Objective: Obesity is associated with insulin-resistance (IR), type 2 diabetes (T2D) and a constellation of cardiovascular risk factors at the early years of life. These features define the so-called metabolic syndrome (MS). Aims: To assess the frequency of the MS among obese pediatric Spanish population and analyse the individual contribution and the predictive potential of individual components to the development of the syndrome. Patients and methods: A total of 429 patients, 220 boys and 209 girls, aged 4-18 years, with a body mass index of O2 standard deviation scores for Spanish normative charts, were included in the study. Forty-seven percent were prepubertal and ten percent had Hispanic ethnicity. HbA1c, lipids, liver enzymes and uric acid levels were determined from blood and a standard 2-h oral glucose tolerance test was performed. MS was defined by the National Cholesterol Education Program's Adult Treatment Panel III criteria modified by Cook as having at least three features among: obesity, low high-density lipoprotein (HDL), hypertriglyceridemia, hypertension (HTA) or impaired glucose metabolism (IGM). We defined IR as homeostatic model assessment of IR index and/or fasting insulin levelsO95th centile of the control population. Results: Almost 18% of the patients had MS, with significantly higher frequency in Hispanic (32%) than in Caucasian (16%) population. There were no differences by sex or pubertal status. Prevalence of low HDL, HTA, hypertriglyceridemia and IGM were 27, 23, 16 and 7% respectively. No silent T2D was identified. According to International Obesity Task Force charts, 22% of the patients were overweight and not obese, but no differences in the frequency of individual features of MS between these two groups were observed. Among IR patients (35% of our population), the frequency of MS reached 28%. IR predicted the presence of MS independently from age and race. Conclusion: MS is present in 18% of our obese pediatric population. IR is closely associated with the components of MS and strongly predicts its development.European Journal of Endocrinology 155 313-319

The aims of this study were to estimate the prevalence of major maturity-onset diabetes of the young (MODY) subtypes in Spanish MODY families and to analyze genotype-phenotype correlations. Twenty-two unrelated pediatric MODY patients and 97 relatives were screened for mutations in the coding region of the glucokinase (GCK), hepatic nuclear factor- HNF-1alpha and HNF4alpha genes using PCR-single strand conformation polymorphism and/or direct sequencing. In families carrying GCK mutations, the influence of genetic defects on fetal growth was investigated by comparing the birth weights of 32 offspring discordant for the mutations. Mutations in MODY genes were identified in 64% of the families. GCK/MODY2 mutations were the most frequently found, in 41%: seven novel (R369P, S411F, M298K, C252Y, Y108C, A188E, and S383L) and 2 already described mutations. Four pedigrees (18%) harbored mutations in the HNF-1alpha/MODY3 gene, including a previously unreported change (R271G). One family (4%) carried a novel mutation in the HNF-4alpha gene (IVS5-2delA), representing the first report of a MODY1 pedigree in the Spanish population. The age at diagnosis was prepubertal in MODY2 index patients and pubertal in MODY3 patients. Overt diabetes was rare in MODY2 and was invariably present in MODY3 index patients. Chronic complications of diabetes were absent in the MODY2 population and were present in more than 40% of all relatives of MODY3. Birth weight was lower in the presence of a GCK fetal mutation when the mutation was of paternal origin. The MODY1 patient was diagnosed at 15 yr of age. She developed intermittent microalbuminuria despite good metabolic control, and severe late-onset complications were common within her family. Mutations in the GCK/MODY2 gene are the most common cause of MODY in our population as recruited from pediatric and adolescent index patients. The inheritance of GCK defects by the fetus results in a reduction of birth weight. Clinical expression of MODY3 and MODY1 mutations, the second and third groups of defects found, was more severe, including the frequent development of chronic complications.

Investigations of adult patients have shown that chemotherapy causes gonadal damage, but much less information is available about the impact of chemotherapy on gonadal function in children with malignant disease. At one time, being prepubertal during therapy was thought to confer some protection against chemotherapy induced gonadal damage. However, recent studies have indicated otherwise. We designed this study to assess gonadal function in 15 postpubertal males who had received polychemotherapy for a malignant disease during childhood and we compared them with 13 control adults males. The mean age of the patients at the time of the study was 18.2 +/- 3.6 years (range 13.8-29.0), and when given chemotherapy treatment was 10.2 +/- 3.0 years (range 6-16). At that time 12 were prepubertal and at the time of the study all were Tanner V. The mean interval from the completion of treatment until the study was 6.42 years (range 2.0-16.5). All patients had received polychemotherapy. We evaluated testicular size, sperm counts, LH and FSH after GnRH test, and testosterone levels. Puberty had progressed normally in all patients. We found no significant differences in testosterone and basal LH levels between patients and controls. However, we detected an appreciable difference in peak LH levels (P < 0.05) and in basal and peak FSH levels (P < 0.001). Seven patients had exaggerated LH response to GnRH, indicating dysfunction of the Leydig cells. The results of semen analyses were: 8 patients had azoospermia, 3 oligospermia, and 1 patient had a normal semen analysis. All patients with semen abnormalities presented a basal and peak FSH higher than the mean +2 SD of the control group. In summary, we found no evidence of gonadal protection in prepubertal patients. We found a high incidence of germinal cell damage, whereas Leydig cell abnormalities were found less often. An endocrine study of patients that have received chemotherapy is warranted.

No abstract

No abstract