Thiamine-Responsive Megaloblastic Anemia-Related Diabetes: Long-Term Clinical Outcomes in 23 Pediatric Patients From the DPV and SWEET Registries.

OBJECTIVES: To describe clinical presentation and long-term outcomes in a large cohort of children diagnosed with thiamine-responsive megaloblastic anemia (TRMA)-related diabetes. METHODS: Data from the Diabetes Patienten Verlaufsdokumentation (DPV) and Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference (SWEET) registries were used to identify cases. Complementary information was collected through a chart review of each case. Descriptive analyses with medians and interquartile ranges and numbers (proportions) were tabulated. RESULTS: We identified 23 cases (52% male) in the 2 registries. Eighteen (78%) had genetic confirmation of TRMA. Median age at diabetes onset was 1.4 (quartiles 0.8 to 3.6) years and median age at initiation of thiamine treatment was 5.9 (2.4 to 12.4) years. At their most recent visit, patients' median age was 14.3 (8.1 to 17.5) years, glycated hemoglobin level was 6.9% (6.1% to 7.9%), insulin dose was 0.9 (0.4 to 1.2) units/kg per day and thiamine dose was 200 (100 to 300) mg/day. Three patients were not treated with insulin or antidiabetic drugs. There was no difference in diabetes outcomes in patients with initiation of thiamine ≤1 year after diabetes onset compared to patients with initiation of thiamine >1 year after diabetes onset. CONCLUSIONS: This is the longest case series of pediatric TRMA-related diabetes reported to date. Diabetes onset often occurs several years before initiation of thiamine supplementation. Early initiation of thiamine (within 1 year of diabetes onset) was not linked to improved diabetes outcome. However, the role of thiamine in pancreatic function needs further assessment. Patients with TRMA-related diabetes maintained good glycemic control even after 9 years (median) of follow up.

Longitudinal analyses of polysomnographic variables, serum androgens, and parameters of glucose metabolism in obese adolescents with polycystic ovarian syndrome.

PURPOSE: The prevalence of obstructive sleep apnea syndrome (OSAS) is clearly increased in adults with polycystic ovarian syndrome (PCOS), whereas OSAS does not seem to be frequent in adolescents with PCOS, pointing towards the fact that some patients with PCOS develop OSAS in the further course of the disease. We therefore aimed to analyze the changes of polysomnographic variables in obese adolescents with PCOS in a longitudinal analysis. METHODS: Fifteen adolescents with PCOS (age 15.3 years ± 1.2, BMI 32.9 kg/m(2) ± 6.4, SDS-BMI 2.5 ± 0.8) underwent overnight 12-channel polysomnography at baseline and after a mean duration of 28 ± 6 months (age 17.8 years ± 1.1, BMI 32.7 kg/m(2) ± 7.0, SDS-BMI 2.1 ± 0.9). After performing the initial polysomnography, we treated hyperandrogenemia and insulin resistance in the study group. We determined parameters of body weight/body composition, parameters of glucose metabolism, and serum androgens in all patients at baseline and follow-up. At follow-up, we compared the polysomnographic variables of the study group to those of healthy female adults. RESULTS: The polysomnographic variables, the parameters of body weight/body composition, and the parameters of glucose metabolism in the study group did not change significantly during the observation period. The serum levels of total testosterone and sex hormone binding globulin increased significantly, whereas free androgen index decreased significantly. At follow-up, the polysomnographic variables of the study group did not differ from those of healthy female adults. CONCLUSIONS: OSAS does not seem to develop in adolescents with PCOS being treated for hyperandrogenism and insulin resistance. The pathogenesis of OSAS in PCOS needs to be examined in larger controlled studies.

Leptin concentrations are a predictor of overweight reduction in a lifestyle intervention.

OBJECTIVE: Leptin resistance is discussed to be involved in the genesis of obesity. Therefore, we hypothesized that leptin levels were negatively associated with degree of weight loss in obese children participating in a lifestyle intervention. METHODS: We studied 248 obese children aged 8-14 years attending the "Obeldicks" lifestyle intervention (mean age 10.6+/-0.2 years, 53% female, 48% pubertal, mean body mass index (BMI) 27.8+/-0.3 kg/m2, and mean standard deviation score [SDS]-BMI 2.43+/-0.03). Baseline leptin concentrations were correlated with change of weight status, waist circumference, and percentage body fat, as calculated from skinfold measurements in the one-year intervention by Pearson correlation and multiple linear regression analyses. Furthermore, the relationship between leptin and cardiovascular risk factors (insulin, insulin resistance index HOMA, blood pressure, lipids, and glucose) were analyzed. RESULTS: A total of 212 children (85%) reduced their overweight, 9 children (4%) dropped out, and 27 children (11%) did not reduce their overweight in the lifestyle intervention "Obeldicks". The mean reduction of SDS-BMI was 0.34+/-0.02. The reduction of SDS-BMI (r=- 0.27), waist circumference (r=- 0.64), and percentage body fat (r=- 0.26) were significantly negatively associated with baseline leptin levels both in univariate analyses and in multiple regression analyses, adjusted to baseline age, BMI, gender and pubertal stage. Baseline leptin concentrations were significantly associated with BMI, pubertal stage, gender, waist circumference, and insulin, but not to any other cardiovascular risk factors in multiple regression analyses. CONCLUSIONS: The finding that baseline leptin concentrations were significantly negatively correlated with the degree of weight loss in a lifestyle intervention supports the hypothesis of leptin resistance in obesity. This study is registered at clinicaltrials.gov (NCT00435734).