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Insulin-like growth factor I, growth hormone, and insulin sensitivity: the effects of a one-year cholecalciferol supplementation in middle-aged overweight and obese subjects.
Kamycheva, E, Berg, V, Jorde, R
Endocrine. 2013;(2):412-8
Abstract
Both altered GH-IGF-I axis and low serum levels of 25-hydroxyvitamin D (25(OH)D) are linked to measures of metabolic syndrome. Our hypothesis was that there is a relation between GH, IGF-I, and 25(OH)D; and that vitamin D supplementation may have an effect on the levels of GH, IGF-I, and IGF-I/IGFBP-3 ratio. 318 overweight and obese subjects completed a one-year randomized intervention with either 40,000 or 20,000 IU cholecalciferol per week or placebo. GH, IGF-I, IGFBP-3 and measures of insulin resistance were evaluated at baseline and at the end of study. There was a significant relation between entities of GH-IGF-I axis and insulin resistance. Subjects with severe obesity had significantly lower serum 25(OH)D and had a significant linear decline in IGF-I/IGFBP-3 ratio with increasing serum 25(OH)D quartiles. Vitamin D status was an independent predictor of GH-IGF-I axis and supplementation with vitamin D decreased IGF-I/IGFBP-3 ratio in subjects without severe obesity. No corresponding effect of vitamin D supplementation on BMI or insulin resistance was observed. Adverse effects of GH-IGF-I axis on glucose metabolism and the development of metabolic syndrome may be in part associated with the changes in vitamin D status.
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2.
Risk factors for diabetes mellitus type 2 and metabolic syndrome are comparable for previously growth hormone-treated young adults born small for gestational age (sga) and untreated short SGA controls.
van Dijk, M, Bannink, EM, van Pareren, YK, Mulder, PG, Hokken-Koelega, AC
The Journal of clinical endocrinology and metabolism. 2007;(1):160-5
Abstract
CONTEXT Low birth weight might increase risk of diabetes mellitus type 2 and metabolic syndrome (MS). GH has insulin-antagonistic properties. Therefore, long-term follow-up of GH-treated children born small for gestational age (SGA) is important. OBJECTIVE AND PATIENTS The objective of the study was to evaluate insulin sensitivity (Si) and disposition index (DI), all components of the MS and IGF-I and IGF binding protein (IGFBP)-3 levels in 37 previously GH-treated young SGA adults in comparison with 25 untreated short SGA controls. RESULTS GH-treated subjects were 22.3 (1.7) yr old. Mean duration of GH treatment had been 7.3 (1.3) yr. Mean period after discontinuation was 6.5 (1.4) yr. Si and DI were comparable for GH-treated and untreated SGA subjects. Fasting glucose and insulin levels increased during GH treatment but recovered after discontinuation. Body mass index, waist circumference, high-density lipoprotein cholesterol levels, and triglycerides were equivalent. Systolic and diastolic blood pressure and cholesterol were significantly lower in GH-treated subjects. Thirty-two percent of untreated controls vs. none of the GH-treated subjects had an increased blood pressure. GH-induced rises in IGF-I and IGFBP-3 levels had completely recovered after GH stop. CONCLUSION At 6.5 yr after discontinuation of long-term GH treatment, Si, DI, fasting levels of glucose and insulin, body mass index, waist circumference, and IGF-I and IGFBP-3 levels were equivalent for GH-treated and untreated young SGA adults. Systolic and diastolic blood pressure and serum cholesterol were even lower in GH-treated subjects. These data are reassuring because they suggest that long-term GH treatment does not increase the risk for diabetes mellitus type 2 and MS in young adults.
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3.
Metabolic effects of oral versus transdermal estrogen in growth hormone-treated girls with turner syndrome.
