The effects of recombinant insulin-like growth factor I administration on growth hormone levels and insulin requirements in adolescents with Type 1 (insulin-dependent) diabetes mellitus

Summary Type 1 (insulin-dependent) diabetes mellitus in adolescence is associated with reduced levels of insulin-like growth factor I, elevated growth hormone concentrations and insulin resistance. In order to determine whether restoring insulin-like growth factor I levels to normal might lead to a reduction in growth hormone levels and insulin requirements, we undertook a double-blind placebo controlled study of a single s. c. dose of recombinant insulin-like growth factor I (40 g/kg body weight) in nine late pubertal subjects with Type 1 diabetes. After administration of placebo or insulin-like growth factor I at 18.00 hours, a variable rate insulin infusion was used to maintain euglycaemia overnight. Plasma insulin-like growth factor I, growth hormone, free insulin, and intermediate metabolite concentrations were monitored throughout the study. Recombinant insulin-like growth factor I led to a rise in plasma concentrations which reached a peak at 5.5 h (413.1±28.2 ng/ml, mean±SEM). Mean growth hormone levels between 20.00 and 08.00 hours were significantly reduced after recombinant insulin-like growth factor I (19.4±4.0 compared with 33.6±5.8 mU/l; p=0.01), as were the insulin requirements for euglycaemia (0.25±0.02 compared with 0.31±0.04 mU · kg^–1 · min^–1; p=0.03). Plasma free insulin levels were lower after recombinant insulin-like growth factor I administration (31.9±2.7 compared with 67.9±16.0 mU/l; p=0.001) but no significant differences in ketone or lactate levels were detected. Recombinant insulin-like growth factor I in a s. c. dose of 40 g/kg body weight leads to a significant reduction in overnight growth hormone levels and insulin requirements in adolescents with Type 1 diabetes.     

Elevated plasma insulin-like growth factor binding protein-1 levels in Type 1 (insulin-dependent) diabetic patients with peripheral neuropathy

Summary Previous studies have suggested that nerve regeneration may be defective in patients with diabetic polyneuropathy. Since insulin-like growth factor I (IGF-I) has been shown to stimulate nerve regeneration, and IGF binding protein-1 is acutely regulated by plasma insulin we have investigated the relationships between plasma IGF-I, IGFBP-1, glucose and insulin in Type 1 (insulin-dependent) diabetic patients with peripheral polyneuropathy. Plasma samples were taken at hourly intervals over an 11-h period (08.00–19.00 hours) in order to characterise secretory profiles for 15 Type 1 diabetic patients (eight neuropathic and seven non-neuropathic) and eight non-diabetic control subjects. In the non-diabetic subjects, mean plasma IGF-I levels were stable throughout the 11-h period with a range of 97 g/l–169 g/l. In contrast, mean plasma IGFBP-1 levels declined steadily from a high level of 1.99 g/l at 08.00 hours to approximately one half (0.86 g/l) at 15.00 hours. Comparison of areas under the curves revealed significant negative correlations between IGFBP-1 and glucose (–0.88, p=0.01), IGFBP-1 and insulin (–0.75, p=0.016), and IGFBP-1 and IGF-I (–0.68, p=0.03). A significant positive correlation was found between insulin and IGF-I (+ 0.89, p=0.001). The diabetic patients had markedly elevated plasma IGFBP-1 levels (area under curve, p=0.01) and lower plasma IGF-I levels (p=0.033) even though these patients were hyperinsulinaemic throughout the study period. The neuropathic diabetic patients had grossly elevated IGFBP-1 levels (–X=40 g/l at 08.00 hours) which were significantly higher (area under curve, p=0.05) than in patients without neuropathy (¯X=15 g/l at 08.00 hours). However, plasma levels of insulin and IGF-I in neuropathic and non-neuropathic subjects were similar, suggesting that the regulation of IGFBP-1 is more resistant to insulin in the neuropathic patients. In contrast to the non-diabetic subjects comparison of area under curve values revealed no positive correlation between insulin and IGF-I or negative correlations between IGF-I and IGFBP-1, and IGFBP-1 and glucose. We conclude that in Type 1 diabetes the relationships between plasma glucose, insulin, IGF-I and IGFBP-1 are clearly abnormal, and these abnormalities are more pronounced in patients with peripheral neuropathy.     

