- 期刊
Latent Autoimmune Diabetes in Adults: The Current Understanding and Challenge
成年隱匿型自體免疫糖尿病：當前的認知與挑戰
摘要
Latent autoimmune diabetes in adults (LADA) is the most prevalent form of adult-onset autoimmune diabetes and probably the most prevalent form of autoimmune diabetes in general. It shares clinical and metabolic features with both type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM). Patients with LADA may initially be diagnosed incorrectly as having T2DM based on their age, particularly if they have risk factors for T2DM such as a strong family history or obesity. The diagnosis of LADA is typically based on the finding of hyperglycemia together with the clinical impression that β-cell failure rather than insulin resistance (IR) is the main cause; detection of a low C-peptide and raised antibodies against the islets of Langerhans support the diagnosis. Highly variable β-cell destruction, different degrees of IR and heterogeneous titer and pattern of islet autoantibody, suggesting different pathophysiological pathways partially explaining the heterogeneous phenotypes of LADA. The decline in β-cell function progresses much faster in LADA than in T2DM, presumably because of the ongoing autoimmune assault in LADA, and therefore necessitates insulin therapy much earlier in LADA than in T2DM. The existence of heterogeneous phenotypes in LADA makes it difficult to establish an a priori treatment algorithm, and therefore, an individualized pharmaceutical therapy is required to preserve residual β-cell function and attain optimal diabetic control to decrease the risk of long-term diabetic complications in patients with LADA. This article aims to give an overview of the current understanding and gaps in knowledge regarding epidemiology, clinical and metabolic features, genetics, immunology, complications and therapeutic strategy of LADA and summarize an update on results from recent studies on the treatment of the disease.
並列摘要
成年隱匿型自體免疫糖尿病乃是成人發作型自體免疫糖尿病中盛行率最高的一種疾病，並且可能在自體免疫糖尿病中大體上也是盛行率最高的一種型式。它同時擁有第一型和第二型糖尿病在臨床和代謝方面的特徵。成年隱匿型自體免疫糖尿病起初可能會被誤診斷為第二型糖尿病基於患者的年紀之故，特別是當他們有第二型糖尿病的危險因子時，譬如有強烈的糖尿病家族史或體型肥胖。通常成年隱匿型自體免疫糖尿病的診斷是由於高血糖的發現，同時有胰島細胞衰竭而不是胰島素阻抗為主要病因的臨床臆斷；檢測到低量的C-胜肽鍊胰島素（C-peptide） 和胰臟蘭氏小島（islets of Langerhans） 抗體的產生則有助於該疾病的診斷。高度多面性胰島細胞的破壞、不同程度的胰島素阻抗和異質性力價（heterogeneous titer） 以及胰島細胞自體抗體的型式，暗示不同的病生理學路徑並不能夠完全地可以解釋成年隱匿型自體免疫糖尿病的異質性表現型（phenotypes）。胰島細胞衰竭的程度，在成年隱匿型自體免疫糖尿病的進展會比第二型糖尿病較快上許多，推測可能與進行中的自體免疫攻擊有關，因此啟動胰島素治療的時程，在成年隱匿型自體免疫糖尿病的時間會比在第二型糖尿病還要快上許多。由於成年隱匿型自體免疫糖尿病存在的異質性表現型，因此要建立一個事先治療的流程是有困難的，所以對於成年隱匿型自體免疫糖尿病的患者，需要個別化的治療方式以保存殘存的胰島細胞功能以達到良好的血糖控制進而減少長期糖尿病併發症的風險。本文旨在闡述當前我們對於成年遲發型自體免疫糖尿病整體性的認知，並討論當前其在流行病學、臨床和代謝型態、遺傳學、免疫學、併發症及治療方法在知識上的分歧，並概括更新關於最近研究在成年遲發型自體免疫糖尿病治療方面的結果。