Pétur Benedikt Júlíusson

Context: Metformin is used in pregnancy in women with gestational diabetes mellitus, polycystic ovary syndrome (PCOS), and obesity. Metformin passes the placenta. Objective: To explore the effects of metformin use in PCOS pregnancies on offspring growth to 4 years of age. Design: Follow-up study of two randomized, double-blind, placebo-controlled trials. Setting: Secondary care centers. Eleven public hospitals in Norway. Participants: One hundred eighty-two children of mothers with PCOS who participated in two randomized controlled trials. Intervention: Metformin 1700 or 2000 mg/d or placebo from first trimester to delivery in the original studies. No intervention in the current study. Main Outcome Measures: Height, weight, body mass index (BMI), and overweight/obesity at 4 years of age and head circumference at 1 year of age, converted to z scores. Results: The difference in height z score means between the groups at 4 years of age was nonsignificant (0.07 [95% confidence interval (CI): -0.22 to 0.36]; P = 0.651). At 4 years of age, the metformin group had higher weight z score than the placebo group [difference in means: 0.38 (0.07 to 0.69); P = 0.017] and higher BMI z score [difference in means: 0.45 (0.11 to 0.78); P = 0.010]. There were more overweight/obese children in the metformin group [26 (32%)] than in the placebo group [14 (18%)] at 4 years of age [odds ratio: 2.17 (1.04 to 4.61); P = 0.038]. The difference in mean head circumference z score at 1 year of age was 0.27 (-0.04 to 0.58; P = 0.093). Conclusion: Metformin-exposed children had higher BMI and increased prevalence of overweight/obesity at 4 years of age.

BACKGROUND: KCNJ11 mutations cause permanent neonatal diabetes through pancreatic ATP-sensitive potassium channel activation. 90% of patients successfully transfer from insulin to oral sulfonylureas with excellent initial glycaemic control; however, whether this control is maintained in the long term is unclear. Sulfonylurea failure is seen in about 44% of people with type 2 diabetes after 5 years of treatment. Therefore, we did a 10-year multicentre follow-up study of a large international cohort of patients with KCNJ11 permanent neonatal diabetes to address the key questions relating to long-term efficacy and safety of sulfonylureas in these patients. METHODS: and sulfonylurea dose. Neurological features associated with KCNJ11 permanent neonatal diabetes were also assessed. This study is registered with ClinicalTrials.gov, number NCT02624817. FINDINGS: was 8·1% (IQR 7·2-9·2; 65·0 mmol/mol [55·2-77·1]) before transfer to sulfonylureas, 5·9% (5·4-6·5; 41·0 mmol/mol [35·5-47·5]; p<0·0001 vs pre-transfer) at 1 year, and 6·4% (5·9-7·3; 46·4 mmol/mol [41·0-56·3]; p<0·0001 vs year 1) at most recent follow-up (median 10·3 years [IQR 9·2-10·9]). In the same patients, median sulfonylurea dose at 1 year was 0·30 mg/kg per day (0·14-0·53) and at most recent follow-up visit was 0·23 mg/kg per day (0·12-0·41; p=0·03). No reports of severe hypoglycaemia were recorded in 809 patient-years of follow-up for the whole cohort (n=81). 11 (14%) patients reported mild, transient side-effects, but did not need to stop sulfonylurea therapy. Seven (9%) patients had microvascular complications; these patients had been taking insulin longer than those without complications (median age at transfer to sulfonylureas 20·5 years [IQR 10·5-24·0] vs 4·1 years [1·3-10·2]; p=0·0005). Initial improvement was noted following transfer to sulfonylureas in 18 (47%) of 38 patients with CNS features. After long-term therapy with sulfonylureas, CNS features were seen in 52 (64%) of 81 patients. INTERPRETATION: High-dose sulfonylurea therapy is an appropriate treatment for patients with KCNJ11 permanent neonatal diabetes from diagnosis. This therapy is safe and highly effective, maintaining excellent glycaemic control for at least 10 years. FUNDING: Wellcome Trust, Diabetes UK, Royal Society, European Research Council, Norwegian Research Council, Kristian Gerhard Jebsen Foundation, Western Norway Regional Health Authority, Southern and Eastern Norway Regional Health Authority, Italian Ministry of Health, Aide aux Jeunes Diabetiques, Societe Francophone du Diabete, Ipsen, Slovak Research and Development Agency, and Research and Development Operational Programme funded by the European Regional Development Fund.