2型糖尿病患者血清GH、IGF-I浓度改变及相关因素的研究

目的通过放免测定方法了解2型DM患者GH／IGF-I轴的改变与1型DM患者有何不同。方法对19例1型DM和98例2型DM患者的血清基础GH及IGF-I浓度进行测定。将2型DM患者血清IGF-I浓度与其各项临床及生化指标进行多元相关回归分析。结果1型DM患者GH水平(2.53士0.51μg/L)明显高于对照组(1.36士0.27μg／L,P＜0.05);IGF-I水平(191.5±14.1μg/L)则显著低于对照组(266.3士17.7μg/L,P＜0.01)。2型DM患者GH(0.60±0.11μg/L)水平与对照组(0.74士0.07μg/L)无显著性差异(P＞0.05),IGF-I(126.1士3.2μg/L)水平较正常(153.4士8.3μg/L)明显降低(P＜0.05)。2型DM患者血清IGF-I浓度与年龄(P＜0.05)及HbA1c(P＜0.05)呈负相关,与平均动脉压(P＜0.05)和空腹胰岛素(P＜0.01)呈正相关。结论2型DM患者血清基础GH和IGF-I改变与1型DM患者有所不同,这种异常改变可能与持续高血糖水平有关。     

Changes in mRNA expression of grouper (Epinephelus coioides) growth hormone and insulin-like growth factor I in response to nutritional status

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are key links to nutritional condition and growth regulation in teleost. To understand the endocrine mechanism of growth regulation in grouper, we cloned the cDNAs for grouper GH and IGF-I and examined their mRNA expression during different nutritional status. Grouper GH cDNA is 936 base pairs (bp) long excluding the poly-A tail. It contained untranslated regions of 85 and 231bp in the 5'- and 3'-ends, respectively. It has an open reading frame of 612bp coding for a signal peptide of 17 amino acids (aa) and a mature hormone of 187aa residues. Based on the aa sequence of the mature hormone, grouper GH shows higher sequence identity (>76%) to GHs of perciforms than to GHs of cyprinids and salmonids (53-69%). Grouper preproIGF-I cDNA consisted of 558bp, which codes for 186aa. This is composed of 44aa for the signal peptide, 68aa for the mature peptide comprising B, C, A, and D domains, and 74aa for the E domain. Mature grouper IGF-I shows very high sequence identity to IGF-I of teleost fishes (84-97%) compared to advanced groups of vertebrates such as chicken, pig, and human (80%). Using DNA primers specific for grouper GH and IGF-I, the changes in mRNA levels of pituitary GH and hepatic IGF-I in response to starvation and refeeding were examined by a semi-quantitative RT-PCR. Significant elevation of GH mRNA level was observed after 2 weeks of food deprivation, and increased further after 3 and 4 weeks of starvation. GH mRNA level in fed-controls did not change significantly during the same period. Hepatic IGF-I mRNA level decreased significantly starting after 1 week of starvation until the 4th week. There was no significant change in IGF-I mRNA levels in fed-controls. One week of refeeding can restore the GH and IGF-I mRNA back to its normal levels. Deprivation of food for 1-4 weeks also resulted in cessation of growth and decrease in condition factor.     

