Fasting IGF-I Research Articles

Circulating growth-and-differentiation factor-15 in early life: relation to prenatal and postnatal growth and adiposity measurements.

Growth-and-differentiation-factor-15 (GDF15) is a regulator of energy homeostasis. To determine the relationship between circulating GDF15 and parameters of metabolic health, we assessed longitudinally GDF15 concentrations in infants born either appropriate- (AGA) or small-for-gestational-age (SGA), the latter population known to be at risk for metabolic alterations, particularly after a rapid postnatal catch-up in weight. The study cohort consisted of 103 infants (70 AGA and 33 SGA). Assessments included body length, weight, and ponderal index (PI); fasting glucose, insulin, IGF-I, high-molecular-weight adiponectin, GDF15; and body composition (by absorptiometry) at birth, and at age 4, 12 and 24 months. GDF15 levels at birth were significantly higher than those at each subsequent time point and were similar in AGA and SGA subjects. GDF15 concentrations dropped at age 4 months, more substantially in SGA infants, and continued to decline in both subgroups reaching adult concentrations by age 24 months. GDF15 levels correlated inversely with the changes in PI, IGF-I and body fat throughout follow-up. Early life is associated with supra-adult concentrations of GDF15. The lower levels of GDF15 in SGA subjects may be an adaptive mechanism to promote catch-up in weight and might increase the risk for obesity later in life.

Vitamin D increases IGF-I and insulin levels in experimental diabetic rats

Introduction and objectivePrevious studies have found that IGF-I may play an important role in glucose metabolism. The aim of this study is to examine the effect of vitamin D intake on the serum levels of glucose, insulin, and IGF-I in experimental diabetic rats. Material and methodsA total of 24 male Sprague–Dawley rats aged six to seven months, with an average weight of 300±30g, were randomly divided into three groups (eight rats per group). The first group served as control and the other two groups received an intraperitoneal injection of 45mg/kg streptozotocin (STZ) to develop diabetes. Then groups were treated for four weeks either with placebo or vitamin D (two injections of 20,000IU/kg). ResultsAt the end of the experiment, two injection of vitamin D were found to result in a significant increase in plasma cholecalciferol, which could improve hyperglycaemia and hypoinsulinemia in diabetic rats. HbA1c concentration had a slight and insignificant decrease following vitamin D intake. In addition, a significant decline was observed in the serum IGF-I level of STZ-treated rats in comparison to the controls, which was compensated in the vitamin D group. The serum vitamin D concentration was positively correlated to the changes in IGF-I level by Pearson test. ConclusionsThese data showed for the first time that vitamin D intake could significantly improve fasting plasma glucose, insulin, and IGF-I in an experimental type 1 diabetes model.

Is GH dosing optimal in female patients with adult-onset GH deficiency? An analysis from the NordiNet® International Outcome Study.

To evaluate gender differences in GH dosing, IGF-I and cardiovascular risk markers in adults with GH deficiency (GHD). NordiNet® International Outcome Study (NCT00960128), a noninterventional, multicentre study, evaluates the long-term effectiveness and safety of Norditropin® (Novo Nordisk A/S) in the real-life clinical setting. Nondiabetic patients (n = 252; 41·7% female) with adult-onset GHD (age ≥20 years at GH start), ≥4 years' GH therapy and glycosylated haemoglobin (HbA1c ) data at baseline and 4 years. Effects of gender (adjusted for baseline age and body mass index [BMI], average GH dose, treatment duration and concomitant medication) on change from baseline to 4 years (∆) in HbA1c , fasting plasma glucose (FPG), IGF-I, lipids and waist circumference were evaluated. GH dose (mean [SE]; mg/day) was similar between females (0·22 [0·02]) and males (0·21 [0·01]) at baseline, but higher in females from year 1 (year 4, females, 0·45 [0·03]; males, 0·32 [0·02]). Mean IGF-I standard deviation score [SDS] was lower in females vs males at each treatment year; more than one-third of females still had an IGF-I SDS below 0 at year 4, compared with only 21·8% of men. An adverse lipid profile at baseline remained poor in more females than males at 4 years. Improvement in total cholesterol was significantly associated with gender (P < 0·0001), improving less in females than in males. These data highlight that, even after 4 years, GH dose is suboptimal in many female patients, which may impact clinical outcomes; therefore, GH titration for women requires further improvement.

