Ziyi Zhang1,2, Anthony L Piro1, Amina Allalou1, Stacey E Alexeeff3, Feihan F Dai1, Erica P Gunderson3,4, Michael B Wheeler1,5. 1. Department of Physiology, Faculty of Medicine, University of Toronto, Ontario M5S 1A8, Canada. 2. Department of Endocrinology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang 310016, China. 3. Division of Research, Kaiser Permanente Northern California, Oakland, CA 94612, USA. 4. Department of Health Systems Science, Kaiser Permanente Bernard J. Tyson School of Medicine, Pasadena, California 91101, USA. 5. Metabolism Research Group, Division of Advanced Diagnostics, Toronto General Hospital Research Institute, Toronto, Ontario M5G 2C4, Canada.
Abstract
CONTEXT: 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. OBJECTIVE: We examined the relationships among prolactin, future T2D risk, and key clinical and metabolic parameters. METHODS: 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). RESULTS: 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. CONCLUSION: 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.
CONTEXT: 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. OBJECTIVE: We examined the relationships among prolactin, future T2D risk, and key clinical and metabolic parameters. METHODS: 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). RESULTS: 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. CONCLUSION: 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.
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