Pancreatitis, Type 2 Diabetes Mellitus, and Pancreatic Cancer (Diabetes Metab J 2025;49:252-63)

Shih-Wei Lai; Kuan-Fu Liao

doi:10.4093/dmj.2025.0237

Articles

Page Path: HOME > Diabetes Metab J > Volume 49(3); 2025 > Article

Letter Pancreatitis, Type 2 Diabetes Mellitus, and Pancreatic Cancer (Diabetes Metab J 2025;49:252-63): Shih-Wei Lai¹, Kuan-Fu Liao²; Diabetes & Metabolism Journal 2025;49(3):518-519.
DOI: https://doi.org/10.4093/dmj.2025.0237
Published online: May 1, 2025

705 Views
24 Download

¹School of Medicine, China Medical University, Taichung; Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan

²College of Medicine, Tzu Chi University, Hualien; Division of Hepatogastroenterology, Department of Internal Medicine, Taichung Tzu Chi Hospital, Taichung, Taiwan

Corresponding author: Kuan-Fu Liao

Division of Hepatogastroenterology, Department of Internal Medicine, Taichung Tzu Chi Hospital, No.66, Sec. 1, Fongsing Road, Tanzi District, Taichung City, 427, Taiwan E-mail: kuanfuliaog@gmail.com

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

prev next

Full Article

Download PDF

NOTES
REFERENCES
About this article

See the reply "Effects of Pancreatitis and Type 2 Diabetes Mellitus on the Development of Pancreatic Cancer: A Nationwide Nested Case-Control Study (Diabetes Metab J 2025;49:252-63)" in Volume 49 on page 522.

See the article "Effects of Pancreatitis and Type 2 Diabetes Mellitus on the Development of Pancreatic Cancer: A Nationwide Nested Case-Control Study" on page 252.

We appreciate the important study by Kim et al. [1] examining the association between pancreatitis, type 2 diabetes mellitus (T2DM), and pancreatic cancer risk. The findings provide valuable insights into high-risk populations. We raise five points not explicitly discussed in the article to help readers better understand and interpret the study results.

First, the study found that both post-pancreatitis diabetes mellitus (PPDM) and T2DM followed by pancreatitis (T2DM-PAN) were associated with a higher pancreatic cancer risk compared to T2DM-only or PAN-only. This suggests a synergistic effect, where the coexistence of T2DM and pancreatitis amplifies pancreatic cancer risk beyond what either condition alone would cause. Future research should explore the underlying mechanisms of this interaction, such as chronic inflammation, metabolic dysregulation, or insulin resistance.

Second, the study reported no significant difference in pancreatic cancer risk between PPDM and T2DM-PAN (adjusted odds ratio [OR], 0.95; 95% confidence interval, 0.81 to 1.12). This suggests that the sequence of disease onset does not significantly impact pancreatic cancer risk; rather, the presence of both conditions—regardless of which appears first—is the key driver of increased risk. This finding is crucial for clinicians assessing high-risk populations and reinforces the need for pancreatic cancer screening in all individuals with both T2DM and pancreatitis.

Third, the study found that PPDM patients on continuous insulin therapy had 17-fold higher odds of pancreatic cancer, with the authors possibly attributing this to difficulty in controlling blood sugar. However, this explanation is incomplete. Insulin prescribing patterns are influenced by clinician habits, clinician medical education, local treatment guidelines, patient expectations, medical care accessibility, and demographic factors [2,3]. Thus, insulin therapy does not necessarily indicate poor glycemic control. In addition, the study did not account for glycosylated hemoglobin (HbA1c) levels, a key marker of long-term glycemic control. The Korean National Health Insurance Service database collects HbA1c values, yet these were not included in the analysis. Without HbA1c data, it remains unclear whether the increased pancreatic cancer risk among insulin users is due to poor glycemic control or another factor, such as pancreatic cancer-induced β-cell dysfunction. If HbA1c levels were not elevated in these insulin users, then their increased pancreatic cancer risk cannot be solely attributed to poor glucose control. This omission represents an important research gap. To address this, we recommend that future studies incorporate HbA1c data to clarify the relationship between glycemic control and pancreatic cancer risk [4]. Specifically, future research should determine: (1) whether better glycemic control lowers or increases pancreatic cancer risk; (2) whether insulin use in well-controlled patients (e.g., HbA1c <7%) carries the same risk as in those with poor control (e.g., HbA1c >9%).

