Clin. Lab. 2011;57:651-657 ©Copyright ORIGINAL ARTICLE Birthweight and Fetal Glycosylated Hemoglobin at Birth in Newborns Carrying the GLUT1 XbaI Gene Polymorphism BERTHOLD HOCHER 1,2 , DIRK HEIMERL 2 , TORSTEN SLOWINSKI 3 , MICHAEL GODES 2 , HORST HALLE 4 , FRIEDRICH PRIEM 5 , THIEMO PFAB 2,6 1 Institute of Nutritional Science, University of Potsdam, Potsdam, Germany 2 Center for Cardiovascular Research/Institute of Pharmacology, Charité, Berlin, Germany 3 Department of Nephrology, Campus Mitte, Charité, Berlin, Germany 4 Department of Obstetrics and Gynecology, Charité, Berlin, Germany 5 Institute of Laboratory Medicine, Charité, Berlin, Germany 6 Department of Nephrology, Campus Benjamin Franklin, Charité, Berlin, Germany SUMMARY Background: Low birthweight is an independent risk factor of glucose intolerance and type 2 diabetes in later life. Genetically determined insulin resistance and subsequently impaired glucose uptake might explain both reduced fetal growth and elevated blood glucose. The glucose transporter 1 (GLUT1) plays an important role for fetal glu- cose uptake as well as for maternal-fetal glucose transfer, and it has been associated with insulin resistance in adults. The present study hypothesized that the common fetal GLUT1 XbaI polymorphism might reduce fetal in- sulin sensitivity and/or glucose supply in utero, thus affecting fetal blood glucose and fetal growth. Methods: A genetic association study was conducted at the obstetrics department of the Charité University Hospi- tal, Berlin, Germany. 1191 white women were included after delivery, and all newborns were genotyped for the GLUT1 XbaI polymorphism. Total glycosylated hemoglobin was quantified, serving as a surrogate of glycemia during the last weeks of pregnancy. Results: The analysis of this large population showed no significant differences in fetal glycosylated hemoglobin or birthweight for the different fetal GLUT1 XbaI genotypes. Only newborns carrying the mutated allele show the previously published inverse association between birthweight and glycosylated hemoglobin. Conclusions: The results suggest that there is no prenatal effect of the fetal GLUT1 XbaI polymorphism on fetal insulin sensitivity, intrauterine fetal glucose supply or fetal growth. However, the polymorphism seems to modu- late the inverse interaction between birthweight and fetal glycemia. (Clin. Lab. 2011;57:651-657) KEY WORDS GLUT1 XbaI gene polymorphism, birthweight, total glycosylated hemoglobin, insulin resistance, fetal pro- gramming. INTRODUCTION Many epidemiological studies have confirmed the finding that low birthweight is an independent risk fac- tor of glucose intolerance and type 2 diabetes in later life [1-5]. Our group demonstrated for the first time that there is an inverse association between birthweight and fetal glycemia at birth [6] and confirmed this later in an independent Asian cohort [7]. Potential mechanisms of this association are controver- sial [8,9]. Hattersley proposes that low birthweight, measures of insulin resistance in life, and ultimately glucose intolerance and diabetes might all be pheno- types of the same insulin-resistant genotype [8]. Geneti- cally determined insulin resistance and subsequently impaired intracellular glucose uptake might explain re- duced fetal growth and elevated blood glucose [8]. An example of a genetically determined alteration of fetal glucose handling and growth has been described for a _____________________________________________ Manuscript accepted January 29, 2011 Clin. Lab. 9+10/2011 651