Top

Published in:

01-12-2018 | Article

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

Authors: Jun Li, Megan S. Rice, Tianyi Huang, Susan E. Hankinson, Charles V. Clevenger, Frank B. Hu, Shelley S. Tworoger

Published in: Diabetologia | Issue 12/2018

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; 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 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.

Available only for authorised users

International Diabetes Federation IDF (2017) Diabetes Atlas. Available from http://www.diabetesatlas.org/key-messages.html

Mathers CD, Loncar D (2006) Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 3:e442CrossRef

Kahn SE, Cooper ME, Del Prato S (2014) Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present, and future. Lancet 383:1068–1083CrossRef

Huang Y, Chang Y (2014) Regulation of pancreatic islet beta-cell mass by growth factor and hormone signaling. Prog Mol Biol Transl Sci 121:321–349CrossRef

Ben-Jonathan N, Hugo ER, Brandebourg TD, LaPensee CR (2006) Focus on prolactin as a metabolic hormone. Trends Endocrinol Metab 17:110–116CrossRef

Bernard V, Young J, Chanson P, Binart N (2015) New insights in prolactin: pathological implications. Nat Rev Endocrinol 11:265–275CrossRef

Brandebourg T, Hugo E, Ben-Jonathan N (2007) Adipocyte prolactin: regulation of release and putative functions. Diabetes Obes Metab 9:464–476CrossRef

Cejkova P, Fojtikova M, Cerna M (2009) Immunomodulatory role of prolactin in diabetes development. Autoimmun Rev 9:23–27CrossRef

Freeman ME, Kanyicska B, Lerant A, Nagy G (2000) Prolactin: structure, function, and regulation of secretion. Physiol Rev 80:1523–1631CrossRef

10.

Terra LF, Garay-Malpartida MH, Wailemann RA, Sogayar MC, Labriola L (2011) Recombinant human prolactin promotes human beta cell survival via inhibition of extrinsic and intrinsic apoptosis pathways. Diabetologia 54:1388–1397CrossRef

11.

Weinhaus AJ, Stout LE, Bhagroo NV, Brelje TC, Sorenson RL (2007) Regulation of glucokinase in pancreatic islets by prolactin: a mechanism for increasing glucose-stimulated insulin secretion during pregnancy. J Endocrinol 193:367–381CrossRef

12.

Ruiz-Herrera X, de Los Rios EA, Diaz JM et al (2017) Prolactin promotes adipose tissue fitness and insulin sensitivity in obese males. Endocrinology 158:56–68PubMed

13.

Yu J, Xiao F, Zhang Q et al (2013) PRLR regulates hepatic insulin sensitivity in mice via STAT5. Diabetes 62:3103–3113CrossRef

14.

Park S, Kim DS, Daily JW, Kim SH (2011) Serum prolactin concentrations determine whether they improve or impair beta-cell function and insulin sensitivity in diabetic rats. Diabetes Metab Res Rev 27:564–574CrossRef

15.

Costanza M, Binart N, Steinman L, Pedotti R (2015) Prolactin: a versatile regulator of inflammation and autoimmune pathology. Autoimmun Rev 14:223–230CrossRef

16.

Wagner R, Heni M, Linder K et al (2014) Age-dependent association of serum prolactin with glycaemia and insulin sensitivity in humans. Acta Diabetol 51:71–78CrossRef

17.

Wang T, Lu J, Xu Y et al (2013) Circulating prolactin associates with diabetes and impaired glucose regulation: a population-based study. Diabetes Care 36:1974–1980CrossRef

18.

Balbach L, Wallaschofski H, Volzke H, Nauck M, Dorr M, Haring R (2013) Serum prolactin concentrations as risk factor of metabolic syndrome or type 2 diabetes? BMC Endocr Disord 13:12CrossRef

19.

Wang T, Xu Y, Xu M et al (2016) Circulating prolactin and risk of type 2 diabetes: a prospective study. Am J Epidemiol 184:295–301CrossRef

20.

Retnakaran R, Ye C, Kramer CK et al (2016) Maternal serum prolactin and prediction of postpartum beta-cell function and risk of prediabetes/diabetes. Diabetes Care 39:1250–1258CrossRef

21.