Effect of growth hormone releasing hormone on growth hormone secretion in Type 2 (non-insulin-dependent) diabetes mellitus

Summary Growth hormone levels following an intravenous bolus injection of 1 g/kg body weight growth hormone releasing hormone were measured in 21 non-obese and 26 obese patients with Type 2 (non-insulin-dependent) diabetes mellitus and in 13 control subjects. Growth hormone responses in non-obese Type 2 diabetic patients were not statistically different from control subjects. However, obese Type 2 diabetic patients had significantly decreased growth hormone responses to growth hormone releasing hormone when compared with non-obese Type 2 diabetic patients (p<0.02). In 9 Type 2 diabetic patients growth hormone releasing hormone tests were performed both during hyperglycaemia and after metabolic improvement by insulin treatment. Growth hormone responses before and after insulin treatment were not statistically different. Our data demonstrate that (1) growth hormone responses to growth hormone releasing hormone in non-obese Type 2 diabetic patients do not differ significantly from control subjects; (2) obesity blunts growth hormone responses to growth hormone releasing hormone in Type 2 diabetes mellitus; and (3) growth hormone responses following growth hormone releasing hormone administration in Type 2 diabetes mellitus are not influenced by the state of metabolic control.     

Regulation of insulin-like growth factor binding protein-1 (IGFBP-1) in insulin-dependent diabetes mellitus

The aim of the present study was to characterize the effect of 44 h of hyperglycaemia on diurnal levels of insulin-like growth factor binding protein-1 (IGFBP-1), insulin-like growth factor-1 (IGF-1), growth hormone (GH) and glucagon in 7 well-controlled subjects with insulin-dependent diabetes mellitus (IDDM). Hyperglycaemia (15 mmol/l) was induced by a glucose infusion, while the degree of insulinisation was similar to that of a corresponding period with near normoglycaemia (6.9 mmol/l). Hyperglycaemia for 44 h did not alter the normal diurnal IGFBP-1 levels when the degree of insulinisation was unchanged. The diurnal secretion pattern of IGFBP-1 was preserved in both genders and without any difference between the control and hyperglycaemic periods. However, the IGFBP-1 levels were increased in these IDDM subjects despite a peripheral hyperinsulinemia. An inverse correlation was found between IGFBP-1 and peripheral insulin levels both during periods of rapid changes in IGFBP-1 and insulin concentrations (i.e. morning hours) as well as during the total 24-h sampling period. Total IGF-1 levels were low, but no further decrease was seen after 24 h of hyperglycaemia in the presence of unchanged insulin levels. In conclusion, the present study clearly shows that the increased IGFBP-1 level seen during poor metabolic control in IDDM is not caused by hyperglycaemia. Glucose levels per se do not influence either total IGF-1 or IGFBP-1 concentrations in well-insulinised diabetic patients.     

Effects of recombinant human insulin-like growth factor I and insulin on counterregulation during acute plasma glucose decrements in normal and Type 2 (non-insulin-dependent) diabetic subjects

Summary Insulin-like growth factor I (65 μg/kg) or insulin (0.1 IU/kg) were injected i.v. on two separate occasions in random order in normal and in Type 2 (non-insulin-dependent) diabetic subjects. Insulin-like growth factor I and insulin injection resulted in identical decrements of plasma glucose concentrations after 30 min but in delayed recovery after insulin-like growth factor I as compared to insulin in both groups (p<0.05 insulin-like growth factor I vs insulin). Counterregulatory increases in plasma glucagon, adrenaline, cortisol and growth hormone concentrations after hypoglycaemia (1.9±0.2 mmol/l) in normal subjects were blunted after insulin-like growth factor I administration compared to insulin (p<0.05). Plasma glucose in Type 2 diabetic subjects did not reach hypoglycaemic levels but the acute glucose decrease to 4.5±0.8 mmol/l was associated with significantly lower responses of plasma glucagon and adrenaline but higher cortisol levels after insulin-like growth factor I compared to insulin (p<0.003). Plasma concentrations of non-esterified fatty acids and leucine decreased similarly after insulin-like growth factor I and insulin in both groups. The present results demonstrate that insulin-like growth factor I is capable of mimicking the acute effects of insulin on metabolic substrates (plasma glucose, non-esterified fatty acids, leucine). The decreases of plasma glucose were similar after both peptides in normal and in diabetic subjects who were presumably insulin resistant. Counterregulatory hormone responses to plasma glucose decrements differed, however, between insulin-like growth factor I and insulin and in the diabetic and the control subjects. After insulin-like growth factor I the increases in adrenaline, cortisol, growth hormone and glucagon were blunted in normal subjects despite slightly lower plasma glucose concentrations.     

