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.

中文翻译：

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严重胰岛素抵抗的遗传综合征。

胰岛素抵抗是世界上最普遍的内分泌紊乱之一，它与全球范围内的主要疾病密切相关，包括糖尿病、动脉粥样硬化、非酒精性脂肪肝和排卵功能障碍。它最常见于肥胖者，但也可能以异常严重的形式出现在具有单基因缺陷的罕见患者中。这些患者可以粗略地分为具有原发性胰岛素信号传导障碍的患者和具有脂肪组织发育或功能缺陷（脂肪营养不良）的患者。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，由不同遗传缺陷引起的临床疾病通常在生化和临床上是不同的，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特定自然病程。然而，在临床实践中，它们经常被漏诊，潜在遗传缺陷的识别率很低，这一问题因命名和分类的混淆和重叠而变得更加复杂。我们现在回顾最近在理解严重胰岛素抵抗和/或脂肪代谢障碍的遗传形式方面的进展，并根据对潜在病理生理学的不断增长的知识提出修订的分类。这意味着对受影响患者的最佳管理应考虑到每种情况的特定自然病程。然而，在临床实践中，它们经常被漏诊，潜在遗传缺陷的识别率很低，这一问题因命名和分类的混淆和重叠而变得更加复杂。我们现在回顾最近在理解严重胰岛素抵抗和/或脂肪代谢障碍的遗传形式方面的进展，并根据对潜在病理生理学的不断增长的知识提出修订的分类。这意味着对受影响患者的最佳管理应考虑到每种情况的特定自然病程。然而，在临床实践中，它们经常被漏诊，潜在遗传缺陷的识别率很低，这一问题因命名和分类的混淆和重叠而变得更加复杂。我们现在回顾最近在理解严重胰岛素抵抗和/或脂肪代谢障碍的遗传形式方面的进展，并根据对潜在病理生理学的不断增长的知识提出修订的分类。