The effect of growth hormone (GH) replacement on blood glucose homeostasis in adult nondiabetic patients with GH deficiency: real-life data from the NordiNet® International Outcome Study.

To assess the effect of 4 years' growth hormone (GH) replacement on glucose homeostasis and evaluate factors affecting glycosylated haemoglobin (HbA1c ) in adults with growth hormone deficiency (GHD). NordiNet® International Outcome Study, a noninterventional study, monitors long-term effectiveness and safety of GH replacement [Norditropin® (somatropin), Novo Nordisk A/S] in real-life clinical practice. Nondiabetic patients (n = 245) with adult-onset GHD (age ≥20 years at GH start), ≥4 years' GH replacement and HbA1c values at baseline and 4 years were included in the analysis. Changes from baseline (∆) to 4 years in HbA1c , fasting plasma glucose (FPG), IGF-I, lipids (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides), waist circumference, glycaemic (HbA1c <5·7%; HbA1c , 5·7-6·5%; HbA1c , ≥6·5%) and metabolic health status were evaluated. Effects of baseline HbA1c , gender, baseline age, average GH dose and baseline body mass index (BMI) on ΔHbA1c were investigated. The models were adjusted for concomitant medication use. Mean (standard deviation) baseline HbA1c was 5·13 (0·65)% and remained at the same level at 4 years. Age at treatment start (P = 0·0094) and BMI (P = 0·0008) had a significant impact on ∆HbA1c . At 4 years, 85% of patients with HbA1c <5·7% (normal levels) at baseline and 55% of patients with HbA1c 5·7-6·5% (impaired glucose tolerance) at baseline remained in the same glycaemic health category. Nineteen patients improved from impaired glucose tolerance to normal HbA1c . Seven patients developed diabetes. These data demonstrate that 4 years' GH replacement therapy did not adversely affect glucose homeostasis in the majority of adults with GHD.

Insulinlike Growth Factor Binding Protein-1 and Ghrelin Predict Health Outcomes Among Older Adults: Cardiovascular Health Study Cohort.

Multiple diseases may explain the association of the growth hormone/insulinlike growth factor-I (GH/IGF-I) axis with longevity. To relate circulating GH/IGF-I system protein levels with major health events. This is a cohort study set in 4 US communities. Adults (N = 2268) 65 years and older free of diabetes and cardiovascular disease. We assessed insulinlike growth factor binding protein-1 (IGFBP-1) and ghrelin in fasting and 2-hour oral glucose tolerance test (OGTT) blood samples, as well as fasting IGF-I and IGFBP-3. Hazard ratios for mortality and a composite outcome for first incident myocardial infarction, stroke, heart failure, hip fracture, or death were adjusted for sociodemographic, behavioral, and physiological covariates. During 13,930 person-years of follow-up, 48.1% of individuals sustained one or more components of the composite outcome and 31.8% died. Versus the lowest quartiles, the highest quartiles of fasting and 2-hour ghrelin were associated with 27% higher (95% confidence interval [CI]: 6%, 53%) and 39% higher (95% CI: 14%, 71%) risks of the composite outcome, respectively. The highest quartile of 2-hour IGFBP-1 was associated with 35% higher (95% CI: 1%, 52%) risk of the composite end point. Similarly, higher mortality was significantly associated with higher fasting and 2-hour ghrelin levels and with 2-hour IGFBP-1 level. When examined together, 2-hour post-OGTT levels of IGFBP-1 and ghrelin tended to predict outcomes better than fasting levels. Circulating IGFBP-1 and ghrelin measured during an OGTT predicted major health events and death in older adults, which may explain the influence of the GH/IGF-I axis on lifespan and health.

Plasma insulin, glucose, IGF-I, IGF-II, and IGFBP-3 and risk of recurrent colorectal adenomas.

