Serum Insulin Growth Factor Research Articles

Early applicability of retinopathy of prematurity score (ROPScore) and serum insulin growth factor-1 (IGF-1) for predicting treatment-requiring retinopathy of prematurity: a prospective cohort study

BackgroundRetinopathy of prematurity is a leading cause of blindness especially in developing countries where the accessibility to screening may not be available. Therefore, early prediction could help reallocate the resources for those at high risk.ObjectivesThis study aimed to evaluate the accuracy of the retinopathy of prematurity score (ROPScore) and serum insulin-like growth factor-1 (IGF-1) for predicting treatment-requiring retinopathy of prematurity.MethodsThis prospective cohort study included 87 preterm neonates (≤ 32 weeks). Neonates were screened using digital fundus photography with indirect ophthalmoscopy performed when retinopathy of prematurity changes was detected. Serum insulin-like growth factor-1 was measured in the 3rd week of life.ResultsNine cases (10.3%) developed treatment-requiring retinopathy of prematurity, while 78 patients had mild retinopathy of prematurity. According to logistic regression analysis, lower birth weight and longer duration of assisted ventilation were independent risk factors for treatment-requiring retinopathy of prematurity. At the 2nd week of life, cut-off value of 14.95 for the retinopathy of prematurity score showed a sensitivity of 100% and a specificity of 67.9% for predicting treatment-requiring retinopathy of prematurity. Moreover, serum insulin-like growth factor-1 was significantly lower in patients with treatment-requiring retinopathy of prematurity (p < 0.001).ConclusionsROPScore applied at week 2 and week 6 of life showed the same sensitivity and specificity to predict treatment-requiring retinopathy of prematurity. Furthermore, serum insulin-like growth factor-1 in the 3rd week of life was significantly lower in patients with treatment-requiring retinopathy of prematurity.

Loss-of-function GHSR variants are associated with short stature and low IGF-I.

The growth hormone (GH) secretagogue receptor, encoded by GHSR, is expressed on somatotrophs of the pituitary gland. Stimulation with its ligand ghrelin, as well as its constitutive activity, enhances GH secretion. Studies in knock-out mice suggest that heterozygous loss-of-function of GHSR is associated with decreased GH response to fasting, but patient observations in small case reports have been equivocal. To establish the phenotype of GHSR haploinsufficiency and their growth response to GH treatment. This case series includes 26 patients with short stature and heterozygous GHSR variants. Pathogenicity was studied in vitro using total protein levels, cell surface expression, and receptor activity in basal, stimulated and inhibited states. Ten different variants were identified, of which six were novel. Variants showed either partial or complete loss-of-function, primarily through loss of constitutive activity. Patients (4.0-15.1 years) had proportionate short stature (height -2.8±0.5 SDS), failure to thrive with low appetite (n=4), a mean serum insulin growth factor I (IGF-I) of -1.6±0.7 SDS, and a normal stimulated GH response. Nine patients received GH treatment, showing a height gain of 0.9±0.4 SDS after 1 year and 1.5±0.4 SDS after 2 years (n=5). This study combines phenotypical and functional data in a uniquely large group of children with short stature carrying GHSR variants, and shows their good response to GH treatment. The results strengthen the hypothesis of GHSR's role in GH secretion.

Preoperative predictors of biochemical remission in somatotroph adenoma resections: a single-institution retrospective review.

There is persistent debate in the literature surrounding the true predictors of biochemical remission after resection of somatotroph adenoma. A multimodal analysis of a large number of patients is needed to better understand which patients may be at higher or lower risk for remission failure after surgery. A retrospective review was performed on patients undergoing somatotroph adenoma resection. Biochemical remission was defined as age- and sex-adjusted normalization of serum insulin growth factor-1 (IGF-1) levels at least 6 months after surgery. Patient case characteristics and clinicopathologic variables were tested for statistical associations with remission and were included in a random forest machine learning model to assess for their importance in determining remission status. Preoperative variables found to be significant remission predictors on statistical testing and important in the random forest model were subsequently assessed via receiver operating characteristic (ROC) analysis to determine numeric thresholds that optimally predicted preoperative likelihood of remission success or failure. Eighty patients were identified with somatotroph adenoma who underwent transsphenoidal resection, with 60 patients (75%) achieving biochemical remission. Statistical testing found that patients with failed remission were more likely to have larger tumors (1.9 vs 1.6 cm by the largest axis, p = 0.014; and 3.61 vs 2.66 cm3 by 3D volume, p = 0.013) that invaded the cavernous sinus more frequently (70% vs 22% of patients, p < 0.001) and have higher preoperative IGF-1 level (860 vs 660 ng/ml, p = 0.044). An optimized random forest machine learning model with 10,000 iterations found that tumor size, preoperative growth hormone and IGF-1 levels, and cavernous sinus invasion were important preoperative predictors of remission status. ROC analysis revealed that 96% of patients with preoperative 3D tumor volume less than 1.51 cm3 (area under the curve [AUC] 0.691, p = 0.003) and 100% with nonadjusted preoperative IGF-1 level less than 718.5 ng/ml (AUC 0.736, p = 0.002) achieved remission. Important preoperative predictors of postoperative remission for somatotroph adenoma resection include serum IGF-1 level, cavernous sinus invasion, and tumor size. Ninety-five percent of patients who achieved postoperative remission had preoperative 3D tumor volume less than 1.51 cm3.

