Diabetes Is Linked to Higher Risk of Pancreatic Cystic Neoplasms

Diabetes was associated with an increased risk of pancreatic cystic neoplasms (PCNs), with longer disease duration linked to progressively higher risk, according to a nationwide population-based cohort study of more than 3.8 million adults in Korea published in JAMA Network Open.¹

“These findings underscore the need for cautious interpretation: while the presence of a cyst may signal an elevated malignant potential in some cases, population-wide surveillance of all cystic lesions, particularly among patients with diabetes (a highly prevalent condition), may not be justified,” wrote the researchers of the study.

This cohort study used data from the Korean National Health Insurance Service (NHIS), which covers approximately 97% of the Korean population. Adults aged 20 years or older who underwent a standardized health examination in 2009 were eligible. After exclusions for missing data, prior pancreatic cysts, pancreatitis-related conditions, or diagnoses within a 1-year lag period, 3,856,676 individuals were included and followed through December 31, 2020. Data were analyzed from March 23, 2023, to February 8, 2024.

Participants were categorized by glycemic status as normoglycemic (fasting glucose < 100 mg/dL), impaired fasting glucose (100–125 mg/dL), shorter diabetes duration (< 5 years), or longer diabetes duration (≥ 5 years). Diabetes was defined using the International Classification for Diseases, Tenth Revision (ICD-10) codes, antidiabetic medication prescriptions, and fasting glucose levels. Incident pancreatic cysts were identified using ICD-10 codes K86.2, D13.6, and D37.7, with exclusions to minimize the inclusion of nonneoplastic cysts.

Adjusted hazard ratios (AHRs) for PCN occurrence were estimated using Cox proportional hazards models. Model 1 adjusted for age, sex, hypertension, dyslipidemia, income, smoking status, alcohol consumption, regular physical activity, and body mass index; Model 2 additionally adjusted for hypertriglyceridemia.

Among 3,856,676 adults (mean [SD] age, 47.1 [14.0] years; 54.5% male), 330,138 (8.6%) had diabetes. The median follow-up was 10.3 years (IQR, 10.1-10.6), totaling 38,906,756.3 person-years. During follow-up, 31,877 individuals (0.8%) developed PCNs, corresponding to an overall incidence of 0.82 per 1000 person-years.

Incidence rates increased across glycemic categories:

• Normoglycemia: 0.72 per 1000 person-years (95% CI, 0.71-0.73)
• Impaired fasting glucose: 0.89 (95% CI, 0.87-0.91)
• Diabetes < 5 years: 1.25 (95% CI, 1.20-1.30)
• Diabetes ≥ 5 years: 1.82 (95% CI, 1.74-1.90)

In multivariable-adjusted analyses, compared with normoglycemia, AHRs were the following:

• 1.06 (95% CI, 1.03-1.08) for impaired fasting glucose
• 1.23 (95% CI, 1.18-1.28) for diabetes < 5 years
• 1.37 (95% CI, 1.31-1.44) for diabetes ≥ 5 years

Subgroup analyses showed stronger associations in certain populations. Among adults younger than 60 years, the AHR was 1.34 (95% CI, 1.27-1.40) compared with 1.21 (95% CI, 1.16-1.27) in those aged 60 years or older (P = .003). Among men, the AHR was 1.32 (95% CI, 1.26-1.38) vs 1.20 (95% CI, 1.15-1.26) in women (P = .005). Current smokers with diabetes had an AHR of 1.40 (95% CI, 1.30-1.51), compared with 1.22 (95% CI, 1.18-1.28) in never-smokers and 1.25 (95% CI, 1.16-1.35) in former smokers (P = .006).

Of the 31,877 individuals with PCNs, 1,315 (4.1%) were subsequently diagnosed with pancreatic cancer. Overall, 25,517 participants (0.7%) developed pancreatic cancer during follow-up.

The researchers noted several limitations. Pancreatic cysts were identified using administrative ICD-10 codes, and imaging modality data were unavailable. Residual confounding cannot be excluded despite multivariable adjustment. Additionally, the observational design precludes causal inference.

An accompanying editorial also offers important clinical context on the association between diabetes and PCNs, emphasizing both the epidemiologic strength and the practical limitations of the findings.² They highlight key methodological constraints, including reliance on ICD-10 codes that do not distinguish cyst subtypes or capture imaging granularity, limited treatment-level data regarding antidiabetic therapies, and the relatively homogeneous East Asian cohort, which may affect generalizability.

“Cho et al. provide valuable epidemiologic evidence that diabetes—particularly long-standing diabetes—is associated with an increased likelihood of a newly diagnosed pancreatic cyst,” wrote the authors. “For clinicians, the message is one of contextualized vigilance: diabetes should not trigger pancreatic imaging in the absence of symptoms or other risk factors, but it may inform diagnostic interpretation once a cyst is identified.”

Despite these limitations, the researchers find that diabetes—particularly a longer duration of 5 years or more—is associated with an increased risk of PCNs.¹ Risk rose progressively with worsening glycemic status and was more pronounced in younger individuals, men, and current smokers. These findings suggest that diabetes status and modifiable lifestyle factors may be associated with PCN development and may inform future surveillance strategies.

References

1. Cho IR, Chang SH, Lee SH, et al. Pancreatic cystic neoplasm risk among individuals with diabetes. JAMA Netw Open. 2026;9(2):e2556951. doi:10.1001/jamanetworkopen

2. Crippa S, Piemonti L. Diabetes and pancreatic cystic neoplasms—dangerous liaisons. JAMA Netw Open. 2026;9(2):e2556869. doi:10.1001/jamanetworkopen