Mean Insulin-like Growth factor-I Levels Research Articles

PMON166 Safety Comparison of 40- vs 60-mg/day Doses of Oral Octreotide Capsules for Treatment of Acromegaly in the CHIASMA OPTIMAL Trial

Abstract Background Oral octreotide capsules (OOC) are a treatment option for patients with acromegaly in the United States who have previously responded to injectable somatostatin receptor ligands (iSRLs, octreotide or lanreotide). In previous phase 3 studies, the safety of OOC was shown to be consistent with iSRLs, without dose-dependent adverse reactions. In the double-blind, placebo-controlled period (DPC) of the CHIASMA OPTIMAL trial (NCT03252353), patients were randomized to twice-daily OOC at 40-mg/day, with the option for up-titration to 80-mg/day. In contrast, patients entered the open-label extension (OLE) at a 60-mg/day dose. Objective Examine the safety of 40-mg/day versus 60-mg/day OOC doses. Methods Eligible patients had the option to enroll in the OLE following the core trial. All patients received OOC 60-mg/day upon entering the OLE regardless of prior treatment in the DPC, including patients who received placebo in the DPC. OOC doses were up- or down-titrated based on insulin-like growth factor I (IGF-I) level and/or acromegaly signs or symptoms. The current analysis compared the incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), TEAE-related study drug discontinuation, and acromegaly-related TEAEs (defined as new or worsening signs or symptoms of acromegaly). Results Twenty-eight patients randomized to OOC in the DPC (40-mg/day dose) and 19 who were originally randomized to placebo and continued into the OLE (60-mg/day dose) were included in the analysis. Biochemical control was similar in both groups as demonstrated by mean IGF-I levels over the respective periods. Ninety-six percent of patients on 40-mg/day and 57.9% on 60-mg/day experienced ≥1 TEAEs. Two patients on 60-mg/day reported a total of 2 SAEs, both deemed unrelated to study drug. Two patients on 40-mg/day experienced TEAEs leading to study drug discontinuation (headache and gastrointestinal symptoms). The incidence of acromegaly-related TEAEs was generally lower in those on 60-mg/day versus 40-mg/day. Conclusions This is the first analysis exploring differences in OOC doses. The nature and incidence of TEAEs occurring with an OOC dose of 60-mg/day versus 40-mg/day were similar, though this analysis was limited by differences in TEAE reporting across sequential phases of a lengthy trial. A trend was observed for decreased incidence of acromegaly-related TEAEs with the 60-mg/day dose. This finding is in line with previous analyses showing no dose-related TEAEs with OOC. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Optimal Monitoring of Weekly IGF-I Levels During Growth Hormone Therapy With Once-Weekly Somapacitan.

ContextSomapacitan is a long-acting growth hormone (GH) in development for once-weekly treatment of GH deficiency (GHD). Optimal monitoring of insulin-like growth factor-I (IGF-I) levels must account for weekly IGF-I fluctuations following somapacitan administration.ObjectiveTo develop and assess the reliability of linear models for predicting mean and peak IGF-I levels from samples taken on different days after dosing.DesignA pharmacokinetic/pharmacodynamic model was used to simulate IGF-I data in adults and children following weekly somapacitan treatment of GHD.Setting and Patients39 200 IGF-I profiles were simulated with reference to data from 26 adults and 23 children with GHD.Intervention(s)The simulated dose range was 0.02 to 0.12 mg/kg for adults and 0.02 to 0.16 mg/kg for children. Simulated data with >4 average standard deviation score were excluded.Main Outcome Measure(s)Linear models for predicting mean and peak IGF-I levels based on IGF-I samples from different days after somapacitan dose.ResultsRobust linear relationships were found between IGF-I sampled on any day after somapacitan dose and the weekly mean (R2 > 0.94) and peak (R2 > 0.84). Prediction uncertainties were generally low when predicting mean from samples taken on any day (residual standard deviation [RSD] ≤ 0.36) and peak from samples taken on day 1 to 4 (RSD ≤ 0.34). IGF-I monitoring on day 4 and day 2 after dose provided the most accurate estimate of IGF-I mean (RSD < 0.2) and peak (RSD < 0.1), respectively.ConclusionsLinear models provided a simple and reliable tool to aid optimal monitoring of IGF-I by predicting mean and peak IGF-I levels based on an IGF-I sample following dosing of somapacitan. A short visual summary of our work is available (1).