Effect of growth rates on hormonal and pubertal status in Nellore heifers early weaned.

This study aimed to determine the effect of growth rates on the hormonal status and puberty onset. Forty-eight Nellore heifers were weaned at 3.0 ± 0.1 (means ± standard error of the mean) months old were blocked according to body weight at weaning (84 ± 2 kg) and randomly assigned to treatments. The treatments were arranged in 2 × 2 factorial according to the feeding program. The first program was high (H; 0.79 kg/day) or control (C; 0.45 kg/day) average daily gain (ADG) from 3rd to 7th month of age (growing phase I). The second program was also high (H; 0.70 kg/day) or control (C; 0.50 kg/day) ADG from the 7th month until puberty (growing phase II), resulting in four treatments: HH (n = 13), HC (n = 10), CH (n = 13), and CC (n = 12). To achieve desired gains, heifers in high ADG program were fed ad libitum dry matter intake (DMI), and the control group was offered around 50% of ad libitum DMI of high group. All heifers received a diet with similar composition. Puberty was assessed weekly by ultrasound examination, and the largest follicle diameter was evaluated every month. Blood samples were collected to quantify leptin, insulin growth factor-1 (IGF1) and luteinizing hormone (LH). At 7 months of age, heifers in high ADG were 35 kg heavier than the control. Heifers in the HH had greater DMI compared with CH in phase II. The puberty rate at 19 months old was greater in the HH treatment (84%) than in the CC (23%), but there was no difference between HC (60%) and CH (50%) treatments. Heifers from HH treatment had greater serum leptin concentration than others at 13 months old, and serum leptin was greater in HH compared with CH and CC at 18 months old. High heifers in phase I had greater serum IGF1 concentration than the control. In addition, HH heifers had a greater diameter of the largest follicle than CC. There was no interaction between phases and age in any variable relative to the LH profile. However, the heifers' age was the main factor that increased the frequency of LH pulse. In conclusion, increasing ADG was associated with greater ADG, serum leptin and IGF-1 concentration, and puberty onset; however, LH concentration was affected mainly by age of the animal. The increasing growth rate at younger age made heifers more efficient.

Screening for possible hypopituitarism following mild traumatic brain injury: The first all-female study. Who do we need to evaluate further?

Studies on hypopituitarism (HP) following mild traumatic brain injury (mTBI) have focused on male populations although women may be more susceptible to the sequelae of mTBI. This is, to the best of our knowledge, the first all-female study screening for HP following mTBI. Screening for possible HP in female athletes reporting a history of one or more mTBI. Pituitary hormone screening blood tests (SBT) were performed in 133 of the 151 female athletes included. Repeated results outside the reference value (O-RV) were considered abnormal necessitating further endocrinological evaluation. Repeated SBT were O-RV in 88 women (66.2%). Decreased levels of serum insulin growth factor 1 (S-IGF1) were found in 55.6% of participants and elevated levels of serum prolactin (S-prolactin) in 22.6%. Serum cortisol levels were below the RV in 6.0% and thyroid hormonal levels in 11.3%. Lower age and increased number of mTBI symptoms correlated significantly with the risk of hormonal results O-RV. The majority of the study population had SBT O-RV, warranting further workup of possible HP. Decreased levels of S-IGF1 were most commonly observed followed by elevated S-prolactin possibly indicating hypothalamic-pituitary impairment. Lower age and increased number of symptoms of mTBI may indicate the need to screen for HP.

