Comorbidity of inflammatory bowel disease in children and adolescents with type 1 diabetes.

AIM: To determine the prevalence of inflammatory bowel disease (IBD) in patients with type 1 diabetes (T1D) and to characterise patients with both diseases. METHODS: Data of 65.147 patients with T1D ≤18 years of 379 centres in Germany and Austria participating in the DPV initiative were analysed. A total of 63 children had comorbid IBD; IBD prevalence was 0.1%. Regression models were used to analyse differences in metabolic control, acute complications and steroid intake. RESULTS: Mean BMI-SDS in patients with T1D and IBD was lower (-0.15 ± 0.11) compared to patients with T1D only (0.27 ± 0.00, p < .001). Patients with T1D and IBD had a significantly higher use of steroids (22% ± 0.05% vs. 1% ± 0.00, p < .001) and a significantly higher rate of severe hypoglycaemic events per patient year (0.33 ± 0.07 vs. 0.16 ± 0.00, p = .001). No differences were found in HbA1c levels, insulin dose and occurrence of DKA. CONCLUSION: Although children and adolescents with T1D and IBD take steroids more often, they suffer from severe hypoglycaemia more frequently and have a lower BMI-SDS. These findings might be explained by chronic intestinal inflammation leading to malabsorption, malnutrition and increased severe hypoglycaemia.

Type 1 diabetes and epilepsy in childhood and adolescence: Do glutamic acid decarboxylase autoantibodies play a role? Data from the German/Austrian/Swiss/Luxembourgian DPV Registry.

AIMS: We aimed to analyze the relationship between epilepsy and glutamic acid decarboxylase autoantibodies (GADA) in patients with type 1 diabetes mellitus (T1DM) and the impact of GADA on demographic, clinical, and metabolic data in T1DM patients with epilepsy. METHODS: We searched for patients with T1DM ≤20 years and GADA measurements, and within this group for patients with epilepsy. We formed groups: T1DM + Epilepsy + GADA positive; T1DM + Epilepsy + GADA negative; T1DM + GADA positive; T1DM + GADA negative. We used logistic regression to analyze the relationship between epilepsy and GADA with odds ratio adjusted for sex, duration of diabetes (DOD), and age at diabetes onset (ADO). We used logistic regression with odds ratio adjusted for DOD and ADO onset using epilepsy as a dependent variable and GADA, HbA1c, ketoacidosis, severe hypoglycemia (SH), sex, celiac disease, and autoimmune thyroiditis as independent variables. We conducted regression analyses adjusted for sex, DOD, and ADO to analyze differences in clinical/metabolic parameters between the groups. RESULTS: Epilepsy was not more frequent in GADA-positive patients (GPP). Logistic regression including all patients with GADA measurements showed that hypoglycemia with coma (HC) correlated with epilepsy when compared to no SH. We found no differences in clinical and metabolic data between GPP and GADA-negative patients (GNP) with epilepsy. SH occurred more often in GPP with epilepsy in comparison to GPP without epilepsy. GNP with epilepsy had a higher rate of HC than GPP without epilepsy. CONCLUSION: We found no relationship between epilepsy and GADA. A relationship between T1DM and epilepsy might be explainable by SH.

Diabetes Mellitus and Autoimmune Hepatitis: Demographical and Clinical Description of a Relatively Rare Phenotype.

We studied demographic, metabolic, and clinical characteristics of patients with diabetes and autoimmune hepatitis (AIH) from the German/Austrian DPV registry. A total of 139 patients with diabetes and AIH were analyzed and compared to 437 728 patients with diabetes without AIH. The prevalence of AIH in patients with T1DM (44.8/100 000) seems higher than in the general population, the prevalence of AIH in patients with T2DM (23.6/100 000) does not seem to be increased. Patients with T2DM and AIH had a shorter duration of diabetes (p=0.007) and a higher proportion of females (p<0.001) compared to T2DM without AIH. Patients with diabetes (T1DM or T2DM) and AIH required higher insulin doses (p<0.001 and p=0.03, respectively) and showed increased liver enzymes (aspartate transaminase, alanine transaminase, gamma-glutamyltransferase) compared to diabetes patients without (all p<0.001). We detected a lower percentage of patients treated with oral antidiabetic drugs (p=0.01) and a higher percentage of patients treated by insulin in patients with T2DM and AIH (p<0.001) compared to patients with T2DM alone. We observed a higher incidence of autoimmune thyroid disease (AIT) in patients with diabetes (T1DM or T2DM) and AIH (p<0.001) compared to diabetes patients without AIH. AIH seems more frequent in patients with T1DM. Patients with diabetes and AIH require intensification of antidiabetic therapy and seem to have a higher prevalence of AIT.

