title: Insulin-like growth factor axis and risk of type 2 diabetes in women.
abstract: IGF-I shares structural homology and in vitro metabolic activity with insulin. Laboratory models suggest that IGF-I and its binding proteins IGFBP-1 and IGFBP-2 have potentially beneficial effects on diabetes risk, whereas IGFBP-3 may have adverse effects. We therefore conducted a prospective nested case-control investigation of incident diabetes (n = 742 case subjects matched 1:1 to control subjects) and its associations with IGF-axis protein levels in the Nurses' Health Study, a cohort of middle-aged women. The median time to diabetes was 9 years. Statistical analyses were adjusted for multiple risk factors, including insulin and C-reactive protein. Diabetes risk was fivefold lower among women with baseline IGFBP-2 levels in the top versus bottom quintile (odds ratio [OR](q5-q1) = 0.17 [95% CI 0.08-0.35]; P trend < 0.0001) and was also negatively associated with IGFBP-1 levels (OR(q5-q1) = 0.37 [0.18-0.73]; P trend = 0.0009). IGFBP-3 was positively associated with diabetes (OR(q5-q1) = 2.05 [1.20-3.51]; P trend = 0.002). Diabetes was not associated with total IGF-I levels, but free IGF-I and diabetes had a significant association that varied (P interaction = 0.003) by insulin levels above the median (OR(q5-q1) = 0.48 [0.26-0.90]; P trend = 0.0001) versus below the median (OR(q5-q1) = 2.52 [1.05-6.06]; P trend < 0.05). Thus, this prospective study found strong associations of incident diabetes with baseline levels of three IGFBPs and free IGF-I, consistent with hypotheses that the IGF axis might influence diabetes risk.
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Swapnil N
authors.initials: SN
authors.lastname: Rajpathak
authors.forename: Meian
authors.initials: M
authors.lastname: He
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kaplan
authors.forename: Radhika
authors.initials: R
authors.lastname: Muzumdar
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Rohan
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.forename: Mimi
authors.initials: M
authors.lastname: Kim
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Pessin
authors.forename: Jeannette
authors.initials: J
authors.lastname: Beasley
authors.forename: Judith
authors.initials: J
authors.lastname: Wylie-Rosett
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: Howard D
authors.initials: HD
authors.lastname: Strickler
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism*; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008875:Middle Aged; D011446:Prospective Studies; D012306:Risk; D012307:Risk Factors
chemical_list: D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I