Gkiafi Z, Rozani S. New-onset diabetes mellitus after distal pancreatectomy: Incidence, predictors and clinical impact. World J Gastrointest Surg 2026; 18(6): 119845 [DOI: 10.4240/wjgs.119845]
Corresponding Author of This Article
Sofia Rozani, MD, PhD, Academic Fellow, Research Fellow, Department of Surgery II, Aretaieio University Hospital, National and Kapodistrian University of Athens, Vasileos Sofias Street 76, Athens 11528, Attikí, Greece. sofrozan@gmail.com
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Gastroenterology & Hepatology
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review-article
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Zoi Gkiafi, Department of Surgery I, Laiko University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens 11527, Attikí, Greece
Sofia Rozani, Department of Surgery II, Aretaieio University Hospital, National and Kapodistrian University of Athens, Athens 11528, Attikí, Greece
Author contributions: Gkiafi Z and Rozani S contributed to data extraction, validation, visualization and writing process at every part of this manuscript.
AI contribution statement: I use Grammarly for language polishing.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Sofia Rozani, MD, PhD, Academic Fellow, Research Fellow, Department of Surgery II, Aretaieio University Hospital, National and Kapodistrian University of Athens, Vasileos Sofias Street 76, Athens 11528, Attikí, Greece. sofrozan@gmail.com
Received: February 7, 2026 Revised: February 25, 2026 Accepted: March 18, 2026 Published online: June 27, 2026 Processing time: 137 Days and 12.8 Hours
Abstract
New-onset diabetes mellitus (NODM) represents a significant postoperative concern following distal pancreatectomy, arising from loss of functional β-cell mass and potential alterations in remnant pancreatic perfusion. With increasing use of distal pancreatectomy for benign and malignant conditions, recognition of its metabolic consequences has become critical in long-term patient management. This review examines current evidence on the incidence, determinants, and clinical relevance of NODM after distal pancreatectomy. Published studies demonstrate a broad range of incidence rates, reflecting variability in surgical techniques, underlying disease processes, and diagnostic criteria for postoperative diabetes. Factors such as preoperative glucose intolerance, pancreatic steatosis, patient age, and the volume of preserved pancreatic tissue appear to play important roles in determining postoperative endocrine function. Additionally, technical considerations-including splenic preservation and maintenance of splenic vessel integrity, may influence the risk of NODM. Clinically, the development of NODM is associated with increased healthcare utilization, lifestyle adjustments, and potential long-term cardiovascular and metabolic complications. This review underscores the importance of early detection, risk stratification, and evidence-based follow-up strategies, while highlighting areas requiring further research to better understand and mitigate NODM after distal pancreatectomy.
Core Tip: New-onset diabetes mellitus is a frequent and clinically important consequence of distal pancreatectomy, driven by loss of β-cell mass and potential impairment of pancreatic remnant perfusion. Its incidence varies widely due to differences in surgical technique, underlying pathology, and patient metabolic status. Key determinants include preoperative glucose intolerance, pancreatic steatosis, patient age, and the volume and vascularization of the remnant gland. Recognizing these risk factors enables improved patient selection, early detection, and tailored follow-up strategies. This review highlights emerging evidence on modifiable operative considerations and underscores the need for targeted research to reduce new-onset diabetes mellitus risk.
Citation: Gkiafi Z, Rozani S. New-onset diabetes mellitus after distal pancreatectomy: Incidence, predictors and clinical impact. World J Gastrointest Surg 2026; 18(6): 119845
Distal pancreatectomy is increasingly performed for benign and low-grade malignant lesions of the pancreatic body and tail, a population that demonstrates markedly better long-term survival compared with those undergoing resection for pancreatic ductal adenocarcinoma[1,2]. Consequently, postoperative metabolic complications, particularly new-onset diabetes mellitus (NODM), have become increasingly relevant due to their impact on long-term health and quality of life. Pancreatic resection can lead to type 3c diabetes mellitus (T3cDM), or pancreatogenic diabetes, which arises from exocrine pancreatic disease or surgical loss of endocrine tissue[1,2]. Unlike type 1 or type 2 diabetes, T3cDM is characterized by concurrent deficiencies of insulin, glucagon, and pancreatic polypeptide, producing a unique metabolic profile that may include significant glycemic instability[3]. Although severe “brittle diabetes” is uncommon in T3cDM, even moderate fluctuations in glucose control can pose challenges for postoperative management[1-3].
