
自引率: 4%
被引量: 14002
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审稿周期: 1.15
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国人发稿量: 23
投稿须知/期刊简介:
Clinical Endocrinology publishes papers and reviews which focus on the practical aspects of clinical endocrinology, such as protocols for investigation of endocrine disorders, imaging in endocrinology and the clinical application of molecular endocrinology. It also features reviews, current therapy papers and cases of the month. Clinical Endocrinology is essential reading not only for those engaged in endocrinological research but also for those involved primarily in clinical practice.
期刊描述简介:
Clinical Endocrinology publishes papers and reviews which focus on the practical aspects of clinical endocrinology, such as protocols for investigation of endocrine disorders, imaging in endocrinology and the clinical application of molecular endocrinology. It also features reviews, current therapy papers and cases of the month. Clinical Endocrinology is essential reading not only for those engaged in endocrinological research but also for those involved primarily in clinical practice.
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Short-term suppression of elevated growth hormone concentrations following insulin-like growth factor 1 administration in young adults with type 1 diabetes does not alter glomerular filtration or albumin excretion rates.
Young adults with type 1 diabetes mellitus (T1DM) have increased glomerular filtration rate (GFR), which may mediate progressive renal disease and microalbuminuria. This may be secondary to low concentrations of insulin-like growth factor (IGF)-I and GH hypersecretion. We tested the hypothesis that restoration of circulating IGF-I concentrations in young adults with T1DM might suppress GH secretion, GFR and urinary albumin excretion. In a randomized double blind crossover study six young adults with T1DM (three men, 19-24 years) received 7 days treatment with rhIGF-I/insulin-like growth factor binding protein (IGFBP)-3 complex (SomatoKine) 0.4 mg/kg/day and placebo. Subjects underwent overnight insulin infusion for euglycaemia, followed by determination of GFR and albumin excretion rate. Following IGF-I/IGFBP-3 complex, overnight insulin requirements (0.15 vs placebo 0.21 mU/kg/min, P < 0.04), plasma insulin (77 vs placebo 152 pmol/l, P < 0.01) and mean overnight GH (2.6 vs placebo 4.8 mU/l, P < 0.04) fell. IGF-I (492 vs placebo 218 ng/ml, P < 0.01) and IGFBP-3 (4.5 vs placebo 3.9 microg/ml, P < 0.05) increased. GFR did not change (145.5 (23.9) ml/min/1.73 m(2) post-IGF-I/IGFBP-3 complex vs 152.2 (19.8) post placebo). Albumin excretion rate did not change 9.5 (5.5-16.6)mg/24 h pre- vs 11.5 (9.9-20.2) post-IGF-I/IGFBP-3 complex and 10.7 (8.1-21.2) pre- vs 11.5 (8.7-29.9) post placebo. Plasma creatinine levels were lower following IGF-I/IGFBP-3 complex (mean +/- SD, 56.2 +/- 16.8 micromol/l) vs placebo (61.5, 45.0, P < 0.02). Seven days treatment with IGF-I/IGFBP-3 complex enhanced overnight insulin sensitivity and reduced GH levels, but there was no effect on glomerular hyperfiltration or albumin excretion rates.
被引量:- 发表:2006
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Increasing urine albumin excretion is associated with growth hormone hypersecretion and reduced clearance of insulin in adolescents and young adults with type 1 diabetes: the Oxford Regional Prospective Study.
We previously described lower insulin-like growth factor I (IGF-I) levels in association with increased microalbuminuria (MA) risk in type 1 diabetic subjects followed from diabetes diagnosis through puberty into adulthood. By inference lower IGF-I levels may be associated with higher GH levels and changes in insulin sensitivity. To test this hypothesis, microalbuminuric subjects (MA+, n = 14) from the same cohort had overnight GH levels measured during euglycaemia (5 mmol/l, 01:00-07:30 h) maintained by a variable rate insulin infusion followed by a 2-step hyperinsulinaemic, euglycaemic clamp study using [6.6 2H2] glucose, and were compared to MA- controls (MA-, n = 14), matched for age (median 19.3 years, range 15.8-30.5), sex, duration of diabetes (11.1 years, range 5.1-16.4). In MA+ cases GH levels, measured by the Pulsar programme, were higher (baseline; 1.8 +/- 1.4 vs. 0.7 +/- 0.5 ng/ml, P = 0.02, mean; 3.8 +/- 1.3 vs. 2.6 +/- 1.6 ng/ml, P = 0.03, maximum; 16.7 +/- 7.0 vs. 12.3 +/- 5.4, P = 0.02), despite similar HbA1(c) levels (9.8%vs. 9.6%, P = 0.6) and body or truncal fat mass. Fourier transform revealed increased GH pulse amplitude at all periodicities and overnight insulin clearance was reduced (11.7 +/- 6.9 vs. 20.1 +/- 6.5 ml/kg/min, P < 0.02). In multiple regression analysis, urine albumin excretion was associated with higher GH levels and reduced insulin clearance, independent of HbA1(c) and body composition. In female cases (n = 9), dextrose requirements were reduced during the first step of the euglycaemic clamp (1.7 +/- 0.8 vs. 2.7 +/- 1.4, P < 0.05) but no such differences existed in males or in the rate of glucose production or disposal. The development of MA during puberty and young adulthood is associated with higher GH levels and abnormalities in insulin metabolism, particularly in females. These data extend support for our previous findings indicating a role for the GH/IGF-I axis in the pathogenesis of MA.
