JCEM:糖尿病对肢端肥大症患者发病率和死亡率的影响

2022-08-08 从医路漫漫 MedSci原创

肢端肥大症的主要治疗是手术切除产生生长激素的腺瘤,但大约一半的患者需要额外的药物治疗和/或放射治疗。

背景:肢端肥大症是由生长激素(GH)过度分泌引起的,通常来自良性的GH分泌型垂体腺瘤,导致胰岛素样生长因子I (IGF-I)水平升高。生长激素和IGF-I长期过量会导致全身共病和死亡率增加,主要是由于心血管疾病。生长激素/IGF-I水平、诊断延迟、年龄和高血压曾被描述为肢端肥大症患者死亡的主要决定因素。因此,治疗肢端肥大症的目标是实现生化缓解和治疗相关的合并症。葡萄糖代谢受损是肢端肥大症的常见并发症,糖尿病的患病率在19%至56%之间。肢端肥大症的糖尿病风险主要是由生长激素诱导的胰岛素抵抗引起的,生长激素直接减弱胰岛素信号并刺激脂肪分解,导致游离脂肪酸增加,从而增加肝脏糖异生并减少外周组织的葡萄糖摄取。

肢端肥大症的主要治疗是手术切除产生生长激素的腺瘤,但大约一半的患者需要额外的药物治疗和/或放射治疗。一线药物治疗是生长抑素类似物,可减少生长激素分泌,也可能减少肿瘤残留;然而,它也会减少胰岛素分泌,因此可能会在易感患者中诱发糖尿病。2型糖尿病与死亡和心血管疾病的额外风险有关,这与代谢控制、糖尿病持续时间和糖尿病相关并发症有关,如大血管疾病、肾病、神经病变和视网膜病变。伴发糖尿病如何以及在多大程度上影响肢端肥大症患者的发病率和死亡率尚不清楚。

目的:研究糖尿病是否影响肢端肥大症患者的发病率和死亡率。

设计:全国性(瑞典)观察性配对队列研究。方法:1987年至2020年间诊断为肢端肥大症的患者在瑞典国家患者注册中心进行识别,同时伴有二型糖尿病的患者在国家糖尿病注册中心和药物注册中心进行识别。使用Cox回归估计总死亡率、心血管死亡率和发病率的风险。

结果:该研究包括254例肢端肥大症伴二型糖尿病患者(肢端糖尿病组)和532例非糖尿病患者(肢端糖尿病组)。在ACRO-DM组和ACRO组中,基线时的平均(SD)年龄分别为62.6 (11.4)和60.0 (12.1)岁(P = 0.004),肢端肥大症的平均(SD)持续时间分别为6.8 (8.1)和6.0 (6.2)年(P = 0.098)。总体平均随访时间为9.2年。各组每1000人年的未调整总死亡率分别为35.1 (95%可信区间:27.2–44.7)和20.1 (95%可信区间:16.5–24.3)。与ACRO组相比,ACRO-DM组校正多重混杂因素后总死亡率的风险比为1.58(95% CI:1.12–2.23)。ACRO-DM组的心血管死亡率[HR 2.11(95% CI:1.09–4.10)]和发病率[HR 1.49(95% CI:1.21–1.82)]也有所增加。

表1 包含在倾向评分模型中的变量和调整后获得的SMD

表2 在整个研究期间治疗肢端肥大症。数据为n (%)。

表3肢端肥大症和二型糖尿病患者与无糖尿病肢端肥大症患者的总体死亡率、心血管死亡率和发病率的风险比

图1总死亡率、心血管死亡率和发病率的风险比。肢端肥大症和二型糖尿病患者与无糖尿病肢端肥大症患者相比,未调整和完全调整的倾向评分风险比。CV,心血管。

图2全因死亡率的卡普兰-迈耶图。(A)肢端肥大症和二型糖尿病患者与无糖尿病的肢端肥大症患者相比的未调整和(B)完全倾向评分调整图。

结论:肢端肥大症患者中糖尿病的存在与总体死亡率增加以及心血管死亡率和发病率增加相关。

原文出处:Esposito D,  Olsson DS,  Franzén S,et al.Impact of Diabetes on Morbidity and Mortality in Patients with Acromegaly.J Clin Endocrinol Metab 2022 Jul 02

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    2022-12-15 smallant2015
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    2022-08-14 achengzhao
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血压较低和较高的患者之间可能出现基线特征不平衡(如疾病严重程度或共病),这可能会使研究结论产生偏差。