Therkelsen KE, Abraham TM, Pedley A et al (2016) Association between prolactin and incidence of cardiovascular risk factors in the Framingham Heart Study. J Am Heart Assoc 5

22.

Sinha YN (1995) Structural variants of prolactin: occurrence and physiological significance. Endocr Rev 16:354–369CrossRef

23.

Hankinson SE, Willett WC, Manson JE et al (1995) Alcohol, height, and adiposity in relation to estrogen and prolactin levels in postmenopausal women. J Natl Cancer Inst 87:1297–1302CrossRef

24.

Zhang X, Tworoger SS, Eliassen AH, Hankinson SE (2013) Postmenopausal plasma sex hormone levels and breast cancer risk over 20 years of follow-up. Breast Cancer Res Treat 137:883–892CrossRef

25.

Tworoger SS, Sluss P, Hankinson SE (2006) Association between plasma prolactin concentrations and risk of breast cancer among predominately premenopausal women. Cancer Res 66:2476–2482CrossRef

26.

Tworoger SS, Eliassen AH, Zhang X et al (2013) A 20-year prospective study of plasma prolactin as a risk marker of breast cancer development. Cancer Res 73:4810–4819CrossRef

27.

Kotsopoulos J, Tworoger SS, Campos H et al (2010) Reproducibility of plasma and urine biomarkers among premenopausal and postmenopausal women from the Nurses’ Health Studies. Cancer Epidemiol Biomark Prev 19:938–946CrossRef

28.

Tworoger SS, Eliassen AH, Rosner B, Sluss P, Hankinson SE (2004) Plasma prolactin concentrations and risk of postmenopausal breast cancer. Cancer Res 64:6814–6819CrossRef

29.

Tworoger SS, Eliassen AH, Sluss P, Hankinson SE (2007) A prospective study of plasma prolactin concentrations and risk of premenopausal and postmenopausal breast cancer. J Clin Oncol 25:1482–1488CrossRef

30.

Tworoger SS, Rice MS, Rosner BA, Feeney YB, Clevenger CV, Hankinson SE (2015) Bioactive prolactin levels and risk of breast cancer: a nested case-control study. Cancer Epidemiol Biomark Prev 24:73–80CrossRef

31.

Heidemann C, Sun Q, van Dam RM et al (2008) Total and high-molecular-weight adiponectin and resistin in relation to the risk for type 2 diabetes in women. Ann Intern Med 149:307–316CrossRef

32.

Qi L, Rifai N, Hu FB (2009) Interleukin-6 receptor gene, plasma C-reactive protein, and diabetes risk in women. Diabetes 58:275–278CrossRef

33.

Rice MS, Tworoger SS, Rosner BA, Pollak MN, Hankinson SE, Tamimi RM (2012) Insulin-like growth factor-1, insulin-like growth factor-binding protein-3, growth hormone, and mammographic density in the Nurses’ Health Studies. Breast Cancer Res Treat 136:805–812CrossRef

34.

Schulze MB, Solomon CG, Rifai N et al (2005) Hyperproinsulinaemia and risk of type 2 diabetes mellitus in women. Diabet Med 22:1178–1184CrossRef

35.

Okereke OI, Pollak MN, Hu FB, Hankinson SE, Selkoe DJ, Grodstein F (2008) Plasma C-peptide levels and rates of cognitive decline in older, community-dwelling women without diabetes. Psychoneuroendocrinology 33:455–461CrossRef

36.

Arroyo C, Hu FB, Ryan LM et al (2004) Depressive symptoms and risk of type 2 diabetes in women. Diabetes Care 27:129–133CrossRef

37.

Manson JE, Rimm EB, Stampfer MJ et al (1991) Physical activity and incidence of non-insulin-dependent diabetes mellitus in women. Lancet 338:774–778CrossRef

38.

National Diabetes Data Group (1979) Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28:1039–1057CrossRef

39.

Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (2003) Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 26(Suppl 1):S5–S20

40.

McCullough ML, Feskanich D, Stampfer MJ et al (2002) Diet quality and major chronic disease risk in men and women: moving toward improved dietary guidance. Am J Clin Nutr 76:1261–1271CrossRef

41.

