Grit Müller

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.

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.

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.

Cortisol and 17-Hydroxyprogesterone Levels in Saliva of Healthy Neonates Normative Data and Relation to Body Mass Index, Arterial Cord Blood pH and Time of Sampling after Birth

The measurement of cortisol and 17-hydroxyprogesterone (17-OHP) in saliva has become a reliable tool for both the scientist and the clinician for studying adrenal cortical function in the adult and the older child. We have now established in parallel normative data for salivary cortisol and 17-OHP levels in healthy neonates. We have asked whether or not there is a circadian rhythm of cortisol and 17-OHP saliva levels in neonates. Furthermore, we have asked whether salivary hormone levels correlated with auxologic and clinical data and time of sampling. Cortisol and 17-OHP levels in saliva samples from 119 healthy neonates (55 girls, 64 boys) were measured using in-house time-resolved fluorescent immunoassays. Saliva samples were obtained using a saliva collecting tube three times a day on the first or second day of life. Gender and gestational age did not influence salivary cortisol and 17-OHP levels. No significant circadian rhythm of salivary hormone levels was detected in this group of newborns. However, body mass index, arterial cord blood pH and time of saliva sampling significantly influenced salivary hormone levels. In conclusion, measurement of cortisol and 17-OHP in saliva is feasible in healthy neonates. The existence of normative data forms the basis for future studies on pathophysiologic states in the newborn period.

Priming with testosterone enhances stimulated growth hormone secretion in boys with delayed puberty

BACKGROUND AND OBJECTIVE Tests for growth hormone (GH) deficiency are not always helpful in the differential diagnosis of physiological delay of growth and puberty and GH deficiency. PATIENTS AND METHODS To enhance diagnostic specificity, we used a single dose testosterone priming before repeating the arginine stimulation test in 26 boys with short stature and only early signs of puberty who failed to show an adequate response of serum GH in the first test. RESULTS 77% (20/26 patients) increased their serum GH peak to more than 10 ng/ml, whereas six patients were still below this concentration. CONCLUSION We propose that testosterone priming is a useful tool to distinguish between physiological delay of growth and puberty and GH deficiency and should be included in the diagnostic procedure.

Prevalence of Obesity and Elevated Blood Pressure as well as Onset of Puberty in German School Children Attending Different Educational Tracks

Background:Obesity and associated comorbidities are increasingly evident in adolescents. This cross-sectional study investigates the relationship between educational level and prevalence of obesity, comorbidities, and onset of puberty in German schoolchildren. Subjects and Methods: 1,488 children from Leipzig attending different types of schools (‘Hauptschule’ or ‘Realschule’, HR, vs. ‘Gymnasium’, GYM) were examined for indices of obesity, pubertal stage and blood pressure. Results: Subjects attending HR had markedly increased body fat compared to age- and gender-matched peers attending GYM. Higher BMIs seen in children attending HR were associated with an earlier onset of puberty. The differences in body fat mass persisted after adjustment for puberty. In addition, children attending HR had higher systolic blood pressure compared to their age- and gender matched peers. This effect vanished when adjusting for BMI. Conclusion:Educational level affects the risk to develop obesity and associated comorbidities already at school age. The strong relationship between the educational track attended and increased BMI as well as elevated blood pressure in schoolchildren implies that comprehensive prevention activities should start already in school age and should be implemented in all educational establishments to target the increasing epidemic of childhood obesity.

Knowing More by Fewer Measurements: About the (In)ability of Bioelectric Impedance to Enhance Obesity Research in Children

The prevalence of obesity is increasing worldwide. The implications for human health can already be observed in children. Consequently, it is desirable to provide good quantitative descriptions of the relationship of body fat and health risks, such as hypertension. Bioelectric impedance analysis has been frequently praised to be useful for assessing body fat. Devices to analyse body composition based on this technique seem to be selling well, while the real gain in information they provide is unclear. Here we show in a cohort of 2,218 schoolchildren that the body mass index (which is more easily and less costly to determine) is a better predictor of hypertension than the data delivered by impedance analysis. Moreover, we demonstrate that the output of a random number generator is competitive with impedance measurement for this purpose. It is explained by simple arguments from physics why the formulas for the computation of body fat from bioelectric impedance obliterate rather than clarify the relationship of obesity and hypertension. As a consequence, we suggest questioning the opinion propagated by others that bioelectric impedance analysis is a useful tool in field studies on body fat in children. Measurements requiring more effort (compared to simpler methods) should be proved to add worthwhile information, otherwise they should be avoided.