| 1. |
- Abs, Roger, et al.
(författare)
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Determinants of cardiovascular risk in 2589 hypopituitary GH-deficient adults - a KIMS database analysis.
- 2006
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 155:1, s. 79-90
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of the present study was to clarify the relationship between GH deficiency (GHD) andsome cardiovascular risk factors and to analyse the effect of GH replacement therapy in a large numberof patients over a prolonged period of time.Design: Data for analysis were retrieved from KIMS (Pfizer International Metabolic Database). Serumconcentrations of total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein(LDL)-cholesterol and triglycerides were obtained from 2589 patients at baseline and from 1206patients after 1 and 2 years of GH replacement therapy. Body mass index (BMI), waist and hip, restingblood pressure and body composition were also measured.Results: At baseline, the unfavourable effects of GHD were most obvious in the lipid profiledemonstrating elevated mean total and LDL-cholesterol, in the increased waist circumference and theelevated BMI. The cholesterol concentration, BMI and body composition were significantly adverselyaffected by a number of factors, including age, sex and the use of anti-epileptic drugs. The therapeuticeffect of GH was essentially uniform across the whole population. GH replacement reduced significantlythe mean total and LDL-cholesterol, the waist circumference and the fat mass and was maintainedduring 2 years.Conclusions: This analysis of a large number of patients confirmed that GHD adults present with anincreased cardiovascular risk. The sustained improvement of the adverse lipid profile and bodycomposition suggests that GH replacement therapy may reduce the risk of cardiovascular disease andthe premature mortality seen in hypopituitary patients with untreated GHD.
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| 2. |
- Andersson, Björn, et al.
(författare)
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Raloxifene does not affect insulin sensitivity or glycemic control in postmenopausal women with type 2 diabetes mellitus: a randomized clinical trial.
- 2002
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 87:1, s. 122-8
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the metabolic or cardiovascular effects of selective ER modulators (SERMs), such as raloxifene hydrochloride (RLX), in postmenopausal women with type 2 diabetes mellitus (DM). Therefore, the effect of RLX vs. placebo (PL) on glycemic control, insulin sensitivity, as well as effects on a number of hormone, lipid, coagulation, and safety factors were determined in 30 postmenopausal women with type 2 DM in a randomized, double blind, cross-over trial. All participants had a SHBG serum concentration below 60 nmol/liter at baseline and had stable diabetes controlled by either oral hypoglycemic agents or diet for 1 month. In the first treatment period, participants received 12 wk of either PL or RLX, followed by an 8-wk washout before the second treatment period. In the second treatment period, participants were crossed over to the other treatment. Compared with PL, RLX did not significantly affect fasting blood glucose, hemoglobin A(1c), lipids, fasting insulin, or insulin sensitivity (as measured by the euglycemic clamp technique). Compared with PL, RLX reduced fibrinogen levels by 0.77 g/liter (P < 0.001), IGF-I by 2.4 nmol/liter (P < 0.001), and free T by 0.73 pmol/liter (P = 0.038) and increased SHBG by 5.5 nmol/liter (P = 0.001) and IGF-binding protein-3 by 0.57 ng/ml (P = 0.007). Our results demonstrate that RLX does not significantly affect glycemic control and has favorable or neutral effects on selected surrogate markers of cardiovascular risk in postmenopausal women with type 2 diabetes mellitus while decreasing hyperandrogenicity in these patients.
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| 3. |
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| 5. |
- Johansson, Jan-Ove, 1955, et al.
(författare)
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Growth hormone (GH) replacement in GH-deficient adults: a crossover trial comparing the effect on metabolic control, well-being and compliance of three injections per week versus daily injections.
- 2003
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Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - 1096-6374. ; 13:6, s. 306-15
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) replacement therapy regimens in adults using daily subcutaneous (sc) injections may not be optimal with respect to carbohydrate and lipid metabolism. The aim of this study was to compare the efficacy of three times weekly injections with daily sc GH injections in terms of serum IGF-I, IGFBPs, lipoprotein levels, serum bone markers, glucose metabolism, body composition, compliance and well-being. Twenty hypopituitary men, 46-76 years, on a course of stable conventional GH replacement therapy for more than 12 months, were included in a 16-week crossover trial. During the first 8 weeks GH was administered three times per week followed by 8 weeks with daily sc injections with the same weekly dose of GH. Fasting serum samples were collected at baseline and on two consecutive days at the end of each 8-week period. Serum IGF-I and IGFBP-3 concentrations were lower both the first and second morning after the last injection during the period with three injections per week. The second morning after the last GH injection in this period the IGF-I/BP-3 ratio, plasma insulin and FFA were lower whereas IGFBP-1 was increased as compared with values obtained during the period with daily injections. Serum Lp(a) levels, body composition, fat distribution, well-being and compliance were not differently affected by the two treatment regimens. These results suggest that the same weekly dose of GH given as three injections per week reduces serum IGF-I and IGFBP-3 levels without affecting Lp(a) levels. The day-to-day variation in glucose metabolism and FFA serum levels differs considerably between the two modes of GH administration.
