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E M Delemarre, J Rotteveel and H A Delemarre-van de Waal

Fetal growth retardation is associated with decreased postnatal growth, resulting in a lower adult height. In addition, a low birth weight is associated with an increased risk of developing diseases during adulthood, such as insulin resistance, type 2 diabetes mellitus, hypertension, dyslipidemia, and cardiovascular diseases. Children with persistent postnatal growth retardation, i.e., incomplete catchup growth, can be treated with human GH. The GH/IGF-I axis is involved in the regulation of carbohydrate and lipid metabolism. The question of whether treatment with GH in children born small for gestational age (SGA) has long-term implications with respect to glucose/insulin and lipid metabolism has not been answered yet. In this article, the available data are reviewed.

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J Rotteveel, M M van Weissenbruch and H A Delemarre-Van de Waal


Low birth weight and preterm birth are associated with growth delay as well as the development of insulin resistance. Insulin resistance is especially seen in subjects with catch-up growth. GH therapy induces growth in short subjects with low birth weight at term, but little is known about the long-term effects on insulin sensitivity. GH therapy is now also proposed for preterms that remain short.


We investigated insulin sensitivity using the gold standard hyperinsulinemic-euglycemic clamp technique in 10 young adult males born small for gestational age (SGA) who had been treated with GH during childhood (GH) in comparison with 15 males born preterm AGA (premAGA), 13 males born preterm SGA (premSGA), and 15 males born at term with normal birth weight (CON). Furthermore, we investigated the presence of the metabolic syndrome.


Insulin sensitivity was decreased in premAGA, premSGA, and GH subjects compared with CON males. The metabolic syndrome was not present in any of the groups.


Insulin sensitivity is decreased in GH-treated SGA born males as well as in preterm born males. With respect to the SGA subjects, whether the difference results from perinatal-, postnatal-, or GH therapy-related factors are not known. With respect to the preterm born subjects, close surveillance is needed when commencing GH therapy.

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Joost Rotteveel, Eline J Belksma, Carry M Renders, Remy A Hirasing and Henriette A Delemarre-Van de Waal

Objective: The worldwide trend towards obesity in childhood is also observed in the Netherlands and one of the consequences may be type 2 diabetes. In this study, we assessed the number of children with type 2 diabetes, diagnosed by paediatricians, in the Netherlands.

Methods: In 2003 and 2004 the Dutch Paediatric Surveillance Unit, a nationwide paediatric register, was used to assess new cases of diabetes mellitus. Data on socio-demographic and clinical characteristics were collected by means of a questionnaire. A second questionnaire was sent to the reporting paediatrician if the diagnosis was inconclusive or if the diagnosis was type 1 diabetes in combination with overweight or obesity, according to international criteria.

Results: During the 24 months of registration, the paediatricians reported 1142 new cases of diabetes, 943 of which were eligible for analysis. Initially, 14 patients (1.5%) were reported with type 2 diabetes. Only seven of these patients were classified as type 2 diabetes according to the ADA criteria, as information on C-peptides or antibodies was often missing. Based on clinical characteristics, the other seven patients were very likely to have type 2 diabetes. After the second questionnaire, six more patients met the ADA criteria and two were very likely to have type 2 diabetes. Most of the patients were female (95%), 14% were of Turkish and 18% of Moroccan origin.

Conclusion: This study shows a discrepancy between the number of patients with type 2 diabetes diagnosed by paediatricians in daily practice and diagnosed according to the ADA criteria. Moreover, a considerable amount of reported patients were misclassified. Finally, 2.4% patients were classified as (very likely) type 2 diabetes. The development of programmes and protocols for prevention, diagnosis and classification applicable in daily practice is warranted.

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Anna M E Noten, Eva M Loomans, Tanja G M Vrijkotte, Peter M van de Ven, A S Paul van Trotsenburg, Joost Rotteveel, Manon van Eijsden and Martijn J J Finken


Overt hypothyroidism in pregnant women is associated with a lower intelligence quotient in their children. More recently, subtle decreases in maternal thyroid function have also been associated with neurodevelopmental impairment in offspring. We tested the effect of hypothyroxinaemia during early pregnancy on school performance.


This was a longitudinal study that included the data of 1196 mother-child pairs from the Amsterdam Born Children and Their Development study.


Maternal serum free thyroxine (T4) and TSH were obtained at a median gestational age of 12.9 (interquartile range: 11.9–14.3) weeks. School performance was assessed at age 5 years and based on scores obtained in arithmetic and language tests from the national monitoring and evaluation system. Poor school performance was defined as a test result <25th percentile and subnormal school performance as a result <50th percentile of the norm population. To estimate the impact of possible non-response bias, we conducted inverse-probability weighted analyses.


Maternal hypothyroxinaemia (i.e., a maternal free T4 in the lowest 10% of distribution) was associated with a 1.61 (95% CI: 1.05–2.47) -fold increased odds of subnormal arithmetic performance after adjustment for confounders (P=0.03). However, the odds ratio dropped to 1.48 (95% CI: 0.94–2.32) after inverse-probability weighting (P=0.09). No such relations were found with TSH.


Maternal hypothyroxinaemia at the end of the first trimester was associated with reduced performance in an arithmetic test, but not in a language test, in 5-year-old offspring. However, our results should be interpreted carefully because of possible non-response bias.