A longitudinal study of serum insulin-like growth factor-I levels over 6 years in a large cohort of children and adolescents with type 1 diabetes mellitus: A marker reflecting diabetic retinopathy.

To evaluate longitudinal serum insulin-like growth factor-I (IGF-I) in a large cohort of children and adolescents with type 1 diabetes in relation to hemoglobin A1c (HbA1c), age, diabetes duration, and body mass index (BMI), its association to height and retinopathy, and in comparison with healthy subject references. A total of 2683 serum IGF-I values were obtained from 806 children and adolescents with T1DM, from annual blood samples for up to 6 consecutive years. In a multiple regression analysis IGF-I values were negatively correlated to HbA1c and diabetes duration, and positively correlated to BMI (P < .001, P < .001, and P < .001, respectively, adjusted r2 = 0.102). Children and adolescents with T1DM had lower mean IGF-I levels and reference interval limits compared to healthy subjects. In boys, mean (SD) IGF-I SD score (SDS) levels were -1.04 (±1.3) calculated from the healthy reference. IGF-I peaked at 15 years of age, similarly to healthy controls, but with markedly lower levels in late puberty. Girls were more affected at later stages of puberty but with a slightly less depressed overall mean IGF-I SDS of -0.69 (±1.2). In a subgroup of 746 subjects with fundus photography, a negative correlation was seen between individual mean IGF-I SDS and preproliferative retinopathy (P = .004, adjusted r2 = 0.021). In another subgroup of 84 adolescents, no correlation was seen between individual mean IGF-I SDS and target height SDS or distance to target height SDS. Poor metabolic control and diabetes duration impact negatively on serum IGF-I levels. A low individual mean IGF-I level was associated with progression of retinopathy independently of HbA1c, age, gender, and diabetes duration. Disease, sex and age related IGF-I SDS may become clinical helpful as a supplement to HbA1c in predicting the long-term outcome for children and adolescents with T1DM.

Insulin-Like Growth Factor I, Insulin-like Growth factor Binding Protein 3, and Atrial Fibrillation in the Elderly

Insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) are involved in oxidative stress and atherosclerosis; however, the relationship between the IGF-I system and atrial fibrillation (AF) is not known. The objective of this analysis was to assess, the relationship between IGF-I and IGFBP-3 serum levels and AF among elderly participants. In this cross-sectional study, 719 participants (mean age [SD] years: 78.2 [6.8]; 31.8% men) were evaluated during an outpatient geriatric assessment. AF was determined by electrocardiogram or medical record. Participants were classified into two groups: Participants with AF (n = 91) or without AF (n = 628). IGF-I and IGFBP-3 serum levels were determined by enzyme linked immunosorbent assay. After adjusting for age and sex, the mean IGF-I and IGFBP-3 serum levels were significantly lower among AF participants than among non-AF participants (mean IGF-I ng/mL [SD] = 133.8 [66.6] vs 157.9 [80.0], p = .02; mean IGFBP-3 ng/mL [SD] = 3,653 [1,393] vs 4,151 [1,583], p = .03, respectively). After adjusting for confounding factors (age, gender, beta blocker medication, heart rate, hypertension, stroke, and chronic heart failure), low IGF-I serum level (OR [95% CI] = 0.66 [0.49-0.87]) and low IGFBP-3 serum level (0.71 [0.54-0.93]) remained independent determinants of AF. Low IGF-I and low IGFBP-3 serum levels were independently associated with AF in this elderly population. This result should be confirmed in a longitudinal study to evaluate whether IGF-I and/or IGFBP-3 serum levels are predictive of incident AF.

Clinical implications of insulin-like growth factor I (IGF-I) and II (IGF-II) in stage IIIB cervical cancer.

