Low Serum Insulin-like Growth factor-I Research Articles

Human Growth Hormone but Not Human Insulin-Like Growth Factor-I Enhances Recovery from Neonatal Malnutrition in Rats

The ability of hormonal therapy to enhance recovery from neonatal mainutrition was assessed in rats. Pups were mainourished via maternal food restriction (60% control intake). On d 16, restricted pups (n = 50) (62% control body wt) were refed until d 20 and were given growth hormone, insulin-like growth factor-I, destripeptide [1,3] insulin-like growth factor-I, or saline (placebo). Refed-placebo pups attained 80% of control body weight by d 20. Growth hormone treatment caused a greater weight gain than refeeding alone (P ≤ 0.05). Treatment with insulin-like growth factor-I and destripeptide [1,3] insulin-like growth factor-I did not affact body weight. All three hormones increased spleen and kidney weights (P ≤ 0.05) compared with the refedplacebo group, whereas only growth hormone increased muscle weight (P ≤0.05). Mainourished pups had lower serum insulin-like growth factor-I (P ≤ 0.05) and insulin-like growth factor binding protein-3 (P ≤ 0.05), and higher serum insulin-like growth factor binding protein-2 (P ≤ 0.05) and hepatic insulin-like growth factor binding protein-2 mRNA (P ≤ 0.05) than controls. Refeeding increased serum insulin-like growth factor-I compared with restricted pups (P ≤ 0.05), and insulin-like growth factor-I treatment caused a further increased in serum insulin-like growth factor-I compared with the refedplacebo group (P ≤ 0.05). These results show that growth hormone was moderately effective at increasing body weight gain and muscle growth during recovery from mainutrition.

Low Serum Insulin-like Growth Factor-I Is Associated with Decline in Hippocampal Volume in Stable Mild Cognitive Impairment but not in Alzheimer’s Disease

Background:Serum insulin-like growth factor-I (IGF-I) has shown some association with hippocampal volume in healthy subjects, but this relation has not been investigated in stable mild cognitive impairment (sMCI) or Alzheimer’s disease (AD).Objective:At a single memory clinic, we investigated whether serum IGF-I was associated with baseline magnetic resonance imaging (MRI)-estimated brain volumes and longitudinal alterations, defined as annualized changes, up to 6 years of follow-up.Methods:A prospective study of patients with sMCI (n = 110) and AD (n = 60). Brain regions included the hippocampus and amygdala as well as the temporal, parietal, frontal, and occipital lobes, respectively.Results:Serum IGF-I was statistically similar in sMCI and AD patients (112 versus 123 ng/mL, p = 0.31). In sMCI, serum IGF-I correlated positively with all baseline MRI variables except for the occipital lobe, and there was also a positive correlation between serum IGF-I and the annualized change in hippocampal volume (rs = 0.32, p = 0.02). Furthermore, sMCI patients having serum IGF-I above the median had lower annual loss of hippocampal volume than those with IGF-I below the median (p = 0.02). In contrast, in AD patients, IGF-I did not associate with baseline levels or annualized changes in brain volumes.Conclusion:In sMCI patients, our results suggest that IGF-I exerted neuroprotective effects on the brain, thereby maintaining hippocampal volume. In AD, serum IGF-I did not associate with brain volumes, indicating that IGF-I could not induce neuroprotection in this disease. This supports the notion of IGF-I resistance in AD.

