| 61. |
- Svensson, Johan, 1964, et al.
(author)
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Treatment of obese subjects with the oral growth hormone secretagogue MK-677 affects serum concentrations of several lipoproteins, but not lipoprotein(a).
- 1999
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 84:6, s. 2028-33
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Journal article (peer-reviewed)abstract
- Obesity is associated with blunted GH secretion and an unfavorable lipoprotein pattern. The objective of this study was to investigate the effects of treatment with the oral GH secretagogue MK-677 on lipoproteins in otherwise healthy obese males. The study was randomized, double blind, and parallel. Twenty-four obese males, aged 18-50 yr, with body mass index greater than 30 kg/m2 and waist/hip ratio above 0.95 were treated with 25 mg MK-677 (n = 12) or placebo (n = 12) daily for 8 weeks. MK-677 treatment did not significantly change serum lipoprotein(a) [Lp(a)] levels. Serum apolipoprotein A-I and E (apoA-I and apoE) were increased at 2 weeks (P < 0.001 and P < 0.01 vs. placebo, respectively), but were not changed at study end. Serum total cholesterol and low density lipoprotein (LDL) cholesterol (LDL-C) levels were not significantly changed by MK-677 treatment. Serum high density lipoprotein (HDL) cholesterol (HDL-C) was increased at 2 weeks of MK-677 treatment (P < 0.01 vs. placebo), but not at 8 weeks. The LDL-C/HDL-C ratio was reduced after 8 weeks of MK-677 treatment (P < 0.05 vs. placebo). Mean LDL particle diameter was decreased at 2 weeks (P < 0.05 vs. placebo), but was unchanged compared with baseline values at 8 weeks (P = NS vs. placebo). The level of serum triglycerides was increased at 2 (P < 0.05 vs. placebo), but not at 8, weeks. Lipoprotein lipase activity in abdominal and gluteal sc adipose tissue was not affected by active treatment. In conclusion, treatment with the oral GH secretagogue MK-677 affected circulating lipoproteins. The effects on serum apoA-1, apoE, triglycerides, and mean LDL particle diameter were transient. At study end, the LDL-C/HDL-C ratio was decreased. MK-677 treatment did not significantly affect serum Lp(a) concentrations at the present dose and administration protocol.
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| 62. |
- Svensson, Johan, 1964, et al.
(author)
-
Treatment with the oral growth hormone secretagogue MK-677 increases markers of bone formation and bone resorption in obese young males.
- 1998
-
In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 0884-0431. ; 13:7, s. 1158-66
-
Journal article (peer-reviewed)abstract
- The effect of 2 months of treatment with the oral growth hormone (GH) secretagogue MK-677 on markers of bone metabolism was determined in healthy obese male subjects. This was a randomized, double-blind, parallel, placebo-controlled study. Twenty-four healthy obese males, 19-49 years of age, with body mass index > 30 kg/m2 were treated with MK-677 (25 mg/day; n = 12) or placebo (n = 12) for 8 weeks. MK-677 increased markers of bone formation; a 23% increase in the carboxy-terminal propeptide of type I procollagen levels and a 28% increase in procollagen III peptide levels were seen with as little as 2 weeks of MK-677 treatment (p < 0.01 and p = 0.001 vs. placebo, respectively) while a 15% increase in serum levels of osteocalcin was not detected until 8 weeks of treatment (p < 0.01 vs. placebo). Markers of bone resorption were induced within 2 weeks of treatment with MK-677; serum levels of the carboxy-terminal cross-linked telopeptide of type I collagen were increased 26% at 8 weeks (p = 0.001 vs. placebo), and urine hydroxyproline/creatinine and calcium/creatinine ratios at 8 weeks were increased by 23% (p < 0.05 vs. placebo) and 46% (p < 0.05 vs placebo), respectively, MK-677 increased serum insulin-like growth factor binding protein-5 (IGFBP-5) by 43-44% after 2-8 weeks of treatment (p < 0.01 vs. placebo). Serum IGFBP-4 was increased by 25% after 2 weeks of treatment (p < 0.001 vs. placebo) but no significant change from baseline was observed after 8 weeks of treatment. Plasma interleukin-6 was not significantly changed by active treatment. In conclusion, short-term treatment of healthy obese male volunteers with the GH secretagogue MK-677 increases markers of both bone resorption and formation. Large increases in serum levels of IGF-1 and IGFBP-5 and a transient increase in serum IGFBP-4 were found. Future long-term studies are needed to investigate if prolonged treatment with MK-677 increases bone mass.
