| 1. |
- 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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| 2. |
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| 3. |
- Bengtsson, B A, et al.
(författare)
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Treatment of growth hormone deficiency in adults.
- 2000
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 85:3, s. 933-42
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Tidskriftsartikel (refereegranskat)abstract
- In analogy with other hormonal replacement therapy GH treatment should be commenced with a low starting dose, independent of body weight or body surface area. Hormonal replacement should mimic the normal physiology to minimize the risk of side effects in the life-long replacement of adults. We should, therefore, consider individual responsiveness and also be aware of the difference between pattern of GH under normal condition and during s.c. administration. The safety and monitoring of GH replacement therapy in adults have been addressed in the Growth Hormone Research Society Consensus Guidelines for Diagnosis and Treatment of Adults with GH Deficiency from the Port Stephens Workshop, April 1997. Besides finding better and more accurate biochemical markers for choosing correct GH replacement dose, future research should address the long-term benefits and safety with GH replacement in adults, with special emphasize on incipient risks in terms of cardiovascular disease and of neoplasia, in particular.
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| 4. |
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| 5. |
- Boguszewski, Margaret C S, 1964, et al.
(författare)
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Low birth size and final height predict high sympathetic nerve activity in adulthood.
- 2004
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Ingår i: Journal of hypertension. - 0263-6352. ; 22:6, s. 1157-63
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Being born small for gestational age (SGA) is associated with insulin resistance, hypertension and increased cardiovascular morbidity/mortality in adulthood. Sympathetic nerve hyperactivity is a well-known risk factor for cardiovascular disease mortality and is proposed to link insulin resistance with hypertension. The objective of this study was to test the hypothesis that sympathetic nerve activity is altered in individuals born SGA. DESIGN: A cross-sectional, comparative study of 20 healthy adults (21-25 years old) born SGA (birth weight < -2SD score for healthy newborns) with normal and short stature, and 12 age, gender and body mass index matched individuals, born appropriate for gestational age (AGA) with normal stature. METHODS: Direct recordings of resting sympathetic nerve activity to the muscle vascular bed (MSA) were obtained from the peroneal nerve posterior to the fibular head. Heart rate, respiration and blood pressure were recorded during the microneurographic session. RESULTS: MSA was increased in both groups of young adults born SGA as compared to those born AGA (P < 0.05 and P < 0.005, respectively). In the combined study group MSA was inversely correlated to birth weight, length (r = -0.59, P < 0.001 and r = -0.69, P < 0.0005, respectively) and final adult height (r = -0.58; P < 0.001). CONCLUSIONS: Being born SGA and achieving a short final height is associated with increased sympathetic nerve traffic. We suggest that the increase in sympathetic nerve traffic in young adults born SGA with normal and short stature may be the link between low birth size, hypertension and cardiovascular morbidity later in life.
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| 6. |
- Fors, H, et al.
(författare)
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Currently used growth-promoting treatment of children results in normal bone mass and density. A prospective trial of discontinuing growth hormone treatment in adolescents.
- 2001
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Ingår i: Clinical endocrinology. - 0300-0664. ; 55:5, s. 617-24
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Tidskriftsartikel (refereegranskat)abstract
- The need for continued GH replacement in patients with childhood-onset GH deficiency (GHD) into adulthood has been recognized. The consequences of discontinuing GH treatment on bone mineralization in adolescent patients with GHD and short stature were examined over a period of 2 years.Forty adolescents (aged 16-21 years) treated with GH for more than 3 years and 16 closely matched healthy controls were studied. After a baseline visit, GH treatment was discontinued. The patients were then re-examined with the same protocol after 1 and 2 years. Twenty-one patients had continuing severe GHD into adulthood, while 19 patients were regarded as having sufficient endogenous GH secretion (GHS).At baseline, there were no differences between the groups in total bone mineral content (BMC) or bone mineral density (BMD). After 2 years without GH treatment, BMC increased similarly in the GHD and GHS groups. BMC of the lumbar spine (L2-L4) increased only in the GHD group. Lumbar spine BMD increased in the GHD and the GHS groups. No changes were observed in the femoral neck region. Biochemical measurements showed that carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) and bone specific alkaline phosphates (ALP) were higher in the GHD and GHS groups at baseline compared with controls. Osteocalcin, carboxy-terminal propeptide of type I procollagen (PICP), ICTP and ALP decreased during the 2 years off treatment in both the GHD and GHS groups. PICP was also lower after 2 years in the GHD group compared with both the GHS group and controls.After discontinuation of GH therapy in adolescents at or near final height, there was a continued increase in BMC and BMD both for adolescents with growth hormone deficiency and for those classified as growth hormone sufficient. These groups did not differ from controls at baseline or after 2 years. In the growth hormone deficiency group, biochemical markers for bone formation decreased to levels below those in the growth hormone sufficient and healthy control groups. Although the number of patients and controls in this study were small, the results indicate that the present treatment of Swedish GH-deficient children to final height results in normal BMD.
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| 7. |
- Franco, C, et al.
(författare)
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Visceral obesity and the role of the somatotropic axis in the development of metabolic complications.