e15505 Background: The IGF (Insulin like Growth Factor) family has been implicated in the pathogenesis of cervical cancer. We aim to correlate pre and post treatment levels of IGF-I and IGF-II in stage IIIB cervical cancer and identify if serum IGF-I and IGF-II can be used as a marker to predict response to chemo-radiotherapy. Methods: We recruited 80 previously untreated patients of histopathologically proven squamous cell carcinoma of stage IIIB cancer of uterine cervix from January 2011 to May 2011. The age of patients ranged from 30 to 65 years and were of ECOG performance status of less than or equal to 2. Along with the routine investigations the pretreatment serum levels of IGF-I and IGF-II were done by ELISA kits in all the patients. The serum level of IGF-I was 246.3 ± 72.5 ng/ml and IGF-II was 1585 ± 352 ng/ml. All patients were given concurrent cisplatin (30 mg/m2) weekly along with radiation (50Gy/25#) with conventional portals followed by two sittings of intracavitory radiotherapy (7.5 Gy each) on mHDR. Blood samples for IGF-I and IGF-II levels were collected before the start of the therapy, 1 month after the completion of treatment and 6 months after the completion of the treatment. Results: The trend seen was that mean IGF-I levels were always in the lower range as compared to IGF-II levels in all individuals. The mean serum levels of IGF-I and IGF-II in patients who achieve complete response (45%) returned to normal whereas the mean serum levels of IGF-I and IGF-II in patients who achieved partial response (43%) was 149 ng/ml and 838 ng/ml respectively. The mean serum levels of IGF-I and IGF-II in patients who achieved no response (12%) was 331 ng/ml and 1840 ng/ml respectively. Conclusions: The serum levels of IGF-I and IGF-II may be a reliable prognostic and predictive marker in cervical cancer however further large randomized studies are required to validate the results. IGF-I and IGF-II can serve as potential markers in cervical cancer to risk stratify patients, assess treatment response and possibly act as therapeutic targets in the future.

A Single-Center Open-Label Study To Investigate The Efficacy And Safety Of Repeated Subcutaneous Injections Of Lanreotide Autogel In Patients With Acromegaly Previously Treated With Octreotide

To evaluate the efficacy of lanreotide Autogel, a depot preparation of a long-acting somatostatin analogue, in patients with acromegaly who were previously treated with octreotide. In a prospective single-center, open-label, comparative study, 13 patients were switched from octreotide treatment (baseline) to lanreotide Autogel therapy at a fixed dosage of 90 mg/4 wk. After 6 injections, the dosage was titrated to 60, 90, or 120 mg/4 wk, on the basis of growth hormone (GH) levels, for a further 6 injections. Mean GH and insulinlike growth factor-I (IGF-I) levels were determined at baseline, during treatment (to 48 weeks), and up to 8 weeks after the last injection. There was no significant change in the proportion of patients with GH and IGF-I control from baseline to week 48 (GH, 85% to 89%; IGF-I, 46% to 62%). Mean GH levels changed little from baseline, but mean IGF-I levels were significantly lower after 32 weeks (P<.05) and 48 weeks (P<.02). Data collected at 6 and 8 weeks after the last injection suggested that the efficacy of lanreotide Autogel can persist for longer than 4 weeks. This small study suggests that lanreotide Autogel is at least as effective as octreotide in the control of acromegaly and may last for longer than the recommended 4 weeks. It appears to be a useful alternative to long-acting octreotide in the treatment of acromegaly.

Efficacy of long-term lanreotide treatment in patients with acromegaly

We investigated the effectiveness of lanreotide for the treatment of active acromegaly in a retrospectively multicenter case series including 53 patients (24 male, 29 female; mean age at diagnosis, 49.5 +/- 13.9 years) with acromegaly treated with lanreotide in nine different centers. Mean tumor diameter was 20 +/- 13 mm; mean basal levels of growth hormone (GH) and insulin-like growth factor I (IGF-I) were 21.3 +/- 26.3 and 579 +/- 177 mug/l, respectively. The primary mode of treatment was surgery in 70% of patients. Twenty-nine patients received only lanreotide (Prolonged Release, Autogel), whereas 24 subjects were also treated with octreotide at another treatment stage. Primary therapy with lanreotide was administered in five patients. Maximal monthly dose of lanreotide Autogel (n = 44) was 60 mg in 45%, 90 mg in 26%, 120 mg in 21% and 180 mg in 8%. During 36 months of lanreotide treatment, mean IGF-I levels decreased from 443 +/- 238 to 276 +/- 147 mug/l (P < 0.001), and mean GH levels, from 5.2 +/- 6.4 to 3.2 +/- 3.0 mug/l (P < 0.001). IGF-I levels normalized in 51% of patients and decreased by >50% towards normal in 32%; the normalization rate was higher in women (65%) than men (33%, P = 0.04). Safe random GH levels (</=2 mug/l) were achieved in 49% of patients. Both IGF-I normalization and safe GH levels were reached in 32% of the cohort. Lanreotide is an effective treatment for active acromegaly. Female sex was associated with higher rates of IGF-I normalization.

