Gestational diabetes exhibits lack of carnitine deficiency despite relatively low carnitine levels and alterations in ketogenesis KALLIOPI I. PAPPA 1,2 , NICHOLAS P. ANAGNOU 3 , EMMANUEL SALAMALEKIS 2 , STYLIANOS BIKOUVARAKIS 4 , GEORGE MAROPOULOS 5 , NEKTARIA ANOGIANAKI 6 , ATHANASIOS EVANGELIOU 7 , & EUGENE KOUMANTAKIS 1 1 Department of Obstetrics and Gynecology, University of Crete School of Medicine, Heraklion, Greece, 2 Third Department of Obstetrics and Gynecology, University of Athens School of Medicine, Athens, Greece, 3 Laboratory of Biology, University of Athens School of Medicine, Athens and Institute of Molecular Biology and Biotechnology, Heraklion, Greece, 4 Division of Neonatology, Department of Pediatrics, University of Crete School of Medicine, Heraklion, Greece, 5 Department of Biochemistry, Laikon University Hospital, Athens, Greece, 6 Division of Biostatistics, Department of Social Medicine, University of Crete School of Medicine, Heraklion, Greece, and 7 Department of Neurology and Sensory Organs, University of Crete School of Medicine, Heraklion, Greece Abstract Objective: Previous studies have underlined the importance of the carnitine shuttle system and its dysfunction both in normal pregnancy and in type 1 and 2 diabetes. The objective of this paper was to delineate more systematically the role of the carnitine shuttle system in normal pregnancy and in gestational diabetes. Methods: A total of 119 women matched for age comprised three groups: 40 normal adult non-pregnant women (NNP), 46 normal pregnant women with uncomplicated pregnancy (NP) and 33 women with gestational diabetes (GDM). The latter group was further subdivided into those being managed either by diet alone (25 women, GDM-D) or by insulin (8 women, GDM-I). The following biochemical parameters were assayed: fasting plasma total, free and acyl-carnitine, FFA and b-OH- butyrate, together with several essential anthropometric parameters. Results: Women with GDM, in contrast to the control groups, displayed the biochemical features characteristic of insulin resistance: higher body weight, higher BMI, higher skinfold and higher HbA1c levels. No differences on any parameters were found between the two GDM subgroups. Both NP and GDM groups had low levels of total carnitine compared to NNP control group, but surprisingly, the GDM group did not exhibit any further decrease of carnitine levels, as would have been expected by the combination of pregnancy and diabetes. Both groups, despite these low carnitine levels, had no clinical symptoms of carnitine deficiency. Furthermore, the GDM group displayed higher levels of FFA and b-hydroxybutyrate, which were statistically significant compared to the other two control groups. Conclusions: The data corroborate the negative effect of normal gestation on the carnitine shuttle system, while they document for the first time that GDM does not further affect the efficiency of the carnitine system. The mild effect of GDM on carnitine status could be explained by the concurrent increased gluconeogenesis, a process which does not affect directly carnitine metabolism. Keywords: Gestational diabetes mellitus, l-carnitine shuttle system, ketogenesis, lipid metabolism Introduction Through normal pregnancy, significant alterations in maternal physiology occur. Several important para- meters of this altered profile have been delineated [1]. However, the characterization of the complete profile of maternal metabolism, especially in cases of pregnancy associated with complications, such as diabetes mellitus, remains elusive [2]. In normal pregnancy, two components of energy demand are operating: the fetal placental unit and the pregnant woman. The fetal-placental unit em- ploys maternal glucose as its primary energy source. Adequate glucose supply is ensured by placental hormones (placental lactogen, cortisol, estrogen and progesterone) that lead to maternal insulin resistance by reducing insulin affinity to its receptors. The second component gains its energy needs through free fatty acid (FFA) mobilization [3]. Thus, the key issue in pregnancy is the maintenance of extended high glucose levels for placental transfer to the fetus and the minimization of maternal use of glucose [2]. Correspondence: Kalliopi I. Pappa, Department of Obstetrics and Gynecology, University of Athens School of Medicine, Attikon University Hospital, 124 62 Athens, Greece. Tel: + 30 210 5326 427. Fax. + 30 210 5326 447. E-mail: kpappa@imbb.forth.gr The Journal of Maternal-Fetal and Neonatal Medicine, January 2005; 17(1): 63–68 ISSN 1476-7058 print/ISSN 1476-4954 online # 2005 Taylor & Francis Group Ltd DOI: 10.1080/14767050400028733