Insulin-like Growth Factor 1 Z-score Research Articles

7858 Increasing Severity of Growth Hormone Deficiency is Associated with Lower Vertebral Strength

Abstract Disclosure: R. Boutin: None. M. Haines: None. R. Shahid: None. C. Mark: None. C. Gill: None. M. Bredella: None. K.K. Miller: Other; Self; Pfizer, Inc. L.E. Dichtel: Consulting Fee; Self; Lumos Pharma. Grant Recipient; Self; Lumos Pharma, Perspectum Ltd. Research Investigator; Self; Recordati, Novo Nordisk. Stock Owner; Self; Marea Therapeutics. Other; Self; Third Rock Ventures. Objective: Growth hormone (GH) stimulates osteoblast differentiation, while insulin-like growth factor-1 (IGF-1) stimulates osteoblast proliferation and bone formation. Retrospective studies have demonstrated a 2-to-3-fold increased fracture risk in adults with GH deficiency (GHD) due to organic hypothalamic or pituitary disease, particularly at vertebral sites. Adults with overweight/obesity produce relatively less GH than lean individuals, and serum IGF-1 levels are associated positively with BMD in adults with obesity. Yet, no published studies have examined the relationship between degree of GHD across these groups and vertebral strength, an understudied measure of bone quality in part because HR-pQCT cannot image this skeletal site. We hypothesized that there would be an inverse association between degree of GHD and vertebral strength, independent of age and BMI. Methods: Cross-sectional study of 134 estrogen-replete (with regular menses or taking estrogen) women: 16 with GHD secondary to hypopituitarism (HP, severe GHD), 91 with obesity (OB) without a hypothalamic/pituitary disorder (relative GHD), and 37 lean controls (LC) without a hypothalamic/pituitary disorder (normal GH production). Peak-stimulated GH was assessed by GHRH-arginine testing. CT imaging at the L4 vertebra was performed to determine vertebral cross-sectional area and total integrated volumetric bone mineral density (Int.vBMD), from which estimates of vertebral strength were calculated. Results: Mean age [44±9 (mean±SD) (HP) vs. 35±7 (OB) vs. 30±7 (LC) y, p<0.005] and BMI [30±6 (HP) vs. 34±6 (OB) vs. 22±2 (LC) kg/m2, p<0.004] differed between all groups. As expected, peak-stimulated GH was highest in LC (28.3 ± 9.5 ng/mL) followed by OB (12.4 ± 8.9 ng/mL) and HP (2.4 ± 1.7 ng/mL), p<0.0001. IGF-1 Z-scores were higher in LC (0.0 ± 0.6) and OB (0.0 ± 0.7) vs. HP (-1.4 ± 0.7), p<0.0001. Int.vBMD and vertebral strength were higher in LC and OB vs. HP [Int.vBMD (g/cm3) LC 0.21±0.04 and OB 0.21±0.04 vs. HP 0.16±0.03, and vertebral strength (N) LC 4540±850 and 4743±91 vs. HP 3542±651, both p<0.0001], which remained significant when adjusted for age and BMI (p≤0.01). Peak-stimulated GH and IGF-1 Z-scores were positively associated with vertebral strength (GH R=0.33, p=0.003 and IGF-1 Z-score R=0.41, p<0.0001) and Int.vBMD (GH R=0.46, p<0.0001 and IGF-1 Z-score R=0.40, p<0.0001), which remained significant when adjusted for age and BMI. Among the subset of patients without organic pituitary disease (LC and OB only), IGF-1 Z-scores remained positively associated with vertebral strength (R=0.24, p<0.03) and Int.vBMD (R=0.22, p<0.05). Conclusions: These findings suggest that severe GHD is associated with impaired vertebral volumetric bone density and strength. Moreover, the relative GHD of obesity may contribute to lower vertebral bone density and strength in otherwise healthy adults with overweight/obesity. Presentation: 6/3/2024

12566 Adult Growth Hormone Deficiency, Replacement Therapy Use, and IGF1 Levels in Association with Physical, Psychosocial, and Neurocognitive Outcomes Among Childhood Cancer Survivors