被引量:6 发表:2005
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Growth hormone, IGF-I and its binding proteins (IGFBP-1 and -3) in adult uraemic patients undergoing peritoneal dialysis and haemodialysis.
The GH/IGF axis is altered in chronic renal failure (CRF). CRF patients usually show normal or high serum concentrations of GH and IGF-I, whereas all IGF binding proteins (IGFBP-1 to -6), except IGFBP-5, considerably increase with declining renal function. The aims of the present study were to quantify serum concentrations of GH, IGF-I, IGFBP-1 and IGFBP-3 in a group of patients with CRF, and determine whether there were differences according to the type of dialysis, that is, peritoneal dialysis (PD) and haemodialysis (HD). A cross-sectional study in the setting of a dialysis unit of a general hospital. We studied 108 dialysis patients treated by PD (n = 54, 32 males and 22 females, mean age 61.0 +/- 1.4 years) or HD (n = 54, 31 males and 23 females, age 62.6 +/- 1.5 years). A group of 42 healthy subjects of similar age, sex and body mass index (BMI) served as the control group. Baseline serum concentrations of GH, insulin, IGF-I, IGFBP-1 and IGFBP-3 were measured in all patients and control subjects. Fasting serum concentrations of IGF-I and its binding proteins (IGFBP-1 and IGFBP-3) were significantly higher in dialysis patients than in subjects with normal renal function. IGF-I (248.9 +/- 23.4 vs. 205.5 +/- 15.5 micro g/l, NS), IGFBP-3 (5.6 +/- 0.4 vs. 5.5 +/- 0.2 mg/l, NS) and IGFBP-1 (36.1 +/- 5.9 vs. 44.1 +/- 6.5 micro g/l, NS) concentrations were similar in both groups of dialysis (PD vs. HD) patients. However, GH (2.3 +/- 0.3 vs. 1.1 +/- 0.1 micro g/l, P < 0.001) and insulin (40.4 +/- 4.5 vs. 30.1 +/- 3.1 micro U/ml, P < 0.05) levels were significantly higher in the PD group than in the HD group. Both groups of dialysis patients showed significantly higher levels of insulin than healthy subjects (14.7 +/- 1.9 micro U/ml, P < 0.0001 and P < 0.01 for PD and HD, respectively). In both groups of dialysis patients, IGF-I correlated inversely with IGFBP-1 (PD group r = -0.46, P = 0.0006; HD group r = -0.57, P = 0.0001) and directly with IGFBP-3 (PD group r = 0.44, P = 0.001; HD group r = 0.73, P = 0.001). No correlation between insulin and IGFBP-1 was found in any of the groups studied. These findings demonstrate that adult dialysis patients have elevated IGF-I, IGFBP-1 and IGFBP-3 serum concentrations compared with subjects with normal renal function. Only GH and insulin show statistically significant differences in relation to type of dialysis. Finally, the negative correlation between IGF-I and IGFBP-1 and the positive correlation between IGF-I and IGFBP-3 are maintained in both groups of adult dialysis patients.
被引量:- 发表:2004
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Dehydroepiandrosterone supplementation in women with adrenal failure: impact on twenty-four hour GH secretion and IGF-related parameters.