Insulin-like growth factor I levels during growth hormone (GH) replacement in GH-deficient adults: a gender difference

To evaluate the variation of serum IGF-1 levels during GH replacement and observe gender differences, 29 adults with GH deficiency (mean age 42.5 ± 10.1 year), were studied. Serum IGF-1 was assessed every 4 weeks during the titration period and afterwards every 3 months of GH therapy. At baseline 77.7% of women and 45.4% of men had serum baseline IGF-1 levels below the lower limit of normal age-related reference range. The time to reach the maintenance dose was lower in men than women (p < 0.05). There was an increase in IGF-1 levels after one year of GH therapy, significant only in men (p < 0.01). IGF-1 concentrations were higher in men than women (p < 0.05), at the 12th and 18th months of GH therapy. GH dose was reduced by 25% in men (p < 0.01). At the end of the study the mean GH dose was lower in men than in women (p < 0.05). The factor responsible for these findings is not known, however a possible role of androgens has been suggested.     

Effect of intraperitoneal insulin delivery on growth hormone binding protein,insulin-like growth factor (IGF)-I,and IGF-binding protein-3 in IDDM

Summary Low plasma insulin-like growth factor (IGF)-I despite high circulating growth hormone (GH) in insulin-dependent diabetes mellitus (IDDM) indicate a hepatic GH resistance. This state may be reflected by the reduction of the circulating GH binding protein (GHBP), corresponding to the extracellular domain of the GH receptor, and the reduction of insulin-like growth factor binding protein (IGFBP)-3, major IGF-I binding protein, upregulated by GH. We carried out two studies. In the first, plasma GHBP activity was compared in patients with IDDM on continuous subcutaneous insulin infusion (CSII) or on conventional therapy and in healthy subjects. In the second study, the 18 patients on CSII at baseline were then treated by continuous intraperitoneal insulin infusion with an implantable pump (CPII) and prospectively studied for GH-IGF-I axis. Although HbA_{1 c} was lower in patients on CSII than in those on conventional therapy, GHBP was similarly reduced in both when compared to control subjects (10.2 ± 0.8 and 11.6 ± 0.9 % vs 21.0 ± 1.3, p < 0.01). CPII for 12 months resulted in: a slight and transient improvement in HbA_{1 c} (Time (T)0: 7.6 ± 0.2 %, T3:7.1 ± 0.2 %, T12: 7.5 ± 0.2 %, p < 0.02), improvement in GHBP (T0: 10.2 ± 0.8 %, T12: 15.5 ± 1.5, p < 0.0001), near-normalization of IGF-I (T0: 89.4 ± 8.8 ng/ml, T12: 146.9 ± 15.6, p < 0.002) and normalization of IGFBP-3 (T0: 1974 ± 121 ng/ml, T12: 3534 ± 305, p < 0.0001). The hepatic GH resistance profile in IDDM does not seem to be related to glycaemic control, but partly to insufficient portal insulinization. Intraperitoneal insulin delivery, allowing primary portal venous absorption, may influence GH sensitivity, and improve hepatic IGF-I and IGFBP-3 generation. [Diabetologia (1996) 39: 1498–1504] Received: 23 March 1996 and in revised form: 22 July 1996     

Absence of the dawn phenomenon and abnormal lipolysis in Type 1 (insulin-dependent) diabetic patients with chronic growth hormone deficiency