A Rare Cause of Recurrent Hypoglycemia - The “Big-IGF-II” Factor

Abstract Introduction: Hormone secreting tumors are a rare cause of hypoglycemia. Here we present an interesting case of paraneoplastic phenomenon resulting in a non-islet cell tumor causing hypoglycemia (NICTH) from a solitary fibrous tumor (SFT). Clinical Case: An 83-year-old female with a history of hypertension presented with recurrent episodes of lightheadedness and falls for one month. Review of systems was negative except for insignificant weight loss. Her vital signs and physical examination were unremarkable. Only significant finding on initial blood work was a blood glucose level of 30 mg/dL (n: >70mg/dL). Additional work-up of hypoglycemia revealed a low serum free insulin level 0.6 IU/mL (n:1.5 - 14.9 IU/mL), low proinsulin <4 pmol/L (n: <18.8 pmol/L), low C-peptide level 0.14 ng/mL (n: 0.80-3.85 ng/mL), low serum insulin-like growth factor-I (IGF-I) 33 ng/ml (n:34-246 ng/ml) and elevated IGF-II levels 370 ng/mL (n:47-350 ng/mL). Blood sulfonylurea and insulin antibodies screen were negative, ACTH and morning cortisol levels were within normal limits. A CT scan of chest, abdomen and pelvis for neoplastic workup demonstrated a large heterogeneous mass within the lower lobe of the right lung. A CT-guided biopsy disclosed spindle cell neoplasm, positive for signal transducer and activator of transcription-6 (STAT6) and CD34. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed the NGFI-A binding protein 2 (NAB2) and STAT6 fusion which is specific for solitary fibrous tumor (SFT). She underwent surgical resection of the thoracic mass which resulted in complete resolution of her symptoms. Clinical Lessons: NICTH is a paraneoplastic syndrome associated with various benign and malignant tumors including SFT, hemangiopericytoma and metastatic hepatocellular carcinoma to name a few. Our case is an example of NICTH associated with SFT called Doege-Potter syndrome. The prevalence of hypoglycemia is seen in less than 5% of patients with SFT. It is often secondary to ectopic overexpression of unprocessed precursor ‘big’ IGF-II molecule, which binds to IGF-I receptor, resulting in tumorigenesis. An IGF-II/IGF-1 ratio is a sensitive marker and a value of more than 10 suggests excess production of IGF-II and is likely the cause of NICTH. Physicians should be cognizant of NICTH, especially in non-diabetic, otherwise healthy individuals in whom preliminary workup for hypoglycemia is negative and should look to identify any potential tumor as the likely cause. Surgical treatment is often the only curative option. Frequent meals, dextrose infusion, glucagon and growth hormone are bridging modalities until definitive surgical treatment.

Anthropometric, biochemical and hormonal profiles of the partially admixed pygmoid group in Rampasasa (Flores, Indonesia).

We performed a cross-sectional study on anthropometric and laboratory characteristics of inhabitants of Rampasasa (Flores, Indonesia). Adults were categorised according to ancestry into three groups: pygmoid (P/P, offspring of pygmoid parents, n=8), mixed pygmoid (P/N, offspring of pygmoid and non-pygmoid parents, n=12) and non-pygmoid (N/N, n=10). Children (n=28) were P/N. Measurements included height, weight, sitting height, arm span, head circumference, haematological analysis and serum albumin, calcium, vitamin D, insulin-like growth factor-I (IGF-I) and IGF binding protein 3 (IGFBP-3). Pubertal stage and bone age was assessed in children. Anthropometric data were expressed as standard deviation score (SDS) for age. IGF-I, IGFBP-3 and IGF-I/IGFBP-3 ratio were expressed as SDS for age, bone age and pubertal stage. Mean height SDS showed a gradient from P/P (-4.0) via P/N (-3.2) to N/N (-2.3) (-3.4,-3.1 and-2.2 adjusted for age-associated shrinking). Sitting height and head circumference showed similar gradients. Serum IGF-I SDS was similar among groups (approximately-1 SDS). IGFBP-3 SDS tended toward a gradient from P/P (-1.9) via P/N (-1.5) to N/N (-1.1), but IGF-I/IGFBP-3 ratio was normal in all groups. In P/P and P/N, mean head circumference SDS was >2SD greater than mean height SDS. Children showed a progressive growth failure and bone age delay, delayed female pubertal onset and an initial low serum IGF-I, normal IGFBP-3 and low IGF-I/IGFBP-3 ratio. P/P showed proportionate short stature with relative macrocephaly and relatively low IGFBP-3; P/N presented an intermediate pattern. P/N children were progressively short, showed delayed skeletal maturation, delayed puberty in girls and low IGF-I and IGF-I/IGFBP-3.

Circulating Insulin-Like Growth Factor I is Involved in the Effect of High Fat Diet on Peripheral Amyloid β Clearance.