Abstract Disclosure: T. Yoshida: None. J.L. Baedke: None. H. Wang: None. C.H. Yu: None. C.L. Wilson: None. D.A. Mulrooney: None. S.B. Dixon: None. I. Huang: None. T.M. Brinkman: None. K.R. Krull: None. S. Mostoufi-Moab: None. J. Miguel Martínez: None. K.K. Ness: None. M.M. Hudson: None. Y. Yasui: None. A. Delaney: None. Background: Adult growth hormone deficiency (aGHD) is a common and often untreated late effect among childhood cancer survivors. Untreated aGHD likely adds to the burden of health outcomes in survivors already experiencing cancer treatment related late toxicities. As comprehensive data on the consequences of untreated aGHD in survivors are scarce, we assessed the clinical impact of untreated aGHD among survivors, together with socioeconomic factors as potential contributing factors, utilizing a large, clinically characterized cohort of childhood cancer survivors. Methods: 3902 five-year survivors ≥ 18 years old [median (25th-75th percentile) age, 31.7y (25.2-40.0); age at cancer diagnosis 8.1y (3.5-13.6); 47.5% female] were examined. We assessed the: 1) proportion of survivors with aGHD on GH therapy (GHT); 2) association between GHT and socioeconomic factors (e.g., household income, area deprivation index) by multivariable logistic regression; and 3) associations between age- and sex-adjusted insulin-like growth factor 1 (IGF1) z-score and prevalence of clinically-assessed (i.e., body composition, metabolic/cardiovascular factors, neurocognitive function) and self-reported [i.e., quality of life (QoL), emotional symptom] outcomes by multivariable logistic regression with trend test, adjusting for potential confounders (e.g., radiation to the hypothalamic-pituitary region). Results: aGHD was observed in 9.1% (354/3902) of survivors; among them, 9.0% (32/354) were on GHT. Survivors on GHT were more likely to have higher household income, hold health insurance, and reside in less socioeconomically disadvantaged neighborhoods, compared to survivors with untreated aGHD. Socioeconomic factors had significant independent associations with GHT use in multivariable analysis [e.g., annual household income <$40,000 vs. ≥$80,000, adjusted odds ratio (aOR) of GHT use, 0.28; 95% confidence interval (CI), 0.08-0.86]. Lower IGF1 z-score (IGF1 z-score ≤ -2, vs. IGF1 z-score >0) was associated with a higher prevalence of various outcomes (aOR, 95% CI), such as abdominal obesity (2.56, 1.98-5.26), weak handgrip strength (2.49, 1.65-3.73), hypertension (1.47, 1.06-2.04), abnormal glucose metabolism (2.07, 1.49-2.86), impaired health-related QoL (e.g., physical functioning, 1.97, 1.35-2.86), depression (1.58, 1.06-2.33), and impairment in multiple neurocognitive functions (e.g., verbal reasoning, a global measure of intelligence, 2.22, 1.49-3.30) with a dose-response relationship. Conclusions: Our data support a negative impact of untreated aGHD on physical, psychosocial, and neurocognitive outcomes among survivors and suggest the potential of GHT to improve QoL of survivors with aGHD. As lower socioeconomic status may affect survivors’ access to GHT, this disparity should be considered in interventions evaluating GHT for survivors with aGHD. Presentation: 6/3/2024

Utility of insulin-like growth factor-1 (IGF-1) in growth hormone-treated short children – An experience from a tertiary level center

Introduction: Very few studies have been conducted in low-middle-income countries to assess the response to growth hormone (GH) therapy by measuring the improvement in insulin-like growth factor-1 (IGF-1) concentrations. Objectives: The objective is to assess IGF-1 concentrations in patients receiving GH therapy to correlate the height increment with respect to increase in the IGF-1 concentrations, including IGF-1 Z-scores as a measure of safety profile. Methods: Clinical and anthropometric data were extracted retrospectively from hospital records of children aged 0–18 who received GH and had IGF-1 measured during the study period. Serum IGF-1 concentrations were analyzed by a solid-phase enzyme-linked immunosorbent assay. Patients with GH deficiency (GHD) and multiple pituitary hormone deficiency (MPHD) were grouped as group A, while participants receiving GH therapy for non-GHD/MPHD were clubbed as group B. Results: We report a significant positive correlation between an increase in IGF-1 values and increase in height. The improvement in height Z-scores was significantly higher in participants of group A as compared to B, with no significant difference in increase in IGF-1 Z-scores between the two groups. A total of 18.75% of subjects had IGF-1 Z-scores between +2 and +3, and these were largely subjects belonging to group B. Conclusion: The increment in height and height velocity Z-scores in the patients on GH correlated with increase in the IGF-1 concentrations, particularly in GHD/MPHD group of patients.

