Journal
DIABETOLOGIA
Volume 61, Issue 12, Pages 2549-2560Publisher
SPRINGER
DOI: 10.1007/s00125-018-4733-9
Keywords
Hormone; Insulin; Prolactin; Type 2 diabetes
Categories
Funding
- National Cancer Institute [UM1 CA186107, P01 CA87969, R01 CA49449, UM1 CA176726, R01 CA67262, R01 CA119139, R01 CA138580, R01 CA163451]
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01 AR049880]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK46200, DK112940]
- ADA-Pfizer New England Cardiovascular-Metabolic Fellowship Award [9-17-CMF-011]
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Aims/hypothesisProlactin, 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.MethodsWe analysed the prospective relationship between circulating prolactin concentrations and type 2 diabetes risk in the Nurses' Health Study (NHS) and NHSII with up to 22years 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.ResultsA 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; p(trend)=0.02). The associations were similar by menopausal status and other risk factors (p(interaction)>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, p(difference)=0.11). The inverse association of total prolactin with type 2 diabetes was significant during the first 9years 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.Conclusions/interpretationA normally high circulating total prolactin concentration was associated with a lower type 2 diabetes risk within 9-10years 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.
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