BACKGROUND: Previous growth references for Norwegian children were based on measurements from the 1970s and 1980s. New reference data, collected through the Bergen Growth Study and the Medical Birth Registry of Norway, are presented as LMS values. MATERIALS AND METHODS: A cross-sectional sample of children aged 0-19 years in stratified randomized design measured in 2003-2006 as a part of the Bergen Growth Study (n = 7291) and birth data of children born in 1999-2003 from the Medical Birth Registry of Norway (n = 12 576) was used to estimate the new references by the means of the LMS method. Measurement reliability was assessed by test-rest studies. RESULTS: New references were constructed for length/height, weight, body mass index (BMI) and head circumference. Length/height and weight for children aged 0-4 years were similar to previous Norwegian references, but mean height increased up to a maximum of 3.4 cm in boys and 2.5 cm in girls during the pubertal years. Mean height was similar to (or slightly higher) in comparison with other recent European references. Reliability of the measurements compared well with published estimates. CONCLUSION: Because of the observed secular trends in growth, it is advised to use the new references, which have been endorsed by the Norwegian Department of Health.

AIM: The aim of this study was to estimate the prevalence of childhood overweight and obesity and to identify socio-demographic risk factors in Norwegian children. METHODS: The body mass index of 6386 children aged 2-19 years was compared with the International Obesity Task Force (IOTF) cut-off values to estimate the prevalence of overweight including obesity (OWOB) and obesity (OB). The effect of socio-demographic factors on this prevalence was analysed using multiple ordinal logistic regression analysis in a subsample of 3793 children. RESULTS: The overall prevalence of OWOB was 13.8% (13.2% in boys and 14.5% in girls, p = 0.146), but the prevalence was higher in primary school children aged 6-11 years (17%, p < 0.001). The risk of being OWOB or OB increased in children with fever siblings (p = 0.003) and with lower parental educational level (p = 0.001). There was no association with parental employment status, single-parent families or origin. CONCLUSION: The prevalence of OWOB and OB in Norwegian primary school children is of concern. Socio-demographic factors have pronounced effects on the current prevalence of overweight and obesity in a cohort of Norwegian children. This knowledge could help to work out strategies to reduce the burden of overweight and obesity in children.

In 2015-2017, the fourth round of the World Health Organization (WHO) European Childhood Obesity Surveillance Initiative (COSI) was conducted in 36 countries. National representative samples of children aged 6-9 (203,323) were measured by trained staff, with similar equipment and using a standardized protocol. This paper assesses the children's body weight status and compares the burden of childhood overweight, obesity, and thinness in Northern, Eastern, and Southern Europe and Central Asia. The results show great geographic variability in height, weight, and body mass index. On average, the children of Northern Europe were the tallest, those of Southern Europe the heaviest, and the children living in Central Asia the lightest and the shortest. Overall, 28.7% of boys and 26.5% of girls were overweight (including obesity) and 2.5% and 1.9%, respectively, were thin according to the WHO definitions. The prevalence of obesity varied from 1.8% of boys and 1.1% of girls in Tajikistan to 21.5% and 19.2%, respectively, in Cyprus, and tended to be higher for boys than for girls. Levels of thinness, stunting, and underweight were relatively low, except in Eastern Europe (for thinness) and in Central Asia. Despite the efforts to halt it, unhealthy weight status is still an important problem in the WHO European Region.