Diabetes, plasma glucose and incidence of pancreatic cancer: A prospective study of 0.5 million Chinese adults and a meta‐analysis of 22 cohort studies

Abstract

Diabetes is associated with an increased risk of pancreatic cancer (PC) in Western populations. Uncertainty remains, however, about the relevance of plasma glucose for PC among people without diabetes and about the associations of diabetes and high blood glucose with PC in China where the increase in diabetes prevalence has been very recent. The prospective China Kadoorie Biobank (CKB) study recruited 512,000 adults aged 30‐79 years from 10 diverse areas of China during 2004‐2008, recording 595 PC cases during 8 years of follow‐up. Cox regression yielded adjusted hazard ratios (HRs) for PC associated with diabetes (previously diagnosed or screen‐detected) and, among those without previously diagnosed diabetes, with levels of random plasma glucose (RPG). These were further meta‐analysed with 22 published prospective studies. Overall 5.8% of CKB participants had diabetes at baseline. Diabetes was associated with almost twofold increased risk of PC (adjusted HR = 1.87, 95% CI 1.48‐2.37), with excess risk higher in those with longer duration since diagnosis (p for trend = 0.01). Among those without previously diagnosed diabetes, each 1 mmol/L higher usual RPG was associated with a HR of 1.12 (1.04‐1.21). In meta‐analysis of CKB and 22 other studies, previously diagnosed diabetes was associated with a 52% excess risk (1.52, 1.43‐1.63). Among those without diabetes, each 1 mmol/L higher blood glucose was associated with a 15% (1.15, 1.09‐1.21) excess risk. In Chinese and non‐Chinese populations, diabetes and higher blood glucose levels among those without diabetes are associated with an increased risk of PC.

Long-term patterns of fasting blood glucose levels and pancreatic cancer incidence

“…All of our study participants were Koreans and thus, our findings might not generalize into other ethnic groups. In light of a recent meta-analysis that observed a stronger association between diabetes and PaC incidence in studies from East Asia than in those from Europe and North American, 33 our findings are expected to overestimate the risk estimates in other ethnic groups.…”

Pancreatic Cancer and Diabetes Mellitus

“…This erroneously reduces the risk of PDAC in NOD. The 3-year cumulative incidence of PDAC in studies by Munigala et al , Boursi et al , Mokhoul et al and Pang et al , all using physician diagnosis of NOD have consistently observe a risk of 0.25%−0.40%, significantly lower (by nearly half) than that reported in studies using glycemic criteria for NOD by Chari et al and Sharma et al (0.85%−1.25%) [42, 43●●, 37, 44, 39, 45●●]. This highlights that using physician diagnosis-NOD underestimates the incidence of PDAC in DM.…”

A review of lifestyle, metabolic risk factors, and blood‐based biomarkers for early diagnosis of pancreatic ductal adenocarcinoma

“…A meta‐analysis of nine prospective studies reported a RR of 1.46 (1.36–1.56) when further adjusting for BMI . Among participants without diabetes, there is a positive association between blood glucose and risk of PDAC, with RRs of 1.11 (1.02–1.20), 1.15 (1.09–1.21), and 1.13 (1.08–1.19) per 1 mmol/L higher fasting blood glucose, random blood glucose, and post‐load blood glucose, respectively . The association of diabetes may also be confounded by reverse causation (i.e.…”

“…11 A recent meta-analysis involving 34 prospective studies and 35 761 PDAC cases showed that participants with diabetes have a twofold higher risk (RR = 1.98 [1.92-2.03]), and the pooled RR was 1.52 (1.43-1.63) when restricting to 22 prospective cohort studies. 18 The association of diabetes with PDAC is independent of obesity. A meta-analysis of nine prospective studies reported a RR of 1.46 (1.36-1.56) when further adjusting for BMI.…”