Hormonal changes in veterans with Gulf War Illness

AimsGulf War Illness (GWI) is a multi-system condition of complex etiology and pathophysiology without specific treatment. There is an overlap between the symptoms of GWI and endocrinopathies. This study aimed to identify hormonal alterations in 1990–91 Gulf War (GW) veterans and the relationship between GWI and hormonal dysregulation. Main methodsData from 81 GW veterans (54 with GWI and 27 controls without GWI) was analyzed in a cross-sectional, case-control observational study. Participants completed multiple questionnaires, neuropsychiatric assessments, and a comprehensive set of hormone assays including a glucagon stimulation test (GST) for adult growth hormone deficiency (AGHD) and a high-dose adrenocorticotropic hormone (ACTH) stimulation test for adrenal insufficiency. Key findingsThe GWI group had lower quality of life and greater severity of all symptoms compared to controls. Pain intensity and pain-related interference with general activity were also higher in the GWI group. AGHD was observed in 18 of 51 veterans with GWI (35.3 %) and 2 of 26 veterans without GWI (7.7 %) (p = 0.012 for interaction). Veterans with GWI also exhibited reduced insulin-like growth factor 1 (IGF-1) levels and IGF-1 Z-scores compared to controls. One participant with GWI met the criteria for adrenal insufficiency. No significant changes were observed in other hormonal axes. SignificanceThe frequency of AGHD was significantly higher in veterans with GWI compared to controls. Recombinant human growth hormone replacement therapy (GHRT) may become a breakthrough therapeutic option for this subgroup. A large clinical trial is needed to evaluate the efficacy of GHRT in patients with GWI and AGHD.

A low serum IGF-1 is correlated with sarcopenia in subjects with type 1 diabetes mellitus: Findings from a post-hoc analysis of the iDIAMOND study

AimOur previous study revealed that sarcopenia was frequently observed in subjects with type 1 diabetes mellitus (T1DM). However, the factors associated with sarcopenia that are related to T1DM have not yet been clarified. Insulin-like growth factor-1 (IGF-1) has been shown to play a role in skeletal muscle growth, differentiation, and regeneration. The present study, therefore, investigated the association between the serum IGF-1 level and sarcopenia and low skeletal muscle mass in subjects with T1DM. MethodsThis cross-sectional study enrolled subjects with T1DM (n = 168) and without diabetes (n = 59) who had had their clinical data on serum IGF-1 collected in the iDIAMOND study. ResultsThe z-score of serum IGF-1 was significantly lower in the subjects with T1DM than that in those without diabetes (p < 0.001). Among subjects with T1DM, the z-score of serum IGF-1 was significantly lower in sarcopenic subjects than in non-sarcopenic subjects. The multivariable logistic regression analysis showed that the serum IGF-1 z-score was an independent determinant of sarcopenia and a low skeletal muscle mass index, but not low grip strength nor slow gait speed in subjects with T1DM. ConclusionsA low serum IGF-1 level is correlated with sarcopenia and low skeletal muscle mass in subjects with T1DM.

Abstract 13454: Relationship Between Brain-type Natriuretic Peptide and Serum Growth Factors in Infants With Single Ventricle Heart Disease and Shunt- or Ductal-dependent Pulmonary Blood Flow