IGF-I and IGFBP-3 polymorphisms in relation to circulating levels among African American and Caucasian women.

Circulating insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) levels have been associated with common diseases. Although family-based studies suggest that genetic variation contributes to circulating IGF-I and IGFBP-3 levels, analyses of associations with multiple IGF-I and IGFBP-3 single nucleotide polymorphisms (SNP) have been limited, especially among African Americans. We evaluated 30 IGF-I and 15 IGFBP-3 SNPs and estimated diplotypes in association with plasma IGF-I and IGFBP-3 among 984 premenopausal African American and Caucasian women. In both races, IGFBP-3 rs2854746 (Ala32Gly) was positively associated with plasma IGFBP-3 (CC versus GG mean difference among Caucasians, 631 ng/mL; 95% confidence interval, 398-864; African Americans, 897 ng/mL; 95% confidence interval, 656-1,138), and IGFBP-3 diplotypes with the rs2854746 GG genotype had lower mean IGFBP-3 levels than reference diplotypes with the CG genotype, whereas IGFBP-3 diplotypes with the CC genotype had higher mean IGFBP-3 levels. IGFBP-3 rs2854744 (-202 A/C) was in strong linkage disequilibrium with rs2854746 in Caucasians only, but was associated with plasma IGFBP-3 in both races. Eight additional IGFBP-3 SNPs were associated with >or=5% differences in mean IGFBP-3 levels, with generally consistent associations between races. Twelve IGF-I SNPs were associated with >or=10% differences in mean IGF-I levels, but associations were generally discordant between races. Diplotype associations with plasma IGF-I did not parallel IGF-I SNP associations. Our study supports that common IGFBP-3 SNPs, especially rs2854746, influence plasma IGFBP-3 levels among African Americans and Caucasians but provides less evidence that IGF-I SNPs affect plasma IGF-I levels.

Effects of the route of estrogen administration on insulinlike growth factor-I, IGF binding protein-3, and insulin resistance in healthy postmenopausal women

Oral estrogen therapy suppresses insulin like growth factor I (IGF-I) levels, whereas conventional dose transdermal estradiol (E2) does not. However, it has been proposed that if sufficiently high serum E2 levels are achieved, nonoral E2 will also suppress serum IGF-I. The aim of the study was to investigate the effects of intranasal E2 with norethisterone (E2/NET) versus oral E2/NET acetate on IGF-I, IGF binding protein 3, and insulin resistance in postmenopausal women. This was a randomized, multicenter, double-blind, double-dummy trial. Postmenopausal women were randomized to receive either daily intranasal E2/NET (175 microg/275 microg) as a spray and a placebo tablet (n = 41) or oral E2/NET acetate (1 mg/0.5 mg) plus placebo intranasal spray (n = 41) for 1 year. Fasting plasma concentrations of IGF-I, IGF binding protein 3, glucose and insulin, glucose and insulin at 120 minutes post-glucose challenge, and the homeostasis model assessment for insulin resistance were assessed at baseline and after 52 weeks of treatment. The two groups were well matched for all clinical and biochemical parameters at baseline. There were no significant between-group differences for fasting and 120-minute glucose, insulin, homeostasis model assessment for insulin resistance, and IGF binding protein 3. The mean IGF-I level at week 52 was significantly lower for women treated with oral versus intranasal therapy (116 +/- 21 [SD] versus 134 +/- 33 [SD], P = 0.005) and the mean difference in change over 52 weeks in IGF-I was significantly different between groups (-19, 95% CI:-37 to -1, P = 0.04). In healthy postmenopausal women, intranasal E2 at a dose that results in serum levels that exceed the proposed threshold for growth hormone and IGF-I effects, does not alter IGF-I levels. This suggests that the effect of exogenous estrogen on IGF-I is a function of the method of administration rather than being dose related.