Summary To determine the role of growth hormone in overnight insulin requirements and lipolysis, five patients with chronic growth hormone deficiency and Type 1 (insulin-dependent) diabetes mellitus and six control patients with diabetes were each studied on two separate nights. Insulin was infused at a variable rate throughout one night to maintain euglycaemia and fixed at 04.00 hours on another. During the variable infusion, euglycaemia was maintained in control patients by a 36% increase in insulin infusion rate between 03.00 and 08.00 hours while a 46% decrease in the rate was required in growth hormone deficient patients (p<0.02). Despite this difference, mean free insulin values were equivalent. This finding is suggestive of increased insulin clearance in growth hormone sufficient patients. Glucose levels rose in control and fell in growth hormone deficient patients when insulin infusion rates were fixed at 04.00 hours. Glycerol production and non-esterified fatty acid concentrations were significantly lower in the growth hormone deficient diabetic patients, p<0.001, and when normalized with a heparin infusion, had no effect on insulin requirements. We conclude that: (1) growth hormone contributes to the development of the dawn phenomenon, possibly by increasing insulin clearance (2) growth hormone helps sustain nocturnal lipolysis in Type 1 diabetes and (3) non-esterified fatty acids are not involved in the dawn phenomenon.     

重组人生长激素对生长激素缺乏症患儿成年身高的影响

目的观察重组人生长激素(rhGH)对生长激素缺乏症(GHD)患儿成年身高(FAH)的影响。方法对11例GHD患儿(男7,女4)应用rhGH治疗,每晚睡前皮下注射,剂量为0．7 IU·kg~(-1)·w~(-1),疗程1．1～7．3年。治疗结束后定期复诊,年生长速度＜1cm,或女性患儿骨龄(BA)≥14岁,男性患儿BA≥16岁时的身高视为近似成年身高或FAH。分析FAH和影响FAH的因素。结果FAH标准差分值(SDS)在男性患儿为(-1．47±0．37),女性患儿为(-1．07±0．60)。85．7%(6/7)男性患儿的FAH达到或超过遗传靶身高(THt)范围,50%(2/4)女性患儿的FAH达到或超过THt范围,男女患儿的FAHSDS与THtSDS比较差异无统计学意义(P＞0．05)。男性患儿的FAHSDS与治疗开始的年龄呈负相关,与治疗开始按年龄的身高SDS(HtSDS_(CA))、青春发育时HtSDS_(CA)和疗程呈正相关；逐步回归分析显示,青春发育时HtSDS_(CA)是影响男性患儿FAHSDS(F=32．58,P=0．002)的独立因素。而女性患儿的FAHSDS与上述因素不相关。孤立性GHD患儿的FAHSDS与由垂体病变引起的多激素缺乏症患儿相比差异无统计学意义(P＞0．05)。结论rhGH能改善GHD患儿的FAH。影响FAH的最主要因素是青春发育时的身高。因此,为达到满意的成年身高,对GHD患儿必须尽早诊断,尽早治疗,以使在青春发育前达到较理想的身高,而对于青春期开始治疗者,必须采用足够的剂量以获得较好FAH。     

IGF-I measurements in the diagnosis of adult growth hormone deficiency

Although serum insulin-like growth factor I (IGF-I) concentrations have utility as a screening test for growth hormone (GH) deficiency in children and young adults, they are less accurate for screening in adults over 40 years of age. There are two main limitations in the clinical use of IGF-I levels as a marker of GH secretion. First, IGF-I synthesis is not only regulated by GH but also by nutrient supply and by other hormones; second, low IGF-I levels in the presence of normal or increased GH secretion may reflect a peripheral resistance to GH action. Although serum IGF-I cannot be used as a stand-alone test for the diagnosis of adult GH deficiency, very low IGF-I levels in the context of documented hypothalamic or pituitary disease may be helpful in identifying patients with a high probability of GH deficiency. In the presence of two or more additional pituitary hormone deficiencies, an IGF-I level <84 μg/l (assayed by Esoterix Endocrinology, Inc. Calabasas Hills, CA, USA) indicates a 99% probability of GH deficiency. As this cut-off value has not been validated for other IGF-I assays, an IGF-I standard deviation score (SDS) of <-3 may be considered in adults over age 28; an even lower IGF-I SDS is needed for diagnosis in younger adults. In clinical practice, other causes of low serum IGF-I such as malnutrition, diabetes, hypothyroidism, liver disease, etc., should be excluded before applying these diagnostic criteria.     