The impact of insulin resistance and hyperandrogenemia on polysomnographic variables in obese adolescents with polycystic ovarian syndrome.

PURPOSE: We aimed to determine the impact of insulin resistance and hyperandrogenemia on polysomnographic variables in obese adolescents with polycystic ovarian syndrome (PCOS), as studies in adults with PCOS suggest that parameters of glucose metabolism and serum androgens are related to respiratory polysomnographic variables (RPV), and the symptoms of PCOS usually begin around menarche. METHODS: We divided our study group of obese adolescents with PCOS according to HOMA-index and in a second analysis according to free androgen index (FAI). Study group A consisted of 14 girls with HOMA-index <4, study group B of 17 girls with HOMA-index >4. Study group C consisted of 19 girls with FAI <10, and study group D of 18 girls with FAI >10. The control group for both analyses consisted of 19 healthy obese adolescents without PCOS. All girls underwent overnight 12-channel polysomnography. RESULTS: In both analyses, we found no differences between the groups concerning the RPV. Study group B demonstrated a significantly lower percentage of REM-sleep than the control group (p = 0.02). Study group D demonstrated a significantly lower percentage sleep stages 3 and 4 of non-REM-sleep than study group C and the controls (p = 0.008). Study group D demonstrated significantly lower sleep efficiency than the controls (p = 0.03). CONCLUSIONS: Insulin resistance and hyperandrogenemia do not seem to have a significant impact on RPV in obese adolescents with PCOS. Differences in sleep architecture found between patients with PCOS and controls, however, are possibly influenced by insulin resistance and/or serum androgens.

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.

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

The aim of this study was to compare polysomnographic variables of obese adolescents with polycystic ovarian syndrome (PCOS) to those of healthy controls and to analyse whether polysomnographic variables correlate to parameters of body weight/body composition, to serum androgens and to parameters of glucose metabolism. Thirty-one obese adolescents with PCOS (15.0 years ± 1.0, body mass index 32.7 kg per m(2) ± 6.2) and 19 healthy obese adolescents without PCOS (15.2 years ± 1.1, body mass index 32.4 kg per m(2) ± 4.0) underwent polysomnography to compare apnoea index, hypopnoea index, apnoea-hypopnoea index, the absolute number of obstructive apnoeas, percentage sleep Stages 1, 2, 3 and 4 of non-rapid eye movement (NREM) sleep, percentage of REM sleep, TIB, total sleep time (TST), sleep-onset latency, total wake time (TWT), wakefulness after sleep onset (WASO) and sleep efficiency. Furthermore, we correlated polysomnographic variables to parameters of body weight/body composition, to serum androgens and to parameters of glucose metabolism. We found no differences between the two groups concerning the respiratory indices, percentage sleep Stages 2, 3 and 4 of NREM sleep, TIB and sleep-onset latency. The girls with PCOS differed significantly from the controls regarding TST, WASO, TWT, sleep efficiency, percentage Stage 1 of NREM sleep and percentage of REM sleep. We found a weak significant correlation between insulin resistance and apnoea index and between insulin resistance and apnoea-hypopnoea index. Concerning the respiratory variables, adolescents with PCOS do not seem to differ from healthy controls; however, there seem to be differences concerning sleep architecture.

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.

Association between androgens, intima-media thickness and the metabolic syndrome in obese adolescent girls.

