High Insulin-like Growth Factor Binding Protein-1 Research Articles

Abstract 12938: Intrathoracic Visceral Adiposity is Inversely Associated With Insulin Like Growth Factor Binding Protein 1: The Longenity Study

Introduction: Higher insulin-like growth factor binding protein 1 (IGFBP-1) level in serum has been variably associated with better insulin sensitivity and lower rates of obesity, diabetes mellitus, and atherosclerosis; suggesting that it may have a protective role in cardiometabolic aging. We hypothesized that epicardial, intrathoracic, or total thoracic adiposity (EAT, IAT, or TTA, respectively) measured on thoracic CT, were inversely associated with IGFBP-1, providing an assessment of cardiometabolic status by computed tomography (CT). Methods: Participants (n=104) were prospectively enrolled from the LonGenity study at Albert Einstein Institute of Aging. Participants were of Ashkenazi descent and ≥65 years, 53% were offspring of parents with exceptional longevity (OPEL) and 47% were offspring with usual survival (OPUS). Exclusion criteria were prior coronary artery bypass or stent, heart rate > 100 beats/minute or not in sinus rhythm. Participants underwent a non-contrast gated CT. Adiposity was quantified using QFAT software (Cedars Sinai, CA). IGFBP-1 measures closest to the CT were used, ranging from 58 months before to 16 months after, with the majority within 1 year of the scan. Associations between IGFBP-1 and the adiposity were evaluated with linear regression with square-root of adiposity measures as the outcome. Each subject was weighted by the inverse of the years between CT and closest IGFBP-1 measurement. Results: IGFBP-1 levels were inversely associated with EAT (p =0.007), IAT (p = 0.003) and TTA (p = 0.003) after adjustment for age, sex, body mass index, OPEL/OPUS, diabetic medication, statin use, and high- and low-density lipoprotein levels. BMI explained 27.2% of the variation of TTA (p < 0.001) and IGFBP-1 explained an additional 6% of the variation. There was no association of OPEL/OPUS status with adiposity measures. Conclusion: In conclusion, higher IGFBP-1 was associated with lower cross-sectional TTA, suggesting that IGFBP-1 may be indicative of a favorable cardiometabolic environment in aging. Future studies should evaluate the utility of IGFBP-1, epicardial and thoracic visceral adiposity as indicators of cardiometabolic disease.

IGFBP1 Is a Predictive Factor for Haematogenous Metastasis in Patients With Gastric Cancer.

The clinicopathological significance and prognostic value of insulin-like growth factor binding protein 1 (IGFBP1) in gastric cancer have not been investigated to date. This study aimed to investigate the relationship of IGFBP1 expression with clinicopathological variables and prognosis. The correlation of IGFBP1 expression with the clinicopathological factors and the correlation of clinicopathogical factors with haematogenous metastasis in 219 gastric cancer patients who underwent surgery was examined. High IGFBP1 expression was significantly associated with a poorer disease-specific survival (p<0.001) and relapse-free survival (p<0.001) in univariable analysis although IGFBP1 was not an independent prognostic factor. High IGFBP1 expression was the only independent risk factor of haematogenous metastasis. High IGFBP1 expression was associated with haematogenous metastasis and poor survival. IGFBP1 might become a new prognostic factor and a target of molecular targeted therapy of gastric cancer.

High insulin-like growth factor-binding protein-1 (IGFBP-1) is associated with low relative muscle mass in older women