The bone mineral density in acquired growth hormone deficiency correlates with circulating levels of insulin-like growth factor I.

Insulin-like growth factor I (IGF-I) is an important anabolic factor for osteoblasts in vitro. Low plasma levels of IGF-I have been observed in young men with osteoporosis. In the present study, we have studied bone mineral density (BMD) and the circulating levels of IGF-I and growth hormone (GH) in adults with acquired GH deficiency. BMD was determined by dual-energy x-ray absorptiometry in 17 men and 12 women (age 27-54 years). Spinal BMD was positively correlated with the plasma levels of IGF-I (r = 0.43, P = 0.019), with the median of GH values obtained by repeated sampling at night (r = 0.43, P = 0.0019), and with the peak of GH values during GHRH provocation test (r = 0.49, P = 0.039). The total BMD was positively related to plasma IGF-I and median of GH values, but not to peak GH by GHRH provocation. In a multiple regression analysis model, IGF-I, peak GH by GHRH provocation test and duration of GH deficiency explained 49% of the variation in spinal BMD. As compared to healthy controls, total, but not spinal, bone mass was lower in men with GH deficiency, but no clinical symptoms of osteoporosis were observed. The positive relationships between BMD and circulating IGF-I and other indices of GH secretion suggest that IGF-I has an endocrine effect on bone mass.     

老年代谢综合征患者血胰岛素样生长因子1与代谢综合征的关系

目的了解代谢综合征(metabolic syndrome,MS)患者血胰岛素样生长因子1(IGF1)水平及其与MS的关系。方法按2005年国际糖尿病联盟(IDF)颁布的MS定义,将老年患者465例分为MS组255例和对照组210例。查空腹血糖、胰岛素、C肽、餐后2 h血糖、血脂全套、血IGF1并计算体质指数(BMI)。两组按是否并存糖尿病再分为糖尿病和非糖尿病两个亚组。结果(1) MS组除高密度脂蛋白胆固醇(HDL-C)低于对照组外,其他血液指标均高于对照组(P<0．01);两组IGF1水平与年龄、BMI均呈负相关(P<0．05)。(2)MS糖尿病组IGF1(163．5±128．1)μg／L、胰岛素(14．3±10．5)mU／L高于MS非糖尿病组(114．0±52．6)μg／L、(8．46±4．4)mU／L,C肽(1．1±0．4)μg／L低于MS非糖尿病组(2．5±0．4)μg／L,均为P<0．01;IGF1水平与胰岛素、C肽无相关性,与冠心病呈负相关(P<0．05)。(3)对照糖尿病组IGF1(129．2±49．1)μg／L低于对照非糖尿病组(136．6±80．5)μg／L,胰岛素(14．1±11．7)mU／L、C肽(3．28±2．23)μg／L高于对照非糖尿病组(10．3±6．1)mU／L、(2．9±1．7)μg／L,P<0．01或0．05。对照组IGF1与C肽负相关,与甘油三酯正相关;对照糖尿病组IGF1与胰岛素、C肽负相关(均为P<0．01或0．05)。结论MS患者存在高血IGF1现象,这与单纯糖尿病患者低IGF1不同;MS患者IGF1水平较低时发生冠心病的机率较高。     

Dawn phenomenon in Type 1 (insulin-dependent) diabetic adolescents: influence of nocturnal growth hormone secretion