Obesity is a risk factor for Alzheimer’s disease (AD), but underlying mechanisms are not clear. We analyzed peripheral clearance of amyloid β (Aβ) in overweight mice because its systemic elimination may impact brain Aβ load, a major landmark of AD pathology. We also analyzed whether circulating insulin-like growth factor I (IGF-I) intervenes in the effects of overweight as this growth factor modulates brain Aβ clearance and is increased in the serum of overweight mice. Overweight mice showed increased Aβ accumulation by the liver, the major site of elimination of systemic Aβ, but unaltered brain Aβ levels. We also found that Aβ accumulation by hepatocytes is stimulated by IGF-I, and that mice with low serum IGF-I levels show reduced liver Aβ accumulation—ameliorated by IGF-I administration, and unchanged brain Aβ levels. In the brain, IGF-I favored the association of its receptor (IGF-IR) with the Aβ precursor protein (APP), and at the same time, stimulated non-amyloidogenic processing of APP in astrocytes, as indicated by an increased sAPPα/sAPPβ ratio after IGF-I treatment. Since serum IGF-I enters into the brain in an activity-dependent manner, we analyzed in overweight mice the effect of brain activation by environmental enrichment (EE) on brain IGF-IR phosphorylation and its association to APP, as a readout of IGF-I activity. After EE, significantly reduced brain IGF-IR phosphorylation and APP/IGF-IR association were found in overweight mice as compared to lean controls. Collectively, these results indicate that a high-fat diet influences peripheral clearance of Aβ without affecting brain Aβ load. Increased serum IGF-I likely contributes to enhanced peripheral Aβ clearance in overweight mice, without affecting brain Aβ load probably because its brain entrance is reduced.

Current concepts of the diagnosis of adult growth hormone deficiency

In adults, growth hormone (GH) deficiency is associated with increased visceral adiposity, decreased lean body mass, bone mineral density and exercise capacity, dyslipidemia, insulin resistance, increased cardiometabolic and fracture risk, and impaired quality of life. The aim of the present article is to review the diagnosis of GH deficiency in adults. To avoid overdiagnosis of GH deficiency, it is critical to evaluate only patients at risk for pituitary dysfunction, including those who have had sellar masses, pituitary surgery, radiation therapy, traumatic brain injury, subarachnoid hemorrhage or childhood onset GH deficiency. Evaluation for GH deficiency should be undertaken after testing and replacement of other pituitary hormone deficits. Since GH secretion is pulsatile, measuring serum GH levels randomly is not helpful in establishing the diagnosis of GH deficiency. Serum insulin-like growth factor I (IGF-I) levels lack substantial diurnal variation but also lack sufficient sensitivity and specificity in the diagnosis of GH deficiency in adults. However, adults with multiple (≥3) additional pituitary hormone deficiencies, risk factors for hypopituitarism and low serum IGF-I levels are very likely to be GH deficient. In most cases, the diagnosis of GH deficiency requires stimulation testing. These tests involve the administration of a pharmacologic agent that normally stimulates GH release from pituitary somatotrophs, including insulin, glucagon, growth hormone releasing hormone-arginine or macimorelin, followed by sampling of serum specimens at regular intervals for GH assay. Patients with a peak GH level that is below a predetermined cutpoint are classified as GH deficient. A systematic approach to the diagnosis of GH deficiency is essential in order to accurately identify adults who may benefit from GH replacement.

1946-P: Insulin-Like Growth Factor-1 Protects against the Detrimental Effects of Advanced Glycation End Products and High Glucose in Myoblastic C2C12 Cells

