Skeletal muscle mass is associated with bone geometry and microstructure and serum insulin-like growth factor binding protein-2 levels in adult women and men

Skeletal muscle and bone form highly‐integrated systems that undergo significant age‐related changes, but the relationships between muscle mass and trabecular versus cortical bone or trabecular microarchitecture have not been systematically investigated. Thus, we examined the association between appendicular skeletal muscle mass (ASM) relative to height squared (relative ASM) and bone parameters at several sites assessed by conventional as well as high‐resolution peripheral QCT in a cohort of 272 women and 317 men aged 20 to 97 years. In women, relative ASM was associated with cortical thickness (CtTh) at the femoral neck, lumbar spine, radius, and tibia (age‐and physical activity adjusted r = 0.19–0.32; all p < 0.01). Relative ASM was also associated with trabecular volumetric bone mineral density (vBMD) at the femoral neck and spine (all p < 0.05), and trabecular bone volume to tissue volume (BV/TV), number (TbN), thickness (TbTh), and separation (TbSp) at the radius (all p ≤ 0.05). In all men, relative ASM was associated with CtTh at all sites (age‐ and physical activity–adjusted r = 0.17–0.28; all p < 0.01). Associations between relative ASM and trabecular vBMD at the spine in men were lost after adjusting for age; however, relative ASM was associated with trabecular vBMD at the femoral neck and TbN and TbSp at the radius (all p < 0.01). We also investigated circulating factors associated with bone health that may be indicative of relative ASM and found that serum insulin‐like growth factor (IGF) binding protein‐2 (IGFBP‐2) levels were the most robust negative predictors of relative ASM in both sexes. Collectively, these data add to the growing body of evidence supporting the highly‐integrated nature of skeletal muscle and bone, and provide new insights into potential biomarkers that reflect the health of the musculoskeletal system. © 2012 American Society for Bone and Mineral Research.     

Insulin-like growth factor-1, growth hormone-dependent insulin-like growth factor-binding protein and growth in children with chronic renal failure

Insulin-like growth factor-binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) levels were measured by specific radioimmunoassays in children with all degrees of chronic renal failure (CRF). Study group 1 comprised 29 children (10 on dialysis) who had been studied one to four times over 2 years to determine whether IGF-1 and IGFBP-3 levels differed from those in age-matched healthy children and to examine the relationship between these levels and heights. IGF-1 and IGFBP-3 levels did not differ from those in normal children. IGF-1 and IGFBP-3 were significantly correlated, increased with pubertal stage in all children and with age in non-dialysis patients. IGF-1, but not IGFBP-3, correlated with age in dialysis patients. There was no correlation between IGF-1 or IGFBP-3 levels (corrected for age) and height standard deviation score (SDS) in either non-dialysis or dialysis patients. Study group 2 comprised 19 children (7 on dialysis) who were studied prospectively for 1–2 years to examine the relationship between IGF-1 and IGFBP-3 levels, growth rates and nutritional parameters. Mean values of IGF-1 and IGFBP-3 (corrected for age) did not change over 1-year periods, while height SDS fell by –0.38 ±0.21 SD/year in dialysis patients and by –0.11 ±0.29 SD/year in non-dialysis patients. No significant correlations were found between IGF-1 or IGFBP-3 levels and growth rates or nutritional parameters. Thus growth retardation in children with CRF is not related to circulating levels of IGF-1 or IGFBP-3.     

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 500mg 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.     

Serum concentrations of insulin-like growth factor (IGF)-1, IGF-2 and unsaturated somatomedin carrier proteins in children with chronic renal failure

