Angela Galler

Clinical aspects of obesity in childhood and adolescence

The level of fatness of a child at which morbidity acutely and/or later in life increases is determined on an acturial basis. Direct measurements of body fat content, e.g. hydrodensitometry, bioimpedance, or DEXA, are useful tools in scientific studies. However, body mass index (BMI) is easy to calculate and is generally accepted now to be used to define obesity in children and adolescents clinically. An increased risk of death from cardiovascular disease in adults has been found in subjects whose BMI had been greater than the 75th percentile as adolescents. Childhood obesity seems to substantially increase the risk of subsequent morbidity whether or not obesity persists into adulthood. The genetic basis of childhood obesity has been elucidated to some extent through the discovery of leptin, the ob gene product, and the increasing knowledge on the role of neuropeptides such as POMC, neuropeptide Y (NPY) and the melanocyte concentrating hormone receptors (for example, MC4R). Environmental/exogenous factors largely contribute to the development of a high degree of body fatness early in life. Twin studies suggest that approximately 50% of the tendency toward obesity is inherited. There are numerous disorders including a number of endocrine disorders (Cushings syndrome, hypothyroidism, etc.) and genetic syndromes (Prader‐Labhard–Willi syndrome, Bardet Biedl syndrome, etc.) that can present with obesity. A simple diagnostic algorithm allows for the differentiation between primary or secondary obesity. Among the most common sequelae of primary childhood obesity are hypertension, dyslipidemia, back pain and psychosocial problems. Therapeutic strategies include psychological and family therapy, lifestyle/behaviour modification and nutrition education. The role of regular exercise and exercise programmes is emphasized. Surgical procedures and drugs used in adult obesity are still not generally recommended in children and adolescents with obesity. As obesity is the most common chronic disorder in industrialized societies, its impact on individual lives as well as on health economics has to be recognized more widely. This review is aimed towards defining the clinical problem of childhood obesity on the basis of current knowledge and towards outlining future research areas in the field of energy homoeostasis and food intake in relation to child health. Finally, one should aim to increase public awareness of the ever increasing health burden and economic dimension of the childhood obesity epidemic that is present around the globe.

Diabetic Nephropathy in 27,805 Children, Adolescents, and Adults With Type 1 Diabetes: Effect of diabetes duration, A1C, hypertension, dyslipidemia, diabetes onset, and sex

OBJECTIVE—To give an up-to-date profile of nephropathy and the involvement of risk factors in a large, prospective cohort of patients with type 1 diabetes and largely pediatric and adolescent onset of disease. RESEARCH DESIGN AND METHODS—A total of 27,805 patients from the nationwide, prospective German Diabetes Documentation System survey were included in the present analysis. Inclusion criteria were at least two documented urine analyses with identical classification. Urine analyses, treatment regimens, diabetes complications, and risk factors were recorded prospectively. Baseline characteristics were age at diagnosis 9.94 years (median [interquartile range 5.8–14.3]), age at last visit 16.34 years (12.5–22.2), and follow-up time 2.5 years (0.43–5.3). Cumulative incidence of nephropathy was tested by Kaplan-Meier analysis and association with risk factors by logistic regression. RESULTS—Nephropathy was classified as normal in 26,605, microalbuminuric in 919, macroalbuminuric in 78, and end-stage renal disease (ESRD) in 203 patients. After calculated diabetes duration of 40 years, 25.4% (95% CI 22.3–28.3) had microalbuminuria and 9.4% (8.3–11.4) had macroalbuminuria or ESRD. Risk factors for microalbuminuria were diabetes duration (odds ratio 1.033, P < 0.0001), A1C (1.13, P < 0.0001), LDL cholesterol (1.003, P < 0.0074), and blood pressure (1.008, P < 0.0074), while childhood diabetes onset (1.011, P < 0.0001) was protective. Male sex was associated with the development of macroalbuminuria. CONCLUSIONS—Diabetes duration, A1C, dyslipidemia, blood pressure, and male sex were identified as risk factors for nephropathy. Therefore, besides the best possible metabolic control, early diagnosis and prompt treatment of dyslipidemia and hypertension is mandatory in patients with type 1 diabetes.

Evaluation of patients' opinion and metabolic control after transfer of young adults with type 1 diabetes from a pediatric diabetes clinic to adult care.

