@article{69eab46b06fb41448bb457de5e2186fb,
title = "Diabetes mellitus, glycated haemoglobin and C-peptide levels in relation to pancreatic cancer risk: A study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort",
abstract = "Aims/hypothesis: There has been long-standing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development. Prospective epidemiological studies have shown variable relationships between pancreatic cancer risk and 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 levels of HbA1c and C-peptide were measured for 466 participants with pancreatic cancer and 466 individually matched controls within the European Prospective Investigation into Cancer and Nutrition. Conditional logistic regression models were used to estimate ORs for pancreatic cancer. Results: Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA1c levels up to an OR of 2.42 (95% CI 1.33, 4.39 highest [≥6.5%, 48 mmol/mol] vs lowest [≤5.4%, 36 mmol/mol] category), even for individuals with HbA1c levels within the non-diabetic range. C-peptide levels showed no significant relationship with pancreatic cancer risk, irrespective of fasting status. Analyses showed no clear trends towards increasing hyperglycaemia (as marked by HbA1c levels) or reduced pancreatic beta cell responsiveness (as marked by C-peptide levels) with decreasing time intervals from blood donation to cancer diagnosis. Conclusions/interpretation: Our data on HbA1c show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in HbA1c levels, relatively independently of obesity and insulin resistance-the classic and major risk factors for type 2 diabetes. While there is no strong difference by lag time, more data are needed on this in order to reach a firm conclusion.",
keywords = "C-peptide, Cohort study, Diabetes, EPIC, HbA, Pancreatic cancer",
author = "Grote, {V. A.} and S. Rohrmann and A. Nieters and L. Dossus and A. Tj{\o}nneland and J. Halkj{\ae}r and K. Overvad and G. Fagherazzi and Boutron-Ruault, {M. C.} and S. Morois and B. Teucher and S. Becker and D. Sluik and H. Boeing and A. Trichopoulou and P. Lagiou and D. Trichopoulos and D. Palli and V. Pala and R. Tumino and P. Vineis and S. Panico and L. Rodr{\'i}guez and Duell, {E. J.} and E. Molina-Montes and M. Dorronsoro and Huerta, {J. M.} and E. Ardanaz and Jeurnink, {S. M.} and Beulens, {J. W.J.} and Peeters, {P. H.M.} and M. Sund and W. Ye and B. Lindkvist and D. Johansen and Khaw, {K. T.} and N. Wareham and N. Allen and F. Crowe and M. Jenab and I. Romieu and Michaud, {D. S.} and E. Riboli and D. Romaguera and Bueno-De-Mesquita, {H. B.} and R. Kaaks",
note = "Funding Information: Acknowledgements We thank B. Lederer, S. Henke (German Cancer Research Center, Heidelberg, Germany) and P. Matha (Karolinska University Hospital, Stockholm, Sweden) for their excellent work in performing the assays for C-peptide and HbA1c for this study. V.A. Grote was funded by a studentship from the German Research Foundation, Graduiertenkolleg 793 {\textquoteleft}Epidemiology of communicable and chronic non-communicable diseases and their interrelationships{\textquoteright} and this work was, in part, supported by WCRF-UK and WCRF International, grant no 2009/39. The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G{\'e}n{\'e}rale de l{\textquoteright}{\'E}ducation Nationale, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale (Inserm) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation and the Hellenic Ministry of Health and Social Solidarity (Greece); Italian Association for Research on Cancer (AIRC) and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (the Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health. (Norway); Health Research Fund (FIS), Regional Governments of Andaluc{\'i}a, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council and Regional Government of Sk{\aa}ne and V{\"a}sterbotten (Sweden); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, and Wellcome Trust (UK).",
year = "2011",
month = dec,
doi = "10.1007/s00125-011-2316-0",
language = "English",
volume = "54",
pages = "3037--3046",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "12",
}