脂肪营养不良综合征培训课件.ppt

1、本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。definition and classificationClinical Findings of the Major Lipodystrophy SubtypesClinical CharacteristicsstructureDiagnosisTherapies本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。definition andClassification本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或

2、本人删除。A heterogeneous group of congenital or acquired disorders characterized by either complete or partial lack of adipose tissue，which may occur in conjunction with pathological accumulation of fat in other distinct regions of the body，Belonged to the autonomic nervous system diseases definition3本文

3、档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。classification congenital generalized lipodystrophy(CGL)acquired generalized lipodystrophy(AGL)acquired partial lipodystrophy(APL)familial partial lipodystrophy(FPL)HAART-associated lipodystrophy syndrome本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。CG

4、L(先天性全身脂肪营养不良),or Berardinelli-Seip syndrome（伯拉迪尼-塞普综合征）,is an autosomal recessive常染色体隐性遗传 disorder characterized by a generalized lack of adipose tissue at birth or shortly thereafter(within the first year of life),and is accompanied by prominent muscularity and subcutaneous veins.Congenital Genera

5、lized Lipodystrophy5本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。In early childhood,patients with CGL may exhibit hyperphagia 食欲过盛(possibly a manifestation of underlying leptin deficiency),accelerated linear growth,advanced bone age骨龄超前,or acromegaloid features(enlarged hands,feet,and mandible),w

6、hile later in childhood,acanthosis nigricans黑棘皮症 can develop and become widespread.Hyperinsulinemia and hypertriglyceridemia高胰岛素血症和高甘油三酯血症 can occur at an early age,with ketosis-resistant diabetes mellitus酮症性糖尿病 usually developing later in adolescence.Congenital Generalized Lipodystrophy6本文档所提供的信息仅供

7、参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Hepatomegaly from severe hepatic steatosis is common and can progress to steatohepatitis脂肪性肝炎,cirrhosis,and liver failure.females with CGL may have hirsutism,clitoromegaly,irregular menstrual periods,polycystic ovaries,and/or infertility.There are at least three

8、kinds of disease-causing genes,clinically divided into three subtypes:CGL1,CGL2,CGL3.95%of CGL for the first two subtypes,and mutations associated基因突变 AGPAT2 and BSCL2.Congenital Generalized Lipodystrophy7本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Congenital Generalized Lipodystrophy Congenital

9、 generalized lipodystrophy in A,a 6-month-old infant with promi-nent muscularity and veins,B,a 16-year-old girl with acanthosis nigricans and umbilical prominence,C,a 15-year-old boy with umbilical prominence and otherwise normal appearing muscular habitus.本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或

10、本人删除。AGL(获得性全身脂肪营养不良),or Lawrence syndrome(劳伦斯综合征),in contrast to CGL,patients with AGL are born with normal fat distribution but lose fat in a generalized fashion,typically starting in childhood or adolescence(rarely beginning after 30 years of age)acquired generalized lipodystrophy 9本文档所提供的信息仅供参考之

11、用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Progressive fat loss usually occurs over a period of months to years,or as rapid as a few weeks for some patients,and affects large areas of the body,especially the face and extremities(including the palms and soles).Intra-abdominal fat loss is vari-able,and there m

12、ay be sparing of bone marrow骨髓 and retroorbital眶后的 fat.acquired generalized lipodystrophy 10本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。In some patients,the onset of AGL is heralded by the development of subcutaneous inflammatory nodules皮下炎性结节(panniculitis);AGL occurs in approximately 3 times as

13、 many women as men.In a case series of 79 patients,AGL was classified into panniculitis-associated脂膜炎(25%of cases),autoimmune自身免疫(25%),and idiopathic types特发性(50%)on the basis of clinical findings.Autoimmune diseases,especially juvenile dermatomyositis儿童皮肌炎 and autoimmune hepatitis,occur commonly wi

14、th AGL,suggesting that AGL could represent an autoimmune disease itself,but the inciting factors(autoantigens or effector mechanisms)remain to be elucidated.acquired generalized lipodystrophy 11本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。acquired generalized lipodystrophy Acquired generalized li

