Owen Katharine R
University of Oxford, UK.
Best Pract Res Clin Endocrinol Metab. 2016 Jun;30(3):455-67. doi: 10.1016/j.beem.2016.05.002. Epub 2016 May 27.
It is increasingly recognised that diabetes in young adults has a wide differential diagnosis. There are many monogenic causes, including monogenic beta-cell dysfunction, mitochondrial diabetes and severe insulin resistance. Type 2 diabetes in the young is becoming more prevalent, particularly after adolescence. It's important to understand the clinical features and diagnostic tools available to classify the different forms of young adult diabetes. Classic type 1 diabetes is characterised by positive β-cell antibodies and absence of endogenous insulin secretion. Young type 2 diabetes is accompanied by metabolic syndrome with obesity, hypertension and dyslipidaemia. Monogenic β-cell dysfunction is characterised by non-autoimmune, C-peptide positive diabetes with a strong family history, while mitochondrial diabetes features deafness and other neurological involvement. Severe insulin resistance involves a young-onset metabolic syndrome often with a disproportionately low BMI. A suspected diagnosis of monogenic diabetes is confirmed with genetic testing, which is widely available in specialist centres across the world. Treatment of young adult diabetes is similarly diverse. Mutations in the transcription factors HNF1A and HNF4A and in the β-cell potassium ATP channel components cause diabetes which responds to low dose and high dose sulfonylurea agents, respectively, while glucokinase mutations require no treatment. Monogenic insulin resistance and young-onset type 2 diabetes are both challenging to treat, but first line management involves insulin sensitisers and aggressive management of cardiovascular risk. Outcomes are poor in young-onset type 2 diabetes compared to both older onset type 2 and type 1 diabetes diagnosed at a similar age. The evidence base for treatments in monogenic and young-onset type 2 diabetes relies on studies of moderate quality at best and largely on extrapolation from work conducted in older type 2 diabetes subjects. Better quality, larger studies, particularly of newer agents would improve treatment prospects for young adults with diabetes.
越来越多的人认识到,年轻成年人患糖尿病的鉴别诊断范围很广。有许多单基因病因,包括单基因β细胞功能障碍、线粒体糖尿病和严重胰岛素抵抗。年轻人群中的2型糖尿病正变得越来越普遍,尤其是在青春期之后。了解可用于区分不同类型年轻成年人糖尿病的临床特征和诊断工具非常重要。经典1型糖尿病的特征是β细胞抗体呈阳性且缺乏内源性胰岛素分泌。年轻的2型糖尿病伴有肥胖、高血压和血脂异常的代谢综合征。单基因β细胞功能障碍的特征是具有强烈家族史的非自身免疫性、C肽阳性糖尿病,而线粒体糖尿病的特征是耳聋和其他神经受累。严重胰岛素抵抗涉及通常BMI极低的早发性代谢综合征。通过基因检测可确诊疑似单基因糖尿病,这种检测在世界各地的专科中心广泛开展。年轻成年人糖尿病的治疗同样多种多样。转录因子HNF1A和HNF4A以及β细胞钾ATP通道成分的突变分别导致对低剂量和高剂量磺脲类药物有反应的糖尿病,而葡萄糖激酶突变则无需治疗。单基因胰岛素抵抗和早发性2型糖尿病的治疗都具有挑战性,但一线治疗包括胰岛素增敏剂和积极管理心血管风险。与年龄较大时发病的2型糖尿病和在相似年龄诊断的1型糖尿病相比,早发性2型糖尿病的预后较差。单基因和早发性2型糖尿病治疗的证据基础充其量依赖于中等质量的研究,并且很大程度上是从对老年2型糖尿病患者进行的研究推断而来。开展质量更高、规模更大的研究,尤其是对新型药物的研究,将改善年轻糖尿病患者的治疗前景。