Assessing skeletal maturity by using blood spot insulin-like growth factor I (IGF-I) testing

Accurate determination of skeletal maturity and remaining growth is crucial to many orthodontic, orthognathic, and dental-implant timing decisions. Cervical vertebral stages and hand-wrist radiographs are currently used to identify peak mandibular bone growth. These are highly subjective techniques that not only involve radiographic exposure but also lack the ability to determine the intensity of the growth spurt and the end of growth. Insulin-like growth factor I (IGF-I) is a circulating growth hormone-dependent factor whose level correlates with sexual maturity; it is used to diagnose growth hormone deficiency and excess. We hypothesized that IGF-I levels would also correlate with cervical skeletal maturity and would be highest at the cervical stages that correspond to the greatest amount of facial growth. We measured mean blood spot IGF-I levels in a cross-sectional study of 83 patients (44 female, 39 male) on recall to begin orthodontic treatment, in active treatment, or in posttreatment follow-up. Mean blood spot IGF-I levels were significantly higher in the late pubertal stages than in the prepubertal, early pubertal, and postpubertal stages. Linear correlation showed that IGF-I levels had a significant positive correlation with cervical skeletal maturity from the prepubertal to the late pubertal stages, and a significant negative correlation from the late pubertal to the postpubertal stages. In the postpubertal stage, IGF-I levels had a negative linear correlation with increasing time since the onset of puberty and with chronological age. Blood spot IGF-I could be used as a skeletal maturity indicator and might be useful in detecting residual mandibular growth in young adults.

An Examination of the Role of Feeding Regimens in Regulating Metabolism During the Broiler Breeder Grower Period. 2. Plasma Hormones and Metabolites

A trial was conducted to determine the effects of different feeding regimens on plasma hormone and metabolite levels in 16-wk-old broiler breeder pullets. A flock of 350 Cobb 500 breeder pullets was divided in 2 at 28 d of age and fed either every day (ED, 5 pens of 35 birds) or skip-a-day (SKIP, 5 pens of 35 birds) from 28 to 112 d of age. Total feed intake did not differ between the 2 groups. At 112 d, 52 randomly selected pullets from the larger flock of ED-fed pullets, and 76 from the SKIP-fed pullets were individually caged and fed a meal of 74 g (ED) or 148 g (SKIP). Blood samples were collected from 4 pullets in each group by cardiac puncture at intervals after feeding. Plasma was analyzed for insulin, glucagon, insulin-like growth factor-I and insulin-like growth factor-II, triiodothyronine and thyroxine, corticosterone, leptin, glucose, nonesterified fatty acids, triglycerides, and uric acid. Feed retention in the crop was also noted at each interval. In ED birds, the crop was empty by 12 h and in SKIP birds, the crop was empty by 24 h after feeding. The physiological responses to fasting, such as increased glucagon and corticosterone and reduced plasma triglyceride, occurred at times coincidental with crop emptying in both ED and SKIP birds. Overall, mean insulin-like growth factor-I levels were higher (P < 0.05) in ED birds. Triiodothyronine was higher (P = 0.09) in SKIP birds. Overall mean plasma corticosterone was 2-fold higher in SKIP-fed birds, which may be related to the increased length of fasting periods, hunger, and stress. Plasma leptin was consistently higher in ED-fed birds, which was indicative of their more consistent food supply and more stable energy status. In summary, the experiment reported here shows that different feeding regimens can alter hormone and metabolite profiles, in spite of total feed intakes being equal.

Association of serum levels of IGF-I and IGFBP-1 with renal function in patients with type 2 diabetes mellitus

Objective Our aim was to determine whether serum Insulin-like growth factor-I (IGF-I) and Insulin-like growth factor binding protein-1 (IGFBP-1) levels were different between type 2 diabetic patients and non-diabetic control group. We also aimed to establish any relationship that might exist between the serum IGF-I and IGFBP-1 levels with the urinary albumin excretion (UAE), creatinine clearance and urinary N-acetyl-β- d-glucosaminidase (NAG) excretion (as a marker of renal tubular dysfunction) and other parameters (such as age, duration of diabetes, treatment, etc.) in patients with type 2 diabetes mellitus (DM). Design Fifty-nine type 2 diabetic patients and thirty-one non-diabetic controls were included in this study. Results Mean serum IGF-I levels in diabetic patients were lower than the non-diabetic controls (158 ± 12 vs. 287 ± 26 μg/l), ( p < 0.001). Serum IGFBP-1 levels were also higher in type 2 diabetic patients compared to the control group (67 ± 5 vs. 35 ± 4 μg/l), ( p < 0.001). No relationship was obtained between IGF-I and IGFBP-1 levels with neither UAE nor urinary NAG excretion. A significant negative relationship was observed between creatinine clearance and serum IGFBP-1 level ( r = −0.39, p = 0.004). In multiple regression analysis IGF-I was independently and negatively associated with age and insulin treatment. On the other hand, IGFBP-1 was negatively related with creatinine clearance and positively related with the duration of diabetes. Conclusion These results suggest that type 2 DM leads to a decrease in the IGF-I while elevating the IGFBP-1 levels. Further studies are needed to clarify a potential role of increased levels of IGFBP-1 in decreased creatinine clearance in type 2 DM.

Serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) in IVF patients with polycystic ovary syndrome: correlations with outcome

To evaluate serum insulin-like growth factor I (IGF-I) and IGF-binding protein 3 (IGFBP-3) levels during stimulation in polycystic ovary syndrome (PCOS) and control populations as factors predictive of IVF outcome. Observational study. Academic medical center-based IVF practice. Forty-three PCOS and 33 male-factor control patients undergoing IVF from 2002 to 2004. Treatment with a dual suppression protocol incorporating oral contraceptive pills (OCPs) and GnRH agonist suppression followed by low-dose gonadotropin therapy. The PCOS and control patients' serum IGF-I and IGFBP-3 levels were compared and correlated with IVF outcome. PCOS and control patients were comparable in terms of demographics and IVF outcome. In both, mean serum IGF-I levels increased during stimulation. PCOS patients whose IGF-I levels decreased from day 3 to day of hCG had a significantly higher mean number of immature oocytes retrieved (4.8 +/- 1.1 vs. 2.4 +/- 0.4; P=.02). IGFBP-3 levels increased during stimulation in PCOS patients but tended to decrease in control patients. In PCOS patients, an increase in IGFBP-3 levels during stimulation was associated with a greater likelihood of becoming pregnant (P=.03) and of ongoing pregnancy (P=.02). The bioavailability of IGF-I appears to play a key role in oocyte maturation in PCOS patients. Alterations in IGFBP-3 concentration during stimulation may be a critical mechanism in modulating IGF-I activity.

Serum Insulin-Like Growth Factor-I Levels Among Women in Hawaii and Japan With Different Levels of Tofu Intake

: Insulin-like growth factor-I (IGF-I) has been proposed as the link between diet and breast cancer risk. Due to their estrogen-like structure, soy isoflavones may affect IGF-I levels in a similar way as exogenous estrogens. In a cross-sectional design, we compared IGF-I levels between women with high and low soy intake. The analysis included 611 pre- and postmenopausal women: Japanese in Japan and Japanese and Caucasians in Hawaii. The subjects had participated in a previous study, were never diagnosed with breast cancer, provided a screening mammogram and a blood sample, and completed validated food-frequency questionnaires. The same laboratory analyzed all serum samples for IGF-I and IGF binding protein (IGFBP)-3 by enzyme-linked immunosorbent assay. We estimated covariate-adjusted mean IGF-I and IGFBP-3 levels by tofu intake. The respective mean IGF-I levels were 213, 257, and 255 ng/ml for Japanese in Japan, Japanese in Hawaii, and Caucasians in Hawaii. Tofu intake was higher in Japan than among Japanese and Caucasians in Hawaii (11.0 vs. 9.4 and 4.9 g/1,000 kcal). Mean IGF-I levels were 11% lower among women in the highest tofu intake category compared with the lowest, but the difference in IGF-I levels between the highest and lowest tofu category was only significant among women in Japan. Inclusion of total energy, total protein, meat, and dairy intake did not materially alter the association between tofu consumption and IGF-I levels. These findings suggest that a diet rich in soy foods and low in meats may be related to lower IGF-I levels, but it is unclear whether soy or other characteristics of diet and lifestyle are responsible for this association.

Premenopausal breast cancer and the association between estrogen receptor status, insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein-3 (IGFBP-3) and leptin