ObjectiveSkeletal muscles serve several important roles in maintaining good health. Insulin-like growth factor-1 (IGF-1) is a promoter of protein synthesis in skeletal muscle. Its binding protein, Insulin-like growth factor-binding protein-1 (IGFBP-1) can be one determinant of IGF-1 activity. In the present study we investigate the association between serum IGFBP-1 and muscle mass. DesignCross-sectional analysis of 4908 women, between 55 and 85years old, participating in the Swedish Mammography Cohort-Clinical. MethodsWe defined low relative muscle mass (LRMM) as an appendicular lean mass divided by height squared of less than 5.45 (kg/m2), assessed by dual energy x-ray absorptiometry. IGFBP-1 was measured by radioimmunoassay. Logistic regression was used to calculate odds-ratios of LRMM across quartiles of IGFBP-1. ResultsThe odds of LRMM increased across quartiles of IGFBP-1. In the age-adjusted model the odds-ratio (OR) of LRMM was 3.41 (95% CI: 2.55–4.56), comparing the highest to the lowest quartile. This estimate was attenuated in multivariate models (OR: 1.84, 95% CI: 1.34–2.53), mainly due to inclusion of fat mass index. ConclusionWomen with higher IGFBP-1 were more likely to have a low relative muscle mass. High IGFBP-1 may be a marker of a catabolic state.

Insulin-Like Growth Factor Binding Protein 1 Could Improve Glucose Regulation and Insulin Sensitivity Through Its RGD Domain.

Low circulating levels of insulin-like growth factor binding protein 1 (IGFBP-1) are associated with insulin resistance and predict the development of type 2 diabetes. IGFBP-1 can affect cellular functions independently of IGF binding through an Arg-Gly-Asp (RGD) integrin-binding motif. Whether causal mechanisms underlie the favorable association of high IGFBP-1 levels with insulin sensitivity and whether these could be exploited therapeutically remain unexplored. We used recombinant IGFBP-1 and a synthetic RGD-containing hexapeptide in complementary in vitro signaling assays and in vivo metabolic profiling in obese mice to investigate the effects of IGFBP-1 and its RGD domain on insulin sensitivity, insulin secretion, and whole-body glucose regulation. The RGD integrin-binding domain of IGFBP-1, through integrin engagement, focal adhesion kinase, and integrin-linked kinase, enhanced insulin sensitivity and insulin secretion in C2C12 myotubes and INS-1 832/13 pancreatic β-cells. Both acute administration and chronic infusion of an RGD synthetic peptide to obese C57BL/6 mice improved glucose clearance and insulin sensitivity. These favorable effects on metabolic homeostasis suggest that the RGD integrin-binding domain of IGFBP-1 may be a promising candidate for therapeutic development in the field of insulin resistance.

Effects of lifestyle on plasma levels of the IGF system and the antioxidants coenzyme Q10 and vitamin E in Kenyan rural and urban populations

ObjectiveOvernight fasting blood plasma insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-1 (IGFBP-1), coenzyme Q10, (CoQ) vitamin E and plasma lipids were compared between a semi-nomadic Samburu population and relatively urbanized cohorts from Nairobi, Kenya. Research design and methods143 middle aged subjects without known diabetes were included. IGF-I and IGFBP-1 were analyzed by RIA, and CoQ and vitamin E by HPLC. Plasma lipid levels were analyzed by standard laboratory methods routinely used in the clinics. ResultsThe age adjusted IGF-I serum levels were low in the Samburu male and female populations, ranging from 0 to −4 IGFSD-score (SDS), and a minor part of the investigated population reaching as low as −5 and −7 SDS. The Nairobi cohorts showed significantly higher values reaching from −2.5 to +1 SDS (P<0.0001). The nomadic Samburu population showed fasting IGFBP-1 values ranging from 30–100μg/l, while that of the urbanized Nairobi cohorts was considerably lower (25–60μg/l) (P<0.0001). CoQ concentrations of the Nairobi cohorts were 1.5–2.0nmol/ml similar to the levels found in several European countries. The Samburu population on the other hand showed extremely high CoQ values ranging from 2 to 9nmol/ml (P<0.0001). Vitamin E levels of the Nairobi group were low (5–20nmol/ml), but the Samburu population had even lower levels ranging from 3 to 15nmol/ml (P<0.0001). Plasma lipid levels such as cholesterol, triglycerides, LDL/HDL, ApoB/ApoA ratios as well as BMI and weight were significantly higher in the Nairobi population (P<0.0001). ConclusionsLow IGF-I and high IGFBP-1 levels of the Samburu cohorts indicate malnutrition. High lipid levels of the Nairobi cohorts indicate that these groups have several risk factors for cardiovascular diseases and diabetes type2.

