Circulating Prolactin and Risk of Type 2 Diabetes

A Prospective Study

TiangeWang; Yu Xu; Min Xu; Guang Ning; Jieli Lu; Meng Dai; Baihui Xu; Jichao Sun; Wanwan Sun; Shenghan Lai; Yufang Bi; Weiqing Wang*


Am J Epidemiol. 2016;184(4):295-301. 

In This Article

Abstract and Introduction


Prolactin plays an important role in maintaining a normal glucose homeostasis during pregnancy and beyond. Studies investigating the association between prolactin and type 2 diabetes beyond pregnancy are rare and none is prospective. We aimed to examine whether prolactin associates with type 2 diabetes prospectively in a Chinese population. In 2009, 2,377 participants aged 40 years or older were enrolled from Shanghai, China. Among 1,596 diabetes-free participants at baseline, 1,510 completed the follow-up investigation in 2013. Participants who had a fasting plasma glucose ≥126 mg/dL and/or a 2-hour plasma glucose ≥200 mg/dL during a 75-g oral glucose tolerance test had a definite diagnosis of type 2 diabetes or received antidiabetic therapies during follow-up were classified as having type 2 diabetes. During a mean follow-up of 3.7 years, 189 new cases of type 2 diabetes were documented. After multivariate adjustment, women in the highest quartile of prolactin showed the lowest risk for diabetes compared with those in the lowest quartile (hazard ratio = 0.48, 95% confidence interval: 0.26, 0.90). However, such significant associations were not observed in men. Prolactin may be a mediator in the pathogenesis of type 2 diabetes in women; however, more studies are needed to elucidate the underlying sex-specific mechanism.


Prolactin is a polypeptide with highly versatile functions, which are related to lactation, reproduction, metabolism, and immune regulation. Physiological changes in circulating prolactin have been associated with pregnancy, lactation, physical activity, sleep, and stress.[1,2] During the pregnancy period, maternal prolactin increases concurrently with the increased demand for insulin to stimulate β-cell proliferation, insulin production, and secretion, in order to accommodate the growing fetal compartment as well as the substantial increase in insulin resistance.[3,4] On the other hand, during the nonpregnancy period, prolactin is also responsible for normal glucose homeostasis by promoting cumulative insulin secretion and inhibiting key caspases of the extrinsic and intrinsic pathways leading to islet apoptosis.[5–7]

So far, evidence linking prolactin and glucose metabolism is derived mainly from experimental studies, and relevant population studies are rare. We previously studied the association between circulating prolactin and glucose metabolism and first reported that high circulating prolactin levels are associated with a lower prevalence of diabetes and impaired glucose regulation in middle-aged and elderly Chinese men and postmenopausal women.[8] Epidemiologic studies investigating the association between prolactin and type 2 diabetes are limited, and none is prospective. In the present study, we aim to study the association between circulating prolactin and incident type 2 diabetes among Chinese men and women in a prospective study.