title: New-onset type 2 diabetes, elevated HbA1c, anti-diabetic medications, and risk of pancreatic cancer.
abstract: BACKGROUND
  Associations between type 2 diabetes, anti-diabetic medications and pancreatic cancer are controversial. This study aims to clarify such associations with new-onset type 2 diabetes and repeated measurements of glycated haemoglobin (HbA1c) levels.
  
  
  METHODS
  A nested case-control study was initiated from the Health Improvement Network (THIN) in UK from 1996 to 2010. Information of pancreatic cancer cases was retrieved electronically from the medical records and manually validated. Control subjects were randomly selected and frequency-matched to the cases on sex, age, and calendar years. Multivariable unconditional logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI), and adjusted for potential confounders.
  
  
  RESULTS
  Among 1,574,768 person-years of follow-up, 529 pancreatic cancer cases and 5000 controls were identified. Type 2 diabetes, or changed HbA1c levels (rather than HbA1c levels at diabetes diagnosis) in diabetes patients (⩾4 mmol mol(-1) compared with <0 mmol mol(-1)) were followed by an increased OR of pancreatic cancer (OR, 2.16, 95% CI 1.72-2.72 and OR, 5.06, 95% CI 1.52-16.87, respectively). Among the anti-diabetic medications in diabetes patients, the OR for insulin users was 25.57 (95% CI 11.55-56.60), sulphonylureas 2.22 (95% CI 1.13, 4.40), and metformin users 1.46 (95% CI 0.85-2.52), compared with no use of any anti-diabetic medications.
  
  
  CONCLUSIONS
  New-onset type 2 diabetes and, particularly, diabetes with rising HbA1c seem to be independent risk factors for pancreatic cancer. The relation between different anti-diabetic medications and pancreatic cancer seems to vary in strength, with the highest risk among users of insulin.
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 171 76, Sweden.|Department of Epidemiology and Biostatistics, Imperial College London, London W2 1PG, UK.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Centro Español de Investigación Farmacoepidemiológica, Madrid 28004, Spain.
authors.forename: Luis Alberto
authors.initials: LA
authors.lastname: García Rodríguez
authors.affiliation: Department of Clinical Sciences, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm 171 77, Sweden.
authors.forename: Linnéa
authors.initials: L
authors.lastname: Malgerud
authors.affiliation: Centro Español de Investigación Farmacoepidemiológica, Madrid 28004, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Pérez
authors.affiliation: Centro Español de Investigación Farmacoepidemiológica, Madrid 28004, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Martín-Pérez
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 171 76, Sweden.|Division of Cancer Studies, King's College London, London WC2R 2LS, UK.
authors.forename: Jesper
authors.initials: J
authors.lastname: Lagergren
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm 171 76, Sweden.|Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 171 77, Sweden.
authors.forename: Tomas S
authors.initials: TS
authors.lastname: Bexelius
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000453:epidemiology*; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D013997:Time Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D013453:Sulfonylurea Compounds; C517652:hemoglobin A1c protein, human