Abstract B78: Adiposity and the IGF-axis in girls during pubertal development

Abstract Background: Increased childhood adiposity has been associated with decreased breast cancer risk, but the biologic mechanisms underlying this association are not well understood. Pubertal growth is in part driven by the insulin-like growth factor (IGF) system and adult measures of IGF have been associated with breast cancer. We hypothesize that childhood adiposity is associated with the IGF-axis and that levels set in childhood affect later breast cancer risk. We prospectively examine associations between childhood adiposity, as measured by body mass index (BMI)-for-age percentile (BMIPCT), and serum IGF-axis biomarkers (IGF-I, IGF binding protein 1(IGFBP-1), and IGF binding protein 3 (IGFBP-3)) among girls in the Dietary Intervention Study in Children (DISC). Methods: Data are from an ancillary hormone study of 268 of the 301 girls who participated in the DISC. Girls were 8-10 years old at baseline with a median follow-up of 7 years. Data from intervention and control groups were combined and intervention status was included in adjusted analyses. Fasting blood samples (n=563) collected at baseline, years 3, 5 and last visit were available for 219 premenarcheal and 201 postmenarcheal girls. Levels of IGF-I, IGFBP-1, and IGFBP-3 were determined using radioimmunoassays. Weight and height measurements were taken at baseline and subsequent visits by trained interviewers. BMI (weight/height2)–for-age percentiles were determined using the CDC growth chart. To mitigate skewness, biomarkers were log transformed. Adjusted geometric means of IGF biomarkers were calculated by quintiles of baseline BMIPCT. All adjusted analyses included age, age2, treatment group, baseline height, and physical activity. Associations of longitudinal BMIPCT with IGF biomarkers were estimated using multivariable linear mixed-effect models, accounting for repeated BMIPCT and IGF measurements within each girl across follow-up visits. Trend tests were performed on continuous BMIPCT using adjusted mixed-effect models to estimate percentage changes in IGF biomarkers during follow-up. Results: In adjusted analyses, premenarcheal girls in the lowest quintile of baseline BMIPCT had lower geometric mean IGF-I levels than all other quintiles (Q1= 236 ng/mL (95% confidence interval (CI): 211, 264) vs. Q5 mean=271 ng/ml (95% CI: 240, 307)). Girls in the lowest quintile of BMIPCT had higher IGFBP-1 levels that decreased linearly with BMIPCT quintile (Ptrend &amp;lt;0.0001). In continuous analyses, each 10 percentile increment in baseline BMIPCT was associated with a 2.4% increase (95% CI: 0.5%, 4.2%) in IGF-I (Ptrend=0.01) and a 7.2% decrease (95% CI: 4.9%, 9.6%) in IGFBP-1 (Ptrend&amp;lt;0.0001). There was no significant association between IGFBP-3 and BMIPCT. In post-menarcheal girls, each 10 percentile increment in baseline BMIPCT was associated with a 12.0% decrease (95% CI: 8.4 %,15.6%) in IGFBP-1 (Ptrend&amp;lt;0.0001), but no significant association with IGF-I or IGFBP-3. Conclusion: This study suggests that premenarcheal girls in the lowest quintile of BMI-for-age have lower IGF-I levels than in all other quintiles. Results also show increased adiposity, as measured by BMI-for-age, is significantly associated with decreased IGFBP-1 in both pre- and postmenarcheal girls. Further research is needed to confirm these findings, as well as to explore possible associations with breast development and potentially breast cancer risk. Citation Format: Ellen M. Velie, Zhenzhen Zhang, Jean M. Kerver, Joseph C. Gardiner, Clifford J. Rosen, Joanne F. Dorgan. Adiposity and the IGF-axis in girls during pubertal development. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B78.