Introduction: For infants with shunt- or ductal-dependent single-ventricle heart disease (SD-SVHD), poor growth is common and associated with morbidity and impaired neurodevelopmental outcome. While attention has focused on nutrition to promote weight gain, little is known about the contribution of heart failure to diminished growth. Methods: A prospective observational pilot study was performed to assess the relationship between heart failure, assessed by brain natriuretic peptide (BNP), and growth factors [insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3)] at 4 visits: 1) prior to discharge from neonatal intervention, 2) immediately prior to stage 2 palliation, 3) prior to discharge after stage 2 palliation, and 4) 3-6 months after stage 2 discharge. IGF-1 Z-scores were generated by the analysis lab using reference data. The relationship between log-transformed BNP and growth factors was analyzed using pairwise correlations at each visit and modeled over time with a linear mixed-effects model. Correlations were considered statistically significant using a p-value &lt;0.10, given the exploratory nature of the study. Results: The study included 38 infants (66% male, 68% hypoplastic left heart syndrome). Median BNP was elevated at Visit 1 and decreased over time [287 pg/dL (IQR 147, 794), 85 pg/dL (52, 183), 90 pg/dL (70, 138), and 47 pg/dL (43, 135)]. Median IGF Z-score was &lt;0 at each visit but increased over time [-0.9 (IQR -1.1, 0.1), -0.7 (-1.2, 0.1), -0.5 (-1.2, 0), and -0.2 (-0.8, 0)]. Inverse correlations were noted between log BNP and IGF-1 Z-score at Visit 1 (r = -0.45, p=0.06) and Visit 3 (r = -0.50, p=0.02), and between log BNP and IFGBP-3 at Visit 1 (r = -0.44, p=0.06) and Visit 2 (r = -0.34, p=0.08). There was a small effect of log BNP on IGF-1 Z-score over all time periods (coefficient: -0.23, 95% CI: -0.49, 0.024, p=0.07). Conclusions: This pilot study demonstrates an inverse correlation between BNP and growth factors, suggesting that the heart failure state associated with this physiology may play a mechanistic role in impaired growth. Further work directed at therapies that target the underlying heart failure state might help to optimize the potential for growth in this vulnerable patient population.

MON-088 Impact of Vertebral Fracture on Auxological Profile and Insulin-Like Growth Factors of Children After Acute Lymphoblastic Leukemia Treatment

Purpose: To investigate the overall prevalence of vertebral fractures (VF) following childhood acute lymphoblastic leukemia (ALL) treatment and examine the association of VF with growth trajectory and insulin-like growth factors. Methods: Children (n=172; 59.3 % male) diagnosed with ALL at age between 2 and 18 years were assessed for VF by screening the lateral thoracolumbar spine radiographs (Genant’s semi-quantitative method) when treatment was completed (baseline). Anthropometric measurements between pre- to post-treatment period were obtained and the association of VF with insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) were examined. Results: Thirty-five children (20.3 %) had vertebral fractures at baseline. Among children with vertebral fractures, 97.1 % had either mild or moderate deformity, and the 5th lumbar vertebrae was the most frequently injured site (20.0 %). Median lumbar spine bone mineral density Z-score was -1.0 (IQR of -1.6 and -0.8) in children with VF. Baseline Z-scores for height and weight were lower in children with VF than without VF (-0.5±1.3 and 0.0±0.9, P=0.01; -0.2±1.6 and 0.3±1.1, P=0.04, respectively). Height Z-score in children with VF had greater height decline than without VF (0.5±0.6 and 0.2±0.8; P=0.02). Children with VF had lower IGF-1 and IGFBP-3 Z-score than without VF at baseline (-1.2±1.0 and 0.0±0.8, P<0.01; -2.3±1.1 and -1.3±1.0, P<0.01). Decrease in IGF-1 level was associated with the presence of VF (OR=0.3(95 % CI of 0.2-0.5), P<0.01). Conclusion: Substantial number of children encounter VF after ALL treatment is completed and the presence of VF might be associated with compromised auxological state, prominent height decline and IGF-1 deficiency.

Elevated HbA1c Is Associated with Altered Cortical and Trabecular Microarchitecture in Girls with Type 1 Diabetes.

Skeletal fragility is a significant complication of type 1 diabetes (T1D), with an increased risk of fracture observed starting in childhood. Altered bone accrual and microarchitectural development during the critical peripubertal years may contribute to this fragility. To evaluate differences in skeletal microarchitecture between girls with T1D and controls and to assess factors associated with these differences. Cross-sectional comparison. Girls ages 10-16 years, 62 with T1D and 61 controls. Areal bone mineral density (BMD) measured by dual-energy x-ray absorptiometry did not differ between girls with and without T1D. At the distal tibia, trabecular BMD was 7.3 ± 2.9% lower in T1D (P = 0.013), with fewer plate-like and axially-aligned trabeculae. Cortical porosity was 21.5 ± 10.5% higher, while the estimated failure load was 4.7 ± 2.2% lower in T1D (P = 0.043 and P = 0.037, respectively). At the distal radius, BMD and microarchitecture showed similar differences between the groups but did not reach statistical significance. After stratifying by HbA1c, only those girls with T1D and HbA1c > 8.5% differed significantly from controls. P1NP, a marker of bone formation, was lower in T1D while CTX and TRAcP5b, markers of bone resorption and osteoclast number, respectively, did not differ. The insulin-like growth factor 1 (IGF-1) Z-score was lower in T1D, and after adjustment for the IGF-1 Z-score, associations between T1D status and trabecular microarchitecture were largely attenuated. Skeletal microarchitecture is altered in T1D early in the course of disease and among those with higher average glycemia. Suppressed bone formation and lower circulating IGF-1 likely contribute to this phenotype.

