Moutschen M P, Scheen A J, Lefebvre P J
Division of Diabetes, Nutrition, and Metabolic disorders, CHU-Sart Tilman, Liège, Belgium.
Diabete Metab. 1992 May-Jun;18(3):187-201.
The reasons why diabetic patients present with an increased susceptibility to frequent and protracted infections remain unclear. The virtual absence of epidemiological studies of the independent risk factors involved contrasts with the multitude of in vitro models focused on the metabolism and function of immune cells from diabetic patients. This review analyzes some of these models and their clinical relevance. The different levels of diabetes pathogenesis: genetic (Type 1), autoimmune (Type 1) and metabolic (Type 1 and Type 2) are responsible for immune abnormalities demonstrated in in vitro models. The participation of genetic and autoimmune factors has been mainly characterized on T lymphocyte function. The B8 DR3 haplotype is associated with several minor immunologic abnormalities in vitro. However, the high frequency of this haplotype in healthy individuals argues against its involvement in significant defects of antimicrobial immunity. Genetic deficiency of C4, present in 25% of Type 1 diabetic patients could, on the other hand, be responsible for opsonization defects against encapsulated pathogens. Several immunological abnormalities related to the autoimmune process preceding the onset of Type 1 diabetes mellitus, such as the depletion of memory CD4+ cells and the defective natural killer activity could transiently impair host defences against viral diseases. Several in vitro functional defects of the immune system have been correlated with the metabolic control of diabetic patients. This suggests the involvement of insulinopenia in some of the abnormalities observed. Insulinopenia-induced enzymatic defects have often been proposed to inhibit energy-requiring functions of phagocytes and lymphocytes. However, the relevance of this mechanism could be confined to patients with extremely severe metabolic abnormalities. The importance of systemic consequences of insulinopenia such as hyperglycaemia and ketosis has also been addressed. Usually, the defects induced in vitro by these factors are slight and require supraphysiologic concentrations of glucose or ketone bodies. Recent studies have shown abnormalities of signal transduction mechanisms in which insulinopenia itself and other factors such as circulating immune complexes could be involved. Despite numerous controversies, many in vitro studies of the immune cells of diabetic patients have demonstrated significant defects which bear quantitative similarities with abnormalities described in other immunodeficiency syndromes. Furthermore, several mechanisms have been proposed to link the different defects observed with the specific infections encountered in diabetic patients.
糖尿病患者为何对频繁且持久的感染易感性增加，原因尚不清楚。对相关独立危险因素的流行病学研究几乎没有，这与众多聚焦糖尿病患者免疫细胞代谢和功能的体外模型形成对比。本综述分析了其中一些模型及其临床相关性。糖尿病发病机制的不同层面：遗传（1型）、自身免疫（1型）和代谢（1型和2型）导致了体外模型中显示的免疫异常。遗传和自身免疫因素的参与主要体现在T淋巴细胞功能上。B8 DR3单倍型与体外一些轻微的免疫异常有关。然而，该单倍型在健康个体中的高频率表明它不太可能参与抗菌免疫的显著缺陷。另一方面，25%的1型糖尿病患者存在的C4基因缺陷可能导致针对包膜病原体的调理缺陷。与1型糖尿病发病前自身免疫过程相关的一些免疫异常，如记忆CD4 +细胞耗竭和自然杀伤活性缺陷，可能会暂时损害宿主对病毒疾病的防御能力。免疫系统的一些体外功能缺陷与糖尿病患者的代谢控制相关。这表明胰岛素缺乏参与了所观察到的一些异常情况。胰岛素缺乏诱导的酶缺陷常被认为会抑制吞噬细胞和淋巴细胞需要能量的功能。然而，这种机制的相关性可能仅限于代谢异常极其严重的患者。胰岛素缺乏的全身后果如高血糖和酮症的重要性也已得到探讨。通常，这些因素在体外诱导的缺陷很轻微，需要超生理浓度的葡萄糖或酮体。最近的研究表明信号转导机制存在异常，胰岛素缺乏本身以及其他因素如循环免疫复合物可能参与其中。尽管存在诸多争议，但许多对糖尿病患者免疫细胞的体外研究已证明存在显著缺陷，这些缺陷在数量上与其他免疫缺陷综合征中描述的异常相似。此外，已经提出了几种机制来将观察到的不同缺陷与糖尿病患者遇到的特定感染联系起来。
