title: Diabetes, use of antidiabetic drugs, and the risk of glioma.
abstract: BACKGROUND
  Prior epidemiologic studies suggest inverse relations between diabetes and glioma risk, but the underlying mechanisms, including use of antidiabetic drugs, are unknown.
  
  
  METHODS
  We therefore performed a matched case-control analysis using the Clinical Practice Research Datalink (CPRD). We identified incident glioma cases diagnosed between 1995 and 2012 and matched each case with 10 controls on age, gender, calendar time, general practice, and years of active history in the CPRD. We performed conditional logistic regression to estimate odds ratios (ORs) with 95% CIs, adjusted for body mass index and smoking.
  
  
  RESULTS
  We identified 2005 cases and 20 050 controls. Diabetes was associated with decreased risk of glioma (OR = 0.74; 95% CI = 0.60-0.93), particularly glioblastoma (OR = 0.69; 95% CI = 0.51-0.94). Glioblastoma risk reduction was markedly pronounced among diabetic men (OR = 0.60; 95% CI = 0.40-0.90), most apparently for those with diabetes of long-term duration (OR for >5 vs 0 y = 0.46; 95% CI = 0.26-0.82) or poor glycemic control (OR for HbA1c ≥ 8 vs <6.5% = 0.20; 95% CI = 0.06-0.70). In contrast, the effect of diabetes on glioblastoma risk was absent among women (OR = 0.85; 95% CI = 0.53-1.36). No significant associations with glioma were found for use of metformin (OR for ≥ 30 vs 0 prescriptions = 0.72; 95% CI = 0.38-1.39), sulfonylureas (OR = 0.71; 95% CI = 0.39-1.30), or insulin (OR = 0.79; 95% CI = 0.37-1.69).
  
  
  CONCLUSIONS
  Antidiabetic treatment appears to be unrelated to glioma, but long-term diabetes duration and increased HbA1c both show decreased glioma risk. Stronger findings in men than women suggest low androgen levels concurrent with diabetes as a biologic mechanism.
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany (C.S., U.B., P.H.); Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany (C.R., M.F.L.); Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland (C.R.M., M.B.); Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Boston University, Boston, Massachusetts, (C.R.M., S.S.J.); Hospital Pharmacy, University Hospital Basel, Basel, Switzerland (C.R.M.); Department of General Internal Medicine, University of Bern, Inselspital/Universitätsspital, Bern, Switzerland (M.B.).
authors.forename: Corinna
authors.initials: C
authors.lastname: Seliger
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany (C.S., U.B., P.H.); Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany (C.R., M.F.L.); Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland (C.R.M., M.B.); Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Boston University, Boston, Massachusetts, (C.R.M., S.S.J.); Hospital Pharmacy, University Hospital Basel, Basel, Switzerland (C.R.M.); Department of General Internal Medicine, University of Bern, Inselspital/Universitätsspital, Bern, Switzerland (M.B.).
authors.forename: Cristian
authors.initials: C
authors.lastname: Ricci
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany (C.S., U.B., P.H.); Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany (C.R., M.F.L.); Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland (C.R.M., M.B.); Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Boston University, Boston, Massachusetts, (C.R.M., S.S.J.); Hospital Pharmacy, University Hospital Basel, Basel, Switzerland (C.R.M.); Department of General Internal Medicine, University of Bern, Inselspital/Universitätsspital, Bern, Switzerland (M.B.).
authors.forename: Christoph R
authors.initials: CR
authors.lastname: Meier
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany (C.S., U.B., P.H.); Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany (C.R., M.F.L.); Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland (C.R.M., M.B.); Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Boston University, Boston, Massachusetts, (C.R.M., S.S.J.); Hospital Pharmacy, University Hospital Basel, Basel, Switzerland (C.R.M.); Department of General Internal Medicine, University of Bern, Inselspital/Universitätsspital, Bern, Switzerland (M.B.).
authors.forename: Michael
authors.initials: M
authors.lastname: Bodmer
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany (C.S., U.B., P.H.); Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany (C.R., M.F.L.); Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland (C.R.M., M.B.); Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Boston University, Boston, Massachusetts, (C.R.M., S.S.J.); Hospital Pharmacy, University Hospital Basel, Basel, Switzerland (C.R.M.); Department of General Internal Medicine, University of Bern, Inselspital/Universitätsspital, Bern, Switzerland (M.B.).
authors.forename: Susan S
authors.initials: SS
authors.lastname: Jick
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany (C.S., U.B., P.H.); Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany (C.R., M.F.L.); Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland (C.R.M., M.B.); Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Boston University, Boston, Massachusetts, (C.R.M., S.S.J.); Hospital Pharmacy, University Hospital Basel, Basel, Switzerland (C.R.M.); Department of General Internal Medicine, University of Bern, Inselspital/Universitätsspital, Bern, Switzerland (M.B.).
authors.forename: Ulrich
authors.initials: U
authors.lastname: Bogdahn
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany (C.S., U.B., P.H.); Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany (C.R., M.F.L.); Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland (C.R.M., M.B.); Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Boston University, Boston, Massachusetts, (C.R.M., S.S.J.); Hospital Pharmacy, University Hospital Basel, Basel, Switzerland (C.R.M.); Department of General Internal Medicine, University of Bern, Inselspital/Universitätsspital, Bern, Switzerland (M.B.).
authors.forename: Peter
authors.initials: P
authors.lastname: Hau
authors.affiliation: Department of Neurology and Wilhelm Sander-NeuroOncology Unit, Regensburg University Hospital, Regensburg, Germany (C.S., U.B., P.H.); Department of Epidemiology and Preventive Medicine, University of Regensburg, Regensburg, Germany (C.R., M.F.L.); Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacy and Epidemiology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland (C.R.M., M.B.); Boston Collaborative Drug Surveillance Program, Boston University School of Public Health, Boston University, Boston, Massachusetts, (C.R.M., S.S.J.); Hospital Pharmacy, University Hospital Basel, Basel, Switzerland (C.R.M.); Department of General Internal Medicine, University of Bern, Inselspital/Universitätsspital, Bern, Switzerland (M.B.).
authors.forename: Michael F
authors.initials: MF
authors.lastname: Leitzmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D003920:Diabetes Mellitus / Q000188:drug therapy*; D005260:Female; D005910:Glioma / Q000139:chemically induced; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007223:Infant; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012727:Sex Characteristics; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents
keywords: diabetes; epidemiology; glioma; metformin; testosterone