Low serum 25-hydroxyvitamin D level predicts progression to type 2 diabetes in individuals with prediabetes but not with normal glucose tolerance

Vitamin D deficiency may increase the risk of type 2 diabetes. We therefore investigated whether serum concentrations of 25-hydroxyvitamin D [25(OH)D] would predict the development of prediabetes (impaired fasting glucose, impaired glucose tolerance or the two combined) and type 2 diabetes, either on their own or when combined with serum concentrations of IGF-1 or IGF-binding protein-1 (IGFBP-1), which may interact with 25(OH)D. At baseline, participants aged 35-56 years without known type 2 diabetes were examined using OGTTs, 25(OH)D and IGF peptide measurements, and anthropometric and lifestyle data. Participants who had prediabetes or type 2 diabetes at follow-up 8-10 years later were selected as cases; these were then age- and sex-matched to controls with normal glucose tolerance (NGT) at both baseline and follow-up, giving a total of 980 women and 1,398 men. Men but not women in the highest quartile of 25(OH)D level had a decreased OR for developing type 2 diabetes after adjustment for confounders (OR 0.52, 95% CI 0.30, 0.90), an effect accounted for by individuals with prediabetes, but not with NGT, at baseline. In both sexes, progression from prediabetes to type 2 diabetes was reduced by about 25% per 10 nmol/l increase in 25(OH)D. A high IGFBP-1 value was a better predictor of a reduced risk of type 2 diabetes than high 25(OH)D for both sexes, whereas high IGF-1 concentrations predicted a decreased risk only in men. High serum 25(OH)D concentrations predict a reduced risk of type 2 diabetes in individuals with prediabetes, but not NGT. There were no significant interactions between 25(OH)D and IGFBP-1 or IGF-1 in terms of risk of diabetes. Our data suggest that vitamin D supplementation should be evaluated for the prevention of type 2 diabetes in prediabetic individuals.

Total Insulinlike Growth Factor 1 and Insulinlike Growth Factor Binding Protein Levels, Functional Status, and Mortality in Older Adults

To assess the association between total insulinlike growth factor (IGF)-1, IGF binding protein-1 (IGFBP-1), and IGFBP-3 levels and functioning and mortality in older adults. Cohort study. One thousand one hundred twenty-two individuals aged 65 and older without prior cardiovascular disease events participating in the Cardiovascular Health Study. Baseline fasting plasma levels of IGF-1, IGFBP-1, and IGFBP-3 (defined as tertiles, T1-T3) were examined in relationship to handgrip strength, time to walk 15 feet, development of new difficulties with activities of daily living (ADLs), and mortality. Higher IGFBP-1 predicted worse handgrip strength (P-trend(T1-T3)<.01) and slower walking speed (P-trend(T1-T3)=.03), lower IGF-1 had a borderline significant association with worse handgrip strength (P-trend(T1-T3)=.06), and better grip strength was observed in the middle IGFBP-3 tertile than in the low or high tertiles (P=.03). Adjusted for age, sex, and race, high IGFBP-1 predicted greater mortality (P-trend(T1-T3)<.001, hazard ratio (HR)(T3vsT1)=1.48, 95% confidence interval (CI)=1.15-1.90); this association was borderline significant after additional confounder adjustment (P-trend(T1-T3)=.05, HR(T3vsT1)=1.35, 95% CI=0.98-1.87). High IGFBP-1 was associated with greater risk of incident ADL difficulties after adjustment for age, sex, race, and other confounders (P-trend(T1-T3)=.04, HR(T3vsT1)=1.40, CI=1.01-1.94). Neither IGF-1 nor IGFBP-3 level predicted mortality or incident ADL difficulties. In adults aged 65 and older, high IGFBP-1 levels were associated with greater risk of mortality and poorer functional ability, whereas IGF-1 and IGFBP-3 had little association with these outcomes.