The Association of Diet and Exercise With Body Composition in Pediatric Crohn's Disease.

In pediatric Crohn's disease, fat mass improves over time with treatment, but lean mass deficits persist. This observational study of the associations of physical activity and dietary intake with lean mass and muscle strength in children with Crohn's disease was ancillary to a previously reported randomized clinical trial of an intervention to improve bone health. In this study, 138 participants were followed at baseline and at 6, 12, and 24 months with evaluation of lean and fat mass using DXA, muscle strength (peak torque), Crohn's characteristics, dietary intake, time in moderate to vigorous physical activity (MVPA), and serum insulin-like growth factor-1 (IGF-1) and tumor necrosis factor-alpha (TNF-α). Race- and sex-specific Z-scores for leg lean mass and whole body fat mass were generated. Quasi least square regression evaluated determinants of changes in body composition and muscle strength. Leg lean mass and muscle strength were positively associated with time in MVPA (P < 0.05) and negatively associated with increasing clinical disease activity (P < 0.05). Both leg lean mass and strength were positively associated with IGF-1 Z-score (P ≤ 0.03) but negatively associated with serum TNF-α (P ≤ 0.04). Neither lean mass nor muscle strength was associated with caloric or protein intake. Persistence of lean mass deficits was related to ongoing Crohn's disease activity but improved with greater time spent in moderate to vigorous physical activity. Future trials are needed to evaluate the efficacy of physical activity in improving lean mass in pediatric Crohn's disease.

Insulin-like growth factor 1 inversely relates to monocyte/macrophage activation markers in HIV.

Monocyte/macrophage activation is increased among people with HIV, and may contribute to the heightened risk of atherosclerosis and neurocognitive dysfunction in this population. Insulin-like growth factor 1 (IGF-1) has been shown to attenuate the innate immune response in animal models of atherosclerosis and inflammatory bowel disease. We investigated, for the first time, relationships of circulating IGF-1 with monocyte/macrophage-specific indices among HIV-infected individuals and uninfected controls. Observational. One hundred and thirty-one HIV-infected patients and 65 well matched controls without known cardiac disease or viral hepatitis were recruited previously. IGF-1, expressed as a z-score relative to the age-adjusted and sex-adjusted population mean, was related to log-transformed inflammatory markers within HIV and non-HIV groups. In HIV, IGF-1 inversely related to sCD163 (r = -0.28, P = 0.002), sCD14 (r = -0.29, P = 0.002), and high-sensitivity IL-6 (r = -0.27, P = 0.006). There was no association of IGF-1 with high-sensitivity CRP, MCP-1, IL-18, or LPS in HIV, or between IGF-1 and any inflammatory marker in controls. Relationships of IGF-1 with sCD163 and sCD14 remained significant in HIV after controlling for age, sex, smoking, BMI, visceral fat, statin use, viral load, and antiretroviral therapy. For every one-unit decline in IGF-1 z-score, sCD163 and sCD14 increased by 14% (95% CI, 0.23-29%) and 29% (95% CI, 1.4-63%), respectively. Low IGF-1 was robustly associated with high sCD163 and sCD14 in HIV. Prospective studies are needed to investigate augmentation of IGF-1 as a novel strategy to reduce monocyte/macrophage activation in this population.

Correlation between GH and IGF-1 during treatment for acromegaly.

