Ravi Retnakaran1, Chang Ye2, Caroline K Kramer3, Philip W Connelly4, Anthony J Hanley5, Mathew Sermer6, Bernard Zinman7. 1. Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada rretnakaran@mtsinai.on.ca. 2. Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada. 3. Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada. 4. Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Ontario, Canada. 5. Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada. 6. Division of Obstetrics and Gynecology, Mount Sinai Hospital, Toronto, Ontario, Canada. 7. Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
Abstract
OBJECTIVE: The insulin resistance of mid- to late pregnancy poses a physiologic stress test for the pancreatic β-cells, which must respond by markedly increasing their secretion of insulin. This response is achieved through an expansion of β-cell mass induced by the hormones prolactin and human placental lactogen (HPL). Conversely, the furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) has recently emerged as a negative regulator of β-cell function in pregnancy. Given their respective roles in the β-cell response to the stress test of gestation, we hypothesized that antepartum prolactin, HPL, and CMPF may relate to a woman's underlying glucoregulatory physiology and hence to her metabolic status after pregnancy. RESEARCH DESIGN AND METHODS: Three hundred and sixty-seven women underwent measurement of fasting serum prolactin, HPL, and CMPF in the late-2nd/early-3rd trimester, followed by an oral glucose tolerance test (OGTT) at 3 months postpartum that enabled assessment of glucose tolerance, insulin sensitivity/resistance, and β-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]). RESULTS: The postpartum OGTT identified 301 women with normal glucose tolerance (NGT) and 66 with prediabetes or diabetes. Serum prolactin in pregnancy was higher in women with postpartum NGT compared with those with postpartum prediabetes/diabetes (mean 98.2 vs. 80.2 ng/mL, P = 0.0003), whereas HPL and CMPF did not differ between the groups. On multiple linear regression analyses, antepartum prolactin was an independent determinant of postpartum ISSI-2 (β = 0.0016, t = 2.96, P = 0.003). Furthermore, higher serum prolactin in pregnancy independently predicted a lower risk of postpartum prediabetes/diabetes (odds ratio 0.50, 95% CI 0.35-0.72, P = 0.0002). CONCLUSIONS: Serum prolactin in pregnancy predicts postpartum β-cell function and risk of prediabetes/diabetes.
OBJECTIVE: The insulin resistance of mid- to late pregnancy poses a physiologic stress test for the pancreatic β-cells, which must respond by markedly increasing their secretion of insulin. This response is achieved through an expansion of β-cell mass induced by the hormones prolactin and humanplacental lactogen (HPL). Conversely, the furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) has recently emerged as a negative regulator of β-cell function in pregnancy. Given their respective roles in the β-cell response to the stress test of gestation, we hypothesized that antepartum prolactin, HPL, and CMPF may relate to a woman's underlying glucoregulatory physiology and hence to her metabolic status after pregnancy. RESEARCH DESIGN AND METHODS: Three hundred and sixty-seven women underwent measurement of fasting serum prolactin, HPL, and CMPF in the late-2nd/early-3rd trimester, followed by an oral glucose tolerance test (OGTT) at 3 months postpartum that enabled assessment of glucose tolerance, insulin sensitivity/resistance, and β-cell function (Insulin Secretion-Sensitivity Index-2 [ISSI-2]). RESULTS: The postpartum OGTT identified 301 women with normal glucose tolerance (NGT) and 66 with prediabetes or diabetes. Serum prolactin in pregnancy was higher in women with postpartum NGT compared with those with postpartum prediabetes/diabetes (mean 98.2 vs. 80.2 ng/mL, P = 0.0003), whereas HPL and CMPF did not differ between the groups. On multiple linear regression analyses, antepartum prolactin was an independent determinant of postpartum ISSI-2 (β = 0.0016, t = 2.96, P = 0.003). Furthermore, higher serum prolactin in pregnancy independently predicted a lower risk of postpartum prediabetes/diabetes (odds ratio 0.50, 95% CI 0.35-0.72, P = 0.0002). CONCLUSIONS: Serum prolactin in pregnancy predicts postpartum β-cell function and risk of prediabetes/diabetes.
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