A Prospective Study of C-Peptide, Insulin-like Growth Factor-I, Insulin-like Growth Factor Binding Protein-1, and the Risk of Colorectal Cancer in Women

Hyperinsulinemia, hyperglycemia, and elevated insulin-like growth factor (IGF)-1 levels have been implicated in the etiology of colorectal cancer. However, the joint effects of insulin and IGF-I have not been considered, and whether hyperinsulinemia or hyperglycemia is more etiologically relevant is unclear. IGF binding protein-1 (IGFBP-1) has been hypothesized to mediate the effects of insulin, but epidemiologic data on IGFBP-1 are sparse. We conducted a nested case-control study among the 32,826 women of the Nurses' Health Study who provided a blood sample in 1989 to 1990. After excluding diabetics, we confirmed 182 incident colorectal cancer cases over 10 years of follow-up and 350 controls. Cases were matched to two controls on year of birth, date of blood draw, and fasting status. C-peptide levels were weakly associated with risk of colon cancer [top quartile (Q4) versus bottom quartile (Q1): multivariable relative risk (MVRR), 1.76; 95% confidence interval (95% CI), 0.85-3.63]. Fasting IGFBP-1 was inversely associated with risk of colon cancer (MVRR, 0.28; 95% CI, 0.11-0.75). We observed no clear association between glycosylated hemoglobin and risk for colorectal cancer. The IGF-I to IGFBP-3 molar ratio was associated with colon cancer risk (MVRR, 2.82; 95% CI, 1.35-5.88), and women with low levels of both IGF-I/IGFBP-3 and C-peptide (or high IGFBP-1) were at low risk, and elevation of either was sufficient to increase risk. Although altering IGF-I levels may not be practical, the growing burden of obesity and consequently hyperinsulinemia, which seems increasingly important for colon cancer, may be a target for effective prevention.

Sex Hormone-Binding Globulin and Insulin-Like Growth Factor-Binding Protein-1 as Indicators of Metabolic Syndrome, Cardiovascular Risk, and Mortality in Elderly Men

Two binding proteins, SHBG and IGF-binding protein-1 (IGFBP-1), are both down-regulated by insulin and therefore could serve as potential indicators of the metabolic syndrome and hyperinsulinemia-related cardiovascular risk. We compared serum SHBG and IGFBP-1 as potential markers of abnormal glucose tolerance, the metabolic syndrome, diabetes mellitus, cardiovascular risk factors, and total, cardiovascular, and coronary heart disease mortality in elderly men. Of the original cohort of 1711 men, 524 were alive on January 1, 1989, and 413 participated in the 30-yr examination, of whom 335 men, aged 70-89 yr, formed the study group for the present analysis. Low SHBG and IGFBP-1 were both associated with an increased prevalence of abnormal glucose tolerance and the metabolic syndrome, but only SHBG was associated with diabetes mellitus. SHBG was less influenced by body mass index than IGFBP-1. Low SHBG indicated increased cardiovascular and coronary disease mortality; the association remained after adjustment for abnormal glucose tolerance, but not after adjustment for prevalent cardiovascular disease. IGFBP-1 had no association with mortality. It is concluded that low SHBG is a better indicator of increased cardiovascular mortality than low or high IGFBP-1.

C-reactive protein and the insulin-like growth factor (IGF)-system in relation to risk of cardiovascular disease in different ethnic groups