Insulin and insulin-like growth factors (IGF's) are associated with an increased risk of colorectal adenomas. The association with recurrent adenomas is inadequately studied. We prospectively examined the relationship between insulin biomarkers and the risk of recurrent adenomas. Our analysis included 167 subjects with one or more adenomas detected on a baseline colonoscopy who had a surveillance colonoscopy within three to five years. We measured serum biomarkers in all subjects at baseline. ELISA was used to measure fasting plasma insulin, IGF-I, IGF-II, and IGF binding protein-3. The hexokinase assay was used to measure fasting plasma glucose by and immuno-turbidimetric assay to measure hemoglobin A1C. Subjects with recurrent adenomas were more likely to be male, overweight and have ≥3 adenomas at baseline. We found no significant associations between insulin (OR=1.6, 95% CI 0.7-3.5), glucose (OR=1.4, 95% CI 0.7-3.1), IGF-I (OR=0.7, 95% CI 0.3-1.5), IGF-II (OR=1.0, 95% CI 0.5-2.3), IGFBP-3 (OR=0.1, 95% CI 0.5-2.1), or anthropometric measures and recurrent adenomas. Our results do not support a role for insulin biomarkers and recurrent colorectal adenomas.

Longitudinal association between IGFBP-1 levels and parameters of the metabolic syndrome in obese children before and after weight loss

Insulin-like growth factor binding protein 1 (IGFBP-1) is a marker of insulin resistance. We hypothesized that IGFBP-1 is associated with the metabolic syndrome (MetS), which is related to insulin resistance. We examined 51 obese Caucasian children (mean age 12.1 ? 2.3, 55% male, mean body mass index [BMI] 31.8 ? 4.8 kg/m(2)). Anthropometrical markers, pubertal stage, hepatic ultrasound, waist circumference, blood pressure, fasting serum IGFBP-1, IGFBP-3, IGF-I, adiponectin, leptin, transaminases, glucose, insulin, triglycerides, and HDL-cholesterol concentrations were determined at onset and the end of the one-year lifestyle intervention. In contrast to IGF-I and IGFBP-3, IGFBP-1 correlated significantly to most parameters of the MetS in cross-sectional (waist circumference: r = -0.45, triglycerides: r = -0.29; insulin: r = -0.31; HOMA: r = -0.30) and longitudinal analyses (? triglycerides: r = ?0.22; ? Insulin: r = ?0.25; ? HOMA: r = ?0.62). The association between changes of HOMA and changes of IGFBP-1 was stronger than the associations between changes of leptin or adiponectin, and changes of HOMA. The risk for the MetS was inversely related to IGFBP-1 levels (odds ratio:-0.05 per additional IGFBP-1 unit; 95% confidence interval: -0.08 up to -0.02; p = 0.019) in a multiple logistic regression analyses adjusted to BMI, pubertal stage, age, and gender. The nine obese children with the MetS had significantly lower IGFBP-1 levels (1.6 ? 1.3 ngm/l) than the 42 obese children without the MetS (4.0 ? 3.8 ng/ml). The eleven obese children with fatty liver assessed by ultrasound had significantly lower IGFBP-1 levels (1.5 ? 1.3 ngm/l) than the 40 obese children without fatty liver (4.2 ? 4.1 ng/ml). The strong relationships between IGFBP-1, insulin resistance, and the MetS suggest that IGFBP-1 might be a promising marker for these entities in obesity. This study is registered at clinicaltrials.gov (NCT00435734).

Obesity due to Melanocortin 4 Receptor (MC4R) Deficiency Is Associated with Increased Linear Growth and Final Height, Fasting Hyperinsulinemia, and Incompletely Suppressed Growth Hormone Secretion

Melanocortin receptor 4 (MC4R) deficiency is characterized by increased linear growth greater than expected for the degree of obesity. The objective of the investigation was to study the somatotroph axis in obese MC4R-deficient patients and equally obese controls. We obtained anthropometric measurements and insulin concentrations in 153 MC4R-deficient subjects and 1392 controls matched for age and severity of obesity. We measured fasting IGF-I, IGF-II, IGF binding protein (IGFBP)-1, IGFBP-3, and acid-labile subunit levels in a subset of 33 MC4R-deficient patients and 36 control subjects. We examined pulsatile GH secretion in six adult MC4R-deficient subjects and six obese controls. Height sd score was significantly greater in MC4R-deficient children under 5 yr of age compared with controls (mean ± SEM: 2.3 ± 0.06 vs. 1.8 ± 0.04, P < 0.001), an effect that persisted throughout childhood. Final height (cm) was greater in MC4R-deficient men (mean ± SEM 173 ± 2.5 vs. 168 ± 2.1, P < 0.001) and women (mean 165 ± 2.1 vs. 158 ± 1.9, P < 0.001). Fasting IGF-I, IGF-II, acid-labile subunit, and IGFBP-3 concentrations were similar in the two groups. GH levels were markedly suppressed in obese controls, but pulsatile GH secretion was retained in MC4R deficiency. The mean maximal GH secretion rate per burst (P < 0.05) and mass per burst (P < 0.05) were increased in MC4R deficiency, consistent with increased pulsatile and total GH secretion. Fasting insulin levels were markedly elevated in MC4R-deficient children. In MC4R deficiency, increased linear growth in childhood leads to increased adult final height, greater than predicted by obesity alone. GH pulsatility is maintained in MC4R deficiency, a finding consistent with animal studies, suggesting a role for MC4R in controlling hypothalamic somatostatinergic tone. Fasting insulin levels are significantly higher in children carrying MC4R mutations. Both of these factors may contribute to the accelerated growth phenotype characteristic of MC4R deficiency.