Past measurements of somatomedins in chronic renal failure have yielded conflicting results because compounds that accumulate in renal failure and interfere with the somatomedin assays were not removed from assay systems. After serum somatomedins were separated from inhibitory substances by acid chromatography, we measured levels of the major somatomedins, insulin-like growth factor (IGF)-1 and IGF-2, in 16 prepubertal children with chronic renal insufficiency and in 16 age- and sex-matched normal children. Radioimmunoassayable IGF-1 levels were 220 +/- 182 (mean +/- SD) ng/mL in children with renal disease, not significantly different from levels of 248 +/- 155 ng/mL found in normal children. Levels of the less potent mitogen IGF-2, measured by radioreceptor assay, were 661 +/- 213 ng/mL in children with renal disease and were significantly greater than those of 433 +/- 139 ng/mL found in normal children (P less than .05). Since all 16 children with renal disease exhibited significant growth delay, we conclude that low serum IGF levels are unlikely to play a role in this growth failure. Further, since unsaturated somatomedin carrier proteins can interfere with the assay and in vitro biologic actions of the IGFs, and since there was more unsaturated carrier protein binding of IGF-1 by the sera of 15 children with renal disease v 15 normal children (17 +/- 3% v 12 +/- 3% binding of [125I]-IGF-1/50 muL serum, P less than .05), we suggest that somatomedin carrier proteins should be evaluated for their role in the growth failure of children with chronic renal failure.     

Subcellular distribution of the insulin‐like growth factor (IGF) binding proteins (IGFBPs) 2 and 3 in articular chondrocytes

The insulin‐like growth factor (IGF) is a major anabolic regulator in articular cartilage. The IGF‐binding proteins (IGFBPs) are increased during osteoarthritis (OA), but the function of the later proteins remains unknown. In general, the IGFBPs are pluripotential effectors capable of IGF regulation and of acting on their own to control key cell functions, including survival and proliferation. The independent functions are often associated with their cell location, and therefore this study explores the distribution of IGFBP‐2 and IGFBP‐3 in articular chondrocytes. Immunohistochemistry was used to localize IGFBP‐2 in normal human articular cartilage. Bovine chondrocytes were used for subcellular fractionation (hypotonic cell lysis) under nonreducing conditions and nuclear purification (centrifugation on sucrose cushions). Cell fraction markers and IGFBPs were assayed in the subcellular fractions by Western immunoblot. The IHC results showed association of IGFBP‐2 with chondrocytes, but not with the nuclei. Subcellular fractionation of isolated chondrocytes yielded intact nuclei as assessed at the light microscopic level; the nuclear marker histone H1 was exclusively associated with this fraction. More than 90% of the cytoplasmic marker GAPDH and all the detectable IGFBP‐2 were in the cytoplasmic fraction. Immunoreactive IGFBP‐3 was found in the cytoplasmic and peri‐nuclear/nuclear fractions. Chondrocytes contain intracellular IGFBP‐2 and IGFBP‐3 but only IGFBP‐3 is associated with nuclei. This suggests the hypothesis that the actions of these IGFBPs in articular cartilage extend beyond the classic modulation of IGF receptor action. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1421–1427, 2008     

Enhanced expression of insulin-like growth factor-binding proteins in human osteoarthritic cartilage detected by immunohistochemistry and in situ hybridization

OBJECTIVE: To determine the roles of insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) in the pathogenesis of osteoarthritis (OA). DESIGN: Cartilage tissues were obtained from the femoral heads of patients with OA, and those from patients with femoral neck fractures were used as a control. The expression of IGFBP-3, -4, and -5 was examined using immunohistochemistry and in situ hybridization, and IGF-I and IGF-I receptors were also immunohistochemically detected. The percentages of positive chondrocytes were determined by counting the total number of chondrocytes over the area of the surface, middle, and deep zones of the cartilage. RESULTS: There was a marked increase in the percentage of positive chondrocytes in all IGFBPs on protein and messenger RNA levels for OA compared to that of the control cartilage. Furthermore, enhanced expression of IGFBPs and the IGF-I/IGF-I receptor was positively correlated with the histologic score for cartilage lesions. CONCLUSION: Up-regulation of IGFBPs as well as IGF-I and its receptor was observed for OA cartilage tissue, suggesting the involvement of IGFBPs in the pathogenesis of OA.     