OBJECTIVE The relationship between growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in patients with acromegaly as serial levels drop over time after treatment has not been examined previously. Knowledge of this relationship is important to correlate pretreatment levels that best predict response to treatment. To examine the correlation between GH and IGF-1 and IGF-1 z-scores over a wide range of GH levels, the authors examined serial GH and IGF-1 levels at intervals before and after surgery and radiosurgery for acromegaly. METHODS This retrospective analysis correlates 414 pairs of GH and IGF-1 values in 93 patients with acromegaly. RESULTS Absolute IGF-1 levels increase linearly with GH levels only up to a GH of 4 ng/ml, and with IGF-1 z-scores only to a GH level of 1 ng/ml. Between GH levels of 1 and 10 ng/ml, increases in IGF-1 z-scores relative to changes in GH diminish and then plateau at GH concentrations of about 10 ng/ml. From patient to patient there is a wide range of threshold GH levels beyond which IGF-1 increases are no longer linear, GH levels at which the IGF-1 response plateaus, IGF-1 levels at similar GH values after the IGF-1 response plateaus, and of IGF-1 levels at similar GH levels. CONCLUSIONS In acromegaly, although IGF-1 levels represent a combination of the integrated effects of GH secretion and GH action, the tumor produces GH, not IGF-1. Nonlinearity between GH and IGF-1 occurs at GH levels far below those previously recognized. To monitor tumor activity and tumor viability requires measurement of GH levels.

IGF-1 and Insulin Resistance Are Major Determinants of Common Carotid Artery Thickness in Morbidly Obese Young Patients.

We assessed the relationship between insulin resistance, serum insulin-like growth factor 1 (IGF-1) levels, and common carotid intima-media thickness (CC-IMT) in morbidly obese young patients. A total of 249 patients (aged 37.9 ± 9.8 years, body mass index [BMI] 45.6 ± 8.3 kg/m(2)) were evaluated (metabolic tests, serum IGF-1 measurements, homeostasis model assessment-insulin resistance [HOMA-IR], and ultrasonographically assessed CC-IMT) in a research program for bariatric surgery candidates. After adjusting for age, gender, BMI, systolic blood pressure, uric acid, antihypertensive and lipid-lowering treatment, metabolic syndrome, and metabolic class, both HOMA-IR and IGF-1 z-score were significantly associated with CC-IMT. These results were confirmed in logistic regression analysis, in which age (β = 1.11, P = .001), gender (β = 3.19, P = .001), HOMA-IR (β = 1.221, P = .005), and IGF-1 z-score (β = 1.734, P = .009) were the only independent determinants of abnormal CC-IMT, presumably modulating the effect of the other risk factors included in the regression. Area under the receiver-operating characteristic curve for the model was 0.841 (confidence interval: 0.776-0.907; P < .001). In conclusion, in morbidly obese young adults, insulin resistance and IGF-1 z-score are significantly associated with CC-IMT, independent of other major cardiovascular risk factors.

Relationship of insulin-like growth factor 1 and bone parameters in 7-15 years old apparently, healthy Indian children.

Objective:Growth hormone through insulin-like growth factor 1 (IGF-1) plays an important role in both bone growth and mineralization. This cross-sectional study was carried out to evaluate the relationship between serum IGF-1 concentrations and dual energy X-ray (DXA) measured whole body less head bone area (BA), lean body mass (LBM), and bone mineral content (BMC).Methods:One hundred and nineteen children (boys = 70, age = 7.3–15.6 years) were studied for their anthropometric parameters by standard methods and bone and body composition by DXA. Their fasting serum IGF-1 concentrations were assessed by enzyme-linked immunosorbent assay and Z-scores were calculated using available reference data. Bone and body composition parameter Z-scores were calculated using ethnic reference data.Results:Mean age of the boys and girls was similar (11.5 ± 1.8 years). The mean serum IGF-1concentrations and IGF-1 Z-scores were similar (P > 0.1) between boys and girls and were of the order of (302.3 ± 140.0 and − 1.4 ± 1.1, respectively). The LBM for age and BA for age Z-score was greater in children with IGF-1 Z-score > median than children with IGF-1 Z-score < median. The mean BMC for age Z-scores were 0.4 ± 0.9 and − 0.2 ± 0.8 in children with above and below the median of IGF-1 Z-score (P > 0.1).Conclusion:Serum IGF-1 levels were more strongly associated with BA and LBM, suggesting that its effect on bone is greater with respect to periosteal bone acquisition and through its effect on muscle mass.

The effect of low magnitude mechanical stimulation (LMMS) on bone density in patients with Rett syndrome: a pilot and feasibility study.