15、podystrophy(AGL)in A,a 19-year-old woman,B,a 9-year-old girl with juvenile dermatomyositis.Some common features among the 2 cases include lack of body fat and acanthosis nigricans,as well as abdominal protuberance.12本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。For both CGL and AGL,the presentatio

16、n of diabetes in association with clinical evidence of insulin resistance胰岛素抵抗(e.g.,high triglyceride levels)in a nonobese pediatric patient should serve as key distinguishing features from type 1 diabetes.it is important to recognize that patients with all forms of generalized lipodystrophy can dev

17、elop ketoacidosis酮症酸中毒,especially under severe metabolic stress.generalized lipodystrophy 13本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。FPL（家族性部分脂肪营养不良）is predominantly inherited in an autosomal dominant 常染色体显性遗传fashion.Patients with FPL usually have normal body fat distribution during infancy a

18、nd early childhood,but,beginning around or after puberty青春期,typically develop variable and progressive loss of subcutaneous fat in the arms and legs resulting in a peripheral muscular appearance with variable loss of fat in the anterior abdomen and chest.Familial Partial Lipodystrophy14本文档所提供的信息仅供参考

19、之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Many patients(especially women)have fat accumulation in the face,neck,and intra-abdominal region,which may lead to a Cushingoid 类库欣appearance.Familial Partial Lipodystrophy15本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Diabetes is more common and more severe in

20、women than in men,particularly among multiparous women with excessive intra-abdominal fat deposition.Most affected women are able to reproduce normally,although some may develop hirsutism多毛 and menstrual irregularities.Familial Partial Lipodystrophy16本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。H

21、ypertriglyceridemia is a common finding in FPL and can be severe,potentially leading to acute pancreatitis急性胰腺炎,while hepatic steatosis and acanthosis nigricans 肝脂肪变性和黑棘皮病may be less clinically impressive than that occurring in patients with generalized forms of lipodystrophy.Finally,some patients w

22、ith FPL may develop myopathy肌病,cardiomyopathy心肌病,and/or conduction system abnormalities传导系统障碍。Familial Partial Lipodystrophy17本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Familial Partial LipodystrophyFamilial partial lipodystrophy in 2 sisters.Both patients are in their early thirties.The patien

23、t on the left has diabetes mellitus,while the patient on the right is nondiabetic.Note increased fat accumulation in the face and neck(A)with subcutaneous fat loss and muscularity in the arm(B).18本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。APL（获得性部分脂肪营养不良）is characterized by a progressive loss o

24、f subcutaneous fat over months to years from the face,neck,arms,thorax,and upper abdomen during childhood or adolescence.Some patients may have excess fat accumulation over the lower abdomen,gluteal region,and legs.Metabolic complications代谢并发症 are less common with APL than with other lipodystrophy s

25、ubtypes亚型.Acquired Partial Lipodystrophy19本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。The main cause of morbidity appears to be chronic renal disease(especially membranoproliferative glomeru-lonephritis膜性增生性肾小球肾炎).APL has also been associated with a number of autoimmune diseases,including dermat

26、omyositis皮肌炎 and systemic lupus erythematosus系统性红斑狼疮.Most patients with APL have low levels of serum complement 3(C3)accompanied by detectable levels of a circulating autoantibody自身抗体,C3 nephritic factor.APL is also more common in women than in men(estimated 4:1 ratio)Acquired Partial Lipodystrophy2

27、0本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Acquired Partial Lipodystrophy21本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。HIV infection can occur in patients receiving highly fat nutrition during anti-retroviral therapy(highly active antiretroviral therapy,HAART)高效抗反转录病毒治疗,especially when the

28、 application of HIV-1 protease inhibitor poor HIV-1 蛋白酶抑制剂,the incidence of up to 40%to 70%,is the most common type of lipodystrophy.HAART-associated lipodystrophy syndrome22本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Although HAART significantly reduced mortality病死率 in patients with HIV infecti

29、on,but HAART-related lipodystrophy(HAART-associated lipodystrophy syndrome,HALS)and secondary metabolism AIDS treatment has become the most important adverse reactions.HALS general performance of the face,extremities,buttocks fat atrophy,and lower abdomen,neck and back fat accumulation.HAART-associa

30、ted lipodystrophy syndrome23本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Risks associated with advanced age HALS occur,the severity of HIV infection,the viral load increases,while low CD4 count and viral hepatitis-related.HALS increased the incidence of AIDS in patients with insulin resistance,di