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| 63. |
- Sverrisdóttir, Yrsa Bergmann, 1960, et al.
(author)
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Intense sympathetic nerve activity in adults with hypopituitarism and untreated growth hormone deficiency.
- 1998
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In: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 83:6, s. 1881-5
-
Journal article (peer-reviewed)abstract
- Perturbations in the sympathetic nervous system may be anticipated in adults with hypopituitarism and untreated GH deficiency, because the syndrome is associated with both peripheral and central factors known to modulate sympathetic traffic. The higher prevalence of hypertension and increased cardiovascular morbidity/mortality reported in GH-deficient patients may suggest increased activity of the sympathetic nervous system. We recorded muscle sympathetic nerve activity (MSNA) in 10 hypopituitary adults with adequate hormonal replacement therapy except GH and in 10 healthy controls matched for age, gender, and body mass index to test whether hormonal aberrations in hypopituitarism and untreated GH deficiency are associated with an increase in sympathetic nerve traffic. Blood samples for insulin-like growth factor I, free T4, and TSH were taken after an overnight fast, followed by an oral glucose tolerance test. Direct intraneural recordings of MSNA were performed with a tungsten microelectrode from the peroneal nerve. The hypopituitary subjects had markedly increased MSNA (54 +/- 4 bursts/min vs. 34 +/- 4 in controls; P < 0.002), which was not related to abdominal obesity or altered glucose metabolism. When assessed for the whole study group, MSNA was inversely correlated to serum insulin-like growth factor I (r = -0.59; P < 0.006) and TSH (r = -0.46; P < 0.04). MSNA was positively correlated to diastolic blood pressure (r = 0.80; P < 0.0005) in patients, but not in controls. The intense sympathetic discharge is suggested to be of central origin and may be an important underlying mechanism for the secondary hypertension and increased cardiovascular morbidity/mortality in this patient group.
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| 64. |
- Trimpou, Penelope, 1973, et al.
(author)
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High correlation between quantitative ultrasound and DXA during 7 years of follow-up.
- 2010
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In: European journal of radiology. - : Elsevier BV. - 1872-7727 .- 0720-048X. ; 73:2, s. 360-4
-
Journal article (peer-reviewed)abstract
- Ultrasound is a quick, cheap and non-radiating device for assessing bone quality. We wanted to validate the method for clinical and epidemiological use. Eighty women, aged 53-73 years, with osteoporosis and/or fractures were followed repeatedly during 7 years. Quantitative ultrasound (QUS) measurements (LUNAR Achilles) were compared with bone mineral density (BMD) and bone mineral content (BMC) estimated by DXA (LUNAR) in regions of interest. Changes in the speed of sound, broadband ultrasound attenuation and stiffness were positively correlated with changes in BMD and BMC in all regions measured with DXA (r=0.20-0.53; p=0.09 to <0.0001). The QUS t-score at the left heel was positively correlated with the t-score at the right heel (r=0.90, p<0.0001). The DXA t-score of the left vs. the right femur was also positively correlated (r=0.72-0.86; p<0.0001). A t-score<-2.5 S.D. was found in 70% and 56% at baseline, and 74% and 65% at follow-up measured with QUS and DXA, respectively. The mean sensitivity of QUS vs. DXA was 79% and the mean specificity 45% over a 7-year period. A QUS t-score of <-3.65 S.D. was consistent with a DXA t-score of <-2.5 S.D. In conclusion, QUS was well correlated with DXA in all regions over the 7-year period. QUS can be used in settings without access to DXA and in epidemiological studies. The sensitivity was high but the specificity was low, implicating that DXA, if available, is recommended before treatment for osteoporosis. However, treatment can be started without DXA at a QUS t-score<-3.65 S.D., and especially in the presence of fractures.
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