Misra Anoop, Garg Abhimanyu
Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, 75390, USA.
Medicine (Baltimore). 2003 Mar;82(2):129-46. doi: 10.1097/00005792-200303000-00007.
We present clinical descriptions, metabolic features, and patterns of body fat loss of 16 patients with acquired generalized lipodystrophy (AGL) seen by us over the last 10 years. In addition, we review 63 cases of AGL reported in the literature. Based on these data, we propose new diagnostic criteria for AGL, the essential criterion being selective loss of body fat from large regions of the body occurring after birth. We also propose a subclassification of AGL into 3 varieties, type 1, the panniculitis variety; type 2, the autoimmune disease variety; and type 3, the idiopathic variety, which affect nearly 25%, 25%, and 50% of patients, respectively. Most of the patients presented in childhood and adolescence. Females were affected approximately 3 times more than males. Subcutaneous fat loss was severe and usually affected the face, trunk, abdomen, and extremities. In some patients, fat loss also involved the palms and soles and intraabdominal region; however, the bone marrow and retroorbital fat were preserved in all patients. Clinically, patients may have voracious appetite, fatigue, and acanthosis nigricans. Hepatomegaly was common, mostly due to hepatic steatosis. Most AGL patients had fasting and/or postprandial hyperinsulinemia, diabetes mellitus, hypertriglyceridemia, and low serum levels of high-density lipoprotein cholesterol, leptin, and adiponectin. Diabetes mellitus and hypertriglyceridemia were less prevalent in the panniculitis variety compared with the idiopathic and autoimmune varieties. The management of AGL includes cosmetic surgery for loss of fat. Severe hypertriglyceridemia should be treated with a very low-fat diet and omega-3 polyunsaturated fatty acid supplementation from fish oils. Management of diabetes is difficult and may necessitate insulin therapy in large doses. Insulin sensitizers such as metformin and thiazolidinediones have been used, although their long-term efficacy and safety remain unknown. Subcutaneous administration of recombinant leptin in AGL patients with hypoleptinemia effectively improves hyperglycemia, hypertriglyceridemia, and hepatic steatosis. Leptin therapy, however, remains investigational. Fibrates alone or in combination with statins may be used to treat hypertriglyceridemia.
我们介绍了过去10年里我们所诊治的16例获得性全身性脂肪营养不良（AGL）患者的临床描述、代谢特征及体脂丢失模式。此外，我们还回顾了文献中报道的63例AGL病例。基于这些数据，我们提出了AGL的新诊断标准，基本标准是出生后身体大面积区域的体脂选择性丢失。我们还提出将AGL分为3个亚型，1型为脂膜炎型；2型为自身免疫病型；3型为特发型，分别影响近25%、25%和50%的患者。大多数患者在儿童期和青春期发病。女性受影响的人数约为男性的3倍。皮下脂肪丢失严重，通常累及面部、躯干、腹部和四肢。在一些患者中，脂肪丢失还涉及手掌、足底和腹腔内区域；然而，所有患者的骨髓和眶后脂肪均得以保留。临床上，患者可能有食欲亢进、疲劳和黑棘皮病。肝肿大很常见，主要是由于肝脂肪变性。大多数AGL患者有空腹和/或餐后高胰岛素血症、糖尿病、高甘油三酯血症以及血清高密度脂蛋白胆固醇、瘦素和脂联素水平降低。与特发型和自身免疫病型相比，脂膜炎型糖尿病和高甘油三酯血症的患病率较低。AGL的治疗包括针对脂肪丢失的整形手术。严重的高甘油三酯血症应采用极低脂肪饮食和补充鱼油中的ω-3多不饱和脂肪酸进行治疗。糖尿病的治疗很困难，可能需要大剂量胰岛素治疗。已使用二甲双胍和噻唑烷二酮类等胰岛素增敏剂，但其长期疗效和安全性尚不清楚。对于低瘦素血症的AGL患者，皮下注射重组瘦素可有效改善高血糖、高甘油三酯血症和肝脂肪变性。然而，瘦素治疗仍处于研究阶段。贝特类药物单独或与他汀类药物联合使用可用于治疗高甘油三酯血症。