Endocrine Abnormalities in Children With Traumatic Brain Injury at a Tertiary Care Center.

Objective Accidental traumatic brain injury (TBI) can lead to severe complications such as endocrine abnormalities and long-term morbidities and can negatively impact patient lives. These conditions are also associated with a high cost of treatment over a lifetime, a significant concern in low-to-middle-income countries (LMICs). In Pakistan, the prevalence of children with endocrine abnormalities secondary to TBI remains largely unexplored. We conducted a retrospective cross-sectional study to estimate the burden of endocrine abnormalities due to TBI among children in our population. Methods Twenty patients previously admitted with head injury between September and October 2019 were retrospectively reviewed with tests for baseline serum sodium, plasma osmolality, cortisol, adrenocorticotropin (ACTH), free thyroxine (fT4), growth hormone (GH), insulin growth factor-1 (IGF-1), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), prolactin, estradiol, and testosterone. Data were collated from the electronic Health and Information Management System (HIMS) and analyzed using SPSS v25. Chi-square and t-tests were used to identify associations between variable groups. Outcomes of interest included correlations between hormonal levels and demographic factors, interventions and hormonal levels, and complication rates and hormonal levels. Results Our study reports three (15% of the total cohort) patients with pituitary hormone deficits (two with low IGF-1 and one with low TSH). High serum IGF-1 and ACTH levels were also observed in three (15%) children. High IGF-1 was associated with female gender (p=0.007), mechanical ventilation (p=0.038), and falls (p=0.028). IGF-1 (p=0.035) and GH (p=0.049) levels were associated with improvement in Extended Glasgow Outcome Scale (GOS-E) score. Testosterone was positively correlated with a high percentile for height (p=0.005) and GOS-E scores on follow-up (p=0.030). High testosterone levels (592.12 ± 102.28 ng/dl) were associated with good functional outcomes in post-pubescent patients (p<0.05). Serum fT4 was linked with a high GOS-E score at discharge in prepubescent patients (p=0.034). Neurosurgical decompression was the only risk factor for hormone deficiency, comprising 67% of the group with hormone deficiencies (p=0.028). The learning difficulties were observed exclusively in children with hormonal deficiencies (7 patients, p=0.000). Conclusion Hormonal dysfunction due to TBI in children can lead to poor outcomes. High serum IGF-1, testosterone, and free T4 levels were associated with improved functional outcomes in children with TBI. Limited follow-up and resources in LMICs are significant barriers to addressing the morbidity associated with these conditions and need to be addressed at a health policy level.

Low IGF1 and high IGFBP1 predict diabetes onset in prediabetic patients.

Some individuals develop type 2 diabetes mellitus (T2DM) despite significant metabolic improvements through lifestyle intervention. We tested the hypotheses that insulin growth factor 1 (IGF1) and its binding proteins 1 and 2 predict the onset of T2DM in prediabetes patients and determine the capacity for metabolic regeneration. We measured fasting serum IGF1, insulin growth factor-binding protein 1 (IGFBP1) and IGFBP2 in three randomized controlled lifestyle intervention trials, covering at least 1 year of intervention period and 1 year of additional follow-up. Within a sample of 414 high-risk prediabetes patients (58% women; 28-80 years), we analyzed fasting serum concentrations of IGF1, IGFBP1 and IGFBP2 in relation to diabetes incidence and metabolic parameters over 2 years. Three hundred and forty-five subjects finished the first year of intervention. The interventions significantly improved body weight (BMI: -3.24%, P < 0.001), liver fat (-36.8%, P < 0.001), insulin sensitivity (IS) (homeostatic model assessment-insulin resistance: -6.3%, P < 0.001) and insulin secretion (disposition index: +35%, P < 0.001) in the cohort. Fourteen percent developed T2DM within 2 years. Mean IGFBP1 levels at baseline were lower in prediabetes compared to a healthy population. Also, prediabetes patients with obesity and nonalcoholic fatty liver disease had lower IGFBP1. Those with impaired glucose tolerance had higher IGFBP1 compared to those with only impaired fasting glucose. Baseline IGF1 was lower (122.5 vs 146.6 µg/L) and IGFBP1 was higher (3.32 vs 2.09 µg/L) in subjects who developed T2DM (n = 57), resulting in a significant prediction of diabetes incidence (hazard ratio (HR) IGF1: 0.991 µg/L, P = 0.003; HR IGFBP1: 1.061 µg/L, P = 0.002). This translates into a 20% and 9% difference in T2DM incidence for IGF1 and IGFBP1, respectively. Despite reduced weight, visceral fat and hepatic fat in response to 1 year of lifestyle intervention, those who developed T2DM had not improved insulin sensitivity, glucose tolerance or IGFBP1. Lower IGF1 and higher IGFBP1 in prediabetes predicted the incidence of T2DM, indicating an impairment of beta-cell function, which explains the unresponsiveness to lifestyle intervention.