Serum insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 in children with chronic renal failure: relationship to growth and glomerular filtration rate

Growth retardation in children with chronic renal failure (CRF) is partly due to an inhibition of insulin-like growth factor (IGF) activity by an excess of high-affinity IGF-binding proteins (IGFBPs). The aim of this study was to analyze the serum levels and forms of IGFBP-4 and IGFBP-5 in CRF patients using specific, recently developed radioimmunoassays (RIAs) and immunoblot analysis. We examined 89 children [age 11.5 (2.8–19.0) years] with CRF [glomerular filtration rate 26.6 (7.0–67.4) ml/min per 1.73 m²], nine of them with end-stage renal disease undergoing peritoneal dialysis. Serum-immunoreactive IGFBP-4 levels were fourfold increased in CRF (prepubertal 1080±268 ng/ml; pubertal 989±299 ng/ml) compared to healthy prepubertal controls (265±73 ng/ml). In contrast, serum IGFBP-5 levels were not significantly increased neither in prepubertal (361±120 ng/ml vs 282±75 ng/ml in controls) nor pubertal CRF children (478±165 ng/ml vs 491±80 ng/ml in controls). Immunoblot analysis showed the presence of intact as well as fragmented IGFBP-4 and IGFBP-5. Serum IGFBP-4, but not IGFBP-5, levels were inversely correlated with GFR (r=–0.39, P<0.001). In prepuber- tal children, IGFBP-4 levels were inversely correlated with standardized height (r=–0.40; P<0.005). In contrast, IGFBP-5 levels were positively correlated both with standardized height (r=0.32, P<0.02) and baseline height velocity (r=0.45, P<0.005). A 3-month therapy with rhGH stimulated serum IGFBP-5 levels by 43% (P<0.01); there was no consistent effect on IGFBP-4 levels. There was a positive correlation between IGFBP-4 and IGFBP-2 (r=0.46, P<0.001); IGFBP-5 was positively correlated with IGF-I (r=0.59, P<0.001), IGF-II (r=0.42, P<0.001) and IGFBP-3 (r=0.47, P<0.001) and inversely correlated with IGFBP-1 (r=–0.41, P<0.001). In summary, serum IGFBP-4 is fourfold elevated in children with CRF in relation to the degree of renal dysfunction and contributes to the marked increase in IGF-binding capacity in CRF serum. The inverse correlation of serum IGFBP-4 with standardized height is consistent with its role as another inhibitor of the biological action of the IGFs on growth plate cartilage. In contrast, serum IGFBP-5 is not elevated in CRF serum and circulates mainly as proteolysed fragments. The positive correlation of serum IGFBP-5 with growth and its increase during GH therapy indicate that IGFBP-5 is a stimulatory IGFBP in patients with CRF, either by enhancing IGF activity through better presentation of IGF to its receptor or by an IGF-independent effect through activation of a specific, recently described putative IGFBP-5-receptor. Received: 24 September 1999 / Revised: 6 January 2000 / Accepted: 13 January 2000 / Accepted: 13 January 2000     

Circulating levels of insulin-like growth factor binding protein 3 (IGFBP-3) and insulin-like growth factor I (IGF-I) in perimenopausal women

The study investigated possible menopause-related changes in circulating insulin-like growth factor binding protein 3 (IGFBP-3) levels and their relationship with insulin-like growth factor I (IGF-I) plasma levels. Forty-three healthy women, aged 45–55 years, were studied (22 premenopausal and 21 postmeno-pausal, matched for age and body mass index); in all subjects plasma IGF-I and IGFBP-3 levels were measured by radioimmunoassay. No difference was found between mean IGFBP-3 plasma levels in the two groups studied (premenopausal 3.42±0.49 v postmenopausal 3.46±0.58 mg/l), while mean IGF-I levels were significantly lower in postmenopausal as compared with premenopausal women (136.7±37.86 v 175.7±51.91 ng/ml,p<0.02). Multiple regression analysis showed no significant effect of age, body mass index and years since menopause on IGFBP-3 levels; however, considering the IGF-I/IGFBP-3 ratio as a possible parameter of circulating free somatomedin C, an inverse correlation was found with years since menopause (n=43,r=–0.499,p<0.001). We conclude that lack of oestrogen induces different effects on circulating IGF-I and IGFBP-3, possibly reflecting a real decrease in IGF-I activity.     