640 Background: The IGF pathway and leptin are associated with breast cancer risk in premenopausal women. These proteins are implicated in breast carcinogenesis through their interactions with the estrogen pathway, potentially resulting in specific breast cancer histopathologic subtypes. Methods: Pretreatment serum IGF-I, IGFBP-3 and leptin levels were examined in newly diagnosed premenopausal breast cancer cases to determine whether an association with tumor estrogen receptor status exists. Odds ratios were determined by logistic regression analysis. Likelihood ratio tests for interaction with BMI were conducted. Results: One hundred and eight women were evaluated (mean age 42); 82 were ER positive and 26 were ER negative. 62 were normal weight (BMI&lt;25) and 46 were overweight and obese (BMI≥25). Mean IGF-I, IGFBP-3 and leptin levels did not differ between the ER positive and ER negative tumors. No associations were found between IGF-I, IGFBP-3 or leptin and ER status of tumors overall or by subset analysis in normal weight versus overweight and obese individuals. A suggestion that elevated IGFBP-3 was associated with ER-negative disease did not reach statistical significance. Additionally, normal-weight women with ER-negative disease had higher leptin levels than their normal-weight ER-positive counterparts, although we lacked statistical power to detect an effect of BMI on the association between leptin levels and tumor hormone receptor status. Conclusions: This is the first report examining the IGF pathway and leptin in relation to ER status in premenopausal women with newly diagnosed breast cancer. Our small number of cases suggests a number of intriguing findings that should be evaluated in larger studies. Determining links between ER status and IGFBP-3 and leptin may help better define risk factors and potentially appropriate interventions for ER-negative versus ER-positive breast cancer. No significant financial relationships to disclose.

Soy Intake and Insulin‐like Growth Factor‐I Levels among Women in Hawaii and Japan

Insulin-like growth factor-I (IGF-I) has been proposed as the link between diet and breast cancer risk. Due to their estrogen-like structure, soy isoflavones may affect IGF-I levels in a similar way as exogenous estrogens. In a cross-sectional design, we compared IGF-I levels between women with high and low soy intake. The analysis included 611 pre- and postmenopausal women: Japanese in Japan (JJ), and Japanese (JH) and Caucasians (CH) in Hawaii. The subjects had participated in a previous study, were never diagnosed with breast cancer, and provided a screening mammogram and blood sample. The same lab analyzed all serum samples for IGF-I and IGF binding protein (IGFBP)-3 by double-antibody ELISA. Soy intake was assessed by validated food frequency questionnaires. We estimated mean IGF-I and IGFBP-3 levels by tofu intake after adjustment for covariates. The respective mean IGF-I levels were 213, 257, and 255 ng/ml for JJ, JH, and CH. Tofu intake was higher among JJ than among JH and CH (11.0 vs. 9.4 and 4.9 g/1000kcal). Mean IGF-I levels were 11% lower (p = 0.01) and mean IGFBP-3 levels were 5% higher (p = 0.22) among women in the highest tofu intake category as compared to the lowest, but the relation was strongest among JJ women. These findings suggest that a diet rich in soy foods may be related to lower IGF-I levels. This project was funded by NCI grants R03 CA105948 and R01 CA80843 and by AICR grant 02A021.

Serum Insulin-Like Growth Factor-I Levels and Prostatic Intraepithelial Neoplasia: A Clue to the Relationship Between IGF-I Physiology and Prostate Cancer Risk

Serum insulin-like growth factor-I (IGF-I) levels at the higher end of the reference range have been associated with increased risk for the future development of prostate cancer. We determined whether high serum IGF-I levels are associated with precancerous lesions of the prostate. We conducted a case-control study to determine whether high serum IGF-I levels were associated with the presence of high-grade prostatic intraepithelial neoplasia (HGPIN) among patients who presented for prostate biopsy because of an abnormal serum prostate-specific antigen level or digital rectal exam. We measured serum IGF-I and insulin-like growth factor binding protein-3 (IGFBP-3) prior to prostate biopsy and compared them between 103 men with HGPIN (cases) and 205 men with normal prostate histology (controls). The mean IGF-I level in patients with HGPIN (130.2 ng/mL) was significantly higher compared with controls (118.8 ng/mL, P = 0.01). The mean IGFBP-3 level in patients with HGPIN (2,393.9 ng/mL) was also higher compared with controls (2,276.0 ng/mL, P = 0.06). After adjusting for age, prostate-specific antigen, digital rectal examination, and ethnic background, the odds ratio for a HGPIN diagnosis among men in the highest relative to the lowest quartile of serum IGF-I level was 1.94 (95% confidence interval, 1.0-3.7; P = 0.04). The potential association between a high serum IGF-I level and the presence of HGPIN may represent an important clue to understanding the basis for the relationship between IGF-I physiology and prostate cancer risk. Larger studies will be required to confirm this relationship.

Age, body mass index, current smoking history, and serum insulin-like growth factor-I levels associated with bone mineral density in middle-aged Korean men.