Previous studies have shown that diabetes mellitus increases the risk of sarcopenia. We previously reported that higher serum advanced glycation end product (AGE) and lower serum insulin-like growth factor-I (IGF-I) were independently associated with muscle mass reduction in patients with type 2 diabetes. The present study examined effects of AGEs and IGF-I on myogenic differentiation and apoptosis in C2C12 cells. Real-time PCR and western blot analyses showed that AGE3 significantly decreased the mRNA and protein expressions of MyoD and Myogenin, whereas IGF-I significantly increased them and reversed the effects of AGE3. AGE3 significantly decreased endogenous IGF-I expression and suppressed IGF-I-induced Akt activation. High glucose (22 mM), but not AGE3, significantly increased expression of receptor for AGEs (RAGE), while IGF-I significantly decreased it. Moreover, DNA fragment ELISA showed that AGE2 and AGE3 significantly increased apoptosis of C2C12 cells, whereas IGF-I significantly suppressed the AGE2- and AGE3-induced apoptosis. To investigate whether high glucose enhances the AGE3’ effects, the effects of co-treatment with high glucose and AGE3 were examined. Although high glucose alone did not affect the apoptosis of C2C12 cells, it enhanced AGE3-induced apoptosis. IGF-I significantly reversed the effects of co-incubation of high glucose and AGEs on the expression of MyoD and Myogenin as well as the apoptosis. These findings indicate that AGE3 inhibits myogenic differentiation and increases apoptosis in C2C12 cells, and that high glucose increases RAGE and enhances the AGE3-induced apoptosis, suggesting that AGEs and high glucose might contribute to the reduction of muscle mass and function. Moreover, IGF-I reversed the detrimental effects of AGEs and high glucose in myoblastic cells; thus, IGF-I-Akt signal could be a therapeutic target of DM-induced sarcopenia. Disclosure I. Kanazawa: None. N. Adachi: None. K. Tanaka: None. A. Takeno: None. M. Notsu: None. S. Tanaka: None. T. Sugimoto: None.

Relative Risks of Contributing Factors to Morbidity and Mortality in Adults With Craniopharyngioma on Growth Hormone Replacement.

In adults, craniopharyngioma (CP) of either childhood-onset (CO-CP) or adult-onset (AO-CP) is associated with increased morbidity and mortality, but data on the relative risks (RRs) of contributing factors are lacking. To assess the RRs of factors contributing to morbidity and mortality in adults with CO-CP and AO-CP. Data on 1669 patients with CP from KIMS (Pfizer International Metabolic Database) were analyzed using univariate and multiple Poisson and Cox regression methods. When CO-CP and AO-CP groups were combined, history of stroke and hyperlipidemia increased cardiovascular risk, higher body mass index (BMI) and radiotherapy increased cerebrovascular risk, and increased waist circumference increased the risk of developing diabetes mellitus (DM). Compared with patients with CO-CP, patients with AO-CP had a threefold higher risk of tumor recurrence, whereas being female and previous radiotherapy exposure conferred lower risks. Radiotherapy and older age with every 10 years from disease onset conferred a 2.3- to 3.5-fold risk for developing new intracranial tumors, whereas older age, greater and/or increasing BMI, history of stroke, and lower insulinlike growth factor I (IGF-I) standard deviation score measured at last sampling before death were related to increased all-cause mortality. Compared with the general population, adults with CP had 9.3-, 8.1-, and 2.2-fold risks of developing DM, new intracranial tumors, and early death, respectively. Conventional factors that increase the risks of cardio- and cerebrovascular diseases and DM and risks for developing new intracranial tumors contributed to excess morbidity and mortality. In addition, lower serum IGF-I level measured from the last sample before death was inversely associated with mortality risk in patients with CP.

Low serum insulin-like growth factor-I (IGF-I) level is associated with increased risk of vascular dementia

BackgroundInsulin-like growth factor-I (IGF-I) is important for the adult brain, but little is known of the role of IGF-I in Alzheimeŕs disease (AD) or vascular dementia (VaD). MethodsA prospective study of 342 patients with subjective or objective mild cognitive impairment recruited at a single memory clinic. We determined whether serum IGF-I concentrations at baseline were associated with the risk of all-cause dementia, AD, or VaD. Patients developing mixed forms of AD and VaD were defined as suffering from VaD. The statistical analyses included Cox proportional hazards regression analysis. ResultsDuring the follow-up (mean 3.6 years), 95 (28%) of the patients developed all-cause dementia [AD, n=37 (11%) and VaD, n=42 (12%)]. Low as well as high serum IGF-I (quartile 1 or 4 vs. quartiles 2–3) did not associate with all-cause dementia [crude hazard ratio (HR) 1.30, 95% confidence interval (CI): 0.81–2.08 and crude HR 1.05, 95% CI: 0.63–1.75, respectively] or AD (crude HR 0.79, 95% CI: 0.35–1.79 and crude HR 0.94, 95% CI: 0.43–2.06, respectively]. In contrast, low serum IGF-I concentrations were associated with increased risk of VaD (quartile 1 vs. quartiles 2–3, crude HR 2.22, 95% CI: 1.13–4.36). The latter association remained significant also after adjustment for multiple covariates. ConclusionsIn a memory clinic population, low serum IGF-I was a risk marker for subsequent VaD whereas low IGF-I did not associate with the risk of AD. High serum IGF-I was not related to the risk of conversion to dementia.