RESEARCH PROCESS
This narrative review was conducted to synthesize current evidence regarding the incidence, pathophysiology, predictors, clinical impact, and management of NODM following distal pancreatectomy. A comprehensive literature search was performed using PubMed, MEDLINE, and Scopus databases for articles published in English. The search was executed between November2025 and December 2025. Search terms included combinations of “distal pancreatectomy”, “new-onset diabetes”, “pancreatogenic diabetes”, “type 3c diabetes”, “endocrine insufficiency”, “pancreatectomy”, and “distal pancreatectomy”. Original clinical studies, systematic reviews, meta-analyses, and relevant guideline statements were prioritized. Studies were included if they provided original clinical data or expert consensus on glycemic outcomes in adult patients undergoing distal pancreatectomy. Conversely, we excluded pediatric studies, case reports with fewer than five patients, and all forms of gray literature or conference abstracts to ensure the inclusion of only high-quality, peer-reviewed evidence. Reference lists of key articles were manually screened to identify additional pertinent publications. Studies focusing on pancreatic ductal adenocarcinoma exclusively or total pancreatectomy were reviewed selectively when they provided mechanistic or comparative insights. The literature selection was performed through a collaborative consensus approach; given the narrative nature of this review, potential conflicts in study selection were resolved through internal discussion rather than a formal blinded adjudication process. The retrieved literature was qualitatively synthesized, with emphasis on clinically relevant findings and areas of consensus or ongoing uncertainty. Given the narrative design of our study, no formal risk-of-bias assessment was undertaken.
INCIDENCE
The incidence of NODM after distal pancreatectomy is substantial but varies widely across studies owing to differences in patient population, surgical indication, diagnostic criteria, and length of follow-up. Systematic reviews report overall incidence rates of approximately 29%-39% among previously nondiabetic patients, with higher rates observed in individuals undergoing resection for chronic pancreatitis compared with those treated for benign or low-grade neoplastic lesions[4,5]. Longitudinal cohorts further demonstrate that the risk of diabetes increases over time, rising from roughly 14% within the first postoperative year to more than 30% with extended follow-up approaching a decade[5]. Differences in residual pancreatic volume and preoperative metabolic status also contribute to this variability, underscoring the heterogeneity of endocrine outcomes after distal pancreatectomy. These data indicate that postoperative dysglycemia is common and often under-recognized, reinforcing the necessity for routine metabolic surveillance in this patient population[5-7].
When compared with other forms of pancreatic resection, distal pancreatectomy is consistently associated with a higher risk of postoperative diabetes[6,7]. Multiple clinical series and reviews report that patients undergoing distal resection develop new-onset diabetes more frequently and at higher rates than those undergoing pancreaticoduodenectomy, a difference that persists even after adjusting for variations in patient characteristics and follow-up[3,7]. This elevated risk reflects the larger impact of distal resection on postoperative endocrine function and further emphasizes the need for careful metabolic assessment in this patient group[7,8].
This reported heterogeneity is largely driven by methodological differences in surveillance and the biological nature of the underlying disease. Studies utilizing the oral glucose tolerance test or glycated hemoglobin (HbA1c) frequently report higher incidence rates compared to those relying on fasting plasma glucose or patient self-reporting, as the latter may fail to capture early-stage postprandial dysglycemia. Furthermore, the timing of assessment is a critical modifier; early postoperative hyperglycemia (within 6 months) often reflects surgical stress and immediate volume loss, whereas late-onset NODM (detected after 24 months) is more likely influenced by progressive parenchymal atrophy or underlying chronic pancreatitis, which carries a significantly higher hazard ratio (odds ratio = 2.27) for endocrine failure compared to cystic neoplasms.
