Rajpathak, Swapnil N.He, MeianSun, QiKaplan, Robert C.Muzumdar, RadhikaRohan, Thomas E.Gunter, Marc J.Pollak, MichaelKim, MimiPessin, Jeffrey E.Beasley, JeannetteWylie-Rosett, JudithHu, FrankStrickler, Howard D.2014-03-102012Rajpathak, S. N., M. He, Q. Sun, R. C. Kaplan, R. Muzumdar, T. E. Rohan, M. J. Gunter, et al. 2012. “Insulin-Like Growth Factor Axis and Risk of Type 2 Diabetes in Women.” Diabetes 61 (9): 2248-2254. doi:10.2337/db11-1488. http://dx.doi.org/10.2337/db11-1488.0012-1797http://nrs.harvard.edu/urn-3:HUL.InstRepos:11876990IGF-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 (ORq5–q1 = 0.37 [0.18–0.73]; P trend = 0.0009). IGFBP-3 was positively associated with diabetes (ORq5–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 (ORq5–q1 = 0.48 [0.26–0.90]; P trend = 0.0001) versus below the median (ORq5–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.en-USJournal Article2014-03-1010.2337/db11-1488