We used CPI as an index of BISC, and a postoperative CPI <1.0 was defined as a decrease in BISC that marked the occurrence of the event of interest. Postoperative CPI was significantly lower than preoperative CPI in approximately 85% of the patients, regardless of surgical procedure. The proportion of remnant pancreas volume by surgical procedure was significantly greater in DP than in PD, but there were no significant differences in the event rates. We identified preoperative CPI in PD patients as a predictor of post-CPI <1.0, whereas no significant factors were observed for DP patients. Preoperative non-diabetic patients had a significantly lower rate of insulin therapy induction after pancreatectomy than preoperative medically treated patients. In a comparison between preoperative non-diabetic patients and patients on diabetic medication, there were no significant differences in the postoperative CPI and event occurrence rates. However, the postoperative insulin induction rates were significantly lower in preoperative non-diabetic patients than in patients on diabetic medication.
A previous report suggested preoperative 24-h urinary C-peptide excretion measurement and multiplication of this value by the predicted pancreatic volume as a predictor of postoperative endocrine function [11]. However, 24-h urine storage is a complicated and burdensome test for patients and is considered less versatile. However, CPI is a simple indicator that can be measured using blood tests and is considered more versatile.
The results of this study suggest that in terms of predictors of postoperative decreased BISC, the factors that are significant in PD are not significant in DP, suggesting that the predictors differ by surgical procedure. This difference might be due to the heterogeneous distribution of the islets of Langerhans in the pancreas. Generally, the islets of Langerhans are largely distributed in the pancreatic tail [4-6]. In PD, the pancreatic head, which has a large volume, is removed, whereas the pancreatic tail, which is thought to contain many islets of Langerhans, is preserved. Therefore, it was suggested that BISC after PD strongly reflects the index of preoperative BISC, which is represented by preoperative CPI. Since the residual pancreatic volume was large in DP cases, we evaluated the index considering the PRPV but did not obtain significant results. In a previous report, PRPV was not a risk factor for NODM after DP, and obese patients were significantly more likely to develop NODM [19]. Preoperative BMI was a candidate predictor of event occurrence in DP patients of this study, but it was not significant on multivariate analysis.
Regulation of insulin secretion is through stimulation by hyperglycemia or effects of various endocrine hormones. Incretin is a general term for gastrointestinal-derived hormones that act on pancreatic β-cells to promote insulin secretion [20,21]. Glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide are known as incretins, and their mechanisms of enhancing incretin effects and inhibiting metabolism have been elucidated and clinically applied as therapeutic targets for DM [20,21]. Muscogiuri et al. showed that duodenal resection in PD resulted in an increase in GLP-1 concentration, which was expected to increase insulin secretory capacity, but in fact, they reported a decrease in insulin secretory capacity [22]. This decrease is hypothesized to be the result of the suppression of insulin secretion by increased glucagon levels [22]. Although we did not measure glucagon or incretin levels before and after surgery in this study, we believe that it is necessary to understand the behavior of hormones involved in glucose tolerance before and after surgery to elucidate the pathogenesis of changes in glucose tolerance due to pancreatectomy, and this is a topic for future studies.
In the present study, most non-diabetic patients with post-CPI <1.0 did not progress to diabetes that would require insulin therapy postoperatively. It is hypothesized that factors other than a short-term decrease in BISC are involved in the development of NODM. Mezza et al. stated that even if there is forced removal of β-cells by pancreatectomy, the function of the remaining β-cells will not lead to insulin deficiency if there is no insulin resistance [23]. However, if there is insulin resistance at the time of pancreatectomy, the residual β-cells overload postoperatively, leading to insulin deficiency and NODM. In other words, the true determinant of the development of NODM is not forced removal of β-cells by pancreatectomy but the presence or absence of a pre-existing diabetic milieu, which may lead to type 2 DM, a condition accelerated by surgery [23]. Similar to the previous report, in this study, preoperative non-diabetic patients had a significantly lower rate of postoperative insulin introduction than patients on preoperative diabetic medication. These results suggest that the coexistence of pancreatectomy induced BISC reduction and insulin resistance, which is considered one of the pathophysiological features of type 2 DM, may promote postoperative insulin deficiency, resulting in the need for insulin therapy.
Although the etiology of insulin resistance is not fully understood, obesity has been identified as an acquired risk [23]. Patients who are expected to have decreased BISC after pancreatectomy may reduce the development of NODM by weight control based on appropriate diet and exercise therapy, with appropriate intervention through follow-ups being essential in the future.
This study has some limitations, including the single-center, retrospective design. Using the three explanatory variables of age, sex, and predictors of event occurrence in multivariate analysis to determine the minimum sample size, a minimum of 30 cases of event occurrence were required per surgical procedure, and assuming an event occurrence rate of 40%, the total number of cases should be at least 75 each per surgical procedure. Since the overall numbers of cases and events were limited in this study, further analysis with a larger number of cases is crucial. Furthermore, medium- to long-term follow-up is necessary to clarify how early postoperative decline in BISC changes over the medium to long term and whether it leads to the development of NODM.