- 2001
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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. ; 11 Suppl A, s. S97-102
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Forskningsöversikt (refereegranskat)abstract
- It is well recognized that aberrant fat localization such as visceral obesity rather than total body fat mass is a major risk factor for cardiovascular disease and type 2 diabetes mellitus. During recent decades, several studies have described a range of metabolic disturbances associated with abdominal obesity, including glucose intolerance, hyperinsulinaemia, insulin resistance, hypertension and dyslipoproteinaemia, now widely known as the metabolic syndrome. Several abnormalities in the hypothalamic-pituitary axis have been described associated with visceral obesity, suggesting a central neuroendocrine dysregulation including increased cortisol concentration and impaired gonadotropin and growth hormone (GH) secretion. Some steps in the chain of events in this theory still remain unclear, however, although these findings have introduced new therapeutic possibilities. These include therapy with sex steroids in both viscerally obese men and women, and several attempts to use GH to treat the endocrine abnormalities present in visceral obesity. The results of these studies are promising, but the therapies are still not recommended for general use.
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| 8. |
- Gibney, James, et al.
(författare)
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Long-term monitoring of insulin-like growth factor I in adult growth hormone deficiency: a critical appraisal.
- 2004
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Ingår i: Hormone research. - : S. Karger AG. - 0301-0163. ; 62 Suppl 1, s. 66-72
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Tidskriftsartikel (refereegranskat)abstract
- Serum insulin-like growth factor I (IGF-I) levels predominantly reflect the hepatic effect of growth hormone (GH). Compared with serum GH levels, which reflect pulsatile GH secretion, serum IGF-I levels exhibit no major diurnal variation and thus provide a better estimate of integrated GH secretion in an individual patient. Measurement of serum IGF-I levels allows reliable identification of states of GH excess. In contrast, in a large proportion of adults with severe GH deficiency, serum IGF-I levels are within the normal range. Serum IGF-I levels increase markedly in response to GH administration and are often used as a surrogate variable for overall responsiveness to such treatment. Current data, however, suggest a poor relationship between changes in or levels of IGF-I and efficacy variables such as body composition, muscle function and well-being. The use of serum IGF-I as a guide during dose titration in the initial phase of treatment and during long-term monitoring of GH replacement therapy in adults, and its use as a safety marker or predictor of future morbidity and mortality are discussed here.
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| 9. |
- Gibney, James, et al.
(författare)
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Safety of growth hormone replacement therapy in adults.
- 2004
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Ingår i: Expert opinion on drug safety. - 1744-764X. ; 3:4, s. 305-16
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) is a powerful metabolic hormone that regulates fuel homeostasis through its protein anabolic and lipolytic actions. The introduction of recombinant human GH has expanded the narrow indication of treating children with severe GH deficiency (GHD) to include a broader target population of children with growth retardation and short stature and adults with hypopituitarism and severe GHD. Furthermore, because children continue to receive GH replacement therapy into adult life, the duration of treatment exposure has increased and the safety of long-term GH treatment has become increasingly important. This is of particular concern given that GH-deficient children and adults may be more vulnerable to the mitogenic stimuli of GH and insulin-like growth factor-1, both because of the underlying cause of GHD and also because of previous treatment such as radiotherapy and chemotherapy. This review focuses on the safety of treating adults with severe GHD, with specific emphasis on dose regimens, carbohydrate metabolism, neoplasia, and morbidity and mortality. Available experience from long-term replacement therapy, studies using supraphysiological doses of GH in adults and lessons learned from patients with acromegaly who have high endogenous GH levels over many years, is considered.
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| 10. |
- Gil Berglund, E, et al.
(författare)
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Growth hormone replacement therapy induces codeine clearance.
- 2002
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Ingår i: European journal of clinical investigation. - : Wiley. - 0014-2972. ; 32:7, s. 507-12
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Tidskriftsartikel (refereegranskat)abstract
- The increasing clinical use of growth hormone (GH) has raised questions about other than growth-related metabolic effects of this treatment. GH regulates the expression of several hepatic drug metabolising enzymes in the rat, but it is not known whether GH treatment alters the expression of such liver enzymes in man. We have investigated the effects of GH on codeine clearance and two enzymes of the cytochrome P450 (CYP) family, CYP3A and CYP2D6, and UDP-glucuronosyl transferase (UDPGT). These enzymes have a superior importance in hepatic biotransformation of numerous drugs. In addition, CYP3A and UDPGT are catalysts of many reactions with endobiotics such as steroid hormones.We used codeine as a probe drug for assessment of the enzyme activities. Codeine was administered as a single-dose prior to, and after 3 months of GH substitution in GH-deficient patients. Total clearance, and clearance along each of the three primary metabolic pathways of codeine, was assessed.Three months of GH substitution increased the total clearance of codeine (21%, P < 0.01) and clearance catalysed by UDPGT significantly (31%, P < 0.05). The treatment tended to increase the clearance via the CYP3A pathway (83%, P = 0.05).The effects of GH replacement therapy on drug metabolism may have clinical implications when combined with drugs that are substrates of UDPGT and CYP3A. Effects on steroid hormone metabolism with endocrine consequences can not be ruled out.
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