PATHOPHYSIOLOGY
The metabolic disturbance observed after distal pancreatectomy is classified as type 3c pancreatogenic diabetes, reflecting endocrine failure that arises from structural loss of pancreatic tissue[3,9]. In the context of this review, NODM is strictly defined as the de novo development of diabetes in patients who were normoglycemic prior to surgery. This clinical entity is distinct from the postoperative exacerbation of pre-existing type 2 diabetes, which involves a different baseline of insulin resistance. While the terms are often used interchangeably, it is important to note that T3cDM specifically refers to diabetes secondary to pancreatic disease or resection, often requiring confirmed exocrine insufficiency or structural pathology for formal diagnosis. Thus, while all NODM cases following distal pancreatectomy are pancreatogenic in origin, they may only be classified as T3cDM when they meet these broader diagnostic consensus criteria. The most prominent feature is absolute or near-absolute insulin deficiency resulting from resection of islet-rich distal parenchyma and consequent reduction in β-cell mass[3]. Unlike type 2 diabetes, in which insulin resistance predominates, the primary defect in NODM is diminished insulin availability, often leading to reduced glycemic reserve and an earlier need for exogenous insulin. Resection also compromises α-cell function, resulting in impaired glucagon secretion and a blunted counter-regulatory response to hypoglycemia, thereby increasing susceptibility to glycemic instability[3,10]. In addition to islet hormone loss, postoperative changes in gastrointestinal-pancreatic signaling may further influence glucose homeostasis (Table 1). Altered nutrient transit and disruption of enteroendocrine feedback can attenuate physiologic insulin responses and promote postprandial glucose variability[10]. Moreover, exocrine pancreatic insufficiency, a common consequence of duodenum-preserving pancreatic head resection, may exacerbate glycemic instability through impaired nutrient absorption, malabsorption-related weight loss, and inconsistent caloric intake, further complicating postoperative metabolic control[11,12]. Together, these features distinguish NODM from both type 1 and type 2 diabetes and create a unique clinical challenge. The combination of reduced insulin and glucagon secretion, disrupted incretin and nutrient signaling, and frequent exocrine dysfunction produces a phenotype that is often more labile and less predictable, necessitating tailored monitoring and carefully managed therapeutic strategies[3,11,12].
Table 1 Pathophysiological and diagnostic differences between new-onset diabetes mellitus, type 3c diabetes mellitus, and postoperative hyperglycemia.
Feature
NODM
T3cDM
Postoperative hyperglycemia
Definition
De novo diabetes in previously normoglycemic patients
A growing body of literature demonstrates that the development of NODM after distal pancreatectomy is multifactorial, reflecting both patient-specific metabolic vulnerability and the extent of surgical disruption to endocrine pancreatic tissue. Identifying these predictors is clinically relevant, as it allows targeted preoperative counseling, risk stratification, and long-term metabolic follow-up[13-16].
Preoperative predictors play a major role in determining postoperative endocrine outcomes. Patients with pre-existing dysglycemia, including prediabetes, impaired fasting glucose, or elevated HbA1c, have reduced metabolic reserve and are more likely to progress to overt diabetes after resection[16,17]. Obesity and insulin resistance further increase susceptibility by placing additional stress on remaining β-cell function. Older age, associated with diminished β-cell regenerative capacity, and chronic pancreatitis, which often involves pre-existing parenchymal and islet loss, also consistently confer higher risk[13-16]. Operative predictors are largely related to the magnitude and technical characteristics of the resection. The volume of pancreas removed remains one of the strongest determinants of postoperative endocrine function, with larger resections resulting in greater loss of insulin-producing tissue[15-17]. Surgical indication can influence risk when lesions require more extensive parenchymal sacrifice, as seen with certain cystic neoplasms or neuroendocrine tumors. Some series also report higher rates of NODM when splenic preservation is not achieved, although the mechanistic basis of this association remains unclear[17-19]. Regarding technical approach, recent prospective evidence highlights splenic preservation as a critical factor; splenectomy during duodenum-preserving pancreatic head resection appears to be an independent risk factor for glucose dysregulation, potentially due to the loss of splenocyte-mediated β-cell neogenesis and compromised splenic artery perfusion to the pancreatic remnant. While parenchyma-sparing techniques like central pancreatectomy may further reduce NODM risk by preserving critical islet volume, these metabolic benefits must be critically weighed against oncologic requirements, as radical lymphadenectomy and clear margins remains the priority for malignant lesions. Postoperative and anatomic predictors reflect the functional capacity of the pancreatic remnant over time. A small remnant volume and subsequent parenchymal atrophy are associated with reduced endocrine reserve and increased likelihood of dysglycemia[16,17,19]. In addition, exocrine pancreatic insufficiency frequently coexists after distal pancreatectomy and may aggravate glucose instability through malabsorption, weight loss, and irregular nutrient delivery, further complicating metabolic control[17-19].
