Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Department of Pediatrics, Sanno Hospital, Tokyo, Japan.
J Diabetes Investig. 2022 Sep;13(9):1636-1638. doi: 10.1111/jdi.13827. Epub 2022 Jun 10.
Leptin replacement therapy (LRT) has drastically improved the prognosis of patients with lipodystrophy, but pro-inflammatory properties of leptin could become evident in the long term. Here, we report a 30-year-old Japanese woman with generalized lipodystrophy-associated progeroid syndrome due to a heterozygous LMNA variant (c.29C > T; p.T10I), who was diagnosed with severe aortic stenosis (AS) after more than a decade of LRT, which required transcatheter aortic valve implantation. Given her marked hypoadiponectinemia and the LMNA variant, our patient might have been susceptible to progeria-associated disorders, including aortic stenosis, which could have been exaggerated by the prolonged 'imbalanced adipokines' caused by LRT between pro-inflammatory leptin and anti-inflammatory adiponectin. Thus, long-term LRT could be associated with AS in patients with the LMNA variant to cause generalized lipodystrophy-associated progeroid syndrome and hypoadiponectinemia.
瘦素替代疗法 (LRT) 极大地改善了脂肪营养不良患者的预后，但瘦素的促炎特性可能会在长期内显现出来。在这里，我们报告了一名 30 岁的日本女性，患有由杂合性 LMNA 变异（c.29C>T；p.T10I）引起的全身性脂肪营养不良相关早老综合征，她在接受 LRT 十多年后被诊断出患有严重的主动脉瓣狭窄（AS），需要经导管主动脉瓣植入术。鉴于她明显的脂联素血症和 LMNA 变异，我们的患者可能容易患上早老症相关疾病，包括主动脉瓣狭窄，这可能是由 LRT 引起的“不平衡脂肪因子”（促炎瘦素和抗炎脂联素）长期失衡所导致的。因此，在携带 LMNA 变异的患者中，长期 LRT 可能与 AS 相关，导致全身性脂肪营养不良相关早老综合征和脂联素血症。
