[Maturity-onset diabetes of the young]. / Erfelijke ouderdomsdiabetes bij jongeren.

Maturity-onset diabetes of the young (MODY) is the most common type of monogenic diabetes mellitus, estimated to account for approximately 1-4% of patients with diabetes. The predicted prevalence is, therefore, 20,000 patients in The Netherlands. Unfortunately less than 5% of these patients are confirmed by molecular genetic analysis. MODY is a clinically heterogeneous group of disorders caused by ß-cell dysfunction, which is caused by mutations in multiple genes. MODY is characterized by an early onset of diabetes (often before the age of 30 years) and autosomal dominant inheritance. Patients do not usually require insulin at diagnosis. To emphasize the importance of genetic analysis we describe a 7-year-old boy and his siblings with MODY type 2. Molecular genetic testing is essential for individual patient care, as treatment options differ between the various forms of MODY; it also provides an opportunity to screen relatives.

Bone mineral density in children and adolescents with Prader-Willi syndrome: a longitudinal study during puberty and 9 years of growth hormone treatment.

CONTEXT: Longitudinal data on bone mineral density (BMD) in children and adolescents with Prader-Willi Syndrome (PWS) during long-term GH treatment are not available. OBJECTIVE: This study aimed to determine effects of long-term GH treatment and puberty on BMD of total body (BMDTB), lumbar spine (BMDLS), and bone mineral apparent density of the lumbar spine (BMADLS) in children with PWS. DESIGN AND SETTING: This was a prospective longitudinal study of a Dutch PWS cohort. PARTICIPANTS: Seventy-seven children with PWS who remained prepubertal during GH treatment for 4 years and 64 children with PWS who received GH treatment for 9 years participated in the study. INTERVENTION: The children received GH treatment, 1 mg/m(2)/day (≅ 0.035 mg/kg/d). MAIN OUTCOME MEASURES: BMDTB, BMDLS, and BMADLS was measured by using the same dual-energy x-ray absorptiometry machine for all annual measurements. RESULTS: In the prepubertal group, BMDTB standard deviation score (SDS) and BMDLSSDS significantly increased during 4 years of GH treatment whereas BMADLSSDS remained stable. During adolescence, BMDTBSDS and BMADLSSDS decreased significantly, in girls from the age of 11 years and in boys from the ages of 14 and 16 years, respectively, but all BMD parameters remained within the normal range. Higher Tanner stages tended to be associated with lower BMDTBSDS (P = .083) and a significantly lower BMADLSSDS (P = .016). After 9 years of GH treatment, lean body mass SDS was the most powerful predictor of BMDTBSDS and BMDLSSDS in adolescents with PWS. CONCLUSIONS: This long-term GH study demonstrates that BMDTB, BMDLS, and BMADLS remain stable in prepubertal children with PWS but decreases during adolescence, parallel to incomplete pubertal development. Based on our findings, clinicians should start sex hormone therapy from the age of 11 years in girls and 14 years in boys unless there is a normal progression of puberty.

New insights into factors influencing adult height in short SGA children: Results of a large multicentre growth hormone trial.

BACKGROUND: Growth hormone (GH) treatment is effective in improving adult height (AH) in short children born SGA. However, there is a wide variation in height gain, even after adjustment for predictive variables. It is therefore important to investigate new factors which can influence the response to GH. OBJECTIVE: To investigate the efficacy of GH treatment (1 mg/m(2/) day) in short SGA children on AH. To assess the relation between spontaneous catch-up growth after birth and growth during puberty on the total height gain SDS to AH. PATIENTS: Longitudinal GH trial in 170 children. RESULTS: Median age at start of GH was 7·1 years and height -3·0 SDS. AH was -1·8 SDS (TH-corrected AH -1·1 SDS) in boys and -1·9 SDS (TH-corrected AH -1·3 SDS) in girls. Spontaneous catch-up growth after birth was ≥0·5 SDS in 42% of children. In contrast to expectation, spontaneous catch-up growth was negatively correlated with total height gain SDS during GH (P = 0·009). During puberty, height SDS declined (-0·4 SDS in boys and -0·5 SDS in girls) resulting in a lower total height gain SDS than expected. Pubertal height gain was 25·5 cm in boys and 15·3 cm in girls, significantly lower compared to AGA children (P < 0·001). At onset of puberty, BA for boys and girls was moderately advanced (P = 0·02 and P < 0·001, respectively). Growth velocity was comparable to AGA children during the first two years of puberty, but thereafter significantly lower until reaching AH (P < 0·001). CONCLUSION: In contrast to our hypothesis, children with greater spontaneous catch-up growth after birth show a lower total height gain SDS during GH. Height SDS declines from mid-puberty, due to a marked early deceleration of growth velocity.