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| 6. |
- Leonsson, Maria, et al.
(författare)
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Intima-media thickness in cardiovascularly asymptomatic hypopituitary adults with growth hormone deficiency: relation to body mass index, gender, and other cardiovascular risk factors.
- 2002
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Ingår i: Clinical endocrinology. - 0300-0664. ; 57:6, s. 751-9
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Tidskriftsartikel (refereegranskat)abstract
- Increased cardiovascular mortality and carotid atherosclerosis have been observed in hypopituitary patients with untreated GH deficiency (GHD), but results are contradictory and relations to cardiovascular risk factors are not clear. The aim of this study was to investigate intima-media thickness (IMT) in relation to cardiovascular risk factors in adults with GHD.Cross-sectional observational study of 21 men and 13 women with GHD, but without cardiovascular disease, compared to two healthy control groups matched for age, sex and smoking habits. One control group was matched for body mass index (BMI) and the other group was nonobese.IMT of the carotid and femoral arteries, blood pressure, blood samples and anthropometric data.Patients had 12% thicker composite carotid IMT [(IMT of common carotid artery + IMT of bulb)/2] compared to nonobese controls (P = 0.022), but IMT was not different compared to BMI-matched controls. Femoral IMT did not differ between patients and controls. Patients had higher waist : hip ratio (WHR), heart rate, serum triglycerides and fasting insulin concentrations in combination with lower high-density lipoprotein (HDL) cholesterol and smaller low-density lipoprotein (LDL) peak particle size compared to both nonobese and to BMI-matched controls. This cardiovascular risk pattern was more pronounced in female patients than in male patients compared to their gender controls. Carotid IMT was related to age, serum cholesterol, LDL cholesterol and smoking in the patient group. Only age was independently related to carotid IMT in multivariate analysis.These results indicate that high BMI in GH-deficient patients contribute to their increased intima-media thickness. However, several cardiovascular risk factors are present in this patient group independent of their increased BMI, especially in women.
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| 7. |
- Svensson, Johan, et al.
(författare)
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Increased orderliness of growth hormone (GH) secretion in GH-deficient adults with low serum insulin-like growth factor I.
- 2002
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 87:6, s. 2863-9
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Tidskriftsartikel (refereegranskat)abstract
- Available studies suggest that a proportion of GH-deficient (GHD) adults maintain serum IGF-I concentrations within the age- and sex-matched normal range. The basis for this distinction is not known. In this study 24-h GH profiles (sampling every 30 min) were appraised in five GHD adults with low serum IGF-I concentrations (<2 SD of the age- and sex-matched normal range), five GHD adults with normal serum IGF-I levels (within +/-2 SD), and five healthy subjects. Serial GH concentrations, measured using a chemiluminescence assay, were analyzed by deconvolution and approximate entropy (ApEn; regularity) analyses. The apparent half-duration of GH secretory bursts was longer in both GHD groups than in the healthy controls, as determined by deconvolution analysis (P < 0.05 each). The GH burst frequency was higher, the interburst interval was shorter, and the GH burst amplitude was lower in GHD adults with normal serum IGF-I than in healthy controls (P < 0.05, P < 0.05, and P < 0.01, respectively). The percentage of total daily GH secretion that was pulsatile was also reduced in the GHD adults with normal serum IGF-I compared with the other two groups (P < 0.05 and P < 0.05, respectively). In contrast, ApEn ratios were lower in the GHD adults with low serum IGF-I than in the GHD adults with normal IGF-I and controls (P < 0.01 and P < 0.05, respectively). Serum IGF-I concentrations correlated positively with ApEn ratios in the total study population (n = 15) and in the GHD adults (n = 10). In conclusion, 24-h patterns of GH release differed in GHD adults with low vs. normal serum IGF-I concentrations. GHD adults with low IGF-I levels maintain low ApEn ratios (denoting greater relative orderliness of GH secretion), whereas GHD patients with normal IGF-I values generate a high frequency, low amplitude GH output. The foregoing contrasts point to distinct neuroendocrine features of the GH-deficient state of adults, which can be related to concurrent IGF-I production.
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