TY - JOUR
T1 - Importance of Intestinal Environment and Cellular Plasticity of Islets in the Development of Postpancreatectomy Diabetes
AU - Fukuda, Tatsuya
AU - Bouchi, Ryotaro
AU - Takeuchi, Takato
AU - Amo-Shiinoki, Kikuko
AU - Kudo, Atsushi
AU - Tanaka, Shinji
AU - Tanabe, Minoru
AU - Akashi, Takumi
AU - Hirayama, Kazuhiro
AU - Odamaki, Toshitaka
AU - Igarashi, Miki
AU - Kimura, Ikuo
AU - Tanabe, Katsuya
AU - Tanizawa, Yukio
AU - Yamada, Tetsuya
AU - Ogawa, Yoshihiro
N1 - Funding Information:
Acknowledgments.Theauthorsthankallofthe staff of Department of Molecular Endocrinology and Metabolism, Department of Hepatobiliary and Pancreatic Surgery, and Department of Human Pathology of Tokyo Medical and Dental University for their contributions. Funding. This work was funded by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (15K-19507), the Japan Foundation for Applied Enzymology, Takeda Science Foundation, and AstraZeneca.
Publisher Copyright:
© 2021, American Diabetes Association Inc.. All rights reserved.
PY - 2021/4
Y1 - 2021/4
N2 - OBJECTIVE To elucidate the pathogenesis of postpancreatectomy diabetes mellitus (PPDM). RESEARCH DESIGN AND METHODS Forty-eight patients without diabetes undergoing either pancreatoduodenectomy (PD) (n = 20) or distal pancreatectomy (DP) (n = 28) were included. A 75-g oral glucose tolerance test was performed every 6 months. Microbiome composition and short-chain fatty acids (SCFAs) in feces were examined before and 6 months after surgery. The association of histological characteristics of the resected pancreas with PPDM was examined. RESULTS During follow-up (median 3.19 years), 2 of 20 PD patients and 16 of 28 DP patients developed PPDM.Proteobacteria relative abundance,plasma glucagon-like peptide 1 (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 preexisting insulin resistance compared with nonprogressors, 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. CONCLUSIONS We postulate that a greater removal of β-cells contributes to the development of PPDM after DP. Islet expansion along with preexisting insulin resistance is associatedwithhigh cellular plasticity, which maypredict thedevelopment ofPPDM 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.
AB - OBJECTIVE To elucidate the pathogenesis of postpancreatectomy diabetes mellitus (PPDM). RESEARCH DESIGN AND METHODS Forty-eight patients without diabetes undergoing either pancreatoduodenectomy (PD) (n = 20) or distal pancreatectomy (DP) (n = 28) were included. A 75-g oral glucose tolerance test was performed every 6 months. Microbiome composition and short-chain fatty acids (SCFAs) in feces were examined before and 6 months after surgery. The association of histological characteristics of the resected pancreas with PPDM was examined. RESULTS During follow-up (median 3.19 years), 2 of 20 PD patients and 16 of 28 DP patients developed PPDM.Proteobacteria relative abundance,plasma glucagon-like peptide 1 (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 preexisting insulin resistance compared with nonprogressors, 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. CONCLUSIONS We postulate that a greater removal of β-cells contributes to the development of PPDM after DP. Islet expansion along with preexisting insulin resistance is associatedwithhigh cellular plasticity, which maypredict thedevelopment ofPPDM 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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U2 - 10.2337/DC20-0864
DO - 10.2337/DC20-0864
M3 - Article
C2 - 33627367
AN - SCOPUS:85103305436
SN - 0149-5992
VL - 44
SP - 1002
EP - 1011
JO - Diabetes care
JF - Diabetes care
IS - 4
ER -
