Yu Liu1,2, Alan Kuang3, James R Bain4,5,6, Michael J Muehlbauer4,5, Olga R Ilkayeva4,5,6, Lynn P Lowe3, Boyd E Metzger1, Christopher B Newgard4,5,6, Denise M Scholtens3, William L Lowe2. 1. Department of Endocrinology and Metabolism, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200127, P. R. China. 2. Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. 3. Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. 4. Sarah W. Stedman Nutrition and Metabolism Center, Duke University School of Medicine, Durham, North Carolina 27705, USA. 5. Duke Molecular Physiology Institute, Durham, North Carolina 27701, USA. 6. Department of Medicine, Duke University School of Medicine, Durham, North Carolina 27707, USA.
Abstract
CONTEXT: Gestational diabetes is associated with a long-term risk of developing a disorder of glucose metabolism. However, neither the metabolic changes characteristic of gestational diabetes in a large, multi-ancestry cohort nor the ability of metabolic changes during pregnancy, beyond glucose levels, to identify women at high risk for progression to a disorder of glucose metabolism has been examined. OBJECTIVE: This work aims to identify circulating metabolites present at approximately 28 weeks' gestation associated with gestational diabetes mellitus (GDM) and development of a disorder of glucose metabolism 10 to 14 years later. METHODS: Conventional clinical and targeted metabolomics analyses were performed on fasting and 1-hour serum samples following a 75-g glucose load at approximately 28 weeks' gestation from 2290 women who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. Postpartum metabolic traits included fasting and 2-hour plasma glucose following a 75-g glucose load, insulin resistance estimated by the homeostasis model assessment of insulin resistance, and disorders of glucose metabolism (prediabetes and type 2 diabetes) during the HAPO Follow-Up Study. RESULTS: Per-metabolite analyses identified numerous metabolites, ranging from amino acids and carbohydrates to fatty acids and lipids, before and 1-hour after a glucose load that were associated with GDM as well as development of a disorder of glucose metabolism and metabolic traits 10 to 14 years post partum. A core group of fasting and 1-hour metabolites mediated, in part, the relationship between GDM and postpartum disorders of glucose metabolism, with the fasting and 1-hour metabolites accounting for 15.7% (7.1%-30.8%) and 35.4% (14.3%-101.0%) of the total effect size, respectively. For prediction of a postpartum disorder of glucose metabolism, the addition of circulating fasting or 1-hour metabolites at approximately 28 weeks' gestation showed little improvement in prediction performance compared to clinical factors alone. CONCLUSION: The results demonstrate an association of multiple metabolites with GDM and postpartum metabolic traits and begin to define the underlying pathophysiology of the transition from GDM to a postpartum disorder of glucose metabolism.
CONTEXT: Gestational diabetes is associated with a long-term risk of developing a disorder of glucose metabolism. However, neither the metabolic changes characteristic of gestational diabetes in a large, multi-ancestry cohort nor the ability of metabolic changes during pregnancy, beyond glucose levels, to identify women at high risk for progression to a disorder of glucose metabolism has been examined. OBJECTIVE: This work aims to identify circulating metabolites present at approximately 28 weeks' gestation associated with gestational diabetes mellitus (GDM) and development of a disorder of glucose metabolism 10 to 14 years later. METHODS: Conventional clinical and targeted metabolomics analyses were performed on fasting and 1-hour serum samples following a 75-g glucose load at approximately 28 weeks' gestation from 2290 women who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. Postpartum metabolic traits included fasting and 2-hour plasma glucose following a 75-g glucose load, insulin resistance estimated by the homeostasis model assessment of insulin resistance, and disorders of glucose metabolism (prediabetes and type 2 diabetes) during the HAPO Follow-Up Study. RESULTS: Per-metabolite analyses identified numerous metabolites, ranging from amino acids and carbohydrates to fatty acids and lipids, before and 1-hour after a glucose load that were associated with GDM as well as development of a disorder of glucose metabolism and metabolic traits 10 to 14 years post partum. A core group of fasting and 1-hour metabolites mediated, in part, the relationship between GDM and postpartum disorders of glucose metabolism, with the fasting and 1-hour metabolites accounting for 15.7% (7.1%-30.8%) and 35.4% (14.3%-101.0%) of the total effect size, respectively. For prediction of a postpartum disorder of glucose metabolism, the addition of circulating fasting or 1-hour metabolites at approximately 28 weeks' gestation showed little improvement in prediction performance compared to clinical factors alone. CONCLUSION: The results demonstrate an association of multiple metabolites with GDM and postpartum metabolic traits and begin to define the underlying pathophysiology of the transition from GDM to a postpartum disorder of glucose metabolism.
Authors: Boyd E Metzger; Lynn P Lowe; Alan R Dyer; Elisabeth R Trimble; Udom Chaovarindr; Donald R Coustan; David R Hadden; David R McCance; Moshe Hod; Harold David McIntyre; Jeremy J N Oats; Bengt Persson; Michael S Rogers; David A Sacks Journal: N Engl J Med Date: 2008-05-08 Impact factor: 91.245
Authors: Alan Kuang; M Geoffrey Hayes; Marie-France Hivert; Raji Balasubramanian; William L Lowe; Denise M Scholtens Journal: Metabolites Date: 2022-06-02