Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of diabetes. Herein, we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates (NHPs) models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 patients. Multi-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and humans. Minor and limited phenotypic and histopathological changes were observed in adult models. Systemic proteomics and metabolomics results indicated metabolic disorders, mainly enriched in insulin resistance pathways, in infected adult NHPs, along with elevated fasting C-peptide and C-peptide/glucose ratio levels. Furthermore, in elder COVID-19 NHPs, SARS-CoV-2 infection causes loss of beta (β) cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis, activation of α-SMA and aggravated fibrosis consisting of lower collagen in serum, an increase of pancreatic inflammation and stress markers, ICAM-1 and G3BP1, along with more severe glycometabolic dysfunction. In contrast, vaccination maintained glucose homeostasis by activating insulin receptor α and insulin receptor β. Overall, the cumulative risk of diabetes post-COVID-19 is closely tied to age, suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.

有证据表明，COVID-19 患者或疫苗与糖代谢功能障碍以及更高的糖尿病发生风险之间存在关联。在此，我们回顾性分析了 2020 年至 2023 年 67 个 SARS-CoV-2 感染的非人灵长类动物 (NHP) 模型和 121 个接种疫苗和感染的 NHP 以及 COVID-19 患者尸检组织中的胰腺病变。多标记免疫荧光显示 NHP 和人类的外分泌和内分泌胰腺细胞均被病毒直接感染。在成人模型中观察到轻微且有限的表型和组织病理学变化。全身蛋白质组学和代谢组学结果表明，受感染的成人 NHP 存在代谢紊乱，主要富集于胰岛素抵抗途径，同时空腹 C 肽和 C 肽/葡萄糖比率水平升高。此外，在老年 COVID-19 NHP 中，SARS-CoV-2 感染会导致 β (β) 细胞损失和原位胰岛素表达降低，其特征是胰岛淀粉样变性和坏死、α-SMA 激活以及由胶原蛋白降低组成的加重纤维化。血清中，胰腺炎症和应激标记物 ICAM-1 和 G3BP1 增加，以及更严重的糖代谢功能障碍。相反，疫苗接种通过激活胰岛素受体α和胰岛素受体β来维持葡萄糖稳态。总体而言，COVID-19后糖尿病的累积风险与年龄密切相关，这表明应更加关注老年COVID-19患者的血糖管理。