脂肪组织的原发性疾病是由于脂肪组织的生理功能(脂质储备和内分泌功能)受损而导致的罕见疾病。主要是指皮下脂肪组织萎缩和/或脂肪组织的身体分布改变导致胰岛素抵抗的脂肪营养不良综合征。糖尿病,肝脂肪变性,血脂异常,女性心血管并发症和多囊卵巢综合征。这些综合征是先天性或获得性的,和脂肪萎缩是部分或广泛的。脂肪代谢障碍综合征的诊断通常无法识别,延迟和/或不准确,虽然调整调查以寻找特定的合并症非常重要,特别是心血管受累,建立多学科护理,在某些情况下,还有特定的治疗方法。医师必须认识到允许建立诊断的临床和生物学因素。应该考虑脂肪营养不良综合征,特别是,在年轻的糖尿病患者中,BMI正常或低,阴性胰腺自身抗体,呈现脂肪营养不良和胰岛素抵抗的临床症状(黑棘皮病,雄激素过多症,肝脂肪变性,高胰岛素剂量)。糖尿病与严重和/或早期心血管疾病家族史(冠状动脉粥样硬化,有节律和/或传导障碍的心肌病)可能会显示邓尼根综合征,家族性脂肪营养不良最常见的形式,由于LMNA致病变异。临床评估主要通过临床检查完成:黑棘皮病,脂肪组织分布异常,脂肪萎缩,肌肉肥大,肢端类或库欣类动物特征,脂肪瘤,高度可见的皮下静脉,可能是显露出来的迹象。循环脂肪因子的量可能反映了低瘦素血症和脂联素血症的脂肪功能障碍。其他生物代谢参数(高甘油三酯血症,高胰岛素血症,高血糖和肝酶)也可能代表胰岛素抵抗的标志物。通过阻抗测量法或双光子X射线吸收法(DEXA)对总脂肪进行定量显示,总体重下降,与脂肪组织萎缩相关;代谢磁共振成像还可以量化腹膜内和腹部脂肪以及肝脏脂肪变性的程度。显示结构异常的脂肪组织的组织学分析应保留用于临床研究。获得性脂肪营养不良综合征通常导致与全身性或部分性脂肪萎缩的先天性综合征相似的临床表型。最常见的原因是旧的抗HIV治疗或糖皮质激素治疗。家族史,治疗史和临床检查,包括仔细的体检,是诊断的关键。
Primary diseases of adipose tissue are rare disorders resulting from impairments in the physiological functions of adipose tissue (lipid stockage and endocrine function). It mainly refers to lipodystrophy syndromes with subcutaneous adipose tissue atrophy and/or altered body distribution of adipose tissue leading to insulin resistance, diabetes, hepatic steatosis, dyslipidemia, cardiovascular complications and polycystic ovary syndrome in women. Those syndromes are congenital or acquired, and lipoatrophy is
partial or generalized. The diagnosis of lipodystrophy syndromes is often unrecognized, delayed and/or inaccurate, while it is of major importance to adapt investigations to search for specific comorbidities, in particular cardiovascular involvement, and set up multidisciplinary care, and in some cases specific treatment. Physicians have to recognize the clinical and biological elements allowing to establish the diagnosis. Lipodystrophic syndromes should be considered, notably, in patients with diabetes at a young age, with a normal or low BMI, negative pancreatic autoantibodies, presenting clinical signs of lipodystrophy and insulin resistance (acanthosis nigricans, hyperandrogenism, hepatic steatosis, high insulin doses). The association of diabetes and a family history of severe and/or early cardiovascular disease (coronary atherosclerosis, cardiomyopathy with rhythm and/or conduction disorders) may reveal Dunnigan syndrome, the most frequent form of familial lipodystrophy, due to LMNA pathogenic variants. Clinical assessment is primarily done through clinical examination: acanthosis nigricans, abnormal adipose tissue distribution, lipoatrophy, muscular hypertrophy, acromegaloid or Cushingoid features, lipomas, highly visible subcutaneous veins, may be revealing signs. The amount of circulating adipokines may reflect of adipose dysfunction with low leptinemia and adiponectinemia. Other biological metabolic parameters (hypertriglyceridemia, hyperinsulinemia, increased glycemia and hepatic enzymes) may also represent markers of insulin resistance. Quantification of total body fat by impedancemetry or dual-photon X-ray absorptiometry (DEXA) reveals decreased total body mass, in correlation with adipose tissue atrophy; metabolic magnetic resonance imaging can also quantify intraperitoneal and abdominal fat and the degree of hepatic steatosis. Histological analysis of adipose tissue showing structural abnormalities should be reserved for clinical research. Acquired lipodystrophic syndromes most often lead to similar clinical phenotype as congenital syndromes with generalized or
partial lipoatrophy. The most frequent causes are old anti-HIV therapy or glucocorticoid treatments. Family history, history of treatments and clinical examination, including a careful physical examination, are keys for diagnosis.