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.


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.


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.


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.


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