Circulating prolactin concentrations and risk of type 2 diabetes in US women

Abstract

Aims/hypothesis 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. Methods 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. Results 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. Conclusions/interpretation 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.

Plasma Prolactin and Progesterone Levels and the Risk of Gestational Diabetes: A Prospective and Longitudinal Study in a Multiracial Cohort

“…The seemingly contradictory findings might be explained by potentially dose-dependent effects of prolactin on glucose homeostasis, as observed in an animal study, where a modest increase (2.5 folds) in prolactin levels promoted glucose-stimulated insulin secretion and reduced insulin resistance, but a large increase (11.8 folds) worsened insulin resistance, although both conditions stimulated β-cell expansion (32). Indeed, prolactin levels were much lower in the studies among non-pregnant, middleaged individuals (median prolactin levels were 8-11 ng/mL) (11,12) than in the studies among hyperprolactinemia patients (median prolactin levels ranges between 59 and 3,354 ng/mL) and in our study (median prolactin levels were 42 and 124 ng/mL at gestational weeks 10-14 and 15-26, respectively).…”

“…Our finding of a positive association between prolactin levels and GDM risk in pregnancy is in line with findings among non-pregnant populations with prolactinoma, where elevated prolactin levels above the normal range (i.e., hyperprolactinemia) were associated with adverse metabolic outcomes including hyperinsulinemia (6), insulin resistance (6)(7)(8), and increased body weight (9,10), and normalizing prolactin levels reverted the adverse metabolic outcomes (8-10); these findings support a role of hyperprolactinemia in worsening metabolic outcomes. In contrast, among non-pregnant, middle-aged populations, higher prolactin levels within the normal range (i.e., 2-18 ng/mL for men and 2-29 ng/mL for non-pregnant women) has been prospectively associated with lower risks of diabetes (11,12) and impaired glucose regulation (11). The seemingly contradictory findings might be explained by potentially dose-dependent effects of prolactin on glucose homeostasis, as observed in an animal study, where a modest increase (2.5 folds) in prolactin levels promoted glucose-stimulated insulin secretion and reduced insulin resistance, but a large increase (11.8 folds) worsened insulin resistance, although both conditions stimulated β-cell expansion (32).…”

“…For example, elevated prolactin levels above the normal range (i.e., hyperprolactinemia) such as in the case of prolactinoma have been associated with adverse outcomes including hyperinsulinemia (6), insulin resistance (6)(7)(8), and increased body weight (9,10). In contrast, higher prolactin levels within the normal range have been linked to lower risks of diabetes in middle-aged, non-pregnant populations (11,12). As prolactin levels increase well-beyond the normal non-pregnant levels during pregnancy, higher prolactin levels during pregnancy might contribute to worsening glucose homeostasis.…”

Hyperprolactinaemia

“…In large population-based studies from China and USA, normal to high-normal PRL levels (but within the reference range) were related to favourable glucose metabolism profile and low risk of diabetes mellitus type 2 [124,125]. There is limited data on hyperprolactinaemia and metabolic parameters.…”

The Effect of Pituitary Gland Disorders on Glucose Metabolism: From Pathophysiology to Management

“…In their study, Li et al attempted to evaluate whether healthy women with high prolactin levels were more protected from T2DM when compared to those with lower circulating prolactin. In their 22 year follow-up, Li et al demonstrated that the higher the prolactin levels were (not exceeding the normal range), the lower the risk for the development of T2DM was [56]. This dose-dependent effect of prolactin on glycemic control demonstrates the need for further studies to truly comprehend the effect prolactin has on glucose metabolism.…”