BACKGROUND: While an association between androgens and the metabolic syndrome (MS) is well established in obese women, studies concerning this relationship are scarce in obese adolescent girls. Therefore, we analysed the relationships between androgens, MS and intima-media thickness (IMT) in this age-group. METHODS: In 160 obese girls (aged 12-18 years, mean BMI: 32.6 +/- 5.0 kg/m((2))), androgens [testosterone, dehydroepiandrosterone sulphate (DHEA-S), androstenedione], SHBG and the components of MS (waist circumference, blood pressure (BP), lipids, uric acid, insulin, glucose, 2 h glucose in oral glucose tolerance test (oGTT)) were studied. Furthermore, IMT was determined in a subgroup of 71 randomly chosen girls. RESULTS: Testosterone correlated significantly to systolic BP (r = 0.20), diastolic BP (r = 0.24), 2 h glucose in oGTT (r = 0.30), triglycerides (r = 0.19), uric acid (r = 0.17), waist circumference (r = 0.25) and IMT (r = 0.54). These relationships (except for waist circumference and uric acid) were independent of BMI and insulin resistance index homeostasis model assessment. In contrast to testosterone, DHEA-S, androstenedione and SHBG showed no or weaker correlations to any parameter of MS. The 48 girls with MS demonstrated significantly higher testosterone (1.8 +/- 0.7 nmol/l; P = 0.025) and DHEA-S (4.7 +/- 2.3 micromol/l; P = 0.008) concentrations as compared with the 112 girls without MS (mean testosterone 1.5 +/- 0.7 nmol/l, mean DHEA-S 3.6 +/- 2.3 micromol/l). CONCLUSIONS: Testosterone was significantly related to MS and its components in obese adolescent girls independently of BMI and insulin resistance. As IMT was significantly associated with testosterone, this supports the clinical relevance of this finding.

A comparison of polysomnographic variables between obese adolescents with polycystic ovarian syndrome and healthy, normal-weight and obese adolescents.

PURPOSE: The purpose of this study was to determine the differences in polysomnographic variables between obese adolescents with polycystic ovarian syndrome (PCOS) and healthy, normal-weight and obese controls, as the prevalence of obstructive sleep apnea syndrome (OSAS) is increased in adults with PCOS. METHODS: Twenty-two obese adolescents with PCOS (mean age 15.2 +/- 1.3 years, mean BMI 31.7 +/- 6.2 kg/m(2)), 18 healthy, normal-weight adolescents (mean age 15.0 +/- 0.9 years, mean BMI 20.6 +/- 2.3 kg/m(2)), and 11 healthy, obese adolescents (mean age 15.0 +/- 1.0 years, mean BMI 34.8 +/- 8.7 kg/m(2)) underwent polysomnography to compare mean transcutaneous arterial oxygen saturation (Sat O(2)), apnea index (AI), hypopnea index (HI), apnea-hypopnea index (AHI), the absolute number of obstructive apneas (NOA), percentage sleep stages 3 and 4 of non-REM sleep (stages 3 and 4), percentage of REM sleep (%REM), sleep-onset latency, and sleep efficiency. RESULTS: We found no differences between the three groups concerning Sat O(2), AI, HI, AHI, NOA, and stages 3 and 4. The girls with PCOS differed from normal-weight and obese controls regarding sleep-onset latency and sleep efficiency and from the normal-weight controls regarding %REM. CONCLUSIONS: OSAS does not seem to be more prevalent in adolescents with PCOS. Concerning the respiratory variables, adolescents with PCOS do not seem to differ from healthy controls; however, there seem to be differences concerning sleep architecture.

Parental diabetes, pubertal stage, and extreme obesity are the main risk factors for prediabetes in children and adolescents: a simple risk score to identify children at risk for prediabetes.