CLINICAL IMPACT
NODM after distal pancreatectomy has important implications for long-term patient health and healthcare utilization. The onset of a chronic metabolic disorder can affect daily functioning, dietary habits, and overall quality of life, particularly in patients who undergo resection for benign or low-grade malignant lesions and therefore have otherwise favorable survival prospects[3,17-20]. Even modest postoperative dysglycemia can increase the likelihood of complications require additional medical evaluation, and contribute to psychological and lifestyle burdens[19-21]. Over time, NODM confers risk for microvascular and macrovascular complications comparable to other forms of diabetes, reinforcing its relevance as a clinically meaningful postoperative outcome[21]. Appreciation of these impacts highlights the need for heightened awareness and proactive surveillance in this patient population[19-21].
NODM is associated with several metabolic consequences that can influence patient safety and symptom burden. One of the most clinically significant is an increased susceptibility to hypoglycemia, a result of reduced counter-regulatory hormone responses, which can pose substantial risk in daily life and complicate recognition of glycemic excursions[21,22]. In addition, the marked reduction in endogenous insulin reserve often leads to a more rapid transition from normoglycemia to clinically relevant hyperglycemia compared with other diabetes phenotypes[21-23]. Glucose variability is another notable feature, particularly when exocrine pancreatic insufficiency is present and disrupts consistent nutrient absorption. This variability can contribute to unpredictable glycemic patterns and may manifest as fluctuating symptoms that impact daily activities and nutritional status[21-25]. Together, these metabolic characteristics distinguish NODM as a clinically distinct form of diabetes with implications that extend beyond laboratory measures to real-world patient experience[24,25].
POSTOPERATIVE AND LONG-TERM OUTCOMES
Poorly controlled hyperglycemia in the early postoperative period can influence several aspects of recovery. Elevated glucose levels impair neutrophil function, delay collagen synthesis[3,8], and weaken tissue repair, which may collectively increase susceptibility to postoperative infections[19-25]. In the context of distal pancreatectomy, where patients already face risks of pancreatic fistula, delayed gastric emptying, and intra-abdominal abscess, dysglycemia may act as an additive factor contributing to complications and prolonged hospital stay[23-27].
Hyperglycemia has also been associated with impaired wound healing and increased likelihood of readmission. Patients who develop NODM may require more intensive postoperative monitoring and may present more frequently with dehydration, symptoms related to electrolyte imbalance, or labile glucose values[3,8,26,27]. These metabolic derangements can complicate postoperative recovery and increase resource utilization, particularly in patients with limited physiological reserve or coexisting malnutrition[22,26,27].
In the long term, patients with NODM appear to face cardiovascular risks comparable to individuals with type 2 diabetes. Although the underlying mechanisms differ - NODM reflecting loss of endocrine pancreas rather than insulin resistance, the downstream vascular consequences are similar[23-27]. This parallels evidence from pancreatogenic diabetes in chronic pancreatitis and total pancreatectomy cohorts, where accelerated atherosclerosis and increased risk of ischemic events have been noted. Therefore, cardiovascular risk assessment and standard preventive strategies are important components of survivorship care in this population[23-27]. Nutritional challenges can further complicate the clinical course, particularly when exocrine pancreatic insufficiency accompanies endocrine dysfunction[19,23]. Distal pancreatectomy patients frequently develop some degree of impaired enzyme secretion, which may result in steatorrhea, bloating, weight loss, and reduced absorption of fat-soluble vitamins[19,26,27]. Deficiencies in vitamin A, vitamin D, vitamin E, and vitamin K can contribute to bone loss, impaired immune function, and coagulopathy if not identified and corrected. Over time, chronic malabsorption can exacerbate glycemic instability due to inconsistent nutrient delivery and altered gastrointestinal transit[3,8,19,26-28].
