| 1. |
- 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. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Serum leptin concentration and insulin sensitivity in men with abdominal obesity.
- 1998
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Ingår i: Obesity research. - 1071-7323. ; 6:6, s. 416-21
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Tidskriftsartikel (refereegranskat)abstract
- We have examined the association between generalized adiposity, abdominal adiposity, insulin sensitivity, and serum levels of leptin in a cross-sectional study of abdominally obese men.Thirty men, 48 to 66 years of age with a body mass index (BMI) of between 25 kg/m2 and 35 kg/m2 and a waist hip ratio of >0.95, were included in the study. Serum leptin concentration was measured using radioimmunoassay. Total body fat percentage was determined from total body potassium, abdominal adiposity was measured by computed tomography, and the glucose disposal rate (GDR) was measured during an euglycemic, hyperinsulinemic glucose clamp.Significant correlations were found between serum leptin concentration and BMI, percentage body fat, abdominal subcutaneous adipose tissue, serum insulin, GDR, and 24-hour urinary-free cortisol. In a multiple regression analysis, it was shown that abdominal subcutaneous adipose tissue, GDR, and BMI explained 72% of the variability of serum leptin concentration. GDR demonstrated an independent inverse correlation with serum leptin concentration.In abdominally obese men with insulin resistance, it was demonstrated that most of the individual variability in serum leptin concentration was explained by the amount of subcutaneous abdominal adipose tissue, insulin sensitivity, and BMI.
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| 3. |
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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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Effects of 1 year of growth hormone therapy on serum lipoprotein levels in growth hormone-deficient adults. Influence of gender and Apo(a) and ApoE phenotypes.
- 1995
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Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1079-5642. ; 15:12, s. 2142-50
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the influence of gender and apoE and apo(a) phenotypes as well as the effect of the metabolic effects of growth hormone (GH) on the effect of GH therapy on serum lipoprotein concentrations in GH-deficient (GHD) adults. Forty-four consecutive patients, 30 men and 14 women aged 46.5 (range, 19 to 76) years with GHD due mainly to pituitary tumors, were treated with recombinant human GH for 12 months. Serum concentrations of lipoproteins, insulin, thyroxine, and insulin-like growth factor-I were determined, body composition was assessed by bioelectrical impedance, and apo(a) and apoE phenotypes were analyzed. Lipoprotein(a) [Lp(a)] concentrations in the GHD subjects were compared with a gender- and apo(a) phenotype-matched control group. After 12 months of GH treatment, the total cholesterol, LDL cholesterol, and apoB concentrations decreased, the HDL cholesterol and apoE concentrations increased, and the apoA-I and triglyceride concentrations were unchanged. Before treatment, the Lp(a) concentration was similar to that in the control group. However, after 12 months of treatment, the Lp(a) concentration had increased by 44% and 101% above baseline and the control group, respectively. Men and women responded differently to GH, with a more marked increase in Lp(a) concentration and fat-free mass and a more pronounced decrease in body-fat mass in men. Apo(a) phenotypes had no major influence on the effect of GH therapy. The only significant difference between apoE phenotypes was a higher baseline Lp(a) concentration among apoE4 heterozygotes.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 6. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Growth hormone and the acquisition of bone mass.
- 1997
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Ingår i: Hormone research. - 0301-0163. ; 48 Suppl 5, s. 72-7
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Forskningsöversikt (refereegranskat)abstract
- Bone remodelling is a continuous, closely coupled process of bone resorption followed by bone formation. This process is regulated by factors and hormones which include GH, IGF-I and gonadal steroids. GH deficiency in childhood results in short stature and delayed bone maturation and a reduced peak bone mass might account for reduced BMC and BMD. Possible pathophysiological mechanisms for reduced bone mass in both childhood- and adult-onset GH deficiency are discussed. GH treatment effects on bone metabolism include increased remodelling, with increases in BMC, BMD and bone area. Increases in BMC and BMD are delayed while these changes are incorporated into the skeleton. BMC increases to a greater extent than BMD. At a cellular level, GH and IGF-I have direct and indirect effects on osteoblast and osteoclast precursors and fully differentiated cells. Osteoblasts possess both oestrogen and androgen receptors and bone loss accelerates with the loss of gonadal function. There are gender differences in GH effects on bone. BMD is related to fracture risk in the hip and lumbar spine in women. GH treatment might decrease fracture risk at a level comparable to oestrogen or bisphosphonate treatment. Patients with the lowest BMD prior to treatment derive the greatest benefit from GH therapy.
