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Leptin and Soluble Leptin Receptor Levels in Plasma and Risk of Type 2 Diabetes in US Women: A Prospective Study

  1. Qi Sun (qisun{at}hsph.harvard.edu)1,
  2. Rob M. van Dam1,2,4,
  3. James B. Meigs5,
  4. Oscar H. Franco6,
  5. Christos S. Mantzoros7 and
  6. Frank B. Hu1,2,4
  1. From the 1Departments of Nutrition
  2. 2Epidemiology, and
  3. 3Environmental Health (Dr. Mantzoros), Harvard School of Public Health, Boston, MA 02115, USA
  4. 4Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA
  5. 5General Medicine Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02115, USA
  6. 6Health Sciences Research Institute, University of Warwick, Coventry, CV4 7AL, UK; and
  7. 7Division of Endocrinology, Diabetes, & Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, MA 02115, USA

    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 cases of type 2 diabetes were identified and confirmed during 1990-2004 and 1,254 matched controls 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 to women in the lowest quintile, the odds ratios (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 2nd to 5th quintiles of sOB-R levels, respectively. In contrast, plasma leptin levels were not significantly associated with the risk of type 2 diabetes: The odds ratio (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

      • Received September 9, 2009.
      • Accepted November 16, 2009.

    This Article

    1. Published online before print December 3, 2009, doi: 10.2337/db09-1343 Diabetes December 3, 2009
    1. » Abstract
    2. Full Text (PDF)
    3. All Versions of this Article:
      1. db09-1343v1
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