[University home]

The University of Manchester Library

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

Heald, A H; Siddals, K W; Fraser, W; Taylor, W; Kaushal, K; Morris, J; Young, R J; White, A; Gibson, J M

Diabetes. 2002;51(8):2629-2636.

Access to files

Full-text and supplementary files are not available from Manchester eScholar. Use our list of Related resources to find this item elsewhere.

Abstract

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 mug/l [33.7-63.6]) than in patients with no vascular pathology (80.0 mug/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 mug/l [35.1-55.2]; no macrovascular disease, 75.8 mug/l [56.2-95.3]; F = 4.8, P = 0.01). Logistic regression showed that for every decrease of 2.73 mug/l in IGFBP-1 concentration, there was a 43% increase in the odds of a subject having macrovascular disease (odds ratio 0.57 [95% Cl 0.40-0.83]; P = 0.001). hplGFBP-1 correlated negatively with systolic blood pressure (p = -0.30, P < 0.01), diastolic blood pressure (p = -0.45, P < 0.001), and mean arterial pressure (MAP) (p = -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 (IpIGFBP-1) were unrelated to macrovascular disease or hypertension but did correlate positively with fasting glucose concentration (p = 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, p = -0.46). Such an effect was not apparent for IpIGFBP-1. We conclude that low circulating levels of hpIGFBP-1 are closely correlated with macrovascular disease and hypertension in type 2 diabetes, whereas IpIGFBP-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.

Bibliographic metadata

Type of resource:
Content type:
Published date:
Journal title:
Volume:
51
Issue:
8
Start page:
2629
End page:
2636
Total:
8
Pagination:
2629-2636
Digital Object Identifier:
10.2337/diabetes.51.8.2629
ISI Accession Number:
ISI:000177185900038
Related website(s):
  • Related website <Go to ISI>://000177185900038
Access state:
Active

Institutional metadata

University researcher(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:151215
Created by:
Gibson, Martin
Created:
15th January, 2012, 15:04:06
Last modified by:
Gibson, Martin
Last modified:
1st February, 2013, 19:48:56