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IGF1 and its binding proteins 3 and 1 are differentially associated with metabolic syndrome in older men

¹ School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6009, Australia
² Department of Endocrinology and Diabetes
³ PathWest Laboratory Medicine, Fremantle Hospital, Fremantle, Western Australia 6160, Australia
⁴ Pituitary Research Unit, Garvan Institute of Medical Research, Sydney, New South Wales 2010, Australia
⁵ WA Centre for Health and Ageing, Centre for Medical Research
⁶ School of Surgery, University of Western Australia, Perth, Western Australia 6009, Australia
⁷ School of Population Health and Clinical Practice, University of Adelaide, Adelaide, South Australia 5000, Australia

(Correspondence should be addressed to B B Yeap at School of Medicine and Pharmacology, Level 2, T Block, Fremantle Hospital, Alma Street, Fremantle, Western Australia 6160, Australia; Email: byeap{at}cyllene.uwa.edu.au)

Objective: Circulating IGF1 declines with age, and reduced circulating IGF1 is associated with increased cardiovascular mortality in some but not all studies. The relationship between IGF-binding proteins 3 and 1 (IGFBP3 and IGFBP1) with risk of cardiovascular disease remains unclear. We sought to examine associations between IGF1, IGFBP3 and IGFBP1 with metabolic syndrome in older men.

Design: Cross-sectional analysis of 3980 community-dwelling men aged 70 years.

Methods: Morning plasma levels of IGF1, IGFBP3 and IGFBP1 were assayed. Metabolic syndrome was defined according to National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) criteria.

Results: For IGF1 and IGFBP3, there was a U-shaped relationship, with middle quintiles possessing the lowest odds ratios (OR) for metabolic syndrome (reference Q1, Q3 IGF1: OR 0.74, 95% confidence intervals 0.57–0.96, Q3 IGFBP3: OR 0.67, 0.51–0.87). Increasing IGFBP1 was associated with reduced risk of metabolic syndrome with a dose–response gradient (reference Q1, OR for Q2 to Q5 IGFBP1: 0.56, 0.33, 0.22 and 0.12 respectively, P<0.001). IGF1 was associated with two, IGFBP1 with four and IGFBP3 with all five components of the metabolic syndrome. The ratio of IGF1/IGFBP3 was not associated with metabolic syndrome.

Conclusions: In older men, both lower and higher IGF1 and IGFBP3 levels may be metabolically unfavourable. IGFBP1, as a marker of insulin sensitivity, is relevant in the assessment of metabolic syndrome, while the IGF1/IGFBP3 ratio is less informative. Longitudinal follow-up of this cohort would be needed to determine whether these distributions of IGF1, IGFBP3 and IGFBP1 predict incidence of cardiovascular events during male ageing.