Background: Transferring adolescents with diabetes from pediatric to adult care remains a challenge and the outcome is often unknown. The aims of this study were to determine the patients’ perception of transfer arrangements and to analyze health care use and metabolic control. Methods: A telephone questionnaire was conducted for patients who had been transferred from the pediatric clinic to adult care between 1995 and 2003. Of 161 identified patients, 101 (58 females, 43 males, mean age 22.1 ± 2.4 years) were interviewed. Pediatric case notes and, if available (n = 44), current notes were analyzed to validate answers from the interview. Results: After transfer, 52.5% of patients changed their health care provider at least once. The mean frequency of changes was 1.47. There was a significant decrease in clinic attendance rate after transition (8.5 ± 2.3/years vs. 6.7 ± 3.2/years). Patients criticized the lack of arrangements, poor information about transfer and the specific age for transition (18 years) set by legislation. The transfer was considered a negative experience by 58 patients. The patients assumed their metabolic control (HbA1c) was better than it really was (7.5 ± 1.3% vs. 8.3 ± 1.6%, p < 0.05). Actual HbA1c from case notes pre- and post-transfer did not change significantly (8.5 ± 1.5% vs. 8.4 ± 1.7%, n = 44, p = 0.441). Conclusion: The establishment of transition clinics and closer cooperation between specialists in pediatric and adult medicine is mandatory. Such changes are demanded by patients and would ensure better uptake of health care services after transfer.

Type 2 diabetes mellitus in children and adolescents: a review from a European perspective.

Changes in food consumption and exercise are fuelling a worldwide increase in obesity in children and adolescents. As a consequence of this dramatic development, an increasing rate of type 2 diabetes mellitus has been recorded in children and adolescents in the USA and, more recently, in many countries around the world. Both genetic and environmental factors contribute to the pathogenesis of type 2 diabetes. Lower susceptibility in white Caucasians and higher susceptibility in Asians, Hispanics and blacks have been noted. There is a high hidden prevalence and a lack of exact data on the epidemiology of the disease in Europe: in Germany only 70 patients below the age of 15 years were identified in the systematic, nationwide DPV (Diabetessoftware für prospektive Verlaufsdokumentation) diabetes survey, but our calculations suggest that more than 5000 young people in Germany at present would meet the diagnostic criteria of type 2 diabetes. In Australasia, the prevalence of type 2 diabetes is reportedly high in some ethnic groups and again is linked very closely to the obesity epidemic. No uniform and evidence-based treatment strategy is available: many groups use metformin, exercise programmes and nutritional education as a comprehensive approach to treat type 2 diabetes in childhood and adolescence. The lack of clear epidemiological data and a strong need for accepted treatment strategies point to the key role of preventive programmes. Prevention of obesity will help to counteract the emerging worldwide epidemic of type 2 diabetes in youth. Preventive programmes should focus on exercise training and reducing sedentary behaviour such as television viewing, encouraging healthy nutrition and supporting general education programmes since shorter school education is clearly associated with higher rates of obesity and hence the susceptibility of an individual to acquire type 2 diabetes.

Expanded clinical spectrum in hepatocyte nuclear factor 1B-maturity-onset diabetes of the young

AIMS HNF1B-maturity-onset diabetes of the young is caused by abnormalities in the HNF1B gene encoding the transcription factor HNF-1beta. We aimed to investigate detailed clinical features and the type of HNF1B gene anomaly in five pediatric cases with HNF1B-MODY. METHODS From a cohort of 995 children and adolescents with diabetes, we analyzed the most frequent maturity-onset diabetes of the young genes (GCK, HNF1A, HNF4A) including HNF1B sequencing and deletion analysis by quantitative Multiplex-PCR of Short Fluorescent Fragments (QMPSF) if patients were islet autoantibody-negative and had one parent with diabetes or associated extrapancreatic features or detectable C-peptide outside honeymoon phase. Presence and size of disease-causing chromosomal rearrangements detected by QMPSF were further analyzed by array comparative genomic hybridization. RESULTS Overall, five patients had a heterozygous HNF1B deletion, presenting renal disease, elevated liver enzymes, and diabetes. Diabetes was characterized by insulin resistance and adolescent onset of hyperglycemia. Additionally, clinical features in some patients were pancreas dysplasia and exocrine insufficiency (two of five patients), genital defects (three of five), mental retardation (two of five), and eye abnormalities (coloboma, cataract in two of five). One case also had severe growth deficit combined with congenital cholestasis, and another case had common variable immune deficiency. All patients reported here had monoallelic loss of the entire HNF1B gene. Whole genome array comparative genomic hybridization confirmed a precurrent genomic deletion of approximately 1.3-1.7 Mb in size. CONCLUSION The clinical data of our cases enlarge the wide spectrum of patients with HNF1B anomaly. The underlying molecular defect in all cases was a 1.3- to 1.7-Mb deletion, and paired, segmental duplications along with breakpoints were most likely involved in this recurrent chromosomal microdeletion.

Use of complementary and alternative medicine in children with type 1 diabetes mellitus - prevalence, patterns of use, and costs.