A Coordinated Action of Blood-Borne and Brain Insulin-Like Growth Factor I in the Response to Traumatic Brain Injury.

In response to injury, the brain produces different neuroprotective molecules, such as insulin-like growth factor I (IGF-I). However, IGF-I is also taken up by the brain from the circulation in response to physiological stimuli. Herein, we analyzed in mice the relative contribution of circulating and locally produced IGF-I to increased brain IGF-I levels after insult. Traumatic brain injury (TBI) induced by a controlled impact resulted in increased IGF-I levels in the vicinity of the lesion, but mice with low serum IGF-I showed significantly lower increases. Indeed, in normal mice, peripheral IGF-I accumulated at the lesion site after injury, and at the same time serum IGF-I levels decreased. Collectively, these data suggest that serum IGF-I enter into the brain after TBI and contributes to increased brain IGF-I levels at the injury site. This connection between central and circulating IGF-I provides an amenable route for treatment, as subcutaneous administration of IGF-I to TBI mice led to functional recovery. These latter results add further support to the use of systemic IGF-I or its mimetics for treatment of brain injuries.

A Concerted Action Of Estradiol And Insulin Like Growth Factor I Underlies Sex Differences In Mood Regulation By Exercise

Mood homeostasis present sexually dimorphic traits which may explain sex differences in the incidence of mood disorders. We explored whether diverse behavioral-setting components of mood may be differentially regulated in males and females by exercise, a known modulator of mood. We found that exercise decreases anxiety only in males. Conversely, exercise enhanced resilience to stress and physical arousal, two other important components of mood, only in females. Because exercise increases brain input of circulating insulin-like growth factor I (IGF-I), a potent modulator of mood, we explored whether sex-specific actions of exercise on mood homeostasis relate to changes in brain IGF-I input. We found that exercise increased hippocampal IGF-I levels only in cycling females. Underlying mechanism involved activation of estrogen (E2) receptors in brain vessels that led to increased uptake of serum IGF-I as E2 was found to stimulate IGF-I uptake in brain endothelial cells. Indeed, modulatory effects of exercise on mood were absent in female mice with low serum IGF-I levels or after either ovariectomy or administration of an E2 receptor antagonist. These results suggest that sex-specific brain IGF-I responses to physiological stimuli such as exercise contribute to dimorphic mood homeostasis that may explain sex differences in affective disorders.

Effect of insulin-like growth factor-I during the early postnatal period in intrauterine growth-restricted rats.

Insulin-like growth factor-I (IGF-I) is essential for perinatal growth and development; low serum IGF-I has been observed during intrauterine growth restriction (IUGR). We investigated the effects of recombinant human (rh) IGF-I in IUGR rats during the early postnatal period. Intrauterine growth restriction was induced by bilateral uterine artery ligation in pregnant rats. IUGR pups were divided into two groups injected daily with rhIGF-I (2 mg/kg; IUGR/IGF-I, n = 16) or saline (IUGR/physiologic saline solution (PSS), n = 16) from postnatal day (PND) 7 to 13. Maternal sham-operated pups injected with saline were used as controls (control, n = 16). Serum IGF-I and IGF binding proteins (IGFBP) 3 and 5 were measured on PND25. The expression of Igf-i, IGF-I receptor (Igf-ir), Igfbp3, and 5 mRNA in the liver and brain was measured using real-time polymerase chain reaction on PND25. Immunohistochemical staining of the liver for IGF expression was performed. Mean bodyweight on PND3 and PND25 in the IUGR pups (IUGR/IGF-I and IUGR/PSS) was significantly lower than that of the control pups. Serum IGF-I and hepatic Igf-ir mRNA in the IUGR pups were significantly lower than those in the control pups. In the IUGR/IGF-I group, hepatic Igfbp3 mRNA and liver immunohistochemical staining were increased. In the IUGR/PSS and control pups, there were no significant differences between these two groups in serum IGFBP3 and IGFBP5, hepatic Igf-i and Igfbp-5 mRNA, or brain Igf mRNA. No benefits on body and brain weight gain but an effective increase in hepatic IGFBP-3 was observed after treatment with 2 mg/kg rhIGF-I during the early postnatal period.

