Insulin-Like Growth Factor Axis and Risk of Type 2 Diabetes in Women

  1. Howard D. Strickler1
  1. 1Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
  2. 2Department of Medicine, Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York
  3. 3Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
  4. 4Institute of Occupational Medicine and the Ministry of Education Key Laboratory of Environment and Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
  5. 5Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
  6. 6Department of Pediatrics, Division of Pediatric Endocrinology, Albert Einstein College of Medicine, Bronx, New York
  7. 7Department of Medicine and Oncology, Cancer Prevention Research Unit, Lady Davis Research Institute of Jewish General Hospital, McGill University, Montreal, Quebec, Canada
  8. 8Group Health Research Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington
  9. 9Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
  1. Corresponding author: Howard D. Strickler, howard.strickler{at}
  1. F.B.H. and H.D.S., the two senior authors, contributed equally to this study.


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 (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.

  • Received October 28, 2011.
  • Accepted March 19, 2012.

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  1. Diabetes vol. 61 no. 9 2248-2254
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