Risk Factors for Pancreatic Cancer in Patients with New-Onset Diabetes: A Systematic Review and Meta-Analysis

SIMPLE SUMMARY: New onset diabetes patients are a high-risk group for pancreatic cancer. Since pancreatic cancer is responsible for less than 1% of new-onset diabetes cases, testing all of them might lead to an unfavorable risk/benefit balance. Additional risk factors can contribute to a better definition of the population that needs further screening. Currently, 22 studies examining additional risk factors have been published, but often they have a limited number of participants for the individual risk factor. By pooling their results in a meta-analysis, we could establish the magnitude of several risk factors. We found that pancreatic cancer cases were older than controls by 6.14 years (CI 3.64–8.65, 11 studies). Among new-onset diabetes patients, the highest risk of pancreatic cancer involved a family history of pancreatic cancer (3.78, CI 2.03–7.05, 4 studies), pancreatitis (5.66, CI 2.75–11.66, 9 studies), gallstones (2.5, CI 1.4–4.45, 4 studies), weight loss (2.49, CI 1.47–4.22, 4 studies), and high/rapidly increasing glycemia (2.33, CI 1.85–2.95, 4 studies) leading to more insulin use (4.91, CI 1.62–14.86, 5 studies). Risk factors or symptoms were distinct in the new-onset diabetes patient group. They are strongly connected to pancreatic cancer and are ideal for targeted screening, using a score or model as the first step. ABSTRACT: (1) Background: Patients with new-onset diabetes (NOD) are at risk of pancreatic ductal adenocarcinoma (PDAC), but the most relevant additional risk factors and clinical characteristics are not well established. (2) Objectives: To compare the risk for PDAC in NOD patients to persons without diabetes. Identify risk factors of PDAC among NOD patients. (3) Methods: Medline, Embase, and Google Scholar were last searched in June 2022 for observational studies on NOD patients and assessing risk factors for developing PDAC. Data were extracted, and Meta-Analysis was performed. Pooled effect sizes with 95% confidence intervals (CI) were estimated with DerSimonian & Laird random effects models. (4) Findings: Twenty-two studies were included, and 576,210 patients with NOD contributed to the analysis, of which 3560 had PDAC. PDAC cases were older than controls by 6.14 years (CI 3.64–8.65, 11 studies). The highest risk of PDAC involved a family history of PDAC (3.78, CI 2.03–7.05, 4 studies), pancreatitis (5.66, CI 2.75–11.66, 9 studies), cholecystitis (2.5, CI 1.4–4.45, 4 studies), weight loss (2.49, CI 1.47–4.22, 4 studies), and high/rapidly increasing glycemia (2.33, CI 1.85–2.95, 4 studies) leading to more insulin use (4.91, CI 1.62–14.86, 5 studies). Smoking (ES 1.20, CI 1.03–1.41, 9 studies) and alcohol (ES 1.23, CI 1.09–1.38, 9 studies) have a smaller effect. (5) Conclusion: Important risk factors for PDAC among NOD patients are age, family history, and gallstones/pancreatitis. Symptoms are weight loss and rapid increase in glycemia. The identified risk factors could be used to develop a diagnostic model to screen NOD patients.