Prolactin and Maternal Metabolism in Women With a Recent GDM Pregnancy and Links to Future T2D: The SWIFT Study

• Published in: The journal of clinical endocrinology and metabolism Vol. 107; no. 9; pp. 2652 - 2665
• Main Authors: Zhang, Ziyi, Piro, Anthony L, Allalou, Amina, Alexeeff, Stacey E, Dai, Feihan F, Gunderson, Erica P, Wheeler, Michael B
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-09-2022
• Subjects: Analysis; Blood Glucose - metabolism; Case-Control Studies; Cholesterol, HDL; Clinical; Dextrose; Diabetes Mellitus, Type 2 - epidemiology; Diabetes, Gestational; Female; Glucose; Glucose tolerance tests; Health maintenance organizations; Humans; Infants; Insulin; Insulin resistance; Leptin; Lipids; Medical records; Metabolites; Physiological aspects; Pregnancy; Pregnant women; Prolactin; Prospective Studies; Risk Factors; Triglycerides; Type 2 diabetes; Canada; California; prolactin; type 2 diabetes; gestational diabetes; lactation; maternal metabolism
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgac346

Prolactin is a multifaceted hormone known to regulate lactation. In women with gestational diabetes mellitus (GDM) history, intensive lactation has been associated with lower relative risk of future type 2 diabetes (T2D). However, the role of prolactin in T2D development and maternal metabolism in women with a recent GDM pregnancy has not been ascertained.
We examined the relationships among prolactin, future T2D risk, and key clinical and metabolic parameters.
We utilized a prospective GDM research cohort (the SWIFT study) and followed T2D onset by performing 2-hour 75-g research oral glucose tolerance test (OGTT) at study baseline (6-9 weeks postpartum) and again annually for 2 years, and also by retrieving clinical diagnoses of T2D from 2 years through 10 years of follow up from electronic medical records. Targeted metabolomics and lipidomics were applied on fasting plasma samples collected at study baseline from 2-hour 75-g research OGTTs in a nested case-control study (100 future incident T2D cases vs 100 no T2D controls).
Decreasing prolactin quartiles were associated with increased future T2D risk (adjusted odds ratio 2.48; 95% CI, 0.81-7.58; P = 0.05). In women who maintained normoglycemia during the 10-year follow-up period, higher prolactin at baseline was associated with higher insulin sensitivity (P = 0.038) and HDL-cholesterol (P = 0.01), but lower BMI (P = 0.001) and leptin (P = 0.002). Remarkably, among women who developed future T2D, prolactin was not correlated with a favorable metabolic status (all P > 0.05). Metabolomics and lipidomics showed that lower circulating prolactin strongly correlated with a T2D-high risk lipid profile, with elevated circulating neutral lipids and lower concentrations of specific phospholipids/sphingolipids.
In women with recent GDM pregnancy, low circulating prolactin is associated with specific clinical and metabolic parameters and lipid metabolites linked to a high risk of developing T2D.