OBJECTIVES: The current worldwide increase of prediabetes defined as impaired fasting glucose or impaired glucose tolerance and type 2 diabetes mellitus (T2DM) coincides the increase of obesity. However, it is unclear that which children have an increased risk and should be screened for prediabetes. METHODS: We studied 437 overweight children and adolescents to identify risk factors for prediabetes. A risk score for prediabetes was calculated using logistic regression. This score was examined in a second, independent cohort of 567 overweight children and adolescents. History of T2DM in parents and grandparents, degree of overweight, age, pubertal stage, birth weight, hypertension, dyslipidemia, acanthosis nigricans, and abdominal obesity were considered as potential risk factors. RESULTS: The frequency of prediabetes was 6% in sample 1 and 17% in sample 2. The strongest association was observed for history of parental diabetes with an adjusted odds ratio (aOR) of 9.5 [95% confidence interval (CI) 2.5-36.4] in sample 1 and 6.3 (95% CI 3.7-10.7) in sample 2, followed by pubertal stage with an aOR of 5.5 (95% CI 0.7-45.4) in sample 1 and 6.2 (95% CI 2.4-15.6) in sample 2, and by extreme obesity with an aOR of 5.0 (95% CI 1.7-15.3) in sample 1 and 3.3 (95% CI 2.0-5.4) in sample 2. CONCLUSIONS: The main risk factors for prediabetes were parental diabetes, pubertal stage, and extreme obesity. Screening for prediabetes seems meaningful in subjects with either a parental history of diabetes or a combination of extreme obesity and pubertal stage and detected nearly 90% of the overweight children and adolescents with prediabetes.

Insulin-like growth factor-I, insulin-like growth factor binding protein-3 and growth in obese children before and after reduction of overweight.

UNLABELLED: Little longitudinal information is available on changes of growth, insulin-like growth factor-I (IGF-I), its main binding protein (IGFBP-3) and their relationships to leptin and insulin in obese children reducing their overweight. We compared these parameters between baseline and after participating in a one-year lifestyle intervention in 319 obese children. The control group comprised 52 lean children. Obese children demonstrated significantly increased IGFBP-3, leptin, and insulin concentrations and were taller compared to the lean children, while they did not differ in respect to their IGF-I concentrations. Reduction of overweight was associated with a significant decrease of IGFBP-3 SDS, leptin, and insulin concentrations. IGF-I SDS and height SDS did not change after weight loss. CONCLUSIONS: IGFBP-3, leptin and insulin concentrations are increased in obese children and normalized in weight loss demonstrating the reversibility of these alterations. Weight loss due to lifestyle intervention was not associated with growth disturbances.

Obestatin and ghrelin levels in obese children and adolescents before and after reduction of overweight.

OBJECTIVES: Obestatin and ghrelin, which are derived from the same gene, are observed to have opposite effects on weight status. The aims of this study were to compare obestatin concentrations in obese and normal-weight children and to analyse the effect of weight loss on obestatin and ghrelin levels. METHODS: We examined anthropometrical markers and fasting serum obestatin, ghrelin, leptin, glucose and insulin concentrations in 44 obese children (mean age 11.2 years) before and after participating in a 1-year outpatient obesity intervention programme based on a high-carbohydrate, fat-reduced diet and increased physical activity. Additionally, total ghrelin, obestatin and leptin levels were determined in 22 normal-weight healthy children of similar age, gender and pubertal stage. RESULTS: Obestatin and leptin concentrations were significantly (P < 0.001) higher and ghrelin concentrations were significantly (P < 0.001) lower in obese children compared to nonobese children. In contrast to the 13 children without weight loss, substantial weight loss in 31 children led to a significant (P = 0.007) increase in obestatin and to a significant (P < 0.05) decrease in leptin and insulin concentrations, while ghrelin concentrations did not change significantly. Children with substantial weight loss demonstrated significantly (P = 0.009) lower obestatin and a tendency (P = 0.064) to higher ghrelin concentrations at baseline. Changes in insulin were not related to changes in ghrelin or obestatin. CONCLUSION: The increase in obestatin and the decrease in ghrelin in obese children point towards an adaptation process of weight status. Weight reduction due to a long-term lifestyle intervention resulted in an increase in obestatin levels.

Thyroid hormones and their relation to weight status.