Decreased serum insulin-like growth factor-I level is associated with the increased mortality in type 2 diabetes mellitus.

Mortality is increased in type 2 diabetes mellitus (T2DM). Although previous studies showed that decreased serum insulin-like growth factor-I (IGF-I) levels are associated with diabetic complications, little is known about the association between serum IGF-I level and the mortality in patients with T2DM. This is a historical cohort study with end-point of all-cause mortality in 234 men and 191 women with T2DM. Standard deviation of serum IGF-I [IGF-I (SD)] was calculated by adjusting for age and gender. Of 234 male and 191 female, 46 and 25 patients died, respectively, for the follow-up period of almost 7 years. Unadjusted survival analyses showed that lower IGF-I was associated with higher mortality in men and women (p<0.001 and p=0.004, respectively). In Cox regression analyses adjusted for age, duration of diabetes, body mass index, HbA1c, and serum creatinine, serum IGF-I was inversely associated with the mortality [men, hazard ratio (HR)=0.40, 95% confidence interval (CI)=0.25-0.64 per SD increase, p<0.001; women, HR=0.28, 95%CI 0.08-0.96, p=0.043]. When IGF-I was replaced to IGF-I (SD), the relationships are still significant. After additional adjustments for serum albumin, systolic blood pressure, ALT, LDL-cholesterol, smoking, and past history of cardiovascular disease, the association between serum IGF-I and the mortality in men remained significant (HR=0.31, 95%CI 0.15-0.65, p=0.002), but not in women. The present study showed that lower serum IGF-I levels were associated with the increased all-cause mortality in patients with T2DM, suggesting that serum IGF-I could be clinically useful for assessing the risk of mortality in the population.

Serum insulin-like growth factor-I and amyloid beta protein in Alzheimer's disease: relationship with cognitive function.

Previous studies have suggested that insulin-like growth factor-I (IGF-I) deficiency may lead to cognitive deficits in neurodegenerative diseases such as Alzheimer's disease. The present study aimed to investigate the possible relationship between cognitive function and concentration of IGF-I or amyloid beta protein (Aβ) in serum in Alzheimer's patients. A total of 81 Japanese patients were enrolled in this study. Concentrations of IGF-I, Aβ42, and Aβ40 in serum were measured. Two neuropsychological tests, Mini-Mental State Examination and Hasegawa's Dementia Scale-Revised (HDS-R), were also performed. Linear correlations among the age, serum IGF-I, serum Aβ42 or Aβ40, Aβ42/Aβ40 ratio, Mini-Mental State Examination or HDS-R total score, and the scores for six HDS-R subscales were analyzed by regression analysis. IGF-I showed a significant negative correlation with age (β = -0.357, P = 0.002) and a positive correlation with Aβ42/Aβ40 ratio (β = 0.318, P = 0.007). Serum IGF-I and both the Mini-Mental State Examination and the HDS-R total score also correlated (β = 0.505, β = 0.524, P < 0.01). Among the HDS-R subscales, 'Recall' (ρ = 0.379, P < 0.01), 'Verbal fluency' (ρ = 0.360, P < 0.01), and 'Attention and calculation' (ρ = 0.389, P < 0.01) showed significant positive correlations with serum IGF-I. The results, specifically that lower serum IGF-I was associated with cognitive impairment, suggest that metabolism of IGF-I may be involved in the pathogenesis of cognitive deficits in Alzheimer's disease.

The relationship between serum insulin-like growth factor I levels and ischemic stroke risk.

