Pozzilli Paolo, Pieralice Silvia
Department of Endocrinology & Diabetes, University Campus Bio-Medico, Rome, Italy.
Centre of Immunobiology, Blizard Institute, Barts and the London School of Medicine, Queen Mary, University of London, London, UK.
Endocrinol Metab (Seoul). 2018 Jun;33(2):147-159. doi: 10.3803/EnM.2018.33.2.147.
Autoimmune diabetes is a heterogeneous disease which can arise at any age. Subjects with adult-onset autoimmune diabetes who do not necessitate insulin-therapy for at least 6 months after diagnosis are demarcated as having latent autoimmune diabetes in adults (LADA). This condition is more heterogeneous than young-onset autoimmune diabetes and shares clinical and metabolic characteristics with both type 2 and type 1 diabetes. Patients with LADA are considered by having highly variable β-cell destruction, different degrees of insulin resistance and heterogeneous titre and pattern of islet autoantibody, suggesting different pathophysiological pathways partially explaining the heterogeneous phenotypes of LADA. To date the heterogeneity of LADA does not allow to establish a priori treatment algorithm and no specific guidelines for LADA therapy are available. These subjects are mostly treated as affected by type 2 diabetes, a factor that might lead to the progression to insulin-dependency quickly. A personalised medicine approach is necessary to attain optimal metabolic control and preserve β-cell function to decrease the risk of long-term diabetes complications. Recent data concerning the use of oral antidiabetic agents as dipeptidyl peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists indicate up-and-coming results in term of protect C-peptide levels and improving glycaemic control. This review summarises current knowledge on LADA, emphasising controversies regarding its pathophysiology and clinical features. Moreover, we discuss data available about novel therapeutic approaches that can be considered for prevention of β-cell loss in LADA.
自身免疫性糖尿病是一种可在任何年龄出现的异质性疾病。诊断后至少6个月无需胰岛素治疗的成人迟发性自身免疫性糖尿病患者被界定为成人隐匿性自身免疫性糖尿病(LADA)。这种情况比青少年起病的自身免疫性糖尿病更具异质性,并且与2型和1型糖尿病具有共同的临床和代谢特征。LADA患者被认为具有高度可变的β细胞破坏、不同程度的胰岛素抵抗以及异质性的胰岛自身抗体滴度和模式,提示不同的病理生理途径部分解释了LADA的异质表型。迄今为止,LADA的异质性使得无法建立先验的治疗算法,并且尚无LADA治疗的具体指南。这些患者大多被当作2型糖尿病患者进行治疗,这可能导致其迅速进展为胰岛素依赖。采用个性化医疗方法对于实现最佳代谢控制和保留β细胞功能以降低长期糖尿病并发症风险是必要的。有关使用二肽基肽酶4抑制剂和胰高血糖素样肽1受体激动剂等口服抗糖尿病药物的最新数据表明,在保护C肽水平和改善血糖控制方面有新的成果。本综述总结了目前关于LADA的知识,强调了其病理生理学和临床特征方面的争议。此外,我们讨论了可考虑用于预防LADA患者β细胞丢失的新型治疗方法的现有数据。