BACKGROUND/AIMS: The aim of this study was to analyze thyroid hormones in female adolescents with obesity and anorexia nervosa (AN) before and after normalization of weight. METHODS: Thyroid-stimulating hormone (TSH), fT3, and fT4 were determined in 100 obese girls, 32 normal-weight girls and 20 girls with AN aged 14-18 years at baseline and 1 year later. Additionally, leptin, insulin, and the insulin resistance index HOMA were analyzed in the obese and normal-weight girls. RESULTS: TSH and fT3 levels of girls with AN were significantly lower compared to TSH concentrations of normal-weight girls, while TSH and fT3 levels of the obese girls were significantly higher. The 21 obese females with weight loss >5% demonstrated a significant decrease in fT3 and TSH, while the 9 adolescents with AN and weight gain >5% showed a significant increase in fT3 and TSH. Insulin and HOMA were not significantly correlated to TSH, fT3 and fT4, while leptin was correlated to TSH and fT3 in both cross-sectional and longitudinal analysis. CONCLUSIONS: Thyroid function seems to be reversibly related to weight status with increased TSH and fT3 concentrations in obesity and decreased TSH and fT3 levels in AN. We hypothesize that leptin may be the link between weight status and TSH.

Precocious pseudopuberty due to autonomous ovarian cysts: a report of ten cases and long-term follow-up.

We report the findings and clinical course of ten girls aged 0.2 to 6.3 years with precocious pseudopuberty due to autonomous ovarian cysts. We found elevated oestrogen levels in five patients and failure of gonadotropin response to GnRH stimulation in four patients during the first episode, of the disease. In one patient, a GnRH stimulation test was not performed. Pelvic ultrasound examination showed large ovarian cysts in all ten patients. Following the initial episode the secondary sexual characteristics of nine patients regressed completely without treatment. The cyst of one girl was removed surgically on demand of her parents. Three girls presented recurrent autonomous ovarian cysts. Two of these girls developed central precocious puberty requiring treatment with a GnRH-agonist after repeated episodes of precocious pseudopuberty. We started treating the third girl with a GnRH agonist after the second relapse of the autonomous ovarian cyst because of rapidly advancing bone age. We conclude that in the majority of cases autonomous ovarian cysts regress spontaneously and that surgery is in general not indicated. Furthermore, autonomous ovarian cysts can relapse before the onset of physiological puberty and accelerate biological maturation leading to central precocious puberty and consequent decrease of height potential.

Diabetes mellitus in Friedreich Ataxia: A case series of 19 patients from the German-Austrian diabetes mellitus registry.

Friedreich ataxia (FRDA) is a multisystem autosomal recessive disease with progressive clinical course involving the neuromuscular and endocrine system. Diabetes mellitus (DM) is one typical non-neurological manifestation, caused by beta cell failure and insulin resistance. Because of its rarity, knowledge on DM in FRDA is limited. Based on data from 200,301 patients with DM of the German-Austrian diabetes registry (DPV) and two exemplary patient reports, characteristics of patients with DM and FRDA are compared with classical type 1 or type 2 diabetes. Diabetes phenotype in FRDA is intermediate between type 1 and type 2 diabetes with ketoacidosis being frequent at presentation and blood glucose levels similar to T1Dm but higher than in T2Dm (356 ±â€¯165 and 384 ±â€¯203 mg/dl). 63.2% of FRDA patients received insulin monotherapy, 21% insulin plus oral antidiabetics and 15.8% lifestyle change only, applying similar doses of insulin in all three groups. FRDA patients did not show overweight and HbA1c levels were even lower than in T1Dm or T2Dm patients, respectively, indicating good overall diabetes control. FRDADm can be controlled by individualized treatment regimen with insulin or oral antidiabetics. Patients with DM in FRDA may show a relevant risk to ketoacidotic complications, which should be avoided.

Definable somatic disorders in overweight children and adolescents.