Fibroblast Growth Factor-21 May Mediate Growth Hormone Resistance in Anorexia Nervosa

Anorexia nervosa (AN), a state of chronic nutritional deprivation, is characterized by GH resistance with elevated GH levels and decreased levels of IGF-I. Fibroblast growth factor (FGF)-21, a hormone produced in the liver and adipocytes, is induced in the liver by fasting and peroxisome proliferator-activated receptor-alpha agonists. In a transgenic mouse model, FGF-21 reduces IGF-I levels by inhibiting signal transducer and activator of transcription-5, a mediator of the intracellular effects of GH. The objective of the study was to investigate the relationship between FGF-21, GH, and IGF-I in AN. This was a cross-sectional study. The study was conducted at a clinical research center. Patients included 23 girls: 11 with AN (16.5 +/- 0.6 yr) and 12 normal-weight controls (15.7 +/- 0.5 yr). There were no interventions. We measured fasting FGF-21, glucose, insulin, IGF-I, and total area under the curve for GH (GH-AUC) and leptin during 12-h overnight frequent sampling. FGF-21 levels were significantly higher in AN compared with controls, and there was a positive correlation between FGF-21 and GH-AUC (P = 0.03) after controlling for percent body fat and insulin resistance. In subjects with elevated FGF-21 levels, there was a strong inverse association between FGF-21 and IGF-I (R = -0.88, P = 0.004). FGF-21 strongly correlated with total area under the curve for leptin (R = 0.67, P = 0.02). FGF-21 levels are higher in AN independent of the effects of percent body fat and insulin resistance. The positive association between FGF-21 and GH-AUC and the inverse association between elevated FGF-21 levels and IGF-I suggests that above the normal range, FGF-21 may mediate a state of GH resistance in AN.

Efficacy and Safety of Long-Term Continuous Growth Hormone Treatment in Children with Prader-Willi Syndrome

Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects. The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters. We conducted a multicenter prospective trial. Fifty-five children with a mean +/- sd age of 5.9 +/- 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m(2) . d). Data were annually obtained in one center: fat percentage (fat%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. sd scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDS(PWS)). Fat%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean +/- sd height normalized from -2.27 +/- 1.2 SDS to -0.24 +/- 1.2 SDS (P < 0.0001). Head circumference SDS increased from -0.79 +/- 1.0 at start to 0.07 +/- 1.1 SDS after 4 yr. BMISDS(PWS) significantly decreased. Mean +/- sd IGF-I and the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 +/- 1.1 and 2.32 +/- 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids. Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m(2) . d) improves body composition by decreasing fat%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS.

The Efficacy of Octreotide LAR as Firstline Therapy for Patients with Newly Diagnosed Acromegaly is Independent of Tumor Extension: Predictive Factors of Tumor and Biochemical Response

Surgical outcome of acromegaly depends on the preoperatory tumor size and extension. Somatostatin analogues are also a highly effective treatment for acromegalic patients. Nevertheless, the response of GH-secreting adenomas to primary medical therapy is variable. The aim of the present study was to evaluate the efficacy of octreotide LAR as primary therapy for acromegalic patients as a function of initial tumor extension. We performed a multicentre, prospective, observational and analytical study recruiting 19 "naive" acromegalic patients (5 microadenomas, 10 intrasellar, and 4 extrasellar macroadenomas). All of them were treated with octreotide LAR for 12 months. Basal GH and fasting IGF-I concentrations, and tumor volume were measured at baseline and after 6 and 12 months of treatment. Six patients withdrew the study. The patients who completed the protocol showed a significant reduction of tumor volume (25+/-23%, Wilk's lambda=0.506, F=4.400, p=0.046) independently of tumor extension at study entry (Wilk's lambda=0.826, F=0.452, p=0.769). A shrinkage >25% of baseline tumor volume was achieved in 8 (42%) patients with no differences between tumor extension subgroups. Basal GH levels (76+/-18%) and fasting IGF-I (52+/-31%) decreased throughout the study. Six (46%) patients normalized their IGF-I levels. Octreotide LAR is an effective first-line treatment for a large group of acromegalic patients independent of initial tumor extension.