ObjectiveThe aim of the study was to assess the relationship between insulin-like growth factor I (IGF-I) serum levels and acute ischemic stroke (AIS) in a Chinese population.MethodsAll consecutive patients with first-ever AIS from August 1, 2011 to July 31, 2013 were recruited to participate in the study. The control group comprised 200 subjects matched for age, gender, and conventional vascular risk factors. IGF-I serum levels were determined by chemiluminescence immunoassay. The National Institutes of Health Stroke Scale (NIHSS) score was assessed on admission blinded to serum IGF-I levels.ResultsThe median serum IGF-1 levels were significantly (P = 0.011) lower in AIS patients (129; IQR, 109–153 ng/mL) compared with control cases (140; IQR, 125–159 ng/mL). We found that an increased risk of AIS was associated with IGF-I levels ≤135 ng/mL (unadjusted OR: 4.17; 95% CI: 2.52–6.89; P = 0.000). This relationship was confirmed in the dose-response model. In multivariate analysis, there was still an increased risk of AIS associated with IGF-I levels ≤135 ng/mL (OR: 2.16; 95% CI:1.33–3.52; P = 0.002) after adjusting for possible confounders.ConclusionLower IGF-I levels are significantly related to risk of stroke, independent from other traditional and emerging risk factors, suggesting that they may play a role in the pathogenesis of AIS. Thus, strokes were more likely to occur in patients with low serum IGF-I levels in the Chinese population; further, post-ischemic IGF-I therapy may be beneficial for stroke.

Linear growth and endocrine function in children with ataxia telangiectasia.

Introduction:Ataxia telangiectasia (AT) is a rare, genetic, primary immune deficiency disease characterized by immunodeficiency and neurological manifestations, with an increased tendency to infection, malignancy, and autoimmune diseases. Both growth delay and endocrine abnormalities are occasionally reported in these patients.Patients and Methods:We studied growth parameters height (Ht), weight, body mass index (BMI) and calculated the Ht standard deviation scores (HtSDS) of 13 patients (age 7.7 ± 3.5 years-age range: 3–14.5 years) with AT in relation to their mid-parental Ht SDS (MPHtSDS). We measured their serum calcium (Ca), phosphorus (PO4), alkaline phosphatase, alanine transferase (ALT), serum ferritin, creatinine and albumin concentrations. Endocrine investigations included the assessment of serum free thyroxine (FT4), thyrotropin (TSH), insulin-like growth factor-I (IGF-I) and morning cortisol. Complete blood count and serum immunoglobulins (IgG, IgM and IgA antibodies) were also measured. Growth data were correlated to hormonal and immune data.Results:About 31% of patients with AT had short stature (HtSDS <−2). However, their MPHtSDS denoted that their short stature was familial because four out of 13 had MPHtSDS <−2. They had low BMI, and two of them had low serum albumin and IGF-I, denoting malnutrition or disturbed growth hormone secretion. Elevated serum ALT and ferritin in some patients suggest immune-related inflammation in the liver. 30% of patients had high TSH, two of them had low FT4 diagnosing overt (15%) and sub-clinical (15%) hypothyroidism. Anti-thyroid peroxidase antibodies were high in two out of 13 patients denoting immune-related thyroid aggression. Eight out of 13 patients had Vitamin D deficiency (<20 ng/ml) however, their serum Ca and PO4 levels were in the normal range. One adolescent girl (14.5 years) had hyper-gonadotropic hypogonadism (low estradiol and high follicle stimulating hormone). All patients had normal 8 AM cortisol and renal function. None of the growth parameters were correlated with the IgG, IgM or IgA levels.In summary:Patients with AT had a high prevalence of growth retardation and endocrine dysfunction in the form of low IGF-I, overt and subclinical hypothyroidism and hypogonadism. Physicians should be aware of these possible endocrinopathies for an early diagnosis and proper treatment.