OBJECTIVE: To analyze the frequencies and clinical presentation of definable somatic disorders in children who are overweight. STUDY DESIGN: We assessed prospectively 1405 children aged 4 to 16 years who were overweight and came to our specialized clinic for endocrinology and obesity with a standardized diagnostic procedure. In a subgroup of 223 children, we sought mutations in the melanocortin-4-receptor gene (MC4R). RESULTS: Endocrine or syndromal disorders were diagnosed in 13 children (<1%; 4 with hypothyroidism, 1 with Cushing's syndrome, 1 with growth hormone deficiency, 2 with pseudohypoparathyroidism, 1 with pseudopseudohypoparathyroidism, 2 with Prader-Willi syndrome, 1 with Bardet-Biedl syndrome, 1 with Klinefelter syndrome). A total of 85% of these children had short stature, in marked contrast to only 0.6% of the other children. Moderately elevated thyrotropin and cortisol concentrations were observed in 4% and 5%, respectively, of all children. Non-synonymous MC4R mutations were found in 6% of the children. CONCLUSIONS: In contrast to MC4R mutations, endocrine and clinically identifiable syndromal disorders were rare in children who were overweight and always associated with further symptoms. All children who are overweight with short stature or reduced growth velocity should be carefully examined for endocrine or syndromal disorders. A general screening with laboratory measurements cannot be recommended because thyrotropin and cortisol levels are frequently moderately elevated in children who are overweight, thus entailing further superfluous diagnostic procedures.

Vitamin D status and parathyroid hormone in obese children before and after weight loss.

OBJECTIVE: The roles of vitamin D and parathyroid hormone (PTH) are discussed controversially in obesity, and studies of these hormones in obese children are limited. Therefore, we studied the relationships between PTH, 1,25-dihydroxy-vitamin D (1,25-OH Vit D), 25-hydroxy-vitamin D (25-OH Vit D), weight status, and insulin sensitivity before and after weight loss in obese children. METHODS: Fasting serum PTH, 1,25-OH Vit D, 25-OH Vit D, inorganic phosphate, calcium, alkaline phosphatase (AP), insulin, glucose, and weight status (SDS-BMI and percentage body fat) were determined in 133 obese children (median age 12.1 years) and compared with 23 non-obese children. Furthermore, these parameters were analyzed in 67 obese children before and after participating in a 1-year obesity intervention program. RESULTS: Obese children had significantly (P < 0.001) higher PTH and lower 25-OH Vit D concentrations compared with non-obese children, while calcium, phosphate, AP, and 1,25-OH Vit D did not differ significantly. Changes of PTH (r = 0.23, P = 0.031) and 25-OH Vit D (r = -0.27, P = 0.013) correlated significantly with changes of SDS-BMI, but not with changes of insulin sensitivity (homeostasis model assessment; HOMA-B%). Reduction of overweight in 35 children led to a significant (P < 0.01) decrease of PTH concentrations and an increase in 25-OH Vit D levels. CONCLUSIONS: PTH levels were positively and 25-OH Vit D concentrations were negatively related to weight status. Since these alterations normalized after weight loss, these changes are consequences rather than causes of overweight. A relationship between PTH, vitamin D, and insulin sensitivity based on the HOMA index was not found in obese children. Further longitudinal clamp studies are necessary to study the relationship between vitamin D and insulin sensitivity.

Fasting glucagon-like peptide-1 and its relation to insulin in obese children before and after weight loss.

OBJECTIVE: To study the relationships between glucagon-like peptide-1 (GLP-1), weight status, insulin, and insulin resistance in the fasting state. PATIENTS AND METHODS: Fasting GLP-1, glucose and insulin concentrations, insulin resistance index as homeostasis model assessment (HOMA), body mass index (BMI), and percentage body fat based on skinfold thickness measurements were determined in 42 obese (median age 11 years) and in 16 lean children of the same age. The HOMA model was used to calculate degree of insulin resistance. Furthermore, the changes in GLP-1, glucose, insulin, and HOMA in the course of 1 year were analyzed in the 42 obese children participating in an obesity intervention. RESULTS: GLP-1 concentrations did not differ significantly between obese and lean children. In multiple linear regression analyses, GLP-1 was significantly related to insulin (P = 0.028) and HOMA (P = 0.019) but not to glucose, age, sex, pubertal stage, BMI, or percentage body fat. The 15 obese children with substantial weight reduction demonstrated significantly (P < 0.05) decreased GLP-1, insulin, and HOMA levels, whereas these parameters did not change in 27 obese children without substantial weight loss. Changes in GLP-1 correlated significantly with changes in insulin (r = 0.46, P = 0.001) and HOMA (r = 0.28, P = 0.036) but not with changes in glucose, BMI, or percentage of body fat. CONCLUSIONS: In children, fasting GLP-1 concentrations are independent of age, sex, and pubertal stage. Although GLP-1 did not differ between lean and obese children, weight loss was associated with decreasing GLP-1. Inasmuch as GLP-1 levels were related to insulin concentrations in both cross-sectional and longitudinal analyses, we hypothesize a relationship between GLP-1 and insulin in the fasting state.

