Insulin-Like Growth Factor Axis and Risk of Type 2 Diabetes in Women
- Swapnil N. Rajpathak1,2,
- Meian He3,4,
- Qi Sun3,5,
- Robert C. Kaplan1,
- Radhika Muzumdar6,
- Thomas E. Rohan1,
- Marc J. Gunter1,
- Michael Pollak7,
- Mimi Kim1,
- Jeffrey E. Pessin2,
- Jeannette Beasley8,
- Judith Wylie-Rosett1,
- Frank B. Hu3,5,9 and
- Howard D. Strickler1⇓
- 1Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
- 2Department of Medicine, Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York
- 3Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts
- 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
- 5Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
- 6Department of Pediatrics, Division of Pediatric Endocrinology, Albert Einstein College of Medicine, Bronx, New York
- 7Department of Medicine and Oncology, Cancer Prevention Research Unit, Lady Davis Research Institute of Jewish General Hospital, McGill University, Montreal, Quebec, Canada
- 8Group Health Research Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington
- 9Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts
- Corresponding author: Howard D. Strickler, .
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.
- © 2012 by the American Diabetes Association.
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