Pattern of increasing HbA1c levels in patients with diabetes mellitus before clinical detection of pancreatic cancer - a population-based nationwide case-control study.

Background: Diabetes mellitus is a risk factor for pancreatic cancer. Impaired insulin resistance might precede the clinical detection of this cancer by several years.

Methods: This was a nested case-control population-based study assessing the pattern of glycated hemoglobin (HbA1c) change before clinical detection of pancreatic cancer in a population of individuals with diabetes mellitus. All patients registered in the Swedish National Diabetes Register with a prescription of an anti-diabetic drug between 2005 and 2011 were identified. For each case of pancreatic cancer, 10 controls were randomly selected, matched for age, sex, and factors related to diabetes mellitus. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between HbA1c and pancreatic cancer.

Results: In total, 391 cases and 3910 matched controls were identified. The risk of pancreatic cancer was increased more than two-fold in individuals with the highest HbA1c quartile compared with the lowest (OR 1.96, 95% CI 1.40-2.75). The risk of pancreatic cancer remained elevated when comparing the highest HbA1c quartile measured within five years from the clinical detection of pancreatic cancer to the lowest HbA1c quartile (p-value for trend < 0.05). No association was found between HbA1c and pancreatic cancer if HbA1c was measured > 5 years before the clinical detection of pancreatic cancer.

Conclusions: The pattern of increasing HbA1c in patients with diabetes mellitus preceded the clinical detection of pancreatic cancer by up to five years. These findings indicate that there is a lead time of several years during which the development of pancreatic cancer might be detectable through screening in patients with diabetes mellitus.