Inflammatory processes, marked in part by the acute phase reactant C-reactive protein (CRP) and insulin resistance are implicated in atherogenesis. Low insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) concentrations are closely associated with insulin resistance. We examined CRP in ethnic groups with differing risk for cardiovascular disease and type 2 diabetes and its relationship with insulin sensitivity (Homeostasis model assessment (HOMA)-S) and the IGF system. European ( n=155), Pakistani ( n=108) and African–Caribbean (African Caribbean) ( n=177) origin participants were randomly sampled from population registers. All underwent basic anthropometry, glucose tolerance testing and measurement of insulin sensitivity, CRP and other metabolic variables. CRP was significantly lower in African Caribbean men and women than in other ethnic groups. Across all groups CRP correlated negatively with (HOMA-S) (ρ=−0.29, P<0.001). Regression analysis which included ethnicity and body mass index (BMI) showed that low HOMA-S (β=−0.17, P<0.001) and low IGFBP-1 (β=−0.14, P<0.001) were independently and inversely associated with CRP, but the effect was modified by obesity. In obese subjects insulin sensitivity was not associated with CRP. However, for the whole population, a 2.7 mg/l increase in CRP was associated with a 50% (95% confidence interval (CI) 10–210%) greater risk of WHO defined metabolic syndrome, independent of IGF-I (odds ratio (OR) 0.46 (95% CI 0.22–0.96)), IGFBP-1 (OR 0.58 (0.44–0.76)), female sex (OR 0.43 (0.22–0.84)), NEFA (OR 1.06 (1.03–1.09)) and Pakistani ethnicity. High CRP (as a measure of chronic subclinical inflammation), low IGF-I and low IGFBP-1 are independently associated with the presence of the metabolic syndrome and with insulin resistance. In obese subjects insulin sensitivity is not associated with changes in CRP whilst in non-obese subjects CRP independently contributes to variation in HOMA-S.

Serum insulin-like growth factor (IGF)-I and IGF-binding protein-1 in elderly people: relationships with cardiovascular risk factors, body composition, size at birth, and childhood growth.

The IGF system is important in regulation of fetal and childhood growth. In later life, IGF-I and IGF-binding protein-1 (IGFBP-1) have been implicated in the pathogenesis of arteriosclerosis. They are, thus, potential candidates in explaining the link between early growth and adult cardiovascular disease. We measured fasting serum IGF-I and IGFBP-1 concentrations in 394 men and women from a cohort of 7086 individuals, born between 1924 and 1933 in Helsinki, Finland, whose weight and height were recorded at birth and from 7 to 15 yr of age. They also underwent clinical examination, including measurement of body fat using bioimpedance, blood pressure, glucose tolerance, and plasma insulin and fibrinogen concentrations. Serum IGF-I was positively correlated with fasting glucose (r = 0.10, P = 0.06) and fibrinogen (r = 0.19, P = 0.0001) concentrations and blood pressure (systolic and diastolic r = 0.10, P </= 0.05) and inversely with percentage body fat (r = -0.13, P = 0.01) and waist circumference (r = -0.11, P = 0.03). IGFBP-1 was inversely correlated with adult body mass index (BMI) (r = -0.46, P < 0.0001), fasting glucose and insulin concentrations, and blood pressure. There were correlations between the adult level of IGFBP-1 and birth weight (r = 0.11, P = 0.03) and ponderal index (weight/length(3)) at birth (r = 0.13, P = 0.01), but IGF-I was not related to birth measurements. There were interactive effects between childhood height or BMI and adult BMI on IGF-I and IGFBP-1 in adulthood. Tall height and high BMI at 7 yr were associated with low IGF-I (P = 0.03 for height and P = 0.003 for BMI) and high IGFBP-1 (P = 0.02 and P = 0.06) in adulthood but only in those subjects whose current BMI was below median. On further analysis these interactive effects were particularly strong for height in childhood and adult lean BMI (lean body mass/height(2)). Among men and women of below-average lean BMI, tall height at 7 yr was associated with low adult IGF-I (P = 0.007) and high IGFBP-1 (P = 0.0004) concentrations [interaction (7-yr height x adult lean BMI); P = 0.008 for IGF-I and 0.001 for IGFBP-1]. There is no evidence that reduced fetal growth programs IGF-I concentrations in old age. An association between small size at birth and low IGFBP-1 concentrations may in part reflect fetal programming effects on insulin resistance. Given the anabolic effects of the GH-IGF-I axis, subjects with tall height in childhood but low adult lean body mass may be at risk of late-life GH-IGF-I axis dysfunction. Prospective studies should address whether this group is susceptible to type 2 diabetes, coronary heart disease, and osteoporosis.

High serum insulin-like growth factor binding protein-1 is associated with increased cardiovascular mortality in elderly men.