Background:  Complementary and alternative medicine (CAM) is increasingly used in adults and children. Studies on CAM in diabetes have mainly focused on the adult population and its use among children with type 1 diabetes has not been well characterized.

Body fat mass, leptin and puberty.

Leptin, the ob gene product, provides a molecular basis for the lipostatic theory of the regulation of energy balance. Leptin circulates as a monomeric 16 kDa protein in rodent and human plasma and is also bound to leptin binding proteins that may form large high molecular weight complexes. Initial models of leptin action included leptin-deficient ob/ob mice and leptin-insensitive db/db mice. Peripheral or central administration of leptin reduced body weight, adiposity, and food intake in ob/ob mice but not in db/db mice. In ob/ob mice leptin treatment restored fertility. Leptin interacts with many messenger molecules in the brain. For example, leptin suppresses neuropeptide Y (NPY) expression in the arcuate nucleus. Increased NPY activity has an inhibitory effect on the gonadotropin axis and represents a direct mechanism for inhibiting sexual maturation and reproductive function in conditions of food restriction and/or energy expenditure. By modulating the hypothalamo-pituitary-gonadal axis both directly and indirectly, leptin may thus serve as the signal from fat to the brain about the adequacy of fat stores for pubertal development and reproduction. Normal leptin secretion is necessary for normal reproductive function to proceed and leptin may be a signal allowing for the point of initiation of and progression toward puberty.

Associations Between Media Consumption Habits, Physical Activity, Socioeconomic Status, and Glycemic Control in Children, Adolescents, and Young Adults With Type 1 Diabetes

OBJECTIVE To evaluate the relationship between media consumption habits, physical activity, socioeconomic status, and glycemic control in youths with type 1 diabetes. RESEARCH DESIGN AND METHODS In the cross-sectional study, self-report questionnaires were used to assess media consumption habits, physical activity, and socioeconomic status in 296 children, adolescents, and young adults with type 1 diabetes. Clinical data and HbA1c levels were collected. Risk factors were analyzed by multiple regression. RESULTS Youths with type 1 diabetes (aged 13.7 ± 4.1 years, HbA1c 8.7 ± 1.6%, diabetes duration 6.1 ± 3.3 years) spent 2.9 ± 1.8 h per day watching television and using computers. Weekly physical activity was 5.1 ± 4.5 h. Multiple regression analysis identified diabetes duration, socioeconomic status, and daily media consumption time as significant risk factors for glycemic control. CONCLUSIONS Diabetes duration, socioeconomic status, and daily media consumption time, but not physical activity, were significant risk factors for glycemic control in youths with type 1 diabetes.

Elevated serum levels of adiponectin in children, adolescents and young adults with type 1 diabetes and the impact of age, gender, body mass index and metabolic control: a longitudinal study

OBJECTIVE Adiponectin plays an important role in pathophysiology of obesity, type 2 diabetes and cardiovascular disease. The aim of this study was to determine adiponectin concentrations in children and adolescents with type 1 diabetes in a longitudinal manner and to study the impact of age, gender, body mass index (BMI) and metabolic control. RESEARCH DESIGN AND METHODS In this study, 88 children and adolescents with type 1 diabetes were followed longitudinally. At baseline and during follow-up, serum levels of adiponectin were measured by enzyme-linked immunoassay and correlated with clinical data, HbA1c and lipids. Healthy children (n = 259) were chosen as a control group. RESULTS Serum adiponectin levels were significantly higher in children with type 1 diabetes compared with healthy children (13.1 vs 9.1 microg/ml at baseline, P < 0.001). Adiponectin concentrations inversely correlated with BMI s.d.s (P < 0.001). No significant difference of adiponectin levels regarding gender, diabetes duration or HbA1c was seen. Adiponectin concentrations decreased in males with type 1 diabetes during puberty (P = 0.03) while there was no significant change in females. In a subgroup of patients with new onset type 1 diabetes, adiponectin concentrations were not different from adiponectin levels in control subjects but increased during follow-up (P = 0.007). Stepwise multiple regression analysis showed that most important predictors of adiponectin levels in type 1 diabetes at the end of the study were adiponectin concentration at baseline (beta = 0.574, P < 0.001) and BMI s.d.s (beta = -0.302, P = 0.001, r2 = 0.56). CONCLUSIONS Children and adolescents with type 1 diabetes have BMI-dependent elevated serum concentrations of adiponectin compared with healthy children.

Increased arterial stiffness in children and adolescents with type 1 diabetes: no association between arterial stiffness and serum levels of adiponectin

Galler A, Heitmann A, Siekmeyer W, Gelbrich G, Kapellen T, Kratzsch J, Kiess W. Increased arterial stiffness in children and adolescents with type 1 diabetes: no association between arterial stiffness and serum levels of adiponectin.