Increase in tendon protein synthesis in response to insulin-like growth factor-I is preserved in elderly men

Insulin-like growth factor-I (IGF-I) is known to be an anabolic factor in tendon, and the systemic levels are reduced with aging. However, it is uncertain how tendon fibroblasts are involved in tendon aging and how aging cells respond to IGF-I. The purpose of this study was to investigate the in vivo IGF-I stimulation of tendon protein synthesis in elderly compared with young men. We injected IGF-I in the patellar tendons of young (n = 11, 20-30 yr of age) and old (n = 11, 66-75 yr of age) men, and the acute fractional synthesis rate (FSR) of tendon protein was measured with the stable isotope technique and compared with the contralateral side (injected with saline as control). We found that tendons injected with IGF-I had significantly higher protein FSR compared with controls (old group: 0.018 ± 0.015 vs. 0.008 ± 0.008, young group: 0.016 ± 0.009 vs. 0.009 ± 0.006%/h, mean ± SE, P < 0.01). This increase in protein synthesis was seen in both young and old men, with no differences between age groups. The old group had markedly lower serum IGF-I levels compared with young (165 ± 17 vs. 281 ± 27 ng/ml, P < 0.01). In conclusion, local IGF-I stimulated tendon protein synthesis in both young and old men, despite lower systemic IGF-I levels in the old group. This could indicate that the changed phenotype in aging tendon is not caused by decreased fibroblast function.

Serum Insulin-like Growth Factor-I Level Is an Independent Predictor of Recurrence and Survival in Early Hepatocellular Carcinoma: A Prospective Cohort Study

Insulin-like growth factor-I (IGF-I) reflects hepatic synthetic function and plays an important role in the development and progression of various cancers. In this study, we investigated whether pretreatment serum IGF-I levels predict time-to-recurrence (TTR) and overall survival (OS) in patients with early-stage hepatocellular carcinoma after curative treatment. Consecutive patients with hepatocellular carcinoma who had undergone surgical resection, radiofrequency ablation, or percutaneous ethanol injection as curative treatments of early hepatocellular carcinoma were included from two prospective cohorts and the training set (n = 101) and the validation set (n = 91) were established. Serum samples were collected before treatment and the levels of IGF-I and IGF-binding protein-3 (IGFBP-3) were analyzed with regard to their associations with recurrence and survival. In the training set, patients with low IGF-I levels showed significantly shorter TTR [median, 14.6 months; 95% confidence interval (CI), 1.8-27.5] than patients with high IGF-I levels (median, 50.8 months; 95% CI, 36.9-64.7; P < 0.001) during a median follow-up period of 52.4 months. In the multivariate analysis, low levels of IGF-I were an independent predictor of recurrence (HR, 2.49; 95% CI, 1.52-4.08; P < 0.001). Furthermore, together with high-serum α-fetoprotein and multiple tumors, low levels of IGF-I remained an independent predictor of poorer survival (HR, 8.00; 95% CI, 1.94-33.01; P = 0.004). Applied to the independent validation set, low-serum IGF-I levels maintained their prognostic value for shorter TTR and OS. Low-baseline IGF-I levels independently correlated with shorter TTR and poorer survival in patients with early-stage hepatocellular carcinoma after curative treatment.

Effects of Raloxifene on Bone Metabolism in Hemodialysis Patients

Effects of Raloxifene on Bone Metabolism in Hemodialysis Patients

Bone quality and vitamin K2 in type 2 diabetes: Review of preclinical and clinical studies

Type 2 diabetic patients are at high risk of bone fractures even if their bone mineral density is normal or high. This is likely explained by poor bone quality and extraskeletal factors. The present review was conducted to provide an overview of the currently available preclinical and clinical evidence on the effect of vitamin K(2) on bone quality in persons with type 2 diabetes. Vitamin K(2) stimulates γ-carboxylation of osteocalcin and can increase bone formation through steroid and xenobiotic receptors. Clinical studies of type 2 diabetic patients have shown detrimental collagen cross-links in bone; low serum insulin-like growth factor-I and osteocalcin concentration are associated with an increased risk of fractures. A therapeutic strategy for preventing fractures in type 2 diabetic patients remains to be established. One recent preclinical study showed that vitamin K(2) administration in a type 2 diabetic rat model had the following skeletal benefits: increased serum osteocalcin, improved collagen cross-link profiles, and increased bone strength. These new findings suggesting a possible beneficial effect of vitamin K(2) supplementation on bone quality in type 2 diabetes warrant further investigation.