Linking insulin like growth factor-1 (IGF-1) rs6214 gene polymorphism and its serum level with risk of colorectal cancer

BackgroundColorectal Cancer is found one of the most profound type of cancer around globe, affecting men and women with different ethnic and racial groups. Insulin-like growth factor 1 is known as peptide growth factor found to increase the proliferation of cell and prevent apoptosis. Insulin pathway might have linked with progression of colorectal cancer.MethodsThis study conducted on total 160 subjects, including 80 patients with colorectal cancer with 80 age and gender match controls. Clinical parameters were compared between the control group and Colorectal cancer group. Blood serum IGF-1 was quantified by using ELISA and IGF-1 rs6214(C/T) variations were investigated using TaqMan allelic discrimination assay.ResultsBlood serum level of Insulin growth factor-I (ng/ml) showed substantial association concerning groups while IGF-1 rs6214(C/T) genotype distribution observed increased in colorectal cancer patients as compared to controls with significant association. The variant TT and CT genotype frequency observed more common in cases as compared to control. However, the wild type CC genotype were common in cases used to compared with controls. The Odds Ratio reveal the risk of variant IGF-1 rs6214 T allele to increase 3 times compared to wild type allele.ConclusionThe homozygous TT genotypes and T variant allele of IGF-1 rs6214(C/T) showed association with high serum Insulin growth factor level 1, may increase susceptibility to the colorectal cancer. This work will use to investigate the associations between Insulin-like growth factor 1 and rs6214(C/T) gene variant and blood serum level with the vulnerability to treat Colorectal. In summary, we have investigated the relationship between Insulin growth factor level hormone and colorectal cancer. Further studies are required to understand the association between colorectal cancer and polymorphism. However, this study can be serve as an informative study to uncover mechanisms behind main cause of colon cancer. Therefore, the genomic profiling of Insulin-like growth factor-1 can be helpful to treat colorectal cancer patients.

Systematic training in master swimmer athletes increases serum insulin growth factor-1 and decreases myostatin and irisin levels

During ageing, anabolic status is essential to prevent the decrease in quantity and quality of skeletal muscle mass (SMM). Exercise modulates endocrine markers of muscle status. We studied the differences of endocrine markers for muscle status in 62 non-sarcopenic Mexican swimmer adults aged 30–70 y/o, allocated into two groups: the systematic training (ST) group including master athletes with a physical activity level (PAL) >1.6, and the non-systematic training group (NST) composed by subjects with a PAL <1.5. Body composition, diet, biochemical and endocrine markers were analyzed. The ST group showed lower myostatin (MSTN) and irisin (IRI) levels, two strong regulators of SMM. The insulin growth factor-1 (IGF-1) was higher in the ST. This is consistent with most of the evidence in young athletes and resistance training programs, where IGF-1 and IRI seem to play a crucial role in maintaining anabolic status in master athletes.

Acute effects of different types of exercises on insulin-like growth factor-1, homocysteine and cortisol levels in veteran athletes

This study aimed to investigate acute effects of table tennis (physical+cognitive exercise), aerobic running (physical exercise), and chess (cognitive exercise) exercise sessions of veteran male athletes in their branches on the serum homocysteine (Hcy), insulin growth factor-1 (IGF-1), and cortisol (Cor) levels. Thirty veteran athletes [10 table tennis players (TT), 10 long-distance runners (LR), 10 chess players (CP)] and 10 sedentary controls (SC) between 50 and 65 years of age participated in the study. Blood samples were obtained before and immediately after exercise to determine serum Hcy, IGF-1, and Cor levels. According to their branch, each veteran athlete performed exercise sessions (70-75% of the participants' heart rate reserve) of 10-min of warm-up followed by 40-min of table tennis, aerobic running, or chess. TT and LR groups demonstrated significant increases in the serum IGF-1, Cor, and Hcy levels from pre to post-exercise (p&lt;0.05). In contrast, the CP group showed significant increases only in the serum Hcy levels (p&lt;0.05). Serum IGF-1 and Hcy, in response to exercise, were not significantly different between exercise groups (p&gt;0.05). LR group had a greater serum Cor increase than all exercise groups (p&lt;0.05). The TT group showed significantly greater changes in serum Cor levels than the CP group (p&lt;0.05). In conclusion, although a single bout of aerobic running and table tennis exercise induces a remarkable increase in all measured biomarkers, chess exercise only elicits an increase in Hcy levels. Although aerobic running is more effective in increasing Cor levels than other types of exercise, the current study's findings suggest that serum Hcy and IGF-1 levels in veteran male athletes are not affected by the type of exercise.

