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- Johannsson, Gudmundur, 1960, et al.
(författare)
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Growth hormone and the metabolic syndrome.
- 1999
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Ingår i: Journal of endocrinological investigation. - 0391-4097. ; 22:5 Suppl, s. 41-6
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Forskningsöversikt (refereegranskat)abstract
- The association of several risk factors, obesity, dyslipoproteinemia, hepatic steatosis, insulin resistance and hypertension with Type 2 (non-insulin-dependent) diabetes mellitus and myocardial infarction has long been known and has been termed the "metabolic syndrome". In 1988 Reaven introduced syndrome X as the link between insulin resistance and hypertension. It has been suggested that a critical factor in the association between obesity, Type 2 diabetes and cardiovascular morbidity is the mass of intraabdominal fat. Striking similarities exist between the metabolic syndrome and untreated growth hormone (GH) deficiency in adults. The central findings in both these syndromes are abdominal/visceral obesity and insulin resistance. Other features common to both conditions are premature atherosclerosis and increased mortality from cardiovascular diseases. These similarities indicate that undetectable and low levels of GH may be of importance in the metabolic aberrations observed in both these conditions. Recent investigations have found that abdominal/visceral distribution of adipose tissue is associated with endocrine disturbances including increased activity of the hypothalamic-pituitary-adrenal axis and a blunted secretion of GH and sex steroids. Theoretically, these endocrine perturbations can be a consequence of obesity, but the endocrine aberrations may have causal effects. We studied moderately obese, middle-aged men with a preponderance of abdominal body fat. As a group, they had slight to moderate metabolic changes known to be associated with abdominal/visceral obesity. Nine months of GH treatment reduced their total body fat and resulted in a specific and a marked decrease in both abdominal subcutaneous and visceral adipose tissue. Moreover, insulin sensitivity improved and serum concentrations of total cholesterol and triglyceride decreased. Diastolic blood pressure also decreased. The finding that GH replacement in men with abdominal obesity can diminish the negative metabolic consequences of visceral obesity suggests that low levels of this hormone are of importance for the metabolic aberrations associated with visceral/abdominal obesity.
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| 2. |
- Leonsson, M, et al.
(författare)
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Growth hormone (GH) therapy in GH-deficient adults influences the response to a dietary load of cholesterol and saturated fat in terms of cholesterol synthesis, but not serum low density lipoprotein cholesterol levels.
- 1999
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 84:4, s. 1296-303
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Tidskriftsartikel (refereegranskat)abstract
- An increased dietary load of cholesterol (ch) and saturated fat increases serum low density lipoprotein ch (LDL-ch) levels. GH therapy in GH-deficient adults decreases serum LDL-ch levels. In the rat, GH is important for resistance to dietary cholesterol in terms of serum cholesterol levels. The aim of this study was to investigate the influence of GH on the effects of an increase in the intake of cholesterol and saturated fat on serum lipoproteins and markers for cholesterol synthesis in man. Six GH-deficient adults were given an isocaloric diet enriched in cholesterol and saturated fat for 17 days with and without GH therapy (1-1.5 U/day). Serum cholesterol, LDL-ch, apolipoprotein B (apoB), and apoA1 levels increased during the diet period with GH therapy and tended to increase during the diet period without GH. However, GH therapy did not influence the dietary effect on serum cholesterol, LDL-ch, apoA1, or apoB levels. Serum levels of triglycerides, very low density lipoprotein ch, high density lipoprotein ch, and apoE were not affected by diet or GH therapy. GH therapy increased serum lipoprotein(a) levels, but did not affect the response to diet. The serum total delta7-lathosterol/cholesterol ratio increased less during the diet period with GH therapy than during the diet period without GH. Serum 7alpha-hydroxy-4-cholesten-3-one levels tended to increase during both diet periods, but were not influenced by GH treatment. Serum plant sterol levels did not change. These results indicate that GH counteracts an increase in cholesterol synthesis induced by a high fat diet without affecting bile acid synthesis or sterol absorption. GH therapy did not have any major influence on the dietary effects on serum lipoprotein levels.
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| 4. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Discontinuation of growth hormone (GH) treatment: metabolic effects in GH-deficient and GH-sufficient adolescent patients compared with control subjects. Swedish Study Group for Growth Hormone Treatment in Children.
- 1999
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 84:12, s. 4516-24
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Tidskriftsartikel (refereegranskat)abstract
- The need for continuing GH replacement in patients with childhood-onset GH deficiency continuing into adulthood has been recognized. The metabolic consequences of discontinuing GH in adolescent patients with childhood-onset GH deficiency and short stature were examined over a period of 2 yr. Forty adolescents (aged 16-21 yr) receiving GH treatment for more than 3 yr and 16 closely matched healthy controls were studied. After a baseline visit, GH treatment was discontinued. The patients were then examined with the same protocol once a year for 2 yr. Twenty-one patients had severe GH deficiency (GHD) into adulthood, whereas 19 patients were regarded as having sufficient endogenous GH secretion (GHS). After 2 yr without GH treatment, the serum insulin-like growth factor I level was lower in GHD than in both GHS and control subjects. Both before and 2 yr after GH treatment was discontinued, serum concentrations of total cholesterol (C), low density lipoprotein C, and apolipoprotein B were higher in the GHD than in both GHS and control subjects. Serum concentrations of high density lipoprotein C decreased in the GHD group and increased in the other 2 study groups. The amount of total body and abdominal fat mass throughout the study and the increment in these masses were more marked in the GHD than in the GHS and control subjects when GH treatment was discontinued. The discontinuation of GH therapy in adolescents with severe GHD continuing into adulthood results over a period of 2 yr in the accumulation of important cardiovascular risk factors that are associated with GHD in adults.
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| 5. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Double-blind, placebo-controlled study of growth hormone treatment in elderly patients undergoing chronic hemodialysis: anabolic effect and functional improvement.
- 1999
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Ingår i: American journal of kidney diseases : the official journal of the National Kidney Foundation. - 1523-6838. ; 33:4, s. 709-17
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Tidskriftsartikel (refereegranskat)abstract
- Elderly patients with end-stage renal disease often have protein and/or caloric malnutrition that severely affects general well-being and mortality. Uremia is associated with resistance to the action of growth hormone (GH). This resistance could be of clinical importance in elderly dialysis patients. In the present study, the effects of GH treatment were assessed in elderly patients receiving chronic hemodialysis. Twenty hemodialysis patients with a mean age of 71.7 years (range, 53 to 92 years) were included on a 6-month, randomized, double-blind, placebo-controlled trial of GH treatment. The dose of GH was 66.7 microgram/kg, administered subcutaneously three times weekly immediately after each dialysis session. Body composition was measured using total-body potassium levels, computed tomography of the lower leg, and bioelectrical impedance analysis. Serum albumin concentrations and handgrip strength were also measured. GH treatment increased the serum concentration of insulin-like growth factor-I (IGF-I), IGF-I/IGF-binding protein-3 ratio, fat-free mass, and the serum concentration of albumin compared with placebo. The number of patients with serum albumin levels less than 40 g/L was reduced by a factor of three in the GH-treated group. Handgrip strength increased in response to GH treatment compared with placebo. Six months of GH treatment in elderly hemodialysis patients produced anabolic effects, with improved muscle performance. Also, the number of patients with low albumin levels was markedly reduced, indicating improved nutritional status and/or attenuated catabolism. These are all important beneficial effects for individual patient outcomes.
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| 6. |
- Svensson, Johan, 1964, et al.
(författare)
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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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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 84:6, s. 2028-33
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Tidskriftsartikel (refereegranskat)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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