Erectile dysfunction is associated with low bioactive testosterone levels and visceral adiposity in men with type 2 diabetes

Low testosterone levels in men are associated with type 2 diabetes mellitus. Erectile dysfunction (ED) is a frequent complication of type 2 diabetes. The aim of our cross-sectional study was to investigate the relationship between ED and total, bioavailable and free testosterone levels in 198 men with type 2 diabetes. In addition, we examined the associations of various cardiovascular risk factors involved in the development of ED in type 2 diabetic men. We found that bioavailable and free testosterone levels were significantly lower in men with ED (p = 0.006 and 0.027 respectively) than those without ED. Sex hormone-binding globulin levels were also reduced, but there was no significant difference in total testosterone (TT) levels between men with and without ED. The severity of ED as assessed by International Index of Erectile Function scores was significantly associated with TT (r = 0.32; p < 0.001), bioavailable testosterone (r = 0.32; p < 0.001) and calculated free testosterone (r = 0.35; p < 0.001) levels. ED was more frequently observed in men with hypertension and a higher waist circumference (p = 0.03). There was also a higher prevalence of ED among smokers (p = 0.06), but there were no significant associations between ED and alcohol consumption or with BMI > 30. This study has shown that ED is associated with low bioavailable and free testosterone levels, age, visceral adiposity and hypertension in type 2 diabetic men.     

Bone matrix insulin-like growth factor (IGF)-I, IGF-II and transforming growth factor (TGF)-beta1 levels in men and postmenopausal women with osteoporosis: lack of association with circulating growth factors and bone mineral density

Previous clinical studies have suggested a positive correlation between serum insulin-like growth factor components and bone mass in both men and women with or without osteoporosis. The aim of the present study was to analyze the relationship between the skeletal levels of insulin-like growth factors and transforming growth factor-b1 and bone mineral density in a group of men and postmenopausal women in whom osteoporosis was diagnosed previously. Bone matrix extraction was achieved by passive dialysis against tetrasodium EDTA-guanidine-HCL. IGF's were quantified by radioimmunoassay. TGF-b1 was assessed by a specific enzyme-linked immunoassay. No correlation between BMD and the concentration of IGF-I, IGF-II and TGF-b1 in bone matrix was detected in either men or postmenopausal women with osteoporosis. In addition, circulating growth factors levels failed to be associated with the concentration of IGF-I, IGF-II and TGF-b1 in the skeleton. Thus, our study provides no evidence for a major role of bone matrix IGF's or TGF-b1 as determinants of bone mass in men or postmenopausal women with osteoporosis.     

Lichen sclerosus in men is associated with elevated body mass index, diabetes mellitus, coronary artery disease and smoking

Purpose

To elucidate disease associations and possible etiology of lichen sclerosus (LS), we identified comorbidities present in men with LS. LS is a chronic inflammatory disease of unknown etiology affecting genitals and urethra of men commonly resulting in strictures.

Methods

Men with LS of the urethra, penis, prepuce and scrotum were identified. A control population was generated from men seen in the Department of Urology matched by age and race in a 5:1 ratio. A case–control study was performed and comorbidities identified by ICD9, CPT codes and medication use via systematic electronic medical record review. Subgroup analysis of men with urethral strictures was performed based on their LS status.

Results

Men with LS had a significantly higher mean body mass index [31.0 (range 18.9–52.6)] compared to controls [28.1 (16.8–64.1), p = 0.001], significantly increased rate of coronary artery disease (CAD) (15.3 vs. 8.9 %, p = 0.05) as well as a twofold higher rate of diabetes mellitus (15.5 vs. 8.3 %, p = 0.02). Of men with LS and stricture disease, 11/19 (58 %) were current or former smokers, compared to 28 % of men with strictures without LS (p = 0.006). No association of LS with other morbidities like hyperlipidemia, hypertension, cerebrovascular disease, peripheral vascular disease or dermatologic disorders was found.

Conclusions

Men suffering from LS have an increased BMI and a higher prevalence of concomitant CAD, diabetes mellitus and tobacco use. Development and chronicity of LS may not be a purely dermatologic condition, but be associated or confounded by systemic or vascular compromise from disorders of CAD, DM and smoking.     