Low magnitude mechanical stimulation (LMMS) has been used successfully to promote bone formation in certain patient populations. This study evaluated the feasibility and effectiveness of LMMS on improving bone mineral density (BMD) in patients with Rett syndrome. A 12-month crossover pilot study design of 6 months of intervention with LMMS and 6 months without was studied in 14 subjects divided in two subgroups. BMD was assessed using Dual Energy X-ray Absorptiometry (DXA). The levels of 25-hydroxy vitamin D (25OHD), Parathyroid Hormone (PTH), Insulin-Like Growth Factor 1 (IGF-1), and circulating markers of bone resorption (NTx) were analyzed in blood samples. Health questionnaires and diet logs were obtained at 0, 6, and 12 months. Of the 11 subjects who completed the protocol, 9 had an adherence of > 65% and showed an increase in spine BMD Z-scores from the intervention (Z: -2.51) compared to non-intervention period (Z: -2.27) of 0.23 SD (p=0.048). Following intervention, favorable trends were also observed for IGF-1 (p=0.06) and right distal femur BMD Z-scores (p=0.07). These preliminary results are promising for a larger, placebo-controlled randomized study of subjects with Rett syndrome.

Evaluation of Insulin-Like Growth Factor-1 in Indian Growth Hormone-Deficient Children on Growth Hormone Therapy

Objective. To evaluate the impact of recombinant human growth hormone therapy (GHT) on serum insulin-like growth factor 1 (IGF-1) concentrations in Indian children with growth hormone deficiency. Methods. Data on anthropometry and serum IGF-1 concentrations were collected from 28 growth hormone-deficient prepubertal children (8.6 ± 2.9 years) on growth hormone therapy, 6 monthly over the period of 2 years. Results. Height z-scores showed a steady increase from baseline to 24 months. However, IGF-1 z-scores showed a plateau after the first 6 months and then a small dip followed by a rise. The pattern of increase of IGF-1 z-scores was dissimilar to that of the height z-scores. Conclusion. The change in serum IGF-1 z-scores in response to GHT in Indian children may not be a good indicator for monitoring growth hormone responsiveness.

Role of two nutritional hepatic markers (insulin‐like growth factor 1 and transthyretin) in the clinical assessment and follow‐up of acute intermittent porphyria patients

Acute intermittent porphyria (AIP) is caused by a deficiency of hydroxymethylbilane synthase. Clinical manifestations are abdominal pain and neurovisceral symptoms, accompanied by overproduction of heme-precursors in the liver, which frequently remains long-lasting in AIP patients. We tested the hypothesis that this condition may be associated with alterations of hepatic proteins known to be either increased or decreased in serum according to diverse pathological conditions including malnutrition, inflammation or liver disease. Serum proteins were analyzed in 26 biochemically active AIP patients that were classified according to the EPI (European Porphyria Initiative) guidelines as follows: (i) patients who presented a single acute attack having remained so far free of clinical symptoms; (ii) patients who present recurrent attacks or chronic symptoms associated with exacerbations of AIP. Most of the serum proteins were within normal limits, however insulin-like growth factor 1 (IGF-1) was decreased in 53.8% of AIP patients (z-score = -2.86 +/- 0.37) and transthyretin (prealbumin) was found significantly decreased in 38.5% of them. The IGF-1 z-score was lower in group B versus group A patients (-2.66 vs. -1.43; P = 0.024). The coincident decrease of both IGF-1 and transthyretin was associated with worsening of the clinical condition. This first study in humans suggests that the clinical expression AIP is associated with a state of under-nutrition and/or with hepatic inflammation due to the sustained accumulation of heme-precursors. We propose the use of both IGF-1 and transthyretin as biomarkers of disease morbidity/severity for the clinical follow-up of AIP patients.