Hyperthyrotropinemia in obese children is reversible after weight loss and is not related to lipids.

CONTEXT: There is some controversy whether T(4) treatment is indicated in obese humans with hyperthyrotropinemia. OBJECTIVE: The objective of this study was to examine whether hyperthyrotropinemia is a cause or a consequence of obesity. DESIGN: The study was designed as a cross-sectional comparison between obese and lean children and includes a 1-yr follow-up study. SETTING: The study was set in a primary care facility. PATIENTS: The patients were 246 obese and 71 lean children. INTERVENTION: The 1-yr intervention program was based on exercise, behavior therapy, and nutrition education. MAIN OUTCOME MEASURES: The main outcome measures were TSH, free T(3) (fT3), free T(4) (fT4), high-density lipoprotein, low-density lipoprotein, and total cholesterol at baseline and 1 yr later. RESULTS: TSH (P = 0.009) and fT3 (P = 0.003) concentrations were significantly higher in obese children than in normal weight children, whereas there was no difference in fT4 levels (P = 0.804). Lipids did not correlate significantly to thyroid hormones in cross-sectional and longitudinal analyses. fT3, fT4, and lipids did not differ significantly in the 43 (17%) children with TSH levels above the normal range from the children with TSH levels within the normal range. Substantial weight loss in 49 obese children led to a significant reduction of TSH (P = 0.035) and fT3 (P = 0.036). The 197 obese children without substantial weight loss demonstrated no significant changes of thyroid hormones. CONCLUSIONS: Because fT3 and TSH were moderately increased in obese children and weight loss led to a reduction, the elevation of these hormones seems to be rather a consequence of obesity than a cause of obesity. Because fT3 and TSH were both increased in obesity and thyroid hormones were not associated to lipids, we put forward the hypothesis that there is no necessity for thyroxine treatment.

Long-term follow-up of cardiovascular disease risk factors in children after an obesity intervention.

BACKGROUND: Data concerning the long-term improvement of cardiovascular disease (CVD) risk factors after an obesity intervention in children are limited. OBJECTIVE: We studied changes in weight status and CVD risk factors in children in an intervention program and evaluated whether these changes were sustained 1 y after the end of the intervention. DESIGN: We analyzed changes in the SD score (SDS) of body mass index [BMI; in kg/m2 (SDS-BMI)], blood pressure (BP), lipids, and homeostasis model assessment index of insulin resistance (HOMA-IR) over the course of 2 y in 240 obese (BMI > 97th percentile) children aged 6-14 y (x age: 10.4 y; x BMI: 26.9). Of these 240 children, 203 participated in a 1-y intervention program of physical exercise, nutrition education, and behavior therapy. We compared these children with 37 obese children who underwent no intervention and with 12 normal-weight children of the same age and sex. RESULTS: Obese children had significantly (P < 0.05) higher BP, HOMA-IR, and insulin, triacylglycerol, and LDL-cholesterol concentrations and lower HDL-cholesterol concentrations than did normal-weight children. Twenty-nine children dropped out of the intervention. Only in the 126 children who reduced their SDS-BMI did BP (8% and 12% decreases in systolic and diastolic BP, respectively), lipids (12% and 5% decreases in triacylglycerol and LDL cholesterol, respectively; 7% increase in HDL cholesterol), insulin (13% decrease), and HOMA-IR (17% decrease) improve significantly (P < 0.05). Reduction in SDS-BMI and all benefits regarding CVD risk factors were sustained 1 y after the end of the intervention in the children whose SDS-BMI decreased. CONCLUSIONS: Long-term multidisciplinary intervention led to a reduction in SDS-BMI in most of the obese children 1 y after the end of the intervention. Reduction in SDS-BMI was accompanied by an improvement in CVD risk factors.