Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Circulating IGF binding protein (IGFBP)-1 levels have been associated with insulin sensitivity, the metabolic syndrome, several cardiovascular risk factors, and possibly with cancer. We examined long-term nutrient intake and metabolic and anthropometric factors in relation to IGFBP-1 levels in 226 men, 42-76 yr old, who completed 14 24-h diet recall interviews. Spearman rank correlation coefficients were calculated. Serum IGFBP-1 levels were significantly inversely correlated with insulin, homeostasis model assessment-insulin resistance, and IGF-I and positively correlated with age. Furthermore, IGFBP-1 was inversely correlated with anthropometric measures reflecting obesity, somewhat stronger in middle-aged (<65 yr) than in older men. Serum IGFBP-1 increased with higher energy and carbohydrate intake but only in the younger age group. The difference in mean IGFBP-1 levels comparing men in the top quartile of carbohydrate intake with those in the bottom quartile was 45% in men of age 42-54 yr (P = 0.01). Insulin, body mass index, and carbohydrate intake together explained 39% of the variability in IGFBP-1 levels in men 42-54 yr of age, 27% in men 55-64 yr, and 6% in men 65 or more years old. Our data suggest that metabolic, anthropometric, and nutritional factors are important determinants of IGFBP-1 levels in healthy men.
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PMID:Metabolic, anthropometric, and nutritional factors as predictors of circulating insulin-like growth factor binding protein-1 levels in middle-aged and elderly men. 1507 Sep 59

Metabolic syndrome was initially described as an aggregation of risk factors for the development of coronary artery disease with insulin resistance and compensatory hyperinsulinemia as the underlying factor. In an earlier review, we suggested that hyperinsulinemia may also lead to prostate cancer (PCa), the most common male cancer in industrialized nations. Furthermore, we suggested that diet and exercise, known to be important in the development of insulin resistance, may also be important in the development of PCa. When we placed men from the United States on a low-fat diet and/or exercise program, serum levels of insulin, free testosterone, estradiol and insulin-like growth factor (IGF)-1 were reduced while sex hormone-binding globulin (SHBG) and insulin-like growth factor binding protein (IGFBP)-1 were elevated. These in vivo serum changes directly impacted on androgen-dependent prostate cancer cell lines in vitro to reduce cell growth and induce apoptosis. The reduction in serum IGF-1 and increase in IGFBP-1 with diet and exercise appear to be the most significant, as these changes lead to an increase in tumor cell p53 protein and its down-stream effector p21, which are responsible for the reduction in cell growth and induced apoptosis. Preliminary results from a clinical study with men on "watchful waiting" indicate that the observed in vitro effects of diet and exercise on prostate cancer cell growth also occur in vivo.
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PMID:Preclinical models relevant to diet, exercise, and cancer risk. 1564 82

Hepatic sex-hormone binding globulin (SHBG) production is down-regulated by insulin and low levels reflect insulin resistance. Because insulin resistance is closely related to the development of cardiovascular disease in different ethnic groups we examined ethnic variation in SHBG across populations with different baseline cardiovascular risk and metabolic syndrome prevalence. Participants were population-based, of European (n = 142), Pakistani (n = 130), and African-Caribbean (AfC) origin (n = 193). SHBG, fasting lipids, and glucose concentrations plus insulin sensitivity (HOMA-S) were determined. Age adjusted SHBG was significantly lower in both Pakistani men and women. Circulating SHBG levels were lower in those with impaired vs. normal glucose homeostasis. SHBG correlated positively with HOMA-S (rho = 0.28, p < 0.001), and negatively with WHR (rho = - 0.38, p < 0.001), BMI (r = - 0.30, p < 0.001), and diastolic blood pressure (rho = - 0.14, p < 0.01) across all ethnic groups. In multivariate logistic regression analysis a low SHBG increased the likelihood of the metabolic syndrome (odds ratio [OR] = 0.42 [0.21 - 0.82], p = 0.01) as did higher fasting NEFA (OR 1.47 [1.04 - 2.08], p = 0.03), low IGFBP-1 concentrations (OR 0.6 [0.44 - 0.81], p = 0.001), age (OR 1.05 [1.02 - 1.09], p = 0.003), and Pakistani ethnicity (p = 0.001) in a model which also contained gender, lnCRP, IGF-I, and IGF-II. As ethnic differences in SHBG level closely parallel differences in insulin resistance. Its measurement may be useful in identifying individuals at particular risk of the metabolic syndrome, for early intervention.
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PMID:Low sex hormone binding globulin is a potential marker for the metabolic syndrome in different ethnic groups. 1623 54