Insulin-like growth factor binding protein-1 (IGFBP-1) has been implicated in the development of cardiovascular disease, but it is not known whether IGFBP-1 is related to cardiovascular mortality. We examined the relation of circulating IGFBP-1 to death from coronary heart disease, cardiovascular disease, and all causes in a cohort study consisting of 622 men aged 65 - 84 years, at baseline in 1984. Fasting serum IGFBP-1 and other risk factors were measured in 1984 and 1989. Cardiovascular events for those who died between 1984 and 1995 were analyzed, and cardiovascular diagnoses were coded centrally according to standardized procedures. Of the 622 men, 358 died between 1984 and 1995; 160 deaths were due to cardiovascular causes, 113 of which were coronary deaths. High fasting serum IGFBP-1 concentration (> 75 percentile) in 1984 was associated with increased five-year total mortality (OR 2.05, 95 % CI 1.41 - 2.99; p < 0.0002), cardiovascular mortality (OR 2.20, 95 % CI 1.37 - 3.50; p < 0.0009) and coronary heart disease mortality (OR 2.29, 95 % CI 1.35 - 3.88; p < 0.002). After adjustment for age, high serum IGFBP-1 concentrations still carried an increased risk of total mortality due to (OR 1.73, 95 % CI 1.16 - 2.59; p < 0.007), cardiovascular (OR 1.91 95 % CI 1.18 - 3.09; p < 0.008) and coronary heart disease (OR 2.02. 95 % CI 1.18 - 3.47; p < 0.01). In conclusion, high fasting serum IGFBP-1 is related to increased five-year total and cardiovascular mortality in elderly men.

Circulating IGF binding protein-1 is inversely associated with leptin in non-obese men and obese postmenopausal women.

Hyperleptinaemia and hyperinsulinaemia interrelate to insulin-like growth factor binding protein 1 (IGFBP-1), and disturbances in the growth hormone-IGF-I axis are linked to obesity and cardiovascular diseases. However, whether the association between leptin and the GH-IGF-I axis is altered with increasing obesity is not known. We therefore examined the relationship between leptin, IGF-I, IGFBP-1, insulin and proinsulin in men and women with or without obesity in a population study. Healthy subjects (n=158; 85 men and 73 pre- and postmenopausal women) from the Northern Sweden MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease) population were studied with a cross-sectional design. Anthropometric measurements (body mass index (BMI) and waist circumference) and oral glucose tolerance tests were performed. Radioimmunoassays were used for the analyses of leptin, IGF-I and IGFBP-1, and ELISAs for specific insulin and proinsulin. Leptin inversely correlated to IGFBP-1 in non-obese men (P<0.05) and obese postmenopausal women (P<0.05). In contrast, leptin did not correlate to IGF-I. IGFBP-1 was also significantly associated with proinsulin in non-obese men (P<0.01) and non-obese premenopausal women (P<0.05). The association between leptin and IGFBP-1 was lost after adjustment for insulin. In multivariate analyses taking measures of adiposity into account, low proinsulin, and IGF-I in combination with old age, but not leptin, predicted high IGFBP-1 levels. Leptin was inversely associated with IGFBP-1 in non-obese men and obese postmenopausal women, and proinsulin was inversely associated with IGFBP-1 in non-obese men and premenopausal women. However, these associations were lost with increasing central obesity in men and premenopausal women and after control for insulin. Therefore, this study suggests (i) that leptin is of minor importance for regulation of IGFBP-1 levels and (ii) that the insulin resistance syndrome is characterised by an altered relationship between leptin, IGFBP-1 and insulin.

Serum levels of free insulin-like growth factor (IGF)-I and IGF-binding protein-1 in prepubertal children with idiopathic short stature.