Comparison of the difference in serum insulin growth factor-1 levels between chronological age and bone age among children

ObjectiveBy measuring serum insulin-like growth factor-1 (IGF-1) levels in children aged 2–16, we aimed to analyze the changes in IGF-1 levels in different sex and age groups, and compare the consistency of IGF-1 results evaluated by chronological age (CA) and bone age (BA) in children. MethodsA cross-sectional study was conducted between January 2017 and December 2020 among 2979 relatively healthy children who attended the Department of Growth and Development outpatient clinic and health care center of the Affiliated Children’s Hospital of the Capital Institute of Pediatrics and underwent health examination and development assessment. Height, weight, and Tanner pubertal stage were measured by pediatricians. The CHN method was used to estimate BA. Venous blood samples were collected from the children, and IGF-1 levels were determined via chemiluminescence. ResultsIGF-1 levels in childhood increased slowly with age, dramatically during puberty,and continuously withgrowth until to 15 years for boys and reached a peak value at 13 years for girls based on CA. IGF-1 levels reached peak values at 14 and 13 years for boys and girls, respectively, based on BA. There were differences in IGF-1 values between the CA and BA groups at the age of 10–11 years for boys and 7–11 years for girls. A total of 103 boys (7.7%) and 17 girls (1.0%) had IGF-1 levels below the lower limit of the reference range based on CA; evaluating based on BA, there were 82 boys (6.1%) and 15 girls (0.9%) still had IGF-1 values less than the lower limit of the reference range. Eighteen boys (1.3%) and 173 girls (10.5%) had IGF-1 levels above the upper limit of the reference range based on CA; evaluating based on BA, these numbers reduced to 5 (0.4%) among boys and 41 (2.5%) among girls. ConclusionsThere is a significant difference between BA and CA in evaluating IGF-1 levels in children, which can significantly reduce the proportion of IGF-1 values above the upper limit of the kit reference range in children. This suggests that children with BA advanced in pubertal period, the evaluating results of IGF-1 should be corrected by using BA.

Using growth hormone as an adjuvant in IVF: Live birth outcomes from various poor prognosis scenarios

Following 5 recent studies at PIVET several female factors were defined which enabled the clear categorization for a poor prognosis in IVF, namely advanced female age ≥42 years, very low antral follicle count (AFC &lt;5), very low serum anti-Mullerian hormone level (AMH&lt;5pmol/L), serum Insulin growth factor-1 (IGF-1 level) in the lowest quartile, repetitive failed IVF cycles (≥3) and the failure of residual embryos to undergo cryopreservation. Following an Assessment Cycle (AC) to define the first 4 factors in IVF-naïve women, women were offered recombinant growth hormone (rGH) as an adjuvant at 1.0 IU daily for 6 weeks in the lead-up to the oocyte pick-up of their first IVF treatment cycle. Of 1173 women who proceeded directly into IVF after completing an AC, 252 women (21.5%) utilized rGH initiating 426 IVF cycles. Very low AFC and AMH levels were defined in 51 of the women who proceeded through 90 IVF treatment cycles utilizing rGH. Clinical outcomes included cancellation rates (reduced among rGH users, p&lt;0.01), oocytes retrieved (no significant benefit from rGH), oocyte utilization (apparent benefit for rGH in older women with several factors), significant improvement in embryo utilization rates for older women with several factors (incremental cycles ≥3; p&lt;0.002) or failure to achieve cryopreserved embryos (p&lt;0.02). However, these benefits failed to translate into an improved pregnancy or live birth productivity rate nor a reduction in miscarriage rates; partly due to the low numbers of women with several poor prognosis factors. Furthermore, a note of caution emerged from this study as younger women who did not receive rGH had significantly better live birth outcomes (p&lt;0.0001 from initiated cycles), regardless of the number of poor prognosis factors identified. Nonetheless, we encourage prospective studies to continue, focusing only on older women ≥40 years with low ovarian reserve and additional poor prognosis factors.