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| 7. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Long-term cardiovascular effects of growth hormone treatment in GH-deficient adults. Preliminary data in a small group of patients.
- 1996
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Ingår i: Clinical endocrinology. - 0300-0664. ; 45:3, s. 305-14
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Tidskriftsartikel (refereegranskat)abstract
- The long-term cardiovascular effects of GH administration in adults are of major clinical importance, given the increasing use of such treatment. We have evaluated long-term cardiovascular effects of recombinant human GH (rhGH) substitution in GH deficient men.S.c. rhGH 0.5 U/kg/week or placebo was administered in a 6-month double-blind, cross-over study, followed (after a year without substitution) by a 42-month period of open GH substitution.We evaluated 7 GH-deficient men serially and compared the results with 21 men matched in terms of age and height.Investigations included exercise tests and Doppler-echocardiography to determine exercise capacity and cardiovascular performance.Heart rate and systolic blood pressure at rest increased with GH substitution to the level of the controls, as did diastolic blood pressure after an initial reduction. Age-adjusted exercise capacity increased during the study and we found no evidence of ischaemic heart disease on exercise ECG. Stroke volume increased with GH substitution, thereby normalizing the initially reduced cardiac index. There was no significant change in left atrial or ventricular internal dimensions, systolic function as measured by fractional shortening, or diastolic function as measured by isovolumic relaxation time and left ventricular filling (A/E ratio). However, a lower atrial emptying index than that seen among controls might indicate some diastolic disturbance and there was a definite increase in left ventricular wall thickness compared with controls (to 25.1 +/- 1.5 vs 19.7 +/- 0.4 mm, P < 0.001).We found that GH substitution in GH-deficient adults had a beneficial effect on physical performance and cardiac output. The concomitant increase in left ventricular mass index might be an effect of an excessive substitution dose.
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| 8. |
- Johansson, J O, et al.
(författare)
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Long-term treatment with growth hormone decreases plasminogen activator inhibitor-1 and tissue plasminogen activator in growth hormone-deficient adults.
- 1996
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Ingår i: Thrombosis and haemostasis. - 0340-6245. ; 76:3, s. 422-8
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Tidskriftsartikel (refereegranskat)abstract
- The syndrome of growth hormone deficiency (GHD) in adults is associated with premature atherosclerosis, increased cardiovascular mortality, abnormal lipoprotein patterns and abnormal body composition. We have previously shown that GH-deficient adults have increased concentrations of fibrinogen and plasminogen activator inhibitor (PAI-1) activity. The aim of the present investigation was to study coagulation and fibrinolysis in 17 patients with adult-onset GHD during two years of treatment with recombinant human GH (12 micrograms/kg body weight/day). The impact of the contemporary changes in metabolic variables and body composition on coagulation and fibrinolysis was studied. The patients received conventional thyroid, adrenal and gonadal hormone replacement therapy. PAI-1 activity, PAI-1 antigen and tissue plasminogen activator (t-PA) antigen levels decreased during the GH treatment period (p < 0.05). The decrease was more pronounced in patients with high pre-treatment levels of the different variables. alpha 2-antiplasmin decreased (p < 0.05), while plasminogen was unchanged during two years of GH treatment. Fibrinogen concentrations tended to decrease after two years of GH treatment (p = 0.06), while the coagulation factors VII and VIII were unchanged. von Willebrand factor demonstrated a transient decrease after 18 months of GH treatment. The coagulation inhibitor, protein C, decreased (p < 0.05), while antithrombin was unchanged. Fasting plasma insulin increased (p < 0.01), but blood glucose did not differ after two years of GH treatment. Serum high-density lipoprotein cholesterol, total cholesterol and triglycerides were unaltered. Body fat decreased during the initial GH treatment but was unaltered after two years, while lean body mass increased (p < 0.001) and the waist over hip circumference ratio tended to decrease (p = 0.06). In conclusion, PAI-1 activity, PAI-1 antigen and t-PA antigen decreased during long-term GH treatment. These changes may be a direct effect of GH itself or may be secondary to the favourable changes in body composition. It remains to be seen whether changes in these fibrinolytic variables during rhGH treatment reduces the cardiovascular risk in patients with GHD. The present results suggest that GH plays a role in the regulation of fibrinolysis.
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| 9. |
- Boguszewski, C L, et al.
(författare)
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Circulating non-22-kilodalton growth hormone isoforms in acromegalic men before and after transsphenoidal surgery.