Eight years of growth hormone treatment in children with Prader-Willi syndrome: maintaining the positive effects.

BACKGROUND: The most important reason for treating children with Prader-Willi syndrome (PWS) with GH is to optimize their body composition. OBJECTIVES: The aim of this ongoing study was to determine whether long-term GH treatment can counteract the clinical course of increasing obesity in PWS by maintaining the improved body composition brought during early treatment. SETTING: This was a multicenter prospective cohort study. METHODS: We have been following 60 prepubertal children for 8 years of continuous GH treatment (1 mg/m(2)/d ≈ 0.035 mg/kg/d) and used the same dual-energy x-ray absorptiometry machine for annual measurements of lean body mass and percent fat. RESULTS: After a significant increase during the first year of GH treatment (P < .0001), lean body mass remained stable for 7 years at a level above baseline (P < .0001). After a significant decrease in the first year, percent fat SD score (SDS) and body mass index SDS remained stable at a level not significantly higher than at baseline (P = .06, P = .14, resp.). However, body mass index SDSPWS was significantly lower after 8 years of GH treatment than at baseline (P < .0001). After 8 years of treatment, height SDS and head circumference SDS had completely normalized. IGF-1 SDS increased to +2.36 SDS during the first year of treatment (P < .0001) and remained stable since then. GH treatment did not adversely affect glucose homeostasis, serum lipids, blood pressure, and bone maturation. CONCLUSION: This 8-year study demonstrates that GH treatment is a potent force for counteracting the clinical course of obesity in children with PWS.

Long-term effect of lifestyle intervention on adiposity, metabolic parameters, inflammation and physical fitness in obese children: a randomized controlled trial.

BACKGROUND: Behavioral lifestyle intervention, combined with parental involvement, is preferred over standard care or self-help in childhood obesity. The short-term results of such interventions are promising, but long-term follow-up results are equivocal. OBJECTIVE: The objective of the present study was the short (3 months) and long-term (1 and 2 years follow-up) effect evaluation of a family-based multidisciplinary cognitive behavioral lifestyle intervention on markers of adiposity, metabolism, inflammation and physical fitness compared with standard care in children with obesity. Also the association between these outcome variables was determined. METHODS: In this prospective longitudinal clinical trial, obese children were randomly assigned to a 3-month family-based cognitive behavioral multidisciplinary lifestyle treatment (n=40; body mass index-standard deviation score (BMI-SDS) 4.2±0.7; age; 13.3±2.0 years) or to a control group receiving an initial advice on physical activity and nutrition (n=39; BMI-SDS 4.3±0.6; age 13.1±1.9 years). Anthropometric data, physical fitness, metabolic parameters and inflammatory state were evaluated at baseline, after intervention (at 3 months) and at 1-year follow-up. At 2-year follow-up, anthropometric data and physical fitness were measured in the intervention group. RESULTS: An intervention effect after 1 year was found for adiposity (P=0.02 for BMI-SDS, P=0.03 for waist circumference (WC)-SDS), physical fitness (absolute measured peak value of oxygen uptake (ml min(-1)), standardized for age and gender (VO2peak-SDS), P<0.01) and insulin resistance (HOMA-SDS, P=0.04). No significant intervention effect was found for serum lipid profile, high-sensitive C-reactive protein or for adiponectin. At 2-year follow-up, BMI-SDS in the intervention group (n=31) was 3.8±1.2 SDS, significantly less than at baseline (P=0.02). CONCLUSION: A positive 1-year follow-up treatment effect was found for adiposity, physical fitness and glucose homeostasis, but not for inflammatory markers. There was a significant long-term treatment effect on adiposity, although almost all children remained obese.