MANAGEMENT CONSIDERATIONS
Surveillance plays a central role in minimizing the burden of NODM after distal pancreatectomy. Glucose and HbA1c assessment should begin during the immediate postoperative period, when stress-induced hyperglycemia may mask or precipitate emerging endocrine insufficiency. Because a substantial proportion of patients exhibit delayed onset of NODM, particularly within the first 6-18 months after surgery, continued structured monitoring is essential even in individuals who remain normoglycemic at discharge[8,29,30].
Annual long-term metabolic monitoring is recommended for all distal pancreatectomy survivors, regardless of initial postoperative results. This follow-up strategy reflects the recognition that progressive decline in pancreatic endocrine reserve, evolving parenchymal atrophy, and changes in body composition can lead to late presentation of dysglycemia. Early detection enables timely introduction of lifestyle, nutritional, or pharmacologic interventions before complications occur[29,30]. Therapeutically, insulin remains the mainstay for many patients with NODM due to reduced β-cell reserve. However, dosing strategies should be conservative to mitigate the heightened risk of hypoglycemia that accompanies impaired counter-regulation[29,30]. When residual endocrine function is adequate, oral agents such as metformin may be considered, particularly in overweight individuals or those with mild hyperglycemia. Patient selection is important, as gastrointestinal side effects and variable nutrient absorption may influence tolerability[29,30].
Pancreatic enzyme replacement therapy is an important adjunct when exocrine insufficiency is present. By improving fat and nutrient absorption, enzyme therapy may help stabilize energy intake, reduce steatorrhea, and attenuate some of the glycemic variability associated with malabsorption. Adequate dosing, taken with all meals and snacks, is essential for achieving these benefits, and vitamin supplementation should be incorporated when deficiencies are identified[8,29-31].
Lifestyle and nutrition counseling serve as foundational elements of postoperative management. Patients benefit from guidance regarding balanced carbohydrate intake, meal timing, and avoidance of large postprandial glucose fluctuations. Nutrition specialists can help tailor strategies to individual tolerance levels, especially in those who experience gastrointestinal symptoms after surgery. Long-term adherence to dietary recommendations can significantly improve energy balance and metabolic control[31,32]. Given the multifaceted nature of NODM and its interaction with nutritional and surgical factors, multidisciplinary coordination is critical. Optimal care incorporates the expertise of surgeons, endocrinologists, dietitians, diabetes educators, and primary-care providers. This collaborative approach ensures that metabolic, nutritional, and surgical concerns are addressed comprehensively and consistently over time, supporting improved quality of life and long-term outcomes for patients following distal pancreatectomy[31,32]. Table 2 summarizes the key studies on diabetes and pancreatic function in pancreatic disease and post-pancreatectomy, highlighting risk factors and post-pancreatectomy outcomes.
Table 2 Key prospective and observational studies on diabetes and pancreatic function in patients with pancreatic disease and post-pancreatectomy outcomes.
