Abstract
Background: Prolactin, a multifunctional hormone, is involved in regulating insulin sensitivity and glucose homeostasis in experimental and cross-sectional human studies. However, whether circulating levels of prolactin are associated with risk of type 2 diabetes (T2D) remains unclear. Methods: We analyzed the prospective relationship between circulating prolactin levels and T2D risk in in the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII) with up to 22 years of follow-up. Total plasma prolactin was measured using immunoassay in 8,637 women free of T2D and cardiovascular disease at baseline blood collection (NHSI: 1989-1990; NHSII: 1996-1999) and a subset of 1,017 NHS women who provided a second blood sample in 2000-2002. In addition, baseline bioactive prolactin levels were measured in a subset of 2,658 women using the Nb2 lymphoma cell bioassay. We calculated hazard ratios (HRs) using Cox regressions. Results: A total of 701 incident T2D cases were documented during 159,517 person-years of follow-up. Circulating prolactin levels were inversely associated with T2D risk; the multivariable HR comparing the highest with the lowest quartile of prolactin levels was 0.71 (95% confidence interval, 0.54-0.93; P trend =0.02). The associations were similar by menopausal status and risk factors ( P >0.70 for interaction). Additional adjustment for sex hormones, growth factors, adipokine, and inflammatory markers did not alter the results. The association of bioactive prolactin with T2D risk was suggestively stronger than that of total prolactin (comparable HR=0.56 vs. 0.82 among the 2,658 women). The inverse association of total plasma prolactin with incident T2D waned linearly with time, with a significant association observed during the first 9 years after blood draw. Conclusion: High circulating prolactin level was independently associated with lower risk of T2D in women. Our findings are consistent with experimental evidence, supporting a possible protective role for prolactin in the pathogenesis of T2D.
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