Linked Life Data

12145180

Source:http://linkedlifedata.com/resource/pubmed/id/12145180

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-7-29
pubmed:abstractText
The IGF system is increasingly implicated in the development of cardiovascular disease. The effects of circulating IGFs on the vasculature are largely modulated by IGFBPs, which control their access to cell-surface IGF receptors. IGFBP-1 has been proposed as the acute regulator of IGF bioavailability because of its metabolic regulation by glucoregulatory hormones. Posttranslational phosphorylation of IGFBP-1 significantly increases its affinity for IGF-I and therefore represents a further mechanism for controlling IGF bioavailability. We have therefore examined the IGF system and IGFBP-1 phosphorylation status, using specifically developed immunoassays, in a cohort of 160 extensively characterized type 2 diabetic subjects on two occasions 12 months apart. Total IGFBP-1 (tIGFBP-1), which is predominantly highly phosphorylated, was significantly lower in subjects with known macrovascular disease (geometric mean [95% CI], 48.7 microg/l [33.7-63.6]) than in patients with no vascular pathology (80.0 microg/l [52.2-107]; F = 5.4, P = 0.01). A similar relationship was found for highly phosphorylated IGFBP-1 (hpIGFBP-1) concentration (known macrovascular disease, 45.1 microg/l [35.1-55.2]; no macrovascular disease, 75.8 microg/l [56.2-95.3]; F = 4.8, P = 0.01). Logistic regression showed that for every decrease of 2.73 microg/l in IGFBP-1 concentration, there was a 43% increase in the odds of a subject having macrovascular disease (odds ratio 0.57 [95% CI 0.40-0.83]; P = 0.001). hpIGFBP-1 correlated negatively with systolic blood pressure (rho = -0.30, P < 0.01), diastolic blood pressure (rho = -0.45, P < 0.001), and mean arterial pressure (MAP) (rho = -0.41, P < 0.001). Linear regression modeling showed that 40% of the variance in tIGFBP-1 was accounted for by MAP, triglycerides, and nonesterified fatty acids. In contrast, levels of nonphosphorylated and lesser-phosphorylated IGFBP-1 (lpIGFBP-1) were unrelated to macrovascular disease or hypertension but did correlate positively with fasting glucose concentration (rho = 0.350, P < 0.01). tIGFBP-1 concentrations were higher in subjects treated with insulin alone (n = 29) than for any other group. This effect persisted after adjustment of tIGFBP-1 levels for BMI, C-peptide, age, and sex (F = 6.5, P < 0.001, rho = - 0.46). Such an effect was not apparent for lpIGFBP-1. We conclude that low circulating levels of hpIGFBP-1 are closely correlated with macrovascular disease and hypertension in type 2 diabetes, whereas lpIGFBP-1 isoforms are associated with glycemic control, suggesting a dual role for IGFBP-1 in the regulation of IGF actions in type 2 diabetes. Our data suggest that high circulating concentrations of highly phosphorylated IGFBP-1 may protect against the development of hypertension and cardiovascular disease by reducing the mitogenic potential of IGFs on the vasculature.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2629-36
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:12145180-Biological Markers, pubmed-meshheading:12145180-Blood Glucose, pubmed-meshheading:12145180-Blood Pressure, pubmed-meshheading:12145180-C-Peptide, pubmed-meshheading:12145180-Cholesterol, pubmed-meshheading:12145180-Cholesterol, HDL, pubmed-meshheading:12145180-Cholesterol, LDL, pubmed-meshheading:12145180-Diabetes Mellitus, Type 2, pubmed-meshheading:12145180-Diabetic Angiopathies, pubmed-meshheading:12145180-Ethnic Groups, pubmed-meshheading:12145180-Humans, pubmed-meshheading:12145180-Hypertension, pubmed-meshheading:12145180-Insulin, pubmed-meshheading:12145180-Insulin-Like Growth Factor Binding Protein 1, pubmed-meshheading:12145180-Insulin-Like Growth Factor I, pubmed-meshheading:12145180-Insulin-Like Growth Factor II, pubmed-meshheading:12145180-Odds Ratio, pubmed-meshheading:12145180-Phosphorylation, pubmed-meshheading:12145180-Predictive Value of Tests, pubmed-meshheading:12145180-Regression Analysis, pubmed-meshheading:12145180-Triglycerides
pubmed:year
2002
pubmed:articleTitle
Low circulating levels of insulin-like growth factor binding protein-1 (IGFBP-1) are closely associated with the presence of macrovascular disease and hypertension in type 2 diabetes.
pubmed:affiliation
Faculty of Medicine, Endocrine Sciences Research Group, University of Manchester, Manchester, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Multicenter Study