REGULAR ARTICLE Differences in insulin resistance markers between children born small for gestational age or born preterm appropriate for gestational age Anna Kistner (anna.kistner@ki.se) 1 *, Alexander Rakow 2 *, Lena Legnevall 2 , Giovanna Marchini 2 , Kerstin Brismar 1 , Kerstin Hall 1 , Mireille Vanpée 2 1.Department of Molecular Medicine and Surgery, Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden 2.Department of Women and Child Health, Karolinska Institutet, Neonatal Unit, Astrid Lindgrens Childrens Hospital, Karolinska University Hospital, Stockholm, Sweden Keywords IGFBP-1, Insulin resistance, Low birth weight, Oral glucose tolerance test Correspondence Anna Kistner, M.D., Ph.D., Department of Molecular Medicine and Surgery, M1:3, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden. Tel: +46-8-51779153 | Fax: +46-8-51773658 | Email: anna.kistner@ki.se Received 29 April 2012; revised 5 August 2012; accepted 22 August 2012. DOI:10.1111/apa.12005 *First and second authors have contributed equally. ABSTRACT Aim: To evaluate the impact of prenatal or postnatal compromised environment on glucose homoeostasis in children born preterm and appropriate for gestational age or small for gestational age (SGA) at term. Method: Seventy-seven children (median 9.9 years, range 8.5–10) born at Karo- linska Hospital were allocated to three groups: 21 subjects born before 30 weeks of gesta- tional age (preterm), 26 SGA at term and 30 at term with appropriate birth weight (control). Anthropometric measurements were taken, and fasting blood samples for hae- moglobin A1c, glucose, insulin, IGFBP-1, IGF-1 and lipid profile were taken. Glucose, insulin and IGFBP-1 samples were taken at 0, 30 and 120 min during an oral glucose tolerance test (OGTT). Results: Subjects born preterm or SGA were shorter and thinner compared with Controls. After adjustment for body mass index (BMI), the SGA group had higher basal insulin levels (p = 0.029), higher homoeostasis model assessment—insulin resistance (p = 0.012) and lower whole-body insulin sensitivity index (p = 0.007) than Controls. IGFBP-1 decrease during OGTT was attenuated in the Preterm group compared with the Control (p = 0.045) and SGA groups (p = 0.007). Conclusion: The higher fasting insulin level in the SGA children, adjusted for BMI, could indicate peripheral insulin resistance. Preterm born children had reduced suppression of IGFBP-1 during OGTT, suggesting hepatic insulin resistance. INTRODUCTION Low birth weight (LBW), defined as a birth weight below 2500 g, is related to an increased risk of type 2 diabetes mellitus (DM), metabolic syndrome and cardiovascular dis- ease (1). In a recent population study of middle-aged men and women, the risk of DM was reduced by 51% with a birth weight increase of 1 kg (2). LBW is a consequence of either intrauterine growth restriction (IUGR) resulting in infants born small for gestational age (SGA) or preterm interruption of gestation. Preterm infants face an adverse postnatal environment with stress, malnutrition and often severe illness, whereas infants with IUGR experience a compromised environment during intrauterine life. Children born with LBW represent an increasing propor- tion of our society. In European countries, preterm births, defined as born below 37 weeks of gestation, account for 5– 9% of all pregnancies, and in Sweden, LBW at term (SGA) accounts for 4.2% of all births (3,4). Very LBW is a term used for infants weighing <1500 g corresponding to birth below 30 weeks of gestation. In Sweden, approximately 0.8% of the infants are born below 1500 g, of which approx- imately 25% are also SGA. In developing countries, the inci- dence of LBW infants is 16.5%, where a third is estimated to Abbreviations AGA, Appropriate for gestational age; Apo, Apolipoprotein; HbA1c, Haemoglobin A1c; HDL, High-density lipids; HOMA- IR, Homoeostasis model assessment—insulin resistance; HsCRP, High-sensitive C-reactive protein; IUGR, Intrauterine growth retardation; LBW, Low birth weight; LDL, Low-density lipids; OGTT, Oral glucose tolerance test; SAA, Serum amyloid A pro- tein; SDS, Standard deviation score; SGA, Small for gestational age; WBISI, Whole-body insulin sensitivity index. Key notes • Subjects born preterm or SGA at term are shorter and thinner compared with controls at 9 years of age. • Children born small for gestational age have elevated fasting insulin, indicating peripheral insulin resistance. • Preterm born children had reduced suppression of IG- FBP-1 during oral glucose tolerance test, suggesting hepatic insulin resistance. Acta Pædiatrica ISSN 0803–5253 ª2012 The Author(s)/Acta Pædiatrica ª2012 Foundation Acta Pædiatrica 2012 101, pp. 1217–1224 1217