Bioactive IGF-I in Obesity

Bioactive IGF-I in Obesity

Bioactive Insulin-Like Growth Factor-I in Obesity

In obesity, total IGF-I is not reduced to the degree predicted by low GH levels, and free IGF-I levels are normal to high. Total and free IGF-I may not reflect IGF-I biological activity because immunoassays cannot account for the modifying effects of IGF binding proteins on interactions between IGF-I and its receptor. The aim of the study was to investigate the biological activity of IGF-I in obesity. We conducted a cross-sectional study at a General Clinical Research Center. Thirty-four healthy women (11 lean, 12 overweight, and 11 obese) of comparable age (overall mean, 30.7 +/- 1.3 yr) participated in the study. There were no interventions. We measured bioactive IGF-I (as measured by a kinase receptor activation assay), IGFBP-1, and GH using 6-h pools of serum collected every 10 min for 24 h, and fasting IGF-I and IGFBP-3. Mean 24-h GH (R = -0.76; P < 0.0001), total IGF-I (R = -0.36; P = 0.040), and IGFBP-1 (R = -0.41; P = 0.017) levels were inversely associated with BMI, whereas bioactive IGF-I and IGFBP-3 levels were not. Mean bioactive IGF-I was similar in the groups [2.72 +/- 0.22 (lean), 3.10 +/- 0.32 (overweight), and 2.43 +/- 0.23 [corrected] (obese) microg/liter; overall P = 0.22]. Percentage bioactive IGF-I [(bioactive/total IGF-I) x 100] was higher in obese subjects than both lean and overweight subjects (P = 0.039). Despite low GH secretion in obesity and decreasing IGFBP-1 with increasing BMI, 24-h mean bioactive IGF-I levels are not reduced in obese women and do not correlate with BMI or IGFBP-1 levels. This argues against elevated bioactive IGF-I as the etiology of reduced GH secretion through a feedback mechanism in obesity.

Short-term effects of growth hormone treatment on the upper airways of non severely obese children with Prader-Willi syndrome

The aim of this study was to establish whether short-term GH treatment causes obstructive apnea in patients with Prader-Willi syndrome and normal upper airway patency. We performed an observational longitudinal 6-week GH treatment study. Thirty-four non-severely obese Prader-Willi syndrome patients (20 boys, age range 0.94-11.8 yr, median 2.24 yr) entered an observational longitudinal 6-week study. Sixteen boys received recombinant human GH (rhGH) treatment; the remaining 18 represented the control group and received no treatment. Polysomnography monitoring and othorhinolaringoiatric video endoscopy were performed one night before and after 6 weeks of rhGH treatment (0.03 mg/kg body weight/day). All patients underwent auxologic assessment, fasting blood glucose, insulin and IGF-I evaluation. The main polysomnographic parameter considered was total apnea hypopnea index, consisting of two components: central apnea hypopnea index and obstructive apnea hypopnea index. All patients were free of severe or moderate upper airway obstruction when rhGH treatment began. After 6 weeks of rhGH therapy, obstructive apnea hypopnea index increased in 8/16 (50%), decreased in 5/16 (31%), and did not change in 3/16 (19%) patients. The changes were not statistically significant. The rhGH-treated group did not differ from the control group for the apnea hypopnea index both before and after 6 weeks of treatment. Adenoids and tonsils showed a slight increase in 1 and 2 patients on rhGH treatment, respectively, and did not change in the untreated patients. Our data show that short-term rhGH treatment does not cause restrictions of the upper airways in patients with Prader-Willi syndrome and normal upper airway patency.