Bone changes during and after treatment of childhood acute lymphoblastic leukaemia

Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, with a survival rate of 80%. Major complications of leukemia include osteoporosis that requires both a clinically significant fracture history and low bone mineral density (BMD). The present study aims to assess BMD among acute lymphoblastic leukemia patients and survivors using dual-energy x-ray absorptiometry and serum insulin growth factor binding protein 3. The study was approved by the Independent Ethics Committee and the Scientific Council of the Menoufia University, Egypt. Thirty patients with ALL and thirty survivors who were diagnosed with ALL but completely recovered were enrolled in this study. Sex and age matched normal controls while full history was taken. Patients and survivors were examined for anthropometric measurement. Laboratory including serum IGFBP3and dual-energy x-ray absorptiometry was done for all. It has been found out that patients and survivors showed a markedly lower BMD than normal population but no history of fracture was found in survivors. In this study, the prevalence of low BMD is 26/30 (86.6%) patients and 25/30 (83.3%) survivors. Also, there was a statistically significant decrease of DEXA scan measures in patients and survivors groups than the control group with a statistically significant decrease in both BMD and Z- score measures in patients and survivors groups than control group. Patients and long-term survivors of childhood ALL are at risk for morbidity associated with low BMD. They may benefit from interventions to optimize bone health as they age.

Growth Hormone Pulses and Liver Gene Expression Are Differentially Regulated by the Circadian Clock Gene Bmal1.

In this study, we found that loss of the circadian clock gene Bmal1 causes disruptions throughout the growth hormone (GH) axis, from hepatic gene expression to production of urinary pheromones and pheromone-dependent behavior. First, we show that Bmal1 knockout (KO) males elicit reduced aggressive responses from wild-type (WT) males and secrete lower levels of major urinary proteins (MUPs); however, we also found that a liver-specific KO of Bmal1 (liver-Bmal1-KO) produces a similar reduction in MUP secretion without a defect in aggressive behavior, indicating that the decrease in elicited aggression arises from another factor. We then shifted our investigation to determine the cause of MUP dysregulation in Bmal1 KO animals. Because the pulse pattern of GH drives sexually dimorphic expression of hepatic genes including MUPs, we examined GH pulsatility. We found that Bmal1 KO males have a female-like pattern of GH release, whereas liver-Bmal1-KO mice are not significantly different from either WT or Bmal1 KO. Since differential patterns of GH release regulate the transcription of many sexually dimorphic genes in the liver, we then examined hepatic gene transcription in Bmal1 KO and liver-Bmal1-KO mice. We found that while some female-predominant genes increase in the Bmal1 KO, there was no decrease in male-predominant genes, and little change in the liver-Bmal1-KO. We also found disrupted serum insulin growth factor 1 (IGF-1) and liver Igf1 messenger RNA in the Bmal1 KO mice, which may underlie the disrupted GH release. Overall, our findings differentiate between GH-pulse-driven and circadian-driven effects on hepatic genes, and the functional consequences of altered GH pulsatility.

The effectiveness of growth hormone replacement on energy expenditure and body composition in patients with adult growth hormone deficiency.

Numerous studies have shown that growth hormone (GH) replacement in adult GH deficiency (AGHD) improves the body composition and metabolic rate; however, data about the relationship between body composition and energy expenditure in these patients is scarce. Our study aimed to investigate the changes in resting energy expenditure (REE) and body composition after GH replacement in patients with AGHD. We enrolled 15 patients diagnosed with AGHD and evaluated the effect of GH replacement administered once daily for 12 months on REE, body composition measured by bioelectrical impedance analysis, and serological markers. GH replacement therapy significantly increased the serum insulin growth factor-1 levels after 4, 8, and 12 months. The REE and REE/basal energy expenditure (REE/BEE) ratio significantly increased from 1278.0 ± 490.0 kcal/day and 0.87 ± 0.23 at baseline to 1505.5 ± 449.2 kcal/day and 1.11 ± 0.21 at 4 months, 1,918.7 ± 631.2 kcal/day and 1.29 ± 0.27 at 8 months, and 1,511.1 ± 271.2 kcal/day, 1.14 ± 0.29 at 12 months (p < 0.005, p < 0.005; p < 0.01, p < 0.01; p < 0.01, p < 0.005, respectively). There was no change in the body weight, while the lean body mass increased significantly from 45.8 ± 9.5 kg at baseline to 46.9 ± 9.4 kg at 4 months and 47.5 ± 10.1 kg at 8 months (p < 0.005, p < 0.01, respectively). The fat mass also decreased at 12 months. Lipid metabolism improved after 4 and 8 months. GH replacement therapy in patients with AGHD significantly improved the REE and body composition.

