Association of Acylcarnitines With Maternal Cardiometabolic Risk Factors Is Defined by Chain Length: The S-PRESTO Study

• Published in: The journal of clinical endocrinology and metabolism 2024-10, Vol.109 (11), p.2831-2846
• Main Authors: Chen, Li, Goh, Xue Ping, Bendt, Anne K, Tan, Karen Mei-Ling, Leow, Melvin Khee-Shing, Tan, Kok Hian, Chan, Jerry Kok Yen, Chan, Shiao-Yng, Chong, Yap Seng, Gluckman, Peter D, Eriksson, Johan G, Wenk, Markus R, Mir, Sartaj Ahmad
• Format: Article
• Language: English
• Subjects: Amino acids; Body mass index; Carbohydrate metabolism; Carnitine; Diabetes mellitus; Glucose metabolism; Homeostasis; Insulin resistance; Lipid metabolism; Liquid chromatography; Mass spectroscopy; Metabolism; Physiology; Plasma; Postpartum; Postpartum period; Pregnancy; Pregnancy complications; Risk factors
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgae255

Abstract Context Due to the essential role of carnitine as an intermediary in amino acid, carbohydrate, and lipid metabolism, a detailed characterization of circulating and urinary carnitine concentrations will aid in elucidating the molecular basis of impaired maternal metabolic flexibility and facilitating timely intervention for expectant mothers. Objective To investigate the association of maternal plasma and urinary free carnitine and acylcarnitines with cardiometabolic risk factors. Methods Liquid chromatography tandem mass spectrometry–based quantification of free carnitine and acylcarnitines (C2-C18) was performed on 765 plasma and 702 urine samples collected at preconception, 26 to 28 weeks’ pregnancy, and 3 months postpartum in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort study. Results Plasma concentrations of free carnitine and acylcarnitines decreased coupled with increased renal clearance in pregnancy compared with preconception and postpartum. Renal clearance of carnitine increased with an increase in prepregnancy body mass index (ppBMI) and gestational weight gain. Plasma short-chain acylcarnitines were positively associated with ppBMI, irrespective of the physiological state, while medium- and long-chain acylcarnitines were negatively associated with ppBMI at preconception and postpartum but showed a positive association in pregnancy. Similarly, plasma short-chain acylcarnitines were positively associated with Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) whereas medium- and long-chain acylcarnitines were negatively associated with HOMA-IR at preconception and in pregnancy. Mothers who developed gestational diabetes mellitus during pregnancy had ∼10% higher plasma propionylcarnitine concentration and ∼18% higher urine tiglylcarnitine concentration than mothers with normal glucose metabolism at preconception. Conclusion This study provides the metabolic and physiological basis of maternal carnitine homeostasis, which can be used in assessment of maternal cardiometabolic health at preconception to improve pregnancy outcomes.