Osteoporosis is a growing health problem in women and in men. This cross-sectional study examined the association of anthropometric, lifestyle, and hormonal factors with bone mineral density (BMD) in 152 healthy Korean middle-aged men. Smoking habits and alcohol consumption were assessed by interview. Serum testosterone and insulin-like growth factor-I (IGF-I) levels were measured by radioimmunoassay, and serum growth hormone (GH) levels were measured by immunoradiometric assay. GH stimulation tests were performed after the ingestion of 500 mg of L-dopa. BMD was measured at the lumbar spine and at the femoral neck by dual-energy X-ray absorptiometry. Of the middle-aged men, 3.9% were osteoporotic and 28.3% were osteopenic at the lumbar spine site, and 5.9% were osteoporotic and 45.4% were osteopenic at the femoral neck site. Lumbar spine BMD correlated significantly with body mass index (BMI), and femoral neck BMD correlated significantly with age, BMI, and serum IGF-I levels. The lowest quartile group for serum IGF-I levels showed the lowest femoral neck BMD. Osteoporotic men by lumbar spine BMD showed significant differences from the normal BMD group in terms of BMI and smoking habits. Also, osteoporotic men by femoral neck BMD were significantly different for mean age, BMI, and serum IGF-I levels compared with the normal BMD group. On multiple regression analysis, BMI was found to be the only independent predictor of lumbar spine BMD, whereas both BMI and serum IGF-I levels were found to be the independent predictors of femoral neck BMD. Overall, 28.3%-45.4% of middle-aged Korean men were osteopenic. We suggest that higher age, a lower BMI, current smoking history, and lower serum IGF-I levels are risk factors for lower BMD in middle-aged Korean men; however, serum testosterone levels and GH secretory capacity were not found to be correlated with BMD.

Investigation of serum IGF-I levels amongst diabetic and non-diabetic cats

Since insulin-like growth factor-I (IGF-I) was first discovered as a mediator of glucose homeostasis, it has been extensively investigated in diabetes research in humans, rodents and primates. To date, however, relatively little work has been carried out on this hormone in the cat, despite the pathophysiological similarities between human and feline diabetes mellitus, as well as the relatively common nature of the disease in cats. This study reports on the IGF-I concentrations of 42 insulin treated diabetic cats and 25 normal cats. Diabetic subjects were grouped according to length of insulin treatment as either short, medium or long term. Analysis of variance (ANOVA) and Fischer's pair-wise comparisons revealed that mean IGF-I levels in short-term diabetic cats were significantly lower than those in normal cats whilst mean levels in long-term diabetics were significantly higher. The direction and extent of these alterations may have implications for our understanding of the pathophysiology of feline diabetes mellitus and for the use of this hormone in the diagnosis of acromegaly in diabetic cats.

Increased insulin-like growth factor-I levels in women with polycystic ovary syndrome, and beneficial effects of metformin therapy

We aimed to investigate whether metformin would reverse the endocrinopathy of polycystic ovary syndrome (PCOS), allowing resumption of cyclic ovulation and regular menses, and whether metformin causes any change in the serum concentration of insulin-like growth factor-I (IGF-I) in patients with PCOS. Fifty-eight women with PCOS participated in the study and received metformin at a dose of 850 mg three times a day (total 2550 mg) for 16 weeks. Serum concentrations of luteinizing hormone, follicle stimulating hormone, estradiol, free testosterone, total testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, fasting insulin, IGF-I, sex hormone binding globulin and insulin-like growth factor binding protein-1 (IGFBP-1) were evaluated before and after metformin treatment. Patients were divided into two groups as responders and non-responders according to the achievement of regular menstrual periods. The mean IGF-I levels decreased significantly on metformin therapy. After 16 weeks of metformin treatment, 55.17% of PCOS patients achieved regular menses. Only the change in serum levels of progesterone and IGF-I on metformin were statistically significant between responders and non-responders; metformin-induced decremental change in IGF-I levels were greater in responders. In conclusion, we observed that elevated IGF-I levels may have a crucial role in many consequences of PCOS in addition to hyperinsulinemia. By decreasing insulin and IGF-I levels, metformin therapy offers additional beneficial effects in resumption of regular menses. Thus, in PCOS patients with elevated levels of IGF-I, metformin may be considered as an appropriate agent to be used for the regulation of menstrual cycles.