- 1997
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 82:5, s. 1516-21
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Tidskriftsartikel (refereegranskat)abstract
- GH represents several molecular isoforms in addition to the main 22-kDa (22K) GH. There have been reports suggesting that circulating non-22K GH isoforms are increased in acromegaly, but the possible implications of such observations in the management of the disease have not been addressed. The aim of this study was to evaluate the proportion of circulating non-22K GH isoforms in acromegaly. In addition, the relationships between the amount of non-22K GH and tumor size, biochemical measurements, and body composition also were investigated. Samples with different GH levels were selected from 24-h GH profiles from 15 acromegalic men evaluated before and 1 yr after transsphenoidal surgery and from 13 healthy men. The serum non-22K GH levels, expressed as percentage of total GH concentration, were determined by the 22K GH exclusion assay, which is based on immunomagnetic extraction of 22K GH from serum and quantitation of non-22K GH using a polyclonal GH assay. The proportion of non-22K GH isoforms was fairly constant in different samples from the same patient, regardless of the GH level. However, a wide variation of values was observed among acromegalics, both before (14-51%) and after surgery (8-62%). The proportion of non-22K GH isoforms was increased in untreated patients, compared with controls (26.6 vs. 17.4%; P < 0.01), and the values correlated significantly to tumor size, mean 24-h GH concentration, serum PRL, and extracellular water. After surgery, patients not truly cured, with mean 24-h GH concentration of 1 microg/L or more, had an increased proportion of non-22K GH, compared with those with levels less than 1 microg/L (P < 0.01). In the former group, the median values were similar than those in untreated acromegalics (34 vs. 26.6%, respectively), whereas in the latter, they were comparable with those in the controls (15.2 vs. 17.4%, respectively). We conclude that acromegalics have an increased proportion of circulating non-22K GH isoforms. The values are fairly constant in different samples from an individual, regardless of GH level, but a large spectrum can be observed among patients. This variability suggests that different pituitary adenomas secrete GH isoforms in variable amounts. Our observation that a higher proportion of non-22K GH isoforms is present in patients not truly cured after surgery suggests that the evaluation of non-22K GH isoforms can be useful in the follow-up of acromegalic patients.
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| 10. |
- Svensson, J, et al.
(författare)
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Insulin-like growth factor-I in growth hormone-deficient adults: relationship to population-based normal values, body composition and insulin tolerance test.
- 1997
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Ingår i: Clinical endocrinology. - 0300-0664. ; 46:5, s. 579-86
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Tidskriftsartikel (refereegranskat)abstract
- Although an insulin tolerance test (ITT) is the most commonly used method for detecting growth hormone (GH) deficiency (GHD) in adults, measurements of serum insulin-like growth factor-I (IGF-I) may also be of value.To validate the use of serum IGF-I concentration in the diagnosis of GHD in adults.A cross-sectional study.One hundred and four patients, 60 men and 44 women, with known pituitary disease and verified GHD based on ITT.Serum IGF-I was determined by radioimmunoassay after acid-ethanol extraction. Body composition was estimated with total body potassium combined with total body water assessments.According to age- and sex-adjusted population-based references values, 51 patients had serum IGF-I concentrations below -2 SD of the predicted values and 53 had concentrations within 2 SD. Fifty-seven per cent of the patients aged 41 years (25th percentile) or below and 39% of the patients aged 57 years (75th percentile) or above had serum IGF-I concentrations below -2 SD. Women had lower mean IGF-I SD scores than men (P < 0.01). Serum IGF-I was correlated with peak GH response during ITT (r = 0.40; P < 0.001), age (r = -0.27; P < 0.01), duration of hypopituitarism (r = -0.52; P < 0.001), number of pituitary hormonal deficiencies (r = -0.35; P < 0.001), body cell mass (r = 0.30; P < 0.01) and serum insulin (r = 0.21; P < 0.05). The peak GH response during ITT correlated with spontaneous GH secretion, duration (P = -0.48; P < 0.001) and number of deficiencies (r = -0.50; P 0.001).The measurement of serum IGF-I concentrations is not suitable as a single diagnostic test for growth hormone deficiency in adults. Even as a screening test, its use appears to be limited, especially in elderly subjects. The serum level of IGF-I was influenced by several factors in addition to GH, such as age, gender, anthropodometry and serum insulin level. The peak GH response during the insulin tolerance test appears to be influenced to a lesser degree by these factors.
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