Prospective observational study in a tertiary referral center. Inclusion of 364 patients with PDAC. Assessment of diabetes status and timing relative to PDAC diagnosis. Classification of diabetes as: Long-duration, short-duration, concomitant with PDAC, early-onset after PDAC diagnosis, late-onset after PDAC diagnosis. Biochemical evaluation: Fasting blood glucose, insulin and/or C-peptide, HbA1c, anti-islet antibodies
Overall diabetes prevalence in PDAC patients: 67%. Diabetes present at PDAC diagnosis: 174 patients (47.8%). Clinical and biochemical profile similar to T2D. Associated with classic T2D risk factors (age, sex, BMI, family history). Evidence of both insulin resistance and β-cell dysfunction. Diabetes developing after PDAC diagnosis: 70 patients (19.2%). Strongly associated with β-cell mass loss after pancreatectomy. Occurred mainly in patients with pre-existing T2D risk factors. Overall interpretation: PDAC-associated diabetes largely overlaps with T2D phenotypes. Diabetes onset alone is a weak marker for early, asymptomatic PDAC. Identification of diabetes-independent PDAC biomarkers is needed
Prospective follow-up of 91 patients undergoing pancreatic resection (2014-2015). Surgical procedures: PD: 72%, LP: 28%. Assessment of pancreatic insufficiency at 6 months: ExoPI: Fecal elastase < 200 μg/g. EndoPI: Fasting glucose > 126 mg/dL or worsening of preexisting diabetes. Measurement of residual pancreatic volume using standardized volumetric methods
6-month incidence: ExoPI: 75.9%, EndoPI: 30.8%. ExoPI significantly more frequent after PD vs LP (98% vs 21%; P < 0.001). EndoPI rates similar between PD and LP (28% vs 38.5%; P = 0.412). No difference in ExoPI between reconstruction techniques (PG vs PJ). Residual pancreatic volume < 39.5% predictive of ExoPI. ExoPI occurs almost universally after PD, regardless of reconstruction method
Prospective, multicenter observational cohort study. Inclusion of patients ≥ 60 years with new-onset diabetes (≤ 6 months). Exclusion criteria: Alcohol abuse, chronic pancreatitis, prior pancreatic surgery, pregnancy, active malignancy, type 1 diabetes. Follow-up every 6 months for up to 36 months. Data collection at each visit: Questionnaires, clinical symptoms and body weight, fasting blood samples. Every second visit: CA 19-9 measurement, blood sampling for biobank, plasma analysis using mass spectrometry-based metabolomics. Patients with suspicious findings undergo MRI and/or endoscopic ultrasound, with surgical referral if indicated
Validation of metabolomic biomarkers for early PDAC detection in new-onset diabetes. Identification of PDAC at an early, operable stage. Estimation of PDAC incidence in patients with newly diagnosed diabetes. Potential reduction in PDAC-related morbidity, mortality, and healthcare burden
Cross-sectional study in six Dutch centers. Inclusion of patients ≥ 3 years after PD or LP. Indications: Premalignant and benign (non-pancreatitis) pancreatic disease. Assessment tools: EQ-5D-5 L (generic quality of life), EORTC QLQ-C30. Questionnaires on exocrine and endocrine pancreatic insufficiency. PAID20 (diabetes-related distress)
153/183 patients responded (84% response rate); median follow-up 6.3 years. Surgery-related complaints in 47% of patients, 8.4% would not choose surgery again. EQ-5D-5 L VAS lower than general population (76 vs 82; P < 0.001). Global health status (QLQ-C30) similar to general population. Exocrine pancreatic insufficiency in 41%, with symptom relief from enzymes in 48%. New-onset diabetes in 14%. Low diabetes-related distress (median PAID20 6.9/20). Despite preserved overall quality of life, persistent symptoms highlight need for long-term follow-up and counseling
Prospective observational study, inclusion of 224 patients after partial pancreatectomy. PD: 152 (67.9%), DP: 72 (32.1%). Comprehensive glucose assessment: 75 g oral glucose tolerance test. Performed preoperatively, and at 1 week, 12 weeks, and 52 weeks postoperatively. Long-term follow-up up to 3 years. Outcomes monitored: NODM in patients without baseline DM; worsening of glucose regulation (≥ 1% increase in HbA1c) in patients with preexisting DM
Disposition index decreased at 1 week postoperatively in both groups. Recovery and improvement of β-cell function above baseline in PD group. Persistent β-cell dysfunction in DP group, with significant between-group difference at 1 year (P < 0.001). DP associated with higher risk of: NODM (HR = 4.29, 95%CI: 1.49-12.3). Worsening glucose regulation (HR = 2.15, 95%CI: 1.09-4.24). Distal DP and spleen preservation linked to better glucose outcomes. DP showed stronger association with glucose dysregulation than PD