Novel Relationships of Age, Visceral Adiposity, Insulin-Like Growth Factor (IGF)-I and IGF Binding Protein Concentrations to Growth Hormone (GH) Releasing-Hormone and GH Releasing-Peptide Efficacies in Men during Experimental Hypogonadal Clamp

Sex steroids influence GH secretion in complex ways. Analyses in a low sex-steroid milieu will help unveil the effects of age and other nonsteroidal regulators on GH secretion. The study was conducted in a tertiary medical center. The study group included 13 healthy young men and 12 healthy older men. We used GnRH agonist-induced down-regulation of testosterone and estradiol secretion, followed by consecutive infusion of l-arginine and GHRH or GHRP-2, to test secretagogue efficacies. We measured basal and pulsatile GH secretion. During experimental testosterone/estradiol deprivation, older (57 +/- 1.7 yr) men maintained: 1) 6.8-fold less pulsatile GH secretion (P < 0.001); and 2) 2-fold lower maximal GH responses to GHRH (P = 0.0065) and GHRP-2 (P = 0.022) than young (23 +/- 1.1 yr old) individuals. Stepwise forward-selection regression analyses identified: 1) abdominal visceral fat as a dominant negative predictor of both GHRH (R(2) = 0.49; P = 0.001) and GHRP-2 (R(2) = 0.38; P = 0.005) efficacies; and 2) fasting IGF-I concentration as a major positive correlate of GHRH (R(2) = 0.52; P < 0.001) and GHRP-2 (R(2) = 0.31; P = 0.018) efficacies. Unstimulated pulsatile GH secretion was jointly correlated with IGF-I and IGFBP-3 (P = 0.039). Measures of body composition (abdominal visceral fat) and pulsatile GH action (IGF-I) explain up to one half of interindividual variability in the efficacies of GHRH and GHRP-2 in sex steroid-depleted men. Accordingly, normative ranges for maximal single peptide-stimulated GH secretion in short-term hypogonadal states should incorporate the influence of these determinants as well as age.

IGF-I, IGFBP-3, and IGF-I/IGFBP-3 Ratio: No Association with Incident Colorectal Cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study

The insulin-like growth factor (IGF) signaling system is thought to affect tissue growth and development ([1][1]), with IGF-I and IGF binding protein-3 (IGFBP-3) having putative procarcinogenic and anticarcinogenic properties, respectively. A recent meta-analysis of four prospective studies found

Bone Metabolism in Adolescent Boys with Anorexia Nervosa

Anorexia nervosa (AN) is a condition of severe undernutrition associated with low bone mineral density (BMD) in adolescent females with this disorder. Although primarily a disease in females, AN is increasingly being recognized in males. However, there are few or no data regarding BMD, bone turnover markers or their predictors in adolescent AN boys. We hypothesized that BMD would be low in adolescent boys with AN compared with controls associated with a decrease in bone turnover markers, and that the gonadal steroids, testosterone and estradiol, and levels of IGF-I and the appetite regulatory hormones leptin, ghrelin, and peptide YY would predict BMD and bone turnover markers. We assessed BMD using dual-energy x-ray absorptiometry and measured fasting testosterone, estradiol, IGF-I, leptin, ghrelin, and peptide YY and a bone formation (aminoterminal propeptide of type 1 procollagen) and bone resorption (N-telopeptide of type 1 collagen) marker in 17 AN boys and 17 controls 12-19 yr old. Boys with AN had lower BMD and corresponding Z-scores at the spine, hip, femoral neck, trochanter, intertrochanteric region, and whole body, compared with controls. Height-adjusted measures (lumbar bone mineral apparent density and whole body bone mineral content/height) were also lower. Bone formation and resorption markers were reduced in AN, indicating decreased bone turnover. Testosterone and lean mass predicted BMD. IGF-I was an important predictor of bone turnover markers. AN boys have low BMD at multiple sites associated with decreased bone turnover markers at a time when bone mass accrual is critical for attainment of peak bone mass.

