Targeting therapy to molecular mechanism of disease in obesity and related metabolic disorders

肥胖及其并发症，如糖尿病，是日益严重的重大公共卫生问题。我们一直在研究与人类肥胖和胰岛素抵抗有关的遗传因素，胰岛素抵抗会导致糖尿病，我们关注的是早期患有这些严重疾病的患者。我们在导致这些疾病的几个基因中发现了缺陷。在一种叫做先天性瘦素缺乏症的疾病中，我们已经能够证明瘦素治疗的显著有益效果。我们现在想研究不同饮食和药物治疗的效果，包括瘦素在其他患者群体中的作用。确定患有已知影响身体关键系统的遗传疾病的患者的治疗反应将有助于我们理解和治疗这些患者，同时也指导我们研究这些重要疾病的更常见形式。

Obesity and its complications such as diabetes are major and growing public health problems. We have been investigating genetic factors involved in human obesity and a condition called insulin resistance which leads to diabetes, by focusing on patients with severe forms of these diseases from an early age. We have found defects in several genes that cause these diseases. In one disease, called congenital leptin deficiency, we have been able to show the dramatically beneficial effects of leptin therapy. We now want to study the effects of different diets and drug treatments including leptin in additional patient groups. Defining treatment responses in patients with a known genetic condition that effects a key system in the body will help us to understand and treat these patients but also guide our approach to the more common forms of these important diseases.