Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
Endocr Rev. 2011 Aug;32(4):498-514. doi: 10.1210/er.2010-0020. Epub 2011 May 2.
Insulin resistance is among the most prevalent endocrine derangements in the world, and it is closely associated with major diseases of global reach including diabetes mellitus, atherosclerosis, nonalcoholic fatty liver disease, and ovulatory dysfunction. It is most commonly found in those with obesity but may also occur in an unusually severe form in rare patients with monogenic defects. Such patients may loosely be grouped into those with primary disorders of insulin signaling and those with defects in adipose tissue development or function (lipodystrophy). The severe insulin resistance of both subgroups puts patients at risk of accelerated complications and poses severe challenges in clinical management. However, the clinical disorders produced by different genetic defects are often biochemically and clinically distinct and are associated with distinct risks of complications. This means that optimal management of affected patients should take into account the specific natural history of each condition. In clinical practice, they are often underdiagnosed, however, with low rates of identification of the underlying genetic defect, a problem compounded by confusing and overlapping nomenclature and classification. We now review recent developments in understanding of genetic forms of severe insulin resistance and/or lipodystrophy and suggest a revised classification based on growing knowledge of the underlying pathophysiology.
胰岛素抵抗是世界上最常见的内分泌紊乱之一，它与糖尿病、动脉粥样硬化、非酒精性脂肪肝和排卵功能障碍等具有全球影响力的主要疾病密切相关。它最常见于肥胖者，但在罕见的单基因缺陷患者中，也可能以异常严重的形式发生。这些患者可以大致分为胰岛素信号的原发性疾病和脂肪组织发育或功能（脂肪萎缩症）的缺陷。这两个亚组的严重胰岛素抵抗使患者面临加速并发症的风险，并对临床管理提出了严峻挑战。然而，不同遗传缺陷引起的临床疾病在生化和临床上往往是不同的，并且与不同的并发症风险相关。这意味着对受影响患者的最佳管理应考虑到每种情况的具体自然病史。然而，在临床实践中，这些疾病经常被漏诊，而且对潜在遗传缺陷的识别率很低，这一问题因命名法和分类的混乱和重叠而更加复杂。我们现在回顾了对严重胰岛素抵抗和/或脂肪萎缩症的遗传形式的理解的最新进展，并根据对潜在病理生理学的不断增长的认识提出了一种经过修订的分类。