Multicenter study in six centers in China, inclusion of 1211 PDAC patients undergoing R0 resection. Patients categorized by diabetes status: Non-diabetes mellitus (non-DM): 602 (49.7%), long-term diabetes (LTD): 127 (10.5%), NOD: 482 (39.8%). Comparison of perioperative outcomes (e.g., pancreatic fistula) and oncological outcomes (overall and recurrence-free survival)
NOD patients had higher rates of fatty pancreas and POPF (P < 0.05). Median OS: Non-DM: 29.4 months, NOD: 24.6 months (P < 0.001), LTD: 25.2 months (P = 0.041 vs non-DM). Median RFS: Non-DM: 15.8 months, NOD: 13.3 months (P < 0.001), LTD: 13.8 months (P = 0.007 vs non-DM). No significant survival difference between NOD and LTD groups. Multivariate analysis: NOD, LTD, larger tumor size, and poor tumor differentiation independently associated with worse OS and RFS. Conclusion: NOD increases risk of POPF and both NOD and LTD are linked to worse long-term survival after PDAC resection
This review demonstrates that NODM represents a frequent and clinically significant sequela of distal pancreatectomy, with implications that extend beyond metabolic control to influence postoperative recovery, long-term morbidity, and survivorship. As indications for distal pancreatectomy increasingly include benign and low-grade malignant lesions, postoperative endocrine outcomes have become an essential component of surgical quality assessment rather than a secondary consideration.
Among pancreatic resections, distal pancreatectomy is consistently associated with a higher incidence of postoperative diabetes. This association is anatomically and physiologically plausible, given the preferential concentration of insulin-secreting islets within the pancreatic body and tail. The variability in reported incidence across studies reflects heterogeneity in surgical indication, extent of parenchymal resection, baseline metabolic status, and duration of follow-up. Importantly, several longitudinal series indicate a progressive increase in diabetes incidence over time, suggesting that endocrine failure may evolve gradually rather than manifest exclusively in the immediate postoperative period. These findings underscore the limitations of short-term outcome reporting and support the inclusion of long-term endocrine endpoints in surgical follow-up protocols.
The pathophysiology of diabetes following distal pancreatectomy differs fundamentally from that of type 2 diabetes, which predominates in the general population. Pancreatogenic diabetes is characterized by combined deficiencies of insulin and glucagon, resulting in impaired glycemic regulation and reduced counter-regulatory capacity. Although severe brittle diabetes is uncommon, this altered hormonal milieu predisposes patients to hypoglycemia and glucose variability, particularly in those requiring insulin therapy. These features have direct implications for postoperative management and distinguish NODM as a surgically induced metabolic disorder rather than a coincidental comorbidity. Exocrine pancreatic insufficiency frequently coexists after distal pancreatectomy and may exacerbate endocrine dysfunction through malabsorption, weight loss, and irregular nutrient delivery. From a surgical standpoint, this interaction highlights the importance of recognizing combined endocrine-exocrine failure as a unified postoperative syndrome rather than isolated complications. Failure to address exocrine insufficiency may undermine glycemic control and contribute to nutritional deterioration, thereby affecting functional recovery and long-term outcomes.
The clinical impact of NODM extends to both short-term and long-term postoperative outcomes. Perioperative hyperglycemia has been associated with increased risk of infectious complications, impaired wound healing, and prolonged hospitalization. In the long term, patients who develop NODM appear to face cardiovascular risks comparable to those observed in other forms of diabetes, reinforcing its relevance as a determinant of non-procedure-related morbidity. These considerations are particularly salient in patients undergoing distal pancreatectomy for non-malignant disease, in whom long-term functional outcomes are a central measure of surgical success. Despite its frequency and clinical relevance, NODM remains underrepresented in perioperative counseling and postoperative surveillance strategies. There is currently no consensus regarding optimal screening intervals, diagnostic thresholds, or management algorithms specific to distal pancreatectomy. This lack of standardization contributes to delayed diagnosis and inconsistent treatment. From a surgical quality perspective, structured metabolic surveillance should be regarded as an extension of postoperative care rather than an ancillary responsibility.