Song M, Hu FB, Wu K et al (2016) Trajectory of body shape in early and middle life and all cause and cause specific mortality: results from two prospective US cohort studies. BMJ 353:i2195CrossRef

42.

Rosner B (1983) Percentage points for a generalized ESD many-outlier procedure. Technometrics 25:165–172CrossRef

43.

Rosner B, Cook N, Portman R, Daniels S, Falkner B (2008) Determination of blood pressure percentiles in normal-weight children: some methodological issues. Am J Epidemiol 167:653–666CrossRef

44.

Daimon M, Kamba A, Murakami H et al (2017) Association between serum prolactin levels and insulin resistance in non-diabetic men. PLoS One 12:e0175204CrossRef

45.

Newey PJ, Gorvin CM, Cleland SJ et al (2013) Mutant prolactin receptor and familial hyperprolactinemia. N Engl J Med 369:2012–2020CrossRef

46.

Berinder K, Nystrom T, Hoybye C, Hall K, Hulting AL (2011) Insulin sensitivity and lipid profile in prolactinoma patients before and after normalization of prolactin by dopamine agonist therapy. Pituitary 14:199–207CrossRef

47.

Majumdar A, Mangal NS (2013) Hyperprolactinemia. J Hum Reprod Sci 6:168–175CrossRef

48.

Hankinson SE, Manson JE, Spiegelman D, Willett WC, Longcope C, Speizer FE (1995) Reproducibility of plasma hormone levels in postmenopausal women over a 2-3-year period. Cancer Epidemiol Biomark Prev 4:649–654

49.

Lawson DM, Sensui N, Haisenleder DH, Gala RR (1982) Rat lymphoma cell bioassay for prolactin: observations on its use and comparison with radioimmunoassay. Life Sci 31:3063–3070CrossRef

50.

Tanaka T, Shiu RP, Gout PW, Beer CT, Noble RL, Friesen HG (1980) A new sensitive and specific bioassay for lactogenic hormones: measurement of prolactin and growth hormone in human serum. J Clin Endocrinol Metab 51:1058–1063CrossRef

51.

Schernhammer ES, Tworoger SS, Eliassen AH et al (2007) Body shape throughout life and correlations with IGFs and GH. Endocr Relat Cancer 14:721–732CrossRef

52.

Moldrup A, Petersen ED, Nielsen JH (1993) Effects of sex and pregnancy hormones on growth hormone and prolactin receptor gene expression in insulin-producing cells. Endocrinology 133:1165–1172CrossRef

53.

Sorenson RL, Brelje TC (1997) Adaptation of islets of Langerhans to pregnancy: beta-cell growth, enhanced insulin secretion and the role of lactogenic hormones. Horm Metab Res 29:301–307CrossRef

54.

Tovar S, Dieguez C (2014) Prolactin and energy homeostasis: pathophysiological mechanisms and therapeutic considerations. Endocrinology 155:659–662CrossRef

55.

Jones AG, Hattersley AT (2013) The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med 30:803–817CrossRef

56.

Polonsky KS, Rubenstein AH (1984) C-peptide as a measure of the secretion and hepatic extraction of insulin: pitfalls and limitations. Diabetes 33:486–494CrossRef

Title: Circulating prolactin concentrations and risk of type 2 diabetes in US women
Authors: Jun Li
Megan S. Rice
Tianyi Huang
Susan E. Hankinson
Charles V. Clevenger
Frank B. Hu
Shelley S. Tworoger
Publication date: 01-12-2018
Publisher: Springer Berlin Heidelberg
Published in: Diabetologia / Issue 12/2018
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-018-4733-9

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

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

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Please log in to get access to this content

Other articles of this Issue 12/2018

Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

Which is more important for cardiometabolic health: sedentary time, higher intensity physical activity or cardiorespiratory fitness? The Maastricht Study

The impact of maternal gestational weight gain on cardiometabolic risk factors in children

Up Front

Detection and quantification of beta cells by PET imaging: why clinical implementation has never been closer

Impact of daily incremental change in environmental temperature on beta cell function and the risk of gestational diabetes in pregnant women

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page