Postpancreatitis Diabetes Confers Higher Risk for Pancreatic Cancer Than Type 2 Diabetes: Results From a Nationwide Cancer Registry

Abstract

Pancreatitis and diabetes are established risk factors for pancreatic cancer. However, to date, studies have investigated only the risk associated with either of them alone. The aim of this study was to investigate the effect of pancreatitis and diabetes combined, as well as their temporal relationship, on the risk of pancreatic cancer. RESEARCH DESIGN AND METHODSNationwide cancer registry was linked to hospital discharge and mortality data from 1998 to 2015 in New Zealand. Incidence of primary pancreatic cancer in the four study groups (type 2 diabetes [T2D] alone, pancreatitis alone, T2D followed by pancreatitis, and postpancreatitis diabetes mellitus [PPDM]) was identified. Multivariable Cox regression analyses were conducted, with T2D as the reference group. A head-to-head comparison between the T2D followed by pancreatitis and PPDM groups was also performed. RESULTSAmong 139,843 individuals (735,541 person-years), 913 (0.7%) were diagnosed with pancreatic cancer. The proportion of pancreatic cancer was 3.1%, 2.3%, 2.0%, and 0.6% in individuals with PPDM, T2D followed by pancreatitis, pancreatitis alone, and T2D alone, respectively. PPDM (hazard ratio [HR] 6.94; 95% CI 4.09-11.77) and T2D followed by pancreatitis (HR 5.35; 95% CI 3.52-8.14) were associated with significantly higher risks of pancreatic cancer compared with T2D alone. In the headto-head comparison, PPDM was associated with a higher risk of pancreatic cancer compared with T2D followed by pancreatitis (HR 2.35; 95% CI 1.12-4.93). CONCLUSIONSPancreatitis significantly increases the risk of pancreatic cancer in individuals with diabetes. In particular, PPDM poses the highest risk for pancreatic cancer.Pancreatic cancer is one of the leading causes of cancer-specific mortality, with a 5-year survival rate of ,10% (1), and it is projected to become the leading cause of cancer deaths by 2050 (2). Diabetes is often regarded as a risk factor for pancreatic cancer. A meta-analysis of 35 cohort studies reported that individuals with diabetes were at a 1.9-times-higher risk for pancreatic cancer compared with the risk for those

The Relationship between Abdominal Fat Phenotypes and Insulin Resistance in Non-Obese Individuals after Acute Pancreatitis

“…The present study adds to the existing literature on factors that characterize NODAP. Several studies have demonstrated that there are differences between NODAP and T2DM in the gut hormone response [8], blood glucose control [9], risk of pancreatic cancer [10], risk of mortality [11], and survival benefit following the use of common antidiabetic medications [12,13]. To date, only one study has linked IPFD to insulin sensitivity in individuals with NODAP [26].…”

“…There are also several lines of epidemiological evidence that showed that outcomes of NODAP and T2DM are different. These include the risks of poor glycemic control [9], pancreatic cancer [10], mortality [11], and the risk-benefit ratio of common antidiabetic medications [12,13]. Hence, a thorough understanding of the mechanisms behind impaired glucose metabolism in patients after AP is critical with a view to improving clinical management and identifying potential novel targets for prevention and treatment.…”

Chronic Pancreatitis Is Characterized by Elevated Circulating Periostin Levels Related to Intra-Pancreatic Fat Deposition

“…However, all individuals included in the study were non-athletic and did not report any sudden weight gain or weight loss. Fourth, given that CP itself is a risk factor for the development of pancreatic cancer and taken into account that it is already known that periostin is elevated in pancreatic cancer, there is a possibility that the elevated plasma levels of periostin in the CP group (compared with the AP and healthy control groups) might have been related to pancreatic cancer that was masked as CP [ 38 , 48 , 49 ]. However, all participants underwent MRI and pancreatic cancer was excluded a priori.…”

Post-pancreatitis diabetes mellitus and excess intra-pancreatic fat deposition as harbingers of pancreatic cancer

“…Its epidemiology, risk factors, pathogenesis, and management were comprehensively reviewed elsewhere[ 12 ]. A large 2020 cohort study by Cho et al [ 13 ] compared the risks of developing pancreatic cancer in PPDM vs type 2 diabetes mellitus without history of pancreatitis and showed that PPDM was associated with a 7-times significantly higher risk for pancreatic cancer (adjusted hazard ratio 6.94; 95% confidence interval 4.09 to 11.77). This held true after adjustment for age, sex, ethnicity, social deprivation index, alcohol abuse, tobacco smoking, history of gallstones, cholecystectomy, and Charlson comorbidity index.…”

“…When a 12-mo lag period between diabetes diagnosis and pancreatic cancer diagnosis was introduced (to minimize the possibility of reverse causality), the results did not change materially (adjusted hazard ratio 7.93; 95% confidence interval 3.53 to 17.81). Also, people with history of pancreatitis (without diabetes mellitus) had a 4.8-times significantly higher risk of pancreatic cancer (95% confidence interval 3.38 to 6.99) than those with type 2 diabetes mellitus without history of pancreatitis[ 13 ]. This suggests that diabetes mellitus without history of pancreatitis is not a major risk factor for pancreatic cancer; rather it is pancreatitis that is a major risk factor for pancreatic cancer in individuals with diabetes.…”