内科学
糖尿病
医学
胃肠病学
丁酸盐
发病机制
胰腺
内分泌学
胰腺切除术
远端胰腺切除术
作者
Tatsuya Fukuda,Ryotaro Bouchi,Takato Takeuchi,Kikuko Amo-Shiinoki,Atsushi Kudo,Shinji Tanaka,Minoru Tanabe,Takumi Akashi,Kazuhiro Hirayama,Toshitaka Odamaki,Miki Igarashi,Ikuo Kimura,Katsuya Tanabe,Yukio Tanizawa,Tetsuya Yamada,Yoshihiro Ogawa
标识
DOI:10.2337/figshare.13626788
摘要
<b>OBJECTIVE</b> <p>To elucidate the pathogenesis of post-pancreatectomy diabetes (PPDM).</p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>Forty-eight patients without diabetes undergoing either pancreatoduodenectomy (PD) (n = 20) or distal pancreatectomy (DP) (n = 28) were included. 75-g oral glucose tolerance test was performed every 6 months. Microbiome composition and short-chain fatty acids in feces were examined before and 6 months after surgery. The association of histological characteristics of the resected pancreas with PPDM were examined.</p> <p><b>RESULTS</b></p> <p>During follow-up (median, 3.19 years), 2 out of 20 PD patients and 16 out of 28 DP patients developed PPDM. Proteobacteria relative abundance, plasma GLP-1, and fecal butyrate levels increased only after PD. Postsurgical butyrate levels were correlated with postsurgical GLP-1 levels. With no significant difference in the volume of the resected pancreas between the surgical procedures, both β-cell and α-cell areas in the resected pancreas were significantly higher in DP patients than in PD patients. In DP patients, the progressors to diabetes showed pre-existing insulin resistance compared with non-progressors, and both increased α- and β-cell areas were predictors of PPDM. Furthermore, in DP patients, α-cell and β-cell areas were associated with ALDH1A3 expression in islets.</p> <p><b>CONCLUSIONS</b></p> We postulate that a greater removal of β-cells contributes to the development of PPDM after DP. Islet expansion along with pre-existing insulin resistance is associated with high cellular-plasticity, which may predict the development of PPDM after DP. In contrast, PD is associated with alterations of gut microbiome and increases in SCFA production and GLP-1 secretion, possibly protecting against PPDM development.
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