Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
Diabetes Care. 2021 Apr;44(4):1002-1011. doi: 10.2337/dc20-0864. Epub 2021 Feb 24.
To elucidate the pathogenesis of postpancreatectomy diabetes mellitus (PPDM).
Forty-eight patients without diabetes undergoing either pancreatoduodenectomy (PD) ( = 20) or distal pancreatectomy (DP) ( = 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.
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.
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 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.
阐明胰切除术后糖尿病（PPDM）的发病机制。
纳入 48 例无糖尿病的患者，分别行胰十二指肠切除术（PD）（=20 例）或胰体尾切除术（DP）（=28 例）。每 6 个月进行一次 75g 口服葡萄糖耐量试验。手术前后检测粪便微生物群组成和短链脂肪酸（SCFA）。检查切除胰腺的组织学特征与 PPDM 的关系。
在随访期间（中位数 3.19 年），20 例 PD 患者中有 2 例和 28 例 DP 患者中有 16 例发生 PPDM。PD 后仅观察到变形菌相对丰度、血浆胰高血糖素样肽 1（GLP-1）和粪便丁酸盐水平增加。术后丁酸盐水平与术后 GLP-1 水平相关。虽然 PD 和 DP 手术切除的胰腺体积无显著差异，但 DP 患者的β细胞和α细胞面积均明显高于 PD 患者。在 DP 患者中，与非进展者相比，糖尿病进展者存在胰岛素抵抗，且α细胞和β细胞面积均为 PPDM 的预测因素。此外，在 DP 患者中，α细胞和β细胞面积与胰岛中 ALDH1A3 表达相关。
我们推测 DP 后β细胞的大量去除导致 PPDM 的发生。与胰岛素抵抗相关的胰岛扩张与高细胞可塑性相关，这可能预测 DP 后 PPDM 的发生。相比之下，PD 与肠道微生物群的改变、SCFA 产生和 GLP-1 分泌增加相关，可能有助于预防 PPDM 的发生。
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