(Neuro) Peptides, Physical Activity, and Cognition

Regular physical activity (PA) improves cognitive functions, prevents brain atrophy, and delays the onset of cognitive decline, dementia, and Alzheimer’s disease. Presently, there are no specific recommendations for PA producing positive effects on brain health and little is known on its mediators. PA affects production and release of several peptides secreted from peripheral and central tissues, targeting receptors located in the central nervous system (CNS). This review will provide a summary of the current knowledge on the association between PA and cognition with a focus on the role of (neuro)peptides. For the review we define peptides as molecules with less than 100 amino acids and exclude myokines. Tachykinins, somatostatin, and opioid peptides were excluded from this review since they were not affected by PA. There is evidence suggesting that PA increases peripheral insulin growth factor 1 (IGF-1) levels and elevated serum IGF-1 levels are associated with improved cognitive performance. It is therefore likely that IGF-1 plays a role in PA induced improvement of cognition. Other neuropeptides such as neuropeptide Y (NPY), ghrelin, galanin, and vasoactive intestinal peptide (VIP) could mediate the beneficial effects of PA on cognition, but the current literature regarding these (neuro)peptides is limited.

PERSISTENCE OF ACCELERATED VASCULAR AGING FOLLOWING THERAPY IN OLDER CANCER SURVIVORS

Chemotherapy destroys cells indiscriminantly and releases proinflammatory factors into the bloodstream that can adhere to endothelial cells (ECs); resulting in phenotypical changes consistent with “accelerated vascular aging”. This pilot study examined associations between markers of EC integrity, vascular aging, and cognition in 15 female breast cancer survivors 12–18 months after chemotherapy (median age: 57 years) and 2 non-cancer controls (58/59 years). EC integrity was evaluated using frequency-dependent electrical impedance (Z4000Hz) and levels of apoptosis (caspase-3/7), inflammation (NFkB activation), and oxidative stress (NRF2 activation) in cultured human endothelial cells (EC) exposed to the subject’s serum. Vascular aging was characterized by low serum insulin growth factor ([IGF1a] <85mg/dL) and laterality in cerebral oxygenation (Lat-FLOX), an in-vivo marker of altered cerebral blood flow (near-infrared spectroscopy). Z4000Hz were higher in cells treated with serum from survivors (520-1100 ohms) than controls (400-450 ohms). Higher Z4000Hz was associated with higher amounts of EC oxidative stress (rNRF2= -.55), inflammation (rNFkB= .43), apoptosis (rcapsase=.76), and Lat-FLOX (r=.39). Higher Z4000Hz (r= -.48) and Lat-FLOX (r= -.66) were associated with lower cognitive function, as measured by the Montreal Cognitive Assessment (MOCA). At lower Z4000Hz, combined Lat-FLOX and low IGF1a characterized persons with cognitive impairment (MOCA < 26). These findings suggest that proinflammatory factors related to cancer and/or its treatment persist for months following active treatment. Cognitive symptoms occur when EC damage results in alterations in cerebral blood flow. With depletion of growth factors, like IGF-1, these symptoms may occur at lower levels of EC damage.

The expression and significance of miR-29b and IGF-1 in type 2 diabetes mellitus patients with depression