Mauras, N, Shulman, D, Hsiang, HY, Balagopal, P, Welch, S
The Journal of clinical endocrinology and metabolism. 2007;(11):4154-60
Abstract
BACKGROUND Transdermal (TD) estrogen is often preferred over the oral route in postmenopausal and GH-deficient women taking estrogen, but this has not been studied in detail in girls. OBJECTIVE Our objective was to study the metabolic effects of oral vs. TD estrogen in GH-treated girls with Turner syndrome. DESIGN AND METHODS Eleven girls with Turner syndrome, mean age 13.4 +/- 0.5 (se) yr, on GH for at least 6 months were recruited. Studies included [(13)C]leucine and d5-glycerol infusions, indirect calorimetry, dual-emission x-ray absorptiometry, and hormone and substrate measurements. They received, in random order, 17beta-estradiol orally (0.5, 1, and 2 mg for 2 wk each) and TD (0.025, 0.0375, and 0.05 mg for 2 wk each), and studies were repeated after each 6-wk course with 4 wk washout in between. RESULTS Rates of whole-body protein turnover, oxidation and synthesis, lipolysis, lipid and carbohydrate oxidation, and resting energy expenditure were unaffected by either form of estrogen; nor were lipids, insulin, and fibrinogen concentrations affected. Plasma IGF-I concentrations did not change clinically significantly with either form of estrogen, despite higher estrogen concentrations after oral estrogen. Estradiol concentrations did not correlate with any variables measured. CONCLUSIONS In GH-treated girls with Turner syndrome, neither oral nor TD estrogen adversely affected rates of protein turnover, lipolysis, and lipid oxidation rates or plasma lipids, fibrinogen, or fasting insulin concentrations. There was no clinically significant change in IGF-I concentrations after either form of estrogen. In aggregate, these data suggest that the route of delivery of estrogen does not adversely affect these metabolic effects of GH in young girls with Turner syndrome.
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Two years of growth hormone replacement therapy in a group of patients with Sheehan's syndrome.
Soares, DV, Spina, LD, de Lima Oliveira Brasil, RR, Lobo, PM, Salles, E, Coeli, CM, Conceição, FL, Vaisman, M
Pituitary. 2006;(2):127-35
Abstract
To investigate the effects of GH replacement on lipid profile, carotid artery intima-media thickness (IMT), glucose metabolism and visceral fat in patients with Sheehan's syndrome, ten patients, mean age 44.8+/-9.5 yr, compared with 10 controls matched for age and body mass index were studied. Total cholesterol, Triglycerides (TG), HDL-c, LDL-c, Apolipoprotein A and B (apoA and apoB) and Lipoprotein (a), serum IGF-1, ultrasonography of the carotid arteries, oral glucose tolerance test (OGTT), HOMA insulin resistance index, insulin sensitivity index (ISI)-composite and abdominal CT scan were performed. When compared to a control group, patients presented lower HDL concentrations (p=0.05) and 2-h OGTT insulin levels (p<0.04) and increased TG levels (p<0.04). After 24 months of GH replacement a reduction in the relation ApoB/ApoA (p=0.04) was observed, as well as an increase in HDL (p<0.004). A decrease in carotid artery IMT and in visceral fat over time was found, p<0.03 and p<0.04 respectively, though without any significant differences during post hoc comparisons of means, which may be explained by the small number of cases studied, but there was a tendency, p=0.08 and p=0.09 respectively. The 2-h OGTT insulin levels increased (p<0.02) as well as the prevalence of glucose intolerance (prevalence = 42.8%, p<0.05). GH replacement therapy promoted favorable effects on carotid artery IMT, lipid profile and visceral fat in patients with Sheehan's syndrome. On the other hand, patients developed abnormal glucose tolerance probably due to an increase in insulin resistance, demonstrated by higher insulin levels, despite favorable changes in body composition.
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5.
Effect of metformin on the growth hormone response to growth hormone-releasing hormone in obese women with polycystic ovary syndrome.
Guido, M, Romualdi, D, Giuliani, M, Suriano, R, Tienforti, D, Costantini, B, Lanzone, A
Fertility and sterility. 2005;(5):1470-6
Abstract
OBJECTIVE Obese women with polycystic ovary syndrome (PCOS) show a marked growth hormone (GH) hyporesponsiveness to several stimuli. We aimed to evaluate the impact of insulin metabolism on the GH secretion impairment in these subjects in relation to food ingestion. DESIGN Prospective clinical study. SETTING Academic research center. PATIENT(S): Nine obese women with PCOS. INTERVENTION(S): Metformin (1,500 mg/daily) was administered for three months. The study protocol, which was performed before and after therapy, included hormonal and lipid assays, oral glucose tolerance test (75 g), euglycemic hyperinsulinemic clamp, and growth hormone-releasing hormone (GHRH) test (50 microg/ev), both on fasting and after a standard meal. MAIN OUTCOME MEASURE(S): Growth hormone response to GHRH (expressed as the area under the curve) in different experimental conditions. RESULT(S): The preprandial GH response to GHRH was not modified by the therapy, whereas a significant increase (P<.05) occurred in the postprandial GH secretion, thus resembling the response of obese normal persons. This change was accompanied by a trend towards improvement, though not statistically significant, of all the evaluated glycoinsulinemic parameters. A significant reduction in cholesterol (P<.01) and androstenedione (P<.05) and an increase in sex hormone-binding globulin (P<.05) were also achieved. CONCLUSION(S): These data suggest that metformin is able to affect GH secretion in obese women with PCOS, even with minimal metabolic modifications.