To bridge the gap between clinical recognition and action, a standardized surveillance algorithm is proposed for patients following distal pancreatectomy. Given the high incidence of occult dysglycemia, an oral glucose tolerance test should be performed at the 6-month postoperative interval, as it serves as the most sensitive tool for detecting surgically induced endocrine failure that fasting glucose may overlook. Subsequently, annual screening with HbA1c is recommended for all patients. For high-risk individuals - defined as those with preoperative prediabetes (HbA1c 5.7%-6.4%), a body mass index > 30 kg/m2, or a resected pancreatic volume exceeding 60% - a more intensive biannual HbA1c screening is appropriate for the first two postoperative years. Clear criteria for formal referral to an endocrinology specialist include a confirmed HbA1c ≥ 6.5%, persistent fasting glucose > 126 mg/dL, or clinical evidence of “brittle” diabetes, characterized by high glycemic variability and recurrent hypoglycemia.
From a surgical perspective, the development of NODM reflects both the absolute loss of endocrine tissue and the functional capacity of the pancreatic remnant. The volume of pancreas resected remains a principal determinant of postoperative endocrine function, with larger resections conferring greater risk. Remnant atrophy over time further contributes to declining endocrine reserve. While spleen-preserving techniques and parenchyma-sparing approaches have been proposed as strategies to mitigate endocrine dysfunction, current evidence remains inconsistent, and the oncologic or technical feasibility of such approaches must be weighed carefully against potential metabolic benefit.
This review has several limitations inherent to its narrative design. The absence of a formal systematic methodology and quantitative synthesis precludes pooled estimates of incidence or risk and limits the ability to draw causal inferences. Considerable heterogeneity exists among the included studies with respect to patient populations, surgical indications, extent of resection, definitions of diabetes, and duration of follow-up, which complicates direct comparison and interpretation of reported outcomes. In addition, many available data are derived from retrospective single-center series, introducing potential selection bias and limiting generalizability. Variations in diagnostic criteria for diabetes and inconsistent reporting of preoperative metabolic status further constrain the precision of reported incidence rates. Finally, limited prospective data evaluating standardized surveillance and management strategies restrict the ability to define evidence-based postoperative protocols. These limitations highlight the need for well-designed prospective studies with uniform definitions and long-term follow-up to better characterize endocrine outcomes after distal pancreatectomy. Future efforts should focus on integrating endocrine outcomes into surgical planning and follow-up. Prospective studies incorporating remnant pancreatic volume, preoperative metabolic risk factors, and standardized definitions of NODM are needed to refine risk stratification. Advances in imaging, quantitative volumetry, and predictive modeling may allow identification of patients at heightened risk and support individualized operative and postoperative strategies. Ultimately, optimizing outcomes after distal pancreatectomy requires a shift toward comprehensive functional assessment that encompasses not only technical success and oncologic adequacy but also long-term metabolic integrity.
CONCLUSION
NODM represents a frequent and clinically significant consequence of distal pancreatectomy, reflecting the combined effects of endocrine tissue loss, altered hormonal signaling, and frequent coexistence of exocrine pancreatic insufficiency. Its incidence increases over time and is influenced by preoperative metabolic status, operative factors, and the functional capacity of the pancreatic remnant. Beyond its metabolic manifestations, NODM carries meaningful implications for postoperative recovery, long-term cardiovascular risk, nutritional status, and overall quality of life. Early recognition, structured surveillance, and individualized management are therefore essential to mitigating its impact. A multidisciplinary framework - integrating surgical, endocrine, nutritional, and primary care expertise - offers the most effective strategy for optimizing outcomes. Continued research is needed to refine predictive tools, standardize surveillance protocols, and develop targeted interventions that preserve endocrine function and improve long-term survivorship for patients undergoing distal pancreatectomy.
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