Objective To detect the levels of serum micro RNA (miRNA) -29b and insulin growth factor-1 (IGF-1) in patients with type 2 diabetes mellitus (T2DM) and depression, and to analyze their clinical significance. Methods 504 patients with T2DM admitted to our hospital from February 2016 to February 2018 were selected, among them, 264 patients without depression, the other 240 patients with depression were selected as the study group, and 200 patients with physical examination were selected as the control group. Serum triglyceride (TG), cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), glycosylated hemoglobin (HbA1c), fasting blood glucose (FPG) were measured by automatic biochemical analyzer. Levels of serum IGF-1 were measured by automatic chemiluminescence instrument in all subjects. The expression of miR-29b in serum was detected by quantitative real-time polymerase chain reaction (qRT-PCR). All subjects were scored with 24 Hamilton Scales (HAMD). Results The serum TC, TG, LDL, FPG, HbA1c, and HAMD scores of patients with depression in T2DM were significantly higher than those of control group and patients with T2DM (P<0.05); the serum TC, TG, FPG, HbA1c of patients with T2DM were significantly higher than those of the control group (P<0.05). The levels of serum miR-29b in patients with T2DM and depression were significantly lower than those in patients with T2DM and control group (P<0.05), while the level of IGF-1 was significantly higher than that in patients with T2DM and in control group (P<0.05); the level of serum miR-29b in patients with T2DM was significantly lower than that in control group (P<0.05), while the level of IGF-1 was significantly higher than that in control group (P<0.05). The levels of serum miR-29b in patients with severe depression and T2DM were significantly lower than those in patients with mild or moderate depression (P<0.05), while the level of IGF-1 showed the opposite (P<0.05). There was a significant negative correlation between serum miR-29b and IGF-1 level in patients with T2DM and depression (P<0.05). Logistic regression analysis showed that high levels of serum HbA1c (≥11.06%) and IGF-1 (≥25.74 ng/ml) were risk factors for depression in patients with T2DM, and high level of serum miR-29b (≥0.39) was protective (P<0.05). Conclusions The serum levels of IGF-1 increased and miR-29b decreased in patients with type 2 diabetes mellitus and depression. Serum levels of miR-29b were negatively correlated with the levels of IGF-1. High levels of IGF-1 were risk factors for depression in patients with type 2 diabetes mellitus, and high levels of miR-29b were protective factors. Key words: MicroRNAs; Insulin-like growth factor I; Diabetes mellitus, type 2; Depressive disorder

Elastography detected solid organ stiffness increased in patients with acromegaly.

Elastography is a method to examine the increase in solid organs stiffness (SOS), and there is no data in the literature regarding to its use in patients with acromegaly. In this study, we aimed to investigate the change of SOS in patients with acromegaly and to determine the parameters closely related to SOS in same patient groups.We included 40 subjects with acromegaly and 40 healthy control subjects. In addition to routine renal, liver and thyroid ultrasonography (USG), SOS for 3 solid organs were measured by elastography. The participants of the study were divided into 3 groups as the control (Group-I), acromegaly patients with remission (Group-II), and acromegaly patients without remission (Group-III).Insulin growth factor-1 (IGF-1) level significantly increased from Group-I to Group-III. Glucose, creatinine, albuminuria, alkaline phosphatase, TSH, and growth factor levels were highest in Group-III and statistically significance was found only between Group-I and Group-III. Liver, kidney and thyroid size and echogenicity were increased from Group-I to Group-III. Liver and renal stiffness and thyroid gland strain ratio significantly increased from Group-I to Group-III and these parameters were statistically different between all groups. In linear regression analysis, IGF-1 levels were independent determinants of SOS.SOS values of acromegaly patients with active disease were significantly increased compared to both the control group and the acromegaly patients in remission phase. Serum IGF-1 levels were independently associated with SOS in these patients. SOS measurement should be part of a routine USG examination in patients with acromegaly, especially in patients during active disease.

Effect of Iron Deficiency Anemia on IGF-1 Level Among Sample of Children

Background and objectives:Iron-deficiency anemia is a worldwide nutritional problem and an important public health problem especially in developing countries. The aim of this study was to compare the mean insulin like growth factor-1 of anemic children with that of non-anemic children and to correlate the levels of insulin like growth factor-1 with the levels of serum ferritin. Methods:cross-sectional study included fifty children. Measurement of levels of insulin like growth factor-1 was done in 25 children with iron deficiency anemia and compared with twenty-five age- and sex- matched non anemic children. Results: The mean age + SD were 6.11 + 3.31 years, ranging. There was significant difference detected between the iron deficiency anemia and control group regarding the mean values of insulin like growth factor-1 level as there was more than one third of iron deficiency anemia group had insulin like growth factor-1 levels lower than that of the control group. There was a relatively strong, significant positive correlation between serum ferritin levels with insulin like growth factor-1 levels. Conclusions:A significant correlation was observed between serum ferritin and serum insulin growth factor-1 level, since less serum ferritin levels is associated with less insulin growth factor-1 levels among anemic group compared with control group, implying that the effect of IDA on insulin like growth factor-1 level may differ according to body iron status.