Remnant Pancreas Volume Affects New-Onset Impaired Glucose Homeostasis Secondary to Pancreatic Cancer

Abstract

Background: New-onset diabetes (NOD) has been identified as a high-risk factor for the early detection of pancreatic ductal adenocarcinoma (PDAC). The role of tumor volume and remnant pancreas volume (RPV) in the progression from normal to NOD in PDAC patients is not fully illustrated yet.

Methods: In this cross-sectional study, glycemic metabolism traits of 95 PDAC patients before pancreatic surgery were described and compared with chronic pancreatitis and type 2 diabetes mellitus patients based on the oral glucose tolerance test. The remnant RPV and tumor volume, calculated by three-dimensional reconstruction of radiological images, were included in the ordinal logistic regression models.

Results: The prevalence of NOD was high among PDAC patients (38.9%). However, normal glucose tolerance (NGT) or prediabetes mellitus status were present as more than half (24/44) of advanced tumor stage patients. Indexes reflecting beta-cell function but not insulin sensitivity gradually worsened from NGT to NOD patients (all p < 0.05). The remnant pancreas volume (RPV) was identified as a potential protective factor for diabetes secondary to PDAC (odds ratio 0.95, 95% CI [0.92, 0.97], p < 0.001).

Conclusions: Reduced RPV causing beta-cell dysfunction might be one of the mechanisms of NOD secondary to PDAC. Subjects with sufficient pancreas volume could not be detected earlier when regarding patients with NOD as the population at risk for PDAC.

Keywords: beta-cell function; diabetes mellitus; pancreatic ductal adenocarcinoma; remnant pancreas volume; tumor stage.

Figure 1

Flow chart of the study.

Figure 2

Glucose metabolism indexes in PDAC and CP patients with different glucose tolerance statuses (NGT, preDM, and NOD) and type 2 DM patients. (A) HOMA2-%beta, (B) insulinogenic index, (C) insulin secretion–sensitivity index-2 (ISSI-2, or disposition index), (D) HOMA2-S, (E) HOMA2-IR, (F) Matsuda index. * p value less than 0.05, ** p value less than 0.01, *** p value less than 0.001, **** p value less than 0.0001; ns, no significance.

Figure 3

Calculation of tumor volume and remnant pancreas volume based on three-dimensional reconstruction of CT images. (A) Three-dimensional image of the pancreas and surrounding organs. The yellow region represents the pancreas, the orange region represents the tumor, the red region represents the duodenum, and the green region represents the bile and pancreatic ducts. The remnant pancreas volume was determined by identifying the entire pancreatic region and subtracting the tumor volume and the volume of the extended pancreatic duct and bile duct. Comparison of (B) remnant pancreas volume and (C) tumor volume between PDAC patients with different glucose tolerance statuses. * p value less than 0.05, *** p value less than 0.001, **** p value less than 0.0001; ns, no significance.

Figure 4

Correlation between remnant pancreas volume and glucose metabolism indexes in PDAC patients. (A) Plasma fasting and 2 h glucose levels following OGTT, (B) HOMA2-%beta, (C) insulinogenic index, and (D) ISSI-2.

Figure 5

Graphic of the main findings of the study. Given the protective efficacy of RPV, when regarding patients with NOD as the risk population of PDAC, only early-stage patients with insufficient RPV could be identified due to the decreased beta-cell function. While early-stage patients with sufficient RPV might not develop NOD, when the PDAC progresses to a certain degree (such as the advanced stage) and causes insufficient RPV, subjects could be detected through NOD.