Insulin-like growth factor binding protein-2 (IGFBP-2) is a marker for the metabolic syndrome

Aims/hypothesis: IGFs and their binding proteins are increasingly recognised as important in understanding the pathogenesis of cardiovascular disease. Low IGFBP-1, particularly coupled with low IGF-I, is associated with increased cardiovascular risk. In relation to structural and regulatory parallels between IGFBP-1 and -2 we have now examined the hypothesis that IGFBP-2 may be a marker for cardiovascular risk. Methods: Fasting IGFBP-2, IGFBP-1, IGFBP-3, IGF-I, IGF-II, insulin, C-peptide, glucose, lipids, NEFAs, and HbA1c were measured in a cohort of 163 patients with type 2 diabetes. Individuals were categorised according to the presence or absence of the metabolic syndrome. Results: Patients with the metabolic syndrome had a lower IGFBP-2 concentration. Low circulating IGFBP-2 was associated with elevated fasting glucose (ρ = -0.23, p = 0.003). IGFBP-2 correlated negatively with triglycerides (ρ = -0.19, p = 0.01) and LDL-cholesterol (ρ = -0.20, p = 0.01), and positively with insulin sensitivity (HOMA-S) (ρ = 0.26, p = 0.02). Multivariate logistic regression demonstrated that low IGFBP-2 was independently associated with an increased risk of the metabolic syndrome (OR 0.31 [95% CI 0.11-0.90]; p = 0.03). IGFBP-3 did not differ according to the presence or absence of metabolic syndrome. Conclusion/interpretation: Low IGFBP-2 is associated with multiple cardiovascular risk factors similarly to IGFBP-1. Such associations were not apparent for IGFBP-3. Lack of marked prandial regulation of IGFBP-2, in contradistinction to IGFBP-1, may make IGFBP-2 a more robust biomarker for identification of insulin-resistant individuals at high cardiovascular risk in epidemiological studies. © J. A. Barth Verlag in Georg Thieme Verlag KG.