Circulating prolactin concentrations and risk of type 2 diabetes in US women
Prolactin, a multifunctional hormone, is involved in regulating insulin sensitivity and glucose homeostasis in experimental studies. However, whether circulating concentrations of prolactin are associated with risk of type 2 diabetes remains uncertain.
We analysed the prospective relationship between circulating prolactin concentrations and type 2 diabetes risk in the Nurses’ Health Study (NHS) and NHSII with up to 22 years of follow-up. Total plasma prolactin was measured using immunoassay in 8615 women free of type 2 diabetes and cardiovascular disease at baseline blood collection (NHS 1989–1990; NHSII 1996–1999) and a subset of 998 NHS women providing a second blood sample during 2000–2002. Baseline bioactive prolactin was measured in a subset of 2478 women using the Nb2 bioassay. HRs were estimated using Cox regression.
A total of 699 incident type 2 diabetes cases were documented during 156,140 person-years of follow-up. Total plasma prolactin levels were inversely associated with type 2 diabetes risk; the multivariable HR comparing the highest with the lowest quartile was 0.73 (95% CI 0.55, 0.95; ptrend = 0.02). The associations were similar by menopausal status and other risk factors (pinteraction > 0.70). Additional adjustment for sex and growth hormones, adiponectin, and inflammatory and insulin markers did not significantly alter the results. The association of plasma bioactive prolactin with type 2 diabetes risk was non-significantly stronger than that of total prolactin (HR comparing extreme quartiles, 0.53 vs 0.81 among the subset of 2478 women, pdifference = 0.11). The inverse association of total prolactin with type 2 diabetes was significant during the first 9 years after blood draw but waned linearly with time, whereas for bioactive prolactin, the inverse relationship persisted for a longer follow-up time after blood draw.
A normally high circulating total prolactin concentration was associated with a lower type 2 diabetes risk within 9–10 years of follow-up since blood draw in US women. Our findings are consistent with experimental evidence, suggesting that among healthy women, prolactin within the biologically normal range may play a protective role in the pathogenesis of type 2 diabetes.
KeywordsHormone Insulin Prolactin Type 2 diabetes
Alternative Healthy Eating Index
High-sensitivity C-reactive protein
Intra-class correlation coefficient
IGF binding protein-3
Limit of detection
Five-item Mental Health Inventory
Nurses’ Health Study
Nurses’ Health Study II
Sex hormone binding globin
This research was conducted using data and resources from the NHS and NHSII of the Channing Division of Network Medicine in the Department of Medicine at the Brigham and Women’s Hospital and Harvard Medical School. The authors thank the NHS and NHSII investigators for their important contributions in resource development and intellectual input.
FBH and SST generated the conception and designed the study. SST, MSR, SEH and CVC collected and processed the data. JL, TH and SST analysed and interpreted the data. JL drafted the manuscript. All authors revised the manuscript critically for important intellectual content, and approved the final version of the article and submission to the journal. SST is responsible for the integrity of the work as a whole.
This study was funded by the National Cancer Institute grants UM1 CA186107, P01 CA87969, R01 CA49449, UM1 CA176726, R01 CA67262, R01 CA119139, R01 CA138580 and R01 CA163451; the National Institute of Arthritis and Musculoskeletal and Skin Diseases grant R01 AR049880; and the National Institute of Diabetes and Digestive and Kidney Diseases grants DK46200 and DK112940. JL is a recipient of the ADA-Pfizer New England Cardiovascular-Metabolic Fellowship Award (9-17-CMF-011). The funders had no role in study design, data collection, data analysis, data interpretation, the writing of the report or decision of publication of the results.
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
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