Visceral Adiposity without Overweight in Children Born Small for Gestational Age

Children born small for gestational age (SGA) tend to develop catch-up growth in infancy and become overweight by the age of 6 yr. Weight control is advocated as a preventive measure, but it is unknown whether such control suffices to prevent visceral fat excess and hypoadiponectinemia. The study was performed at a university hospital. A total of 64 children (32 matched pairs) aged 6 yr, of whom 32 were born appropriate for gestational age and 32 were born SGA, and had subsequently developed spontaneous catch-up growth were included in the study; matching was performed for gender, height, weight, and, thus, body mass index. Fasting insulin, IGF-I, high molecular weight adiponectin, leptin, visfatin, and lean and fat mass were calculated by absorptiometry, and abdominally sc and visceral fat by magnetic resonance imaging. After strict matching, SGA children had a total lean mass, total fat mass, leptinemia, and visfatinemia comparable to those in the appropriate for gestational age children, but they still had higher fasting insulin and IGF-I levels (P < 0.01), much lower high molecular weight adiponectin levels (P < 0.0001), and a striking shift from abdominally sc to visceral fat (P < 0.0001). Fasting insulin (r = 0.52; P < 0.00001) was a major determinant of visceral fat in boys and girls, explaining 28% of its variance. SGA children tend to be viscerally adipose and hypo-adiponectinemic, even if they are not overweight. Therefore, measures beyond weight control seem to be needed to allow most SGA children to normalize their body composition and endocrine-metabolic homeostasis.

Study of insulin resistance in relation to serum IGF-I levels in subjects with different degrees of glucose tolerance

AIM:We studied the correlations between fasting and post-lunch serum IGF-I concentrations, and insulin resistance and insulin sensitivity in subjects with various degrees of glucose tolerance.MATERIALS AND METHODS:A total of 12 nondiabetic subjects, 09 subjects with impaired glucose tolerance (IGT) and 18 patients with newly diagnosed type-2 diabetes of either sex (mean age, 46 years) were recruited. None of the participants received any drug treatment at the commencement of the study. Fasting as well as post-lunch blood samples were collected from all the subjects and anthropometric and biochemical parameters were analyzed.RESULTS:Fasting serum IGF-I concentrations were negatively correlated with fasting serum glucose, insulin, C-peptide, triglycerides, total LDL and VLDL cholesterol, homeostatic model assessment of insulin resistance (HOMA-IR), and age. Fasting serum IGF-I concentrations were positively correlated with fasting blood HDL cholesterol and homeostatic model assessment of insulin sensitivity (HOMA-S) in only diabetic subjects. Post-lunch serum IGF-I concentrations were positively correlated with HDL and LDL cholesterol. Correlations with HOMA-S with these metabolic anthropometric variables were of similar magnitude and direction as that of IGF-I concentrations. IGF-I concentrations were significantly lower in the subjects with World Health Organization-defined metabolic syndrome compared with the subjects without metabolic syndrome (P < 0.0001).CONCLUSIONS:Our data indicate that IGF-I could be a useful marker in the insulin resistance syndrome. The post-lunch low-IGF-I levels help in better identification of subjects at risk for type-2 diabetes mellitus and cardiovascular disease.

Effects of the long-acting somatostatin analogue Lanreotide Autogel on glucose tolerance and insulin resistance in acromegaly

Treatment with somatostatin analogues (SA) not only inhibits GH secretion but may also impair insulin secretion. In order to evaluate the influence of SA on glucose metabolism, we investigated insulin resistance (IR) and beta-cell function, using the recommended combination of homeostatic model assessment of IR (HOMA-IR) and beta-cell function (HOMA-beta). This is a prospective, cross-sectional study. We measured fasting insulin, blood glucose and IGF-I. Insulin and blood glucose measurements were taken 120 min after an oral glucose tolerance test with 75 g glucose. We studied 51 patients (27 female/24 male, age 54 years (20-75)). Eighteen patients were on Lanreotide Autogel (LA) treatment, 33 had no medical treatment. GH-levels of more than 2.5 ng/ml was reached by 59% of the patients, 74.5% had normal IGF-I levels. We found no significant influence of disease activity on HOMA-IR and HOMA-beta. In the 33 of 51 subjects without any drug treatment, median HOMA-beta was 170.4% (36.0-624.0%). In contrast, in the 18 patients on LA treatment, median HOMA-beta was found to be significantly lower (84.2% (36.5-346.2%); P = 0.001). Despite this, there was no difference in HOMA-IR in both groups (2.4 (0.7-8.4) vs 2.3 (0.7-6.1); P < 0.001) despite similar insulin values. In conclusion, we found that LA decreases beta-cell function significantly without affecting IR. Therefore, we think that insulin secretagogues are probably more effective in the treatment of diabetes mellitus in acromegalic patients on LA therapy than insulin sensitizers.