Recently the definition, the pathophysiology and even the clinical utility of metabolic syndrome (MS) have been discussed. The risk induced by each component of the metabolic syndrome is higher than the risk induced by MS alone. MS alone is, in fact, a weaker predictor of cardiovascular disease than diabetes. New criteria to define the metabolic syndrome have been proposed, as adipokines, CRP and PAI-1. IGFBP-1 is related to hyperinsulinemia/insulin resistance and to the risk of diabetes and fatal ischemic heart disease development. IGF/IGFBP system could be a link between insulin resistance and cardiovascular disease. RBP-4 can attenuate insulin signalling in skeletal muscle and induce hepatic gluconeogenesis. The belief that insulin-resistance is the main cause of MS could change in favour of the adipose tissue dysfunction. The most common cause of a reduced capacity of the adipose tissue to store fats is the increased dietary intake, also present in lipodistrophy, type 1 diabetes mellitus and polycystic ovarian syndrome. The adipose tissue production of adipokines and cytokines (such as IL-6, TNF-alpha and TGF-beta) and the excessive lipid flux towards muscles, heart and liver (Ectopic fat storage syndrome) contribute to the MS genesis and to an increased cardiovascular risk. The comprehension of adipose tissue dysfunction mechanisms offers new possibilities of prevention and therapy.
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PMID:[Metabolic syndrome: from insulin resistance to adipose tissue dysfunction]. 1849 27

The aim of the present study was to investigate the specific relationship between hepatic steatosis and insulin resistance in the early stage of obesity. Among general health examinees who received an ultrasound scanning, 131 subjects without fatty liver (non-FL group) and 142 subjects with fatty liver (FL group) were selected so that both groups were matched for age, sex, body mass index, and % body fat. The FL group was then subdivided into 2 groups according to the severity of steatosis by ultrasound. Insulin resistance was assessed by homeostasis model assessment for insulin resistance, serum high-molecular-weight (HMW) adiponectin, and insulin-like growth factor binding protein 1 concentrations. Unexpectedly, the non-FL group showed higher waist circumference than the FL group. Nevertheless, homeostasis model assessment for insulin resistance as well as conventional insulin resistance indexes such as serum insulin, free fatty acid, and triglyceride levels demonstrated a stepwise increase, and HMW adiponectin and insulin-like growth factor binding protein 1 demonstrated a stepwise decrease with increasing degree of hepatic steatosis. Overall, insulin resistance markers correlated with obesity indexes, but only HMW adiponectin no longer showed any meaningful correlation in the presence of fatty liver. The prevalence of BP, fasting serum glucose, and high-density lipoprotein cholesterol above or below cutoff points and subjects having 2 or more metabolic syndrome components were higher in the moderate to severe FL group compared to the non-FL group. In conclusion, these results in nondiabetic and relatively normal-body mass index subjects suggest that hepatic steatosis is independently associated with insulin resistance regardless of extrahepatic adiposity and might be the earliest event in pathogenesis of the metabolic syndrome.
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PMID:Hepatic steatosis rather than visceral adiposity is more closely associated with insulin resistance in the early stage of obesity. 1905 41

The insulin-like growth factor (IGF) system, acting in concert with other hormone axes, is important in normal metabolism. In obesity, the hyperinsulinaemia that accompanies peripheral insulin resistance leads to reduced growth hormone (GH) secretion, while total IGF-I levels are relatively unchanged due to increased hepatic GH sensitivity. IGF-binding protein (IGFBP)-1 levels are suppressed in relation to the increase in insulin levels in obesity and low levels predict the development of type 2 diabetes several years later. Visceral adiposity and hepatic steatosis, along with a chronic inflammation, contribute to the IGF system phenotype in individuals with metabolic syndrome and type 2 diabetes mellitus, including changes in the normal inverse relationship between IGFBP-1 and insulin, with IGFBP-1 concentrations that are inappropriately normal or elevated. The IGF system is implicated in the vascular and other complications of these disorders and is therefore a potential therapeutic target.
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PMID:The Insulin-Like Growth Factor System in Obesity, Insulin Resistance and Type 2 Diabetes Mellitus. 2623 14