Pancreatic adenocarcinoma is a most lethal cancer, and its incidence rate is increasing. A new systematic review and meta-analysis by researchers at National Taiwan University (NTU), published by The BMJ on January 2, shows that the rate of pancreatic adenocarcinoma increases linearly with rising fasting blood glucose across both prediabetes and diabetes. Conducted by Dr. Wei-Chih Liao, an attending physician at the National Taiwan University Hospital, this study is part of his PhD work supervised by Dr. Yu-Kang Tu and Dr. Kuo-Liong Chien, associate professor and professor at the Institute of Epidemiology & Preventive Medicine, College of Public Health, respectively.
“Type 2 diabetes is an established risk factor for pancreatic adenocarcinoma. Whether prediabetes, the precursor of type 2 diabetes, also increases pancreatic cancer risk is controversial, and the dose-response relation between blood glucose level and risk has not been investigated,” said Dr. Tu, the study’s senior author.
Nine observational studies, with a total of 2408 pancreatic cancer patients among 2989500 individuals, were included for this meta-analysis. Random-effects dose-response meta-analysis was conducted to explore potential linear and nonlinear dose-response relation between blood glucose and rate of pancreatic cancer.
There was a strong linear relation between fasting blood glucose and the rate of pancreatic cancer across both prediabetes and diabetes, without significant nonlinear association. The pooled rate ratio of pancreatic cancer per 10 mg/dL increase in fasting blood glucose was 1.14 (95 percent confidence interval 1.06 to 1.22, P<0.001) across the blood glucose range between 73.9 mg/dL and 191 mg/dL. “Every 10 mg/dL increase in fasting blood glucose is associated with a 14% increase in the rate of pancreatic cancer. Prediabetes is also a risk factor for pancreatic cancer,” said Dr. Liao.
Sensitivity analysis excluding blood glucose categories in the range of diabetes showed similar results (pooled rate ratio per 10 mg/dL increase in fasting blood glucose 1.15, 95 percent confidence interval 1.05 to 1.27, P=0.003), strengthening the association between pre-diabetes and pancreatic cancer. There was no significant heterogeneity across the included studies, and no individual study had excessive influence on the summary rate ratio. The results of gender-specific analyses were in line with those of analyses combining both genders, also showing a linear dose-response relation.
In conclusion, Dr. Chien said, “As prediabetes precedes overt type 2 diabetes by years and can be improved or reversed through lifestyle changes, pre-diabetes may be an important window of opportunity for prevention, which is the most effective strategy to reduce pancreatic cancer-related mortality. Early detection of pre-diabetes coupled with lifestyle changes to improve glucose metabolism could curb the increasing incidence of pancreatic cancer and should be further evaluated.”