Fourth, if diabetes were a direct risk factor for pancreatic cancer, one would expect a longer duration of diabetes to correlate with a higher pancreatic cancer risk. However, the study found the opposite— a shorter duration of diabetes was associated with a higher risk, whereas a longer duration was associated with a lower risk. This pattern strongly suggests reverse causality in the study population, meaning pancreatic cancer can lead to the development of diabetes, rather than diabetes increasing the risk of pancreatic cancer as is traditionally thought. That is, in this study population, pancreatic cancer likely causes diabetes, making newly diagnosed diabetes more common in individuals with pancreatic cancer. This provides indirect evidence for reverse causation. Consequently, it implies that surveillance for pancreatic cancer might be warranted in individuals who are newly diagnosed with diabetes [5].

Fifth, because this study follows a case-control design, the reported OR of 17 means that the odds of PPDM with continuous insulin use are 17 times higher among individuals with pancreatic cancer compared to those without pancreatic cancer. However, this does not imply a 17-fold increased risk of developing pancreatic cancer, as case-control studies cannot establish absolute risk or causality—only associations. Participants were selected based on pancreatic cancer status (cases vs. controls), not based on diabetes type or insulin use. Therefore, it is inappropriate to directly infer risk from an OR in a case-control study. Even though a nested case-control study is drawn from a cohort, its analysis follows case-control methodology. Thus, the OR should still be interpreted as a measure of association rather than a direct estimate of risk. The same principle applies to all other ORs reported in the study, which should also be interpreted as measures of association rather than direct estimates of risk.

Addressing these points will help readers better interpret the study’s implications. Recognizing the synergistic effect between T2DM and pancreatitis, understanding that the sequence of disease onset is not a key determinant of risk, and incorporating HbA1c data to clarify the role of glycemic control in pancreatic cancer risk will improve clinical decision-making and risk stratification. We appreciate the authors’ significant contribution to this field and encourage further research incorporating these considerations. The letter aims to discuss medical issues with the authors, not criticize their research. If our points are incorrect, we welcome clarification and further discussion.

NOTES

CONFLICTS OF INTEREST

No potential conflict of interest relevant to this article was reported.

REFERENCES

1. Kim YE, Yu MH, Nam CM, Kang ES. Effects of pancreatitis and type 2 diabetes mellitus on the development of pancreatic cancer: a nationwide nested case-control study. Diabetes Metab J 2025;49:252-63.Article PubMed PMC PDF
2. Yaseen A, Lahiri SW. Health care provider prescribing habits and barriers to use of new type 2 diabetes medications: a single-system survey study. Clin Diabetes 2023;41:490-501.Article PubMed PMC PDF
3. Alfaraj S, Vos R, Spruit M, Groenwold R, Kist J, Mook-Kanamori D. Navigating insulin initiation in type 2 diabetes: unraveling the sociodemographic and biological dynamics. Ann Fam Med 2024;22(Supplement 1):6097.Article PMC
4. Lai SW, Liao KF. New-onset diabetes mellitus and the risk of pancreatic cancer. J Gastroenterol Hepatol 2025;40:341.Article PubMed
5. Ali S, Coory M, Donovan P, Na R, Pandeya N, Pearson SA, et al. Predicting the risk of pancreatic cancer in women with new-onset diabetes mellitus. J Gastroenterol Hepatol 2024;39:1057-64.Article PubMed

Figure & Data

References

Citations

Citations to this article as recorded by

PubReader
ePub Link

Cite this Article

Cite this Article: export Copy Download Format; Close

Download Citation

Download a citation file in RIS format that can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Reference Manager.

Format:

RIS — For EndNote, ProCite, RefWorks, and most other reference management software
BibTeX — For JabRef, BibDesk, and other BibTeX-specific software

Include:

Citation for the content below
Citation and abstract for the content below

Pancreatitis, Type 2 Diabetes Mellitus, and Pancreatic Cancer (Diabetes Metab J 2025;49:252-63)

Diabetes Metab J. 2025;49(3):518-519. Published online May 1, 2025

DOI: https://doi.org/10.4093/dmj.2025.0237

XML Download

Related articles

Pancreatitis, Type 2 Diabetes Mellitus, and Pancreatic Cancer (Diabetes Metab J 2025;49:252-63)

About this article

Lai SW, Liao KF. Pancreatitis, Type 2 Diabetes Mellitus, and Pancreatic Cancer (Diabetes Metab J 2025;49:252-63). Diabetes Metab J. 2025;49(3):518-519.

DOI: https://doi.org/10.4093/dmj.2025.0237.

Download citation ↓