G E N E R A L I N T R O D U C T I O N During the last decades it became evident that the origin of the metabolic syndrome has to be found in childhood and not in adulthood. Originally it was proven by Barker that SGA children are at risk for developing this syndrome in adulthood. Besides, to date the first signs of the syndrome can also be recognized in obese children who are still young. The metabolic impact of obesity is determined by the pattern of lipid partitioning. Lipid storage in insulin sensitive tissues (such as liver and muscle) and in the visceral compartment is associated with a typical metabolic profile characterized by elevated free fatty acids and inflammatory cytokines along-‐ side reduced levels of adiponectin. This combination can lead to peripheral insulin resistance and to endothelial dysfunction. The combination of insulin resistance and early atherogenesis drives the development of altered glucose metabolism and of cardiovascular disease17. Important cardiovascular risk factors in children with obesity are high blood pressure, high cholesterol level, high LDL-‐cholesterol level and low HDL cholesterol level. An association has been described between asthma and obesity, especially during puberty. One of the possible mechanisms is that obesity represents a proinflamma-‐ tory state, and leptin levels influence Th1 cytokine responses23. Also skin disorders can be a consequence of the metabolic syndrome like acan-‐ thosis nigricans. Acanthosis nigricans is associated to hyperinsulinemia. Common sites of involvement include the axillae, posterior region of the neck, antecubital fossae, and groins23. The lesion represents a thickening of the stratum corneum that becomes pigmented in a racially dependent manner. As well insulin as IGF-‐I recep-‐ tors have been identified in cultured human keratinocytes. High levels of insulin can activate both receptors25. Additionally, TNF-‐α and IFNγ cytokines that are often elevated in obesity, can induce up-‐regulation of PPARβ/δ and thereby keratinocyte proliferation26,27. Other skin problems associated with obesity are striae, plantar hyperkeratosis, acrochordons, intertrigo, pseudoacanthosis nigricans, keratosis pilaris, lymphedema and bacterial infections. The presence of striae, pseudoacan-‐ thosis nigricans and bacterial infections may correlate with the degree of obesity28. Psoriasis has been recognized as a systemic disease, associated with metabolic syndrome, type II diabetes, hypertension, dyslipidemia and obesity29-‐34. Further evidence indicates that overweight is a risk factor for the onset of psoriasis and that the BMI is correlated to the PASI (Psoriasis Area Severity Index)28. Small for gestational age children Risk groups for the development of obesity, are SGA children and children suffering from growth hormone deficiency (GHD). The concept of the development of health and disease (DOHaD) of David Barker relates diseases of adulthood like obesity to fetal programming: “The nourishment a baby receives from its mother, and its ex-‐ 15
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