Leptin and Soluble Leptin Receptor Levels in Plasma and Risk of Type 2 Diabetes in U.S. Women
A Prospective Study
- Qi Sun1,
- Rob M. van Dam1,2,3,
- James B. Meigs4,
- Oscar H. Franco5,
- Christos S. Mantzoros6,7 and
- Frank B. Hu1,2,3
- 1Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts;
- 2Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts;
- 3Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts;
- 4General Medicine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts;
- 5Health Sciences Research Institute, University of Warwick, Coventry, U.K.;
- 6Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts;
- 7Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
- Corresponding author: Qi Sun, qisun{at}hsph.harvard.edu.
Abstract
OBJECTIVE We prospectively examined plasma levels of leptin and soluble leptin receptor (sOB-R), as well as their interactions with other diabetes risk factors, in relation to type 2 diabetes to elucidate the complex relation between these two biomarkers and diabetes risk.
RESEARCH DESIGN AND METHODS Of 32,826 Nurses' Health Study participants who provided blood samples during 1989–1990, 1,054 incident case subjects of type 2 diabetes were identified and confirmed during 1990–2004 and 1,254 matched control subjects were selected. Plasma leptin and sOB-R levels were measured among these participants.
RESULTS After multivariate adjustment for BMI, lifestyle practices, and dietary factors, sOB-R levels were significantly associated with a lower risk of type 2 diabetes. In comparison with women in the lowest quintile, the ORs (95% CI) of developing type 2 diabetes were 0.73 (0.55–0.96), 0.51 (0.38–0.68), 0.42 (0.31–0.57), and 0.39 (0.28–0.54; P for trend < 0.0001) for women in the second to fifth quintiles of sOB-R levels, respectively. In contrast, plasma leptin levels were not significantly associated with the risk of type 2 diabetes: The OR (95% CI) was 0.82 (0.62–1.10; P for trend = 0.46) comparing the highest with the lowest quintile of leptin levels. sOB-R levels were consistently associated with a decreased risk of type 2 diabetes at various levels of leptin or high-molecular-weight adiponectin.
CONCLUSIONS These data suggest a strong inverse association between plasma sOB-R levels and risk of type 2 diabetes, independent of BMI, leptin, and adiponectin levels.
Footnotes
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Received September 9, 2009.
- Accepted November 16, 2009.
- © 2010 by the American Diabetes Association.
