Insulin-like growth factor axis and risk of type 2 diabetes in women

Swapnil N. Rajpathak, Meian He, Qi Sun, Robert C. Kaplan, Radhika Muzumdar, Thomas E. Rohan, Marc J. Gunter, Michael Pollak, Mimi Kim, Jeffrey E. Pessin, Jeannette Beasley, Judith Wylie-Rosett, Frank B. Hu, Howard D. Strickler

Research output: Contribution to journalArticlepeer-review


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 (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.

Original languageEnglish (US)
Pages (from-to)2248-2254
Number of pages7
Issue number9
StatePublished - Sep 2012

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism


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