May 3, 2012 -- (Bronx, NY) -- Researchers at Albert Einstein College of Medicine of Yeshiva University in collaboration with Nurses' Health Study investigators have shown that levels of certain related proteins found in blood are associated with a greatly reduced risk for developing type 2 diabetes up to a decade or more later. The findings, published today in the online edition of Diabetes, could open a new front in the war against diabetes.
These proteins are part of what is called the IGF axis. This axis was named for insulin-like growth factor-1, (IGF-1), so called because it has biological effects similar to those of insulin (the hormone that regulates blood glucose levels) but has a greater effect on cell growth than insulin. The researchers also looked at levels of several proteins known as IGF binding proteins, or IGFBPs, that may have strong effects independent of IGF-1.
Researchers have hypothesized that the IGF axis may influence risk for developing diabetes - an idea supported by laboratory and mouse studies, and a few initial studies in humans. However, the current study is the first large, prospective investigation of several components of the IGF-axis and the risk for developing diabetes, according to co-senior author Howard Strickler, M.D., M.P.H., professor of epidemiology & population health at Einstein.
In the current study, the researchers analyzed levels of IGF-1, IGFBP-1, IGFBP-2, and IGFBP-3 in blood taken from 742 women in the Nurses' Health Study who years later developed type 2 diabetes as well as a similar number of women in the study who did not develop diabetes. None of the women had any signs or symptoms of the disease at the time their blood samples were taken. The median time between the taking of blood samples and diabetes onset was nine years.
Each component of the IGF axis (IGF-1 and IGFBP-1, -2, and -3) had a significant independent association with diabetes risk - most notably IGFBP-1 and -2. Compared with women in the bottom 20 percent with respect to their levels of IGFBP-1, having high levels of IGFBP-1 (top 20 percent) was associated with a three-fold reduction in risk for diabetes, while high levels of IGFBP-2 were associated with a more than five-fold reduction in diabetes risk.
"Our data provide important new evidence that circulating IGF-axis proteins may have a role in the development of type 2 diabetes," said Dr. Strickler.
The findings have potential clinical implications. First of all, IGF-axis proteins could help in stratifying people at risk for diabetes. "For example," said Dr. Strickler, "we know that obesity is a major risk factor for diabetes. But some overweight individuals don't develop diabetes, while some thin people do. If our findings are confirmed, they could help doctors more precisely determine who is actually at risk for the disease."
The proteins may also prove useful as targets for novel therapies to prevent or treat diabetes. But Dr. Strickler cautions that it's too early to apply these findings to clinical practice. "IGF-axis proteins have other effects, some beneficial and some not," he notes. "We need to learn more about the connection between the IGF-axis and diabetes before we recommend that people get tested for these substances, and before deciding how we can exploit the IGF-1 axis to help address diabetes."
The Diabetes paper is titled, "The Insulin-Like Growth Factor Axis and Risk of Type 2 Diabetes in Women." The first author was Swapnil Rajpathak (who was at Einstein at the time this work was conducted). The other senior author is Frank B. Hu, M.D., Ph.D, of Harvard School of Public Health, Boston, MA. Additional contributors include Meian He, M.D., Ph.D., (Harvard and Huazhong University of Science and Technology, Wuhan, Hubei, China); Qi Sun M.D., Sc.D., (Harvard); Jeannette Beasley, Ph.D., R.D., M.P.H., (Fred Hutchinson Cancer Research Center, Seattle, WA); Michael Pollak, M.D., (McGill University, Montreal, Quebec, Canada); and Robert Kaplan, Ph.D., Radhika Muzumdar M.D., M.B.B.S., Thomas Rohan, M.D., Ph.D., Mimi Kim, Sci.D., Jeffrey Pessin, Ph.D., and Judith Wylie-Rosett, Ed.D., all of Einstein. Co-author Marc Gunter, Ph.D., contributed to the paper while at Einstein.
The study was supported by grants from the National Institutes of Health. Laboratory testing and data analysis were supported in part by NIDDK 5-R01-DK-080792. The NHS is supported by grants CA-87969, DK-58845, and DK-58785 from the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Child Health and Human Development. Q.S. was supported by a career development award (K99HL098459) from the National Heart, Lung, and Blood Institute. The authors report no conflicts of interest.
About Albert Einstein College of Medicine of Yeshiva University
Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. During the 2011-2012 academic year, Einstein is home to 724 M.D. students, 248 Ph.D. students, 117 students in the combined M.D./Ph.D. program, and 368 postdoctoral research fellows. The College of Medicine has 2,522 full time faculty members located on the main campus and at its clinical affiliates. In 2011, Einstein received nearly $170 million in awards from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore Medical Center, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Through its extensive affiliation network involving Montefiore, Jacobi Medical Center) - Einstein's founding hospital, and five other hospital systems in the Bronx, Manhattan, Long Island and Brooklyn, Einstein runs one of the largest post-graduate medical training programs in the United States, offering approximately 155 residency programs to more than 2,200 physicians in training. For more information, please visit www.einstein.yu.edu and follow us on Twitter @EinsteinMed.