胰岛素和胰岛素样生长因子及其结合蛋白与结直肠癌发生的关系

目的 探讨血清胰岛素、胰岛素样生长因子(IGF-1)、IGF结合蛋白(IGFBPs)及体质量指数(BMI)、腰臀围比(WHR)的变化及与结直肠癌发生、发展的关系.方法 检测对象为2006年6月至2007年10月间住院收治和门诊复查的结直肠癌患者615例(术前检测244例,术后371例)和健康对照者150例.采用酶联免疫吸附法检测血清胰岛素、IGF-1和IGFBPS水平.结果 结直肠癌患者术前血清胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值与健康对照组、术后患者比较,均明显升高,IGFBP-3水平明显降低,差异均有统计学意义(P<0.05,P<0.01).结直肠癌术后未发生转移者与有肝或腹腔远处转移者胰岛素、IGF-1、IGFBP-1、IGFBP-3、IGF-1/IGFBP-3比较.差异均无统计学意义(P>0.05).结直肠癌患者WHR明显高于健康对照组(P<0.01和P<0.05):而BMI与健康对照组比较,差异无统计学意义(P>0.05).结肠癌患者WHR、BMI与胰岛素水平、IGF-1/IGFBP-3比值呈正相关(P<0.01,P<0.05),与IGFBP-3呈负相关(P<0.01,P<0.05);直肠癌患者WHR与血清瘦素、胰岛素水平及BMI与血清IGFBP-1水平均呈正相关(P<0.05),与其他无相关性(P>0.05).结论 胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值升高及IGFBP-3水平降低,可能与结直肠癌的发生有关,但与肿瘤转移与否无关,中心性肥胖是结肠癌发生的危险因素之一.     

胰岛素和胰岛素样生长因子及其结合蛋白与结直肠癌发生的关系

目的探讨血清胰岛素、胰岛素样生长因子（IGF-1）、IGF结合蛋白（IGFBPs）体质量指数（BMI）、腰臀围比（WHR）的变化及与结直肠癌发生、发展的关系。方法检测对象为2006年6月至2007年10月间住院收治和门诊复查的结直肠癌患者615例（术前检测244例,术后371例）和健康对照者150例。采用酶联免疫吸附法检测血清胰岛素、IGF-1和IGFBPS水平。结果结直肠癌患者术前血清胰岛素、IGF-1水平和IGF-I／IGFBP-3比值与健康对照组、术后患者比较,均明显升高,IGFBP-3水平明显降低,差异均有统计学意义（P〈0.05,P〈0.01）。结直肠癌术后未发生转移者与有肝或腹腔远处转移者胰岛素、IGF-1、IGFBP-1、IGFBP-3、IGF-1／IGFBP-3比较,差异均无统计学意义（P〉0.05）。结直肠癌患者WHR明显高于健康对照组（P〈0.01和P〈0.05）;而BMI与健康对照组比较,差异无统计学意义（P〉0.05）。结肠癌患者WHR、BMI与胰岛素水平、IGF-1／IGFBP-3比值呈正相关（P〈0.01,P〈0.05）,与IGFBP-3呈负相关（P〈0.01,P〈0.05）;直肠癌患者WHR与血清瘦素、胰岛素水平及BMI与血清IGFBP-1水平均呈正相关（P〈0.05）,与其他无相关性（P〉0.05）。结论胰岛素、IGF-1水平和IGF-I／IGFBP-3比值升高及IGFBP-3水平降低,可能与结直肠癌的发生有关,但与肿瘤转移与否无关,中心性肥胖是结肠癌发生的危险因素之一。     

胰岛素和胰岛素样生长因子及其结合蛋白与结直肠癌发生的关系

目的 探讨血清胰岛素、胰岛素样生长因子(IGF-1)、IGF结合蛋白(IGFBPs)及体质量指数(BMI)、腰臀围比(WHR)的变化及与结直肠癌发生、发展的关系.方法 检测对象为2006年6月至2007年10月间住院收治和门诊复查的结直肠癌患者615例(术前检测244例,术后371例)和健康对照者150例.采用酶联免疫吸附法检测血清胰岛素、IGF-1和IGFBPS水平.结果 结直肠癌患者术前血清胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值与健康对照组、术后患者比较,均明显升高,IGFBP-3水平明显降低,差异均有统计学意义(P<0.05,P<0.01).结直肠癌术后未发生转移者与有肝或腹腔远处转移者胰岛素、IGF-1、IGFBP-1、IGFBP-3、IGF-1/IGFBP-3比较.差异均无统计学意义(P>0.05).结直肠癌患者WHR明显高于健康对照组(P<0.01和P<0.05):而BMI与健康对照组比较,差异无统计学意义(P>0.05).结肠癌患者WHR、BMI与胰岛素水平、IGF-1/IGFBP-3比值呈正相关(P<0.01,P<0.05),与IGFBP-3呈负相关(P<0.01,P<0.05);直肠癌患者WHR与血清瘦素、胰岛素水平及BMI与血清IGFBP-1水平均呈正相关(P<0.05),与其他无相关性(P>0.05).结论 胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值升高及IGFBP-3水平降低,可能与结直肠癌的发生有关,但与肿瘤转移与否无关,中心性肥胖是结肠癌发生的危险因素之一.     