Summary In order to reassess the role of growth hormone in the dawn phenomenon, we studied eight C-peptide negative diabetic adolescents, who are likely to exhibit important nocturnal growth hormone surges. The insulin infusion rate necessary to maintain euglycaemia was predetermined in each patient from 22.00 hours to 01.00 hours, and then kept constant until 08.00 hours resulting in stable free insulin levels. Blood glucose rose from 4.3±0.7 mmol/l at 01.00 hours to 7.1±1.1 mmol/l at 08.00 hours (p<0.01) secondary to an increased hepatic glucose production. All the subjects presented an important growth hormone secretion, ranging from 20 to 66 ng/ml (peak values) and from 3619 to 8621 ng·min· ml^–1 (areas under the curve). The insulin infusion rate selected for each patient was positively correlated with the nocturnal growth hormone secretion (area under the curve) (r=0.87, p<0.01). On the other hand, there was no relationship between the nocturnal growth hormone secretion and the magnitude of the early morning blood glucose rise (r=–0.48, p>0.2). We conclude that, in Type 1 (insulin-dependent) diabetic adolescents, the dawn phenomenon exists but is moderate despite important growth hormone surges; the nocturnal growth hormone secretion influences the nocturnal insulin requirements but not the dawn phenomenon itself, if insulinisation is adequate.     

Effect of GH and IGF-I treatment on reproduction,growth, and plasma hormone concentrations in domestic nutria (Myocastor coypus)

The role of GH and IGF-I in the control of reproduction, growth, and hormone secretion in domestic nutria was examined. In the first series of experiments, we studied the effects of single and multiple (daily for 20 days) injections of recombinant hGH (15 microg/animal) on plasma triiodothyronine (T3), thyroxine (T4), and progesterone (P) concentrations, as well as on the duration of pregnancy (time between start of mating and birth of pups), number of pups born, and body weight of adult females and their newborn pups. In the second series of experiments, the effects of single and multiple (daily for 28 days) injections of recombinant hIGF-I (1 microg/animal) on plasma IGF-I, IGFBP-3, T3, T4 concentrations, the duration of pregnancy, and number of offspring delivered were assessed. It was found that either single or multiple GH treatment resulted in significant increase in plasma T3, T4, but not P concentration. Furthermore, it significantly increased the body weight of adults and newborn pups. No influence of GH on the duration of pregnancy and the number of offspring was observed. IGF-I treatment caused an increase in plasma IGF-I concentration, a reduction in plasma IGFBP-3, T3, and T4 concentrations, and a shorter duration of pregnancy but did not alter the number of pups delivered. Our observations suggest that GH and IGF-I may be involved in the control of hormone secretion, growth, and reproduction in domestic nutria. Reproductive processes are controlled by IGF-I rather than by GH, whilst GH may be involved in the stimulation of prenatal and postnatal growth. The differential effects of these substances on thyroid hormones and reproductive parameters suggest that the actions of GH on these processes are probably not mediated by IGF-I.     

Serum growth hormone and insulin but not insulin-like growth factor-1 levels are elevated in patients with fibromyalgia syndrome

Standard radioimmunoassay (RIA) was employed to quantify basal serum growth hormone (GH), insulin-like growth factor-I (IGF-1), and insulin levels in 32 normoglycemic patients with clinically active fibromyalgia and in 29 normoglycemic control subjects. The GH concentration was significantly higher (P<0.001) in female fibromyalgia patients than age-matched, normal female subjects. In contrast, basal serum IGF-1 concentrations did not differ between these groups. A scatter plot generated from two-stage, least-squares analysis showed that serum GH lacked correlation with the serum IGF-1 concentrations of normal female subjects (P=0.73) and female fibromyalgia patients (P=0.19). In addition to the results from serum GH and IGF-1 RIA, we also found significantly higher fasting serum insulin levels (P=0.03) in male fibromyalgia patients and a trend toward elevated fasting serum insulin levels in the female fibromyalgia population (P=0.07), with the mean fasting level in the male fibromyalgia group (35.7 U/ml^-1) exceeding the upper limit of normal serum insulin levels (i.e., 27 µU/ml^-1). Based on these results, basal serum GH and fasting serum insulin levels appear to be valuable surrogate markers in clinically active, normoglycemic fibromyalgia patients.     

Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease

Background and aims Pituitary dysfunction including growth hormone (GH) deficiency may be associated with non-alcoholic fatty liver disease (NAFLD). Since the relationships among GH, IGF-1, IGFBP-3, and development of NAFLD without hypopituitarism are unclear, we examined the role of these hormones in the development of NAFLD based on clinical, laboratory and liver histology data. Patients and methods A total of 55 consecutive patients (20 males and 35 females) with NAFLD. Results Aspartate amino transferase (AST), AST/ALT, platelet count and IGF-1, levels were significantly associated with differences in fibrosis, since these variables differed between stage 0–1 and stage 2–3 NAFLD. In multivariate analysis, platelet count (P = 0.0223, relative risk (RR), 5.899; 95% confidence interval (CI), 1.288–27.017), and IGF-1 (P = 0.0363, RR, 4.568; 95% CI, 1.101–18.945) showed significant associations with stage 2–3 NAFLD. Additionally, hyaluronic acid levels had a negative relationship with IGF-1 and the IGF-1/IGFBP-3 ratio. There was no relationship of fibrosis with GH level, but decreased GH (P = 0.0414, RR, 0.199; 95% CI, 0.042–0.989) was significantly associated with steatosis of stage 2–3. Low GH/IGF-1 and GH/IGFBP-3 ratios were found in advanced steatosis. Conclusion GH, IGF-1 and IGFBP-3 are associated with hepatic fibrosis and steatosis in NAFLD. Low levels of IGF-1 might be associated with fibrosis while low level of GH with hepatic steatosis.     

Properdin factor B in black Type 1 (insulin-dependent) diabetic patients

Summary The properdin factor B(Bf) variant F1 was found in 20% of 70 black patients with Type 1 (insulindependent) diabetes compared with 7.3% of 165 control subjects, yielding a significant relative risk of 3.1. In addition, the BfF allele was negatively associated with Type 1 diabetes among blacks, resulting in a relative risk of 0.4. The data suggest that Type 1 diabetes in black Americans may be partially due to admixture of Caucasoid genes.     

Serum levels of growth hormone-binding protein and insulin-like growth factor I in children and adolescents with Type 1 (insulin-dependent) diabetes mellitus

Summary Serum levels of insulin-like growth factor I are reduced in patients with Type 1 (insulin-dependent) diabetes mellitus. To evaluate the role of the hepatic growth hormone receptor in the decreased serum concentrations of insulin-like growth factor I, serum levels of the high affinity growth hormone-binding protein, which is qualitatively and quantitatively related to the hepatic growth hormone receptor, and of insulin-like growth factor I were measured in 70 children and adolescents with Type 1 diabetes and 105 healthy control children. Analysis of variance revealed a significant negative effect of Type 1 diabetes on serum levels of the growth hormone-binding protein and of insulin-like growth factor I. In the diabetic patients, serum levels of the growth hormone-binding protein were positively related to body mass index and to insulin dose per kg body weight, and were not influenced by pubertal stage, gender, or plasma levels of haemoglobin A_1c. Serum levels of insulin-like growth factor I increased during early puberty reaching peak levels at midpuberty and decreasing thereafter. No relationship was found between serum levels of growth hormone-binding protein and of insulin-like growth factor I. Our data suggest that decreased liver somatogenic receptor levels, as reflected by the concentrations of circulating growth hormone-binding protein, play a minor role in the suppressed concentrations of circulating insulin-like growth factor I. Post-growth hormone receptor defects or changes in the insulin-like growth factor binding proteins probably contribute more to the lower serum levels of insulin-like growth factor I.