In women, GH secretion is strongly influenced by oestrogen status, whereas the role of androgens is unclear. We, therefore, examined GH secretory dynamics during low vs. normalized androgen levels in women with adrenal failure. Ten females with adrenal failure (AF), mean age of 42 years (range 22-54 years). The effects of 8 days of oral dehydroepiandrosterone (DHEA; 50 mg/day) were studied in a double-blind placebo-controlled, cross-over design. A control group of healthy women was studied once without any treatment. Before and after each treatment period, blood was sampled for measurement of androgens, IGF-I, IGFBP-3 and GHBP. A 24-h GH profile with measurements every 20 min was performed at the end of each period. DHEA supplementation normalized the mean circulating levels of testosterone and androgen precursors. The secretory pattern of GH was unaltered during DHEA [placebo vs. DHEA; half-life 22.83 +/- 1.24 vs. 21.45 +/- 1.19 (min), P = 0.429; pulse frequency 9.9 +/- 0.7 vs. 10.5 +/- 0.5 (/24 h), P = 0.502; total production rate 62.27 +/- 13.44 vs. 52.61 +/- 7.06 (microg/l/day), P = 0.317]. Subgroup analysis, however, indicated that DHEA treatment increased GH secretion in patients not receiving oestrogen (n = 5), whereas the opposite was observed among patients receiving exogenous oestrogen derivatives (n = 5). Compared to the control group (CON), GH half-life was longer in AF (half-life CON: 16.48 +/- 0.91, P = 0.001). The additional features of GH secretion were similar. Unexpectedly, the levels of IGF-I, IGFBP-3 and GHBP were elevated in the patients as compared to controls, without significant effects of DHEA [AF vs. CON. IGF-I: 186 +/- 20 vs. 144 +/- 7 (microg/l), P = 0.04; IGFBP-3: 5196 +/- 224 vs. 3687 +/- 212 (microg/l), P = 0.001; GHBP: 2.27 +/- 0.25 vs. 1.41 +/- 0.13 (nmol/l), P = 0.002]. (1) Short-term DHEA administration in women with adrenal failure normalizes the circulating levels of androgens without uniformly affecting the GH-IGF axis; (2) The observation that exogenous oestradiol may mask a stimulatory effect of DHEA on GH secretion merits future investigation.
被引量:- 发表:2004
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Carbohydrate metabolism during long-term growth hormone treatment in children with short stature born small for gestational age.
OBJECTIVE:To assess possible side-effects of long-term continuous growth hormone (GH) treatment on carbohydrate (CH) metabolism in children with short stature born small for gestational age. DESIGN:In a prospective, randomised double-blind, dose-response multicentre trial, the effect of GH treatment on CH metabolism was evaluated, comparing two GH dosages [3 vs. 6 IU/(m(2) body surface.day)]. PATIENTS:Seventy-eight children with short stature (height SD-score < - 1.88) born small for gestational age (birth length SD-score < - 1.88) being all prepubertal with a mean (SD) chronological age of 7.3 (2.2) years before start of treatment. MEASUREMENTS:Glucose and insulin concentrations during oral glucose tolerance tests (OGTTs) and glycosylated haemoglobin (HbA(1c)) were measured before and during 6 years of GH treatment. RESULTS:Before treatment, the glucose response to oral glucose after 120 min was in six of the 78 children (8%) above 7.8 mmol/l but below 11.1 mmol/l, indicating impaired glucose tolerance (IGT), whereas after 6 years of GH treatment, IGT was found in 4% of the children. None of the children developed diabetes mellitus. Mean fasting glucose levels had increased significantly by 0.5 mmol/l after 1 year of GH treatment, without a further increase thereafter. The 2-h area under the curve adjusted for fasting levels (AUCab) for glucose and the HbA(1c) levels were lower after 6 years of GH treatment compared to baseline. During GH treatment, all HbA(1c) levels were in the normal range. In contrast to the effects on glucose levels, GH treatment induced considerably higher fasting insulin levels and glucose-stimulated insulin levels. The increase in AUCab for insulin occurred particularly during the first year of treatment, whereas the fasting insulin levels showed a further increase from one to six years. As a result, the 30- and 120-min ratios of insulin to glucose were higher during GH treatment compared to the start of treatment. The children who remained prepubertal during the entire study period showed similar patterns in glucose and insulin levels compared to the children who entered puberty. None of the observed changes were different between the GH dosage groups. CONCLUSIONS:Continuous GH treatment during 6 years in children with short stature born small for gestational age has no adverse effects on glucose levels, even with dosages up to 6 IU/(m(2) d). However, as has been reported in other patient groups, GH treatment induces higher fasting insulin levels and glucose-stimulated insulin levels, indicating relative insulin resistance. Since the consequences of long-term hyperinsulinism during childhood are unknown, careful follow-up of these GH-treated children born small for gestational age is required.
被引量:- 发表:2001