胰岛素和胰岛素样生长因子及其结合蛋白与结直肠癌发生的关系

目的 探讨血清胰岛素、胰岛素样生长因子(IGF-1)、IGF结合蛋白(IGFBPs)及体质量指数(BMI)、腰臀围比(WHR)的变化及与结直肠癌发生、发展的关系.方法 检测对象为2006年6月至2007年10月间住院收治和门诊复查的结直肠癌患者615例(术前检测244例,术后371例)和健康对照者150例.采用酶联免疫吸附法检测血清胰岛素、IGF-1和IGFBPS水平.结果 结直肠癌患者术前血清胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值与健康对照组、术后患者比较,均明显升高,IGFBP-3水平明显降低,差异均有统计学意义(P<0.05,P<0.01).结直肠癌术后未发生转移者与有肝或腹腔远处转移者胰岛素、IGF-1、IGFBP-1、IGFBP-3、IGF-1/IGFBP-3比较.差异均无统计学意义(P>0.05).结直肠癌患者WHR明显高于健康对照组(P<0.01和P<0.05):而BMI与健康对照组比较,差异无统计学意义(P>0.05).结肠癌患者WHR、BMI与胰岛素水平、IGF-1/IGFBP-3比值呈正相关(P<0.01,P<0.05),与IGFBP-3呈负相关(P<0.01,P<0.05);直肠癌患者WHR与血清瘦素、胰岛素水平及BMI与血清IGFBP-1水平均呈正相关(P<0.05),与其他无相关性(P>0.05).结论 胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值升高及IGFBP-3水平降低,可能与结直肠癌的发生有关,但与肿瘤转移与否无关,中心性肥胖是结肠癌发生的危险因素之一.     

胰岛素和胰岛素样生长因子及其结合蛋白与结直肠癌发生的关系

目的 探讨血清胰岛素、胰岛素样生长因子(IGF-1)、IGF结合蛋白(IGFBPs)及体质量指数(BMI)、腰臀围比(WHR)的变化及与结直肠癌发生、发展的关系.方法 检测对象为2006年6月至2007年10月间住院收治和门诊复查的结直肠癌患者615例(术前检测244例,术后371例)和健康对照者150例.采用酶联免疫吸附法检测血清胰岛素、IGF-1和IGFBPS水平.结果 结直肠癌患者术前血清胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值与健康对照组、术后患者比较,均明显升高,IGFBP-3水平明显降低,差异均有统计学意义(P<0.05,P<0.01).结直肠癌术后未发生转移者与有肝或腹腔远处转移者胰岛素、IGF-1、IGFBP-1、IGFBP-3、IGF-1/IGFBP-3比较.差异均无统计学意义(P>0.05).结直肠癌患者WHR明显高于健康对照组(P<0.01和P<0.05):而BMI与健康对照组比较,差异无统计学意义(P>0.05).结肠癌患者WHR、BMI与胰岛素水平、IGF-1/IGFBP-3比值呈正相关(P<0.01,P<0.05),与IGFBP-3呈负相关(P<0.01,P<0.05);直肠癌患者WHR与血清瘦素、胰岛素水平及BMI与血清IGFBP-1水平均呈正相关(P<0.05),与其他无相关性(P>0.05).结论 胰岛素、IGF-1水平和IGF-Ⅰ/IGFBP-3比值升高及IGFBP-3水平降低,可能与结直肠癌的发生有关,但与肿瘤转移与否无关,中心性肥胖是结肠癌发生的危险因素之一.