Calcium acquisition rates do not support age-appropriate gains in total body bone mineral content in prepuberty and late puberty in girls with cystic fibrosis

Few longitudinal data are available characterizing bone development in adolescents with cystic fibrosis (CF) although this is a critical time for bone mineralization. Dual energy X-ray absorptiometry (DXA) scans were obtained at 1- to 4-year intervals in 18 prepubertal and pubertal girls (age 7-18 years) with CF to determine calcium (Ca) accretion rates and changes (Delta) in total body bone mineral content (TBBMC) and lumbar spine bone mineral density (LS BMD) Z-scores. Daily Ca acquisition rates were calculated assuming TBBMC was composed of 32.2% Ca. Bone Ca accretion averaged 82 mg/day (2.05 mmol/day) [(range:-38 to +197 mg/day (-0.95 to 4.9 mmol/day)] on approximately 1,200 mg/day (30 mmol/day) Ca intakes. Estimated mean peak Ca accretion was 160 mg/day (4 mmol/day) at age 13 years; losses of bone Ca occurred in late puberty. Gains in insulin-like growth factor 1 (IGF-1) predicted Ca accretion (p<0.06). Body mass index (BMI) Z-score predicted LS BMD and TBBMC Z-score cross-sectionally but did not predict DeltaTBBMC Z-score. Changes in TBBMC Z-score paralleled Ca accretion rates with age. Bone Ca accretion in girls with CF fell below rates in healthy girls during prepuberty and late puberty despite Ca intakes approaching recommendations. IGF-1 and BMI Z-scores may identify children with CF at risk of compromised bone accretion, and more data are required to elucidate roles of lung function and glucocorticoid use in compromised bone health.

Insulin-like growth factor 1 (IGF-1), a nutritional marker in patients with eating disorders

Background and aims: Though low levels of insulin-like growth factor-1 (IGF-1) have been repeatedly reported in patients with eating disorders, the nutritional significance of IGF-1 has not been evaluated. The study aimed to assess the utility of IGF-1 for screening malnutrition and for monitoring nutrition intervention in patients with eating disorders. Methods: IGF-1 and nutritional status were evaluated in 82 patients, 59 with anorexia nervosa (AN), and 23 with bulimia nervosa (BN). Nutritional assessment included the evaluation of body mass index (BMI), body fat (FAT) and muscle mass (MM), assessed by skinfold anthropometry, serum albumin, transthyretin and retinol-binding protein, energy and protein intake. IGF-1 and nutritional parameters were revaluated in the early phase of refeeding (2–4 weeks) in 20 AN patients who entered a refeeding program. Results: Mean IGF-1 z-score was −1.74±0.74 in AN, and −0.74±0.91 in BN. Serum proteins were reduced in only a minority of patients. IGF-1 correlated with BMI (r=0.64), FAT (r=0.57), MAMC (mid-arm muscle circumference) (r=0.58) and MM (r=0.66) (P<0.001), while it did not correlate with serum proteins. In the early phase of nutritional repletion serum proteins and anthropometric parameters did not vary significantly, while a prompt and marked increase (73.9%) of IGF-1 was observed. Conclusions: IGF-1 represents a biochemical marker of malnutrition and a sensitive index of nutritional repletion in patients with eating disorders.

Nutritional and prognostic significance of insulin-like growth factor 1 in patients with liver cirrhosis

Most of the traditional parameters for nutrition assessment have important limitations in patients with chronic liver disease. Insulin-like growth factor 1 (IGF-1) has been found to be regulated by nutrition and proposed as a nutritional marker. Its nutritional significance in patients with liver cirrhosis, however, has not been investigated. Serum IGF-1 as well as traditional anthropometric, visceral, and immunologic parameters were evaluated in 64 hospitalized cirrhotics, followed up clinically for 2 y. IGF-1 z-score averaged −2.16 ± 1.08 and inversely correlated with Child-Pugh score ( P < 0.01), the most reliable composite score reflecting the severity of liver disease. IGF-1 z-score was not different in patients with or without signs of energy malnutrition, as defined by values of midarm muscle circumference (MAMC) and/or triceps skinfold (TSF) <5th percentile. Moreover, IGF-1 z-score did not correlate with MAMC or TSF. Despite its correlation with all visceral proteins, the reduction of IGF-1 was much greater and more frequent than that of visceral proteins. Patients with IGF-1 z-score < median values (−2.5) showed lower long-term survival rates compared with patients with IGF-1 z-score > −2.5 ( P < 0.01). These data indicate that serum IGF-1 is not related to energy malnutrition in cirrhotic patients, while it appears to be a good predictor of survival and an early marker of liver dysfunction. Multiple factors, most of which are related to the severity of the liver disease, may contribute to the reduction of IGF-1. This multifactorial pathogenesis probably accounts for its prognostic significance.