The study was performed to evaluate the relationships among serum free and total insulin-like growth factor (IGF)-I, IGF-binding protein-1 (IGFBP-1), IGFBP-3, and insulin concentrations in prepubertal children with idiopathic short stature (ISS). Eighteen children with ISS and 15 age-matched controls were included in the study. All short children had a height standard deviation score of more than 2 below the mean, and maximum stimulated GH levels greater than 10 microg/l after two standard provocation tests. The serum levels of free IGF-I were significantly lower in short children (1.6 +/- 0.3 microg/l) than in the controls (2.8 +/- 0.6 microg/l, P<0.05), while total IGF-I levels were slightly, but not significantly, lower in short children than in controls. The serum levels of IGFBP-1 were significantly higher in the ISS group (124.6 +/- 5.6 microg/l) than in controls (80.0 +/- 8.7 microg/l, P < 0.0001). The fasting insulin and IGFBP-3 levels were similar in both groups. A stepwise regression analysis for all subjects revealed that IGFBP-1 is the only independent predictor of log free IGF-I (R2 = 0.23, P<0.01). The present study shows that the serum levels of free IGF-1 are significantly lower and insulin-like growth factor-binding protein-1 levels are higher in prepubertal children with idiopathic short stature, as compared with age-matched controls. The high IGFBP-1 may contribute to growth retardation in a subgroup of idiopathic short stature through a decrease in free IGF-1.

Maternal insulin-like growth factor binding protein-1, body mass index, and fetal growth

AIMTo examine the hypothesis that the maternal insulin-like growth factor system may constrain fetal growth.METHODSA prospective observational study of maternal serum insulin-like growth factor binding protein-1 (IGFBP-1) and fetal growth...

Serum Free and Total Insulin-Like Growth Factor-I, Insulin-Like Growth Factor Binding Protein-1 and Insulin-Like Growth Factor Binding Protein-3Levels in Healthy Elderly Individuals

Background: Little is known about the influence of the free insulin-like growth factor-I/insulin-like growth factor binding protein (IGF-I/IGFBP) system on the quality of health and on disability in the elderly population. Design: In a cross-sectional population based study of 218 healthy elderly subjects (age 55–80 yrs) fasting free and total insulin-like growth factor (IGF-I), insulin-like growth factor binding protein-1 (IGFBP-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels were measured. Subjective quality of health was assessed by asking all participants whether they judged the quality of their health as better, the same or worse than that of their peers. Disability was determined by the Disability Index of the Stanford Health Questionnaire. Results: Mean serum-free IGF-I levels were significantly lower in the 21 subjects who experienced their health as worse than those of their peers, compared to the 181 subjects who experienced their health as better or the same as their peers 0.069 (SE 0.009) vs. 0.093 nmol/l (SE 0.004) (p = 0.04). Mean IGFBP-1 levels were significantly higher in subjects, who felt less healthy than their peers 1.23 (SE 0.26) vs. 0.73 nmol/l (SE 0.82) (p = 0.01). Free and total IGF-I, IGFBP-1 and IGFBP-3 levels, were not different in subjects with the lowest and the highest Disability Index Score. Conclusion: Low free IGF-I and high IGFBP-1 levels are associated with a decreased self-reported quality of health, but are not related to physical disability in the elderly.

Plasma levels of insulin-like growth factor binding protein-1, and growth hormone binding protein activity from birth to the third month of life.

Serum levels of insulin-like growth factors (IGF-1 and IGF-2), insulin, insulin-like growth factor binding protein-1 (IGFBP-1), growth hormone (GH) and growth hormone-binding protein (GH-BP) activity were assessed in a group of healthy newborns and reevaluated at one and three months of life in six of them. A significant decrease in IGFBP-1 plasma levels was observed at one month (p < 0.002) and three months (p < 0.02) of life compared to cord blood values. IGF-1 plasma levels did not change during the first three months of life. In contrast, IGF-2 plasma levels increased significantly at three months of life compared to cord blood values (p < 0.002). GH plasma levels showed a significant decrease at three months of life (p < 0.03). GH-BP activity was low at birth and did not change significantly during the first three months of life. The low GH-BP activity may reflect the GH receptor status, indicating that GH receptors are poorly expressed in early infancy. The high IGFBP-1 plasma levels in newborns could be important in protecting them from hypoglycemia.