gms | German Medical Science

Background: It is a long-standing debate whether diabetes mellitus is a potentially causal risk factor for pancreatic cancer, or more likely a consequence of pancreatic tumour development. Prospective epidemiologic studies have shown variable relationships of pancreas cancer risk with pre-diagnostic blood markers of glucose and insulin metabolism, overall and as a function of lag-times between marker measurements (blood donation) and date of tumour diagnosis.

Methods: Pre-diagnostic blood levels of glycated haemoglobin (HbA1c) and C-peptide were measured for 466 pancreatic cancer cases, prospectively identified within the European Prospective Investigation into Cancer and Nutrition (EPIC), and 466 individually matched controls. Conditional logistic regression models were used to estimate odds ratios for pancreas cancer (ORs), in relation to these pre-diagnostic markers of glucose and insulin metabolism.

Results: Diabetes at baseline was strongly related to risk of pancreatic cancer when the tumour was diagnosed within less than 2 years (OR = 3.41 [95% CI 1.26-9.20]), and somewhat less strongly at longer follow-up times. BMI, by contrast, was only weakly related to pancreas cancer risk overall, although highest BMI levels were observed especially for non-smoking pancreas cancer patients who also had an earlier diagnosis of diabetes. Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA1c levels, even for subjects with HbA1c levels within the non-diabetic range, and up to an odds ratio of 1.83 [95% CI 1.22-2.76] comparing the highest to the lowest quartile; p-trend = 0.001). This association was strongest among never smokers, slightly weaker among ex-smokers, and absent among current smokers. By contrast, C-peptide showed no significant relationship with pancreatic cancer risk overall, irrespective of fasting status or smoking. Analyses showed no clear trends towards aggravating hyperglycaemia or insulin insufficiency with reducing time intervals from blood donation till cancer diagnosis.

Conclusions: Our data indicate that subjects who develop pancreas cancer are characterized by moderately deteriorated glucose metabolism, relatively independently of obesity and insulin resistance – the classical and major risk factors for type-II diabetes. We speculate that long-term, and slowly deteriorating glucose metabolism may have its origin in the pancreas itself, but the precise nature of this defect remains to be identified.