31、abetes,dyslipidemia and cardiovascular 心血管疾病disease.The exact pathogenesis of HALS is not very clear,may be related to protease inhibitors(protease inhibitors,PIs蛋白酶抑制剂)of mitochondrial toxicity线粒体毒性,and PIs also by down-regulation of fat cell transcription factor(PPAR and C/EBP-)of the expression o

32、f fat cell differentiation.HAART-associated lipodystrophy syndrome24本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。HAART-associated lipodystrophy syndrome25本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Clinical Findings of the Major Lipodystrophy Subtypes26本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系

33、网站或本人删除。Clinical Findings of the Major Lipodystrophy Subtypes27本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Clinical Characteristics In one study of over 5000 Dutch patients with diabetes from 3 outpatient clinics where 2 screening criteria were applied(body mass index 27 kg/m2 and use of 100 uni

34、ts of insulin/day),12 out of 24 patients meeting these criteria had further characterization,5 of whom were eventually diagnosed with FPL(3 with confirmed genetic mutations基因突变).本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Clinical Characteristics Although lipodystrophy is often accompanied by me

35、tabolic abnormalities代谢障碍,not all patients manifest them on presentation.Clinical laboratory testing(i.e.,blood glucose,glycated hemoglobin HbA1c,triglyceride level甘油三酯,liver function studies肝功能,etc.)on initial evaluation of the patient with suspected lipodystrophy may still be useful for providing

36、a baseline from which to monitor development of future metabolic abnormalities(if not already present),and should be considered the standard of care.本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Diagnosis1.caliper measurements卡尺测量 of skinfold thickness皮肤褶皱厚度 may be helpful to quantify or character

37、ize fat loss.Approximately 90%of adult men and women will have skinfold thickness values 10 mm and 22 mm;lower thickness values are supportive information for the diagnosis of lipodystrophy.2.When fat loss is not visibly evident by physical manifestations,hyperglycemia高血糖 and hypertriglyceridemia高甘油

38、三脂血症 that are resistant or unresponsive to conventional treatment may serve as the only indication to the clinician that a patient may have lipodystrophy.本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Diagnosis3.Lipodystrophy is typically accompanied by low(or relatively low)levels of the adipocyte

39、-secreted hormone leptin.leptin levels may provide useful supportive information,but are not necessary or specific for the diagnosis of lipodystrophy,as low leptin levels may be observed in other conditions(e.g.,hypothalamic amenorrhea下丘脑性闭经and malnutrition).4.lipodystrophy may also present with ass

40、ociated neuroendocrine神经内分泌 and immunological abnormalities免疫异常(e.g.,amenorrhea and a relative deficiency of T lymphocyte populationsT淋巴细胞缺乏)本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Therapies1.lifestyle modifications(diet and exercise)2.conventional antihyperglycemic and lipid-lowering edicat

41、ions Metformin二甲双胍,sulfonylureas磺脲类,thiazolidinediones噻唑烷二酮,and insulin can be used to manage hyperglycemia,while fibrates贝特类 and statins他汀类 can be used to manage hypertriglyceridemia.Where metabolic abnormalities代谢异常 associated with lipodystrophy are particularly severe,conventional treatments,alon

42、e or in combination,are likely to be inadequate at re-establishing metabolic control.本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Therapies3.Plasmapheresis血浆置换 for lowering dangerously high triglyceride levels to control painful xanthoma黄瘤 and prevent pancreatitis胰腺炎.4.Leptin replacement therapy瘦

43、素替代疗法 sustain reductions in triglyceride甘油三酯,total cholesterol总胆固醇,and HbA1c levels.Metreleptin美曲普汀,a human leptin analog,is currently under review by the U.S.FDA for the treatment of certain metabolic abnormalities associated with lipodystrophy.本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Therapies5.cosmetic美容 management of disfigurements(fat loss,fat redistribution,and outward manifestations of insulin resistance)that can severely impact patient self-image and sense of well-being.6.Roux-en-Y gastric bypass空肠-胃旁路手术本文档所提供的信息仅供参考之用，不能作为科学依据，请勿模仿；如有不当之处，请联系网站或本人删除。Thank you！