胰岛素抵抗与胰腺导管癌的侵袭性相关。

Insulin resistance is associated with the aggressiveness of pancreatic ductal carcinoma.

作者信息

Dugnani Erica, Balzano Gianpaolo, Pasquale Valentina, Scavini Marina, Aleotti Francesca, Liberati Daniela, Di Terlizzi Gaetano, Gandolfi Alessandra, Petrella Giovanna, Reni Michele, Doglioni Claudio, Bosi Emanuele, Falconi Massimo, Piemonti Lorenzo

机构信息

Diabetes Research Institute, IRCCS San Raffaele Scientific Institute, Via Olgettina 60, 20132, Milan, Italy.

Pancreatic Surgery Unit, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.

出版信息

Acta Diabetol. 2016 Dec;53(6):945-956. doi: 10.1007/s00592-016-0893-6. Epub 2016 Aug 23.

DOI:10.1007/s00592-016-0893-6

PMID:27552832

Abstract

AIMS

To study whether insulin resistance accelerates the development and/or the progression of pancreatic adenocarcinoma (PDAC), we hypothesized that patients with insulin resistance, compared with those without insulin resistance, show: (1) a younger age and more advanced PDAC stage at diagnosis and (2) a shorter disease-free and overall survival after PDAC diagnosis.

METHODS

Prospective observational study of patients admitted to a referral center for pancreatic disease. Insulin resistance was defined as a HOMA-IR value greater than the 66th percentile value of the patients included in this study. Survival was estimated according to Kaplan-Meier and by Cox regression.

RESULTS

Of 296 patients with PDAC, 99 (33 %) met criteria for being classified as insulin resistant at diagnosis. Median follow-up time after diagnosis was 5.27 ± 0.23 years. Patients with insulin resistance received a diagnosis of PDAC at a similar age compared to patients without insulin resistance (67.1 ± 9 vs. 66.8 ± 10 years, p = 0.68), but were more likely to have a cancer stage ≥3 (23.2 vs. 14.2 %, p = 0.053) and a residual disease after surgery (R1 56.4 vs. 38 %; p = 0.007). The median overall survival was 1.3 ± 0.14 and 1.79 ± 0.11 years for the patients with and without insulin resistance, respectively (p = 0.016). Results did not change when patients with diabetes at PDAC diagnosis were excluded from the analysis. Multivariate analysis showed that insulin resistance was independently associated with overall survival.

CONCLUSIONS

Insulin resistance is associated with the aggressiveness of PDAC.

摘要

目的

为研究胰岛素抵抗是否会加速胰腺腺癌（PDAC）的发生发展及进展，我们推测，与无胰岛素抵抗的患者相比，有胰岛素抵抗的患者表现为：（1）诊断时年龄较轻且PDAC分期更晚；（2）PDAC诊断后的无病生存期和总生存期更短。

方法

对一家胰腺疾病转诊中心收治的患者进行前瞻性观察研究。胰岛素抵抗定义为稳态模型评估的胰岛素抵抗指数（HOMA-IR）值大于本研究纳入患者的第66百分位数。根据Kaplan-Meier法和Cox回归分析估计生存期。

结果

296例PDAC患者中，99例（33%）在诊断时符合胰岛素抵抗的分类标准。诊断后的中位随访时间为5.27±0.23年。有胰岛素抵抗的患者与无胰岛素抵抗的患者诊断PDAC时的年龄相似（67.1±9岁 vs. 66.8±10岁，p = 0.68），但更有可能处于癌症≥3期（23.2% vs. 14.2%，p = 0.053）且术后有残留病灶（R1期：56.4% vs. 38%；p = 0.007）。有胰岛素抵抗和无胰岛素抵抗的患者的中位总生存期分别为1.3±0.14年和1.79±0.11年（p = 0.016）。将PDAC诊断时患有糖尿病的患者排除在分析之外时，结果没有改变。多因素分析显示，胰岛素抵抗与总生存期独立相关。