
Growth hormone favorably affects bone turnover and bone mineral density in patients with short bowel syndrome undergoing intestinal rehabilitation.
Tangpricha, V, Luo, M, Fernández-Estívariz, C, Gu, LH, Bazargan, N, Klapproth, JM, Sitaraman, SV, Galloway, JR, Leader, LM, Ziegler, TR
JPEN. Journal of parenteral and enteral nutrition. 2006;(6):480-6
Abstract
BACKGROUND Patients with short bowel syndrome (SBS) have a high prevalence of metabolic bone disease due to nutrient malabsorption and potential effects of parenteral nutrition (PN). Human growth hormone (hGH) has been shown in some studies to have anabolic effects on bone, but hGH effects on bone in patients with SBS are unknown. METHODS Adults with PN-dependent SBS underwent a 7-day period of baseline studies while receiving usual oral diet and PN and then began receiving modified diets designed to improve nutrient absorption and daily oral calcium/vitamin D supplements (1500 mg elemental calcium and 600 IU vitamin D, respectively). Subjects were randomized to receive in a double-blind manner either subcutaneous (sc) saline placebo as the control or hGH (0.1 mg/kg/d for 3 weeks, then 0.1 mg/kg 3 days a week for 8 subsequent weeks). Open-label hGH was given from week 13 to week 24 in subjects who required PN after completion of the 12-week double-blind phase. Markers of bone turnover (serum osteocalcin and urinary N-telopeptide [NTX]), vitamin D nutriture (serum calcium, 25-hydroxyvitamin D [25-OH D] and parathyroid hormone [PTH] concentrations), and intestinal calcium absorption were measured at baseline and at weeks 4 and 12. Dual x-ray absorptiometry (DXA) of the hip and spine was performed to determine bone mineral density (BMD) at baseline and weeks 12 and 24. RESULTS The majority of subjects in each group exhibited evidence of vitamin D deficiency at baseline (25-OH D levels<30 ng/mL; 78% and 79% of control and hGH-treated subjects, respectively). Subjects treated with hGH demonstrated a significant increase from baseline in serum osteocalcin levels at 12 weeks (+62%; p<.05). The levels of NTX were increased over time in the hGH-treated group; however, this did not reach statistical significance. Both NTX and osteocalcin remained unchanged in control subjects. BMD of the spine and total hip was unchanged in subjects treated with placebo or hGH at 24 weeks. However, femoral neck BMD was slightly but significantly decreased in the placebo group at this time point but remained unchanged from baseline in the hGH-treated subjects. CONCLUSIONS hGH therapy significantly increased markers of bone turnover during the initial 3 months of therapy and stabilized femoral neck bone mass over a 6-month period in patients with severe SBS undergoing intestinal rehabilitation.